RARE DISEASE
Rare hypoparathyroidism
Rare hypoparathyroidism
Rare hypoparathyroidism
Drug discovery
15
drugs
With orphan designations
Overview
Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia, hyperphosphatemia, and deficient parathyroid hormone (PTH) production. Most cases result from parathyroid gland damage during neck surgery, though autoimmune, genetic, or idiopathic etiologies may occur. Chronic management focuses on calcium and active vitamin D supplementation, with recombinant PTH therapy reserved for refractory cases. Complications include renal impairment, ectopic calcifications, and neuromuscular symptoms, necessitating lifelong monitoring [1][3][13].
Burden
Symptoms: Chronic fatigue, muscle cramps, paresthesia, and neuropsychiatric effects (e.g., depression, cognitive impairment) [4][9][14].
Complications: Nephrocalcinosis, kidney stones, cataracts, basal ganglia calcifications, and increased fracture risk [4][12][16].
Healthcare Impact: High ER visits/hospitalizations, reduced quality of life, and caregiver burden [5][9][12].
Therapies
Calcium (oral/IV) and active vitamin D analogs (calcitriol) to maintain calcium levels [1][3][13].
Recombinant PTH (rhPTH) (e.g., rhPTH [1-84]) for patients with unstable calcium or renal complications [11][13].
Adjuncts: Thiazide diuretics (reduce hypercalciuria), magnesium supplementation, and dietary modifications (low phosphate) [1][18].
Categories: rare endocrine diseases
Research Papers
194 drug discovery papers about Rare hypoparathyroidism, with 18 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
194 drug discovery papers about Rare hypoparathyroidism, with 18 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-11 | Hypocalcaemic cardiomyopathy with recurrent heart failure: a natural rechallenge case report with 30-month follow-up.
Hypocalcaemic cardiomyopathy is a rare but potentially reversible cause of heart failure (HF), yet it remains under-recognized in clinical practice. Evidence supporting a direct causal relationship is limited, particularly with regard to relapse and long-term follow-up. A 71-year-old woman with post-thyroidectomy hypoparathyroidism presented with new-onset HF characterized by progressive exertional dyspnoea, orthopnoea, and paroxysmal nocturnal dyspnoea. Echocardiography revealed left ventricular and left atrial dilatation with a reduced left ventricular ejection fraction (34%) and severe functional mitral regurgitation. Electrocardiography showed sinus rhythm with prolonged corrected QT interval and T-wave inversion. Coronary angiography excluded significant coronary disease, and no alternative causes of HF were identified. Laboratory testing demonstrated severe hypocalcaemia (1.18 mmol/L) and suppressed parathyroid hormone levels. Despite guideline-directed HF therapy, symptoms failed to improve. Intravenous and oral calcium supplementation, together with calcitriol, led to rapid symptomatic and functional recovery. Two months later, discontinuation of calcium supplementation resulted in recurrent hypocalcaemia and relapse of HF, despite ongoing guideline-directed HF therapy, and again resolved after calcium repletion. During 30 months of follow-up, adherence to supplementation maintained calcium homeostasis and was associated with preserved cardiac function, with no further HF recurrence. This case illustrates reversible and recurrent hypocalcaemic cardiomyopathy and highlights the importance of calcium homeostasis. The reproducible dechallenge-rechallenge pattern observed on two occasions provides clinically relevant evidence supporting a causal relationship between hypocalcaemia and myocardial dysfunction. Long-term biochemical monitoring and sustained adherence to calcium and vitamin D supplementation are important to prevent recurrence in patients with hypoparathyroidism.
2026-07-28 | Successful Transition in Rare Metabolic Bone Diseases: One-Year Outcomes of a Multidisciplinary Pediatric-Adult Program.
Background and Objectives: Pediatric-onset metabolic bone diseases, including osteogenesis imperfecta (OI), hypophosphatemic rickets (XLH), hypoparathyroidism, and McCune-Albright syndrome (MAS), require lifelong follow-up because of persistent skeletal fragility, biochemical abnormalities, and functional morbidity extending into adulthood. However, evidence regarding structured transition from pediatric to adult care in these rare disorders remains limited. This study evaluated one-year outcomes of a multidisciplinary transition program for adolescents and young adults with rare metabolic bone diseases. Materials and Methods: This retrospective cohort study included 20 patients aged ≥17 years who underwent evaluation through a structured transition pathway consisting of multidisciplinary team meetings, a joint pediatric-adult transition clinic, and subsequent follow-up in adult endocrinology. Demographic, clinical, treatment, and transition-related data were extracted from medical records. The primary outcome was successful transition, defined as at least one adult endocrinology visit within 12 months. Secondary outcomes included attendance at the transition clinic, follow-up continuity, and treatment modifications. Results: All patients underwent multidisciplinary evaluation, and 85% attended the joint transition clinic. Successful transfer to adult endocrinology was achieved in 90% (18/20), while regular follow-up during the first year was maintained in 75%. Retention was highest in patients with OI, MAS, XLH, vitamin D-dependent rickets, and DiGeorge syndrome (100%). Greater variability was observed in postoperative and primary hypoparathyroidism. Treatment adjustments were required in 40% of patients, including optimization of phosphate/calcitriol replacement and reassessment of bisphosphonate or burosumab therapy. Three patients were lost to follow-up. No acute transition-related complications were observed. Conclusions: In this small exploratory cohort, implementation of a structured multidisciplinary transition pathway was feasible and was accompanied by high transfer and one-year retention rates. Observed differences across diagnostic subgroups should be interpreted cautiously, and larger multicenter comparative studies are needed to evaluate the effectiveness of structured transition frameworks.
2026-05-01 | A RARE CASE OF HYPOCALCEMIA–INDUCED DILATED CARDIOMYOPATHY
Abstract Dilated cardiomyopathy is conventionally characterized by systolic dysfunction and left ventricular or biventricular dilatation not explained byabnormal loading conditions or coronary artery disease. A 41–year–old man was admitted to the ER with shortness of breath. He complained also flu–like syndrome with productive coughin the previous weeks. He had no history of cardiovascular risk factors, and he wasn‘t taking anydaily medication. A TTE revealed a left ventricle slightly dilated with global hypokinesis and reduced systolic function, symmetric tethering of mitral leaflets with associated moderate–to–severe mitral regurgitation. The patient was then admitted to our intensive care unit with a diagnosis of suspected myocarditis. In our ward a severe hypocalcemia (2.52 mg/dl, RR 8.60 – 10.20) was found in blood tests, with associated hyperphosphatemia, hypokalemia, hypomagnesemia and reduced PTH. TSH, FT3, FT4, TPOAb, TRAb, urinary calcium and vit–D were normal. Collecting a more detailedmedical history we found that the patient had clinical manifestations compatible with Trousseau‘s sign for several years, hypocalcemia (6.3 mg/dl) and hyperphosphatemia (7.6 mg/dl) to previous blood tests, and prolonged QT interval to a previous ECG. Coronary angiography showed no coronary stenosis. Cardiac CMR showed severe dilation and diffuse hypokinesiaof both ventricles, without late gadolinium enhancement. Hypocalcaemicdilated cardiomyopathy was diagnosed, probably caused by primary hypoparathyroidism. The patient was treated with high dose of calcium carbonateand calcitriol, with normalization of serum calcium levelsand disappearance of signs and symptoms of hypocalcemia. After two weeks of optimized HFrEF therapywith sacubitril/valsartan, empagliflozin, beta blocker and spironolactone, left ventricle EF did not improve. Therefore, an ICD was implanted. One month after discharge, in the followup echocardiographic evaluation, LV EF and EDVI were improved. Hypocalcemia is a reversible cause of dilated cardiomyopathy that warrants attention, especially in patients with electrolyte imbalances. Regular monitoring of calcium and magnesium levels, especially in patients with hypoparathyroidism or a history of thyroidectomy and prompt recognition and treatment can improve cardiac function and potentially reverse symptoms of DCM, with a favorable outcome. Further studies are needed to better understand the mechanisms linking hypocalcemia and cardiac dysfunction
2026-03-27 | Reversible hypocalcaemic cardiomyopathy following post-thyroidectomy hypoparathyroidism: a case report.
