Endocrine Abstracts

The zonation of the human adrenal cortex has long been established morphologically and histologically as three distinct layers of cells. The outer zona glomerulosa (ZG) comprises densely packed cells arranged in clusters that produce aldosterone; the zona fasciculata (ZF) is composed of cells with large cytoplasm, containing lipid droplets arranged in radial columns that synthetize cortisol; and the zona reticularis is composed of compact and pigmented cells producing androgen...

Objective: To describe the Carney Complex (CNC) manifestations presented by patients harboring the PRKAR1A mutation c.709(-7-2)del (one of the three hotspots) in a large cohort of patients.Methods: Multicenter retrospective study. Age at the diagnosis or at the screening of the different CNC manifestations is described by mean ± standard deviation.Results: Forty patients [12 index cases, 27 females, 46±15 years o...

Illegitimate membrane receptors are known to play a role in cortisol secretion in adrenal adenomas and ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing’s syndrome. Conversely, illegitimate receptors have never been described in primary pigmented nodular adrenal disease (PPNAD). In the normal adrenal gland, serotonin (5-HT) has been shown to stimulate cortisol secretion through activation of 5-HT receptor type 4 (5-HT4) whereas, in some AIMAH tissu...

Some elegant clinical observations of dysregulated cortisol-secretion in cases of ACTH-independent macronodular hyperplasia (AIMAH) and more rarely adrenocortical adenomas (ACA) have led to the concept of ‘aberrant’ or ‘illegitimate’ membrane receptors (AR) in adrenal Cushing syndrome. It this situation cortisol secretion is regulated by an extra-cellular ligand that usually does not stimulate cortisol secretion in normal adrenals. This abnormal response mi...

Illicit expression of membrane receptors for circulating regulatory factors, such as GIP and LH receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of serotonin, arginine vasopressin and ACTH in a subpopulation of steroidogenic cells in two AIMAH tissues. The aim of the present study was: (i) to investigate the presence of ACTH by immunohistochem...

Testicular adrenal rest tumors (TART) are frequently detected in male patients with 21-hydroxylase (21-OH) deficiency. Increase in plasma ACTH levels, due to cortisol deficit, is responsible for TART growth. Indeed, glucocorticoid substitution reduces both plasma ACTH and TART development in the majority of patients. Nevertheless, some patients with TART are resistant to the glucocorticoid treatment, suggesting the existence of other factors stimulating TART growth. The aim of...

We have shown that 5-hydroxytryptamine (5-HT) receptor type 4 (5-HT4R) agonists stimulate aldosterone production in patients with aldosterone-producing adenoma (APA). Moreover, 5-HT-positive cells were observed in APA tissues and 5-HT4R mRNAs were markedly overexpressed in APAs in comparison with normal adrenals. All these results suggested that 5-HT produced by adrenal mast cells could be involved in the physiopathology of APAs. The aim of this work was to investigate the rol...

A 48-year-old woman was referred for ACTH-independent Cushing’s syndrome associated with a left adrenal tumor. Contrasting with hypercortisolism-related hypertension and hypokalemia, renin and aldosterone levels were paradoxically increased. The tumor was surgically removed and pathological examination of the tissue established the diagnosis of corticosurrenaloma. Fragments of the tumor were obtained for in situ hybridization, immunohistochemical and cell incubatio...

In the human adrenal gland, serotonin (5-HT), released by subcapsular mast cells strongly stimulates aldosterone production via activation of the type 4 serotonin receptor (5-HT4R). Consistently, plasma aldosterone levels increase after administration of 5-HT4R agonists like cisapride to healthy volunteers. Previous studies performed in aldosterone producing adenomas (APA) have shown an increase in mast cells density and an overexpression of HTR4 gene, encoding 5-HT4R...

Pheochromocytomas/paragangliomas (PPGL) are catecholamine-producing neuroendocrine tumors that account for less than 1% of all hypertension cases. Despite their rarity, these tumors must be early detected and treated to prevent potentially life-threatening adrenergic crises. Unfortunately, PPGL are frequently unrecognized during pregnancy, leading to a high risk of either maternal or fetal complications. In return, pregnancy can trigger catecholamine secretory discharges in pa...