bluuebunny/crossref_metadata_2025 huggingface dataset:
THYROID HORMONE KINETICS: IMPROVED METHOD FOR QUANTITATIVE SEPARATION AND MEASUREMENT OF THE VARIOUS RADIOIODINATED SPECIES IN SERUM AFTER RADIOIODOTHYRONINE INJECTION
Authors: AICKIN C. M. , FRASER S. , COOPER E. , HALL G. , BURKE C. W.
Published: March 2008

An accurate and reproducible method for measurement of radioactive species in blood after in vivo injection of labelled iodothyronines is described. By extraction with high‐affinity antisera, radioactive reverse T3 and T3 are separated from serum quantitatively. Radioiodide is quantitatively separated from radio‐thyronine species and serum proteins by Sephadex G50 filtration. The residual mixture of radio‐T4 and iodoprotein is quantitatively resolved by ion‐exchange adsorption. Minimal misclassification of radiospecies occurs, and can be corrected for. Mean recoveries of various radiospecies added to serum were: radioiodide 98.9%, radio‐rT3 87.6%, radio‐l‐T3 94.5%, radio‐T4 98.0% and radioiodoprotein 94.5%. The performance of the method is superior to that of chemical methods such as trichloracetic acid precipitation, ion‐exchange or alkaline Sephadex extraction, and chromatographic separation.
LUTEINIZING HORMONE, FOLLICLE STIMULATING HORMONE AND TESTOSTERONE IN NORMAL AND IMPOTENT MEN FOLLOWING LHRH AND HCG STIMULATION
Authors: DELITALA G. , MASALA A. , ALAGNA S. , LOTTI G.
Published: March 2008

The effect of synthetic LHRH on plasma concentrations of LH, FSH, testosterone and testosterone response to i.v. HCG was studied in fifteen normal men and in fifteen men with impotence.

The mean basal concentrations of LH, FSH and testosterone in the men with impotence were not significantly different from those of the normal group. A normal response of gonadotrophins and testosterone was also observed. It is concluded that a normal pituitary sensitivity to synthetic LHRH and a normal response to endogenous and exogenous gonadotrophins exist in this particular disorder.
LINEAR GROWTH AND PUBERTAL DEVELOPMENT IN TREATED CONGENITAL ADRENAL HYPERPLASIA DUE TO 21‐HYDROXYLASE DEFICIENCY
Authors: GHALI ISIS , DAVID MICHEL , DAVID LOUIS
Published: March 2008

21 years experience with management of seventeen cases of congenital adrenal hyperplasia due to 21‐hydroxylase deficiency has been analysed with respect to growth, bone maturation and related events at puberty: age at menarche and the occurrence of menstrual irregularities, this study showed that growth retardation is still a problem; that irregular treatment and prolonged exposure to adrenal androgens or oestrogens, may lead to disturbance in hypothalamo‐pituitary‐gonadal function and may be the cause of delayed menarche, or menstrual irregularities in the case of the female. In males the start of puberty and its completion was within the normal range.
FACTORS INFLUENCING THE RESPONSE TO lα‐HYDROXYVITAMIN D3 IN PATIENTS WITH RENAL BONE DISEASE
Authors: KANIS J. A. , RUSSELL R. G. G. , NAIK R. B. , EARNSHAW M. , SMITH R. , HEYNEN G. , WOODS C. G.
Published: March 2008

Twenty‐three patients with bone disease and chronic renal failure were treated for periods of 4–28 months with lα‐hydroxyvitamin D3 (1α‐OHD3). Improvements in bone histology were consistently seen in patients with features both of osteitis fibrosa and osteomalacia but were not invariably observed in patients with osteitis fibrosa or osteomalacia alone (37 and 50% improved respectively). Several factors influencing the outcome of treatment were assessed on the basis of histological responses in bone. A low level of plasma calcium before treatment, rather than the dose of lα‐OHD3 tolerated, was the major detectable factor which favourably affected the histological outcome. Other factors examined, including initial plasma concentrations of phosphate, immunoreactive parathyroid hormone and alkaline phosphatase, and treatment with haemodialysis or dietary supplements of calcium did not apparently influence the response.
THE EFFECT OF l α–HYDROXY VITAMIN D3 ON CALCIUM AND MINERAL CONTENT OF BONE IN RENAL OSTEODYSTROPHY
Authors: JUNOR B. J. R. , CATTO G. R. D.
Published: March 2008

Ten patients with renal osteodystrophy were treated with l α‐hydroxy vitamin D3 for 18 months. The effect of treatment was measured by a number of different methods and bone mass assessed by mineral and neutron activation analysis. In the majority of patients, raised serum levels of parathyroid hormone and alkaline phosphatase, histological features and radiological changes returned to normal. These effects were inconsistent in patients with a raised serum calcium level before starting treatment. In general, in patients without evidence of severe hyperpara‐thyroidism there was a reduction in the rate of fall or an increase in the mineral and calcium content of the bone.
ADRENAL ANDROGENS IN PATIENTS WITH CHRONIC MARKED ELEVATION OF PROLACTIN
Authors: PARKER L. N. , CHANG SUCKJOO , ODELL W. D.
Published: March 2008

It has been postulated, based on data in animals and the fact that the cortisol‐adrenal androgen ratio is different before and after adrenarche, that prolactin (Prl) may modulate adrenal androgen secretion. As one way of testing this hypothesis, cortisol, androstenedione (A), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were measured by radioimmunoassay in the sera of thirteen patients with suspected or proven pituitary tumours and marked chronic elevations of serum Prl (range 68–990 ng/ml, mean 198.9 ng/ml). Values for cortisol, A, DHA, and DHAS were not significantly different between the groups of normal controls and patients with elevated Prl concentrations. This is interpreted as negative evidence for the theoretical connection between Prl and adrenal androgen secretion.
ADRENAL AND GONADAL STEROIDS IN GIRLS DURING SEXUAL MATURATION
Authors: GENAZZANI A. R. , PINTOR C. , FACCHINETTI F. , CARBONI G. , PELOSI U. , CORDA R.
Published: March 2008