Hypocalcaemic cardiomyopathy is a rare but reversible cause of dilated cardiomyopathy (DCM) and heart failure with reduced ejection fraction, commonly associated with post-operative hypoparathyroidism. Misdiagnosis as other forms of cardiomyopathy can delay appropriate treatment and worsen outcomes. A 36-year-old male presented with progressive dyspnoea, abdominal pain, and peripheral oedema. He had a history of invasive thyroid carcinoma treated with total thyroidectomy and radioactive iodine therapy, complicated by permanent hypoparathyroidism. Despite sustained alcohol abstinence, he was misdiagnosed with alcoholic cardiomyopathy and experienced recurrent hospitalizations for heart failure despite guideline-directed medical therapy (GDMT). Evaluation revealed severe hypocalcaemia, prolonged QTc (557 ms), and echocardiographic findings of DCM with a left ventricular ejection fraction (LVEF) of 28%. Hypocalcaemic cardiomyopathy secondary to post-thyroidectomy hypoparathyroidism was diagnosed. Calcium and calcitriol supplementation, combined with GDMT, led to significant improvement. At 10 months, the patient's LVEF improved to 52%, QTc normalized to 397 ms, and symptoms resolved completely. He was transitioned to endocrinology for long-term management. Hypocalcaemic cardiomyopathy should be suspected in unexplained DCM with a history of hypoparathyroidism. Timely calcium testing and correction, along with GDMT, can reverse cardiac dysfunction and improve outcomes.
2026-03-21 | Delayed Diagnosis of HDR (Hypoparathyroidism, Deafness, and Renal Dysplasia) Syndrome Presenting With Life-Threatening Hypercalcemic Crisis: A Case Report
Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder caused by pathogenic variants in the GATA3 gene. Because the components of the clinical triad may emerge at different stages of life, isolated evaluation of findings by different specialties may lead to delayed syndromic diagnosis. In this report, we present the case of a 39-year-old female patient who was diagnosed with hypoparathyroidism following a hypocalcemia-related tetanic convulsion at the age of five years and was found to have sensorineural hearing loss during childhood. Although chronic kidney disease developed in adulthood, the multisystemic findings were not evaluated collectively, and a syndromic diagnosis was not established. The patient presented to the emergency department with altered consciousness, dehydration, and oliguria. Evaluation revealed severe hypercalcemia (20.7 mg/dL) and acute kidney injury on the background of chronic kidney disease (creatinine: 2.98 mg/dL; estimated glomerular filtration rate: 19 mL/minute/1.73 m²). Following urgent hemodialysis and intensive intravenous hydration, serum calcium levels normalized. However, complete recovery of renal function was not achieved. Genetic analysis identified a heterozygous pathogenic GATA3 frameshift variant (c.431dup), which confirmed the diagnosis of HDR syndrome. This case emphasizes the importance of a syndromic approach and early genetic evaluation in patients presenting with hypoparathyroidism, hearing loss, and renal anomalies. In addition, careful individualization of calcium and active vitamin D replacement in individuals with reduced renal reserve appears critical to prevent life-threatening hypercalcemic complications.
cell therapies
2024-02-20 | Parathyroid Allotransplantation: Report of Outcomes in 3 Patients.
Hypoparathyroidism is a relatively rare endocrine disorder defined as inadequate parathyroid hormone (PTH) secretion leading to a clinical syndrome characterized by hyperphosphatemia and hypocalcemia. This condition has high morbidity; patients present with a heterogeneous range of emotional, mental, and physical symptoms. We present our experience with PTH transplantation, using parathyroid glands surgically removed in the setting of secondary hyperparathyroidism, with a description of the clinical course, immunosuppressive management, and surgical technique. Between 2017 and 2021, 3 patients underwent parathyroid allotransplantation at the University of Illinois at Chicago. The 2 outcomes of interest were (1) symptomatic relief and improvement in calcium levels and (2) time to graft failure, defined as the presence of undetectable PTH levels. All 3 patients experienced dramatic improvement in their debilitating symptoms, even though 2 patients required repeated PTH transplantation procedures. One patient had a remarkable course with symptom resolution, normalization of PTH levels, and a great reduction in calcium supplementation. The use of hyperplastic glands from patients with secondary hyperparathyroidism undergoing 4-gland parathyroidectomy with autotransplantation represents an important source. However, a uniform definition of graft viability and prospective studies with long follow-ups are needed to address how much parathyroid tissue is optimally transplanted and the need for immunosuppression. Most patients affected by hypoparathyroidism are successfully managed by medical treatment; however, some do not respond to therapy and present debilitating symptoms related to hypocalcemia. This subgroup may benefit from parathyroid allotransplantation. Our 3 patients had remarkable improvement in their symptoms with the adoption of hyperplastic glands. Two out of 3 patients required multiple procedures to sustain symptom control.
2023-10-09 | Microencapsulation of parathyroid cells via electric field and non-surgical transplantation approach.
Hypoparathyroidism is a rare disease with low PTH, mostly seen as a consequence of neck surgery. Current management is the prescription of calcium and vitamin D, but the definitive treatment is parathyroid allotransplantation, which frequently triggers an immune response, thus cannot achieve the expected success. To overcome this problem, encapsulation of allogeneic cells is the most promising method. By optimizing the standard alginate cell encapsulation technique with parathyroid cells under high-voltage application, the authors reduced the size of parathyroid-encapsulated beads and evaluated these samples in vitro and in vivo. Parathyroid cells were isolated, and standard-sized alginate macrobeads were prepared without any electrical field application, while microbeads in smaller sizes (< 500 µm), by the application of 13 kV. Bead morphologies, cell viability, and PTH secretion were evaluated in vitro for four weeks. For the in vivo part, beads were transplanted into Sprague-Dawley rats, and after retrieval, immunohistochemistry and PTH release were evaluated in addition to the assessment of cytokine/chemokine levels. The viability of parathyroid cells in micro- and macrobeads did not differ significantly. However, the amount of in vitro PTH secretion from microencapsulated cells was significantly lower than that from macroencapsulated cells, although it increased throughout the incubation period. Immunohistochemistry of PTH staining in both of the encapsulated cells identified as positive after retrieval. Contrary to the literature, a minimal in vivo immune response was developed for alginate-encapsulated parathyroid cells, regardless of bead size. Our findings suggest that injectable, micro-sized beads obtained using high-voltage may be a promising method for a non-surgical transplantation approach.
2019-09-03 | Rare concurrence of ectopic intrathyroidal parathyroid gland and papillary thyroid carcinoma within a thyroid lobe: A care-compliant case report.
The inferior parathyroid glands derive from the third branchial pouch and seldom ectopically migrate to thyroid grand, mediastinum, thymus. Ectopic intrathyroidal parathyroid grand (ETPG) is rare and it cannot be consistently detected by any imaging examinations. The unusual ETPG is easily resected during thyroidectomy, which might cause postoperative hypoparathyroidism. Auto-transplantation of even a parathyroid gland can restore parathyroid function to some extent. Until now, there are not any guidelines on the management of ETPG. Without any symptoms, a 27-year-old female patient was admitted to our hospital for a thyroid nodule. Thyroid ultrasonography demonstrated a hypoechoic nodule, measuring 0.6 cm × 0.6 cm × 0.7 cm, with multiple punctate micro-calcifications within the right thyroid lobe. Thyroid function tests were normal. The invasive fine needle aspiration cytology for the thyroid nodule was rejected by patient. The patient was firstly diagnosed as right thyroid hypoechoic nodule, which was pathologically proved to be papillary thyroid carcinoma (PTC) finally. The patient underwent right thyroidectomy, central compartment neck dissection, parathyroid exploration, and auto-transplantation of the normal ETPG. The right thyroid hypoechoic nodule was diagnosed as PTC by pathological examination. The inferior parathyroid gland could not found in normal locations. On the cut surface of excised thyroid lobe, a yellow and soft nodule was discovered and it was pathologically diagnosed as a normal parathyroid grand. In the end, auto-transplantation of the normal ETPG was conducted. Postoperative follow-ups found both serum calcium and parathyroid hormone tests were normal. ETPG in a patient with PTC is easily overlooked and unexpectedly excised for its rarity. ETPG brings about a failed parathyroid exploration. However, within the thyroid parenchyma, it might be occasionally discovered by cutting a thyroid lobe into slices. Auto-transplantation of normal ETPG is necessary.
2016-12-20 | Living-donor parathyroid allotransplantation for therapy-refractory postsurgical persistent hypoparathyroidism in a nontransplant recipient - three year results: a case report.
Therapy-refractory persistent hypoparathyroidism after extensive neck surgery is a rare but severe complication. Parathyroid allotransplantation may represent a definitive treatment option. A 32-year old female was referred to our hospital with intractable persistent hypocalcemia after neck surgery for papillary thyroid cancer. Despite optimal medical treatment including calcium and vitamin D supplementation and even hormonal replacement therapy hypocalcemic symptoms failed to improve. The quality of life was considered very low. In light of the unsuccessful medical therapy and the young age of the patient parathyroid allotransplantation seemed an attractive treatment option to restore normal calcium homeostasis despite of the need for immunosuppressive therapy after the procedure. Therefore, we performed living-donor allotransplantation of two healthy parathyroid glands to the recipient's left forearm. The surgical intervention was successful. Neither the donor nor the recipient showed any complications. In the postoperative course clinical symptoms of hypocalcemia significantly improved whereas serum calcium and parathyroid hormone (PTH) levels progressively increased into the normal range. Former intense replacement therapy could be discontinued completely in a stepwise fashion. To date, nearly three years after transplantation, the patient remains asymptomatic with normal serum levels of calcium and PTH. Successful living-donor parathyroid allotransplantation for postsurgical hypoparathyroidism represents an innovative therapeutic strategy that could provide the definitive treatment in those patients in which the disease is therapy-refractory. The procedure can be justified even in nontransplant recipients. Retrieval of parathyroid glands from healthy donors is feasible and safe.
2011-07-14 | Cryopreservation of parathyroid glands.
The risk of permanent hypoparathyroidism following thyroid and parathyroid surgery is around 1% in the hands of experienced endocrine surgeons. Although this complication is rare, rendering a patient permanently aparathyroid has significant consequences on the health and quality of life of the patient. Immediate autotransplantation of parathyroid glands that are injured or unintentionally removed offers the best possibility of graft viability and functionality. However, since the majority of cases of hypoparathyroidism are transient, immediate autotransplantation can complicate postoperative surveillance in certain patients, especially those with primary hyperparathyroidism. Cryopreservation of parathyroid tissue is an alternate technique that was developed to treat patients with permanent hypoparathyroidism. This method allows for parathyroid tissue to be stored and then autotransplanted in a delayed fashion once permanent hypoparathyroidism is confirmed. This article provides a contemporary review on cryopreservation of parathyroid tissue and its current role in thyroid and parathyroid surgery.
proteins
2026-09-24 | Contemporary and Emerging Therapeutic Strategies in Hypoparathyroidism: From Conventional Treatment to Restoration of Parathyroid Function
Hypoparathyroidism (HypoPT) is a relatively rare condition characterised by inadequately low levels of calcium and low levels of parathyroid hormone (PTH), or a complete absence of PTH. In consequence, the body loses its ability to correctly regulate the calcium and phosphate metabolism. Low calcium levels (hypocalcemia) and high phosphorus levels (hyperphosphataemia) are observed in the blood serum of patients. Conventional therapy remains the treatment of choice, involving calcium supplementation (most often calcium carbonate) and active forms of vitamin D, such as alfacalcidol or calcitriol. However, this treatment does not always provide optimal control of the disease or a satisfying quality of life for patients. In recent years, development of therapies using PTH analogues has been observed, as well as intensive research into new pharmacological strategies modulating the PTH/PTH1R signalling pathway. The aim of this paper is to present the current state of knowledge on methods of treatment of hypoparathyroidism and to discuss the prospects for the development of new therapeutic strategies.
2026-09-14 | [Resolution of the Joint Meeting of the Expert Council "Hypoparathyroidism in the Era of Complex Problems and Breakthrough Technologies"].
On March 25, 2026, a meeting of the Expert Council entitled "Hypoparathyroidism in the Era of Complex Challenges and Breakthrough Technologies" was held in Moscow at the Endocrinology Research Centre. The meeting focused on the epidemiology of chronic hypoparathyroidism (hypoPT) in Russia, the specifics of patient management with this pathology in other countries, and the similarities and differences between international and Russian clinical guidelines.The meeting discussed advances in improving diagnostics and personalized treatment for patients with hypoPT in Russia, as well as the need to implement best practices in practical healthcare as part of the 2027 clinical guidelines revision.The importance of including chronic hypoPT in the official list of rare (orphan) diseases was highlighted, as was the need to continue studying the characteristics of the disease and its complications, diagnosis, monitoring, and prevention of hypoPT, including in the long term. The meeting also highlighted the relevance of an interdisciplinary professional alliance to achieve optimal treatment outcomes and improve the quality of life of patients with chronic hypoPT. The experts highlighted the need to implement innovative, effective treatment methods, including hormone replacement therapy for hypoPT. The Council discussed the efficacy and safety of the new therapeutic technology, TransCon parathyroid hormone. Invited expert Dilek Gogas Yavuz, MD, Professor at the Marmara University School of Medicine, Department of Endocrinology and Metabolism, Department of Internal Medicine (Istanbul, Turkey), shared her experience with the drug and the results of international clinical trials. This resolution is a summary of the issues discussed in the Council members' presentations and during the professional discussions.
