Search

Patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) usually present bilateral benign adrenocortical macronodules at imaging and variable levels of cortisol excess. PBMAH is a rare cause of primary overt Cushing's syndrome but may represent up to one-third of bilateral adrenal incidentalomas with evidence of cortisol excess. The increased steroidogenesis in PBMAH is often regulated by various G protein–coupled receptors (GPCRs) aberrantly expressed in PBMAH tissues; some receptor ligands are ectopically produced in PBMAH tissues, creating aberrant autocrine/paracrine regulation of steroidogenesis.The bilateral nature of PBMAH and familial aggregation led to the identification of germline heterozygous inactivating mutations of the ARMC5 gene, in 20% to 25% of the apparent sporadic cases and more frequently in familial cases; ARMC5 mutations/pathogenic variants can be associated with meningiomas. More recently, combined germline mutations/pathogenic variants and somatic events inactivating the KDM1A gene were specifically identified in patients affected by glucose-dependent insulinotropic peptide (GIP)-dependent PBMAH. Functional studies demonstrated that inactivation of KDM1A leads to GIP-receptor (GIPR) overexpression and over- or downregulation of other GPCRs. Genetic analysis is now available for early detection of family members of index cases with PBMAH carrying identified germline pathogenic variants. Detailed biochemical, imaging, and comorbidity assessment of the nature and severity of PBMAH is essential for its management. Treatment is reserved for patients with overt or mild cortisol/aldosterone or other steroid excesses, taking in account comorbidities. It previously relied on bilateral adrenalectomy; however, recent studies tend to favor unilateral adrenalectomy or, less frequently, medical treatment with cortisol synthesis inhibitors or specific blockers of aberrant GPCR.

Besides their growth-promoting properties, GH and IGF-1 regulate a broad spectrum of biological functions in several organs, including the kidney. This review focuses on the renal actions of GH and IGF-1, taking into account major advances in renal physiology and hormone biology made over the last 20 years, allowing us to move our understanding of GH/IGF-1 regulation of renal functions from a cellular to a molecular level. The main purpose of this review was to analyze how GH and IGF-1 regulate renal development, glomerular functions, and tubular handling of sodium, calcium, phosphate, and glucose. Whenever possible, the relative contributions, the nephronic topology, and the underlying molecular mechanisms of GH and IGF-1 actions were addressed. Beyond the physiological aspects of GH/IGF-1 action on the kidney, the review describes the impact of GH excess and deficiency on renal architecture and functions. It reports in particular new insights into the pathophysiological mechanism of body fluid retention and of changes in phospho-calcium metabolism in acromegaly as well as of the reciprocal changes in sodium, calcium, and phosphate homeostasis observed in GH deficiency. The second aim of this review was to analyze how the GH/IGF-1 axis contributes to major renal diseases such as diabetic nephropathy, renal failure, renal carcinoma, and polycystic renal disease. It summarizes the consequences of chronic renal failure and glucocorticoid therapy after renal transplantation on GH secretion and action and questions the interest of GH therapy in these conditions.