Faculty Collaboration Database

Adult-onset hypogonadotropic hypogonadism caused by aberrant expression of aromatase in an adrenocortical adenocarcinoma. Endocr J 2010;57(7):651-6

Date

05/15/2010

Pubmed ID

20467160

DOI

10.1507/endocrj.k10e-046

Scopus ID

2-s2.0-77955776534 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Estrogen-secreting adrenal cancers are extremely rare, with feminizing symptoms attributed to aromatase expression in the adrenal tumor. We describe a case of hypogonadotropic hypogonadism as a consequence of aberrant aromatase expression in a patient with adrenocortical adenocarcinoma. A 54 year-old man presented with a two month history of gynecomastia and reduced libido. Endocrine biochemistry at presentation showed hypogonadotropic hypogonadism (LH 2.4 U/L, FSH <1.0 IU/L, testosterone 2.8 nmol/L) with increased serum estrone (E(1), 821 pmol/L) and estradiol (E(2), 797 pmol/L) and subclinical ACTH-independent hypercortisolism (serum cortisol post 1mg overnight dexamethasone suppression test, 291 nmol/L). A right adrenal mass was identified on CT scanning and the patient underwent an open adrenalectomy. Post-operative evaluation showed normalization of serum levels of E(1) (95 pmol/L), E(2 )(109 pmol/L), testosterone (11.4 nmol/L), LH (4.1 U/L) and FSH (5.9 IU/L), and of cortisol dynamics. Immunohistochemistry of the adrenal cancer confirmed aberrant expression of aromatase in most, although not all, carcinoma cells. Transcripts associated with utilization of promoters II, I.1 and I.3 were prominently represented in the tumor aromatase mRNA. This case highlights that clinical features of feminizing adrenocortical carcinomas can be secondary to estrogen production by aberrantly transcribed and translated aromatase within the tumor. Even in males, gonadotropin secretion is subject to predominantly estrogen-mediated feedback-inhibition. The diagnosis of adrenocortical adenocarcinoma should be considered in men presenting with low testosterone and gonadotropins, particularly in the presence of feminizing features.

Author List

Advani A, Johnson SJ, Nicol MR, Papacleovoulou G, Evans DB, Vaikkakara S, Mason JI, Quinton R

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adrenal Cortex Neoplasms
Adult
Age of Onset
Aromatase
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Humans
Hypogonadism
Male
Middle Aged