2026-09-07 | Hypoparathyroidism: translating science from the laboratory to the clinic.
Chronic hypoparathyroidism is a rare endocrine disorder characterised by hypocalcaemia due to insufficient parathyroid hormone (PTH) that is associated with a multidimensional reduced quality of life, impairing physical and cognitive functioning, and compromising emotional, psychological, and social wellbeing. This Review integrates recent findings on hypoparathyroidism diagnosis, PTH analogues, calcilytics, preclinical therapeutic agents, parathyroid tissue transplantation, and pluripotent stem cell-based therapies. Emerging diagnostic technologies, including targeted genetic testing, parathyroid autoimmunity assays, and point-of-care calcium monitoring, could enable individualised and real-time management. PTH analogues with extended action (eg, palopegteriparatide, eneboparatide, and canvuparatide) show sustained activation of PTH receptors with reduced requirements for active forms of vitamin D and calcium supplements. Calcilytics (eg, encaleret) normalise calcium-sensing receptor (CaSR) hyperactivation in patients with autosomal dominant hypocalcaemia type 1 and have the potential for broader application in other forms of hypoparathyroidism. Advances in parathyroid regenerative biology with pluripotent stem cells provide platforms for future curative therapies. Progress in parathyroid autotransplantation, allotransplantation, and graft-preservation strategies further expands the therapeutic landscape. Translational research is redefining the future of hypoparathyroidism management. Developments in receptor-targeted therapies, long-acting PTH analogues, negative allosteric modulators of CaSR, and regenerative approaches reflects a shift towards restoring mineral homoeostasis to a more physiological state.
2026-08-14 | Clinical and genetic characteristics of hypoparathyroidism, deafness, and renal dysplasia syndrome in a chronic kidney disease cohort.
Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder caused by GATA-binding protein 3 (GATA3) haploinsufficiency. Although the clinical triad is well recognized, the phenotype is often incomplete, making clinical diagnosis challenging. This study aimed to elucidate the clinical and genetic characteristics of HDR syndrome in a kidney disease cohort. We retrospectively analyzed patients with absent or mild urinary abnormalities who underwent genetic testing for chronic kidney disease (CKD) between 2010 and 2025. Targeted next-generation sequencing-based kidney disease panels were used, and copy number variations were assessed using array comparative genomic hybridization. Among 1254 families with CKD, pathogenic or likely pathogenic GATA3 variants were identified in 10 patients (seven families). One additional patient with a clinically compatible phenotype carried a missense variant of uncertain significance. The median age at diagnosis was 5 years (IQR, 2-23; range, 0.7-44 years). GATA3 variants included missense (n = 3, including one variant of uncertain significance), nonsense (n = 2), short insertion/deletion (n = 2), and a whole-gene deletion (n = 1). Regarding the classical triad, hypoparathyroidism, deafness, and renal anomalies were observed in 45, 100, and 90% of patients, respectively. Only 40% exhibited the complete triad, whereas half presented deafness and renal manifestations. HDR syndrome identified in kidney disease cohorts often presents with incomplete clinical features. In patients with CKD and sensorineural deafness, HDR syndrome should be considered, and comprehensive genetic testing, including copy number analysis, is essential for accurate diagnosis.
2026-08-01 | EP293 - ECE_2725 - Clinical features of long-standing postoperative hypoparathyroidism with multiple complications
Abstract Relevance Long-standing postoperative hypoparathyroidism is a rare endocrine disorder with significant clinical interest due to its chronic course and systemic complications. Prolonged use of active vitamin D metabolites carries a high risk of renal and extraskeletal complications. Renal complications, including nephrocalcinosis and nephrolithiasis, occur in 20%-40% of patients. This case demonstrates the severe consequences of conventional therapy and highlights the need for reconsideration of treatment strategies. Aim To analyze the clinical course of long-standing postoperative hypoparathyroidism with systemic complications, evaluate limitations and risks of standard therapy using active vitamin D metabolites, and emphasize the need for transition to parathyroid hormone therapy to prevent progression and preserve organ function. Case description Hypoparathyroidism affects approximately 20-40 per 100 000 population, mainly postoperative. In Kazakhstan, reliable epidemiological data are limited due to restricted access to specialized care, insufficient laboratory diagnostics, and absence of national registries. Standard therapy with active vitamin D metabolites does not replicate parathyroid hormone effects and causes chronic hypercalciuria and elevated calcium–phosphate product, mechanisms underlying renal and extraskeletal complications. The patient has a 20-year history of endocrine disease. At 23, she underwent total thyroidectomy for diffuse toxic goiter, complicated by persistent hypoparathyroidism and hypothyroidism, requiring lifelong hormone replacement. Pregnancy at 32 occurred with chronic hypocalcemia, requiring careful monitoring and therapy adjustment. From age 34, she received alfacalcidol 3-5 μg/day, maintaining normocalcemia. At 46, nephrocalcinosis and a left renal calculus were detected; at 48, nephrolithiasis exacerbation led to acute kidney injury (eGFR 24 mL/min). Surgery was performed, and alfacalcidol reduced to 2 μg/day. At 49, partial renal recovery (eGFR 58 mL/min) was observed, but recurrent hypocalcemia required an increase to 3 μg/day. At 50, a right renal calculus was identified. At 52, brain MRI revealed basal ganglia calcifications. Conclusions Even with normocalcemia, conventional therapy with active vitamin D metabolites does not prevent severe systemic complications. Progressive nephrocalcinosis, recurrent nephrolithiasis, renal function decline, and cerebral calcifications highlight the limited efficacy of this approach. Transition to recombinant parathyroid hormone therapy is pathogenetically justified, clinically appropriate, and may help prevent further progression of systemic complications while preserving organ function.
antibodies
2025-05-14 | Severe hypocalcemia due to osteoblastic bone metastases in a patient with hypoparathyroidism: a case report.
Bone metastases in breast cancer are typically osteolytic but can rarely be osteoblastic. While malignancy-related hypercalcemia is well-known, malignancy-related hypocalcemia is rare and often multifactorial. We present a case of a 48-year-old woman with metastatic breast cancer who developed severe hypocalcemia due to a combination of expanding osteoblastic bone metastases and hypoparathyroidism after total thyroidectomy. Despite oral and intravenous calcium supplementation, adequate calcium levels were not achieved until the patient responded to systemic therapy with Trastuzumab Deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate. This case underscores the challenges in finding the cause of and managing hypocalcemia in patients with complex oncological histories and emphasizes the need for close calcium monitoring in patients with bone metastases, particularly those with additional risk factors such as hypoparathyroidism or treatment with anti-resorptive drugs.
small molecules
2026-08-11 | Hypocalcaemic cardiomyopathy with recurrent heart failure: a natural rechallenge case report with 30-month follow-up.
