RARE DISEASE
Primary adrenal insufficiency
Primary adrenal insufficiency
Primary adrenal insufficiency
Drug discovery
5
drugs
With orphan designations
Overview
Primary adrenal insufficiency (PAI) is a rare, life-threatening disorder caused by inadequate cortisol and aldosterone production, most commonly due to autoimmune adrenalitis [1][3][9]. Diagnosis involves low morning cortisol with elevated ACTH and requires lifelong glucocorticoid (hydrocortisone/prednisone) and mineralocorticoid (fludrocortisone) replacement [1][7][14]. Delayed diagnosis increases mortality risk from adrenal crises [1][4][6]. Patient education on medication adherence and stress-dose adjustments is critical [1][5][14].
Burden
Mortality: 2× higher than general population, driven by adrenal crises/infections [2][4][17]
Adrenal crises: Incidence 6–8/100 patient-years requiring hospitalization [4][6][17]
Chronic morbidity: Reduced quality of life, frequent healthcare visits, comorbidities (autoimmune thyroid disease) [4][6][10]
Therapies
Hormone replacement:
Hydrocortisone (10–25 mg/day divided) + fludrocortisone (0.05–0.2 mg/day) [1][7][14]
Emergency protocols: Stress-dose steroids (IV hydrocortisone) during illness/surgery [1][5][14]
Patient education: Sick-day rules, steroid emergency cards, injectable hydrocortisone kits [1][5][14]
Categories: rare endocrine diseases
Research Papers
782 drug discovery papers about Primary adrenal insufficiency, with 3 first-in-class and 24 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
782 drug discovery papers about Primary adrenal insufficiency, with 3 first-in-class and 24 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2025-03-26 | Experience in the treatment of acute adrenal insufficiency developed on COVID-19 (coronavirus infection) in a patient with diabetes
Introduction. The severity condition' of patients with COVID-19 largely depends on the multiplicity lesions and the involvement of vital organs, such as the adrenals, one of the most important components in the adaptation system in acute processes. Literary data indicate structural changes in the adrenals in patients with SARS-CoV-2, and the histological picture indicates the presence of focal necrosis of the adrenal glands and vasculitis of small veins. Studies on the assessment of adrenal function and damage in Covid-19 indicate the development of a chronic process in them. The objective of this study is to study a clinical case associated with the development of acute adrenal insufficiency in a patient with type 2 diabetes on COVID-19. Purpose. To study a clinical case related to the development of acute adrenal insufficiency in a patient with type 2 diabetes mellitus on the background of COVID-19. Material and methods. The source of the information was the primary medical documentation of patient E. «Medical record of a patient receiving medical care in an inpatient setting» (form 003/y). Results. On the 2nd day of hospitalization, signs pathognomonic for acute adrenal insufficiency appear: a swarthy tint of the skin, darkening of the skin folds on the hands, hyponatremia and arterial hypotension. The diagnosis was confirmed by the hormonal tests: ACTH = 63 PG/ml (0,0–46,0 PG/ml), morning cortisol blood = 68 nmol/l (185–624 nmol/l), daily urine cortisol = 55 µg/day (75–520 mg/day). Conclusions. This case describes clinical and laboratory data of acute primary adrenal insufficiency with complete restoration of adrenal function. Stabilization of the hormonal profile during inpatient treatment to parameters that do not require maintenance therapy with hormonal drugs in the future is a feature of this example. This case indicates the degree of the damaging effect of the virus, which can cause acute (reversible) primary adrenal insufficiency. In the presented clinical case shown that the development of adrenal insufficiency in COVID-19 is not always the beginning of a chronic process, even in patients with high comorbidity (type 2 diabetes). And with the timely start of active therapy, it's possible not only to preserve, but also to restore the function of the adrenal glands.
2025-01-14 | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol.
Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test. A novel formulation, Nasacthin, has been developed, which can be delivered intranasally, with the resultant glucocorticoid levels measured in saliva instead of blood. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-2) study aims to clinically validate the Nasacthin test in healthy volunteers. STARLIT-2 is a randomised, placebo-controlled, double-blinded, four-way crossover trial. 32 healthy adults and children will be randomised to receive each of four study drugs (Synacthen, Nasacthin and their respective placebos) over four study visits (one per visit). Paired blood and saliva samples will be collected from participants at baseline, and then at 30, 60, 90 and 120 min after drug administration. Additional salivary samples will be collected at 180, 240, 360 and 480 min after drug administration. The primary outcome measures are to compare the mean serum cortisol at 30 min after Synacthen or Nasacthin dose, with a view to determine non-inferiority; and to compare the mean change from baseline in serum cortisol at 30 min after active and placebo doses of both Synacthen and Nasacthin, aiming to demonstrate superiority of active over placebo. In addition, the proportion of participants for which Nasacthin produces a rise above a preset serum cortisol threshold at 30 min will be determined, with the negative per cent agreement with the SST calculated using the SST as the reference standard. The study and its amendments have been reviewed and approved by South Central-Hampshire A Research Ethics Committee. Results will be disseminated in peer-reviewed journals and conference presentations, and feedback to trial participants will be facilitated following consultation with patient and public involvement and engagement groups. ISRCTN62724177.
2024-10-01 | A rare variant of DAX1 mutation presenting with primary adrenal insufficiency and hypogonadotropic hypogonadism
ABSTRACT DAX1 mutation causes X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in boys. Onset of adrenal insufficiency (AI) usually precedes the diagnosis of HH. Likewise, our patient was first diagnosed with primary AI at the age of 8 years and later presented at 21 years of age with poorly developed secondary sexual characteristics. The hormonal evaluation was suggestive of low luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, suggestive of hypogonadotropic hypogonadism (HH). The possibility of DAX1 mutation was considered. Subsequently, whole-exome sequencing revealed a rare variant, NR0B1; c.881T>C (p.Leu294Pro), confirming our diagnosis. Therefore, a high index of suspicion is required in patients with a past history of AI who present with pubertal delay, in whom early initiation of gonadotropins results in favorable outcomes in terms of fertility. Monitoring pubertal development is important during follow-up because early recognition can help in proper management.
2023-05-26 | Clinical and genetic characteristics of 42 Chinese paediatric patients with X-linked adrenal hypoplasia congenita
Abstract Background X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization. Methods The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed. Results Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy ( P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year. Conclusions This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.
2015-10-01 | Corticotrophin-releasing factor receptor 2 mediates the enhanced activation of satiety-related responses through oxytocin neurons in the paraventricular nucleus of the hypothalamus after adrenalectomy
Adrenalectomy (ADX)-induced hypophagia is associated with increased activation of corticotrophin-releasing factor (CRF) and oxytocin (OT) neurons in the paraventricular nucleus of the hypothalamus (PVN) after refeeding. CRF2- and OT-receptor antagonists abolish the hypophagia and the augmented activation of the nucleus of the solitary tract neurons induced by feeding after ADX. In addition, OT-receptor antagonist reversed CRF-induced anorexia. We evaluated the effect of intracerebroventricular pretreatment with CRF2-receptor antagonist, antisauvagine-30 (AS30), on the activation of OT neurons of the PVN in response to refeeding of sham, adrenalectomized (ADX) and ADX rats replaced with corticosterone (ADX + B). In vehicle-pretreated animals, refeeding increased the number of Fos + OT double labeled neurons in the posterior parvocellular subdivision of the PVN (PaPo) of sham, ADX and ADX + B animals, with higher Fos expression and OT neuronal activation in the ADX group. AS30 reversed refeeding-induced increased activation of OT and non-OT neurons in the PaPo in the ADX group. In the medial parvocellular subdivision of the PVN (PaMP) of vehicle-pretreated animals, the number of Fos- and Fos + OT-immunoreactive neurons was increased after refeeding in ADX group. AS30 in the ADX group attenuated the enhanced Fos expression but not the number of Fos + OT double labeled neurons in the PaMP. In conclusion, CRF2-receptor antagonist reverses the increased activation of OT neurons in the PaPo induced by feeding in ADX animals, suggesting that OT neurons might be downstream mediators of CRF effects on satiety-related responses after ADX.
small molecules
2026-09-19 | Prescription pattern of oral hydrocortisone by Indian healthcare professionals: An online questionnaire-based survey.
