Endocrine Abstracts

In 1981, study of the adrenal findings in 4 cases of Cushing syndrome caused by an unusual bilateral adrenal disorder led to characterization of a unique pathologic condition that was termed primary pigmented nodular adrenal disease (PPNAD). Review of the literature showed that the disorder had occurred in 19 patients, including 6 siblings from 2 families. In 1 family, the disorder occurred in 2 siblings; a third sibling, one without Cushing syndrome, died of cardiac myxoma. To test the hypothesis that there was a connection between PPNAD and cardiac myxoma, a search of the world literature and Mayo Clinic records was launched for patients with both conditions. The search identified 1 Mayo Clinic patient, a 33-year-old woman who died in 1957, with both conditions found at autopsy. The patient’s record revealed that she was “covered in pigmented moles” and had had a “myxomatous fibroadenoma” of the breast excised. A review of the literature on cardiac myxoma revealed that here were 2 types of the tumor, nonfamilial and familial, and that rare cases of the latter were variously associated with cutaneous pigmented spots, cutaneous and mammary myxomas, large–cell calcifying Sertoli cell tumors of the testis, and growth hormone–producing pituitary adenoma. In 1985, all these conditions were assembled into a unifying syndrome and reported as “the complex of myxomas, spotty pigmentation, and endocrine overactivity”; the disorder was subsequently titled the Carney complex. In 1986, autosomal dominant transmission of the syndrome was found. In 2000, mutations of the PRKAR1A gene were found in 30% of affected families. Transgenic mice with downregulation of the gene exhibited non-dexamethasone suppressible hypercorticosteronemia (but not microscopic PPNAD) and a series of benign and malignant neural and soft tissue tumors.