2026-04-24 | Deterioration Of Blood Lipids During Early Postoperative Remission Of Cushing's Syndrome: A Longitudinal Cohort Study.

Cushing´s syndrome (CS) is associated with an unfavorable lipid profile. However, data on lipid alterations during early postoperative remission, a particularly cardiovascular vulnerable period, are lacking. Evaluation of lipid profiles during active CS and the early postoperative period. In this single-center cohort study at LMU Hospital Munich, we analyzed lipid profiles (Total cholesterol, LDL, HDL, ApoA1, ApoB, Lipoprotein (a), Triglycerides and Non-esterified fatty acids) and metabolic markers in 26 patients with endogenous CS before surgery and 1, 3, 6, 12 and 24 months (n=23) after curative surgery, and compared them with 26 age-, BMI-, and sex-matched controls without hypercortisolism at baseline. Paradoxically most lipid parameters postoperatively worsened. One month postoperatively, HDL (1mo postoperative 38 mg/dL [35-46] vs. active CS 49.5 mg/dL [45-61.3], p<0.0001) and ApoA1 concentrations (1mo postoperative 160 mg/dL [147-168] vs. active CS 193 mg/dL [169-211], p<0.0001) were significantly lower compared to preoperative levels. Similarly one month following surgery triglycerides concentrations (1mo postoperative 185 mg/dL [154-218] vs. active CS 129 mg/dL [89.3-186] preoperatively, p<0.0001) were higher. These changes remained evident until 6 months post-surgery. The triglyceride-glucose index increased during early remission and showed a positive correlation with inflammatory markers CRP and IL-6. Non-esterified fatty acids displayed three distinct postoperative trajectories depending on BMI at baseline. During the early remission phase following curative surgery, we observed a further deterioration in lipid parameters. This can affect cardiovascular health and provides the basis for targeted therapy.

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2026-04-09 | "Glucocorticoids, Cushing syndrome and cellular senescence: a mechanistic link to metabolic ageing".

Glucocorticoids are key regulators of immune, stress and inflammatory responses, as well as of multiple metabolic pathways throughout life, and they play an anabolic role in tissue and organ development. Chronic glucocorticoid excess, whether due to endogenous Cushing syndrome, long-term pharmacological treatment or persistent stress, induces tissue-specific alterations that closely resemble those seen during physiological ageing. These shared changes include loss of tissue regenerative capacity, altered body composition, impaired glucose and lipid homeostasis and increased cardiovascular and neuropsychiatric vulnerability. Emerging evidence indicates that glucocorticoid excess can promote cellular senescence, amplify proinflammatory signalling and disrupt interorgan communication, thereby accelerating a state of metabolic ageing. This review synthesises current clinical and experimental data linking glucocorticoid excess with cellular senescence in key metabolic organs and systems, including adipose tissue, skeletal muscle, liver, bone, the cardiovascular system and the brain. Particular emphasis is placed on chronic neoplastic hypercortisolism as a human model, while also considering prolonged pharmacological glucocorticoid exposure and sustained stress as more prevalent, subclinical sources of hormonal overload. By integrating these lines of evidence, we outline the emerging concept of glucocorticoid-driven metabolic ageing and highlight potential mechanistic targets along the glucocorticoid axis and within senescence pathways. A better understanding of these mechanisms may inform strategies to prevent or mitigate age-related metabolic and cardiovascular complications in patients with Cushing syndrome, in individuals exposed to long-term glucocorticoid therapy and in the broader ageing population.

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2026-03-20 | Early hypocortisolism with persistent remission following osilodrostat in a patient with long-standing Cushing disease.

Cushing syndrome is a disorder of endogenous hypercortisolism characterized by increased morbidity and mortality; when surgery is not curative or feasible, medical therapies targeting pituitary adrenocorticotropic hormone or adrenal cortisol production are essential. We report a case of early-onset hypocortisolism and sustained remission following a brief osilodrostat therapy in a 70-year-old woman with Cushing disease who had been treated for many years with pasireotide and metyrapone. Ten days after initiating osilodrostat, she developed clinical signs of adrenal insufficiency and a low morning serum cortisol of 2.8 µg/dL (SI: 76 nmol/L) (reference range 7-25 µg/dL [SI: 193-690 nmol/L]); osilodrostat was discontinued, and glucocorticoid replacement was initiated, remaining glucocorticoid-replacement dependent at low doses for 2 months. Over subsequent follow-up of over 20 months, her 24-hour urinary free cortisol normalized, and she maintained persistent biochemical and clinical eucortisolism off all Cushing therapy, with no relapse of hypercortisolism. She also experienced weight loss of 16.5 kg and marked improvement in diabetes control, enabling discontinuation of insulin and glucagon-like peptide-1 (GLP-1) receptor agonist therapy. This is among the earliest documented cases of osilodrostat-induced hypocortisolism with long sustained hormonal remission after treatment discontinuation, emphasizing the need for early monitoring and prolonged follow-up.

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