Objective. Adrenal insufficiency is predominantly managed by glucocorticoids, from which hydrocortisone is most frequently prescribed. However, limited data are available on prescription patterns among Indian healthcare professionals (HCPs). This study assessed the prescription practices of hydrocortisone among Indian HCPs and evaluated their awareness of tapering protocols and necessity for modified-release formulations of hydrocortisone. Methods. This online questionnaire-based survey involved 300 HCPs across India who prescribe oral hydrocortisone for various endocrinological and non-endocrinological indications. Google Forms were used and survey was carried out over a period of two months. Only fully accomplished responses were included in the analysis and the response rate was calculated. Results. The survey response rate was 84.27%. Among HCPs, 94.7% prescribed oral hydrocortisone with 47.5% using it often and 28.9% very often. Prescription frequency varied from 29.9% (prescribed once weekly) to 25.7% (two or more times weekly). Awareness of approved indications was high (96.8%). Tapering protocols were widely practiced (95.4%) often or very often by 82.7% HCPs. Hydrocortisone was mainly prescribed for primary adrenal insufficiency (77.5%), secondary adrenal insufficiency (63.0%), and congenital adrenal hyperplasia (55.6%). Frequent adverse events included hyperglycemia (43.3%) and weight gain (43.0%). Most HCPs (89.8%) felt need for sustained-release hydrocortisone, particularly for primary adrenal insufficiency (81.7%). Alternatives of hydrocortisone mainly included prednisolone (65.8%), prednisone (37.3%), and dexamethasone (21.8%). Conclusion. Indian HCPs frequently prescribe oral hydrocortisone and are well-versed in tapering protocols. However, frequent adverse events and unmet needs emphasize strong demand for modified-release formulations, particularly for management of adrenal insufficiency.
2026-08-28 | NR5A1 gene variants: variable phenotypes, new variants, and genotype-phenotype correlations.
NR5A1 variants are among the most frequent monogenic causes of disorders of sex development (DSD). However, genotype-phenotype correlations remain unclear, and oligogenic contributions to variability are underexplored in non-consanguineous Chinese populations. In this single-center, retrospective cohort study, we evaluated clinical, hormonal, and genetic features of a single-center Chinese pediatric cohort with NR5A1 variants. We assessed genotype-phenotype correlations and intrafamilial variability and performed whole-exome sequencing in a subset to identify additional candidate variants. In 46,XY patients, gonads were testes in all evaluated cases; three had residual Müllerian structures, and three had primary adrenal insufficiency. The median external masculinization score was 3.0 (2.5-5.0). Among individuals initially assigned female, 73% (33/45) later underwent sex reassignment to male. Follicle-stimulating hormone levels increased significantly during puberty. We identified 76 NR5A1 variants, most commonly in the hinge region (37/76), followed by the DNA-binding (28/76) and ligand-binding (7/76) domains. Intrafamilial phenotypes varied markedly, including primary ovarian insufficiency or irregular menstruation in women and oligospermia or DSD in men. The external masculinization score and penile length standard deviation score did not differ between missense and loss-of-function variants (median score -3.63 vs -4.71; all P > 0.05) and remained similar across functional domains; testis location scores and sex assignment were also comparable. Whole-exome sequencing in 25 patients identified 49 potentially deleterious candidate variants in 36 additional genes. NR5A1-related DSD shows substantial phenotypic and intrafamilial variability without consistent genotype-phenotype correlations. Concomitant variants in other DSD-related genes support an oligogenic contribution to disease expression.
2026-08-19 | The complex relationship between endocrine and psychiatric disorders: an epidemiological study of risk estimates.
Psychiatric comorbidities are frequently observed in patients with endocrine disorders, yet in Romania the extent and nature of this association remains underexplored in clinical settings. This study aims to evaluate the prevalence and characteristics of endocrine disorders, like Cushing's syndrome, Addison's disease, hypo- and hyperthyroidism, in patients diagnosed with depressive, anxious, and manic disorders. We conducted a retrospective cross-sectional study using records from the Hipocrate/H3 electronic medical system between January 1, 2020, and September 1, 2024. Patients with ICD-10-coded endocrine diagnoses were identified, and the presence of documented psychiatric diagnoses was assessed. Odds ratios with 95% confidence intervals and chi-square tests were used to compare the odds of psychiatric comorbidity across endocrine diagnostic groups. The statistical analysis revealed that patients with Addison's disease, Cushing's syndrome and hypothyroidism were associated with significantly higher odds of psychiatric comorbidity (p < 0.0001). In contrast, in the case of patients with hyperthyroidism, we observed significantly lower odds of psychiatric disorders (p < 0.0001). The study demonstrates that psychiatric comorbidities are common among patients with endocrine disorders, underscoring a meaningful relationship between endocrine dysfunction and mental health. Because the study was cross-sectional and based on clinical records, causal interpretation is not possible. The findings support the need for integrated endocrine and psychiatric assessment in patients with selected endocrine disorders.
2026-08-06 | Infectious Diseases Targeting the Adrenal Glands: A Review.
100 years ago in the U.S., tuberculosis was the most common cause of primary adrenal insufficiency (AI) (Addison's disease). Autoimmune adrenalitis is now responsible for 80-90% of AI in this country and Europe; nevertheless today, in the U.S. and certainly abroad, diverse infections can involve the adrenals in both the immunocompetent and immunocompromised and potentially produce AI. Such infections range widely: bacterial (e.g., Mycobacterium tuberculosis, in particular), fungal (e.g., histoplasmosis), viral and even protozoal (e.g., severe Plasmodium falciparum malaria). Suspecting AI, especially if chronic, is not straightforward, delays in AI diagnosis may reach > 6 months in 50%, and 50-75% of patients initially present in overt adrenal crisis. Diagnosing adrenal involvement by an infection may be drawn out, typically requires careful imaging, a thorough infectious disease evaluation, and may require adrenal biopsy.
2026-08-06 | Congenital adrenal hyperplasia in children: a comprehensive review of clinical spectrum, diagnostic strategies, and management approaches.
Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessive disorders and is a leading cause of primary adrenal insufficiency in children. Most cases are due to classic 21-hydroxylase deficiency. Earlier diagnosis has been made possible with newborn screening, which has also reduced the risk of adrenal crises. This review is based on a search of PubMed, Embase, Scopus, and Medline for articles published from 2000 to 2025, using the terms "congenital adrenal hyperplasia", "21-hydroxylase deficiency", "primary adrenal insufficiency", and "steroidogenesis" with a focus on paediatric studies, clinical trials, systematic reviews, and consensus guidelines. The aims of clinical management are appropriate glucocorticoid and mineralocorticoid replacement, prevention of adrenal crises, monitoring of growth, puberty, and metabolic health. The main challenges include balancing androgen suppression with minimising glucocorticoid overexposure and monitoring for long-term complications such as early bone maturation and testicular adrenal rest tumours. Diagnostic accuracy and genotype-phenotype correlations have improved through advances in biochemical testing and molecular genetics. Newer and adjunctive therapies, including modified-release hydrocortisone, CRF1 receptor antagonists, adrenal-targeted drugs, and experimental gene therapies, may further improve disease management and simplify treatment. Effective management of CAH in children requires balancing optimal hormonal control with minimising treatment-related adverse effects. Newer and future therapies are expected to improve physiological management and long-term outcomes. Further research is needed to enhance individualised care and support transition to adult services.
antibodies
2026-08-09 | IFNG-producing self-reactive CD4+ T cells induce autoimmune adrenalitis in a mouse model of Addison's disease.
Autoimmune Addison's disease (AD) is a rare but life-threatening disorder caused by immune-mediated destruction of the adrenal cortex, and progress in therapy has been limited by insufficient mechanistic insight. Here, we establish a model of Experimental Autoimmune Adrenalitis (EAA) that recapitulates key features of AD and reveals sex-dependent differences in disease manifestation within the model. Immunization with peptides derived from the adrenal self-antigen CYP11A1 induces corticosterone insufficiency. We show that autoimmune adrenalitis is driven by IFNG produced by self-reactive CD4+ T cells, promoting granulomatous inflammation in the adrenal cortex. Together, these findings identify IFNG as a central effector of autoimmune adrenalitis and suggest that targeting the IFNG pathway may represent a potential therapeutic strategy for AD.
2026-04-03 | Primary adrenal insufficiency and autoimmune thyroiditis in an adolescent with Castleman-TAFRO syndrome.
The idiopathic multicentric Castleman disease (CD)-TAFRO variant (iMCD-TAFRO) is a rare, clinically aggressive lymphoproliferative disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly. Associated with elevated inflammatory cytokines, iMCD-TAFRO can present severe systemic complications. Here, we report a previously healthy adolescent male presenting with severe systemic inflammation, diffuse lymphadenopathy, anasarca, renal impairment, and hepatosplenomegaly. His clinical course was complicated by suspected bilateral adrenal infarction leading to primary adrenal insufficiency (PAI) requiring glucocorticoid (GC) replacement and new-onset autoimmune thyroiditis (AIT) requiring thyroid hormone replacement, suggesting a broader autoimmune process. Diagnosis of iMCD-TAFRO was supported by a right iliac lymph node biopsy showing CD features. The patient was successfully treated with high-dose GC followed by targeted immunosuppressive therapy with siltuximab, an anti-interleukin-6 monoclonal antibody. This case highlights a rare presentation of iMCD-TAFRO syndrome in a pediatric patient with unique co-occurrence of 2 endocrinopathies; PAI and AIT. Prompt recognition of potential associated endocrinopathies and a multidisciplinary approach are critical for management and improved outcomes in this life-threatening condition.
