Current challenges in Cushing's syndrome testing: blood, saliva, urine, or hair?

Purpose Of Review: Endogenous Cushing's syndrome is one of the most difficult diagnoses in endocrinology. It is mainly based on biochemical tests that assess qualitative and quantitative alterations in cortisol production. Whether performed on blood, saliva, urine, or hair, the biochemical tests currently available have limited diagnostic specificity and sensitivity.

Transgender-Affirming Hormone Therapies, QT Prolongation, and Cardiac Repolarization.

Importance: Transgender women (assigned male at birth) usually take antiandrogens associated with estrogens (or are castrated) to induce feminization, whereas transgender men (assigned female at birth) take testosterone to induce masculinization. However, the cardiovascular outcomes of these gender-affirming hormone therapies (GAHTs) remain poorly studied.

Objective: To examine the association between GAHT intake and cardiac repolarization alterations on electrocardiography in transgender individuals.

Surgery for the treatment of arterial hypertension in patients with unilateral adrenal incidentalomas and mild autonomous cortisol secretion (CHIRACIC): a multicentre, open-label, superiority randomised controlled trial.

Background: Adrenal incidentalomas are found in 3-10% of adults undergoing abdominal imaging. Of these, 30-50% are responsible for mild autonomous cortisol secretion (MACS), which is frequently associated with hypertension. The impact of adrenalectomy on hypertension in patients with unilateral incidentalomas and MACS remains uncertain.

Outcomes and Therapeutic Strategies for Head-and-neck Paragangliomas Associated With Succinate Dehydrogenase Mutations.

Context: Natural history and optimal therapeutic strategies of patients with head-and-neck paragangliomas (HNPGL) associated with germline mutations in succinate dehydrogenase genes (SDHx) are barely known. This study aims to describe the outcome of these patients depending on selected strategies.

Methods: We retrospectively analyzed the outcome of 65 SDHx-mutated patients presenting 108 HNPGL mostly located in the carotid (57%) and jugulotympanic (JT) (21.

The mutational landscape of ARMC5 in Primary Bilateral Macronodular Adrenal Hyperplasia: an update.

Background: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of Cushing's syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 are responsible for 20-25% of apparently sporadic PBMAH cases and 80% of familial presentations. ARMC5 screening is now routinely performed for PBMAH patients and families.

PDE11A Is a Phenotype Modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: Results of a 334-Patient Series.

Context: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal, and morphological levels. ARMC5-inactivating pathogenic variants are causative of PBMAH, and rare variants of PDE11A have been associated with PBMAH.

Objective: The aim of this study, on a large cohort of individuals with PBMAH from Europe and America, was to study the ARMC5 and PDE11A genotype to determine the genotype/phenotype correlation and to investigate the hypothesis that PDE11A could be a modifying gene of the adrenal phenotype.

Approach to the Patient With Cyclical Cushing Syndrome.

Cyclical Cushing syndrome (CS) is a subentity of CS, characterized by repeated episodes of excess cortisol (peaks) followed by spontaneous periods of normal or low cortisol secretion (troughs). Although considered rare, its prevalence reaches 70 of 514 to 91 of 514 (14%-18%) in patients with CS according to its definition in some reported series and can concern all etiologies of CS. Physicians should be alert to the presence of cyclical CS in patients with fluctuating symptoms or where the results of biochemical investigations indicate eucortisolism or hypocortisolism in patients with clinical CS.

Personalized Noninvasive Diagnostic Algorithms Based on Urinary Free Cortisol in ACTH-dependant Cushing's Syndrome.

Context: Current guidelines for distinguishing Cushing's disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary magnetic resonance imaging (MRI) as first-line investigation for all patients. CRH testing is no longer available, and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients.

Objective: To establish noninvasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters.

Impact of exenatide on weight loss and eating behavior in adults with craniopharyngioma-related obesity: the CRANIOEXE randomized placebo-controlled trial.

Importance: A major issue in the management of craniopharyngioma-related obesity (CRO) is the ineffectiveness of the current therapeutic approaches.

Objective: To study the efficacy of glucagon-like peptide-1 analogs compared with placebo in adults with obesity CRO.

Design: A double-blind multicenter superiority randomized clinical in trial in two parallel arms.

Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.

This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.

Diabetes insipidus: Vasopressin deficiency….

