Endocrine Abstracts

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestation...

Cushing syndrome (CS) is a chronic and debilitating condition with high morbidity and mortality. Development of novel, safe, and effective pharmacologic therapies with improved risk-benefit profiles would enrich treatment options for patients. Relacorilant is a selective glucocorticoid receptor (GR) modulator that competitively antagonizes cortisol activity and, unlike the FDA-approved GR antagonist mifepristone, does not bind to the progesterone receptor. In a phase 2 study i...

Cushing’s disease (CD), caused by a corticotroph pituitary adenoma, is associated with multi-system morbidity and when untreated or suboptimally treated with an increased mortality. Transsphenoidal adenomectomy is the first choice of treatment for CD. Medical treatment is an option in patients in whom surgery is not successful or not feasible. Medical therapy for CD can be classified into pituitary-directed drugs, adrenal-blocking drugs and glucocorticoid receptor antagon...

Cushing’s syndrome (CS) is characterized by chronic overproduction of cortisol resulting in significant morbidity and, when untreated, an increased mortality. CS is divided into adrenocorticotropin (ACTH)-dependent CS and ACTH-independent CS. ACTH-dependent CS, the majority of cases, can be caused by a corticotroph pituitary adenoma and, more rarely, by ectopic ACTH production. ACTH-independent CS is usually caused by an unilateral adrenal adenoma and less frequent by an ...

Background: Early diagnosis of Cushing’s syndrome and initiation of effective treatment are essential to limit long-term morbidity and early mortality. However, diagnosis is often delayed due to the non-specificity of symptoms, or because symptoms are not recognised by physicians, leading to more complex treatment needs and a worsening of patient quality of life. A survey was conducted to better understand the patient experience of Cushing’s syndrome and the true b...

Introduction: Adequate hormone replacement therapy in adrenal insufficiency is essential. Patients should have basic knowledge about their condition and what to do in situations which could trigger an adrenal crisis. Education on how and when hydrocortisone replacement therapy should be adjusted as well as instruction and practice an emergency injection are considered important measures to prevent an adrenal crisis. A standardized nurse-led group-based education programme (GEP...

Prolonged spontaneous remission of hypercortisolemia in ectopic ACTH syndrome after long-term treatment with steroidogenesis inhibitors has been described. Direct drug effect on the adrenal glands, effects on tumoral ACTH secretion and/or POMC gene expression have been suggested. Medical treatment could be used for symptoms, but also for disease control.Materials and methods: In human BON-1 and DMS-79 cells, we have evaluated the effects of keto...

Introduction: Temozolomide (TMZ) treatment has been used for aggressive pituitary tumours with positive results, but has proven ineffective in controlling tumour regrowth in cases of disease recurrence. TMZ resistance has been linked to the expression of O6-methyl-guanine-DNA-methyltransferase (MGMT) protein and mismatch repair components (MMR). In the present study, we describe the development of an in vitro model of acquired resistance to TMZ and the mechanisms invo...

Background: Osilodrostat is an oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step in cortisol biosynthesis. In a 22-week, phase II study, osilodrostat treatment normalised mean urinary free cortisol (mUFC) in 78.9% (15/19) of patients with uncontrolled Cushing’s disease and was well tolerated. The present phase 3 study is designed to confirm the safety and efficacy of osilodrostat in patients with uncontrolled Cushing’s disease...

Cushing’s syndrome (CS) during pregnancy is a rare metabolic condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of the overlapping features of fatigue, weight gain, striae, and emotional changes that occur during normal pregnancy. The clinical presentation together with laboratory and imaging findings help to make a diagnosis. However, changes in maternal hormones and their binding proteins complicate assessment of the normal ...