cortodoxone and Adenoma

Topics: 17-Hydroxycorticosteroids; Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Blood Specimen Collection; Circadian Rhythm; Corticotropin-Releasing Hormone; Cortodoxone; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Female; Humans; Hydrocortisone; Metyrapone; Peptides; Pituitary Gland; Pituitary Neoplasms; Potassium; Pregnancy; Tomography, X-Ray Computed

The prevalence of steroid secretion abnormalities was studied by evaluating the 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) responses to adrenocorticotropic hormone (ACTH) stimulation in 48 patients with 'nonfunctioning' incidentalomas and in 10 patients with 'subclinical' Cushing's syndrome.. In all patients the cortisol, 17-OHP, and S levels were measured after ACTH test. Eight patients were reinvestigated after surgery.. In patients with nonfunctioning lesions, the ACTH test induced 17-OHP and S peaks higher than in normals (p < 0.005). In 10 cases an augmented rise of 17-OHP and S was observed. In patients with subclinical Cushing's syndrome, the 17-OHP peak after ACTH was greater than in patients with nonfunctioning lesions and in normals (p < 0.005); the S peak was also higher than in controls (p < 0.005). In 7 of 8 operated patients, the exaggerated 17-OHP peak was normalized.. A combined impairment of different enzyme activities is frequently present in adrenal incidentalomas; the alteration of enzymatic pathways can also coexist with the presence of partial cortisol autonomy.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Aged; Cortodoxone; Cushing Syndrome; Female; Humans; Hydrocortisone; Male; Middle Aged

To compare the insulin hypoglycaemia test with the short overnight metyrapone test in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis posthypophysectomy.. Prospective comparative study of the insulin hypoglycaemia test and the overnight metyrapone test in 32 patients 4-6 weeks after pituitary surgery.. Thirty-two patients with known pituitary disease. None with present or previous Cushing's syndrome.. Maximum serum cortisol achieved during insulin induced hypoglycaemia compared with 0900 hours serum 11-deoxycortisol level following a weight related oral dose of metyrapone at 0000 h.. One of the 32 patients required further surgery and was studied twice after each operation. Thirty-three results are therefore compared. Twenty-six of these had a normal cortisol response of 550 nmol/l or above leading to the cessation of replacement hydrocortisone. Six of these 26 patients however, failed the metyrapone test (11-deoxycortisol level less than 200 nmol/l). After 3-40 months (median 20 months) of follow-up off steroid therapy, no patient to date has displayed any clinical evidence of steroid deficiency. Of the seven patients who failed the insulin hypoglycaemia test, six also failed the metyrapone test.. The overnight metyrapone test identified more patients with possible ACTH deficiency than the insulin hypoglycaemia test. Further follow-up of these patients is required before a final judgement can be made as to whether more subtle but clinically relevant ACTH deficiency can be detected by the metyrapone test. Our clinical follow-up to date would not support this.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Aged; Cortodoxone; Female; Follow-Up Studies; Humans; Hydrocortisone; Hypoglycemic Agents; Hypophysectomy; Hypothalamo-Hypophyseal System; Insulin; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Postoperative Period; Predictive Value of Tests; Prospective Studies

An increased response of 17-hydroxyprogesterone to ACTH stimulation has been observed in adrenal incidentaloma and linked to an impairment of either 21-hydroxylase or of 11beta-hydroxylase activity. To analyse this question further, we investigated the steroidogenic pathways in a series of 17 adrenal incidentalomas.. 17 patients (7 women, 10 men; mean age, 62 +/- 12 years) with non-histologically analyzed adrenal incidentalomas were prospectively evaluated.. The following variables were investigated: 24-h urinary methanephrines and free cortisol excretion; plasma levels of ACTH and dehydroepiandrosterone; overnight dexamethasone suppression test; 1-24 ACTH stimulation test with measurement of: cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, 11-deoxycorticosterone, progesterone, 17-hydroxypregnenolone, Delta4-androstenedione, dehydroepiandrosterone and 21-deoxycortisol.. Discordant features of subclinical hypercorticism were noted in one case. No patient had dehydroepiandrosterone sulfate levels in the normal range for his or her age. Peak 17-hydroxyprogesterone and peak 21-deoxycortisol disclosed impairment of 21-hydroxylase in 11 and 10 cases respectively. An increased 11-deoxycortisol/cortisol ratio identified reduced activity of 11beta-hydroxylase in 11 patients. Eight patients displayed features of mild 17,20-lyase impairment, which was related to 21-hydroxylase dysfunction. Whereas only 2 patients showed no enzyme modification, 9 displayed alterations of at least two pathways.. In our hands, a combination of enzyme dysfunction was frequently observed. Shared biochemical mechanisms could explain combined 17,20-lyase and 21-hydroxylase alterations, whereas coexistence of 21-hydroxylase (particularly when based on peak 21-deoxycortisol) and 11beta-hydroxylase is more puzzling.

