bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALYSIS OF THE RELATION BETWEEN ALOPECIA AND RESISTANCE TO 1,25‐DIHYDROXYVITAMIN D
Authors: MARX S. J. , BLIZIOTES M. M. , NANES M.
Published: March 2008

Alopecia is a frequent feature in hereditary resistance to (1,25(OH)2D). We sought insight into this feature by analysing data from affected members of 30 kindreds. We assessed indices of mineral metabolism in one group with normal hair compared with a group with alopecia. Hereditary resistance to 1,25(OH)2D was diagnosed at an earlier age in alopecic patients (0·9 vs 3·3 years, P> 0·05); this reflected late presentation of metabolic bone disease in some cases with normal hair and could not be attributed to early diagnosis resulting from the striking feature of alopecia. For untreated subjects, serum concentrations of calcium and 1,25(OH)2D were similar in both groups of patients. During calciferol therapy, however, the cases with alopecia showed lower serum calcium (1·9 vs 2·4 mmol/1, P > 0·005), but higher serum 1,25(OH)2D (2900 v 340 pg/ml, P> 0·005). Hair status did not predict the type of defect identified with cultured skin fibroblasts but did correlate with responsiveness of 25(OH)D 24‐hydroxylase to 1,25(OH)2D3 in those cells. Cells from seven of eight kindreds with alopecia showed no 24‐hydroxylase response to high doses of 1,25(OH)2D3 while cells from five of six kindreds with normal hair showed a 24‐hydroxylase response to high doses of 1,25(OH)2D3. We conclude that in cases with hereditary resistance to 1,25(OH)2D alopecia reflects the more severe grades of this resistance based upon earlier age at time of diagnosis, lower potential for calcaemic response to calciferols, and lower potential for 24‐hydroxylase response to 1,25(OH)2D3 by cultured skin fibroblasts.
DEFINITION OF BIOACTIVE PROLACTIN PULSATIONS DURING THE MENSTRUAL CYCLE
Authors: BLANK M. S. , DUFAU MARIA L.
Published: March 2008

Patterns of circulating prolactin bioactivity during three stages of the menstrual cycle were studied in detail in four normally cycling women. Serial blood samples were withdrawn at 10 or 15 min intervals for up to 8 h. Plasma prolaction concentrations were quantitated by a bioassay which is based on the replication of a rat lymphoma cell line (Nb2 node) and by conventional radioimmunoassay. A total of 50–103 samples from each patient was analysed. Using a threshold‐based algorithm, definite pulsations of prolactin biological (B) and immunological (I) activity were detected at most stages of the menstrual cycle. The periodicity of these peaks ranges from 1 to 11/2 h. However, pulsations were less evident in one subject who had asymptomatic hyperprolactinaemia although circulating prolactin was fully bioactive (mean B:I ratios being 1 02–1.25). B:I ratios in the three normoprolactinaemic women were generally lower, ranging from 0.39±0.02 to 0–93±0.03. Elevations in the B:I ratio of normoprolactinaemic women were associated with bioactive peaks; this was not always the case in the hyperprolactinaemic subject. Thus, the lack of symptoms in this hyperprolactinaemic subject could not be due to bioinactive prolactin, but might perhaps be due to the absence of episodic prolactin secretion which would desensitise target organs.
LOSS OF LUTEINIZING HORMONE BIOACTIVITY IN PATIENTS WITH PROSTATIC CANCER TREATED WITH AN LHRH AGONIST AND A PURE ANTIANDROGEN
Authors: ST‐ARNAUD R. , LACHANCE R. , KELLY SUSAN J. , DUPONT BELANGER. A. , LABRIE F.
Published: March 2008

Chronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5α‐dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D‐Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2±0.3 (SEM) to 1.1±0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43±0.04 to 0.030±0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26±0.03 to 0.03±0.01. In the same patients, serum testosterone levels were decreased from 3.91±0.51 to 0.14±0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032±0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with LHRH agonists.
COMPARISON OF BLOOD SPOT, SALIVARY AND SERUM PROGESTERONE ASSAYS IN THE NORMAL MENSTRUAL CYCLE
Authors: PETSOS P. , RATCLIFFE WENDY A. , HEATH D. F. , ANDERSON D. C.
Published: March 2008