The peripheral venous plasma concentrations of gonadotrophins (LH and FSH), prolactin (Prl), cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone‐sulphate (DHA‐S), pregnenolone (Δ5P), progesterone (P), 17‐hydroxyprogesterone (17P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and oestradiol (E2) were measured in girls at different stages of sexual development (from P1 to P4–5 according to Tanner, 1962). Both gonadotrophins increase progressively during sexual maturation, to reach the highest concentrations in P4–5. However, the FSH values were significantly lower in these P4–5 pre‐menarchal girls than those found in adult women in the early follicular phase. No significant changes were found in plasma Prl, cortisol and 17P levels during pubertal development; in contrast, plasma concentrations of DHA tripled from P1 to P4–5, reaching adult levels. A progressive rise was also found in DHA‐S plasma levels. A significant, but less evident increase was found in Δ5P and P plasma concentrations, from group P1 to P4–5. A, T and DHT levels rose progressively and significantly from P1–2 to the end of sexual maturation. In the case of E2, only a moderate increase was found during pubertal development.

All these data indicate that during pubertal development, there is a progressive reduction in the sensitivity towards oestrogen of the hypothalamic centres controlling gonadotrophin secretion.

Prl does not seem to be involved in human sexual maturation, while important changes have been found in adrenal androgens. The constant levels of 17P and cortisol, in comparison with the behaviour of DHA, DHA‐S, T and A, seem to indicate that during this period of life, the adrenal gland is stimulated by unknown factors other than ACTH, acting on the adrenal androgen‐producing cells and responsible for the reported rises in plasma adrenal androgens.
EFFECTS OF IODIDES ON THE HYPOTHALAMIC‐PITUITARY‐THYROID AXIS IN NEUROLOGICAL ENDEMIC CRETINISM: EVIDENCE FOR COMPENSATED THYROIDAL FAILURE IN ADULT LIFE
Authors: MEDEIROS‐NETO G. A. , HOLLANDER C. S. , KNOBEL M. , IMAI I. , KATAOKA K.
Published: March 2008

Thyroid function studies, performed after iodide administration to five patients with neurological endemic cretinism, were indicative of hypothyroidism. All five subjects had either a low serum thyroxine (T4) or a high basal thyrotrophin (TSH) level and a clearly exaggerated TSH response to thyrotrophin releasing hormone (TRH). These findings are in sharp contrast with those we have previously described in goitrous patients without cretinism from the same geographical area. One interpretation of our observations is that there is an underlying mild defect in thyroid hormone synthesis in endemic cretinism predisposing to iodine induced hypothyroidism.
HYPOTHALAMIC FUNCTION IN MEN WITH HYPOGONADOTROPHIC HYPOGONADISM
Authors: WINTERS S. J. , MECKLENBURG R. S. , SHERINS R. J.
Published: March 2008

To determine whether hypothalamic function is normal in patients with idiopathic gonadotrophin deficiency, nine men with this syndrome were studied. Water conservation after overnight dehydration, thermoregulatory responses to a cold (10°C) environmental stress and prolactin secretion following chlorpromazine stimulation were investigated. In response to dehydration, maximal urinary osmolality was 1058 ± 135 mOsm/kg (mean ± SD) and no patient showed further increase after exogenous vasopressin administration. The patients responded to the cold stimulus by vigorous shivering and maintained their core body temperatures. Basal concentrations of prolactin which were 12.7 ± 4.6 ng/ml increased by 15 ng/ml following Thyrotrophin‐releasing hormone in six of seven men tested, indicating normal pituitary reserve. Prolactin concentrations doubled in seven of eight men who received chlorpromazine. All responses were indistinguishable from those of normal men. While a diminished secretion of gonadotrophin releasing hormone by the hypothalamus remains the most plausible cause of idiopathic gonadotrophin deficiency, our data indicate that the associated hypothalamic functions tested are intact in men with this syndrome.
PROTEIN HORMONES IN CEREBROSPINAL FLUID: EVIDENCE FOR RETROGRADE TRANSPORT OF PROLACTIN FROM THE PITUITARY TO THE BRAIN IN MAN
Authors: ASSIES JOHANNA , SCHELLEKENS ANDRIES P. M. , TOUBER JAN L.
Published: March 2008

Plasma and cerebrospinal fluid (CSF) levels of two hormones of similar molecular size, pituitary prolactin (PRL) and human chorionic somatomammotropin (hCS), and of the bigger hormone human chorionic gonadotropin (hCG) were measured in six pregnant women without pituitary disease. For all three hormones, the plasma and CSF levels were closely correlated. The plasma/CSF concentration ratio for hCG (571 ± 378, mean ± SD) was significantly different (P < 0.01) from the hCS ratio (24.6 ± 6.1); the hCS ratio was significantly different (P < 0.005) from the PRL ratio (7.2 ± 1.5). We conclude that (1) the CSF concentration of a protein hormone depends on the plasma concentration and on its molecular size, and (2) pituitary hormones reach the CSF not only via filtration of peripheral blood at the choroid plexuses, but also more directly via retrograde transport from the pituitary to the brain.
BROMOCRIPTINE SUPPRESSION OF THE THYROTROPHIN RESPONSE TO THYROTROPHIN RELEASING HORMONE
Authors: YAP P. L. , DAVIDSON N. McD. , LIDGARD G. P. , FYFFE J. A.
Published: March 2008

A single oral dose of 5 mg of bromocriptine significantly lowered the TSH response to 200 μg TRH intravenously in eight healthy men compared with control experiments in the same subjects. This finding may be relevant in chronic bromocriptine therapy.
THYROGLOBULIN OF VARYING MOLECULAR SIZES WITH DIFFERENT DISAPPEARANCE RATES IN PLASMA FOLLOWING SUBTOTAL THYROIDECTOMY
Authors: FELDT‐RASMUSSEN ULLA , PETERSEN P. H. , NIELSEN H. , DATE J. , MADSEN C. M.
Published: March 2008

To investigate the possible presence of thyroglobulin (Tg) of different molecular sizes in plasma, blood specimens were drawn from patients during and after surgery for thyroid adenoma. Tg was measured in all serum samples by a radioimmunoassay. Selected samples were fractionated on a sepharose CL‐6B column, and the fractions were assayed for Tg antigen.