2026-02-25 | Bilateral adrenal masses and adrenal insufficiency: a rare case of primary adrenal lymphoma.
Primary adrenal lymphoma (PAL) is a rare malignancy typically considered in patients presenting with features of adrenal insufficiency and bilateral adrenal gland enlargement. Early diagnosis and differentiation from other causes of bilateral adrenal masses are essential to guide appropriate management. Prompt initiation of chemotherapy can significantly improve survival outcomes. We present the case of a 72-year-old patient with adrenal insufficiency and imaging-confirmed large bilateral adrenal masses with widespread lymph node involvement. Core biopsy of the adrenal mass confirmed high-grade diffuse large B-cell lymphoma (DLBCL), consistent with a diagnosis of PAL. She was initially managed with systemic chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), achieving a complete metabolic response. Two months later, she presented with relapsed central nervous system disease and died despite intrathecal cytarabine and methotrexate chemotherapy. Given the rarity of this condition, we use the case to illustrate and discuss key aspects of PAL, including demographics, pathogenesis, diagnosis, management, and prognosis. PAL is a rare but important diagnosis to consider in patients presenting with bilateral adrenal masses and adrenal insufficiency, especially in the absence of a known primary. In this case, the patient presented repeatedly with constitutional symptoms before the diagnosis was made through imaging. Whether an earlier diagnosis would have changed the clinical outcome remains unclear. This suggests that early imaging is important to initiate the diagnostic and management cascade in patients presenting with persistent, unexplained symptoms. Following exclusion of phaeochromocytoma, early biopsy and histopathological confirmation is crucial for accurate diagnosis and guiding management. Immunochemotherapy is the mainstay of treatment and may improve survival even in the setting of widespread disease. CNS involvement is important to exclude through MR scan of the brain and CSF sampling. Further research into predictors of recurrence and CNS relapse may improve long-term outcomes in PAL.
2026-01-27 | An Adrenal Crisis After Denosumab Use in a Patient With Addison's Disease: A Case Report.
Primary adrenal insufficiency (Addison's disease) requires lifelong glucocorticoid and mineralocorticoid replacement, and patients are vulnerable to adrenal crisis during physiologic stress or medication-related perturbations. Denosumab, a monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is widely used for osteoporosis treatment and is generally well tolerated. However, to our knowledge, an adrenal crisis temporally associated with denosumab administration has not been previously documented. A 69-year-old female patient with a 35-year history of primary adrenal insufficiency was on stable replacement therapy with 5 mg of oral prednisolone daily. Due to chronic kidney disease, denosumab was selected as an alternative antiresorptive therapy for severe postmenopausal osteoporosis. Approximately 24 hours after receiving 60 mg of subcutaneous denosumab, she developed profound fatigue, vomiting, dizziness, and hypotension. Laboratory evaluation revealed hyponatremia, elevated creatinine, and low morning cortisol with elevated adrenocorticotropic hormone (ACTH), confirming adrenal crisis. Infectious, cardiac, gastrointestinal, and pharmacokinetic triggers - including medications known to accelerate glucocorticoid metabolism - were excluded. She was successfully treated with intravenous hydrocortisone and fluid resuscitation, with full clinical recovery. To our knowledge, this is the first reported case of adrenal crisis temporally linked to denosumab use in a female patient with Addison's disease, suggesting a possible association rather than definite causality, particularly when stress-dose glucocorticoids are not provided. Clinicians should be aware of this potential association and consider individualized risk assessment, pre-treatment glucocorticoid dose adjustments, and close monitoring in patients with adrenal insufficiency receiving denosumab.
2026-01-01 | O-09 BILATERAL ADRENAL MASS AND ADRENAL INSUFFICIENCY CAUSED BY PRIMARY ADRENAL LYMPHOMA; A CASE REPORT
Abstract Introduction Primary adrenal lymphoma (PAL) usually presents as a bilateral heterogeneous adrenal mass on computed tomography (CT). PAL is a rare type of lymphoma originating from adrenal tissue and causes adrenal insufficiency (AI). We present a case of PAL with the complaint of loss of appetite and signs of AI. Clinical Case A 75-year-old male with chief complaints of fatigue, loss of appetite, and 10 kg weight loss from one month ago was referred to the endocrine clinic with the possibility of AI. On physical exam, the patient had slightly dark skin and had hypotension (BP: 90/55). The lab tests revealed hyperkalemia (K+: 5.7 mEq/L), near-normal sodium levels (Na+: 135 mEq/L), and high ferritin levels (ferritin: 791 ng/dL, normal range: 17-327). Table 1 presents the patient's primary lab results. The hormonal evaluation of patients confirmed AI due to low cortisol (Cortisol: 3µg/dL, normal level: 5-25 µg/dL) and high ACTH (ACTH: 2135 pg/dL, normal range: 4.7-48.8 pg/dL). In compound tomography (Figure 1), the patient had bilateral adrenal masses of 58*54mm and 58*48mm on the right and left kidney, with no lymphadenopathy. To evaluate the nature of the mass, an adrenal biopsy was performed, which reported a malignant neoplasm. The IHC study was positive for CD45 with a Ki-65 level of approximately 80%. The IHC study was in favor of high-grade lymphoma. The patient was given 0.1 mg of fludrocortisone and 20 mg of hydrocortisone daily for AI and then was referred to the oncology ward for chemotherapy. Conclusion Adrenal lymphoma can be divided into two categories: primary and secondary adrenal lymphoma. Secondary adrenal lymphoma is the most prevalent type of adrenal lymphoma. PAL is usually seen in the elderly male population and causes a bilateral adrenal mass. PAL causes AI due to the cytokines released from immune cells, in addition to the mass effect. The exact pathophysiology of PAL is unknown, and the most common reported subtype of PAL is DLBCL lymphoma, but other subtypes, such as peripheral T-cell lymphoma and Burkitt`s lymphoma, are also reported. The prognosis of PAL is poor and is associated with high mortality rates. Currently, there are no specific biomarkers for PAL, but studies suggest high LDH and ferritin levels in PAL. Adrenal biopsy is needed to confirm the diagnosis of PAL and determine the exact subtype of PAL. Some of the important markers for PAL are CD45, Ki-67 level, CD10, CD20, MUM1, BCL2, and BCL6. The preferred treatment for PAL is the R-CHOP chemotherapy regimen with a 2-year overall survival rate of 57%.Figure 1:Abdominal CT scan of patient Table 1:The patient`s primary laboratory test results
cell therapies
2026-01-05 | Anti-aging effects of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanisms of action and beneficial effects in older people.
We review the recent remarkable progress of the molecular mechanisms of action of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) regarding their beneficial effects on older people and adrenal regenerative therapy by looking back on our research extending over 50 years since 1971. DHEAS is the most abundant circulating steroid hormone in humans and apes. DHEAS is essential for brain development in adrenarche and for anti-aging in adrenopause as shown by the evolutionary process in primates. The molecular mechanisms of action of DHEA and DHEAS have been clarified by the discovery of many membrane receptors and by the concept of intracrinological action, which is especially important in menopausal women. The genes associated with serum DHEAS concentrations were identified by genome-wide association study meta-analysis of cohort studies. Recent advances in aging research have shown that DHEA and DHEAS have anti-aging action via antioxidants, anti-inflammation, telomere protection, p38MAPK inhibition, anti-cortisol effects, and chaperone induction. DHEA has beneficial effects on the prevention of atherosclerosis based on visceral obesity-induced metabolic syndrome in middle-aged people. DHEA also prevents infection, frailty via reverse metabolism, sarcopenia, and osteoporosis in older people, with a marked decrease in serum DHEAS concentrations. This review discusses adrenal regenerative therapy using steroid-producing cell replacement by overexpressing Ad4BP/steroidogenic factor 1 in mouse or human bone marrow mesenchymal stem cells. This therapy replaces cortisol and DHEAS treatment for the prevention of sudden death by adrenal crisis and severe infection in primary adrenal insufficiency (Addison's disease).
2025-10-18 | Human adrenocortical organoids for tissue regeneration and disease modeling.
