PubMed Health⌕ Search

Biomedical subjects

B Liberman

Publications and source records attributed to B Liberman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Resistance to vasopressin action on the kidney in patients with Cushing's disease.

OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.

Adult↗
PubMed1997

Somatotrophic and corticotrophic function outcome after transesphenoidal surgery in patients with sellar tumors and pre-operative endocrine deficits.

Sixteen patients with sellar tumors that were treated surgically and who had pre-operative somatotrophic and corticotrophic function deficits were submitted to pre- and early post-operative insulin tolerance tests (ITTs). Seven patients had non-functioning adenomas, 5 had prolactinomas, 3 had craniopharyngioma and 1 had cordoma of the clivus. All patients had macro-tumors and none received radiotherapy within the studied period. Seven patients had GH, 4 had cortisol and 5 had both GH/cortisol function pre-operative deficit. Five patients with isolated GH, 4 with isolated cortisol and 3 with both GH/cortisol deficiencies showed a postoperative functional recovery. New cortisol secretion deficits were observed in 2 patients postoperatively and both required long-term steroid replacement. These data suggest that preoperative endocrine deficits may be reversible after surgical decompression of the sellar region and that new endocrine deficits are rarely seen after surgery. All such patients should be tested postoperatively from an endocrinological point of view to reevaluate the need for replacement therapies.

Adult↗
PubMed1997

A novel polymorphism in the coding region of the vasopressin type 2 receptor gene.

Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R)) gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R) gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R) gene have also been reported. In the present study, we analyzed exon 3 of the V2(R) gene in 20 unrelated individuals by direct sequencing. A C-->T alteration in the third position of codon 331 (AGC-->AGT), which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome.

Diabetes Insipidus, Nephrogenic↗
PubMed1996

Growth hormone axis in cushing's syndrome.

All levels of the growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor (IGF) and IGF binding protein (IGFBP) axis are influenced by chronic hypercortisolism. Thus, there is a blunted response to GHRH alone or together with other stimuli associated with a marked suppression of endogenous GH secretion but accompanied by normal GHBP, normal to low IGF-1 and GHBPs 1 and 3 with the correspondent 41.5 and 38.5-kD molecular forms of the latter presenting values similar to normal. These findings may suggest enhanced GH sensitivity with normal or increased IGF-1 bioavailability to the correspondent tissue receptors. In conclusion, the glucocorticoid (GC)-induced target tissue resistance can neither be attributed to the suppression of the GH axis nor to changes in circulating GHBPs 1 and 3. However, it may be related either to the described 12-to-20-kD inhibitor(s) which antagonizes postbinding IGF-1 bioactivity (gene expression) and/or by the downmodulation of activator protein-1 (Fos/Jun) activity by the GC-GC receptor complex.

Carrier Proteins↗
PubMed1996

Pulsatile release and circadian rhythms of thyrotropin and prolactin in children with growth hormone deficiency.

We have measured mean concentrations and have appraised the pulsatile nature of thyrotropin (TSH) and prolactin (PRL) release in children with classical GH deficiency (GHD; n = 4) and neurosecretory GH dysfunction (NSD; n = 4) and have compared the results with those obtained in children with constitutional delay (control; n = 4). Blood samples were obtained at 20-min intervals for 24 h. Pulse analysis of TSH and PRL was undertaken using the Cluster pulse detection algorithm. Circadian rhythmicity of TSH and PRL was assessed using cosinor analysis. The mean 24-h concentration of GH in the control subjects was significantly higher than that obtained in the GHD and NSD groups. With regard to TSH, the mean serum concentration in the GHD and NSD group were higher than that of the control subjects. This augmentation reflects TSH pulses of large amplitude and area, and a higher interpulse valley mean rather than a difference in peak number or peak duration. No differences in mean PRL concentration or characteristics of PRL pulses were found between the control and GHD and NSD subjects. When the 24 h data sets were divided into day (0800-2000 h) and night (2000-0800 h), the mean nighttime TSH concentration was higher than the daytime concentration in the control, GHD, and NSD groups. Although there were no day versus night differences in TSH pulse frequency in either group, peak amplitude, area, and interpulse valley means were increased during the night in the control group, and peak area, duration, and amplitude mean in the NSD group. The nighttime mean PRL concentrations in the control, GHD, and NSD subjects were higher than those found during the day. This increase was accounted for by increases in PRL peak amplitude, area in the control group, and peak area, amplitude, and interpulse valley mean in the GHD and NSD groups. Cosinor analysis of the 24-h TSH and PRL data revealed clear circadian rhythmicity in all groups of subjects. These data suggest that GHD and NSD are associated with an increase in pulsatile TSH secretion due to an increase in pulse amplitude and interpulse valley mean.

