Stratakis C A, Kirschner L S
Unit on Genetics & Endocrinology, Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health & Human Development, NIH, Bethesda, MD 20892-1862, USA.
Horm Metab Res. 1998 Jun-Jul;30(6-7):456-63. doi: 10.1055/s-2007-978914.
Primary bilateral adrenocortical diseases are rare entities that have recently been appreciated as potential causes of Cushing syndrome. They include (i) primary pigmented adrenocortical disease (PPNAD), also known as "micronodular adrenal disease", which is a genetic disorder that is often associated with Carney complex, and (ii) massive macronodular adrenocortical disease (MMAD), a rare disorder of unknown etiology that affects older adults. Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects not only the adrenal cortex, but also the pituitary, thyroid, and gonads. It is associated with pigmentation abnormalities as well as myxomas and other mesenchymal and neural crest neoplasms. The inheritance of the complex is autosomal dominant, and genetic mapping has shown that at least two loci are involved in its pathogenesis. MMAD appears to be an isolated finding in most cases, and a genetic defect has not yet been defined. Ectopic expression of hormone receptors has been implicated in several cases of MMAD, but an underlying deficit has not been detected. Bilateral adrenocortical hyperplasia has also been described in McCune-Albright syndrome and MEN type-1, but this finding is not always associated with hypercortisolism. The genetic defects for these diseases are known, but their role in adrenal cortex pathophysiology has not been fully elucidated. Identification of the molecular defects responsible for bilateral adrenocortical disorders is expected to shed light on many aspects of early adrenal gland differentiation and tumorigenesis.
原发性双侧肾上腺皮质疾病是罕见的疾病，最近被认为是库欣综合征的潜在病因。它们包括：（i）原发性色素沉着性肾上腺皮质疾病（PPNAD），也称为“微结节性肾上腺疾病”，是一种常与卡尼综合征相关的遗传性疾病；（ii）巨大结节性肾上腺皮质疾病（MMAD），一种病因不明的罕见疾病，影响老年人。卡尼综合征是一种多发性内分泌肿瘤（MEN）综合征，不仅影响肾上腺皮质，还影响垂体、甲状腺和性腺。它与色素沉着异常以及黏液瘤和其他间充质和神经嵴肿瘤有关。该综合征的遗传方式为常染色体显性遗传，基因定位显示其发病机制至少涉及两个基因座。在大多数情况下，MMAD似乎是一个孤立的发现，尚未确定其遗传缺陷。在几例MMAD中发现了激素受体的异位表达，但尚未检测到潜在的缺陷。在McCune-Albright综合征和MEN 1型中也描述了双侧肾上腺皮质增生，但这一发现并不总是与皮质醇增多症相关。这些疾病的遗传缺陷是已知的，但其在肾上腺皮质病理生理学中的作用尚未完全阐明。确定导致双侧肾上腺皮质疾病的分子缺陷有望为肾上腺早期分化和肿瘤发生的许多方面提供线索。