The adrenal glands are essential endocrine organs that secrete key hormones maintaining physiological homeostasis. Herein, we established expandable three-dimensional (3D) human adrenocortical organoid (ACO) cultures that preserved the characteristic of zona fasciculata cell lineages and retained their capacity to produce cortisol. The ACOs could secrete glucocorticoids in response to physiological stimuli and thus rescue adrenalectomized mice, indicating their potential for the treatment of primary adrenal insufficiency. Furthermore, by introducing a hotspot pathogenic variant (PRKACA L206R) identified in Cushing's syndrome, we achieved the organoid disease modeling of cortisol-producing adenomas. In summary, this study establishes a human organoid platform to explore homeostasis and dysfunction in adrenal glands, suggesting future applications in disease modeling and regenerative medicine.
2025-10-01 | MON-500 Adrenal Bioprinted Tissue Therapeutics Restore Function in Murine Models of Primary Adrenal Insufficiency
Abstract Disclosure: H. Soliman: None. Z.A. Bazzi: None. O. Nemirovsky: None. S. Keshvani: None. C. Song: None. N.A. Chan: None. S. Gicole: None. R.B. Jalili: None. S. Wadsworth: None. C.T. Dickman: None. Primary adrenal insufficiency, caused by either autoimmune Addison’s disease or congenital adrenal hyperplasia, is a life-threatening condition that requires lifelong adrenal hormone replacement. Current hormone replacement therapies have a high treatment burden and fail to mimic the natural circadian rhythms of hormone secretion. Transplanting functional adrenal cells has the potential to restore the natural hypothalamic-pituitary-adrenal (HPA) axis feedback loop, enabling dynamic hormonal regulation that mimics physiological function rather than relying on fixed-dose steroid replacement. An allogeneic cell therapy that achieves this without the need for chronic immune suppression could be a breakthrough in the treatment of primary adrenal insufficiency. Adrenal Bioprinted Tissue Therapeutics (BTTs) were developed using primary human adrenocortical cells with Aspect Biosystems’ full-stack tissue therapeutic platform, which incorporates proprietary bioprinting technology. These cells were encapsulated in a cell-supporting biomaterial with an immunoprotective outer shell. In vitro assessment of these BTTs indicated that the encapsulated adrenal cells were viable for extended durations and able to sense exogenously administered adrenocorticotrophic hormone (ACTH) and respond by releasing cortisol. Implantation of these xenogeneic adrenal BTTs in adrenalectomized mice led to a dose-dependent, rapid, marked, and sustained responsive elevation of plasma cortisol and reduction in plasma ACTH, as well as an increase in survival. There was a robust response to exogenously administered ACTH resulting in a significant increase in plasma cortisol in mice implanted with adrenal BTTs. ACTH responsive cortisol secretion was observed through study end at six months. To assess whether implanted adrenal BTTs respond to physiological circadian fluctuations in endogenous mouse ACTH levels, plasma cortisol and ACTH were measured mornings and evenings and showed that plasma cortisol levels followed the same secretion pattern as endogenous ACTH in the adrenalectomized mice, indicating responsiveness of the implanted BTTs to physiological fluctuations in ACTH. Adrenal BTTs retrieved from mice at termination after six months demonstrated high viability and remained responsive to in vitro incubation with ACTH. These results indicate that Aspect Biosystems’ adrenal BTTs can restore precise ACTH responsive adrenal function with appropriate circadian rhythm in in vivo models of primary adrenal insufficiency. Such an approach could revolutionize therapy for patients with primary adrenal insufficiency. Presentation: Monday, July 14, 2025
2025-10-01 | P.22: Implantation of NR5A1-induced steroidogenic cells prolongs survival in a mouse model of adrenal insufficiency.
Introduction: Steroid hormones synthesized and secreted by the adrenal cortex play indispensable roles in maintaining physiological homeostasis, including the regulation of glucose metabolism, immune function and stress responses. Histologically, the adrenal cortex is characterized by a rich vascular endothelial network, with steroidogenic cells located in close proximity to endothelial cells. The transcription of all steroidogenic enzymes is regulated by Nuclear receptor 5A1 (NR5A1, also known as Ad4BP/SF1), a master regulator critical for the development of adrenal glands and gonads. Primary adrenal insufficiency, which causes steroid hormone deficiency, is currently treated with lifelong hormone replacement therapy. While this is an established medical intervention, it is associated with metabolic side effects. Moreover, long-term administration suppresses the hypothalamic-pituitary-adrenal axis and fails to accurately replicate physiological hormone levels. Insufficient replacement may lead to adrenal crisis, which can be life-threatening. Therefore, cell therapy using transplanted steroidogenic cells responsive to endogenous ACTH and other physiological stimuli is a promising alternative for hormone replacement. Method: Murine and human mesenchymal stromal cells (MSCs) were transduced with NR5A1 via viral vectors to induce steroidogenic potential. Steroid hormone production and expression levels of key steroidogenic enzymes were assessed. Expression of the melanocortin 2 receptor (MC2R), which mediates ACTH responsiveness, was evaluated alongside in vitro ACTH-stimulated steroidogenesis. To evaluate therapeutic potential in vivo, spheres of NR5A1-induced steroidogenic cells were implanted beneath the renal capsule in bilateral adrenalectomized murine models. Post-implantation survival and circulating steroid hormone concentrations were measured. Additionally, co-culture experiments with vascular endothelial cells were performed to assess their influence on glucocorticoid production. Results: Ectopic expression of NR5A1 in MSCs induced production of both adrenal and gonadal steroids and upregulated the expression levels of steroidogenic enzymes. In vitro, ACTH stimulation enhanced steroidogenesis. Bilateral adrenalectomized mice typically died within a few days due to adrenal insufficiency. However, implantation of NR5A1-induced steroidogenic cell spheres prolonged survival and led to detectable circulating glucocorticoid levels. Co-culture of NR5A1-induced steroidogenic cells with endothelial cells enhanced glucocorticoid, but not gonadal steroid, production. These results suggest that co-culture with endothelial cells may facilitate lineage commitment toward adrenocortical-like phenotypes. Conclusion: Implantation of NR5A1-induced steroidogenic cells derived from mesenchymal stromal cells prolonged survival in mouse models of adrenal insufficiency, demonstrating the potential of steroid replacement via cell therapy.
2024-07-25 | In Vivo Formation of Adrenal Organoids in a Novel Porcine Model of Adrenocortical Cell Transplantation.
Recognizing the limitations of current therapies for Addison's disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam. Hydrocortisone support was provided during adrenocortical cell engraftment and weaned as tolerated. Blood adrenocortical hormone concentrations were monitored, and the transplant site was examined at endpoint. Outcome measures included cellular histochemistry, systemic hormone production, and hydrocortisone independence. Transplanted adrenocortical cells showed a capability to survive and proliferate within the intracutaneous site and an ability to self-organize into discrete tissue organoids with features of the normal adrenal histologic architecture. Interpretation of systemic hormone levels was confounded by the identification of accessory adrenals and regenerative cortical tissue within the adrenal bed postmortem. Corticosteroids were unable to be completely ceased. ACT in a large animal model has not previously been attempted, yet it is an important step toward clinical translation. These results demonstrate rhe potential for ACT based on the development of adrenal organoids at the BTM site. However, the inability to achieve clinically relevant systemic hormone production suggests insufficient function, likely attributable to insufficient cells through delivered dose and subsequent proliferation.
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2023-10-18 | Increased risk of hospitalization, intensive care and death due to COVID‐19 in patients with adrenal insufficiency: A Swedish nationwide study
Abstract Background Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID‐19 is unknown. Methods In this linked Swedish national register‐based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID‐19 outcomes were studied: incidence of COVID‐19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. Results We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID‐19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID‐19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28). Conclusion Patients with AI have a similar incidence of COVID‐19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
2022-10-27 | No need of glucocorticoid dose adjustment in patients with adrenal insufficiency before COVID-19 vaccine.
Coronavirus disease-2019 (COVID-19) causes acute respiratory distress syndrome. Patients with adrenal insufficiency (AI) may develop severe complications due to this infection and should undergo COVID-19 vaccination; however, there is no consensus about the management of their replacement therapy. The aim of our study was to evaluate the tolerability and need for glucocorticoid dose adjustment related to COVID-19 mRNA vaccines in a cohort of patients with AI. We prospectively administered to 88 patients (51 M/37 F; mean age: 62.3 ± 16 years), with AI (28 primary and 60 secondary AI), a questionnaire about the occurrence, severity and duration of the side effects and the need for glucocorticoid dose adjustment within 1 week after the first and the second dose of COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna). Side effects of mild to moderate severity occurred in about 70% of patients after both vaccine doses. The most common adverse events were pain at the injection site, fatigue, fever and flu-like symptoms. The occurrence and severity of the side effects were not correlated to gender, type of AI and mRNA vaccine, but their total number was higher after the second vaccine dose. Doubling the oral glucocorticoid dose was needed in up to 8% of patients, especially after the second vaccine dose, but no parenteral administration was required. COVID-19 mRNA vaccines were well tolerated in patients with AI. Side effects were similar to those observed in the general population, and increasing glucocorticoid replacement therapy before vaccine administration was not needed.