Adolescent↗
PubMed1995

XY gonadal dysgenesis and gonadoblastoma: a study in two sisters with a cryptic deletion of the Y chromosome involving the SRY gene.

This paper reports a case of XY gonadal dysgenesis in two sisters. Both patients presented an eunochoid female phenotype with normal external genitalia. At laparotomy, the elder sister was found to have bilateral gonadoblastoma. Cytogenetic studies, which included G and C banding and in situ hybridization, showed that the patients had an apparently normal 46, XY karyotype. PCR analyses revealed absence of the conserved portion (HMG box) of the SRY gene and of the Y chromosome pseudoautosomal boundary region sequence in both patients. The presence of the ZFY sequence was detected by Southern hybridization in the two affected sisters. The patients' father (46, XY, no mosaicism detected in peripheral blood lymphocytes) was positive for SRY and ZFY sequences. The occurrence of gonadoblastoma is discussed in terms of the genetic factors that may lead to tumor development.

Adolescent↗
PubMed1995

Ectopic ACTH syndrome.

Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4-6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.

Adrenal Glands↗
PubMed1995

Growth hormone pulsatility in active and cured acromegalic subjects.

GH secretion in normal subjects is periodic, with pulses prevailing during sleep. During the day (basal secretion), GH levels are, in general, undetectable. We studied GH secretion by cluster analysis, collecting samples every 20 min for 24 h in 44 subjects: 11 patients with active acromegaly; 16 "cured" acromegalics, and 17 normal subjects. The purpose of this study was to compare GH secretion between patients with active acromegaly and "cured" patients and between "cured" acromegalic patients and normal controls. The number of pulses detected through the 24-h GH profile was not different between acromegalic patients regardless of disease activity (17.5 +/- 4.4 vs. 15.0 +/- 6.0, respectively), but was different when active acromegalic patients and normal controls were compared (8.1 +/- 1.0; P < 0.05) and when cured acromegalic patients and normal controls were compared (P < 0.05). The GH pulsatile secretion/total GH secretion ratio was higher in normal controls than in acromegalic patients regardless of disease activity. We concluded that 1) the increases in GH pulsatility in active and cured acromegalic patients are similar, but most of the 24-h GH secretion is nonpulsatile; 2) half of the GH secretion in normal subjects occurs during pulses; 3) cured acromegalic patients, even those with normal GH and insulin-like growth factor I levels, do not recover a normal GH secretory pattern.

Acromegaly↗
PubMed1995

Estimation of body fat and lean tissue distribution by dual energy X-ray absorptiometry and abdominal body fat evaluation by computed tomography in Cushing's disease.

Body composition determined by dual energy x-ray absorptiometry and the abdominal visceral fat component determined by computed tomographic scanning were examined in women with Cushing's disease and compared with those in obese women with the same anthropometric parameters and those in nonobese women. Patients with Cushing's had no increase in total body fat or the trunk region (android) component, but had a higher intraabdominal fat area compared to the obese subjects. The total lean tissue mass was slightly reduced in Cushing's compared to that in the obese subjects due to a significant decrease in the muscle of the legs and arms; the reduced amounts of fat and lean tissue masses in the arms were the most significant findings in hypercortisolism. The body mineral and bone calcium contents were slightly reduced in Cushing's compared to those in the obese controls. Thus, although obese subjects had more fat and lean tissue and mineral masses than their normal weight counterparts, the Cushing's patients, with the same total fat mass and its components (except in the arms) as obese individuals, present total lean tissue and fractions, including body mineral and bone calcium contents, similar to those in nonobese subjects due to the depletion of the protein depots, as seen in hypercortisolism.

Absorptiometry, Photon↗
PubMed1994

Calcium and prolactin secretion in humans: effects of the channel blocker, verapamil, in the spontaneous and drug-induced hyperprolactinemia.