Hypocalcaemic cardiomyopathy is a rare but potentially reversible cause of heart failure (HF), yet it remains under-recognized in clinical practice. Evidence supporting a direct causal relationship is limited, particularly with regard to relapse and long-term follow-up. A 71-year-old woman with post-thyroidectomy hypoparathyroidism presented with new-onset HF characterized by progressive exertional dyspnoea, orthopnoea, and paroxysmal nocturnal dyspnoea. Echocardiography revealed left ventricular and left atrial dilatation with a reduced left ventricular ejection fraction (34%) and severe functional mitral regurgitation. Electrocardiography showed sinus rhythm with prolonged corrected QT interval and T-wave inversion. Coronary angiography excluded significant coronary disease, and no alternative causes of HF were identified. Laboratory testing demonstrated severe hypocalcaemia (1.18 mmol/L) and suppressed parathyroid hormone levels. Despite guideline-directed HF therapy, symptoms failed to improve. Intravenous and oral calcium supplementation, together with calcitriol, led to rapid symptomatic and functional recovery. Two months later, discontinuation of calcium supplementation resulted in recurrent hypocalcaemia and relapse of HF, despite ongoing guideline-directed HF therapy, and again resolved after calcium repletion. During 30 months of follow-up, adherence to supplementation maintained calcium homeostasis and was associated with preserved cardiac function, with no further HF recurrence. This case illustrates reversible and recurrent hypocalcaemic cardiomyopathy and highlights the importance of calcium homeostasis. The reproducible dechallenge-rechallenge pattern observed on two occasions provides clinically relevant evidence supporting a causal relationship between hypocalcaemia and myocardial dysfunction. Long-term biochemical monitoring and sustained adherence to calcium and vitamin D supplementation are important to prevent recurrence in patients with hypoparathyroidism.
2026-07-28 | Successful Transition in Rare Metabolic Bone Diseases: One-Year Outcomes of a Multidisciplinary Pediatric-Adult Program.
Background and Objectives: Pediatric-onset metabolic bone diseases, including osteogenesis imperfecta (OI), hypophosphatemic rickets (XLH), hypoparathyroidism, and McCune-Albright syndrome (MAS), require lifelong follow-up because of persistent skeletal fragility, biochemical abnormalities, and functional morbidity extending into adulthood. However, evidence regarding structured transition from pediatric to adult care in these rare disorders remains limited. This study evaluated one-year outcomes of a multidisciplinary transition program for adolescents and young adults with rare metabolic bone diseases. Materials and Methods: This retrospective cohort study included 20 patients aged ≥17 years who underwent evaluation through a structured transition pathway consisting of multidisciplinary team meetings, a joint pediatric-adult transition clinic, and subsequent follow-up in adult endocrinology. Demographic, clinical, treatment, and transition-related data were extracted from medical records. The primary outcome was successful transition, defined as at least one adult endocrinology visit within 12 months. Secondary outcomes included attendance at the transition clinic, follow-up continuity, and treatment modifications. Results: All patients underwent multidisciplinary evaluation, and 85% attended the joint transition clinic. Successful transfer to adult endocrinology was achieved in 90% (18/20), while regular follow-up during the first year was maintained in 75%. Retention was highest in patients with OI, MAS, XLH, vitamin D-dependent rickets, and DiGeorge syndrome (100%). Greater variability was observed in postoperative and primary hypoparathyroidism. Treatment adjustments were required in 40% of patients, including optimization of phosphate/calcitriol replacement and reassessment of bisphosphonate or burosumab therapy. Three patients were lost to follow-up. No acute transition-related complications were observed. Conclusions: In this small exploratory cohort, implementation of a structured multidisciplinary transition pathway was feasible and was accompanied by high transfer and one-year retention rates. Observed differences across diagnostic subgroups should be interpreted cautiously, and larger multicenter comparative studies are needed to evaluate the effectiveness of structured transition frameworks.
2026-05-01 | A RARE CASE OF HYPOCALCEMIA–INDUCED DILATED CARDIOMYOPATHY
Abstract Dilated cardiomyopathy is conventionally characterized by systolic dysfunction and left ventricular or biventricular dilatation not explained byabnormal loading conditions or coronary artery disease. A 41–year–old man was admitted to the ER with shortness of breath. He complained also flu–like syndrome with productive coughin the previous weeks. He had no history of cardiovascular risk factors, and he wasn‘t taking anydaily medication. A TTE revealed a left ventricle slightly dilated with global hypokinesis and reduced systolic function, symmetric tethering of mitral leaflets with associated moderate–to–severe mitral regurgitation. The patient was then admitted to our intensive care unit with a diagnosis of suspected myocarditis. In our ward a severe hypocalcemia (2.52 mg/dl, RR 8.60 – 10.20) was found in blood tests, with associated hyperphosphatemia, hypokalemia, hypomagnesemia and reduced PTH. TSH, FT3, FT4, TPOAb, TRAb, urinary calcium and vit–D were normal. Collecting a more detailedmedical history we found that the patient had clinical manifestations compatible with Trousseau‘s sign for several years, hypocalcemia (6.3 mg/dl) and hyperphosphatemia (7.6 mg/dl) to previous blood tests, and prolonged QT interval to a previous ECG. Coronary angiography showed no coronary stenosis. Cardiac CMR showed severe dilation and diffuse hypokinesiaof both ventricles, without late gadolinium enhancement. Hypocalcaemicdilated cardiomyopathy was diagnosed, probably caused by primary hypoparathyroidism. The patient was treated with high dose of calcium carbonateand calcitriol, with normalization of serum calcium levelsand disappearance of signs and symptoms of hypocalcemia. After two weeks of optimized HFrEF therapywith sacubitril/valsartan, empagliflozin, beta blocker and spironolactone, left ventricle EF did not improve. Therefore, an ICD was implanted. One month after discharge, in the followup echocardiographic evaluation, LV EF and EDVI were improved. Hypocalcemia is a reversible cause of dilated cardiomyopathy that warrants attention, especially in patients with electrolyte imbalances. Regular monitoring of calcium and magnesium levels, especially in patients with hypoparathyroidism or a history of thyroidectomy and prompt recognition and treatment can improve cardiac function and potentially reverse symptoms of DCM, with a favorable outcome. Further studies are needed to better understand the mechanisms linking hypocalcemia and cardiac dysfunction
2026-03-27 | Reversible hypocalcaemic cardiomyopathy following post-thyroidectomy hypoparathyroidism: a case report.
Hypocalcaemic cardiomyopathy is a rare but reversible cause of dilated cardiomyopathy (DCM) and heart failure with reduced ejection fraction, commonly associated with post-operative hypoparathyroidism. Misdiagnosis as other forms of cardiomyopathy can delay appropriate treatment and worsen outcomes. A 36-year-old male presented with progressive dyspnoea, abdominal pain, and peripheral oedema. He had a history of invasive thyroid carcinoma treated with total thyroidectomy and radioactive iodine therapy, complicated by permanent hypoparathyroidism. Despite sustained alcohol abstinence, he was misdiagnosed with alcoholic cardiomyopathy and experienced recurrent hospitalizations for heart failure despite guideline-directed medical therapy (GDMT). Evaluation revealed severe hypocalcaemia, prolonged QTc (557 ms), and echocardiographic findings of DCM with a left ventricular ejection fraction (LVEF) of 28%. Hypocalcaemic cardiomyopathy secondary to post-thyroidectomy hypoparathyroidism was diagnosed. Calcium and calcitriol supplementation, combined with GDMT, led to significant improvement. At 10 months, the patient's LVEF improved to 52%, QTc normalized to 397 ms, and symptoms resolved completely. He was transitioned to endocrinology for long-term management. Hypocalcaemic cardiomyopathy should be suspected in unexplained DCM with a history of hypoparathyroidism. Timely calcium testing and correction, along with GDMT, can reverse cardiac dysfunction and improve outcomes.