Diabetes insipidus is a disorder characterized by hypo-osmotic polyuria secondary to abnormal synthesis, regulation, or renal action of antidiuretic hormone. Recently, an expert group, with the support of patient associations, proposed that diabetes insipidus be renamed to avoid confusion with diabetes mellitus. The most common form of diabetes insipidus is secondary to a dysfunction of the neurohypophysis (central diabetes insipidus) and would be therefore named 'vasopressin deficiency'.

Carney complex predisposes to breast cancer: prospective study of 50 women.

Objective: Carney complex (CNC) is a rare genetic syndrome, mostly due to germline loss-of-function pathogenic variants in PRKAR1A. Carney complex includes pigmented skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical dysplasia, and various breast benign tumors.

Design: The present study was designed to describe the characteristics of breast lesions in CNC patients and their association with other manifestations of CNC and PRKAR1A genotype.

Prolonged adrenal insufficiency following discontinuation of osilodrostat treatment for intense hypercortisolism.

The cases of 3 patients with Cushing's disease who developed long-term adrenal insufficiency after discontinuation of prolonged osilodrostat therapy were recently described for the first time. We report 2 additional cases of persistent prolonged adrenal insufficiency after discontinuation of osilodrostat treatment for intense hypercortisolism due to Cushing's disease and ectopic ACTH syndrome. In addition, we show for that adrenal insufficiency in these patients was associated with low/normal 11-deoxycortisol concentrations despite high plasma ACTH concentrations.

Risk factors for intraoperative complications, postoperative complications, and prolonged length of stay after laparoscopic adrenalectomy by transperitoneal lateral approach: a retrospective cohort study of 547 procedures.

Background: Laparoscopic adrenalectomy (LA) is the gold standard for the resection of most adrenal lesions. A precise delineation of factors influencing its outcomes is lacking. The aim of this study was to assess factors associated with intraoperative complications, postoperative complications, and prolonged length of stay (LOS) after LA.

European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas.

Evidence of Persistent Mild Hypercortisolism in Patients Medically Treated for Cushing Disease: the Haircush Study.

Context: Cortisol-lowering drugs may not restore a normal cortisol secretion in Cushing disease (CD).

Objective: This work aimed to assess the long-term cortisol exposure in medically treated CD patients using hair-cortisol (HF) and hair-cortisone (HE) measurement.

Methods: This multicenter prospective study included 3 groups of female patients: CushMed = 16 treated with a stable cortisol-lowering drug dosage and normal urinary free cortisol (UFC); CushSurg = 13 cured by pituitary surgery; CushBla = 15 receiving stable recommended doses of hydrocortisone following bilateral adrenalectomy.

[Guidelines of the French National ENDOCAN-COMETE, Association of Endocrine Surgery, Society of Urology for the management of adrenocortical carcinoma].

The adrenocortical carcinoma (ACC) is a primary malignant tumor developed from the adrenal cortex, defined by a Weiss score≥3. Its prognosis is poor and depends mainly on the stage of the disease at diagnosis. Care is organized in France by the multidisciplinary expert centers of the national ENDOCAN-COMETE "Adrenal Cancers" network, certified by the National Cancer Institute.

Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism.

We report a unique case of a 44-year-old man with paraneoplastic hyperparathyroidism due to an oncocytic adrenocortical carcinoma (stage pT3N0R0M0, ENSAT 2 with a 4% Ki-67). Paraneoplastic hyperparathyroidism was associated with mild adrenocorticotropic hormone (ACTH)-independent hypercortisolism and increased estradiol secretion responsible for gynecomastia and hypogonadism. Biological investigations performed in blood samples from peripheral and adrenal veins revealed that the tumor secreted parathyroid hormone (PTH) and estradiol.

Congenital adrenal hyperplasia: New biomarkers and adult treatments.

Congenital adrenal hyperplasia (CAH) is a genetic disease caused by an enzyme deficiency interrupting adrenal steroidogenesis. It most frequently involves 21-hydroxylase, which induces adrenal insufficiency with hyperandrogenism. Restoring hormonal balance is difficult with glucocorticoids, which are the gold-standard treatment.

Cushing's syndrome in the elderly: data from the European Registry on Cushing's syndrome.

Objective: To evaluate whether age-related differences exist in clinical characteristics, diagnostic approach, and management strategies in patients with Cushing's syndrome (CS) included in the European Registry on Cushing's Syndrome (ERCUSYN).

Design: Cohort study.

Methods: We analyzed 1791 patients with CS, of whom 1234 (69%) had pituitary-dependent CS (PIT-CS), 450 (25%) adrenal-dependent CS (ADR-CS), and 107 (6%) had an ectopic source (ECT-CS).