Topics: 17-alpha-Hydroxypregnenolone; Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Aldosterone; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Desoxycorticosterone; Dexamethasone; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Progesterone; Prospective Studies; Renin; Steroid 17-alpha-Hydroxylase; Steroid 21-Hydroxylase

Recent reports have shown an exaggerated response of 17-hydroxyprogesterone in up to 70% of patients with incidentally detected adrenal adenomas ('incidentalomas'). This has been explained by pre-existing 21-hydroxylase deficiency which may be a pathogenetic factor in the development of adrenal tumours. However, other defects in steroidogenesis, such as mild 11 beta-hydroxylase deficiency, could also result in increased 17-hydroxyprogesterone secretion. We therefore studied the glucocorticoid and mineralocorticoid pathways in patients with adrenal 'incidentalomas' by measuring multiple adrenal steroids before and after 1-24 ACTH stimulation. Twenty patients with adrenal 'incidentalomas' (14 females, 6 males) and 27 healthy controls (14 females, 13 males) were studied. All subjects underwent a 1-24 ACTH stimulation test (250 micrograms i.v.) with determination of progesterone, 11-deoxycorticosterone, corticosterone, 17-hydroxyprogesterone, 11-deoxycortisol and cortisol at 0 and 60 min. All steroids were measured by RIA after extraction and HPLC. Patients with 'incidentalomas' had higher stimulated concentrations of 17-hydroxyprogesterone (21.6 +/- 8.4 vs 4.2 +/- 0.3 nmol/I; P < or = 0.001), 11-deoxycortisol (8.1 +/- 1.2 vs 3.6 +/- 0.3 nmol/I; P < or = 0.001), progesterone (8.28 +/- 2.82, vs 1.08 +/- 0.15 nmol/I; P < or = 0.001), and 11-deoxycorticosterone (2.1 +/- 0.39 vs 0.78 +/- 0.12 nmol/I; P = 0.002) compared with controls. In contrast, cortisol and corticosterone concentrations were not different. There was evidence for impairment of 11 beta-hydroxylase activity by an increased 11-deoxycortisol/ cortisol ratio (0.012 +/- 0.003 vs 0.005 +/- 0.001 in controls; P = 0.002) and 11-deoxycorticosterone/ corticosterone ratio (0.04 +/- 0.003 vs 0.015 +/- 0.003; P = 0.003). The conclusions reached were that patients with adrenal 'incidentalomas' have increased responses of precursors of the mineralocorticoid and glucocorticoid pathway including 17-hydroxyprogesterone after stimulation with ACTH. This seems to be caused by impairment of 11 beta-hydroxylase activity rather than by impaired 21-hydroxylase activity in these tumours.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Gland Neoplasms; Adult; Aged; Cortodoxone; Cosyntropin; Desoxycorticosterone; Female; Humans; Male; Middle Aged; Progesterone; Reference Values; Steroid 11-beta-Hydroxylase; Steroid 21-Hydroxylase

