Cortisol-producing Adenomas Research Articles

Acth sensitivity of isolated human pathological adrenocortical cells: Variability of responses in aldosterone, corticosterone, deoxycorticosterone and cortisol production

In vitro aldosterone, deoxycorticosterone, corticosterone and cortisol production of human adrenocortical cells derived from adenomas (Conn's syndrome, Cushing's syndrome), from hyperplastic adrenals (Cushing's syndrome) and from adrenals surrounding aldosteronoma are described. Cells from adenomas causing either Cushing's syndrome or Conn's syndrome harboured the highest basal and ACTH-stimulated corticosteroid production. Adrenocortical cells derived from micronodular hyperplasia causing Cushing's syndrome and cells from cortisol producing adenoma displayed predominantly cortisol and corticosterone secretion both under basal conditions and following stimulation with ACTH. Aldosteronoma cells showed highly variable aldosterone, deoxyeorticosterone, corticosterone and cortisol response to ACTH. However, in aldosteronoma cell suspensions, the basal and ACTH-stimulated ratios of aldosterone to cortisol were increased when compared to ratios of steroids produced by cells from other adrenal tissues. Chronic treatment with spironolactone of patients with Conn's syndrome before surgery was associated with a decreased ratio of aldosterone to corticosterone, revealing that 18-hydroxylase in aldosteronoma cells may be inhibited during long-term therapy. Non-tumorous cells isolated from adrenals surrounding aldosteronoma displayed less aldosterone prior to and after stimulation with ACTH than aldosteronoma cells.

Presence of ectopic beta-adrenergic receptors on human adrenocortical cortisol-producing adenomas.

A direct binding study of radioligand [3H]dihydroalprenolol (DHA), a potent beta-adrenergic antagonist, was performed on the particulate fractions of four adrenocortical adenomas (three cortisol-producing adenomas and one aldosterone-producing adenoma) and normal adrenal tissues. The effect of epinephrine on cortisol production was also evaluated in vitro from the cultured tumor cells from one cortisol-producing adenoma. Saturable binding of [3H]DHA to the tumor membranes was observed in two of three cortisol-producing adenomas, but not in the aldosterone-producing adenoma or in normal adrenal tissues. Scatchard analysis of equilibrium binding of [3H]DHA revealed a single class of binding sites on the tumor membranes; the apparent dissociation constant (Kd) was 1 nM in each, and the numbers of binding sites were 108 and 45 fmol/mg protein, respectively. Competition by adrenergic agents with [3H]DHA for binding sites on the membranes from one cortisol-producing adenoma revealed that (+/-)propranolol, a beta-adrenergic antagonist, was about 350-fold more potent than phentolamine, an alpha-adrenergic antagonist, suggesting the beta-adrenergic nature of receptor sites. In addition, stereospecificity was demonstrated by about 1000-fold greater affinity of (-)alprenolol than to (+)alprenolol, both of which are stereoisomers of the beta-adrenergic antagonist. Furthermore, production of cortisol from the cultured tumor cells prepared from the same adenoma was significantly stimulated by epinephrine in addition to ACTH. These data indicate that ectopic beta-adrenergic receptor sites are present in some human adrenocortical tumors which may be functionally related to the activation of adenylate cyclase by catecholamines other than ACTH in those tumors, as previously demonstrated. The mechanism by which such altered cellular membrane characteristics occur in association with neoplastic alteration of the endocrine tissues remains unanswered.

Computed tomography in adrenal tumors.

Computed tomography (CT) was used to evaluate 26 patients with a variety of adrenal lesions. Surgical proof was available in 22 patients and clinical confirmation with a variety of other studies in the other four patients. Nine patients ahd aldosterone-producing adrenal adenomas and CT correctly identified seven. Four patients had cortisol-producing adenomas and five patients had cortisol-producing carcinomas; CT identified each of these tumors. Prominent but normal shaped glands were seen in each of the four patients with adrenal hyperplasia. Adrenal metastases from malignant melanoma in two patients were identified. Only one of two pheochromocytomas in two patients could be seen on CT. CT is a noninvasive method of localizing adrenal tumors and may be helpful in distinguishing adenomas from adrenal hyperplasia.

SHORT‐TERM FLUCTUATIONS IN PLASMA CORTISOL IN CUSHING'S SYNDROME

Short-term fluctuations in plasma cortisol were determined overnight in twelve patients with Cushing's syndrome: eight patients with bilateral adrenal hyperplasia of hypothalamic-pituitary orgin, three patients with a cortisol producing adenoma and one patient with a carcinoma of the adrenal cortex. While either secretory episodes in plasma cortisol or a fixed pattern of cortisol secretion were observed both in patients with pituitary dependent and in those with pituitary independent hypercorticism, a typical night-day variation in plasma cortisol was only found in one of the eight patients with Cushing's syndrome of hypothalamic-pituitary origin. The patient with a cortisol producing carcinoma showed only minor fluctuations in plasma cortisol throughout the test period. The results indicate that no discrimination can be made between patients with pituitary dependent or independent Cushing's syndrome by demonstrating an episodic or a fixed secretion of cortisol. It seems, however, that the finding of a typical night-day variation in hormone secretion points to hypercorticism of hypothalamic-pituitary orgin.

131I-19-iodocholesterol scintigraphy of the adrenal cortex.

131-I-19-iodocholesterol scintigraphy of the adrenal cortex has been carried out in 26 patients. In 4 patients with normal adrenocortical function the tracer was equally accumulated on the two sides. In 7 patients with untreated Cushing's syndrome, bilateral uptake was found in 4 patients with bilateral hyperplasia whereas unilateral visualization was obtained in three cases of cortisol producing adenomas. The side localization was confirmed at operation. Eight patients had been operated for Cushings syndrome prior to the scintigraphy. Remnant adrenocortical tissue with negligible or subnormal function (4 patients) could not be visualized. Normo- or hyperfunctioning remnant tissue was visualized in 3 patients. One patient had recurrent hypercorticism due to metastases from a previously removed adrenocortical carcinoma; a single pelvic accumulation was seen, whereas several metastases in the abdomen and thorax were not visualized. Four patients with aldosteronism were investigated. Three had primary aldosteronism due to an adrenocortical adenoma. In two of these, the site of the adrenal lesion was localized pre-operatively. In the third patient, equal bilateral accumulation of iodocholesterol was seen even after suppression with dexamethasone. At operation a small tumour was found. In 1 patient with indeterminate aldosteronism both glands were visualized and at a second examination the uptake was equally suppressed by dexamethasone.