cortodoxone and Pituitary-Neoplasms

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

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

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

We wished to develop optimal criteria for interpreting the single-dose overnight metyrapone test and to compare the diagnostic efficiency of the overnight and the standard 6-dose metyrapone tests for the differential diagnosis of ACTH-dependent Cushing's syndrome.. Retrospective pilot study based on all patients who completed both metyrapone tests and whose diagnoses were subsequently confirmed surgically.. Sixty-three patients, 57 with pituitary tumours and 6 with ectopic ACTH syndrome, were studied.. The sensitivity and specificity were determined using stimulation of plasma 11-deoxycortisol and suppression of plasma cortisol as endpoints for the overnight test and stimulation of urine 17-hydroxysteroid and plasma 11-deoxycortisol as endpoints for the standard test. The lest response that gave the highest sensitivity for the diagnosis of Cushing's disease, with 100% specificity, was determined for each test endpoint.. Both the stimulation of plasma 11-deoxycortisol and the suppression of plasma cortisol were expressed as the ratio of the post-metyrapone value to baseline. A plasma 11-deoxycortisol ratio > than 220 or a plasma cortisol ratio > 0.6 was associated with 100% specificity for diagnosis of Cushing's disease by the overnight test. When these two criteria were combined, the sensitivity was 65%, which was significantly higher than that obtained using either steroid alone: 42% for both plasma 11-deoxycortisol and plasma cortisol. The sensitivity of 65% for the overnight test, at 100% specificity, was nearly identical to that of the standard test in the same patients: 67% for the combined criterion of > 70% stimulation of urine 17-hydroxysteroid or > 480-fold increase of plasma 11-deoxycortisol. When the criteria for both the overnight and standard tests were combined, the sensitivity increased to 84%, which was higher than that obtained using the criteria for either test alone (P < 0.02).. The single-dose overnight metyrapone test, which can be performed in 24 hours and which avoids the disadvantages associated with timed urine collections, has a nearly identical sensitivity (for a specificity of 100%) as the 6-dose standard metyrapone test for the diagnosis of Cushing's disease. Furthermore, the diagnostic performance of a criterion that combines the results of both tests is significantly better than the best criterion for either test alone.

Topics: ACTH Syndrome, Ectopic; Cortodoxone; Cushing Syndrome; Humans; Hydrocortisone; Metyrapone; Pilot Projects; Pituitary Neoplasms; Retrospective Studies; Sensitivity and Specificity

Short term suppression of ACTH by dexamethasone effects limited reduction in plasma deoxycorticosterone (DOC) while cortisol levels are almost completely suppressed in normal control subjects. The zona fasciculata (ZF) microsomal cytochrome P-450(21) appeared less influenced by lack of ACTH than mitochondrial cytochrome P-450(11 beta-18). Eleven patients with hypopituitarism were studied to quantitate basal ZF microsomal and mitochondrial derived steroids and their acute and extended responses to ACTH. Basal levels of 11-deoxycortisol (S) and DOC were modestly reduced (70% and 53%, respectively), while other ZF steroids were almost completely absent. Acute and prolonged ACTH treatment amplified the discrepancy in both plasma levels and production rates. DOC and S demonstrated prompt and sustained increases similar to those in normal controls, while cortisol, 18-hydroxydeoxycorticosterone, and corticosterone showed a slow subnormal recovery of steroid production. The preservation of microsomal cytochrome P-450(21) and P-450(17 alpha) to maintain DOC and S levels contrasts the reduced and delayed responses of steroids dependent on mitochondrial cytochrome P-450(11 beta-18), cortisol, corticosterone, and 18-hydroxydeoxycorticosterone. A greater effect of ACTH deficiency on mitochondrial over microsomal cytochrome P-450 activity is demonstrated, and in addition, the possibility is raised that other non-ACTH regulators sustain microsomal cytochrome P-450(21) and P-450(17 alpha) in a setting of reduced ACTH-stimulated factors.