In serum drawn at maximum Tg concentration, molecular weights of Tg antigen ranging from 660,000 (19S) to less than 100,000 were found. 6 h later the Tg antigen of mol. wt. < 100,000 could not be detected, and after 3 days only 19S Tg was present. Correspondingly the plasma Tg concentration vs. time curve showed a biphasic course from which two half‐lives could be estimated. For 19S Tg, ta1/2, had a mean value of 4.3 days, whereas the over‐all half‐life for the mixture of smaller molecules, tb1/2. had a mean value of 3.7 h.

The smaller molecules also showed different antigenic reactivity in the assay indicating an altered structure of the molecules. The assumption that this might be due to lack of sialic acid would explain the faster catabolic rate.

Preliminary results from this study have been presented at the 11th FEBS Meeting in Copenhagen, 1977, and at the European Thyroid Association 8th Meeting in Lyon, 1977.
ANTIDIURETIC HORMONE IN BRONCHOGENIC CARCINOMA
Authors: MORTON J. J. , KELLY P. , PADFIELD P. L.
Published: March 2008

Immunoactive antidiuretic hormone (ADH) was measured by radioimmunoassay in the plasma, lung tumours and metastatic tumours of nineteen patients with bronchogenic carcinoma.

Ten patients had hyponatraemia and carcinoma of the small oat cell type. Plasma ADH measured in nine of these patients ranged from 11–270 pg/ml and was elevated above the normal range (4.6–6.2 pg/ml) in all subjects. ADH‐immunoreactive material was detectable in all primary lung tumours (range 9–1080 pg/mg wet weight, n= 7) and metastases (range 5–63 pg/mg wet weight, n= 9) obtained from the hyponatraemic patients. A statistical relationship existed between plasma and tumour ADH concentration in six patients where both measurements were performed.

Three patients had small cell carcinomas (two oat cell and one anaplastic) without overt hyponatraemia. ADH‐like material was detectable in the lung tumours (18 and 1.1 pg/mg wet weight) and liver metastases (4 and 1.0 pg/mg wet weight) of two patients but not in the third.

Four of the remaining patients had squamous cell carcinomas and two had adenocarcinomas. None had hyponatraemia. ADH‐like material was undetectable in all lung tumours, metastatic tumours and uninvolved tissue from these patients.

ADH extracted from the pituitaries of four patients ranged from 6400–13200 pg/mg wet weight.

ADH immunoreactive extracts of six lung tumours and nine metastases (all oat cell) showed the same pattern on elution from a Sephadex G‐25 column. A large peak, which made up 65% of the total activity, was eluted in the same position as synthetic arginine vasopressin and contained comparable amounts of immunoreactive and bioactive ADH. Two smaller peaks (8 and 27% of total activity) were eluted in positions of higher molecular weight and contained more immunoreactive than bioactive ADH. In contrast, three of four pituitary extracts showed only a single peak which eluted in the same position as marker vasopressin.
TECHNETIUM UPTAKE IN THE MANAGEMENT OF THYROTOXICOSIS
Authors: HOFF W. VAN'T , POVER G. G. , DRURY PAUL L.
Published: March 2008

The thyroid uptake of 99m‐technetium after 7 days of triiodothyronine was measured at the end of a course of antithyroid drugs in ninety‐seven patients with thyrotoxicosis who were then followed up for at least 1 year. The relapse rate in sixty‐six patients in whom the uptake was suppressed to less than 4% was 21% whereas it was 90% in those patients in whom the uptake was more than 4%. A prediction of the outcome on the basis of whether the uptake was more or less than 4% would have been correct in 82% of patients. Serial tests during treatment show that a correct prediction could have been made one year after starting treatment in 86% of cases depending on whether the uptake at that time suppressed to more or less than 6%. The initial unsuppressed 99m‐technetium successfully predicted the likelihood of relapse after a course of antithyroid drugs in 75% of patients. We recommend that alternative therapy should be advised in those patients whose uptakes fail to suppress below 6% after 1 year of drug therapy.
PLACENTAL SULPHATASE DEFICIENCY: ANTEPARTUM DIFFERENTIAL DIAGNOSIS FROM FOETAL ADRENAL HYPOPLASIA
Authors: OAKEY R. E.
Published: March 2008

Pregnancies complicated by placental sulphatase deficiency and with fetal adrenal hypoplasia present similar clinical features. Antepartum differential diagnosis is required to identify those newborn infants likely to be at risk from adrenal insufficiency. For this purpose, the urinary excretion, near term, of oestrogens and 17‐oxogenic steroids in six pregnancies with placental sulphatase deficiency was compared with the excretion of these groups of steroids by twenty‐one women with an anencephalic foetus. This group served as a model for congenital adrenal hypoplasia.

The mean excretion of oestrogens in placental sulphatase deficiency (7.4 μmo1/24 h, mean ± SD, seventeen urines) was significantly lower (P< 0.001) than that of women with an anencephalic foetus (17 ± 10 μmo1/24 h, twenty‐nine urines). In contrast, mean 17‐oxogenic steroid excretion was higher (P < 0.001) in pregnancies complicated by sulphatase deficiency (46 ± 12 μmo1/24 h, seventeen urines) than in those complicated by anencephaly (26 ± 7 μmo1/24 h, twenty‐nine urines).

All 24 h urine samples from women with placental sulphatase deficiency contained <11.5 μmol oestrogen and > 26 μmol 17‐oxogenic steroids, whereas all results from women with an anencephalic foetus fell outside both these limits.