Sensitive direct (non‐extraction) radioimmunoassays for assay of progesterone (Po) in saliva and capillary blood dried on filter paper have been developed to facilitate collection of specimens for the assessment of luteal function in the investigation of infertility. The antiserum had been raised to a Po I lα‐hemisuccinyl conjugate and the assays employ Po 11α‐glucurony 1‐[25I] tyramine as tracer with separation by solid phase double antibody. Po levels in saliva and capillary blood were compared with those in serum in matched specimens collected daily throughout the menstrual cycle from six female volunteers. The correlation between blood (y) and serum (x) Po levels (y= 0.439x‐2.98, r=0.98) was superior to that between salivary (y) and serum levels (x) (y=0.0637x+0.020. r= 0.89). Blood spot and serum Po levels were uniformly undetectable throughout the follicular phase, whereas in 2 out of 72 saliva specimens Po was inappropriately raised (60 and 120 pmol/l) possibly reflecting contamination of the specimens. Salivary and blood progesterone assays both lack adequate sensitivity to measure Po reliably in early or late luteal phases when serum levels are <12 nmol/l but are well suited to assess luteal function during the mid‐luteal phase of the cycle (4–10 d before menses) when serum levels in the six subjects ranged from 22–84 nmol/l, with corresponding blood levels of 6.2–35 nmol/l and saliva levels of 130–620 pmol/l. We conclude that blood spot and saliva Po levels both correlate well with Po levels in serum, but that blood spot Po levels are more reliable.
THE EFFECT OF PHYSIOLOGICAL CHANGES IN OVARIAN STEROIDS ON THE PROLACTIN RESPONSE TO GONADOTROPHIN RELEASING FACTOR
Authors: TAN Y. M. , STEELE P. A. , JUDD S. J.
Published: March 2008

This study was designed to assess the effect of an altered level of serum oestrogen and progesterone on the prolactin (PRL) response to gonadotrophin releasing hormone (GnRH). Six normal women were studied in the early follicular phase and the mid‐luteal phase of one cycle and five menopausal women were studied before and after treatment with progesterone. Blood samples were collected at 15 min intervals for 6 h after a basal collection period of 30 min. Intravenous boluses of GnRH (1 μg, 10 μg and 50 μg) were given at 0, 2 and 4 h. Basal samples were assayed for 17β‐oestradiol (E2), oestrone (E1) and progesterone (P); LH, FSH and PRL were measured in all samples. Serum PRL was significantly elevated in all groups after 10 μg of GnRH with maximum increments (±SEM) ranging from 3.9±1.3 μg/l in early follicular phase women to 14.7 ± 4.7 μg/l in progesterone‐treated menopausal women. The PRL response to GnRH was significantly greater in the luteal phase and in menopausal women compared to early follicular phase women. There was a significant correlation between the maximum PRL response and the maximum LH response to GnRH in all the women studied (r= 0.7; P < 0.01). A significant correlation was also found between the maximum PRL response and the basal serum oestrogen concentration in the normal cycling women (r= 0.8; P < 0.01), but not when the menopausal women were included in the analysis. Administration of progesterone to menopausal women did not significantly affect the PRL response to GnRH and no significant correlation was found between the basal serum progesterone and the PRL response to GnRH. We conclude that GnRH stimulates the secretion of PRL in normal, cycling and in menopausal women to a degree which is more closely correlated with the LH response than with the circulating oestrogen or progesterone concentration. This is consistent with the hypothesis that GnRH exerts an indirect effect on the lactotrophe by stimulating the prodution of a paracrine factor from the gonadotrophe. We suggest that the action of GnRH on the lactotrophe may be physiological in view of its reported action in synchronizing the secretion of LH and PRL and in maintaining the acute releasable pool of PRL in the lactotrophe.
HORMONAL AND CARDIOVASCULAR RESPONSES TO DDAVP IN MAN
Authors: WILLIAMS T. D. M. , LIGHTMAN S. L. , LEADBEATER M. J.
Published: March 2008

