Vasopressin test in central nervous system-pituitary disorders.
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OBJECTIVES: We wished to compare peak and incremental rise in plasma cortisol in response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon stimulation test (IMGST) and short Synacthen test (SST) in patients with pituitary disease, using a modern radioimmunoassay for cortisol. We compared the three stimulants using receiver operator characteristic (ROC) plots, assuming a cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we used as the standard from which to evaluate the SST and the IMGST. PATIENTS AND DESIGN: We prospectively studied 16 patients (8F, 8M mean age 43.69 +/- 3.72 years) admitted to the investigation ward for IIH stress test and who were asked to undergo two additional tests (IMGST and SST) on consecutive days. MEASUREMENTS: We measured serum cortisol at baseline, 30, 45, 60, 90 and 120 minutes during the IIH stress test; baseline, 150 and 180 minutes during GST, and baseline and 30 minutes during the SST. RESULTS: There was a significant rise in cortisol from baseline in all tests (P < 0.001). There was no significant difference among the peak plasma cortisol responses or the incremental rises in plasma cortisol following IMGST, SST and IIH stress test (repeated measures ANOVA F = 0.704, P = 0.503; F = 0.238, P = 0.79). The ROC plots clearly showed that the SST has poor diagnostic utility at both IIH thresholds, compared with the IMGST. CONCLUSION: The peaks and incremental rises in cortisol following all three tests are comparable. Using the insulin induced hypoglycaemia stress test as a reference and peak cortisol thresholds of 500 and 580 nmol/l as discriminating variables, the short Synacthen displayed poor diagnostic utility when compared to the i.m. glucagon stimulation test. The short Synacthen may be misleading if used as a screening test as advocated by a number of authors.
OBJECTIVES: The overnight 8-mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of ACTH from the pituitary gland, from other kinds of Cushing's syndrome. However, a few patients with ACTH-producing pituitary adenoma show no suppression of plasma cortisol after the administration of 8 mg of dexamethasone. To clarify the relationship between the level of glucocorticoid receptor (GR) in the pituitary adenoma and the sensitivity to dexamethasone in Cushing's disease, we thus examined the levels of GR alpha and GR beta mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH-producing adenomas. MATERIALS: Total RNA was extracted from six pituitary adenomas and pituitary tissue adjacent to one of the adenomas, and the mRNA levels of GR alpha, GR beta, pro-opiomelanocortin (POMC) and beta-actin in these samples were sampled by quantitative RT-PCR. RESULTS: The GR alpha mRNA levels in the adenomas from the two patients who showed no response to the 8-mg dexamethasone suppression test were significantly lower than those in the adenomas of four patients who showed suppression. The GR beta mRNA level was much lower than that of GR alpha mRNA but not significantly different among the six adenomas. CONCLUSIONS: These results suggest strongly that decreased expression of GR alpha in pituitary adenomas may be the major reason for the marked insensitivity to the 8-mg dexamethasone suppression test observed in two patients with Cushing's disease.
Sixteen young women with hyperprolactinaemia and normal or equivocal sella in radiographs underwent computed tomography using a Siemens Somatom II. In all but one case an abnormality was found. The sella was full in seven and partially empty in nine. A tumour was visible in six of the full and in four of the partially empty sellae. All but one of the 10 tumours was unilateral, and in seven the pituitary stalk was deviated away from the tumour. After administration of intravenous contrast (Urografin) four tumours showed diffuse enhancement, four ring enhancement, and two enhanced less than adjacent normal pituitary tissue. Two of the tumours have been subsequently shown histologically to be prolactinomas. Prolactin response to thyrotrophin-releasing hormone predicted a tumour in seven out of eight with visible tumours but also in three out of four without visible tumours; using metoclopramide, a tumour was predicted in six out of seven with tumours, but again in three out of four without visible tumours. Such results question the value of dynamic tests for the discrimination of tumours. We conclude that practically all women with sustained hyperprolactinaemia and a normal or equivocal sella radiologically have pituitary disease.
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The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22 females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients were also submitted to a standard evaluation of their GH secretion, consisting of at least two classical pharmacologic stimulation (CPS) tests, such as ornithine, arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n = 26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV) dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS. There was a large overlap of the individual responses to GRF between the 5 groups, but the mean responses in groups II, IV and V were significantly lower than in group I. Furthermore, the mean responses of groups IV and V were in the lower range of the normal. It is concluded that the GRF test may be useful to ascertain the diagnosis of functional or partial GH deficiency when the responses to CPS and SS are dissociated.
To investigate the self-priming effect of gonadotropin on the anterior pituitary glands, the response of serum gonadotropins to the "LH-RH two step test" (two step administration of 100 micrograms of synthetic LH-RH at a 60 minute interval) was studied in 20 women with normoestrogenic amenorrhea who were responsive to the progesterone test. The patients were divided into two groups according to the results of the clomiphene test. Blood samples were collected before LH-RH stimulation and 30, 60, 90, 120, 180 minutes after the first stimulation, respectively. The P1P2 ratio (2nd peak level/1st peak level) and delta 1 delta 2 ratio (delta 2/delta 1 = 2nd peak level-60 min. level/1st peak level-0 min. level) of LH and FSH in the clomiphene-positive group were significantly higher than those in the clomiphene-negative group. These ratios are regarded as the degree of the self-priming effect, and at least partially reflect the capacity for the synthesis of pituitary gonadotropins. The results demonstrate that the self-priming effect is more restored in the clomiphene-positive group than in the clomiphene-negative group, and the data also indicate that the analysis of the self-priming effect with the "LH-RH two step test" is useful in developing new diagnostic criteria on ovarian dysfunction.