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2025-03-26 | Experience in the treatment of acute adrenal insufficiency developed on COVID-19 (coronavirus infection) in a patient with diabetes
Introduction. The severity condition' of patients with COVID-19 largely depends on the multiplicity lesions and the involvement of vital organs, such as the adrenals, one of the most important components in the adaptation system in acute processes. Literary data indicate structural changes in the adrenals in patients with SARS-CoV-2, and the histological picture indicates the presence of focal necrosis of the adrenal glands and vasculitis of small veins. Studies on the assessment of adrenal function and damage in Covid-19 indicate the development of a chronic process in them. The objective of this study is to study a clinical case associated with the development of acute adrenal insufficiency in a patient with type 2 diabetes on COVID-19. Purpose. To study a clinical case related to the development of acute adrenal insufficiency in a patient with type 2 diabetes mellitus on the background of COVID-19. Material and methods. The source of the information was the primary medical documentation of patient E. «Medical record of a patient receiving medical care in an inpatient setting» (form 003/y). Results. On the 2nd day of hospitalization, signs pathognomonic for acute adrenal insufficiency appear: a swarthy tint of the skin, darkening of the skin folds on the hands, hyponatremia and arterial hypotension. The diagnosis was confirmed by the hormonal tests: ACTH = 63 PG/ml (0,0–46,0 PG/ml), morning cortisol blood = 68 nmol/l (185–624 nmol/l), daily urine cortisol = 55 µg/day (75–520 mg/day). Conclusions. This case describes clinical and laboratory data of acute primary adrenal insufficiency with complete restoration of adrenal function. Stabilization of the hormonal profile during inpatient treatment to parameters that do not require maintenance therapy with hormonal drugs in the future is a feature of this example. This case indicates the degree of the damaging effect of the virus, which can cause acute (reversible) primary adrenal insufficiency. In the presented clinical case shown that the development of adrenal insufficiency in COVID-19 is not always the beginning of a chronic process, even in patients with high comorbidity (type 2 diabetes). And with the timely start of active therapy, it's possible not only to preserve, but also to restore the function of the adrenal glands.
2025-01-14 | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol.
Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test. A novel formulation, Nasacthin, has been developed, which can be delivered intranasally, with the resultant glucocorticoid levels measured in saliva instead of blood. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-2) study aims to clinically validate the Nasacthin test in healthy volunteers. STARLIT-2 is a randomised, placebo-controlled, double-blinded, four-way crossover trial. 32 healthy adults and children will be randomised to receive each of four study drugs (Synacthen, Nasacthin and their respective placebos) over four study visits (one per visit). Paired blood and saliva samples will be collected from participants at baseline, and then at 30, 60, 90 and 120 min after drug administration. Additional salivary samples will be collected at 180, 240, 360 and 480 min after drug administration. The primary outcome measures are to compare the mean serum cortisol at 30 min after Synacthen or Nasacthin dose, with a view to determine non-inferiority; and to compare the mean change from baseline in serum cortisol at 30 min after active and placebo doses of both Synacthen and Nasacthin, aiming to demonstrate superiority of active over placebo. In addition, the proportion of participants for which Nasacthin produces a rise above a preset serum cortisol threshold at 30 min will be determined, with the negative per cent agreement with the SST calculated using the SST as the reference standard. The study and its amendments have been reviewed and approved by South Central-Hampshire A Research Ethics Committee. Results will be disseminated in peer-reviewed journals and conference presentations, and feedback to trial participants will be facilitated following consultation with patient and public involvement and engagement groups. ISRCTN62724177.
2024-10-01 | A rare variant of DAX1 mutation presenting with primary adrenal insufficiency and hypogonadotropic hypogonadism
ABSTRACT DAX1 mutation causes X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in boys. Onset of adrenal insufficiency (AI) usually precedes the diagnosis of HH. Likewise, our patient was first diagnosed with primary AI at the age of 8 years and later presented at 21 years of age with poorly developed secondary sexual characteristics. The hormonal evaluation was suggestive of low luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, suggestive of hypogonadotropic hypogonadism (HH). The possibility of DAX1 mutation was considered. Subsequently, whole-exome sequencing revealed a rare variant, NR0B1; c.881T>C (p.Leu294Pro), confirming our diagnosis. Therefore, a high index of suspicion is required in patients with a past history of AI who present with pubertal delay, in whom early initiation of gonadotropins results in favorable outcomes in terms of fertility. Monitoring pubertal development is important during follow-up because early recognition can help in proper management.
2023-05-26 | Clinical and genetic characteristics of 42 Chinese paediatric patients with X-linked adrenal hypoplasia congenita
Abstract Background X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization. Methods The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed. Results Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy ( P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year. Conclusions This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.
2015-10-01 | Corticotrophin-releasing factor receptor 2 mediates the enhanced activation of satiety-related responses through oxytocin neurons in the paraventricular nucleus of the hypothalamus after adrenalectomy
Adrenalectomy (ADX)-induced hypophagia is associated with increased activation of corticotrophin-releasing factor (CRF) and oxytocin (OT) neurons in the paraventricular nucleus of the hypothalamus (PVN) after refeeding. CRF2- and OT-receptor antagonists abolish the hypophagia and the augmented activation of the nucleus of the solitary tract neurons induced by feeding after ADX. In addition, OT-receptor antagonist reversed CRF-induced anorexia. We evaluated the effect of intracerebroventricular pretreatment with CRF2-receptor antagonist, antisauvagine-30 (AS30), on the activation of OT neurons of the PVN in response to refeeding of sham, adrenalectomized (ADX) and ADX rats replaced with corticosterone (ADX + B). In vehicle-pretreated animals, refeeding increased the number of Fos + OT double labeled neurons in the posterior parvocellular subdivision of the PVN (PaPo) of sham, ADX and ADX + B animals, with higher Fos expression and OT neuronal activation in the ADX group. AS30 reversed refeeding-induced increased activation of OT and non-OT neurons in the PaPo in the ADX group. In the medial parvocellular subdivision of the PVN (PaMP) of vehicle-pretreated animals, the number of Fos- and Fos + OT-immunoreactive neurons was increased after refeeding in ADX group. AS30 in the ADX group attenuated the enhanced Fos expression but not the number of Fos + OT double labeled neurons in the PaMP. In conclusion, CRF2-receptor antagonist reverses the increased activation of OT neurons in the PaPo induced by feeding in ADX animals, suggesting that OT neurons might be downstream mediators of CRF effects on satiety-related responses after ADX.
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2026-09-19 | Prescription pattern of oral hydrocortisone by Indian healthcare professionals: An online questionnaire-based survey.
Objective. Adrenal insufficiency is predominantly managed by glucocorticoids, from which hydrocortisone is most frequently prescribed. However, limited data are available on prescription patterns among Indian healthcare professionals (HCPs). This study assessed the prescription practices of hydrocortisone among Indian HCPs and evaluated their awareness of tapering protocols and necessity for modified-release formulations of hydrocortisone. Methods. This online questionnaire-based survey involved 300 HCPs across India who prescribe oral hydrocortisone for various endocrinological and non-endocrinological indications. Google Forms were used and survey was carried out over a period of two months. Only fully accomplished responses were included in the analysis and the response rate was calculated. Results. The survey response rate was 84.27%. Among HCPs, 94.7% prescribed oral hydrocortisone with 47.5% using it often and 28.9% very often. Prescription frequency varied from 29.9% (prescribed once weekly) to 25.7% (two or more times weekly). Awareness of approved indications was high (96.8%). Tapering protocols were widely practiced (95.4%) often or very often by 82.7% HCPs. Hydrocortisone was mainly prescribed for primary adrenal insufficiency (77.5%), secondary adrenal insufficiency (63.0%), and congenital adrenal hyperplasia (55.6%). Frequent adverse events included hyperglycemia (43.3%) and weight gain (43.0%). Most HCPs (89.8%) felt need for sustained-release hydrocortisone, particularly for primary adrenal insufficiency (81.7%). Alternatives of hydrocortisone mainly included prednisolone (65.8%), prednisone (37.3%), and dexamethasone (21.8%). Conclusion. Indian HCPs frequently prescribe oral hydrocortisone and are well-versed in tapering protocols. However, frequent adverse events and unmet needs emphasize strong demand for modified-release formulations, particularly for management of adrenal insufficiency.
