bluuebunny/crossref_metadata_2025 huggingface dataset:
HYPERPROLACTINAEMIA AND HYPOGONADISM IN MEN: RESPONSE TO EXOGENOUS GONADOTROPHINS
Authors: LUBOSHITZKY R. , ROSEN E. , TRESTIAN S. , SPITZ I. M.
Published: March 2008

Three male patients with pituitary tumours and marked hyperprolactinaemia were investigated. Their prolactin (PRL) levels ranged from 210 to 2500 ng/ml. The subjects had clinical and laboratory characteristics of hypogonadotrophic hypo‐gonadism. All were treated with human chorionic gonadotrophin (HCG) and in one subject human menopausal gonadotrophin (HMG) was given in addition. In all three patients, despite the persistence of hyperprolactinaemia, serum testosterone had risen to normal levels within 4–17 days after starting HCG. Despite the normal testosterone level, impotence persisted in two patients and the third had persistently decreased libido. The hypogonadism in these patients may be related to an absolute reduction in gonadotroph number secondary to destruction by tumour mass. Alternatively, hyperprolactinaemia may inhibit the synthesis or release of the gonado‐trophins or LHRH. Despite hyperprolactinaemia, pharmacological doses of HCG induced testosterone secretion in all these three subjects.
CHRONIC DIPHENYLHYDANTOIN THERAPY DOES NOT REDUCE PLASMA 25‐HYDROXY‐VITAMIN D
Authors: WARK J. D. , LARKINS R. G. , PERRY‐KEENE D. , PETER C. T. , ROSS D. L. , SLOMAN J. G.
Published: March 2008

A randomized controlled study was performed to investigate the effect of 2 years’monitored diphenylhydantoin (DPH) therapy on plasma 25‐hydroxyvitamin D (25‐OHD) in nonepileptic, non‐institutionalized subjects. Mean ± SEM plasma 25‐OHD of 18 DPH‐treated subjects at the end of 2 years’drug treatment was 59 ± 8 nmol/l (23.6 ± 3.2 ng/ml), which was not decreased compared to that of eighteen control subjects (54±8 nmol/l, 21.6±3.2 ng/ml). In addition, mean plasma 25‐OHD had not changed 1 month after ceasing DPH. The treated group had a higher mean serum alkaline phosphatase (SAP) during DPH treatment, attributable to hepatic enzyme induction. It is concluded that therapeutic doses of DPH without other anticonvulsants do not have a clinically significant effect on plasma 25‐OHD.
TREATMENT OF CUSHING'S DISEASE IN JUVENILES WITH INTERSTITIAL PITUITARY IRRADIATION
Authors: CASSAR J. , DOYLE F. H. , MASHITER K. , JOPLIN G. F.
Published: March 2008

Nine juvenile patients (five boys and four girls aged 10–18) with Cushing's disease were treated with pituitary implantation of 198 Au and/or 90Y. No patient had any surgical complication from the procedure. At the latest assessment, 3 months to 17 years after operation, Cushing's disease was in remission in all the patients; the response time following operation was a few days to 3 months. Radiology of the pituitary fossa at time of pituitary implantation was normal in all patients and remains so. The final height in six patients is 149–172 cm (59–67.5 inches) and three patients who continue to grow have increased by 13, 6 and 3 cm since implantation. Only one patient required full pituitary hormone replacement therapy, and he had been previously treated by external irradiation, and one other patient failed to complete puberty. In all the other seven sexual maturation is normal and one has fathered two children. We conclude that pituitary implantation with interstitial irradiation is a satisfactory form of treatment for Cushing's disease in juveniles.
EVALUATION OF RESECTION OF PITUITARY MICROADENOMA FOR THE TREATMENT OF CUSHING'S DISEASE IN PATIENTS WITH RADIOLOGICALLY NORMAL SELLA TURCICA
Authors: WAJCHENBERG B. L. , SILVEIRA A. A. , GOLDMAN J. , CESAR F. P. , MARINO R. , LIMA S. S.
Published: March 2008

Si.: patients with Cushing's disease and a radiologically normal sella turcica have been treated by transsphenoidal hypophysectomy. Microadenomas were found and removed in five. One patient was in complete remission by 2 months and three by 6 months post‐operatively. Two of the remaining patients (one with and the other without a surgically demonstrable tumour) were not cured after 8 and 15 months follow‐up, respectively. Our data suggest that pituitary tumours are present in the majority of patients with Cushing's disease. The possibilities of incomplete adenomectomy or of a tumour buried within the gland should be considered in patients in whom pituitary surgery does not induce remission. In one patient, subsequently proven to have a pituitary adenoma, the disease remitted pre‐operatively with cyproheptadine, suggesting hypothalamic regulation of the tumour and/or direct drug action at the pituitary level.
EFFECTS OF LONG‐TERM TREATMENT WITH METERGOLINE IN PATIENTS WITH IDIOPATHIC OLIGOSPERMIA
Authors: MASALA A. , DELITALA G. , ALAGNA S. , DEVILLA L. , ROVASIO P.P.
Published: March 2008

The effect of metergoline, an ergoline derivative with antiserotonin as well as dopaminergic properties, was studied in forty‐five male patients with idiopathic oligospermia. Metergoline treatment (6 mg daily for 5 months) had no demonstrable effect on spermatogenesis; moreover, it did not influence the serum levels of LH, FSH, testosterone and oestradiol although it significantly reduced prolactin levels. It is concluded that, in all likelihood, serotonin plays little or no part in the pathogenesis of idiopathic oligospermia and that pharmacological reduction of normal prolactin levels has no therapeutic effect on this disease.
IMMUNOREACTIVE SOMATOMEDIN B IN ACROMEGALY AND IN TURNER'S SYNDROME
Authors: BENKER G. , SPIRA G. , ZÄH W. , THARANDT L. , HACKENBERG K. , REINWEIN D.
Published: March 2008

