A Case of Estrogen-secreting Adrenocortical Carcinoma with Subclinical Cushing's Syndrome

Abstract

Abstract.A 25-year-old man was found to have a large right adrenal mass detected by abdominal echography and computed tomography, and presented with a mild gynecomastia. Endocrine study showed increased serum concentrations and urinary excretion of estrogens and dehydroepiandorosterone sulfate (DHEA-S). The patient had no Cushingoid features but autonomous cortisol secretion, compatible with the diagnosis of subclinical Cushing's syndrome. Surgical removal of the adrenal tumor led to normalization of serum and urinary excretion of estrogens and DHEA-S. Histopathological examination revealed a high-grade adrenocortical carcinoma (ACC). The disorganized expression of all the steroidogenic enzymes in individual tumor cells was demonstrated by immunohistochemical analysis, and the abundant expression of both aromatase mRNA and insulin-like growth factor (IGF)-II mRNA was shown by RT-PCR. These data suggest the excessive secretion of estrogen as well as the ineffective steroidogenesis by the adrenal tumor. This is a very rare case of estrogen-secreting ACC associated with subclinical Cushing's syndrome.

Feminizing Adrenocortical Carcinoma with Selective Suppression of Follicle-Stimulating Hormone Secretion and Disorganized Steroidogenesis: A Case Report and Literature Review

“…Cortisol overproduction is often detected in cases with estrogen-producing tumors (17). No hypercortisolemia was observed, although the present case had high levels of 17-OH progesterone, 17-OH pregnenolone and 11deoxycortisol, all precursors of cortisol.…”

“…Previous reports described that a possibility of extra-adrenal aromatization cannot be excluded even though expression of CYP19 was detected in the ACC (22,23). On the other hand, some reports indicated that hypersecretion of estrogen by tumor cells induced feminizing in some ACC cases (17,24,25). Therefore, we think that the cause of the high level of estrogen in the present case was induced by not only an excess production by ACC but also extra-adrenal aromatization.…”

“…Since there was no case with only estrogen-secreting ACC, they described that estrogen-secreting ACC was rare. As shown in Table 3, only five cases have been reported in Japan to date (17).…”

Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma

“…3), while the expression of both CYP17 and CYP11B1 mRNA showed no significant differences between ACC and ACA. The expression of aromatase mRNA increased in only one (Case 1) who showed feminization symptoms [11].…”

“…Two ACC patients (Cases 1, 4) presented with SCS who had suppressed plasma ACTH levels (<5 pg/mL), lack of cortisol diurnal rhythm and its nonsuppressibility of cortisol to high-dose (8mg) dexamethasone suppression test (DST), and one (Case 1) with gynecomastia had high estrogen and DHEA-S levels [11]. Serum DHEA-S levels in ACC were significantly elevated (3137 ±1262 ng/mL) compared to those of ACA (155 ± 44 ng/mL).…”