Pituitary-independent Cushing's syndrome in a horse.
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The human adrenal cortex is a complex endocrine organ that secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids arise from morphologically and biochemically distinct zones of the adrenal gland. Studying secretion of these distinct steroid hormones has, in the past, required the isolation of cells from each of the adrenocortical zones. Indeed, the lack of a human adrenocortical cell line retaining the ability to produce any of the major adrenal steroid products has slowed studies on normal and abnormal adrenal function. This obstacle has now been largely overcome with the availability of H295 cells, which represents the first adrenocortical cell line to maintain the ability, under specified conditions, to produce all the adrenocortical steroids (i.e., mineralocorticoids, glucocorticoids, and adrenal androgens). Thus, H295 cells appear to act as pluripotent adrenocortical cells capable of being directed to produce each of the zone-specific steroids. The H295 cell line should prove to be of value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis.
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The hypothalamic-pituitary-adrenal (HPA) axis in the aging male (adrenopause) is characterized by an unexplained reduction of DHEA secretion while ACTH and cortisol show no major changes, except for a lower amplitude of 24-h fluctuations and a tendency to higher cortisol values in the evening and night (especially in dementia). As a consequence, the cortisol/DHEAS ratio tends to be higher. Adrenocortical morphology reveals an age-related reduction in the thickness of the zona reticularis, and an increase of microhemorrhagic events. This may be one of the underlying causes of the age-dependent high frequency of adrenal nodules incidentally found in the elderly, which may seldom be hormonally active.
We report a rare case of bilateral adrenocortical adenomas causing ACTH-independent Cushing's syndrome at different periods 9 yr apart. The subject, a 24-yr-old woman, in June 1989 had a typical Cushingoid appearance. Her baseline plasma cortisol levels did not show a diurnal rhythm and she had a very low baseline plasma ACTH level. Plasma cortisol levels could not be suppressed by overnight low-dose or two-day high-dose dexamethasone suppression test. Marked uptake of 131I-6beta-iodomethyl-19-norcholesterol (NP-59) was observed in the right adrenal gland. Abdominal computed tomography (CT) showed a right adrenal tumor. The right adrenal gland with adenoma was removed. The non-tumorous part of the adrenal cortex was atrophic. By April 1998, she had experienced a weight gain of more than 20 kg over a two-yr period. The baseline plasma cortisol levels were at the lower limit of the normal range with loss of diurnal rhythmicity. The baseline plasma ACTH levels were very low. Neither a two-day low-dose nor a two-day high-dose dexamethasone suppression test could suppress serum cortisol or urinary free cortisol levels. NP-59 adrenal scan revealed increased uptake of the left adrenal gland at 72 h after intravenous injection of the tracer. Abdominal CT and magnetic resonance imaging (MRI) all demonstrated a left adrenal mass. Left adrenalectomy was performed in June 1998; histological features showed a cortical adenoma and atrophic change in the non-tumorous part of the adrenal cortex. Elevated plasma ACTH levels after bilateral adrenalectomy could be suppressed with conventional corticosteroid replacement therapy and overnight low-dose dexamethasone suppression test.
A case of adenoma of the adrenal cortex accompanied by Conn's syndrome has been described. Its enormous size and interesting microscopic structure draw our particular attention.
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The article reports on a case of functioning adrenal carcinoma in a woman of 40 with concomitant in situ carcinoma of the portio (CIN 3). She had had amenorrhoea for 14 months and early menopause was suspected. Hirsutism and other signs of virilization such as clitoromegaly and voice changes were detected upon hospitalization.. The characteristic of the clinical case is given by hormone production involving not only androgens of prevalently adrenal genesis (dehydroepiandrosterone, dehydroepiandrosterone sulphate and androstenedione), but also testosterone, more suggestive of a gonadal neoplasm. The adrenal carcinoma only produced androgens, as plasma cortisol and aldosterone concentrations were normal. Diagnosis of adrenal carcinoma was first made with hormone assays and then with the adrenal block test using dexamethasone, with adrenal ecography and abdomino-pelvic computed tomography (CT). When amenorrhoea is present and hirsutism and other signs of virilization occur ex-novo in a short period, in a woman of fertile age, a thorough endocrine study must be carried out. According to the hormone profile, the next diagnostic step should be aimed at detecting a prospective ovarian or adrenal neoplasm.
A 47-year-old female presented with hypertension, hypokalaemia, low plasma renin, high plasma aldosterone and was found to have a left adrenal tumour 4 cm in diameter by computerized tomography. Detailed biochemical studies showed high plasma levels of 11-deoxycorticosterone and corticosterone in addition to aldosterone and 18-hydroxycorticosterone. Basal 11-deoxycorticosterone levels were particularly high. Corticosterone, 18-hydroxycorticosterone and aldosterone concentrations were abnormally sensitive to infusions of ACTH and angiotensin II. Plasma cortisol and assays for sex hormones were normal although there was evidence that cortisol derived from the neoplasm. At operation a well-differentiated adrenocortical carcinoma weighing 50 g (56 X 30 X 36 mm) was removed. There was no evidence of metastases following surgery. Adrenal function returned to normal. Review of the literature suggests that adrenocortical carcinoma should be suspected in patients who otherwise have typical features of Conn's syndrome, but whose tumours are more than 3 cm in diameter. Measurement of steroids such as 11-deoxycorticosterone in addition to aldosterone is recommended since abnormally high values may also help to distinguish between hyperaldosteronism due to adenoma and carcinoma. Previously reported cases of isolated aldosterone production by a carcinoma cannot be substantiated.
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