Inferior petrosal sinus sampling (IPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing's syndrome. Diagnostic accuracy is improved by the administration of corticotrophin releasing-factor (CRF) during the procedure to stimulate ACTH secretion. We hypothesized that, given the unavailability of CRF in Australia, stimulation of ACTH secretion from tumorous corticotrophs with metyrapone treatment before IPSS may be useful.. To describe our clinical experience with a novel diagnostic test, and to compare results between IPSS with and without metyrapone pre-treatment.. Metropolitan, Australian university teaching hospital.. 18 patients were studied on 21 occasions: three with Cushing's disease without metyrapone treatment prior to IPSS (M-), 11 with Cushing's disease with metyrapone pretreatment (M+), three with ectopic ACTH syndrome, and one with pseudo-Cushing's syndrome.. Patients received oral metyrapone, median dose 750 mg 6 hourly, for 24 h before IPSS.. No major side effects were noted. Metyrapone increased serum 11-deoxycortisol concentration to a median of 400 nmol/l (range 36-1310) on the morning of the test. Radiological confirmation of correct catheter placement was shown in 36/42 inferior petrosal sinuses (86%). Median peak central: peripheral ACTH ratios were 9.8 for M- pituitary adenomas (range 5.7-13.6), 12.9 for the technically successful M+ pituitary adenomas (range 8-54.1), and 1.6 for M+ ectopic ACTH syndrome cases (range 1.2-3.4). Repeat studies in unoperated patients with ectopic ACTH syndrome showed ratios < 1.6. IPSS showed median peak ACTH concentrations of 190 ng/l for M- pituitary adenomas (range 83-205), 595 ng/l for the technically successful M+ pituitary adenomas (range 80-7630; P = 0.035 compared to M-), and 62 ng/l for M+ ectopic ACTH syndrome cases (range 47-220). IPSS correctly identified the pituitary source of ACTH production in all cases of Cushing's disease (except one technical failure where MRI revealed a lesion). MRI scanning correctly identified a lesion in 3/14 operated Cushing's disease cases. IPSS correctly lateralized 1/3 M- and 7/8 M+ Cushing's disease cases where the procedure was technically successful and surgical descriptions adequate. Pituitary exploration revealed a visible lesion in 75% of cases corresponding to the side predicted by IPSS; 'blind' hemi-hypophysectomy was performed on the side predicted from IPSS in the remainder. All cases of Cushing's disease were cured or improved following surgery, with a median follow-up of 2.8 years (range 0.7-5.9).. Metyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Cortodoxone; Cushing Syndrome; Diagnosis, Differential; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Stimulation, Chemical

In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic-pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histology-proven NFMA were studied and hyperPRL was defined as serum prolactin (PRL) > 200 mIU/l in men and > 600 mIU/l in women. The pituitary-adrenal axis was evaluated by measurement of urinary free cortisol (N = 38), peak cortisol to insulin-induced hypoglycaemia (IIH, N = 36) and to human corticotrophin-releasing hormone (hCRF, N = 40) and by urinary tetrahydrol 11-deoxycortisol (H4S, N = 39), plasma androstenedione increment (N = 39) and serum 11-deoxycortisol (N = 1) after metyrapone. Central hypothyroidism, gonadotrophin deficiency and growth hormone (GH) reserve were also assessed. Twenty patients had hyperPRL (serum PRL 331 (223-1120) mIU/l (median, range) in men and 932 (660-3927) mIU/l in women): urinary free cortisol excretion (p < 0.03) and peak serum cortisol in response to IIH (p < 0.02) were lower in hyperPRL than in normoPRL patients; peak serum cortisol after hCRF was not different between groups but occurred later in hyperPRL patients (at 60vs 30 min, p < 0.03); urinary H4S excretion and androstenedione response after metyrapone were lower in hyperPRL than in normoPRL patients (p < 0.05 for both): 60% of hyperPRL patients and 15% of normoPRL patients had an abnormal H4S response (p < 0.025): central hypothyroidism (overt + subclinical) was present in 74% of hyperPRL and in 60% of normoPRL patients (NS); 78% of hyperPRL and 55% of normoPRL patients had gonadotrophin deficiency (NS): growth hormone (GH) deficiency was present in 83% of hyperPRL and in 89% of normoPRL patients (NS); 73.3% of 75 evaluable pituitary hormone axes were abnormal in hyperPRL patients compared to 53.8% of 78 hormone axes in normoPRL patients (by metyrapone test to examine adrenal function, p < 0.025); and no significant differences in tumour grade and stage distribution were found between hyperPRL and normoPRL patients. It is concluded that hyper-prolactinaemia in NFMA is associated with a higher prevalence of pituitary-adrenal dysfunction, which is likely to be explained at least in part by functional hypothalamic-pituitary interruption.