With these simple urinary steroid assays, it appears possible to distinguish, before delivery, between pregnancies with placental sulphatase deficiency and those with anencephaly, and, by implication, those with congenital adrenal hypoplasia.
HORMONAL REGULATION OF THE MENSTRUAL CYCLE IN WOMEN WITH BREAST CANCER: EFFECT OF ADJUVANT CHEMOTHERAPY
Authors: SHERMAN BARRY M. , WALLACE ROBERT B. , JOCHIMSEN PETER R.
Published: March 2008

The hormonal features of the menstrual cycle determined by measurement of serum LH, FSH, oestradiol, progesterone and prolactin were normal in thirteen breast cancer patients clinically disease free and not taking anti‐tumour therapy. Results of similar studies during seven menstrual cycles in four patients on an adjuvant therapy programme of L‐phenylalanine mustard (L‐PAM) + 5‐flurouracil (5‐FU) also had normal hormonal characteristics after three to fourteen courses of chemotherapy. Amenorrhoea with elevated gonadotrophins occurred after seven courses of chemotherapy in one 48‐year‐old woman. Adjuvant chemotherapy does not appear to result in major alterations in hormone secretion during menstrual cycles of women who continue to menstruate while on therapy.
THE PITUITARY‐GONADAL RESPONSE TO THE GONADOTROPHIN RELEASING HORMONE ANALOGUE D‐SER(TBU)6‐DES GLY10‐LHRH‐ETHYLAMIDE IN NORMAL MEN
Authors: HEATH M. , SCANLON M. F. , MORA B. , SNOW M. H. , GOMEZ‐PAN A. , WATSON M. J. , MULLIGAN F. , HALL REGINALD
Published: March 2008

We have studied the dose‐response characteristics of the LHRH analogue D‐Ser (TBU)6‐Des Gly10‐LHRH‐ethylamide administered subcutaneously to five normal male volunteers. The relative potency of the analogue is about sixty times (FSH) and forty times (LH) that of the parent peptide and the increased potency and duration of action of the analogue lead to enhanced biological effect in terms of testosterone release. The prolonged duration of action of the analogue suggests that a single daily dosage regime could be used although further chronic studies with this potent analogue should be undertaken in normal volunteers to determine optimum dosage schedules.
DECREASED BLOOD PRESSURE IN RESPONSE TO AN ANGIOTENSIN II ANTAGONIST IN ADDISON'S DISEASE
Authors: OGIHARA TOSHIO , HATA TAKESHI , NAKAMARU MITSUAKI , MIKAMI HIROSHI , MARUYAMA ANNA , OAKADA YOSHIAKI , KUMAHARA YUICHI
Published: March 2008

The synthetic angiotensin II antagonist, 1‐sarcosine, 8‐isoleucine angiotensin II was infused in two patients with untreated Addison's disease. Blood pressure decreased following infusion of this angiotensin II antagonist. Re‐infusion of the antagonist after cortisol replacement therapy for one month caused a slight increase in blood pressure. Addison's disease is one of the conditions in which the renin‐angiotensin system is involved in the maintenance of blood pressure.
EFFECT OF SOMATOSTATIN ON ABNORMAL GROWTH HORMONE AND PROLACTIN SECRETION IN PATIENTS WITH THE CARCINOID SYNDROME
Authors: GOMEZ‐PAN A. , SCANLON M. F. , THORNER M. O. , REES L. H. , SCHALLY A. V. , HALL R. , BESSER G. M.
Published: March 2008

Growth hormone (GH) secretion has been studied in two patients with the carcinoid syndrome during glucose loading and growth hormone‐release inhibiting hormone (GHRIH, somatostatin) infusion. Both patients had elevated fasting GH levels which were not suppressed by glucose; GH levels fell rapidly during GHRIH infusion. One patient also had hyperprolactinaemia with galactorrhoea and the prolactin (PRL) levels were unaltered by GHRIH. The association between carcinoid tumours and abnormalities of GH and PRL secretion is discussed.
THE SHORT METYRAPONE TEST: COMPARISON OF THE PLASMA ACTH RESPONSE TO METYRAPONE AND INSULIN‐INDUCED HYPOGLYCAEMIA
Authors: STAUB J. J. , NOELPP B. , GIRARD J. , BAUMANN J. B. , GRAF S. , RATCLIFFE J. G.
Published: March 2008

Plasma ACTH levels in response to metyrapone and insulin hypoglycaemia were compared in subjects with normal pituitary‐adrenal function. After a single dose of 2 g of metyrapone given with a snack at midnight, the ACTH level was 468 ng/l ± 66 (SEM) at 07.30 h the next morning (mean increment approximately nine fold over normal morning values). After insulin‐hypoglycaemia the peak ACTH level was 369 ng/l ± 31 (SEM). Peak ACTH levels greater than 200 ng/l were achieved in twenty of twenty‐one (95%) subjects after metyrapone and twenty of twenty‐four (83%) after insulin. No major side effects were noted after metyrapone.

It is concluded that the short single‐dose metyrapone test produces at least as strong and consistent a stimulus to ACTH release as the standard insulin‐hypoglycaemia test in normal subjects. A direct assay of ACTH avoids misinterpretations which are inherent in a judgement based on compound S increase only. The short test has significant practical advantages over the classical metyrapone test, and provides a convenient and sensitive method of assessing the negative feedback ACTH control mechanism. It may be particularly useful in detecting minor degrees of pituitary suppression. The value of this test in clinical practice for the investigation of patients with hypothalamic‐pituitary diseases in comparison to the classical tests of ACTH stimulation has yet to be demonstrated.
INDUCTION OF PUBERTY LONG‐TERM TREATMENT WITH HIGH‐DOSE LHRH
Authors: BROOK C. G. D. , DOMBEY S.
Published: March 2008

Gonadotrophin releasing hormone 500 mcg was administered twice daily to four patients (two male, two female) with hypogonadotrophic hypogonadism due to LHRH deficiency, for a minimum of 1 year. Despite initially encouraging biochemical responses and physical changes in all four patients, gonadotrophin responsiveness waned, sex steroid levels were not maintained and pubertal development has not occurred. This diminishing responsiveness appears to be a severe limitation on the use of LHRH as a therapeutic agent.
EFFECTS OF 1,25‐DIHYDROXYCHOLECALCIFEROL ON 47CALCIUM ABSORPTION IN POST‐MENOPAUSAL OSTEOPOROSIS
Authors: CANIGGIA A. , VATTIMO A.
Published: March 2008