2026-03-21 | Delayed Diagnosis of HDR (Hypoparathyroidism, Deafness, and Renal Dysplasia) Syndrome Presenting With Life-Threatening Hypercalcemic Crisis: A Case Report
Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder caused by pathogenic variants in the GATA3 gene. Because the components of the clinical triad may emerge at different stages of life, isolated evaluation of findings by different specialties may lead to delayed syndromic diagnosis. In this report, we present the case of a 39-year-old female patient who was diagnosed with hypoparathyroidism following a hypocalcemia-related tetanic convulsion at the age of five years and was found to have sensorineural hearing loss during childhood. Although chronic kidney disease developed in adulthood, the multisystemic findings were not evaluated collectively, and a syndromic diagnosis was not established. The patient presented to the emergency department with altered consciousness, dehydration, and oliguria. Evaluation revealed severe hypercalcemia (20.7 mg/dL) and acute kidney injury on the background of chronic kidney disease (creatinine: 2.98 mg/dL; estimated glomerular filtration rate: 19 mL/minute/1.73 m²). Following urgent hemodialysis and intensive intravenous hydration, serum calcium levels normalized. However, complete recovery of renal function was not achieved. Genetic analysis identified a heterozygous pathogenic GATA3 frameshift variant (c.431dup), which confirmed the diagnosis of HDR syndrome. This case emphasizes the importance of a syndromic approach and early genetic evaluation in patients presenting with hypoparathyroidism, hearing loss, and renal anomalies. In addition, careful individualization of calcium and active vitamin D replacement in individuals with reduced renal reserve appears critical to prevent life-threatening hypercalcemic complications.
cell therapies
2024-02-20 | Parathyroid Allotransplantation: Report of Outcomes in 3 Patients.
Hypoparathyroidism is a relatively rare endocrine disorder defined as inadequate parathyroid hormone (PTH) secretion leading to a clinical syndrome characterized by hyperphosphatemia and hypocalcemia. This condition has high morbidity; patients present with a heterogeneous range of emotional, mental, and physical symptoms. We present our experience with PTH transplantation, using parathyroid glands surgically removed in the setting of secondary hyperparathyroidism, with a description of the clinical course, immunosuppressive management, and surgical technique. Between 2017 and 2021, 3 patients underwent parathyroid allotransplantation at the University of Illinois at Chicago. The 2 outcomes of interest were (1) symptomatic relief and improvement in calcium levels and (2) time to graft failure, defined as the presence of undetectable PTH levels. All 3 patients experienced dramatic improvement in their debilitating symptoms, even though 2 patients required repeated PTH transplantation procedures. One patient had a remarkable course with symptom resolution, normalization of PTH levels, and a great reduction in calcium supplementation. The use of hyperplastic glands from patients with secondary hyperparathyroidism undergoing 4-gland parathyroidectomy with autotransplantation represents an important source. However, a uniform definition of graft viability and prospective studies with long follow-ups are needed to address how much parathyroid tissue is optimally transplanted and the need for immunosuppression. Most patients affected by hypoparathyroidism are successfully managed by medical treatment; however, some do not respond to therapy and present debilitating symptoms related to hypocalcemia. This subgroup may benefit from parathyroid allotransplantation. Our 3 patients had remarkable improvement in their symptoms with the adoption of hyperplastic glands. Two out of 3 patients required multiple procedures to sustain symptom control.
2023-10-09 | Microencapsulation of parathyroid cells via electric field and non-surgical transplantation approach.
Hypoparathyroidism is a rare disease with low PTH, mostly seen as a consequence of neck surgery. Current management is the prescription of calcium and vitamin D, but the definitive treatment is parathyroid allotransplantation, which frequently triggers an immune response, thus cannot achieve the expected success. To overcome this problem, encapsulation of allogeneic cells is the most promising method. By optimizing the standard alginate cell encapsulation technique with parathyroid cells under high-voltage application, the authors reduced the size of parathyroid-encapsulated beads and evaluated these samples in vitro and in vivo. Parathyroid cells were isolated, and standard-sized alginate macrobeads were prepared without any electrical field application, while microbeads in smaller sizes (< 500 µm), by the application of 13 kV. Bead morphologies, cell viability, and PTH secretion were evaluated in vitro for four weeks. For the in vivo part, beads were transplanted into Sprague-Dawley rats, and after retrieval, immunohistochemistry and PTH release were evaluated in addition to the assessment of cytokine/chemokine levels. The viability of parathyroid cells in micro- and macrobeads did not differ significantly. However, the amount of in vitro PTH secretion from microencapsulated cells was significantly lower than that from macroencapsulated cells, although it increased throughout the incubation period. Immunohistochemistry of PTH staining in both of the encapsulated cells identified as positive after retrieval. Contrary to the literature, a minimal in vivo immune response was developed for alginate-encapsulated parathyroid cells, regardless of bead size. Our findings suggest that injectable, micro-sized beads obtained using high-voltage may be a promising method for a non-surgical transplantation approach.
2019-09-03 | Rare concurrence of ectopic intrathyroidal parathyroid gland and papillary thyroid carcinoma within a thyroid lobe: A care-compliant case report.
The inferior parathyroid glands derive from the third branchial pouch and seldom ectopically migrate to thyroid grand, mediastinum, thymus. Ectopic intrathyroidal parathyroid grand (ETPG) is rare and it cannot be consistently detected by any imaging examinations. The unusual ETPG is easily resected during thyroidectomy, which might cause postoperative hypoparathyroidism. Auto-transplantation of even a parathyroid gland can restore parathyroid function to some extent. Until now, there are not any guidelines on the management of ETPG. Without any symptoms, a 27-year-old female patient was admitted to our hospital for a thyroid nodule. Thyroid ultrasonography demonstrated a hypoechoic nodule, measuring 0.6 cm × 0.6 cm × 0.7 cm, with multiple punctate micro-calcifications within the right thyroid lobe. Thyroid function tests were normal. The invasive fine needle aspiration cytology for the thyroid nodule was rejected by patient. The patient was firstly diagnosed as right thyroid hypoechoic nodule, which was pathologically proved to be papillary thyroid carcinoma (PTC) finally. The patient underwent right thyroidectomy, central compartment neck dissection, parathyroid exploration, and auto-transplantation of the normal ETPG. The right thyroid hypoechoic nodule was diagnosed as PTC by pathological examination. The inferior parathyroid gland could not found in normal locations. On the cut surface of excised thyroid lobe, a yellow and soft nodule was discovered and it was pathologically diagnosed as a normal parathyroid grand. In the end, auto-transplantation of the normal ETPG was conducted. Postoperative follow-ups found both serum calcium and parathyroid hormone tests were normal. ETPG in a patient with PTC is easily overlooked and unexpectedly excised for its rarity. ETPG brings about a failed parathyroid exploration. However, within the thyroid parenchyma, it might be occasionally discovered by cutting a thyroid lobe into slices. Auto-transplantation of normal ETPG is necessary.