Hormonal and cardiovascular responses to 1‐desamino‐8‐d‐arginine vasopressin (DDAVP) were investigated in six normal adult volunteers. After overnight fluid deprivation, an intravenous injection of either DDAVP (0.4 μg/kg) or the same volume of normal saline was administered. One hour later an intravenous infusion of hypertonic saline was commenced and continued over two hours. Five minutes following the DDAVP injection, facial flushing, a fall in diastolic blood pressure by an average of 13% and a rise in pulse rate by an average of 18% were observed. There was a significant increase in plasma renin activity and plasma cortisol concentration, but no significant changes were observed in plasma concentrations of LH, FSH, TSH, prolactin or GH. Following osmotic stimulation by hypertonic saline plasma AVP rose to the same extent in both the DDAVP and control studies. DDAVP (0.4 μg/kg) was also administered to five subjects with cranial diabetes insipidus. Again facial flushing, increased facial temperature, a fall in diastolic pressure and a rise in heart rate were all observed, suggesting that DDAVP exerts its cardiovascular actions by a mechanism other than antagonism of circulating endogenous AVP.
RESPONSES OF NEUROHYPOPHYSIAL PEPTIDES TO HYPERTONIC SALINE AND INSULIN‐INDUCED HYPOGLYCAEMIA IN MAN
Authors: NUSSEY S. S. , ANG V. T. Y. , FINER N. , JENKINS J. S.
Published: March 2008

In order to investigate the possible role of oxytocin in osmoregulation and its response to stress, plasma immunoreactive oxytocin was measured during hypertonic saline infusion and insulin‐induced hypoglycaemia in a group of normal subjects, four patients with idiopathic diabetes insipidus and one patient with DIDMOAD syndrome (the syndrome of diabetes insipidus, diabetes mellitus, optic atrophy and deafness). The results were compared with those of plasma immunoreactive vasopressin to the same stimuli. As expected, there was a rise in plasma vasopressin in the normal subjects to both tests: this was absent in the patients with diabetes insipidus. Plasma oxytocin did not rise during hypertonic saline infusion in either group of subjects. The response of oxytocin to insulin‐induced hypoglycaemia (0.15 U/kg soluble insulin) in normal subjects was much more variable. One highly symptomatic volunteer showed a marked rise in oxytocin. Two subjects also showed a rise when retested with 0.19 U/kg soluble insulin. There was no response of oxytocin to a standard‐dose insulin test in the patients with diabetes insipidus. The data suggest that, in man, oxytocin is not involved in osmoregulation but that it may be secreted in response to marked hypoglycaemia.
THE EFFECT OF AMIODARONE ON THYROXINE KINETICS
Authors: PEARCE C. J. , HIMSWORTH R. L.
Published: March 2008

Amiodarone was given by daily intraperitoneal injection (10 mg/kg body weight) to a group of 11 New Zealand white rabbits. Over 6 weeks there were significant increases (P<0–01) in plasma total T4 concentration (43±8 to 60±13 nmol/1; mean±l SD) and rT3 concentration (0.12±0.06 to 0.31 ± 0.16 nmol/1) and a significant fall in total plasma T3 (2.3±0.3 to 1.7 ± 0.2 nmol/1). The plasma clearance of T4 in rabbits treated with amiodarone for 6 weeks was significantly reduced relative to controls (64 ± 25 vs 109 ± 19 ml/kg per day, P<0.01) but the production rate was unchanged (3.8±1.8 vs 3.7±1.4 nmol/kg per day). In the amiodarone treated animals the increased plasma T4 concentration was entirely accounted for by the reduced clearance. It is inferred that the normal output of T4 by the thyroid is pituitary dependent and that TSH secretion is sustained in the presence of hyperthyroxinaemia because of amiodarone induced partial inhibition of T4 utilization by the thyrotroph.
HYPERPROLACTINAEMIA IN CONGENITAL HYPOTHYROIDISM
Authors: McCORMICK K. L.
Published: March 2008