Serum somatomedin B was measured by radioimmunoassay in forty‐seven normal subjects, twenty‐nine patients with acromegaly before and twenty‐four after treatment, and eighteen patients with Turner's syndrome. Somatomedin B levels were significantly elevated in untreated acromegaly and in Turner's syndrome compared with the control group; they decreased following treatment of acromegaly. Because of the overlap between the groups, little information could be obtained from single somatomedin B estimations, which could, therefore, not replace dynamic tests of growth hormone secretion. No correlation between growth hormone and somatomedin B in acromegaly was detected; however, somatomedin B appeared to be related to the insulin response during the oral glucose tolerance test. In Turner's syndrome, no relationship between somatomedin B and insulin production, urinary oestrogen excretion, growth hormone secretion, gonadotrophin levels, age or height was found. The reason for the raised somatomedin B levels in Turner's syndrome remains at present unknown.
CHRONIC DOPAMINE RECEPTOR STIMULATION USING BROMOCRIPTINE: FAILURE TO MODIFY THYROID FUNCTION
Authors: KÖBBERLING J. , DARRAGH A. , POZO E. DEL
Published: March 2008

Administration of 2.5 mg bromocriptine (Parlodel), a dopamine agonist, on two occasions to six normal volunteers did not alter the plasma TSH response to an i.v. injection of 100 μg TRH, but significantly (P < 0.01) blunted it after 200 μg. Chronic bromocriptine treatment (7.5–50 mg/day) of fifteen acromegalic subjects failed to influence basal plasma TSH or the response pattern to 200 μg TRH. The thyroxine Binding Index (TBI) and the levels of T3 and T4 were not modified by treatment. These results indicate that chronic dopaminergic therapy with bromocriptine does not alter thyroid function.
SERUM THYROGLOBULIN IN NORMAL SUBJECTS AND PATIENTS WITH HYPERTHYROIDISM DUE TO GRAVES’DISEASE: EFFECTS OF T3, IODIDE, 131 I AND ANTITHYROID DRUGS
Authors: GARDNER D. F. , ROTHMAN J. , UTIGER R. D.
Published: March 2008

A sensitive, reproducible radioimmunoassay for thyroglobulin (Tg) in unextracted human serum is described. The mean (± SD) serum thyroglobulin concentration in ninety‐three normal subjects was 8±8 ± 5±1 ng/ml. The mean serum Tg concentration in forty‐seven patients with hyperthyroidism due to Graves’disease was 162 ± 145 ng/ml, and in nine patients with subacute thyroiditis 140 ± 75 ng/ml. The administration of T3, 75 /μg daily for 3 weeks to normal subjects, produced parallel and significant decreases in both serum Tg and T4 concentrations. Administration of iodide to normal subjects for 13 days resulted in significant increases in serum Tg concentrations, associated with increases in serum TSH and decreases in serum T4 concentrations. In patients with hyperthyroidism due to Graves’disease, iodide administration had no effect on serum Tg concentrations in five of six patients studied, though all had a reduction in serum T4 and T3. Administration of radioactive iodine, with or without iodide, to hyperthyroid patients resulted in acute increases in serum Tg concentrations in all patients. In patients with hyperthyroidism due to Graves’disease treated with antithyroid drugs, serum Tg concentrations were initially lower (mean 109 ng/ml) and declined to or towards normal during therapy in those who subsequently achieved remission. Initial serum Tg concentrations were higher (mean 207 ng/ml) and serum Tg concentrations did not change in the patients who developed recurrent hyperthyroidism when antithyroid drug therapy was decreased or discontinued. These data suggest that: (1) Tg release by the thyroid is normally under TSH control; (2) iodide inhibits thyroidal T4 and T3 release without affecting Tg secretion; (3) thyroidal injury results in marked increases in serum Tg concentrations; and (4) initial and/or serial Tg determinations may be useful in predicting remission in patients with hyperthyroidism due to Graves’disease treated with antithyroid drugs.
PROLACTIN RELEASE BY INTRAVENOUS CIMETIDINE IN MAN: EVIDENCE FOR A SUPRAPITUITARY LOCUS OF ACTION
Authors: FERRARI C. , CALDARA R. , BARBIERI C. , CAMBIELLI M. , BIERTI L. , ROMUSSI M.
Published: March 2008

In an attempt to identify the sites at which cimetidine stimulates prolactin release, the drug was administered intravenously (6 mg/kg body weight) to healthy subjects under basal conditions, during dopamine infusion (1/μg/Kg‐min for 120 min) and after pretreatment with L‐dopa plus carbidopa (250 plus 25 mg every 6 h for 1 day). The serum prolactin response to cimetidine was abolished by dopamine infusion and almost completely suppressed by L‐dopa plus carbidopa administration. These findings suggest that the drug acts on the central nervous system to stimulate prolactin release. Although the mechanism of this action is unclear, it does not seem to depend on an antidopaminergic effect and may be related to blockade of brain H2 histamine receptors.
AN‘ARTIFICIAL BETA CELL’FOR CONTROL OF DIABETES MELLITUS: EFFECT ON PLASMA GLUCAGON LEVELS
Authors: HORWITZ D. L. , GONEN B. , JASPAN J. B. , LANGER B. G. , RODMAN D. , ZEIDLER A.
Published: March 2008

We have investigated the use of a glucose‐controlled insulin infusion system, or artificial beta cell. On the feedback day, mean plasma glucose was significantly effect of improved control on plasma glucagon levels. Five insulin‐requiring diabetic subjects in stable control were hospitalized for two 24 h periods. During one, they were given their usual dose(s) of subcutaneous insulin. In the other, the‘feedback’day, insulin administration was under feedback control by the artificial beta cell. On the feedback day, mean plasma glucose was significantly‐lower in all subjects. Variability in plasma glucose throughout the day was also significantly less on the feedback day. All five subjects showed a significant fall in serum immunoreactive glucagon levels on the feedback day, suggesting that the glucagon abnormalities of diabetes may be secondary to the insulin deficiency, rather than a second primary defect of diabetes.
COMPARISON OF SINGLE AND REPEATED APPLICATIONS OF A LONG‐ACTING SYNTHETIC ANALOGUE OF LHRH [D‐SER (TBU)6 EA10 LHRH] IN THE ASSESSMENT OF PITUITARY GONADOTROPHIN SECRETORY CAPACITY
Authors: WILLIAMS C. A. VAUGHAN , McNEILLY A. S. , BAIRD D. T.
Published: March 2008

