Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol.

Purpose: To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.

Methods: Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension.

Prolonged Adrenal Insufficiency After Osilodrostat Exposure With Eventual Recovery of Adrenal Function.

Osilodrostat is an 11β-hydroxylase inhibitor used in the treatment of adult patients with Cushing disease. Prolonged adrenal insufficiency (AI) after osilodrostat use is a rare but significant adverse effect. We present the case of a 41-year-old woman treated with osilodrostat for persistent hypercortisolism following pituitary surgery and Gamma Knife radiosurgery.

Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine.

Context: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly.

Objective: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs).

Methods: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.

Improvement in clinical features of hypercortisolism during osilodrostat treatment: findings from the Phase III LINC 3 trial in Cushing's disease.

Purpose: Cushing's disease is associated with substantial morbidity and impaired quality of life (QoL) resulting from excess cortisol exposure. The current study explored improvements in clinical signs and additional specific manifestations of hypercortisolism during osilodrostat (potent oral 11β-hydroxylase inhibitor) therapy by degree of control of mean urinary free cortisol (mUFC).

Methods: LINC 3 (NCT02180217) was a prospective, open-label, 48-week study of osilodrostat (starting dose: 2 mg bid; maximum: 30 mg bid) that enrolled 137 adults with Cushing's disease and mUFC > 1.

Equity in Obesity Review.

Obesity disproportionately affects racial and ethnic minoritized populations and those of lower socioeconomic status. Similarly, disparities exist in the development of its downstream consequences, such as type 2 diabetes and hypertension. The causes of these disparities are multifactorial and are influenced by structural factors such as segregation and healthcare access, and individual-level factors such as weight stigma.

Growth hormone replacement in adults with cured acromegaly: Efficacy and safety.

Between 2% and 60% of patients with cured acromegaly may eventually develop growth hormone deficiency. In adults, growth hormone deficiency is associated with abnormal body composition, decreased exercise capacity and quality of life, dyslipidemia, insulin resistance and increased cardiovascular risk. Similar to patients with other sellar lesions, the diagnosis of growth hormone deficiency in adults with cured acromegaly generally requires stimulation testing, with the exception of patients with very low serum insulin-like growth factor I levels and multiple additional pituitary hormone deficiencies.

Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others.

Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension.

Objective: To investigate the long-term efficacy and tolerability of osilodrostat, a potent oral 11β-hydroxylase inhibitor, for treating Cushing's disease (CD).

Design/methods: A total of 137 adults with CD and mean 24-h urinary free cortisol (mUFC) > 1.5 × upper limit of normal (ULN) received osilodrostat (starting dose 2 mg bid; maximum 30 mg bid) during the prospective, Phase III, 48-week LINC 3 (NCT02180217) core study.

Dose-exposure-IGF-I response of once-weekly somapacitan in adults with GH deficiency.

Objective: Growth hormone (GH) replacement therapy in patients with adult growth hormone deficiency (AGHD) is individually titrated due to variable dose-responses among patients. The aim of this study was to provide clinical guidance on dosing and titration of the novel long-acting GH derivative somapacitan based on analyses of somapacitan dose-insulin-like growth factor I (IGF-I) responses in AGHD patients.

Design: Analyses of dosing information, 4364 somapacitan concentration samples and 4880 IGF-I samples from 330 AGHD patients treated with somapacitan in three phase 3 trials.

Recurrent Acromegaly in a Patient With a Mutation.

Background/objective: is a cell-cycle checkpoint kinase and is part of the ATM-CHEK2-p53 cascade, which is protective against carcinogenesis. We describe a germline CHEK2 mutation in a patient with acromegaly and other tumors.

Case Report: We present a woman with a germline 110delC mutation previously diagnosed with fibroadenoma of the breast and papillary thyroid carcinoma.

Diagnosis and Treatment of Acromegaly: An Update.

Acromegaly is typically caused by a growth hormone-secreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a variety of cardiovascular, respiratory, endocrine, metabolic, musculoskeletal, and neoplastic comorbidities. Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly.

Levoketoconazole: a novel treatment for endogenous Cushing's syndrome.

: Endogenous Cushing's syndrome (CS) is a rare, life-threatening endocrine disorder that is caused by chronic exposure to cortisol overproduction. Levoketoconazole (Recorlev), a 2, 4 stereoisomer of ketoconazole, is a steroidogenesis inhibitor under investigation for the treatment of CS.: This review covers the pharmacology, efficacy, and safety of levoketoconazole for the treatment of patients with endogenous CS.

Growth hormone deficiency in adults with Cushing's disease.

Growth hormone deficiency (GHD) generally occurs in patients with Cushing's disease (CD) as a consequence of cortisol excess. Mass effect may contribute to the development of GHD in the minority of patients with CD due to corticotroph macroadenomas. Patients with CD in remission are at considerable risk of GH deficiency as a consequence of pituitary surgery or radiation therapy.

Adrenally Directed Medical Therapies for Cushing Syndrome.

Context: Endogenous Cushing syndrome (CS) is characterized by excess cortisol secretion, which is driven by tumorous secretion of corticotropin in the majority of patients. Untreated, CS results in substantial morbidity and mortality. Tumor-directed surgery is generally the first-line therapy for CS.

Current concepts of the diagnosis of adult growth hormone deficiency.

In adults, growth hormone (GH) deficiency is associated with increased visceral adiposity, decreased lean body mass, bone mineral density and exercise capacity, dyslipidemia, insulin resistance, increased cardiometabolic and fracture risk, and impaired quality of life. The aim of the present article is to review the diagnosis of GH deficiency in adults. To avoid overdiagnosis of GH deficiency, it is critical to evaluate only patients at risk for pituitary dysfunction, including those who have had sellar masses, pituitary surgery, radiation therapy, traumatic brain injury, subarachnoid hemorrhage or childhood onset GH deficiency.

Advances in the Medical Treatment of Cushing Disease.

Medical therapy has an adjunctive role in management of Cushing disease. Medical therapy is recommended for patients who received pituitary radiotherapy and are awaiting its salutary effects. Medications are used preoperatively to stabilize the condition of seriously ill patients before surgery.

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.

Background: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11β-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease.

Pituitary society guidance: pituitary disease management and patient care recommendations during the COVID-19 pandemic-an international perspective.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced 'lockdowns' are the new 'norm' as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions.