Adrenocortical hyperplasia: A multifaceted disease.

Adrenocortical hyperplasia may develop in different contexts. Primary adrenal hyperplasia may be secondary to primary bilateral macronodular adrenocortical hyperplasia (PBMAH) or micronodular bilateral adrenal hyperplasia (MiBAH) which may be divided in primary pigmented nodular adrenocortical disease (PPNAD) and isolated micronodular adrenocortical disease (i-MAD). Both lead to oversecretion of cortisol and potentially to Cushing's syndrome. Moreover, adrenocortical hyperplasia may be secondary to longstanding ACTH stimulation in ACTH oversecretion as in Cushing's disease, ectopic ACTH secretion or glucocorticoid resistance syndrome and congenital adrenal hyperplasia secondary to various enzymatic defects within the cortex. Finally, idiopathic bilateral adrenal hyperplasia is the most common cause of primary aldosteronism. We will discuss recent findings on the multifaceted forms of adrenocortical hyperplasia.

Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias.

Adrenocortical causes of Cushing's syndrome include the following: common cortisol-producing adenomas, which are usually isolated (without associated tumors) and sporadic (without a family history); rare, but often clinically devastating, adrenocortical carcinomas; and a spectrum of adrenocorticotropin-independent, and almost always bilateral, hyperplasias, which are not rare, and are the most recently recognized cause. The majority of benign lesions of the adrenal cortex seem to be linked to abnormalities of the cyclic AMP signaling pathway, whereas cancer is linked to aberrant expression of insulin-like growth factor II, tumor protein p53 and related molecules. In this article, we propose a new clinical classification and nomenclature for the various forms of adrenocorticotropin-independent adrenocortical hyperplasias that is based on their histologic and genetic features. We also review the molecular genetics of adrenocortical tumors, including recent discoveries relating to the role of phosphodiesterase 11A. This is a timely Review because of recent advances in the clinical and molecular understanding of these diseases.

[Current aspects of diagnosis and treatment of symptomatic arterial hypertension of adrenal genesis]. / Sovremennye aspekty diagnostiki i lecheniia simtomaticheskikh arterial'nykh gipertonii nadpochechnikovogo geneza.

AIM: To analyse the experience in diagnosis and treatment of arterial hypertension (AH) of adrenal genesis. MATERIAL AND METHODS: A total of 243 patients with adrenal AH (mean age 46.3 +/- 3.2 years) were examined. 134 of them had endogenic adrenohypercorticism (EAH), 62--primary hyperaldosteronism (PHA), 47--chromaffin tissue tumors (CTT). Diurnal urinary excretion of adrenal hormones (epinephrine, norepinephrine, aldosteron, hydrocortisone) and peripheral blood hormones (aldosteron, renin, hydrocortisone, ACTH) were measured. Topic diagnosis was made with ultrasound, computed tomography, MR-imaging, angiography, adrenal venous sampling and 123I-MIBG scintigraphy. RESULTS: Adrenalectomy was made in 224 patients (predominantly with tumor lesions). 19 patients (idiopathic hyperaldosteronism, advanced adrenocortical carcinoma) were treated conservatively (calcium antagonists, ACE inhibitors, AT1-receptor blockers, spironolacton). Good results of the surgical treatment were achieved in 60% patients with aldosterone-producing adenoma and adrenal Cushing's syndrome as well as in 80.5% patients with pheochromocytoma. Long-term outcomes depend on hypertension duration, histologic type of the tumor, age and family hypertension history (risk of essential hypertension). CONCLUSION: Hypertension of adrenal origin occurs more frequently than it was supposed previously. Its late diagnosis may be due to lack of typical signs and symptoms, insufficient application of novel diagnostic techniques and poor alertness of physicians. It is recommended to include tests for adrenal hormones in urine and blood and ultrasound investigation of the adrenals in a complex of primary examination of patients with severe refractory hypertension.

Premature pubarche: etiological heterogeneity.

Premature pubarche is characterized by pubic hair, adult type body odor, acne, and axillary hair before 8 yr of age in girls and 9.5 yr of age in boys. Causes of this premature virilization include premature adrenarche, mild errors of steroidogenesis, precocious puberty, and adrenal and gonadal tumors. To determine whether any clinical parameters are helpful in distinguishing which children should undergo further evaluation for mild congenital adrenal hyperplasia, we performed ACTH stimulation tests in 69 children with premature pubarche and 8 pubertal controls. Patients were categorized as having typical (pubic hair with or without axillary hair and body odor) or atypical (pubic hair and genital enlargement) premature pubarche. Blood samples, before and 30 min after iv bolus administration of synthetic ACTH, were obtained for progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 11-deoxycortisol, and cortisol measurements. The patients were divided into 4 groups based on their individual responses to ACTH stimulation: premature adrenarche (no apparent defect in steroidogenesis), possible decreased 21-hydroxylase activity, possible decreased 3 beta-hydroxysteroid dehydrogenase activity, and indeterminate responses. Five of 11 (45%) children with atypical premature pubarche and 7 of 58 (12%) children with typical premature pubarche were found to have evidence of mild defects in steroidogenesis. Similar to previous reports in postpubertal women, only responses to ACTH stimulation allowed accurate classification of these patients.

CT and MR imaging of massive macronodular adrenocortical disease: a rare cause of autonomous primary adrenal hypercortisolism.

We studied four patients with adrenocorticotropic hormone (ACTH)-independent hypercortisolism due to bilateral massive enlargement of the adrenal glands. The combined weight of the adrenal glands ranged from 69 to 149 g and the adrenal cortex was replaced in three of four patients by multiple nodules ranging from microscopic to 4 cm in diameter. One patient had massive diffuse enlargement. All patients had low or undetectable levels of serum ACTH, absence of petrosal sinus to peripheral gradients of ACTH in bilateral samples from the inferior petrosal sinuses before and after stimulation by corticotropin releasing hormone, and absence of an adenoma on MR imaging of the pituitary gland. The marked degree of adrenocortical enlargement and absence of ACTH dependency separates this massive macronodular disease from the more common ACTH-dependent macronodular hyperplasia encountered in older patients with pituitary-dependent Cushing disease. All patients required bilateral adrenalectomy to control hypercortisolism. We present the spectrum of nodular adrenal disease associated with hypercortisolism and a differential diagnosis based on morphologic criteria.