A long‐acting synthetic analogue of LHRH [D‐Ser (TBU)6 EA10 LHRH] was administered intramuscularly to thirteen normal women in the early‐to‐mid follicular phase of the menstrual cycle. Six women received a single injection of 5 μg of analogue and seven received 10 μg of the analogue, followed by 20 and 10 μg at 10 and 24 h after the first injection, respectively. The concentrations of LH, FSH and oestradiol in plasma were measured before, and at intervals up to 72 h after treatment. In the group receiving 5 μg of analogue the concentrations of both LH and FSH rose rapidly to a peak value five times the pre‐injection value, 5 h after injection. The concentrations of both gonadotrophins remained elevated for 10 h, but 24 h after injection had returned to control values. The concentration of oestradiol rose progressively to reach a peak value 7 h after injection. In the second group of women, receiving three injections of analogue, there was a rapid twelvefold increase in the concentration of LH in plasma within 4 h of the initial injection, and plasma concentrations remained elevated for 10 h. The concentration of FSH rose progressively to a peak value, five times the pretreatment value, 5 h after the initial injection and was still elevated after 10 h. The concentrations of both gonadotrophins remained elevated above pretreatment values for at least 34 h after the start of treatment. The concentration of oestradiol rose gradually to a peak value 7 h after the initiation of treatment and remained elevated for 34 h. These results indicate that a single injection of the LHRH analogue is effective in demonstrating pituitary secretory activity, but repeated applications are required to induce and maintain a rise in plasma LH similar in magnitude and duration to the pre‐ovulatory, mid‐cycle surge. This analogue of LHRH provides a simple means of evaluation of the secretory capacity of the anterior pituitary.
STUDIES OF CIRCULATING PARATHYROID HORMONE IN MAN USING A HOMOLOGOUS AMINO‐TERMINAL SPECIFIC IMMUNORADIOMETRIC ASSAY
Authors: PAPAPOULOS S. E. , MANNING R. M. , HENDY G. N. , LEWIN I. G. , O'RIORDAN J. L. H.
Published: March 2008

Circulating immunoreactive parathyroid hormone (PTH) was measured by a homologous, amino‐terminal, specific, immunoradiometric assay in man. In forty‐two healthy subjects the concentrations ranged between < 40 pg/ml and 120 pg/ml. No hormone could be detected in the sera of eleven patients with hypoparathyroidism, but the concentrations were clearly elevated in six patients with pseudohypoparathyroidism (range 190–1120 pg/ml). In thirty‐five patients with primary hyperparathyroidism the mean (±SEM) concentration was 283·4±42·4 pg/ml (range 100–1350 pg/ml). A significant positive correlation was demonstrated between immunoassayable hormone and serum calcium concentrations in these patients. In nine patients PTH concentrations were measured before and after parathyroidectomy. In all of them they were elevated pre‐operatively but fell to the normal range after parathyroidectomy. The disappearance of exogenously administered synthetic human PTH (1–34) from the circulation of two normal subjects was rapid with an apparent plasma half‐disappearance time (t½) between 2 and 3 min; the metabolic clearance rate was 12·9 and 9·0 ml. kg‐1, min‐1 respectively. Similarly, the disappearance of endogenous, amino‐terminal, immunoreactive PTH from the circulation of two patients with primary hyperparathyroidism after parathyroidectomy was rapid; the apparent t½ was approximately 3 min. Homologous amino‐terminal specific immunoassays for PTH can thus be useful for the study of both the acute, and chronic, changes of circulating hormone in man and represent an improvement over heterologous unselected assay systems.
TSH RESPONSES TO TEMPERATURE IN PRIMARY HYPOTHYROIDISM
Authors: O'MALLEY B. P. , DAVIES T. J. , ROSENTHAL F. D.
Published: March 2008

We have studied the serum TSH responses to alterations in body temperature by heating twelve patients with primary hypothyroidism for 48 h and determining the initial and final TSH levels. In four control patients, we estimated the TSH responses to rest and exercise. In a group of three patients, the TSH levels were recorded at frequent intervals over a 48 h period, during which they were rested and subsequently warmed. Our results show that in the twelve patients initially investigated, there was a significant fall in TSH. In the smaller group of three patients studied more intensively, TSH levels were inversely related to cutaneous and core temperature. In primary hypothyroidism alterations in body temperature influence the levels of circulating TSH.
PLASMA DEHYDROEPIANDROSTERONE SULPHATE IN HYPOTHYROID PREMENOPAUSAL WOMEN
Authors: BASSI F. , PUPI A. , GIANNOTTI P. , FIORELLI G. , FORTI G. , PINCHERA A. , SERIO M.
Published: March 2008

Plasma dehydroepiandrosterone sulphate (DHEAS), cortisol (F) and prolactin (PRL) were measured in seventeen premenopausal women with primary hypothyroidism and in fifteen normal premenopausal women. Significantly lower (P < 0·001) DHEAS levels were found in hypothyroid women while F and PRL were in the range of normal controls. No significant relation was found between DHEAS and total thyroxine (T4) and TSH. Our results support the hypothesis that DHEAS secretion is impaired in some women with primary hypothyroidism.
STEROIDS IN OVARIAN AND PERIPHERAL VENOUS BLOOD IN POLYCYSTIC OVARIAN DISEASE
Authors: LAATIKAINEN T. J. , APTER D. L. , PAAVONEN J. A. , WAHLSTRÖM T. R.
Published: March 2008

