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.
Key words
Primary Pigmented Adrenocortical Disease (PPNAD) - Massive Macronodular Adrenocortical
Disease (MMAD) - Carney Complex - MEN 1 - Tumors - Genetics