The effect of a combined test (insulin, TRH, LHRH) on plasma concentrations of LH, FSH, PRL, Cortisol was studied in 18 normal subjects in prepubescent state and in 65 patients in prepubescent state with short stature. In 6 subjects with short stature there was no change of LH, and in 7 subjects with short stature there was no change of FSH. In conclusion the combined test for pituitary stimulation provides an useful method for localizing the lesion in disorders of hypothalamo-pituitary axis.
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The authors studied the response of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), proclatin (PRL) and testosterone (T) to the intravenous injection of 100 microgram of synthetic gonadotropin-releasing hormone (GnRH) in hirsute women in the follicular phase, prior to and after the administration of cyproterone acetate (CPA). The GnRH stimulation before and after the CPA therapy induced a significant increase in plasma LH and FSH levels (P less than 0.01) and a significant drop in the plasma PRL concentration (p less than 0.05). Unchanged plasma T levels were observed during the test, prior to the CPA administration. Following the CPA application there was a significant increment of basal plasma PRL levels (p less than 0.05) and a significant drop of plasma FSH levels (p less than 0.01). No significant changes were observed, however, in LH and T levels. During the GnRH stimulation, after the administration of CPA, a significant decrease in T levels was noted (p less than 0.01). Considering basal concentrations of the hormones studied and the response to the LHR stimulation test, CPA was found to have no beneficial effect on the hypothalamic-pituitary dysfunction typical of androgenization in females.
Two HGH (insulin and L-Dopa) stimulating tests were performed at time interval on 65 subjects with short stature (SDs between -2 and -4.5 according to Tanner) and on 18 control subjects, in order to study the influence of short stature degree on the HGH behaviour during the stimulating tests. The results obtained show that: 1. Statistically the short stature degree does not affect the response to HGH stimulating tests. 2. Two tests are necessary to avoid erroneous diagnosis of dwarfism caused by lack of HGH. 3. No response to HGH stimulating tests in subjects with normal stature may prove a discrepancy between the hormone measured radioimmunologically and its biological action.
Studies were done to determine plasma PRL in response to oral MC 0.2 mg/kg in 17 normal children (NC), 12 males and 5 females aged between 4.7-12.8 years and in 26 idiopathic growth hormone deficient children (IGHD), 15 M, 11 F, between 1.5-14.7 years old. Peak serum GH levels above 10 ng/ml after clonidine test and during insulin induced hypoglycemia were used to distinguish these 2 groups. None of the subjects had secondary sex characteristics. Adrenocortical and thyroid disorders were excluded. The subjects were fasted overnight. Blood samples for PRL determination were obtained at 0, 60, 90, 120 min after oral MC. In 17 NC the basal serum PRL values ranged from 0 to 19.2 ng/ml with the mean +/- SE of 7.24 +/- 1.7 ng/ml. The peak serum PRL response to MC ranges were from 33 to 127 ng/ml with the mean +/- SD and +/- SE of 64.45 +/- 24.22 and +/- 5.88 ng/ml respectively giving the cut point-2SD value of 16.01 ng/ml. Among 26I GHD, only 2 patients (7.69%) being all male, had peak PRL response to MC below 16.01 ng/ml, whereas, the rest (92.31%) had peak PRL levels above it. It is concluded that oral MC 0.2 mg/kg is the potent PRL stimulator in children, which can be safely used to test pituitary PRL secretion effectively. The majority (92.31%) of idiopathic GH deficient children had adequate serum PRL response to oral MC, whilst 7.69 per cent disclosed inadequate response which might indicate different etiologies.
We report the case of a 53 year old patient who was admitted with polyuria, polydipsia associated with fatigue, depression and sexual dysfunction. Central diabetes insipidus with hypogonadotrophic hypogonadism was diagnosed by a water restriction test and different static and dynamic hormonal dosages. Nodular thickening of the pituitary stalk was noted on the MRI and the biopsy permitted a histological diagnosis of infundibulitis.
The capability of the anterior pituitary gland to secrete GH in response to an intravenous injection of growth hormone-releasing factor (GRF) and insulin-induced hypoglycaemia was evaluated in 9 healthy male subjects ranging in age between 37 and 52 years old. Plasma GH response to 100 micrograms human GRF showed considerable intersubject variation and the increment of the peak value from the basal did not exceed 5 ng/ml in four out of 9 subjects. In contrast, insulin-induced hypoglycaemia resulted in a consistent stimulation of GH that exceeded 21 ng/ml in all subjects. The mean peak GH response after insulin-induced hypoglycaemia was significantly higher than that after GRF (27.4 +/- 1.6 vs 10.6 +/- 1.9 ng/ml). These results demonstrate that a significant divergence exists in plasma GH responses between the two provocative tests in the middle-aged subjects and suggest that the stimulation of GH following insulin-induced hypoglycaemia is not mediated solely by endogenous GRF.
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