2016-12-20 | Living-donor parathyroid allotransplantation for therapy-refractory postsurgical persistent hypoparathyroidism in a nontransplant recipient - three year results: a case report.
Therapy-refractory persistent hypoparathyroidism after extensive neck surgery is a rare but severe complication. Parathyroid allotransplantation may represent a definitive treatment option. A 32-year old female was referred to our hospital with intractable persistent hypocalcemia after neck surgery for papillary thyroid cancer. Despite optimal medical treatment including calcium and vitamin D supplementation and even hormonal replacement therapy hypocalcemic symptoms failed to improve. The quality of life was considered very low. In light of the unsuccessful medical therapy and the young age of the patient parathyroid allotransplantation seemed an attractive treatment option to restore normal calcium homeostasis despite of the need for immunosuppressive therapy after the procedure. Therefore, we performed living-donor allotransplantation of two healthy parathyroid glands to the recipient's left forearm. The surgical intervention was successful. Neither the donor nor the recipient showed any complications. In the postoperative course clinical symptoms of hypocalcemia significantly improved whereas serum calcium and parathyroid hormone (PTH) levels progressively increased into the normal range. Former intense replacement therapy could be discontinued completely in a stepwise fashion. To date, nearly three years after transplantation, the patient remains asymptomatic with normal serum levels of calcium and PTH. Successful living-donor parathyroid allotransplantation for postsurgical hypoparathyroidism represents an innovative therapeutic strategy that could provide the definitive treatment in those patients in which the disease is therapy-refractory. The procedure can be justified even in nontransplant recipients. Retrieval of parathyroid glands from healthy donors is feasible and safe.
2011-07-14 | Cryopreservation of parathyroid glands.
The risk of permanent hypoparathyroidism following thyroid and parathyroid surgery is around 1% in the hands of experienced endocrine surgeons. Although this complication is rare, rendering a patient permanently aparathyroid has significant consequences on the health and quality of life of the patient. Immediate autotransplantation of parathyroid glands that are injured or unintentionally removed offers the best possibility of graft viability and functionality. However, since the majority of cases of hypoparathyroidism are transient, immediate autotransplantation can complicate postoperative surveillance in certain patients, especially those with primary hyperparathyroidism. Cryopreservation of parathyroid tissue is an alternate technique that was developed to treat patients with permanent hypoparathyroidism. This method allows for parathyroid tissue to be stored and then autotransplanted in a delayed fashion once permanent hypoparathyroidism is confirmed. This article provides a contemporary review on cryopreservation of parathyroid tissue and its current role in thyroid and parathyroid surgery.
proteins
2026-09-24 | Contemporary and Emerging Therapeutic Strategies in Hypoparathyroidism: From Conventional Treatment to Restoration of Parathyroid Function
Hypoparathyroidism (HypoPT) is a relatively rare condition characterised by inadequately low levels of calcium and low levels of parathyroid hormone (PTH), or a complete absence of PTH. In consequence, the body loses its ability to correctly regulate the calcium and phosphate metabolism. Low calcium levels (hypocalcemia) and high phosphorus levels (hyperphosphataemia) are observed in the blood serum of patients. Conventional therapy remains the treatment of choice, involving calcium supplementation (most often calcium carbonate) and active forms of vitamin D, such as alfacalcidol or calcitriol. However, this treatment does not always provide optimal control of the disease or a satisfying quality of life for patients. In recent years, development of therapies using PTH analogues has been observed, as well as intensive research into new pharmacological strategies modulating the PTH/PTH1R signalling pathway. The aim of this paper is to present the current state of knowledge on methods of treatment of hypoparathyroidism and to discuss the prospects for the development of new therapeutic strategies.
2026-09-14 | [Resolution of the Joint Meeting of the Expert Council "Hypoparathyroidism in the Era of Complex Problems and Breakthrough Technologies"].
On March 25, 2026, a meeting of the Expert Council entitled "Hypoparathyroidism in the Era of Complex Challenges and Breakthrough Technologies" was held in Moscow at the Endocrinology Research Centre. The meeting focused on the epidemiology of chronic hypoparathyroidism (hypoPT) in Russia, the specifics of patient management with this pathology in other countries, and the similarities and differences between international and Russian clinical guidelines.The meeting discussed advances in improving diagnostics and personalized treatment for patients with hypoPT in Russia, as well as the need to implement best practices in practical healthcare as part of the 2027 clinical guidelines revision.The importance of including chronic hypoPT in the official list of rare (orphan) diseases was highlighted, as was the need to continue studying the characteristics of the disease and its complications, diagnosis, monitoring, and prevention of hypoPT, including in the long term. The meeting also highlighted the relevance of an interdisciplinary professional alliance to achieve optimal treatment outcomes and improve the quality of life of patients with chronic hypoPT. The experts highlighted the need to implement innovative, effective treatment methods, including hormone replacement therapy for hypoPT. The Council discussed the efficacy and safety of the new therapeutic technology, TransCon parathyroid hormone. Invited expert Dilek Gogas Yavuz, MD, Professor at the Marmara University School of Medicine, Department of Endocrinology and Metabolism, Department of Internal Medicine (Istanbul, Turkey), shared her experience with the drug and the results of international clinical trials. This resolution is a summary of the issues discussed in the Council members' presentations and during the professional discussions.
2026-09-07 | Hypoparathyroidism: translating science from the laboratory to the clinic.
Chronic hypoparathyroidism is a rare endocrine disorder characterised by hypocalcaemia due to insufficient parathyroid hormone (PTH) that is associated with a multidimensional reduced quality of life, impairing physical and cognitive functioning, and compromising emotional, psychological, and social wellbeing. This Review integrates recent findings on hypoparathyroidism diagnosis, PTH analogues, calcilytics, preclinical therapeutic agents, parathyroid tissue transplantation, and pluripotent stem cell-based therapies. Emerging diagnostic technologies, including targeted genetic testing, parathyroid autoimmunity assays, and point-of-care calcium monitoring, could enable individualised and real-time management. PTH analogues with extended action (eg, palopegteriparatide, eneboparatide, and canvuparatide) show sustained activation of PTH receptors with reduced requirements for active forms of vitamin D and calcium supplements. Calcilytics (eg, encaleret) normalise calcium-sensing receptor (CaSR) hyperactivation in patients with autosomal dominant hypocalcaemia type 1 and have the potential for broader application in other forms of hypoparathyroidism. Advances in parathyroid regenerative biology with pluripotent stem cells provide platforms for future curative therapies. Progress in parathyroid autotransplantation, allotransplantation, and graft-preservation strategies further expands the therapeutic landscape. Translational research is redefining the future of hypoparathyroidism management. Developments in receptor-targeted therapies, long-acting PTH analogues, negative allosteric modulators of CaSR, and regenerative approaches reflects a shift towards restoring mineral homoeostasis to a more physiological state.
2026-08-14 | Clinical and genetic characteristics of hypoparathyroidism, deafness, and renal dysplasia syndrome in a chronic kidney disease cohort.
Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder caused by GATA-binding protein 3 (GATA3) haploinsufficiency. Although the clinical triad is well recognized, the phenotype is often incomplete, making clinical diagnosis challenging. This study aimed to elucidate the clinical and genetic characteristics of HDR syndrome in a kidney disease cohort. We retrospectively analyzed patients with absent or mild urinary abnormalities who underwent genetic testing for chronic kidney disease (CKD) between 2010 and 2025. Targeted next-generation sequencing-based kidney disease panels were used, and copy number variations were assessed using array comparative genomic hybridization. Among 1254 families with CKD, pathogenic or likely pathogenic GATA3 variants were identified in 10 patients (seven families). One additional patient with a clinically compatible phenotype carried a missense variant of uncertain significance. The median age at diagnosis was 5 years (IQR, 2-23; range, 0.7-44 years). GATA3 variants included missense (n = 3, including one variant of uncertain significance), nonsense (n = 2), short insertion/deletion (n = 2), and a whole-gene deletion (n = 1). Regarding the classical triad, hypoparathyroidism, deafness, and renal anomalies were observed in 45, 100, and 90% of patients, respectively. Only 40% exhibited the complete triad, whereas half presented deafness and renal manifestations. HDR syndrome identified in kidney disease cohorts often presents with incomplete clinical features. In patients with CKD and sensorineural deafness, HDR syndrome should be considered, and comprehensive genetic testing, including copy number analysis, is essential for accurate diagnosis.
2026-08-01 | EP293 - ECE_2725 - Clinical features of long-standing postoperative hypoparathyroidism with multiple complications
Abstract Relevance Long-standing postoperative hypoparathyroidism is a rare endocrine disorder with significant clinical interest due to its chronic course and systemic complications. Prolonged use of active vitamin D metabolites carries a high risk of renal and extraskeletal complications. Renal complications, including nephrocalcinosis and nephrolithiasis, occur in 20%-40% of patients. This case demonstrates the severe consequences of conventional therapy and highlights the need for reconsideration of treatment strategies. Aim To analyze the clinical course of long-standing postoperative hypoparathyroidism with systemic complications, evaluate limitations and risks of standard therapy using active vitamin D metabolites, and emphasize the need for transition to parathyroid hormone therapy to prevent progression and preserve organ function. Case description Hypoparathyroidism affects approximately 20-40 per 100 000 population, mainly postoperative. In Kazakhstan, reliable epidemiological data are limited due to restricted access to specialized care, insufficient laboratory diagnostics, and absence of national registries. Standard therapy with active vitamin D metabolites does not replicate parathyroid hormone effects and causes chronic hypercalciuria and elevated calcium–phosphate product, mechanisms underlying renal and extraskeletal complications. The patient has a 20-year history of endocrine disease. At 23, she underwent total thyroidectomy for diffuse toxic goiter, complicated by persistent hypoparathyroidism and hypothyroidism, requiring lifelong hormone replacement. Pregnancy at 32 occurred with chronic hypocalcemia, requiring careful monitoring and therapy adjustment. From age 34, she received alfacalcidol 3-5 μg/day, maintaining normocalcemia. At 46, nephrocalcinosis and a left renal calculus were detected; at 48, nephrolithiasis exacerbation led to acute kidney injury (eGFR 24 mL/min). Surgery was performed, and alfacalcidol reduced to 2 μg/day. At 49, partial renal recovery (eGFR 58 mL/min) was observed, but recurrent hypocalcemia required an increase to 3 μg/day. At 50, a right renal calculus was identified. At 52, brain MRI revealed basal ganglia calcifications. Conclusions Even with normocalcemia, conventional therapy with active vitamin D metabolites does not prevent severe systemic complications. Progressive nephrocalcinosis, recurrent nephrolithiasis, renal function decline, and cerebral calcifications highlight the limited efficacy of this approach. Transition to recombinant parathyroid hormone therapy is pathogenetically justified, clinically appropriate, and may help prevent further progression of systemic complications while preserving organ function.
antibodies
2025-05-14 | Severe hypocalcemia due to osteoblastic bone metastases in a patient with hypoparathyroidism: a case report.
Bone metastases in breast cancer are typically osteolytic but can rarely be osteoblastic. While malignancy-related hypercalcemia is well-known, malignancy-related hypocalcemia is rare and often multifactorial. We present a case of a 48-year-old woman with metastatic breast cancer who developed severe hypocalcemia due to a combination of expanding osteoblastic bone metastases and hypoparathyroidism after total thyroidectomy. Despite oral and intravenous calcium supplementation, adequate calcium levels were not achieved until the patient responded to systemic therapy with Trastuzumab Deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate. This case underscores the challenges in finding the cause of and managing hypocalcemia in patients with complex oncological histories and emphasizes the need for close calcium monitoring in patients with bone metastases, particularly those with additional risk factors such as hypoparathyroidism or treatment with anti-resorptive drugs.
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Drug Discovery Landscape
15 orphan drug designations for Rare hypoparathyroidism, including 5 approved therapies.
15 orphan drug designations for Rare hypoparathyroidism, including 5 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Canvuparatide | peptides | EMA | Somerville Development Partners B.V. | |
fatty acylated parathyroid (prodrug) hormone agonist | peptides | FDA | MBX Biosciences | |
PTH(1-34)-Cys(succinimido-PEG-vitamin D) amide (human) acetate salt | proteins | FDA | Extend Biosciences Inc. | |
[Ala1,3,12,Gln10,Arg11,Trp14]PTH(1-14)/[Ala18,22, Lys26]PTHrP(15-36)COOH | peptides | EMA | Amolyt Pharma | |
Encaleret sulfate | small molecules | EMA | BridgeBio Pharma Europe B.V. | |
H-Ala-Val-Ala-Glu-Ile-Gln-Leu-Met-His-Gln-Arg-Ala-Lys-Trp-Ile-Gln-Asp-Ala-Arg-Arg-Arg-Ala-Phe-Leu-His-Lys-Leu-Ile-Ala-Glu-Ile-His-Thr-Ala-Glu-Ile-OH | peptides | FDA | Amolyt Pharma SAS (formerly Alize Pharma III SAS) | |
Poly(oxy-1,2-ethanediyl), alpha-hydro-omega-methoxy, ether with N-[[[2-[[6-[[1-[3-[[3-(2,3-dihydroxypropoxy)propyl]amino]-3-oxopropyl]-2,5-dioxo-3-pyrrolidinyl]thio]hexyl]amino]ethyl]amino]carbonyl]-2-methylalanyl-teriparatide (2:1) [Yorvipath] | proteins | EMA | Approved | Ascendis Pharma Bone Diseases A/S |
palopegteriparatide [Yorvipath] | proteins | FDA | Approved | Ascendis Pharma Bone Diseases A/S |
Teriparatide | peptides | EMA | Boyd Consultants Limited | |
non-peptide small molecule orally available agonist of the parathyroid hormone receptor type I | small molecules | FDA | Chugai Pharma USA, LLC | |
teriparatide | proteins | FDA | Entera Bio, Ltd. | |
Recombinant human parathyroid hormone [Natpar] | proteins | EMA | Approved | Takeda Pharmaceuticals International AG Ireland Branch |
parathyroid hormone [Natpara] | proteins | FDA | Approved | Takeda Pharmaceuticals U.S.A., Inc. |
Synthetic Human Parathyroid Hormone 1-34 | peptides | FDA | Rare Disease Therapeutics, Inc. | |
Teriparatide [Parathar] | peptides | FDA | Approved | Rhone-Poulenc Rorer Pharmaceuticals, Inc. |
“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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