Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1.
In multiple endocrine neoplasia type 1 (MEN-1), benign enlargement of the adrenal cortex has been found in about one third of necropsy cases. To elucidate the clinical and genetic characteristics of the MEN-1 adrenal lesion, we have investigated 33 MEN-1 patients. Twelve individuals (37%) demonstrated adrenal enlargement, which was bilateral in 7 of them. Histopathology revealed diffuse and nodular cortical hyperplasia, adenomas, and a single case of adrenocortical carcinoma. The apparently benign adrenal enlargements were not associated with presently ascertainable biochemical disturbances in the hypothalamic-pituitary-adrenocortical axis, and they were without radiological signs of progression during follow-up. The individual developing unilateral adrenocortical carcinoma showed rapid adrenal expansion, feminization, and an abnormal urinary steroid profile after 4 yr of observation for bilateral minor adrenal enlargements. Pancreatic endocrine tumors were significantly overrepresented and present in all MEN-1 individuals with adrenal involvement. In agreement with findings in sporadic cases, the MEN-1 adrenocortical carcinoma genome showed loss of constitutional heterozygosity for alleles at 17p, 13q, 11p, and 11q. The benign adrenal lesions retained heterozygosity for the MEN-1 locus at chromosome 11 q 13. Despite its prevalence and malignant potential, the pituitary-independent adrenocortical proliferation does not appear to be a primary lesion in MEN-1, but might represent a secondary phenomenon, perhaps related to the pancreatic endocrine tumor.
Department of Internal Medicine, University Hospital, Sweden.
B
B
Skogseid
C
C
Larsson
P G
PG
Lindgren
E
E
Kvanta
J
J
Rastad
E
E
Theodorsson
L
L
Wide
E
E
Wilander
K
K
Oberg
D000302:Adrenal Cortex / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D002880:Chromosomes, Human, Pair 11; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood; D005260:Female; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D006984:Hypertrophy / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D012150:Polymorphism, Restriction Fragment Length; D013739:Testosterone / Q000097:blood; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
D013739:Testosterone; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone