Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess

Objective: Evaluation of postmenopausal women with suspicion of androgen-secreting tumor. Design and patients: We retrospectively studied 22 postmenopausal women referred to our center for suspicion of androgen-secreting tumor. All patients had clinical, biological, and morphological evaluation. In absence of adrenal tumors, ovarian surgery was most often proposed and immunohistochemistry (IHC) studies were performed. Results: Ovarian tumors were detected by ultrasound and/or magnetic resonance imaging in eight patients. Two adrenal androgen-secreting tumors were diagnosed by an adrenal computed tomography (CT) scan. The clinical presentation of the women with or without tumors was similar. Nevertheless, women with tumor exhibited significantly higher testosterone levels and lower basal FSH and LH levels than the other women (2.6G2.7 vs 0.9G0.9 ng/ml, P!0.05; 26.5G22.9 vs 66.5G 26.0 IU/l, P!0.01; and 12.0G8.6 vs 24.1G8.9 IU/l, P!0.05 respectively). Based on a likelihood ratio test, patients with a tumor had 8.4 and 10.8 times higher risk of having a testosterone level R1.4 ng/ml or an FSH level %35 IU/l. Finally, IHC analysis with an anti-P450c17a antibody allowed the identification of an elevated number of ovarian androgen-producing cells in five patients in whom no tumor was found. Conclusions: Androgen-secreting tumors are clinically difficult to discriminate from other causes of postmenopausal hyperandrogenism. Testosterone and FSH were the two discriminative markers in a multivariate analysis. Ovarian and adrenal tumors were detected by imaging studies. However, ovarian non-tumoral causes of hyperandrogenism may be difficult to detect with conventional histology.

Section: Discussioncontrasting

confidence: 85%

Impact of clinical, hormonal, radiological, and immunohistochemical studies on the diagnosis of postmenopausal hyperandrogenism

Sarfati

Bachelot

Coussieu

et al. 2011

“…administration of 1 mg/kg ovine CRH (oCRH). Assays were performed as previously reported (17)(18)(19).…”

Section: Patientsmentioning

confidence: 99%

Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome

Libé¹,

Coste²,

Guignat³

et al. 2010

Self Cite

Context: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare and heterogeneous condition characterized by abnormal steroid production. Cortisol secretion can be regulated by aberrant hormone receptors. Objective: A large series of patients with AIMAH were evaluated to provide information on the prevalence and profile of aberrant regulations, in relation with the functional status. Design and patients: Thirty-two consecutive patients with AIMAH were prospectively studied: 10 had a Cushing's syndrome (CS), and 22 had a subclinical CS (SCS). Methods: A baseline endocrine evaluation was followed by an in vivo protocol in search of aberrant cortisol responses (seven provocative tests). An acute inhibition test with the somatostatin analog octreotide was also performed. Results: At least one aberrant cortisol response was identified in 28 of 32 (87%) patients. The overall prevalence of aberrant responses was independent of the functional status. Responses to the upright posture and to metoclopramide were frequently observed (67 and 56% respectively). A glucagon response was frequently observed in the SCS group (58%). A cortisol inhibition by octreotide was specifically found in the three CS patients who positively responded to the mixed meal, and was observed also in 12 of 13 (92%) patients with SCS. Conclusions: Cortisol responses indicative of aberrant receptor expression were highly prevalent in AIMAH. Thorough phenotyping of AIMAH may help uncover the underlying pathophysiology.

“…There are principally three forms of adrenocortical hyperfunction, namely, primary aldosteronism (PA), Cushing's syndrome (CS), and congenital adrenal hyperplasia, although extremely rare cases such as androgen-or estrogen-secreting adrenocortical tumors have been reported (1,2). Immunohistochemistry (3)(4)(5) and in situ hybridization (6, 7) for steroidogenic enzymes have been attempted, as it is difficult to determine the adrenal function from the histological findings alone.…”

Section: Introductionmentioning

confidence: 99%

Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

Shigematsu

Nishida²,

Sakai³

et al. 2009

Design and methods: The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. Results: Immunohistochemical analysis showed that 50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria, and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. Conclusions: We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.European Journal of Endocrinology 161 939-945