Measurement of 47Calcium absorption was performed on eleven women with post‐menopausal osteoporosis. The study was repeated after 10 days treatment with 1 μg daily of 1,25(OH)2D3. These patients showed a statistically significant improvement of fractional calcium absorption that was inversely correlated to the basal values. The prompt improvement of the intestinal calcium transport in post‐meno‐pausal osteoporotic women, a few days after the administration of physiological doses of 1,25(OH)2D3 suggests that these patients synthesize inappropriately small amounts of 1,25(OH)2D3 because of their oestrogen deficiency. This could be an important pathogenetic factor in post‐menopausal osteoporosis, as the efficiency of the adaptation of calcium absorption to low calcium intakes is dependent on 1,25(OH)2D3.
EFFECTS OF THYROID HORMONES ON LIVER BINDING SITES FOR HUMAN GROWTH HORMONE, AS STUDIED IN THE RAT*
Authors: DURAN‐GARCIA S. , GOMEZ‐NIETO J. , FOUCHEREAU‐PERON M. , PADRON V. F. , OBREGON M. J. , DE ESCOBAR G. MORREALE , REY F. ESCOBAR DEL
Published: March 2008

Several weeks after thyroidectomy (t̄), female rats stopped growing, and their pituitary GH content had decreased to less than 2‐3% of the values found for age‐matched controls (C). The liver membranes of such animals were explored with human GH (hGH). It was found that in the severely hypothyroid t̄ rat, the number, but not the affinity, of the lactogenic binding sites was markedly reduced. Treatment of these rats for 3 weeks with 1.75 μg or T4 or 0.5 μg T3/100 g body weight/ day restored growth, increased pituitary GH content and restored the number of liver lactogenic binding sites practically to normal. As regards the lactogenic binding sites, similar results were obtained when the severely hypothyroid rats were treated with a much lower T4 dose (0.2 μg/lOO g/day): this dose was clearly growth promoting, and restored to normal both the low circulating GH levels and the pituitary PRL content of the severely hypothyroid rat. The changes in plasma PRL were not clear. The lactogenic binding sites on liver membranes from rats which were both thyroidectomized and hypophysectomized were decreased in number. Treatment with 0.5 μg T3/100 g/day for 30 days (but not for 12 days) resulted in an increase in the number of lactogenic binding sites, though it did not affect growth or the undetectable plasma CH levels. The effect on the lactogenic binding sites was less marked than in t̄ rats with an intact pituitary. It would appear that minute amounts of thyroid hormones are needed for maintenance of liver lactogenic binding sites; it is possible that this not only occurs through mechanism(s) Correspondence: Prof. S. Duran‐Garcia, Hospital Universitario, Planta 7a, Sevilla, Spain.
EFFECT OF AGE ON TESTICULAR FUNCTION IN PATIENTS WITH KLINEFEL TER'S SYNDROME
Authors: GABRILOVE J.L. , FREIBERG E.K. , THORNTON J.C. , NICOLIS G.L.
Published: March 2008

Testicular function in the patient with Klinefelter's syndrome parallels the alterations seen with age in the normal subject. Significant decreases are seen in the Klinefelter group in the plasma level of testosterone and in the plasma testosterone/oestradiol ratio. Testicular function in the patient with Klinefelter's syndrome appears very much like that seen in a chronologically older subject.
SLEEP‐WAKE PATTERNS AND INTEGRATED VALUES OF LUTEINIZING HORMONE, FOLLICLE STIMULATING HORMONE, PROLACTIN, GROWTH HORMONE AND THYROID STIMULATING HORMONE IN NORMAL AND CRYPTORCHID PUBERTAL PATIENTS
Authors: GIUSTI M. , BOLOGNESI F. , MORTARA R. , MIGNONE D. , GRIMALDI P. , GIORDANO G.
Published: March 2008

The sleep‐wake behaviour of LH, FSH, PRL, GH and TSH was studied in seven cryptorchid patients (four unilateral and three bilateral cryptorchids) average age 12 years and in nine normal pubertal boys of 13 years (mean age). Blood samples were collected by a continuous withdrawal pump, every hour, for 24 h. The hormonal concentration for every fraction of time was measured and related to the sleep (SC), wake (WC) and total 24 h period (DC). The integrated concentrations of the corresponding periods (IS, IW, ID) were calculated as well as their ratios (IS/IW; IS/ID%). For GH and TSH, the data obtained demonstrated no differences between cryptorchid and pubertal subjects. The PRL secretion in cryptorchid patients was moderately increased during the hours of nocturnal sleep. A normal pubertal sleep‐wake rhythm was found for gonadotrophins in both groups of subjects. More marked levels of LH secretion were observed in cryptorchid boys compared to normal pubertals. The presence of a sleep‐wake rhythm was also found in the cryptorchid patients and normal pubertal subjects in the P 1 stage. These data suggest that the CNS‘programme’which controls the onset of puberty may be normal in cryptorchid patients.
FUNCTION OF THE HYPOTHALAMO‐HYPOPHYSIAL‐THYROID AXIS IN CHRONIC RENAL FAILURE
Authors: GOMEZ‐PAN A. , ALVAREZ‐UDE F. , YEO P. P. B. , HALL R. , EVERED D. C. , KERR D. N. S.
Published: March 2008