2026-08-28 | NR5A1 gene variants: variable phenotypes, new variants, and genotype-phenotype correlations.
NR5A1 variants are among the most frequent monogenic causes of disorders of sex development (DSD). However, genotype-phenotype correlations remain unclear, and oligogenic contributions to variability are underexplored in non-consanguineous Chinese populations. In this single-center, retrospective cohort study, we evaluated clinical, hormonal, and genetic features of a single-center Chinese pediatric cohort with NR5A1 variants. We assessed genotype-phenotype correlations and intrafamilial variability and performed whole-exome sequencing in a subset to identify additional candidate variants. In 46,XY patients, gonads were testes in all evaluated cases; three had residual Müllerian structures, and three had primary adrenal insufficiency. The median external masculinization score was 3.0 (2.5-5.0). Among individuals initially assigned female, 73% (33/45) later underwent sex reassignment to male. Follicle-stimulating hormone levels increased significantly during puberty. We identified 76 NR5A1 variants, most commonly in the hinge region (37/76), followed by the DNA-binding (28/76) and ligand-binding (7/76) domains. Intrafamilial phenotypes varied markedly, including primary ovarian insufficiency or irregular menstruation in women and oligospermia or DSD in men. The external masculinization score and penile length standard deviation score did not differ between missense and loss-of-function variants (median score -3.63 vs -4.71; all P > 0.05) and remained similar across functional domains; testis location scores and sex assignment were also comparable. Whole-exome sequencing in 25 patients identified 49 potentially deleterious candidate variants in 36 additional genes. NR5A1-related DSD shows substantial phenotypic and intrafamilial variability without consistent genotype-phenotype correlations. Concomitant variants in other DSD-related genes support an oligogenic contribution to disease expression.
2026-08-19 | The complex relationship between endocrine and psychiatric disorders: an epidemiological study of risk estimates.
Psychiatric comorbidities are frequently observed in patients with endocrine disorders, yet in Romania the extent and nature of this association remains underexplored in clinical settings. This study aims to evaluate the prevalence and characteristics of endocrine disorders, like Cushing's syndrome, Addison's disease, hypo- and hyperthyroidism, in patients diagnosed with depressive, anxious, and manic disorders. We conducted a retrospective cross-sectional study using records from the Hipocrate/H3 electronic medical system between January 1, 2020, and September 1, 2024. Patients with ICD-10-coded endocrine diagnoses were identified, and the presence of documented psychiatric diagnoses was assessed. Odds ratios with 95% confidence intervals and chi-square tests were used to compare the odds of psychiatric comorbidity across endocrine diagnostic groups. The statistical analysis revealed that patients with Addison's disease, Cushing's syndrome and hypothyroidism were associated with significantly higher odds of psychiatric comorbidity (p < 0.0001). In contrast, in the case of patients with hyperthyroidism, we observed significantly lower odds of psychiatric disorders (p < 0.0001). The study demonstrates that psychiatric comorbidities are common among patients with endocrine disorders, underscoring a meaningful relationship between endocrine dysfunction and mental health. Because the study was cross-sectional and based on clinical records, causal interpretation is not possible. The findings support the need for integrated endocrine and psychiatric assessment in patients with selected endocrine disorders.
2026-08-06 | Infectious Diseases Targeting the Adrenal Glands: A Review.
100 years ago in the U.S., tuberculosis was the most common cause of primary adrenal insufficiency (AI) (Addison's disease). Autoimmune adrenalitis is now responsible for 80-90% of AI in this country and Europe; nevertheless today, in the U.S. and certainly abroad, diverse infections can involve the adrenals in both the immunocompetent and immunocompromised and potentially produce AI. Such infections range widely: bacterial (e.g., Mycobacterium tuberculosis, in particular), fungal (e.g., histoplasmosis), viral and even protozoal (e.g., severe Plasmodium falciparum malaria). Suspecting AI, especially if chronic, is not straightforward, delays in AI diagnosis may reach > 6 months in 50%, and 50-75% of patients initially present in overt adrenal crisis. Diagnosing adrenal involvement by an infection may be drawn out, typically requires careful imaging, a thorough infectious disease evaluation, and may require adrenal biopsy.
2026-08-06 | Congenital adrenal hyperplasia in children: a comprehensive review of clinical spectrum, diagnostic strategies, and management approaches.
Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessive disorders and is a leading cause of primary adrenal insufficiency in children. Most cases are due to classic 21-hydroxylase deficiency. Earlier diagnosis has been made possible with newborn screening, which has also reduced the risk of adrenal crises. This review is based on a search of PubMed, Embase, Scopus, and Medline for articles published from 2000 to 2025, using the terms "congenital adrenal hyperplasia", "21-hydroxylase deficiency", "primary adrenal insufficiency", and "steroidogenesis" with a focus on paediatric studies, clinical trials, systematic reviews, and consensus guidelines. The aims of clinical management are appropriate glucocorticoid and mineralocorticoid replacement, prevention of adrenal crises, monitoring of growth, puberty, and metabolic health. The main challenges include balancing androgen suppression with minimising glucocorticoid overexposure and monitoring for long-term complications such as early bone maturation and testicular adrenal rest tumours. Diagnostic accuracy and genotype-phenotype correlations have improved through advances in biochemical testing and molecular genetics. Newer and adjunctive therapies, including modified-release hydrocortisone, CRF1 receptor antagonists, adrenal-targeted drugs, and experimental gene therapies, may further improve disease management and simplify treatment. Effective management of CAH in children requires balancing optimal hormonal control with minimising treatment-related adverse effects. Newer and future therapies are expected to improve physiological management and long-term outcomes. Further research is needed to enhance individualised care and support transition to adult services.
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2026-08-09 | IFNG-producing self-reactive CD4+ T cells induce autoimmune adrenalitis in a mouse model of Addison's disease.
Autoimmune Addison's disease (AD) is a rare but life-threatening disorder caused by immune-mediated destruction of the adrenal cortex, and progress in therapy has been limited by insufficient mechanistic insight. Here, we establish a model of Experimental Autoimmune Adrenalitis (EAA) that recapitulates key features of AD and reveals sex-dependent differences in disease manifestation within the model. Immunization with peptides derived from the adrenal self-antigen CYP11A1 induces corticosterone insufficiency. We show that autoimmune adrenalitis is driven by IFNG produced by self-reactive CD4+ T cells, promoting granulomatous inflammation in the adrenal cortex. Together, these findings identify IFNG as a central effector of autoimmune adrenalitis and suggest that targeting the IFNG pathway may represent a potential therapeutic strategy for AD.
2026-04-03 | Primary adrenal insufficiency and autoimmune thyroiditis in an adolescent with Castleman-TAFRO syndrome.
The idiopathic multicentric Castleman disease (CD)-TAFRO variant (iMCD-TAFRO) is a rare, clinically aggressive lymphoproliferative disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly. Associated with elevated inflammatory cytokines, iMCD-TAFRO can present severe systemic complications. Here, we report a previously healthy adolescent male presenting with severe systemic inflammation, diffuse lymphadenopathy, anasarca, renal impairment, and hepatosplenomegaly. His clinical course was complicated by suspected bilateral adrenal infarction leading to primary adrenal insufficiency (PAI) requiring glucocorticoid (GC) replacement and new-onset autoimmune thyroiditis (AIT) requiring thyroid hormone replacement, suggesting a broader autoimmune process. Diagnosis of iMCD-TAFRO was supported by a right iliac lymph node biopsy showing CD features. The patient was successfully treated with high-dose GC followed by targeted immunosuppressive therapy with siltuximab, an anti-interleukin-6 monoclonal antibody. This case highlights a rare presentation of iMCD-TAFRO syndrome in a pediatric patient with unique co-occurrence of 2 endocrinopathies; PAI and AIT. Prompt recognition of potential associated endocrinopathies and a multidisciplinary approach are critical for management and improved outcomes in this life-threatening condition.
2026-02-25 | Bilateral adrenal masses and adrenal insufficiency: a rare case of primary adrenal lymphoma.