Topics: Adenoma; Adult; Aged; Corticotropin-Releasing Hormone; Cortodoxone; Female; Humans; Hydrocortisone; Hyperprolactinemia; Hypoglycemia; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System

A 28-year old female patient with virilization due to left adrenocortical adenoma was studied. The patient had clinical features of hyperandrogenism such as hirsutism and a low pitched voice, but not of hypercorticoidism. Plasma testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were high. Although the basal plasma cortisol concentration and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were within the normal range, the absence of diurnal variation in plasma cortisol and loss of suppressibility by dexamethasone suggested constitutive secretion of cortisol by the tumor. Inappropriate cortisol secretion was also supported by blunted ACTH response to provocative stimuli. After successful removal of the left adrenal tumor, such endocrinological abnormalities were all normalized. Immunohistochemical analysis revealed that tumor cells were positively stained for C21 hydroxylase cytochrome P-450 (P-450C21) and P-450(11) beta which convert 17-hydroxy (OH) progesterone to cortisol as well as P-450SCC, 3 beta-hydroxysteroid dehydrogenase and P-450(17) alpha which are involved in testosterone biosynthesis. These findings suggest that adrenocortical adenoma secretes predominantly testosterone and constitutively cortisol in a young woman patient with virilization.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma; Adrenal Cortex Neoplasms; Adult; Circadian Rhythm; Cortodoxone; Cushing Syndrome; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Female; Humans; Hydrocortisone; Immunohistochemistry; Japan; Testosterone

The in vitro metabolism of [1,2-3H] deoxycorticosterone (DOC), [1,2-3H] 18-hydroxy-11-deoxycorticosterone (18-OHDOC) and [1,2-3H] 11-deoxycortisol (S) was studied in adrenal adenoma homogenates from patients with primary hyperaldosteronism. Tumor tissues actively converted deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone to 18-hydroxycorticosterone and aldosterone. Yields of cortisol and cortisone were also large showing that the tissues did not lack the zona fasciculata-like 11 beta-hydroxylation ability.

Topics: 18-Hydroxycorticosterone; 18-Hydroxydesoxycorticosterone; Adenoma; Adrenal Gland Neoplasms; Aldosterone; Cortisone; Cortodoxone; Desoxycorticosterone; Female; Glucocorticoids; Humans; Hydrocortisone; Hyperaldosteronism; Male; Mineralocorticoids

To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome.. An evaluation of the standard clinical practice at one institution.. Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome.. The acute response to metyrapone was assessed by measuring cortisol, 11-desoxycortisol and ACTH at 0, 1, 2, 3, 4 hours after a test dose of 750 mg of metyrapone. The longer-term effect of metyrapone was judged by measuring serum cortisol at 0900, 1200, 1500, 1800, 2100 and sometimes 2400 h and calculating a mean.. A test dose of 750 mg of metyrapone decreased serum cortisol levels within 2 hours in all groups of patients and this effect was sustained at 4 hours. At the same time, serum 11-desoxycortisol levels increased in all patients, while plasma ACTH increased in patients with pituitary Cushing's disease and the ectopic ACTH-syndrome. Fifty-three patients with Cushing's disease were followed on short-term metyrapone therapy (1 to 16 weeks) before other more definitive therapy. Their mean cortisol levels (median 654 nmol/l, range 408-2240) dropped to the target range of less than 400 nmol/l in 40 patients (75%) on a median metyrapone dose of 2250 mg/day (range 750-6000). Metyrapone was given long term in 24 patients with Cushing's disease who had been given pituitary irradiation, for a median of 27 months (range 3-140) with adequate control of hypercortisolaemia in 20 (83%). In 10 patients with adrenocortical adenomas and six with adrenocortical carcinomas, metyrapone in a median dose of 1750 mg/day (range 750-6000) reduced their mean cortisol levels (median 847 nmol/l, range 408-2000) to less than 400 nmol/l in 13 patients (81%). In 18 patients with the ectopic ACTH-syndrome the 'mean cortisol levels', obtained from five or six samples on the test day (median 1023 nmol/l, range 823-6354) were reduced to less than 400 nmol/l in 13 patients (70%), on a median dose of 4000 mg/day (range 1000-6000). Reduction of cortisol levels was clearly associated with clinical and biochemical improvement. The medication was well tolerated. Transient hypoadrenalism and hirsutism were unusual but were the most common side-effects.. In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adolescent; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Adult; Aged; Carcinoma; Cortodoxone; Cushing Syndrome; Depression, Chemical; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Time Factors