Ovarian and peripheral venous blood samples were collected at operation in six patients with polycystic ovaries (PCO) and seven control subjects with normal ovarian function in the follicular phase of the cycle. Plasma concentrations of unconjugated testosterone, dihydrotestosterone (DHT), androsterone, androstenedione, dehydroepiandrosterone (DHEA), pregnenolone, progesterone, 17α‐hydroxyprogesterone (17α‐OH‐P) and oestradiol were determined by specific radioimmunoassay techniques, and concentrations of DHEA, androsterone and pregnenolone sulphates by gas chromatography. In the control group, ovarian vein concentrations of all unconjugated steroids, except progesterone, were significantly higher than the corresponding peripheral vein concentrations, suggesting ovarian secretion. No significant differences were demonstrated between ovarian and peripheral plasma levels of steroid sulphates. Ovarian vein levels of androstenedione, testosterone and DHEA were markedly elevated in PCO patients compared with the control group, and the levels of DHT and androsterone to a lesser degree. Polycystic ovaries appear to secrete androsterone sulphate, but no significant secretion of DHEA sulphate could be demonstrated. Ovarian venous levels of oestradiol in the PCO group did not differ from those in the control group. Elevated ovarian venous androgen levels in the PCO group seemed to correlate with thecal cell hyperplasia as indicated by histological examination of ovarian biopsies. In one PCO patient, blood levels of different steroids were followed for a month after ovarian wedge resection. Testosterone fell to half the pre‐operative value and a temporary fall was also noticed in other androgens. A marked rise in plasma progesterone concentration at the end of the follow‐up period suggested that ovulation had occurred.
THE EFFECT OF OESTROGENS ON HUMAN CALCITONIN SECRETION AFTER CALCIUM INFUSION IN ELDERLY FEMALE SUBJECTS
Authors: MORIMOTO S. , TSUJI M. , OKADA Y. , ONISHI T. , KUMAHARA Y.
Published: March 2008

The effect of oestrogen administration (4–6 weeks) on the response of human calcitonin (hCT) secretion to 5 min calcium infusions was studied in ten elderly women. There was no significant difference in mean basal plasma hCT levels before and after oestrogen administration. However, the mean increment in plasma hCT in response to calcium infusion (ΔhCT) increased significantly (P < 0·001) from 21·9±6·6 (mean ±SE) before treatment, to 79·6±15·5 ng/l after oestrogen administration. Mean serum calcium levels decreased significantly (P < 0·001) from 2·42 ±0·06 before to 2·19·0±07 mmol/l after oestrogen treatment. Mean plasma immunoreactive PTH (iPTH) levels increased significantly (P < 0·05) from 521·41 before to 696·96 ng/l after oestrogen treatment. To exclude out the possibility that the decreased serum calcium level itself might have influenced ΔhCT, 1α‐hydroxycholecalciferol (1α‐OH‐D3) was administered with oestrogens. While this resulted in a slight increase in serum calcium level, there was no significant difference in ΔhCT in response to calcium infusion following oestrogen treatment alone, and after combination therapy of oestrogen and 1 α‐OH‐D3. The primary action of administered oestrogen may be in stimulating hCT secretion which results in a decrease in plasma calcium concentration and an increase in plasma iPTH level.
OVARIAN AND PLACENTAL HORMONES DURING PROLACTIN SUPPRESSION AND STIMULATION IN EARLY HUMAN PREGNANCY
Authors: ANDERSEN A. N. , HERTZ J. , KJER J. J. , ESKILDSEN P. C. , LARSEN P. S. , SVENSTRUP B. , NIELSEN J. , ARENDS J.
Published: March 2008

Twenty‐seven healthy females referred for legal abortion between the sixth and ninth week of pregnancy were treated for 1 week with either bromocriptine, metoclopramide or placebo. Serum prolactin was significantly (P < 0·01) elevated by metoclopramide and suppressed by bromocriptine. Despite a more than tenfold difference in circulating prolactin levels among these two groups, no significant difference was found in serum levels of progesterone, oestradiol, human chorionic gonadotrophin (hCG) human placental lactogen (hPL) or pregnancy specific B1‐glycoprotein (SP1). These data suggest that circulating levels of prolactin below 150 ng/ml are without effect on either luteal or placental hormone secretion during early human pregnancy.
RESPONSE OF PERIPHERAL SERUM SEX STEROIDS AND SOME OF THEIR PRECURSORS TO A SINGLE INJECTION OF hCG IN ADULT MEN
Authors: MARTIKAINEN H. , HUHTANIEMI I. , VIHKO R.
Published: March 2008

Nine healthy men were given a single intramuscular injection of 5000 iu of human chorionic gonadotrophin (hCG). Peripheral blood samples were serially collected up to 7 days after the injection, and the sera were analysed for hCG and eight steroids hCG reached a maximum, 130·13 (SEM) iu/l, at 8 h and declined thereafter with a half‐life of about 24 h. Testosterone and 17‐hydroxyprogester‐one were elevated at 2 h, to 132·11% and 169·32%, respectively, when compared with the 0 h levels. It is to be observed, however, that in saline injected control men (n= 6) an early increase in serum testosterone was also observed. When compared with the saline‐injected controls, the first significant elevation in testosterone was obtained not earlier than at 12 h, and the maximum was seen at 96 h (239·23% of controls). Correspondingly, the first significant elevation of 17‐hydroxyprogesterone was seen at 8 h and the maximum at 36 h (296·44%) after the hCG injection. The maximum concentration of serum oestradiol was also found at 36 h (230·15%). The patterns of response in serum levels of androstenedione, and, to a lesser extent, in those of 5α‐dihydrotestosterone, were similar to those of testosterone. Progesterone levels decreased during days 3–7 after the hCG injection, and no clear changes were seen in the peripheral serum concentrations of pregnenolone and androsterone. The ‐24 and ‐12 h control samples displayed a diurnal rhythmicity for progesterone, androstenedione, testosterone and androsterone; the 08.00 h levels being significantly higher than those at 20.00 h. Our results show that, in the adult, human testicular androgen biosynthesis responds relatively slowly to additional gonadotrophic stimulation. The late peak of peripheral serum testosterone level after the hCG injection and the stimulatory sequence of its precursor steroids suggest that the side chain cleavage of C21 steroids, beyond 17 α‐hydroxylation, may be a critical step in the human testicular androgen response to this gonadotrophin. The clear increase in serum oestradiol during the hCG stimulation points out the potential importance of endogenous oestrogens in testicular endocrine function.
INAPPROPRIATE GROWTH HORMONE RELEASE IN THE DIENCEPHALIC SYNDROME OF CHILDHOOD: CASE REPORT AND 4 YEAR ENDOCRINOLOGICAL FOLLOW‐UP
Authors: DROP S. L. S. , GUYDA H. J. , COLLE ELEANOR
Published: March 2008