Serum prolactin concentrations were measured in nine untreated hypothyroid infants and 23 euthyroid controls. In the former group the serum prolactin concentrations were tenfold higher than the controls (352 vs 34 μg/1), declining gradually upon treatment. Although serum prolactin concentrations can be mildly elevated in adults with hypothyroidism, congenital hypothyroidism causes a profound and probably uniform hyperprolactinaemia; furthermore, the hormone concentration correlates directly with the simultaneous TSH concentration. The physiological importance, if any, of the hyperprolactinaemia in the fetus or neonate is uncertain.
INFLUENCE OF DOPAMINERGIC, ADRENERGIC AND CHOLINERGIC BLOCKADE AND TRH ADMINISTRATION ON GH RESPONSES TO GRF 1–29
Authors: JORDAN V. , DIEGUEZ C. , LAFAFFIAN I. , RODRIGUEZ‐ARNAO M. D. , GOMEZ‐PAN A. , HALL R. , SCANLON M. F.
Published: March 2008

In order to establish the influence of dopaminergic, á‐adrenergic and cholinergic pathways on GRF‐mediated GH release we have studied the GH responses to GRF 1–29 (100 or 50 μg as i.v. bolus) alone and in combination with metoclopramide (MCP, 10 mg, i.v.), thymoxamine (THYM, 210 μg/min, 150 min infusion), and atropine (1.2 mg, i.v.). We have also investigated any possible interaction between TRH and GRF in view of the reported inhibitory effects of TRH infusion on stimulated GH release. Dopaminergic and á‐adrenergic blockade with MCP and THYM respectively, did not have any effect on the GH responses to GRF. This lack of effect strongly suggests that any action which these neurotransmitters may exert on GH secretion is not at a pituitary level. TRH did not modify the GH response to GRF suggesting that the inhibitory effect on stimulted GH secretion is exerted at a hypothalamic level. In contrast, GH responses to GRF were significantly reduced by prior administration of atropine. These data support the view that cholinergic pathways play an important role in the regulation of GH secretion and such control may be exerted at both hypothalamic and pituitary levels.
FAMILIAL CUSHING'S SYNDROME DUE TO NODULAR ADRENOCORTICAL DYSPLASIA. A PUTATIVE RECEPTOR‐ANTIBODY DISEASE?
Authors: VAN BERKHOUT F. TEDING , CROUGHS R. J. M. , KATER L. , SCHUURMAN H. J. , MEYLING F. J. H. GMELIG , KOOYMAN C. D. , VAN DER GAAG R. D. , JOLINK D. , DREXHAGE H. A.
Published: March 2008

Two sisters aged 13 and 19 years suffering from familial Cushing's syndrome due to nodular adrenocortical dysplasia are described. Pituitary adrenocortical function tests indicated the presence of adrenal autonomy. Adrenal scintigraphy showed bilateral symmetrical uptake indicating the bilateral character of the autonomous process. Complete adrenalectomy was performed in both girls. The adrenals were of about normal weight showing numerous dark brown pigmented nodules and small perivascular lymphocytic infiltrates. Serum immunoglobulin preparations obtained from both girls stimulated adrenocortical cell growth in a cytochemical bioassay system. It is proposed that circulating growth factors may be involved in the pathogenesis of the disease.
PSEUDOHYPOALDOSTERONISM: DECREASED ALDOSTERONE LEVELS WITH AGE WITHOUT SIGNIFICANT CHANGE IN URINARY SODIUM EXCRETION
Authors: YASUDA T. , NODA‐CHO H. , NISHIOKA T. , SASAKI N. , NIIMI H. , NAKAJIMA H.
Published: March 2008

To clarify age‐related changes in the plasma renin activity (PRA)‐aldosterone (ALDO) system in relation to urinary sodium (Na) excretion in pseudohypoal‐dosteronism type I (PHA), we followed a patient with PHA serially by measuring the hormonal balance and urinary electrolyte excretion for 5 years. The patient was diagnosed as PHA mainly on the basis of extremely high PRA (170 ng/ml/h) and ALDO (1670 ng/dl) despite massive urinary Na excretion, a normal ALDO/PRA ratio (mean value = 11), and the ineffectiveness of 9a‐fluorocortisol (Florinef) to reduce urinary Na excretion and PRA‐ALDO. The pattern of reduction in PRA‐ALDO with age in this patient was almost identical with that of normal infants and children and was most remarkable during the first 18 months of life. During this period, there were statistically significant correlations between age and each of the following values: PRA (r=−0.753, n= 9, P<0.05), ALDO (r=−0.736, n= 11, P<0.01) and urinary ALDO excretion (r=−0.840, n= 9, P<0.01). But the reduction of PRA‐ALDO in this patient was not the result of increased urinary Na excretion with age. Although PRA and ALDO values in this patient did decrease with age, they were still high compared with age‐matched controls, suggesting a marginal state of Na balance. Thus, we conclude that PRA‐ALDO levels in PHA decrease with age in the same pattern as in normal infants and children without a significant change in urinary Na excretion, possibly through increased renal conservation of Na, the mechanism of which should be clarified in a future study.
NALOXONE PROVOKES CATECHOLAMINE RELEASE IN PHAEOCHROMOCYTOMAS AND PARAGANGLIOMAS
Authors: BOULOUX P.‐M. G. , GROSSMAN A. , BESSER G. M.
Published: March 2008

The effects of low‐ (2 mg) and high–dose (10 mg) intravenous naloxone administration on circulating plasma catecholamines in four patients with proven and two patients with suspected phaeochromocytomas have been evaluated. In three out of four patients with confirmed phaeochromocytomas or paragangliomas, 10 mg naloxone resulted in a marked rise (290–575%) in circulating noradrenaline; despite combined alpha and beta‐adrenoceptor blockade, in two out of four cases systolic and diastolic pressures rose whilst pulse rate fell. No response was seen to 2 mg naloxone in any patient. No humoral or pressor response was obtained in the fourth patient, who may have been secreting maximal levels of plasma noradrenaline at the time of study. In the two patients with suspected phaeochromocytoma, there was no response to naloxone: further investigations failed to reveal a source of abnormal catecholamine secretion in these patients. It is concluded that naloxone represents a new pharmacological agent which can provoke catecholamine release in patients with phaeochromocytomas; in such patients, endogenous opioids may regulate catecholamine release either from the tumour itself or from the enhanced peripheral catecholamine stores.
THE ROLE OF IMMUNOPEROXIDASE TECHNIQUES ON PARAFFIN EMBEDDED TISSUE IN DETERMINING THE HISTOGENESIS OF UNDIFFERENTIATED THYROID NEOPLASMS
Authors: MYSKOW M. W. , KRAJEWSKI A. S. , DEWAR A. EDNA , MILLAR E. P. , MCLAREN KATHYRYN , FABRE J. W.
Published: March 2008

Twenty cases of undifferentiated thyroid tumours were reviewed histologically. In seven cases the histogenesis was difficult to determine using morphological criteria. Immunohistochemical staining with a panel of antibodies to lymphoid and epithelial cells, including monoclonal antibodies directed against the leucocyte common antigen, cytokeratin, and epithelial membrane antigen confirmed that four of these cases were lymphomas and that one was a medullary carcinoma. In the remaining two cases immunohistochemistry was unhelpful. In the thirteen histologically typical tumours, the immunohistochemical profile was in keeping with their histogenesis as determined by morphological criteria. Immunohistochemical staining with a panel of selected antibodies allows the reliable diagnosis of undifferentiated thyroid neoplasms, when this cannot be reached using routine histological techniques.
3,5‐DIIODOTYROSINE AND THYRONINE IN THE URINE OF PATIENTS WITH CHRONIC RENAL DISEASE
Authors: RAMSDEN D. B. , FARMER M. , MOHAMMED M. N. , Gonigle R. S. S. Mc , SHEPPARD M. C.
Published: March 2008

Urinary 3,5‐diiodotyrosine (DIT) and thyronine (T0) excretion was investigated in 18 patients with chronic renal disease. In accord with previous findings serum T4 and thyroid hormone binding proteins measured in 17 patients were in the low or normal range. Urinary albumin excretion was elevated in all 18 and T4 binding prealbumin (TBPA) in 15 of the 18. Urinary T0 excretion measured in 12 patients was also significantly lower than normal (mean±SD 4.4±2.6 vs 15.8±5.8 nmol/24 h renal vs normal 2 P<0.001). In contrast urinary DIT excretion was significantly elevated in renal patients compared with normal subjects (2.0±1.5 vs 0.75±0.41 nmol/24 h, respectively). Possible sources of the increased DIT are discussed.
PARENTERAL BROMOCRIPTINE IN THE TREATMENT OF HORMONALLY ACTIVE PITUITARY TUMOURS
Authors: BENKER G. , GIESHOFF B. , FREUNDLIEB O. , WINDECK R. , SCHULTE H. M. , LANCRANJAN IONA , REINWEIN D.
Published: March 2008