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Cortodoxone; Cosyntropin; Desoxycorticosterone; Dexamethasone; Female; Humans; Hypopituitarism; Kinetics; Male; Middle Aged; Pituitary Neoplasms; Reference Values; Zona Fasciculata

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

We assessed the need for continued glucocorticoid replacement therapy in postsurgical pituitary tumor patients using a dexamethasone-ACTH test. The patients received 1 mg dexamethasone, orally, at 2300 h and 250 micrograms synthetic ACTH (Cosyntropin), iv, at 0800 h the next morning. The mean +/- SD integrated cortisol response for a 2-h period of the 31 pituitary tumor patients [1264 +/- 924 micrograms X min/dl (34.87 +/- 25.49 mumol X min/liter)] was significantly less (P less than 0.005) than that of 25 normal subjects [3331 +/- 544 micrograms X min/dl (91.90 +/- 17.04 mumol X min/liter)]. Replacement glucocorticoids were abruptly discontinued in 11 patients with responses above 1450 micrograms X min/dl (40.01 mumol X min/liter). No clinical or laboratory evidence of adrenal insufficiency occurred as long as 15 months after discontinuation. Metyrapone tests, however, in the 11 glucocorticoid-withdrawn patients revealed a reduced mean +/- SD serum 11-deoxycortisol level compared with that of 10 normal subjects [8.9 +/- 4.7 vs. 15.6 +/- 5.0 micrograms/dl (0.26 +/- 0.13 vs. 0.45 +/- 0.16 mumol/liter); P less than 0.005]. Our results indicate that the dexamethasone-ACTH test is useful in identifying patients in whom replacement glucocorticoid therapy can be safely withdrawn under nonstressed conditions. The test can be simplified to one plasma cortisol level determined 30 min after ACTH administration.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Cortodoxone; Dexamethasone; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System

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

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

Plasma levels of ACTH, 11-deoxycortisol, androstenedione and testosterone and urinary tetrahydro-11-deoxycortisol were determined during a two day oral metyrapone test using doses of 1.5 g every 6 h. The level of 11-deosycortisol 48 h after the start was distinctive regarding the assessment of pituitary ACTH secretory capacity. The rise of androstenedione concentration after 48 h is distinctive in a similar way, whereas ACTH determination is of little diagnostic value in this respect. Further, an increase in testosterone level can be observed in cases of low basal testosterone production. This increase is probably the result of peripheral conversion of androstenedione to testosterone. Where the basal testosterone concentration was high, no change could be measured.

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Androstenedione; Cortodoxone; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Testosterone; Tetrahydrocortisol; Time Factors

A patient with Cushing's syndrome due to a nonresectable chromophobe adenoma underwent external irradiation of the hypothalamic-pituitary area. The signs of Cushing's syndrome ameliorated subsequently but recurred eventually, necessitating bilateral adrenalectomy 30 months after initial presentation. Response to dexamethasone suppression testing on four occasions varied greatly. These results may reflect alterations in sensitivity of the tumour or the hypothalamic-pituitary axis to feedback inhibition by glucocorticoids.

Topics: Adenoma, Chromophobe; Adult; Cortodoxone; Cushing Syndrome; Dexamethasone; Female; Humans; Hydrocortisone; Metyrapone; Pituitary Neoplasms

Evaluation of single-dose metyrapone tests in children with hypopituitarism; comparison with the prolonged metyrapone and insulin induced hypoglycaemia tests and their relationship with the etiology of hypopituitarism. Acta Paediatr Scand, 65:177, 1976.--Pituitary-adrenal reserve was evaluated in control and hypopituitary subjects by comparing the 8 a.m. plasma 11-deoxycorticoid response (11-DOCS) to a single midnight oral dose of metyrapone (short test) with 1) the 8 a.m. 11-DOCS increase under repeated oral doses of metyrapone (prolonged test) and 2) with the plasma corticoid response during arginine-insulin test. In the short and the prolonged metyrapone tests, the same response was obtained in 25 out of 27 patients. The short test was repeated in 22 patients and the 11-DOCS response did not show a significant difference. In 34 of 40 patients, the response to the short test was comparable to the response during the arginine-insulin test; only 3 patients with a normal 11-DOCS rise to the short test had a low response to insulin and vice versa. Among the low responders to the short test, the mean 11-DOCS value was significantly lower in subjects with operated craniopharyngiomas than in idiopathic hypopituitary patients (p less than 0.001). In the short test, the 8 a.m. baseline cortisol value was positively correlated with the 8 a.m. 11-DOCS response (p less than 0.001), the cortisol level allowing to predict the 11-DOCS response in 28 out of 53 patients. Thus, the short oral metyrapone stimulation was found to be a reliable test in hypopituitary children.

Topics: 17-Hydroxycorticosteroids; Adolescent; Adult; Arginine; Blood Glucose; Child; Cortodoxone; Craniopharyngioma; Evaluation Studies as Topic; Female; Humans; Hypopituitarism; Insulin; Male; Metyrapone; Pituitary Neoplasms