A boy with an astrocytoma in the anterior hypothalamic area and typical features of the diencephalic syndrome of childhood was followed with yearly endocrinological evaluation from 10 months of age until he was 5½‐years‐old. Radiation therapy resulted in temporary clinical improvement. At the time of diagnosis height and bone age were advanced. Basal concentrations of growth hormone (GH) were markedly elevated and could only be partially suppressed by an oral glucose load. There was a paradoxical decline of GH levels following arginine‐insulin infusion and an abnormal GH release with TRH administration. Abnormal GH response to the various stimuli persisted for 2 years after radiation therapy. Pituitary secretion of LH, FSH, TSH, prolactin and ACTH remained intact. The characteristic clinical features as well as the endocrinological findings remain unexplained.
THE PROLACTIN RESPONSE TO METOCLOPRAMIDE IN GROWTH HORMONE DEFICIENT ADOLESCENT MALES
Authors: COHEN H. N. , BEASTALL G. H. , FYFFE J. A. , FITZGERALD V. , THOMSON J. A.
Published: March 2008

The growth hormone (GH) and prolactin (PRL) responses following administration of 10 mg i.v. metoclopramide (MCP) (‘Maxolon’—Beecham Pharmaceuticals) have been examined in thirty adolescent males with short stature and delayed puberty, eight of whom have isolated growth hormone deficiency. The results demonstrate that peak GH and PRL levels following stimulation were highly significantly correlated when all subjects were analysed together (r=0·61, P < 0·001) but when the responses of the GH deficient and non‐deficient groups of subjects were analysed separately no significant correlation was obtained (P > 0·1), this reflected the fact that the PRL response to MCP was significantly lower in the GH deficient group (P < 0·0002). In addition two boys who demonstrated biochemical GH deficiency prior to puberty only, showed PRL responses similar to boys with normal GH reserves. The results suggest that the PRL response to MCP may be of value in the assessment of stimulation tests of GH reserve, as well as in the selection of patients for treatment with G.H.
EFFECTS OF CYPROHEPTADINE ON INSULIN‐INDUCED HYPOGLYCAEMIA SECRETION OF PRL, GH AND CORTISOL
Authors: KLETZKY O. A. , MARRS R. P. , NICOLOFF J. T.
Published: March 2008

The effect of cyproheptadine hydrochloride on release of prolactin (PRL), growth hormone (GH) and cortisol following insulin‐induced hypoglycaemia was investigated in a group of eight adult female and male subjects. The results of this study demonstrated that cyproheptadine does not influence the release of these three hormones under the conditions employed in this study. The conflicting observation concerning the action of cyproheptadine on pituitary function as reported in the literature, may be a reflection of the diversity of pharmacological actions of this drug. Thus, any purported influence this drug might have on pituitary hormonal release should be interpreted with caution.
THE CARDIOVASCULAR EFFECT OF VASOPRESSIN IN RELATION TO ITS PLASMA CONCENTRATION IN MAN AND ITS RELEVANCE TO HIGH BLOOD PRESSURE
Authors: KHOKHAR A. M. , SLATER J. D. H. , MA J. , RAMAGE CHRISTINE M.
Published: March 2008

The cardiovascular response and the changes of plasma arginine vasopressin (AVP) concentration following graded doses of AVP infused intravenously have been defined in six normal young men.The same measurements were also made during fluid deprivation in a patient with both nephrogenic diabetes insipidus and systemic hypertension. When, following AVP infusion, mean diastolic arterial pressure increased from 72·3 mmHg (SEM) to 78·2 mmHg (SEM) in the normal subject group, mean plasma AVP increased by 14·5 fmol/ml. When the patient was deprived of water, diastolic pressure increased, despite the fluid loss, from 90 to 105 mmHg, with a comparable increase of plasma AVP concentration of 15·3 fmol/ml. Further increases of plasma AVP concentration in either the normal subjects or in the patient were not associated with further increments of arterial pressure. We suggest that under pathophysiological circumstances in man plasma AVP concentrations may achieve levels which have a significant cardiovascular effect.
A LOW DOSE REGIME OF 1α HYDROXYVITAMIN D3 IN THE MANAGEMENT OF SENILE OSTEOPOROSIS: A PILOT STUDY
Authors: COHEN H. N. , FARRAH D. , FOGELMAN I. , GOLL C.C. , BEASTALL G. H. , McINTOSH W. B. , FLETCHER M. , BOYLE I. T.
Published: March 2008

A comparison has been made between the metabolic consequences of daily administration for 6 weeks of 1·0 μg and 0·5 μg la hydroxyvitamin D3 (1α(OH)D3) in twenty patients with senile osteoporosis. There was no significant difference in the increase of calcium absorption which occurred in the two treatment groups between the beginning and end of the trial period. Serum and urinary calcium rose significantly in those receiving 1·0 μg 1α(OH)D3 but not in the lower dosage group. Serum parathyroid hormone levels were suppressed in the higher dosage group only. There was a significantly greater rise of serum inorganic phosphate, and fall of serum magnesium, on the higher dosage, but no significant change in serum creatinine occurred in either group. It is, therefore, suggested that in long term therapy regimes for osteoporosis incorporating 1α(OH)D3, 0·5 μg may be a more suitable daily dose than 1·0 μg 1α(OH)D3.
PANCREATIC SOMATOSTATINOMA PRESENTING WITH HYPOGLYCAEMIA
Authors: WRIGHT J. , ABOLFATHI A. , PENMAN ERICA , MARKS V.
Published: March 2008

A 33‐year‐old woman with a 2 month history of vague ill health was admitted to hospital in hypoglycaemic coma. Preoperative investigation suggested malignant insulinoma as the probable cause of illness, but immunohistological examination of the tumour showed it to consist mainly of somatostatin‐containing cells but sparse insulin‐secreting cells were also present. Plasma immuno‐reactive somatostatin levels were from fifty to 200 times the upper limit of normal and rose in response to arginine and fell during diazoxide infusion. The hypoglycaemia was unusually sensitive to the hyperglycaemic effects of diazoxide and chlorothiazide and, with 5‐fluorouracil as the only specific anti‐tumour agent, there has been clinical, biochemical and radiological evidence of tumour regression.
INHIBITION OF PROLACTIN SECRETION BY NOMIFENSINE IN MAN
Authors: MASALA A. , ALAGNA S. , DEVILLA L. , DELITALA G. , ROVASIO P. P.
Published: March 2008

Serum prolactin, TSH and GH levels were measured in thirty healthy volunteers in fasting conditions and following oral administration of 200 mg nomifensine. In addition, the effect of the drug on serum prolactin and TSH response to synthetic TRH was studied in twenty normal subjects. Inhibition of endogenous catecholamine reuptake by nomifensine significantly inhibited prolactin release whereas it had no effect on TSH and GH levels. Nomifensine administration had no appreciable effect on the TRH‐induced release of TSH and prolactin.
β‐ENDORPHIN AND β‐MSH IN HUMAN PLASMA
Authors: MCLOUGHLIN LORRAINE , LOWRY P. J. , RATTER SALLY , BESSER G. M. , REES LESLEY H.
Published: March 2008

The aim of this study was to establish whether or not a peptide with chromatographic and immunological properties of β‐endorphin exists in human plasma. Using direct chromatography under conditions designed to minimize generation of β‐endorphin and β‐MSH from β‐LPH, we invariably found a peptide with β‐endorphin immunoreactivity eluting in the position of βh‐endorphin on gel chromatography in samples of plasma from patients with elevated ACTH and LPH levels. β‐MSH was only found in the plasma of one patient with the ectopic ACTH syndrome.
ANDROGENS AND SEXUAL BEHAVIOUR IN WOMEN USING ORAL CONTRACEPTIVES
Authors: BANCROFT J. , DAVIDSON D. W. , WARNER P. , TYRER G.
Published: March 2008

Twenty women using oral contraceptives and complaining of impaired sexual function were compared with twenty women without sexual problems, matched for age and oral contraceptive. Whilst the sexual behaviour differed in the two groups, the plasma testosterone, androstenedione, oestradiol and SHBG concentrations were very similar. The total androgen levels were low in both groups. Plasma testosterone and oestradiol concentrations were correlated with measures of sexual interest in the no‐problem group, but not in the problem group. Administration of exogenous androstenedione to women in the problem group, using a double blind cross‐over comparison with a placebo, failed to improve their sexual function except in one case. The majority of women showed a rise in androgen and oestradiol between day 24 of one pill cycle and day 4 of the next. The possible behavioural indications of this pattern are discussed.
VASOPRESSIN CONCENTRATIONS IN THE NEONATAL PERIOD
Authors: REES L. , FORSLING M. L. , BROOK C. G. D.
Published: March 2008

Vasopressin concentrations were measured in the cord blood of thirty infants, thirteen delivered vaginally and seventeen by Caesarean section. There was no correlation with maternal values but the concentration following vaginal delivery (13·5 μu/ml ± 7·9 SD) was significantly higher than that following Caesarean section (4·2 μu/ml ± 6·6 SD). Gestational age did not affect the concentrations, which fell during the first week of life and then rose gradually in term and pre‐term infants. High levels were found in seven sick babies. There was no correlation in the first 3 weeks of life between plasma vasopressin and plasma or urine osmolality in well and sick babies.
ABNORMAL SEX STEROID SECRETION AND BINDING IN MASSIVELY OBESE WOMEN
Authors: KOPELMAN P. G. , PILKINGTON T. R. E. , WHITE N. , JEFFCOATE S. L.
Published: March 2008

We have measured the plasma concentrations of sex steroids and sex hormone‐ binding globulin (SHBG) in twenty‐three massively obese women and ten age‐matched lean female volunteers. In the obese women increased plasma testosterone (obese 3·2 ± 0·5 nmol/1 controls 1·7 ± 0·5 nmol/1, P < 0·3) and androstenedione concentrations (obese 9·7 ± 1·2 nmol/1, controls 4·4 ± 0·6 nmol/1, P= < 0·01) an increased ratio of oestrone:oestradiol (obese 2·4 ± 0·4, controls 1·0 ± 0·1, P= < 0·1) and decreased SHBG levels (obese 30 ± 4 nmol/1, controls 60 + 8 nmol/1, P= <0·001) were found. Obesity differed from the polycystic ovary syndrome (in which a similar pattern of changes of sex steroid concentrations and binding are seen) in that it was associated with normal increases in serum luteinizing hormone (LH) follicle stimulating hormone (FSH) levels in response to the administration of LHRH. We conclude that the common occurrence of menstrual abnormalities in obesity results from abnormal secretion and binding of sex steroids. In addition, the unaltered secretion of LH and FSH in the presence of such changes is evidence for a disorder of hypothalamic function.
SEX HORMONE CHANGES IN MALE EPILEPTICS
Authors: TOONE B. K. , WHEELER M. , FENWICK P. B. C.
Published: March 2008

Mean plasma levels of LH, FSH, PRL, and sex‐hormone binding globulin (SHBG) were raised in twenty‐seven epileptics on anticonvulsants compared with age matched controls. Sexual activity appeared to be reduced. Anticonvul‐ sant therapy results in raised SHBG levels which may be associated with a lowered free testosterone level as indicated by raised LH levels and lowered sexual activity.
CLINICAL, CYTOGENETICAL, HISTOLOGICAL, IMMUNOLOGICAL AND HORMONAL STUDIES IN A CASE OF TRUE HERMAPHRODITISM
Authors: ROY C. , ROGER M. , BOCCON‐GIBOD L. , FELLOUS M. , BONNO R. , PASQUALINI J. , HARPEY J. P.
Published: March 2008

A true hermaphrodite with ambiguous genitalia and 46XX karyotype was studied from 18 months of age to 17 years. At 13 years, he developed an ambiguous puberty, with marked bilateral gynaecomastia and pubic hair score three. A relatively high testosterone level (21 nmol/1), not increased by hCG stimulation, was associated with a high LH level (6IU/1). In the venous blood of the right ovotestis, the steroid concentrations were in the adult male range, especially testosterone (1400 nmol/1). After removal of the right gonad, large fluctuations of oestradiol levels were observed (150–810 pmol/1). The testosterone secretion of the left ovotestis was low, concentrations being 4·2 and 130 nmol/1 in peripheral and gonadal blood respectively at 16 years. A significant LH surge was induced by oral ethinyl‐oestradiol before removal of the left gonad. The 5α‐reductase activity was normal in pubic skin. In the left gonad the concentrations of cytosol receptors for testosterone and 5α‐dihydrotestosterone (DHT) were significant: 14·5 and 65·5 fmol/mg protein respectively. However the plasma DHT level was not increased by hCG. Finally, the presence of H‐Y antigen was demonstrated on lymphocytes. This accords with the presence of testicular tissue in an XX subject, and with significant testosterone production. The high testosterone production did not prevent the appearance of a positive oestrogen‐LH feedback. The relative peripheral insensitivity to testosterone, is, in some ways, inconsistent with the presence of receptors for androgens.
PLASMA PROLACTIN LEVELS AFTER ACUTE AND SUBCHRONIC ORAL ADMINISTRATION OF DOMPERIDONE AND OF METOCLOPRAMIDE: A CROSS‐OVER STUDY IN HEALTHY VOLUNTEERS
Authors: BROUWERS J. R. B. J. , ASSIES J. , WIERSINGA W. M. , HUIZING G. , TYTGAT G. N.
Published: March 2008

Domperidone is a new potent anti‐emetic drug which, in contrast with metoclo‐pramide, does not cross the blood brain barrier. The aim of the present study was to find out whether peripheral dopaminergic blockage by domperidone causes prolactin release, and if so, whether this prolactin release persists during longer‐term treatment. For comparison, metoclopramide, which blocks both peripheral and central dopamine receptors, was studied using a cross‐over trial design. After acute oral administration of both drugs, prolactin levels increased 10‐fold. After further treatment with metoclopramide the prolactin levels were further increased to 15‐fold, but after prolonged administration of domperidone a decrease to a plasma level 6‐fold higher than basal was observed. The clinical implications of these findings are discussed.
GROWTH HORMONE CELL ANTIBODIES AND PARTIAL GROWTH HORMONE DEFICIENCY IN A GIRL WITH TURNER'S SYNDROME
Authors: BOTTAZZO G. F. , McINTOSH C. , STANFORD W. , PREECE M.
Published: March 2008

Growth hormone (GH) cell auto‐antibodies have been demonstrated in the serum of a girl with an iso‐chromosome variant of Turner's syndrome. On two occasions she showed an abnormal response of GH release during insulin induced hypoglycaemia. Her response to GH treatment was poor, but this was commenced at a very late bone‐age. It is possible that autoimmunity is a new aetiological factor for GH deficiency in some cases.
HYPERTHYROIDISM DUE TO A PITUITARY TSH SECRETING TUMOUR WITH AMENORRHOEA‐GALACTORRHOEA
Authors: BENOIT R. , PEARSON‐MURPHY B. E. , ROBERT F. , MARCOVITZ S. , HARDY J. , TSOUKAS G. , GARDINER† R. J.
Published: March 2008

A 20–year‐old female presented with thyrotoxicosis associated with amenorrhoea and galactorrhoea after oral contraceptive withdrawal. Serum TSH was persistently elevated (mean: 28 ± 31 μU/ml during 24–h sampling and did not vary significantly after TRH, bromocriptine or somatostatin. Prolactin levels remained constantly at the upper limit of normal (mean: 206 ± 21 ng/ml, with a minimal increase after TRH, a slight decrease after somatostatin (54%) and a marked decrease after bromocriptine (885%). Surgical exploration revealed an unusually firm tumour adherant to the wall of the sella turcica; electron microscopic study showed that it was composed almost exclusively of thyrotrophs. After a transient period of euthyroidism post‐operatively, T3 toxicosis occurred with an increased TSH level (155 μU/ml) and a rise in TSH and alpha subunit in response to TRH. An increase in T4 followed while prolactin remained low.
DYNAMICS OF SERUM rT3 AND 3, 3‐T2 DURING rT3 INFUSION IN PATIENTS TREATED FOR THYROTOXICOSIS WITH PROPYLTHIOURACIL OR METHIMAZOLE
Authors: LAURBERG P. , WEEKE J.
Published: March 2008

rT3 metabolism in patients treated for thyrotoxicosis with propylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT3 and measurements of the increase in serum rT3 and serum 3, 3′‐diiodothyronine.

The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3, 3′‐T2 which was similar whether PTU or MMI was given. However, after stopping rT3 infusion there was a more rapid fall in serum 3, 3′‐T2 during MMI treatment, compatible with an inhibitory effect of PTU on 3, 3′‐T2 degradation.
EPIDEMIOLOGY OF ACROMEGALY IN THE NEWCASTLE REGION
Authors: ALEXANDER L. , APPLETON D. , HALL R. , ROSS W. M. , WILKINSON R.
Published: March 2008

In an attempt to derive estimates of the incidence and prevalence of acromegaly a survey of the population in the area served by the former Newcastle Regional Hospital Board has been conducted to detect cases of acromegaly alive after 1 January 1960 and diagnosed before 31 December 1971. Cases were detected by means of letters to general practitioners, hospital physicians, neurosurgeons and to hospital records officers, as well as from death certificates. From the population of 3.1 millions a firm diagnosis of acromegaly was made in 164 patients, in eighty‐one on clinical grounds alone and in eighty‐three with confirmation by assay of human growth hormone (hGH). The annual incidence of acromegaly appears to be close to three cases per million and the prevalence of diagnosed cases up to forty cases per million. In male acromegalics there was a significant increase in the risk of death from cardiovascular, cerebrovascular, respiratory and malignant diseases but in females from cerebrovascular disease only.
EFFECT OF INTRANASAL LHRH THERAPY ON PLASMA LH, FSH AND TESTOSTERONE, AND RELATION TO CLINICAL RESULTS IN PREPUBERTAL BOYS WITH CRYPTORCHIDISM
Authors: ILLIG RUTH , TORRESANI T. , BUCHER H. , ZACHMANN M. , PRADER A.
Published: March 2008