A serum steroid profile was determined in 11 patients with adrenocortical carcinoma, 5 with adrenocortical adenoma and 10 healthy controls. Seven of the patients with carcinoma had different forms of endocrine symptoms, and of those with adenoma 3 had Cushing's syndrome and 2 primary hyperaldosteronism. Sulphated steroids dominated in serum from both patients and controls, whereas the levels of free and glucuronated steroids were low. All patients with adrenocortical carcinoma had increased levels of sulphated pregn-5-ene-3 beta-ol-20-one (pregnenolone) and pregn-5-ene-3 beta,20 alpha-diol compared with healthy controls and patients with adrenocortical adenoma. Serum levels of 11-deoxycortisol and/or its glucuronated metabolite tetrahydro-11-deoxycortisol were clearly elevated in 8 of the patients with carcinoma. The results are in agreement with those previously found for conjugated urinary steroids in patients with adrenocortical carcinoma. Thus, an impaired function or deficiency of 3 beta-hydroxysteroid dehydrogenase/delta isomerase and in some cases also of 11 beta-hydroxylase could explain the findings. The serum levels of sulphated pregnenolone and/or pregn-5-ene-3 beta,20 alpha-diol, possibly together with free 11-deoxycortisol seem to be useful for preoperative discrimination between malignant and benign adrenocortical tumours.

Topics: Adenoma; Adolescent; Adrenal Cortex Neoplasms; Adult; Aged; Biomarkers, Tumor; Child; Child, Preschool; Cortodoxone; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pregnenolone; Tetrahydrocortisol

The ultrastructural characteristics of a benign adrenal adenoma that produces deoxycorticosterone and 11-deoxycortisol were examined by transmission electron microscopy. Both large, round mitochondria with a few cristae in the peripheral portion and spherical or oval mitochondria with sacrotubular cristae were observed in adenoma cells. The development of agranular or granular endoplasmic reticulum varied from cell to cell. In some cells, many vacuoles and collagenous fibers were also seen. Thus, the adrenal tumor we examined was composed of the cells derived from the fascicular zone, which are associated with Cushing's syndrome, and the cells of the glomerular zone observed in association with primary aldosteronism.

Topics: 17-Hydroxycorticosteroids; Adenoma; Adrenal Gland Neoplasms; Adult; Cortodoxone; Desoxycorticosterone; Endoplasmic Reticulum; Female; Humans; Microscopy, Electron; Mitochondria; Vacuoles

An adult woman with Beckwith-Wiedemann syndrome, hemihypertrophy and an androgen-secreting adrenal adenoma is described. She presented with a 7-year history of progressive virilization and was found to have high plasma levels of testosterone and dehydroepiandrosterone (DHEA) sulphate and elevated levels of urinary metabolites of testosterone and its precursors. Administration of dexamethasone was associated with progressive rises in plasma 17 alpha OH progesterone, 11 beta-desoxycortisol, DHEA sulphate, androstenedione and testosterone, together with increased urinary excretion of androsterone, 11 beta OH androsterone, etiocholanolone, DHEA, and 16 alpha OH DHEA. Hormone levels fell to normal following removal of the tumour.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Gland Neoplasms; Androgens; Androstenedione; Beckwith-Wiedemann Syndrome; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Female; Humans; Hydroxyprogesterones; Middle Aged; Testosterone; Virilism

The case was a 33-year-old woman with hypertension and hypokalemia, who presented depression of renin activity and the abnormal elevation of plasma deoxycorticosterone (DOC) and 11-deoxycortisol on laboratory tests. After admission, abdominal CT scan, 131I-adosterol scintigram and adrenal venogram revealed a tumor in the left adrenal, which histologically seemed to be benign. When the tumor was resected, blood pressure and all the biochemical data returned to normal range. DOC and 11-deoxycortisol levels in the tumor were abnormally elevated as compared with those in the normal adrenal tissue. These findings suggested that the abnormal elevation of hormone levels resulted from depression of 11 beta-hydroxylase. Though numerous adrenal tumors have been documented, we rarely encounter an apparently benign adrenal tumor that produces 2 kinds of hormones. This seemed to be the first case of benign adrenal tumor in which both DOC and 11-deoxycortisol were elevated.