Primary adrenal lymphoma (PAL) is a rare malignancy typically considered in patients presenting with features of adrenal insufficiency and bilateral adrenal gland enlargement. Early diagnosis and differentiation from other causes of bilateral adrenal masses are essential to guide appropriate management. Prompt initiation of chemotherapy can significantly improve survival outcomes. We present the case of a 72-year-old patient with adrenal insufficiency and imaging-confirmed large bilateral adrenal masses with widespread lymph node involvement. Core biopsy of the adrenal mass confirmed high-grade diffuse large B-cell lymphoma (DLBCL), consistent with a diagnosis of PAL. She was initially managed with systemic chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), achieving a complete metabolic response. Two months later, she presented with relapsed central nervous system disease and died despite intrathecal cytarabine and methotrexate chemotherapy. Given the rarity of this condition, we use the case to illustrate and discuss key aspects of PAL, including demographics, pathogenesis, diagnosis, management, and prognosis. PAL is a rare but important diagnosis to consider in patients presenting with bilateral adrenal masses and adrenal insufficiency, especially in the absence of a known primary. In this case, the patient presented repeatedly with constitutional symptoms before the diagnosis was made through imaging. Whether an earlier diagnosis would have changed the clinical outcome remains unclear. This suggests that early imaging is important to initiate the diagnostic and management cascade in patients presenting with persistent, unexplained symptoms. Following exclusion of phaeochromocytoma, early biopsy and histopathological confirmation is crucial for accurate diagnosis and guiding management. Immunochemotherapy is the mainstay of treatment and may improve survival even in the setting of widespread disease. CNS involvement is important to exclude through MR scan of the brain and CSF sampling. Further research into predictors of recurrence and CNS relapse may improve long-term outcomes in PAL.
2026-01-27 | An Adrenal Crisis After Denosumab Use in a Patient With Addison's Disease: A Case Report.
Primary adrenal insufficiency (Addison's disease) requires lifelong glucocorticoid and mineralocorticoid replacement, and patients are vulnerable to adrenal crisis during physiologic stress or medication-related perturbations. Denosumab, a monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is widely used for osteoporosis treatment and is generally well tolerated. However, to our knowledge, an adrenal crisis temporally associated with denosumab administration has not been previously documented. A 69-year-old female patient with a 35-year history of primary adrenal insufficiency was on stable replacement therapy with 5 mg of oral prednisolone daily. Due to chronic kidney disease, denosumab was selected as an alternative antiresorptive therapy for severe postmenopausal osteoporosis. Approximately 24 hours after receiving 60 mg of subcutaneous denosumab, she developed profound fatigue, vomiting, dizziness, and hypotension. Laboratory evaluation revealed hyponatremia, elevated creatinine, and low morning cortisol with elevated adrenocorticotropic hormone (ACTH), confirming adrenal crisis. Infectious, cardiac, gastrointestinal, and pharmacokinetic triggers - including medications known to accelerate glucocorticoid metabolism - were excluded. She was successfully treated with intravenous hydrocortisone and fluid resuscitation, with full clinical recovery. To our knowledge, this is the first reported case of adrenal crisis temporally linked to denosumab use in a female patient with Addison's disease, suggesting a possible association rather than definite causality, particularly when stress-dose glucocorticoids are not provided. Clinicians should be aware of this potential association and consider individualized risk assessment, pre-treatment glucocorticoid dose adjustments, and close monitoring in patients with adrenal insufficiency receiving denosumab.
2026-01-01 | O-09 BILATERAL ADRENAL MASS AND ADRENAL INSUFFICIENCY CAUSED BY PRIMARY ADRENAL LYMPHOMA; A CASE REPORT
Abstract Introduction Primary adrenal lymphoma (PAL) usually presents as a bilateral heterogeneous adrenal mass on computed tomography (CT). PAL is a rare type of lymphoma originating from adrenal tissue and causes adrenal insufficiency (AI). We present a case of PAL with the complaint of loss of appetite and signs of AI. Clinical Case A 75-year-old male with chief complaints of fatigue, loss of appetite, and 10 kg weight loss from one month ago was referred to the endocrine clinic with the possibility of AI. On physical exam, the patient had slightly dark skin and had hypotension (BP: 90/55). The lab tests revealed hyperkalemia (K+: 5.7 mEq/L), near-normal sodium levels (Na+: 135 mEq/L), and high ferritin levels (ferritin: 791 ng/dL, normal range: 17-327). Table 1 presents the patient's primary lab results. The hormonal evaluation of patients confirmed AI due to low cortisol (Cortisol: 3µg/dL, normal level: 5-25 µg/dL) and high ACTH (ACTH: 2135 pg/dL, normal range: 4.7-48.8 pg/dL). In compound tomography (Figure 1), the patient had bilateral adrenal masses of 58*54mm and 58*48mm on the right and left kidney, with no lymphadenopathy. To evaluate the nature of the mass, an adrenal biopsy was performed, which reported a malignant neoplasm. The IHC study was positive for CD45 with a Ki-65 level of approximately 80%. The IHC study was in favor of high-grade lymphoma. The patient was given 0.1 mg of fludrocortisone and 20 mg of hydrocortisone daily for AI and then was referred to the oncology ward for chemotherapy. Conclusion Adrenal lymphoma can be divided into two categories: primary and secondary adrenal lymphoma. Secondary adrenal lymphoma is the most prevalent type of adrenal lymphoma. PAL is usually seen in the elderly male population and causes a bilateral adrenal mass. PAL causes AI due to the cytokines released from immune cells, in addition to the mass effect. The exact pathophysiology of PAL is unknown, and the most common reported subtype of PAL is DLBCL lymphoma, but other subtypes, such as peripheral T-cell lymphoma and Burkitt`s lymphoma, are also reported. The prognosis of PAL is poor and is associated with high mortality rates. Currently, there are no specific biomarkers for PAL, but studies suggest high LDH and ferritin levels in PAL. Adrenal biopsy is needed to confirm the diagnosis of PAL and determine the exact subtype of PAL. Some of the important markers for PAL are CD45, Ki-67 level, CD10, CD20, MUM1, BCL2, and BCL6. The preferred treatment for PAL is the R-CHOP chemotherapy regimen with a 2-year overall survival rate of 57%.Figure 1:Abdominal CT scan of patient Table 1:The patient`s primary laboratory test results
cell therapies
2026-01-05 | Anti-aging effects of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanisms of action and beneficial effects in older people.
We review the recent remarkable progress of the molecular mechanisms of action of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) regarding their beneficial effects on older people and adrenal regenerative therapy by looking back on our research extending over 50 years since 1971. DHEAS is the most abundant circulating steroid hormone in humans and apes. DHEAS is essential for brain development in adrenarche and for anti-aging in adrenopause as shown by the evolutionary process in primates. The molecular mechanisms of action of DHEA and DHEAS have been clarified by the discovery of many membrane receptors and by the concept of intracrinological action, which is especially important in menopausal women. The genes associated with serum DHEAS concentrations were identified by genome-wide association study meta-analysis of cohort studies. Recent advances in aging research have shown that DHEA and DHEAS have anti-aging action via antioxidants, anti-inflammation, telomere protection, p38MAPK inhibition, anti-cortisol effects, and chaperone induction. DHEA has beneficial effects on the prevention of atherosclerosis based on visceral obesity-induced metabolic syndrome in middle-aged people. DHEA also prevents infection, frailty via reverse metabolism, sarcopenia, and osteoporosis in older people, with a marked decrease in serum DHEAS concentrations. This review discusses adrenal regenerative therapy using steroid-producing cell replacement by overexpressing Ad4BP/steroidogenic factor 1 in mouse or human bone marrow mesenchymal stem cells. This therapy replaces cortisol and DHEAS treatment for the prevention of sudden death by adrenal crisis and severe infection in primary adrenal insufficiency (Addison's disease).
2025-10-18 | Human adrenocortical organoids for tissue regeneration and disease modeling.
The adrenal glands are essential endocrine organs that secrete key hormones maintaining physiological homeostasis. Herein, we established expandable three-dimensional (3D) human adrenocortical organoid (ACO) cultures that preserved the characteristic of zona fasciculata cell lineages and retained their capacity to produce cortisol. The ACOs could secrete glucocorticoids in response to physiological stimuli and thus rescue adrenalectomized mice, indicating their potential for the treatment of primary adrenal insufficiency. Furthermore, by introducing a hotspot pathogenic variant (PRKACA L206R) identified in Cushing's syndrome, we achieved the organoid disease modeling of cortisol-producing adenomas. In summary, this study establishes a human organoid platform to explore homeostasis and dysfunction in adrenal glands, suggesting future applications in disease modeling and regenerative medicine.