Eleven patients with PRL and three with GH‐secreting pituitary adenomas were treated with a single intramuscular injection of 50 mg of bromocriptine retard (Parlodel, LA (long‐acting)). There was a marked PRL suppression in 9 prolactinoma patients, in four for a period of at least 6 weeks. In one patient with acromegaly GH plasma levels decreased into the normal range. The size of the pituitary adenoma diminished considerably, as shown by CT scan, in three out of the 9 responding patients with prolactinoma and in the above acromegalic patient. Visual fields normalized within 14 d in one patient with a PRL‐secreting macroadenoma and bitemporal hemianopsia who also had CT scan‐documented shrinkage of the tumour. There were no side‐effects except slight hypotension in two and local tenderness at the injection site in one patient; these symptoms disappeared without treatment. It is concluded that bromocriptine retard is a safe and effective therapeutic tool for shrinking hormonally active pituitary tumours in selected patients. Due to its good tolerance and the rapid hormonal and clinical improvement it may be also considered as the best therapeutic approach to initiate the treatment of PRL‐ and/or GH‐secreting pituitary tumours.
SUPPRESSION OF PARATHYROID HORMONE INHIBITORY ACTIVITY OF PLASMA IN PSEUDOHYPOPARATHYROIDISM TYPE I BY IV CALCIUM
Authors: LOVERIDGE N. , FISCHER J. A. , DEVOGELAER J.‐P. , DE DEUXCHAISNES C. NAGANT
Published: March 2008

The biological response, as measured in the cytochemical bioassay, to the high circulating levels of immunoreactive parathyroid hormone (iPTH) in patients with pseudohypoparathyroidism type I (PSPI) is affected by the presence of an endogenous inhibitor. This is evidenced by the reduced recovery of the biological activity of PTH added to the plasma. Here we have used i.v. calcium infusion to inhibit the release of PTH and studied endogenous PTH bioactivity and immunoreactivity as well as the recovery of the bioactivity of added PTH in a normal subject and two patients with PSPI. In the control subject both bioactive PTH (bioPTH) and iPTH fell in response to the increased levels of plasma calcium and the recovery of the biological activity of PTH added to the plasma remained unchanged. In the PSPI patients, although the level of iPTH fell, the level of bioPTH remained unchanged. However, the level of inhibitory activity of the plasma, as determined by the recovery of added PTH, was transiently normalized in response to the rise in plasma calcium. Thus i.v. calcium infusions not only suppress the release of endogenous iPTH but also the inhibitory activity present in the plasma of PSPI patients.
IMMUNOLOGICAL DISTURBANCES IN PATIENTS WITH PREMATURE OVARIAN FAILURE
Authors: PEKONEN F. , SIEGBERG R. , MÄKINEN T. , MIETTINEN A. , YLI‐KORKALA O.
Published: March 2008

Eighteen patients with postmenopausal gonadotrophin levels and secondary amenorrhoea before the age of 35 years (premature ovarian failure, POF) were examined for the presence of cellular and humoral immune defects. Six patients had an abnormally low natural killer (NK) cell activity. The levels of circulating immune complexes were increased in six patients. Tissue antibodies were detected in six patients and two of these possessed ovarian antibodies. Leukocyte migration inhibition in the presence of ovarian antigen was slightly enhanced in three patients. Altogether 12 patients (66%) with POF had some immunological defect or defects suggesting that immune mechanisms are often involved in the aetiology of POF.
THYROID AUTOANTIBODIES IN HLA‐GENOTYPED TYPE 1 DIABETIC FAMILIES: SEX‐LIMITED DR5 ASSOCIATION WITH THYROID MICROSOMAL ANTIBODY
Authors: ROMAN SHEILA H. , DAVIES T. F. , WITT MARY E. , GINSBERG‐FELLNER FREDDA , RUBINSTEIN P.
Published: March 2008

Thyroid autoantibodies are common in Type I diabetics and their first degree relatives and may be part of the autoimmune diathesis present within such families. We have measured the prevalence of microsomal (M‐Ab) and thyroglobulin (Tg‐Ab) autoantibodies in 84 HLA‐typed families having a Type 1 diabetic child, using enzyme‐linked immunosorbent assay techniques. Thyroid autoantibodies were detectable in 201/407 (49%) individuals in these families. Both autoantibodies were significantly more frequent in the subsets of parents, diabetic children and their non‐diabetic siblings than in groups of control adults and children. The prevalence of these autoantibodies in the diabetic families was increased in both sexes with a female:male ratio of 1.4:1. Antigen DR5 was significantly associated with M‐Ab production but only for male subjects (P= 0.005 after correction for the number of DR antigens tested). No significant associations were encountered for Tg‐Ab. Within‐family analyses indicated that thyroid autoantibodies occurred with increased prevalence in HLA‐identical or haplo‐identical siblings of autoantibody‐positive index cases in comparison to control children. We conclude (1) the DR association with thyroid autoantibody production in this diabetes‐selected population was thyroiditis‐related and not diabetes‐related, and (2) the DR5 association was restricted to males and the production of M‐Ab. These data are consistent with the hypothesis that multiple genetic and non‐genetic factors played a role in the high prevalence of thyroid autoantibodies in this population.
TSH RECEPTOR ANTIBODY INDUCTION OF THYROGLOBULIN RELEASE FROM HUMAN THYROID CELL MONOLAYERS
Authors: FELDMAN A. , SCHWARTZ A. E. , FRIEDMAN E. W. , DAVIES T. F.
Published: March 2008

We investigated the influence of TSH receptor antibody (TRA), as detected by inhibition of 125I‐bTSH binding to detergent solubilized porcine TSH receptors, on in‐vitro thyroglobulin (hTg) production using normal thyroid cells in monolayer. Secretion of hTg into the culture medium was analysed by a noncompetitive enzyme immunosorbent (ELISA) technique utilizing two murine monoclonal antibodies. Basal hTg release (mean ± SD 124 ± 27 ng/105 cells/6 d, n= 5) was stimulated by bTSH (10, 102, 103μU/ml) in a dose related manner (mean ± SD 191 ±24, 587 ±80, 695 ±66 ng/105 cells/6 d, respectively). IgG (2 mg/ml) from seven patients with hyperthyroid Graves' disease, and known titres of TRA, similarly enhanced production of hTg, in a dose and time‐dependent manner, when compared to control IgG. The degree of induction varied from a 140–230% increase in total hTg release over a 6‐day incubation period. There was a direct correlation between the degree of 125I‐bTSH binding inhibitory activity and the hTg response (r= 0.9, P < 001). These data demonstrate that TSH receptor antibodies enhance hTg release from human thyroid cell monolayers and allow an assessment to be made of antibody‐activated post receptor mechanisms.
INSULIN‐LIKE GROWTH FACTOR I (IGF‐I) IN HEALTHY CHILDREN, ADOLESCENTS AND ADULTS AS DETERMINED BY A RADIOIMMUNOASSAY SPECIFIC FOR THE SYNTHETIC 53–70 PEPTIDE REGION
Authors: SILBERGELD A. , LITWIN A. , BRUCHIS S. , VARSANO I. , LARON Z.
Published: March 2008