Topics: 17-Hydroxycorticosteroids; Adenoma; Adrenal Gland Neoplasms; Adult; Cortodoxone; Desoxycorticosterone; Female; Humans; Hypertension; Hypokalemia

Selective adrenal vein catheterization was done preoperatively in 11 patients with Cushing's syndrome owing to either an adrenal adenoma (6) or an adrenal carcinoma (5). Peripheral and adrenal venous blood (tumor side) was analyzed for progesterone, 17-hydroxyprogesterone, testosterone, delta-4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol and 11-deoxycortisol. Comparisons were made of the ratios of precursors to products in the androgen and cortisol production pathways. In adrenal vein samples, cortisol levels were higher in the adenoma patients (p equals 0.06). These patients had a higher ratio of 17-hydroxyprogesterone to delta-4-androstenedione (p less than 0.04). The ratio of 11-deoxycortisol to cortisol was higher in the carcinoma patients (p less than 0.02). In the peripheral samples, the carcinoma patients had higher levels of testosterone and 11-deoxycortisol (p less than 0.02) and progesterone (p equals 0.05). The most striking differences were in the peripheral levels of 17-hydroxyprogesterone, delta-4-androstenedione and dehydroepiandrosterone, which were 10 to 20 times higher in the carcinoma group (p less than 0.005). The ratios of progesterone to 17-hydroxyprogesterone and 17-hydroxyprogesterone to 11-deoxycortisol were higher in the adenoma group (p less than 0.005 and p equals 0.06, respectively). The peripheral blood ratio of 11-deoxycortisol to cortisol was higher in the carcinoma group (p less than 0.03). These data indicate that peripheral and adrenal venous steroid levels and ratios of precursors to products are significantly different in the 2 groups. The carcinomas have a block in the conversion of 11-deoxycortisol to cortisol with a subsequent accumulation in androgen and cortisol precursors. The elevations in 17-hydroxyprogesterone, delta-4-androstenedione and dehydroepiandrosterone, and in the ratio of 11-deoxycortisol to cortisol in the carcinoma group are most striking in the periphery. Peripheral blood steroid measurement in patients with Cushing's syndrome and an adrenal mass aids in the preoperative differentiation of carcinoma from adenoma.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Androstenedione; Carcinoma; Cortodoxone; Cushing Syndrome; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Male; Progesterone; Testosterone

In search for a biochemical marker to differentiate between adrenocortical carcinoma (AC) and adenoma (AA), plasma levels of the following steroids were studied preoperatively and postoperatively: 11-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S), and cortisol (F). Levels were measured by Sephadex LH-20 chromatography and specific radioimmunoassays. The subjects included eight children ages 2 years, 5 months to 9 years, 10 months. There were three girls and 5 boys with pseudoprecocious puberty due to adrenocortical tumors (histologically, four were AC and four, AA). The preoperative showed that DOC and S levels were elevated in all patients, F levels were elevated in four of eight children when compared with age-matched controls, whereas B was normal. Postoperatively, all levels returned to normal. The ratios of B/DOC and F/S as an index of adrenal 11 beta-hydroxylase activity were calculated. The preoperative ratios of B/DOC were markedly decreased in all patients with AC compared to controls (7.7,4.1,5.9,1.9 versus 23.5, median), but normal in three of four patients with AA (16.2, 29.6, 16.1). The F/S ratios were significantly lower in AC and AA when compared with controls. The data indicate a deficiency in 11 beta-hydroxylation in cases of adrenocortical tumors. Despite a still limited number of patients, the decreased B/DOC ratios may possibly indicate malignancy and could be helpful in distinguishing by biochemical means between benign and malignant adrenocortical tumors.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Carcinoma; Child; Child, Preschool; Chromatography, Gel; Corticosterone; Cortodoxone; Desoxycorticosterone; Female; Humans; Hydrocortisone; Male; Puberty, Precocious; Radioimmunoassay; Steroid Hydroxylases

Unstimulated plasma ACTH concentrations remain at or below the detection limit of conventional immunoassays. Grossly elevated ACTH concentrations are diagnostic in suspected adrenal insufficiency, remain elevated well above 200 ng/l during substitution therapy and obviate the need of further tests. For the diagnosis of secondary adrenal failure, plasma ACTH, cortisol and 11-desoxycortisol response to a single midnight dose of metyrapone (1.2 g/m2 = 30 mg/kg) discriminates between a normal (morning ACTH above 100 ng/l), diminished (morning ACTH detectable, but below 100 ng/l), and an absent (ACTH below 20 - 40 ng/l) ACTH reserve. In congenital adrenal hyperplasia, plasma ACTH concentrations mirror, together with 17-alpha-hydroxyprogesterone, the extent of ACTH suppression. Elevated ACTH concentrations were suppressed by prednisolone (25%), dexamethasone (2% of the hydrocortisone dose) or by addition of cyproterone acetate (100 mg/m2/day). Using selective venous catheterisation in clinically and biochemically proven Cushing's syndromes, a pituitary adenoma could be identified and localized in 6 of 8 patients by measuring ACTH concentrations in the left and right petrosal sinus before and after stimulation with corticotrophin releasing hormone.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Gland Diseases; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Child; Cortodoxone; Cushing Syndrome; Humans; Hydrocortisone; Hydroxyprogesterones; Metyrapone; Pituitary Neoplasms

A short overnight metyrapone test and a 30-min ACTH test were performed in ten patients after pituitary surgery. At the initial testing 2 weeks after surgery the 30-min ACTH test was abnormal in two patients while normal increases in s-cortisol were observed in eight patients. These eight patients also had normal responses to ACTH when re-tested after 6-19 months. The short metyrapone test was a much more sensitive indicator of functional disturbances in pituitary/adrenal function. Two weeks after surgery the test was abnormal in seven of the patients. After 6-19 months some normalization of the short metyrapone test had occurred, probably due to disappearance of postoperative oedema and haematoma. However, the test was still abnormal in three patients having normal responses during the 30-min ACTH test. It is suggested that both tests are performed in such patients to specify a high risk group, i.e. both tests abnormal, and a low risk group with a normal 30-min ACTH test but subnormal responses during the short metyrapone test. This would be of help in the decision on cortisol supplementation and offer a high degree of safety for the patients.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenocorticotropic Hormone; Adult; Aged; Cortodoxone; Craniopharyngioma; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Risk

Data are presented concerning a case of female pseudohermaphroditism of unknown etiology. The child was born with labioscrotal fusion and clitoromegaly. From the age of 5 to the age of 25 there was no clinical evidence of a hormonal abnormality. At the age of 25 the patient presented with masculinization and Cushing's syndrome, and a left adrenal tumor was removed. The patient was restudied at the age of 29, when 21-hydroxylase deficiency was excluded. Other types of congenital adrenal hyperplasia are considered unlikely. The possible relationship between the ambiguous genitalia present at birth and the virilizing tumor diagnosed at the age of 25 is analyzed.

Topics: 17-alpha-Hydroxyprogesterone; Adenoma; Adrenal Cortex Neoplasms; Adult; Age Factors; Cortodoxone; Cosyntropin; Disorders of Sex Development; Female; Humans; Hydrocortisone; Hydroxyprogesterones

Six men with prolactin-secreting pituitary macroadenomas and deficiencies of pituitary hormones other than gonadotrophins were treated with bromocriptine for 6 months. During treatment the serum prolactin concentration decreased markedly in all six patients, and in four adenoma size decreased and visual function improved. Two patients who were hypothyroid before bromocriptine treatment were euthyroid during the sixth month of treatment, and the one patient who was hypoadrenal before treatment was euadrenal during treatment. Two of the six men who had subnormal growth hormone secretion before treatment had normal growth hormone secretion during treatment. We conclude that pituitary hormonal functions may improve during bromocriptine treatment for prolactin-secreting pituitary macroadenomas. This improvement may result from decompression of other pituitary cells, because correction of hypothyroidism by bromocriptine was accompanied by conversion from an absent to a normal thyrotrophin response to thyrotrophin-releasing hormone.

Topics: Adenoma; Adult; Bromocriptine; Cortodoxone; Growth Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Testosterone; Thyrotropin

An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. This pattern suggests that the clinical Cushing's syndrome but enough to suppress partially ACTH and, consequently, visualization of the contralateral gland.

Topics: 17-Hydroxycorticosteroids; Adenoma; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Cholesterol; Cortodoxone; Cushing Syndrome; Humans; Hydrocortisone; Male; Middle Aged; Radioisotopes; Radionuclide Imaging; Selenium

Topics: 17-alpha-Hydroxypregnenolone; Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Cortodoxone; Female; Humans; Hydroxyprogesterones; Isomerism; Male; Microsomes; Mitochondria; Steroid Hydroxylases; Structure-Activity Relationship