2025-10-01 | MON-500 Adrenal Bioprinted Tissue Therapeutics Restore Function in Murine Models of Primary Adrenal Insufficiency
Abstract Disclosure: H. Soliman: None. Z.A. Bazzi: None. O. Nemirovsky: None. S. Keshvani: None. C. Song: None. N.A. Chan: None. S. Gicole: None. R.B. Jalili: None. S. Wadsworth: None. C.T. Dickman: None. Primary adrenal insufficiency, caused by either autoimmune Addison’s disease or congenital adrenal hyperplasia, is a life-threatening condition that requires lifelong adrenal hormone replacement. Current hormone replacement therapies have a high treatment burden and fail to mimic the natural circadian rhythms of hormone secretion. Transplanting functional adrenal cells has the potential to restore the natural hypothalamic-pituitary-adrenal (HPA) axis feedback loop, enabling dynamic hormonal regulation that mimics physiological function rather than relying on fixed-dose steroid replacement. An allogeneic cell therapy that achieves this without the need for chronic immune suppression could be a breakthrough in the treatment of primary adrenal insufficiency. Adrenal Bioprinted Tissue Therapeutics (BTTs) were developed using primary human adrenocortical cells with Aspect Biosystems’ full-stack tissue therapeutic platform, which incorporates proprietary bioprinting technology. These cells were encapsulated in a cell-supporting biomaterial with an immunoprotective outer shell. In vitro assessment of these BTTs indicated that the encapsulated adrenal cells were viable for extended durations and able to sense exogenously administered adrenocorticotrophic hormone (ACTH) and respond by releasing cortisol. Implantation of these xenogeneic adrenal BTTs in adrenalectomized mice led to a dose-dependent, rapid, marked, and sustained responsive elevation of plasma cortisol and reduction in plasma ACTH, as well as an increase in survival. There was a robust response to exogenously administered ACTH resulting in a significant increase in plasma cortisol in mice implanted with adrenal BTTs. ACTH responsive cortisol secretion was observed through study end at six months. To assess whether implanted adrenal BTTs respond to physiological circadian fluctuations in endogenous mouse ACTH levels, plasma cortisol and ACTH were measured mornings and evenings and showed that plasma cortisol levels followed the same secretion pattern as endogenous ACTH in the adrenalectomized mice, indicating responsiveness of the implanted BTTs to physiological fluctuations in ACTH. Adrenal BTTs retrieved from mice at termination after six months demonstrated high viability and remained responsive to in vitro incubation with ACTH. These results indicate that Aspect Biosystems’ adrenal BTTs can restore precise ACTH responsive adrenal function with appropriate circadian rhythm in in vivo models of primary adrenal insufficiency. Such an approach could revolutionize therapy for patients with primary adrenal insufficiency. Presentation: Monday, July 14, 2025
2025-10-01 | P.22: Implantation of NR5A1-induced steroidogenic cells prolongs survival in a mouse model of adrenal insufficiency.
Introduction: Steroid hormones synthesized and secreted by the adrenal cortex play indispensable roles in maintaining physiological homeostasis, including the regulation of glucose metabolism, immune function and stress responses. Histologically, the adrenal cortex is characterized by a rich vascular endothelial network, with steroidogenic cells located in close proximity to endothelial cells. The transcription of all steroidogenic enzymes is regulated by Nuclear receptor 5A1 (NR5A1, also known as Ad4BP/SF1), a master regulator critical for the development of adrenal glands and gonads. Primary adrenal insufficiency, which causes steroid hormone deficiency, is currently treated with lifelong hormone replacement therapy. While this is an established medical intervention, it is associated with metabolic side effects. Moreover, long-term administration suppresses the hypothalamic-pituitary-adrenal axis and fails to accurately replicate physiological hormone levels. Insufficient replacement may lead to adrenal crisis, which can be life-threatening. Therefore, cell therapy using transplanted steroidogenic cells responsive to endogenous ACTH and other physiological stimuli is a promising alternative for hormone replacement. Method: Murine and human mesenchymal stromal cells (MSCs) were transduced with NR5A1 via viral vectors to induce steroidogenic potential. Steroid hormone production and expression levels of key steroidogenic enzymes were assessed. Expression of the melanocortin 2 receptor (MC2R), which mediates ACTH responsiveness, was evaluated alongside in vitro ACTH-stimulated steroidogenesis. To evaluate therapeutic potential in vivo, spheres of NR5A1-induced steroidogenic cells were implanted beneath the renal capsule in bilateral adrenalectomized murine models. Post-implantation survival and circulating steroid hormone concentrations were measured. Additionally, co-culture experiments with vascular endothelial cells were performed to assess their influence on glucocorticoid production. Results: Ectopic expression of NR5A1 in MSCs induced production of both adrenal and gonadal steroids and upregulated the expression levels of steroidogenic enzymes. In vitro, ACTH stimulation enhanced steroidogenesis. Bilateral adrenalectomized mice typically died within a few days due to adrenal insufficiency. However, implantation of NR5A1-induced steroidogenic cell spheres prolonged survival and led to detectable circulating glucocorticoid levels. Co-culture of NR5A1-induced steroidogenic cells with endothelial cells enhanced glucocorticoid, but not gonadal steroid, production. These results suggest that co-culture with endothelial cells may facilitate lineage commitment toward adrenocortical-like phenotypes. Conclusion: Implantation of NR5A1-induced steroidogenic cells derived from mesenchymal stromal cells prolonged survival in mouse models of adrenal insufficiency, demonstrating the potential of steroid replacement via cell therapy.
2024-07-25 | In Vivo Formation of Adrenal Organoids in a Novel Porcine Model of Adrenocortical Cell Transplantation.
Recognizing the limitations of current therapies for Addison's disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam. Hydrocortisone support was provided during adrenocortical cell engraftment and weaned as tolerated. Blood adrenocortical hormone concentrations were monitored, and the transplant site was examined at endpoint. Outcome measures included cellular histochemistry, systemic hormone production, and hydrocortisone independence. Transplanted adrenocortical cells showed a capability to survive and proliferate within the intracutaneous site and an ability to self-organize into discrete tissue organoids with features of the normal adrenal histologic architecture. Interpretation of systemic hormone levels was confounded by the identification of accessory adrenals and regenerative cortical tissue within the adrenal bed postmortem. Corticosteroids were unable to be completely ceased. ACT in a large animal model has not previously been attempted, yet it is an important step toward clinical translation. These results demonstrate rhe potential for ACT based on the development of adrenal organoids at the BTM site. However, the inability to achieve clinically relevant systemic hormone production suggests insufficient function, likely attributable to insufficient cells through delivered dose and subsequent proliferation.
other
2023-10-18 | Increased risk of hospitalization, intensive care and death due to COVID‐19 in patients with adrenal insufficiency: A Swedish nationwide study
Abstract Background Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID‐19 is unknown. Methods In this linked Swedish national register‐based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID‐19 outcomes were studied: incidence of COVID‐19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. Results We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID‐19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID‐19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28). Conclusion Patients with AI have a similar incidence of COVID‐19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
2022-10-27 | No need of glucocorticoid dose adjustment in patients with adrenal insufficiency before COVID-19 vaccine.
Coronavirus disease-2019 (COVID-19) causes acute respiratory distress syndrome. Patients with adrenal insufficiency (AI) may develop severe complications due to this infection and should undergo COVID-19 vaccination; however, there is no consensus about the management of their replacement therapy. The aim of our study was to evaluate the tolerability and need for glucocorticoid dose adjustment related to COVID-19 mRNA vaccines in a cohort of patients with AI. We prospectively administered to 88 patients (51 M/37 F; mean age: 62.3 ± 16 years), with AI (28 primary and 60 secondary AI), a questionnaire about the occurrence, severity and duration of the side effects and the need for glucocorticoid dose adjustment within 1 week after the first and the second dose of COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna). Side effects of mild to moderate severity occurred in about 70% of patients after both vaccine doses. The most common adverse events were pain at the injection site, fatigue, fever and flu-like symptoms. The occurrence and severity of the side effects were not correlated to gender, type of AI and mRNA vaccine, but their total number was higher after the second vaccine dose. Doubling the oral glucocorticoid dose was needed in up to 8% of patients, especially after the second vaccine dose, but no parenteral administration was required. COVID-19 mRNA vaccines were well tolerated in patients with AI. Side effects were similar to those observed in the general population, and increasing glucocorticoid replacement therapy before vaccine administration was not needed.
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Drug Discovery Landscape
5 orphan drug designations for Primary adrenal insufficiency.
5 orphan drug designations for Primary adrenal insufficiency.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
hydrocortisone modified release capsules | small molecules | FDA | Diurnal Limited | |
hydrocortisone modified release tabs | small molecules | FDA | Takeda Development Center Americas, Inc. | |
Hydrocortisone [Chronocort] | small molecules | EMA | Immedica Netherlands B.V. | |
Dehydroepiandrosterone (DHEA) | small molecules | FDA | Paladin Labs, Inc. | |
Prasterone | small molecules | EMA | Medicom Healthcare BV |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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