Hypothalamo‐hypophysial‐thyroid function has been studied in twenty‐five patients with chronic renal failure. Eight were receiving conservative treatment, nine peritoneal dialysis and eight haemodialysis. All were clinically euthyroid. Total thyroxine (T4) and triiodothyronine (T3) levels were reduced but free T4 levels were normal, while free T3 was reduced in patients with the most severe renal failure. It is suggested that the binding of thyroid hormones by the transport proteins is reduced and that peripheral conversion of T4 to T3 is impaired in renal failure. The thyrotrophin response to thyrotrophin‐releasing hormone (TRH) is reduced in renal failure but this reduction is probably independent of alterations in thyroid hormone metabolism. Growth hormone was released by TRH in seven of the patients studied, possibly as a result of protein malnutrition.
INTERACTION BETWEEN THE THYROTROPHIN‐RELEASING HORMONE‐INDUCED GROWTH HORMONE RISE AND DOPAMINERGIC DRUGS: STUDIES IN PATHOLOGIC CONDITIONS OF THE ANIMAL AND MAN
Authors: MÜLLER E. E. , SALERNO F. , COCCHI D. , LOCATELLI V. , PANERAI A. E.
Published: March 2008

A rise in plasma growth hormone (GH) after thyrotrophin‐releasing hormone (TRH) and a striking reduction after dopaminergic drugs is present in acromegalic (‘responder’) patients. We have investigated the GH response to dopaminergic stimuli in two conditions of animals and man, which, like acromegaly, are characterized by a TRH‐induced GH rise, i.e. rats with electrolytic lesions of the median eminence (ME) and patients with hepatic cirrhosis. In addition, we have studied the TRH‐induced GH rise in rats with ME lesions, in the cirrhotic patients and in a group of‘responder’acromegalics before and after administration of dopaminergic drugs. In rats with ME lesions an infusion of dopamine (DA) neither modified baseline GH levels nor the TRH‐induced GH rise. In five out of six cirrhotic patients oral administration of l‐Dopa was followed by the usual rise in plasma GH. Infusion of DA increased plasma GH levels in three out of seven cirrhotic patients and in four out of five subjects an earlier GH rise after TRH was seen. However, in the‘responder’acromegalics, the infusion of DA, besides lowering baseline plasma GH, was capable of reducing the TRH‐induced GH rise. Collectively these data indicate that the TRH‐induced GH rise emphasizes defects in the neurohormonal links between the central nervous system and the anterior pituitary. Instead, the paradoxical fall of GH after dopaminergic drugs appears to be a prerequisite of acromegaly and may be attributable to receptors for DA located on the tumorous tissue.
HUMORAL AND CELL‐MEDIATED IMMUNITY IN LARGE NON‐TOXIC MULTINODULAR GOITRE
Authors: MOTA N. G. S. , KIY Y. , REZKALLAH‐IWASSO M. T. , PERAÇOLI M. T. S.
Published: March 2008

Humoral and cell‐mediated immunity was investigated in fourteen patients with non‐toxic multinodular goitre and ten healthy controls by in vitro methods. These included determination of sheep erythrocyte and complement rosette‐forming cells in the peripheral blood, immunoglobulin levels, titres of thyroglobulin and microsomal antibodies and migration inhibition test using thyroid extract and phytohemagglutinin. When compared with controls the patients showed high IgA levels and positive response to thyroid antigen in the leucocyte migration inhibition test. There was no correlation between the leucocyte migration results and the presence of auto‐antibodies. These findings indicate a possible role of cell‐mediated immunity in non‐toxic multinodular goitre.
HYPOTHALAMO‐PITUITARY OVARIAN FUNCTION IN THIRTY‐ONE WOMEN WITH CHRONIC ALCOHOLISM
Authors: HUGUES J. N. , COSTE T. , PERRET G. , JAYLE M. F. , SEBAOUN J. , MODIGLIANI E.
Published: March 2008

A study of hypothalamo‐pituitary function was carried out in chronic alcoholic women aged 29–66 years, with chronic pancreatitis or cirrhosis of the liver. Amenorrhoea was present in most of them (67%). The hormonal investigation included assessment of basal plasma steroids, gonadotrophin and prolactin values, followed by an anterior pituitary function test. Clomiphene stimulation and/or hCG tests were performed. The subjects were divided into four groups according to their oestrogen status on the one hand, and the baseline gonadotrophin concentration on the other. Results were compared with two control groups composed of twelve healthy post‐menopausal women and ten normal women of reproductive age. Five different patterns of hypothalamo‐pituitary ovarian activity could be distinguished: post‐menopausal women (eight), perimenopausal women (eight), hypothalamic amenorrhoea (five), anovulation (four) and inadequate luteal phase (six). A normal peri‐ or post‐menopausal hormonal profile was found in most (77%) chronic alcoholics of more than 45 years of age. In contrast, 84% of patients of reproductive age had functional hypothalamic disorders. These observations suggest that chronic alcoholism affects sexual function at the hypothalamo‐pituitary level chiefly during the reproductive period. The pathogenesis of these endocrine changes is not clear. The relative importance of ethanol consumption, liver damage and non‐specific factors such as nutritional status and chronic illness are discussed.
ADRENAL STEROIDOGENESIS IN HIRSUTE WOMEN
Authors: CHILD D. F. , BU'LOCK D. E. , ANDERSON D. C.
Published: March 2008

Adrenal steroidogenesis has been studied in vivo in ten hirsute and ten normal women. Serum levels of nine steroids on the biosynthetic pathway: the Δ53 β‐hydroxysteroids, pregnenolone (Pe), 17α‐hydroxypregnenolone (17 Pe), dehydroepiandrosterone (DHEA), androstenediol (Adiol), and their Δ43 keto counterparts, progesterone (Po), 17α‐hydroxyprogesterone (17 Po), androstenedione (Adione), and testosterone (T), as well as cortisol, were measured following ACTH stimulation from a dexamethasone‐suppressed state. The results are complicated by the finding of marked heterogeneity in the adrenal steroid response between different subjects in the normal population. One of the ten normal women had a much greater increment of Po and 17Po than the others following ACTH stimulation, suggesting that she has reduced 21‐hydroxylase activity. A similar heterogeneity was also seen in the hirsute women, three of the ten having an exaggerated 17Po response to ACTH. Two of the same hirsute women also had greater Adione responses than normal. Adrenal steroidogenesis was normal in most of the hirsute women, while a subtle adrenal variant, possibly of 21‐hydroxylase, has been demonstrated in a minority as in normal individuals; we do not yet know whether this is of aetiological importance. Our data do not support previous suggestions that adrenal 3β‐hydroxysteroid dehydrogenase activity is reduced in hirsute women.
MOLECULAR FORMS OF SOMATOSTATIN IN NORMAL SUBJECTS AND IN PATIENTS WITH PANCREATIC SOMATOSTATINOMA
Authors: PENMAN ERICA , LOWRY P. J. , WASS J. A. H. , MARKS V. , DAWSON A. M. , BESSER G. M. , REES LESLEY H.
Published: March 2008

Two patients with somatostatin‐secreting pancreatic tumours are described, one presenting with hypoglycaemia due to hyperinsulinism, and the other with Cushing's syndrome due to ectopic ACTH production. When plasma from these patients was subjected to gel chromatography under conditions designed to prevent somatostatin binding to larger proteins, a peak of monomeric immunoreactive somatostatin was observed as well as several large molecular weight forms. These larger forms of somatostatin could be dissociated into monomeric somatostatin by dithiothreitol. Similar studies on plasma obtained from normal subjects also showed heterogeneity of circulating somatostatin. Extracts of tumour tissue from both patients contained predominantly monomeric somatostatin, but only small amounts of high molecular weight somatostatin which differed from the profile seen in plasma. The site(s) of origin of the large molecular weight forms of somatostatin seen in plasma and their relative biological activities remain to be established.
HYPERPROLACTINAEMIA AND LONG‐TERM LACTATIONAL AMENORRHOEA
Authors: DUCHEN M. R. , MCNEILLY A. S.
Published: March 2008

Clinical details of lactational and menstrual history post‐partum have been correlated with measurements of serum prolactin, luteinizing hormone, follicle stimulating hormone, oestradiol and progesterone in Transkei women in order to gain further insight into the role of prolactin in the maintenance of post‐partum lactational amenorrhoea. Of seventy‐four breast‐feeding mothers studied, sixty‐six had elevated serum levels of prolactin. Forty‐four women were amenorrhoeic with minimal or absent endocrine evidence of ovarian activity. Of the twenty‐seven lactating women who reported menstruation, twelve had high levels of prolactin and no apparent ovarian activity, eleven had lower prolactin levels and increased oestradiol levels suggesting ovarian follicular development, while only four women had increased progesterone levels indicating definite luteal activity. Three lactating women were pregnant. The results support previous reports that lactational amenorrhoea is associated with hyperprolactinaemia and a possible sequence of endocrine events resulting in the return of post‐partum fertility is proposed.
STUDIES ON THE ROLE OF HISTAMINE IN HUMAN PITUITARY FUNCTION
Authors: CARLSON HAROLD E. , CHANG R. JEFFREY
Published: March 2008

To elucidate further the role of histamine in pituitary regulation, TRH and L‐DOPA stimulation tests were performed with and without diphenhydramine, cimetidine, or betazole pre‐treatment. Betazole blunted the GH response to L‐DOPA and slightly enhanced the T3 response to TRH without altering the TSH or PRL increments. Neither diphenhydramine nor cimetidine had any acute effect on the hormonal responses examined. Histamine appears to play only a limited role in these aspects of human pituitary regulation.
RENIN AND ALDOSTERONE IN HYPOTHYROIDISM: RELATION TO EXCRETION OF SODIUM AND POTASSIUM
Authors: SARUTA T. , KITAJIMA W. , HAYASHI M. , KATO E. , MATSUKI S.
Published: March 2008

Changes in plasma renin activity (PRA) and plasma aldosterone (PA) were studied together with the urinary excretion of sodium and potassium in patients with hypothyroidism. The basal levels of PRA and PA were significantly less than those in normal subjects. However, there was no significant relationship between PRA and PA. The response of PRA after administration of 40 mg of frusemide in patients with hypothyroidism was significantly less than that in normal subjects, although the excretion of sodium was slightly higher than that in normal subjects. On the other hand, the excretion of potassium in patients with hypothyroidism was significantly lower than that in normal subjects. The responses of PA to various stimulations, such as ACTH, angiotensin II, potassium and frusemide, were equally suppressed. These results suggest that PRA and PA may be suppressed independently in hypothyroidism, probably due to dysfunction of juxtaglomerular cells and glomerulosa cells, respectively, and the possibility that suppression of PRA and PA in patients with hypothyroidism is related to exaggerated sodium excretion and a decrease in potassium excretion cannot be ruled out.
CORTICOSTERONE‐SECRETING TUMOURS: WITH AND WITHOUT RENAL ARTERY STENOSIS
Authors: MILLS I. H. , COOK R. F. , GALLEY J. M. , EDWARDS O. M. , TAIT A. D.
Published: March 2008

Two cases of corticosterone‐secreting adrenal adenomata are reported. Both patients were middle‐aged females in whom the clinical course spanned several years before the diagnosis was made. Severe hypertension and recurrent hypo‐kalaemia refractory to standard treatments were outstanding features. The importance of measuring the production rates of all mineralocorticoids when a tumour is suspected is emphasized by Case 1 where the production rate of corticosterone alone was elevated. Bilateral renal artery stenosis was responsible for unsuppressed plasma renin activity in Case 2.
HYPERINSULINAEMIA IN HYPERPROLACTINAEMIC WOMEN
Authors: JOHNSTON D. G. , ALBERTI K. G. M. M. , NATTRASS M. , BURRIN J. M. , BLESA‐MALPICA G. , HALL K. , HALL R.
Published: March 2008

The metabolic sequelae of hyperprolactinaemia were studied over a 12 h period of normal meals and activity in nine young female hyperprolactinaemic subjects and fourteen matched controls. In the patients, fasting blood glucose and serum insulin concentrations were normal, as was the blood glucose response to meals; the insulin rise with meals was, however, exaggerated and hyperinsulinaemia persisted throughout the day (mean ± SEM 12 h serum insulin, 26 ± 8 vs. 16 ± 9 mu/l, P < 0.01). Blood lactate, pyruvate and alanine response to meals was also increased. Blood glycerol (mean 12 h blood glycerol 0.06 ± 0.01 vs. 0.09 ± 0.01 mmol/l, P < 0.01) and blood 3‐hydroxybutyrate (mean 12 h blood 3‐hydroxybutyrate 0.03 ± 0.01 vs. 0.05 ± 0.01 mmol/l, P < 0.05) concentrations were lower in hyperprolactinaemic subjects. There was a strong negative correlation between mean insulin and mean 3‐hydroxybutyrate levels in the afternoon period (rs = ‐0.92, P < 0.01). Excess circulating prolactin in young females is associated with normoglycaemic hyperinsulinaemia. The changes in blood metabolite levels observed are probably secondary to the increased insulin concentrations.
CLINICAL IMPLICATIONS OF THE MEASUREMENT OF FREE THYROID HORMONES IN THYROID DISEASE
Authors: And L. BALDET , JAFFIOL C.
Published: March 2008

We determined the dialysable fractions of T3 (DFT3) and T4 (DFT4) to study the behaviour of free thyroid hormones in different states of thyroid function.

The relationship between DFT4/TBG and DFT3/TBG in forty‐nine individuals, (nine hyperthyroid, ten euthyroid, ten hypothyroid patients, ten pregnant women and ten subjects taking oral contraceptives) was best described in both instances by two regression curves. The first regression showed that both DFT4 and DFT3 were inversely correlated with TBG. The second regression described the nine most biochemically toxic patients. They were statistically independent of the first, and being almost perpendicularly disposed to the TBG axis were interpreted as saturation curves. Analysis of the discriminant value of free thyroid hormone levels (AFT3, AFT4) derived from DFT3 and DFT4 showed that free thyroid hormone measurements were in no way superior to total thyroid hormone measurement in the biochemical diagnosis of hyper‐ and hypothyroidism. Furthermore, there were no signficant differences in DFT3, DFT4, AFT3 and AFT4 between patients and controls in subjects whose only abnormality was a decreased (n=18) or exaggerated (n=9) TSH response in the TRH test. Finally, mean total T3 and AFT3 were both significantly higher than controls in patients with hot nodules who were hyperthyroid (n=9) but only AFT3 was higher in corresponding patients (n=9) who were euthyroid.
PLASMA TESTOSTERONE GLUCOSIDURONATE: A RELIABLE INDICATOR OF FEMALE HYPERANDROGENISM (IDIOPATHIC HIRSUTISM AND ANDROGENIC ALOPECIA)
Authors: TAMM J. , VOLKWEIN U. , TRESGUERRES J. A. F.
Published: March 2008

Plasma concentrations of testosterone glucosiduronate (TG) have been determined by direct radioimmunoassay in seventeen normal females, twenty females with idiopathic hirsutism, and in twelve female subjects with androgenetic alopecia without hirsutism, respectively. The corresponding mean concentrations (SD) of TG were 0.47 ± 0.18; 1.42 ± 0.55; 0.96 ± 0.22 ng/ml. There was no overlapping of plasma TG levels of both groups with hyperandrogenism with those obtained in normal females. On the contrary, plasma concentrations of testosterone and dihydrotestosterone were found within the normal ranges in about 50% of the patients with hyperandrogenism. The synchronously estimated urinary excretion of TG revealed marked fluctuations (mean ± SD): 27.0 ± 12.0; 60.5 ± 24.6; 36.3 ± 14.1 μg/24 h respectively.
DOPAMINE INHIBITS THE NALOXONE INDUCED GONADOTROPHIN RISE IN MAN
Authors: DELITALA G. , DEVILLA L. , BIASO D. DI
Published: March 2008

Twenty milligrams of the opiate receptor antagonist naloxone were infused over 3 h to five young male volunteers. Naloxone produced a significant rise in both LH and FSH, but did not affect serum prolactin levels. The infusion of dopamine (4μgkg−1min−1) completely abolished the naloxone effect on gonadotrophin release. The results suggest a possible interaction between dopamine, opioid receptors and gonadotrophin secretion in man.
TWO NEW DOPAMINE AGONISTS THAT ARE LONG ACTING IN VIVO BUT SHORT ACTING IN VITRO
Authors: GROSSMAN A. , YEO T. , DELITALA G. , HATHWAY N. R. , BESSER G. M.
Published: March 2008

The effects of two new ergolines, pergolide and CH29–717, on prolactin secretion in vitro and in vivo were compared with those of bromocriptine. Both ergolines had in vitro potencies similar to that of bromocriptine, but had a shorter duration of action. However, in vivo both were longer acting than bromocriptine after a single dose of 100 μg, and effectively suppressed prolactin secretion for greater than 24 h. It would appear that the pharmacokinetics of these ergolines are different to those of bromocriptine, and this may have considerable therapeutic importance.
VITAMIN D RESISTANT RICKETS WITH ALOPECIA: A FORM OF END ORGAN RESISTANCE TO 1,25 DIHYDROXY VITAMIN D
Authors: BEER S. , TIEDER M. , KOHELET D. , LIBERMAN O. A. , VURE E. , BAR‐JOSEPH G. , GABIZON D. , BOROCHOWITZ Z. U. , VARON M. , MODAI D.
Published: March 2008

A 4‐year‐old girl presented with severe clinical and radiological rickets, and alopecia since the age of 1 year. Laboratory studies revealed: hypocalcaemia, hypophosphataemia, secondary hyperparathyroidism, abnormally low intestinal calcium absorption, and markedly elevated circulating 1,25(OH)2D3 levels. A normal calcaemic response to parathyroid extract was obtained. Treatment attempts with vitamin D2, 1 α (OH)D3 and 1,25(OH)2D3 were totally ineffective. Intestinal resistance to the action of 1,25(OH)2D3 appeared well established in this case. Refractoriness of bone to this hormone seems less certain. From this new entity of‘Vitamin D resistant rickets due to end organ unresponsiveness', six cases have been hitherto reported in the literature. However, only two have enough resemblance to our case, to constitute a distinct and well denned nosologic subunit. The molecular basis of this disorder(s) remains to be elucidated.