CLINICAL AND GENETIC-ANALYSIS OF PRIMARY BILATERAL ADRENAL DISEASES (MICRO-AND MACRONODULAR DISEASE) LEADING TO CUSHING-SYNDROME

Primary bilateral adrenocortical diseases are rare entities that have recently been appreciated as potential causes of Gushing syndrome. The y include (i) primary pigmented adrenocortical disease (PPNAD), also k nown as ''micronodular adrenal disease'', which is a genetic disorder that is often associated with Carney complex, and (ii) massive macrono dular adrenocortical disease (MMAD), a rare disorder of unknown etiolo gy that affects older adults. Carney complex is a multiple endocrine n eoplasia (MEN) syndrome that affects not only the adrenal cortex, but also the pituitary, thyroid, and gonads. It is associated with pigment ation abnormalities as well as myxomas and other mesenchymal and neura l crest neoplasms. The inheritance of the complex is autosomal dominan t, and genetic mapping has shown that at least two loci are involved i n its pathogenesis. MMAD appears to be an isolated finding in most cas es, 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 M EN type-1, but this finding is not always associated with hypercortiso lism. The genetic defects for these diseases are known, but their role in adrenal cortex pathophysiology has not been fully elucidated. Iden tification of the molecular defects responsible for bilateral adrenoco rtical disorders is expected to shed light on many aspects of early ad renal gland differentiation and tumorigenesis.