Synthetic LHRH (HOE 471) administered intranasally over a period of 4 weeks for treatment of uni‐ or bilateral cryptorchidism in nineteen otherwise healthy prepubertal boys led to increased basal and peak LH values and to markedly decreased peak FSH values in the i.v. LHRH test. Basal testosterone remained unchanged. Sixteen cryptorchid boys treated with placebo served as a control group. The reduced FSH response to i.v. LHRH could be due to induction of a gonadal feedback mechanism rather than pituitary depletion of FSH, in view of the favourable therapeutic effect and the increased LH secretion seen in some of our patients. Pretreatment LHRH tests were available in twenty successfully and in twenty‐eight unsuccessfully treated boys. LH values were similar in both groups, whereas FSH peak values were significantly higher in boys who responded successfully to subsequent therapy. Testicular descent occurred most readily in boys with a large pool of easily releasable FSH and without a significant rise in testosterone (in contrast to HCG treatment). We suggest that FSH induces changes that potentiate the local action of testosterone.
SERUM CONCENTRATION OF HUMAN CHORIONIC GONADOTROPIN AND ITS ALPHA AND BETA SUBUNITS. 2. TROPHOBLASTIC TUMOURS
Authors: GASPARD U. J. , REUTER AIMÉE M. , DEVÌLLE J‐L. , VRINDTS‐GEVAERT YVONNE , BAGSHAWE K. D. , FRANCHIMONT P.
Published: March 2008

Using specific homologous radioimmunoassays of native hCG and its α and β subunits, we determined the levels of these glycoproteins in unfiltered maternal blood serially obtained in five non‐invasive hydatidiform moles before and after evacuation. Some of these samples were assayed after gel filtration chromatography on Sephadex G 100. Twelve samples, obtained in cases of invasive trophoblastic tumour after ablative surgery and chemotherapy, were also assessed for their hCG, hCGα and hCGβ content. In unaborted moles, mean circulating levels of native hCG and free hCGβ were considerably increased (seven and thirteen times, respectively) as compared to normal pregnancies of the same age, whereas levels of free hCGα were either normal or slightly elevated. Chromatographic analyses of molar sera confirmed the presence of free circulating subunits, and separated hCGβ in its monomeric form from its higher molecular weight form, the latter being in greater quantity than in normal pregnancy sera. In contrast, the elution profile of serum native hCG was comparable in cases of normal and molar pregnancy. Successful curettage was accompanied by a return to normal levels of the native hCG and its α and β subunits in 40–90 days. Persistence of tumour tissue was indicated by a slight increase in levels of native hCG and the β subunit. Determination of α subunit level was less useful for the detection of any relapse.
REVERSIBLE HYPERTENSION AND HYPOTHYROIDISM
Authors: BING R. F. , BRIGGS R. S. J. , BURDEN A. C. , RUSSELL G. I. , SWALES J. D. , THURSTON H.
Published: March 2008

Six patients with hypothyroidism and hypertension whose blood pressure fell to normal when treated with thyroxine (172.7.2/112.2.1 to 140.3.2/84.1.6 mmHg, P<0.001) are described. Plasma renin activity (1.76±0.63 ng angiotensin I.ml−1.h−1) was low before treatment. Hypertension with low plasma renin is consistent with sodium retention. Hypertension in the hypothyroid patient only requires further evaluation if it persists after adequate treatment with thyroxine.
VITAMIN D METABOLITES AND THEIR RELATIONSHIP TO AZOTAEMIC OSTEODYSTROPHY*
Authors: MASON REBECCA S. , LISSNER DIANNE , WILKINSON MARGARET , POSEN S.
Published: March 2008

Bone biopsies were performed and serum concentrations of vitamin D metabolites were measured in twenty‐four patients with chronic renal failure. The concentrations of three metabolites‐25‐dihydroxyvitamin D (25‐OHD). 24,25‐dihydroxyvitarnin D (24,25‐OH2D) and 1,25‐dihydroxyvitamin D (1,25‐OH2D)‐were significantly lower in uraemic than in normal sera. There was a positive correlation between serum 24,25‐OH2D and serum 25‐OHD, whereas serum 1,25‐OH2D values, which were independent of those of the other vitamin D metabolites, were negatively correlated with serum creatinine and serum inorganic phosphate. The two major skeletal lesions, osteomalacia and parathyroid osteopathy, while coexisting in many patients, varied independently in relation to their severity and were correlated with different vitamin D metabolites. The severity of osteomalacia was negatively correlated with the serum concentrations of 25‐OHD and 24,25‐OH2D while the severity of parathyroid osteopathy was negatively correlated with serum 1,25‐OH2D values. To our knowledge these are the first systematic studies correlating skeletal histology with dihydroxylated vitamin D metabolites in renal failure in man.
THE ACCURACY AND STANDARDIZATION OF TBG KITS
Authors: HOWORTH P. J. N. , RAOUF A. A. M. , KEIGHTLEY H. G. , MARSDEN P. , O'GORMAN P.
Published: March 2008

Three kits for measurement of serum thyroxine‐binding globulin (TBG) were compared with a reference radioimmunoassay in forty‐three normal euthyroid subjects. The Corning Immophase kit gave similar results to those with the reference method with satisfactory precision and accuracy. The Behringwerke AG RIA‐gnost kit gave results with adequate but lower correlation with the reference method (r = 0.80) than that of the Corning kit trial (r = 0.92). The mean value was significantly greater than the reference method mean, indicating that the Behringwerke kit was inaccurately standardized. The CEA‐Sorin TBG kit (Eurotope services) gave results with a poor correlation against the reference method (r = 0.59). The mean value was also significantly greater than the reference mean indicating that this kit is both inaccurately standardized and less precise than the other two. It is stressed that TBG‐kits need to be periodically standardized against reference methods in the absence of properly validated primary standards in all batches.