The effects of the intravenous administration of a calcium channel blocker, verapamil (0.0833 mg/min for 2-3 h after a 5 mg bolus) on prolactin (PRL) and thyrotropin (TSH) circulating levels were assessed in 7 normal subjects and in 17 patients with hyperprolactinemia (11 with prolactinoma and 6 sulpriride-induced). In the normal group a non-significant increase in PRL levels occurred (mean +/- SEM = 11.7 +/- 2.9 micrograms/l verapamil vs. 8.5 +/- 1.4 micrograms/l saline). In this control group the peak response of PRL and TSH to TRH (thyrotrophin releasing hormone) during verapamil or saline was also determined: PRL = 112.0 +/- 27.0 micrograms/l on verapamil vs. 53.6 micrograms/l on saline, p = 0.02; TSH 7.1 +/- 0.7 microU/l on verapamil vs. 9.0 +/- 0.6 mU/l on saline, p = 0.01. In the hyperprolactinemic subjects verapamil induced opposite effects on PRL levels, the prolactinoma group exhibiting an increase in the mean values (168.5 +/- 22.3 micrograms/l vs. 150.8 +/- 23.6 micrograms/l on saline, p = 0.04) whereas in the sulpiride-induced there was a reduction in the mean PRL levels (61.1 +/- 13.8 micrograms/l vs. 78.5 +/- 19.3 micrograms/l on saline, p = 0.002). In both groups of hyperprolactinemic patients no effects on TSH levels were observed. The authors discuss the possibility that the divergent effects of verapamil in hyperprolactinemia of different etiologies could be related to the balance between dopamine and calcium channel effects on hypothalamus and/or pituitary.

Adult↗
PubMed1993

Exercise tolerance is lower in type I diabetics compared with normal young men.

The present investigation was conducted to study metabolic and hormonal responses to prolonged exercise to exhaustion in insulin-dependent diabetic subjects. Sixteen healthy subjects (control) and 15 diabetics with no-insulin administration for 12 hours were studied. They were submitted to short-term exercise to exhaustion on a cycle ergometer at 55% to 60% of maximum oxygen consumption (VO2max). Exercise tolerance was significantly lower in diabetic subjects (66 +/- 6.7 v 117 +/- 9.4 minutes), and glucose concentration was significantly higher in these subjects. At exhaustion, only diabetic subjects showed a significant decrease in glycemia (142 +/- 20 v 111 +/- 16 mg/dL). Lactate concentration increased significantly during exercise up to 30 minutes, but at exhaustion only control subjects showed a reduction. No significant difference in free fatty acid (FFA) concentrations was observed between the groups during a 30-minute exercise period; however, at exhaustion levels were significantly higher in control subjects. Prolactin and C-peptide concentrations were significantly lower in diabetic subjects, whereas glucagon concentration was higher. No significant differences between the groups were observed for cortisol and growth hormone (GH) concentrations. We conclude that (1) diabetic subjects show reduced exercise tolerance when no insulin is administered for 12 hours, and (2) exercise to exhaustion reduces serum glucose concentrations in insulin-dependent diabetics.

Adult↗
PubMed1993

The desmopressin stimulation test in the differential diagnosis of Cushing's syndrome.

OBJECTIVE: We assessed the ability of desmopressin to stimulate the pituitary-adrenal axis in patients with Cushing's syndrome. DESIGN AND SUBJECTS: The cortisol response to 5 ot 10 micrograms of intravenous desmopressin was evaluated in 31 patients with Cushing's syndrome of several aetiologies and in 15 normal subjects. RESULTS: Cortisol responses were observed in 15 out of 16 patients with pituitary dependence and in two patients with adrenal nodular hyperplasia, the increase above baseline ranging from 61 to 379% in the responders. Eight patients with adrenal tumours and one with the ectopic ACTH syndrome did not respond to desmopressin, having shown changes in their cortisol levels from -5 to 42% above baseline. Responses occurred in two out of the 15 normal individuals, whose cortisol increased 58 and 69% above baseline, respectively. Stimulation tests with standard agents as lysine vasopressin or ovine corticotrophin-releasing hormone were performed in the same patients and there was a high degree of concordance. No serious adverse reactions were observed in the tests with desmopressin. CONCLUSIONS: Desmopressin was able to stimulate the pituitary-adrenal axis in patients with Cushing's disease and, like corticotrophin releasing hormone, it may prove useful in the differential diagnosis of Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed1992

Effects of testosterone on growth hormone secretion and somatomedin-C generation in prepubertal growth hormone deficient male patients.

1. The role of testosterone (T) in growth was evaluated in 11 prepubertal hypopituitary males during two 15-day periods separated by a 4-week interval, i.e., before (PRE-T period) and during T ester treatment (50 mg every 5 days, 3 im doses-T period). 2. T increased growth hormone (GH) secretion, assessed by 4-h rhythm (mean +/- SEM = 1.90 +/- 0.27 vs 1.77 +/- 0.21 ng/ml; P < 0.05) and after a GHRH stimulus (3.42 +/- 0.54 vs 3.08 +/- 0.43 ng/ml; P < 0.05) as compared to the PRE-T period. 3. T also increased basal somatomedin-C (SM-C) levels (0.20 +/- 0.03 vs 0.15 +/- 0.02 U/ml; P < 0.001) and SM-C generation. After GH was administered in 4 im doses (0.01, 0.02, 0.05 and 0.1 U/kg), SM-C levels were 0.31 +/- 0.08 vs 0.24 +/- 0.07 U/ml, P < 0.001. T did not change incremental (absolute minus basal) SM-C levels (0.15 +/- 0.08 vs 0.12 +/- 0.07 U/ml; P > 0.05). 4. The results suggest that T increased plasma SM-C levels by stimulating residual GH secretion in hypopituitary males.

Adolescent↗
PubMed1988

Somatomedin levels in the diagnosis and therapy of growth hormone deficiency.

Serum somatomedin-C (SM-C) and somatomedin (SM) concentrations were measured by, respectively, radioimmuno (SM-C RIA) and radioreceptor assays (SM RRA) in 3 groups of children with short stature. The patient population was different from previously reported series in that it was urban Brazilian, low income, and significantly older. Group A consisted of 6 male and 3 female children, aged 7.7-16.0 years, whose average peak plasma immunoreactive growth hormone (GH) was above 10 ng/ml. Group B contained 8 male and 5 female untreated GH-deficient patients, ranging in age from 9.5 to 21.0 years. In Group C there were 4 male and 1 female GH-deficient subjects treated with I.M. injections of GH (0.1 U/kg) from 1 month to 7 years. The mean +/- SE basal RIA SM-C (ng/ml) concentrations were significantly lower in groups B (34.2 +/- 8.8) and C (43.8 +/- 13.7) than A (214.3 +/- 42.7): A X B, P less than 0.001 and A X C, P less than 0.02. Likewise the mean +/- SE basal RRA SM (ng/ml) concentrations were significantly lower in groups B (78.9 +/- 17.6) and C (90.8 +/- 19.3) than group A (316.3 +/- 43.0): A X B, P less than 0.001 and A X C, P less than 0.002. A significant linear correlation was observed between RIA and RRA in group B (r = 0.84; P less than 0.001) and C (r = 0.96; P less than 0.01), but not for A (r = 0.61; P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Glucocorticoids and glucose metabolism: hepatic glucose production in untreated Addisonian patients and on two different levels of glucocorticoid administration.

Plasma glucose, insulin levels and hepatic glucose production rates were studied after an overnight fast in six Addisonian patients in three different conditions: off replacement treatment, on substitution therapy and on high-dose glucocorticoid treatment. For comparison eight normal subjects were evaluated in basal conditions. Fasting plasma glucose and hepatic glucose production did not change significantly with either level of glucocorticoid treatment when compared to the untreated state and the normal controls, but there was a significant increase in plasma glucose levels in the high-dose cortisone-treated Addisonian patients when compared to the untreated state. Insulin levels were significantly lower in the untreated state and significantly higher in the high dose-treated patients when compared to the normal controls. It is suggested that in these experimental conditions the peripheral actions of glucocorticoids are predominant over the hepatic effects by virtue of their ability to produce secondary changes in insulin levels, keeping the hepatic glucose production constant.

Addison Disease↗
PubMed1987

Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia.

The effect of somatostatin (SRIF: 10 micrograms/min during 120 min) on serum prolactin (PRL) levels was studied in eleven patients with hyperprolactinemia of varying causes: 2 patients with acromegaly; 2 with primary hypothyroidism; 4 with prolactinoma and 3 with drug (sulpiride) induced hyperprolactinemia. During SRIF infusion, no significant change in PRL levels was observed in any of the 4 groups studied except in one female patient with a prolactinoma. The biological activity of SRIF was demonstrated by the significant inhibition (P less than 0.05) of insulin levels seen in all 11 patients (52% fall in relation to basal) without simultaneous modification of glycemia. These data suggest that SRIF does not decrease PRL secretion in most patients with hyperprolactinemia.

Acromegaly↗