A radioimmunoassay (RIA) specific for the synthetic 53–70 peptide region of human insulin‐like growth factor I (IGF‐I) was used to determine IGF‐I in the serum of 191 healthy newborns, children and adolescents and in 26 adults. The results compare favourably with reported values obtained using RIA systems for the native IGF‐I molecule. Intra‐ and inter‐assay CV were 3.3 and 7.2% respectively. In childhood, mean ± SD IGF‐I levels rise from 60 ± 3.5 nmol/l in newborns to 16.5±4.0 nmol/l at 8–11 years in both sexes. At the onset of puberty, IGF‐I levels in females (24.9 ± 6.6 nmol/l) are significantly (P > 0.005) higher than in males (17.2 ± 4.2 nmol/l). With further pubertal development IGF‐I levels continue to rise, reaching peak values at pubertal stage P4 (40.6 ± 4.5 nmol/l in males, 42.8 ± 5.1 nmol/l in females) and decline thereafter to lower values during adulthood: 16.5 ± 5.8 nmol/l (males) and 24.2 ± 7.0 nmol/l (females) (P > 0.001). In pubertal males, IGF‐I correlates significantly with height (r= 0.66, P < 0.001), bone age (r= 0.69, P > 0.001) and growth velocity (r= 0.64, P= 0.025) as well as with testosterone levels (r= 0.69, P < 0.001). In pubertal females a significant correlation is found between IGF‐I and height (r= 0.55, P < 0.020). The ready availability of a simple, precise and reproducible IGF‐I RIA, should contribute much to evaluating the importance of IGF‐I measurements in normal growth and in the diagnosis and therapy of various growth disorders.
THE EFFECT OF OVINE CORTICOTROPHIN RELEASING FACTOR (oCRF), BROMOCRIPTINE AND TRH ON THE SECRETION OF ACTH AND α‐MSH IN NELSON'S SYNDROME AND CUSHING'S DISEASE
Authors: ABRAHAM R. R. , CAMPBELL E. A. , GILLHAM B. , THODY A. J. , ALTAHER A. R. H. , PRYSOR‐JONES A. , WYNN V. , JONES M. T. , JENKINS J.
Published: March 2008

The circulating levels of ACTH and α‐melanocyte stimulating hormone (α‐MSH) were measured in 9 patients with Nelson's syndrome after the administration of saline, ovine corticotrophin releasing factor (oCRF), bromocriptine or TRH. The concentrations of ACTH were grossly elevated and α‐MSH levels ranged from undetectable to higher than the normal range. In seven of eight subjects there was a rapid corticotrophic response, but no change in the α‐MSH level, following oCRF. This response was delayed in one subject. Following oCRF injection, the plasma oCRF profile was variable but circulating oCRF was detectable even at the end of the experiment in all cases. There was no significant change in circulating ACTH or α‐MSH following either bromocriptine or TRH. Cultured tumour cells from one case of Cushing's disease showed a corticotrophic response but no change in α‐MSH to oCRF and the response was enhanced by vasopressin. Bromocriptine added to the same tumour depressed ACTH secretion without affecting the output of α‐MSH. The present data suggest that the tumours in these subjects are responsive to oCRF and arise from corticotrophs rather than melanotrophs.
ADRENERGIC ACTIVITY AND ALDOSTERONE REGULATION: NO EVIDENCE FOR AN ALPHA‐1 ADRENOCEPTOR‐MEDIATED INFLUENCE IN NORMAL SUBJECTS
Authors: BIANCHETTI L. , FERRIER C. , BERETTA‐PICCOLI C. , FRASER R. , MORTON J. J. , ZIEGLER W. H.
Published: March 2008

In normal man the sympathetic nervous system could exert an inhibitory influence on aldosterone responsiveness to angiotensin II. The possible role of alpha‐1 adrenoceptors in the modulation of aldosterone response was assessed by studying the changes of plasma aldosterone during infusion of angiotensin II at the doses of 1, 2, 5 and 10 ng/kg.min or after 1–24corticotrophin injection, 0.25 mg, in 9 normal subjects before and after treatment with the selective alpha‐1 adrenoceptor antagonist, prazosin. Prazosin, given during 3 weeks, did not modify supine arterial pressure, heart rate and the plasma levels of angiotensin II, renin, aldosterone or adrenaline but caused a significant (P < 005) increase of plasma noradrenaline. The correlation relating plasma aldosterone to plasma angiotensin II levels before and during angiotensin II infusion and the response of plasma aldosterone to corticotrophin was not modified by prazosin. These findings suggest that in normal man there is no inhibitory influence of the noradrenergic system on aldosterone responsiveness to angiotensin II mediated by an alpha‐1 dependent mechanism.
INTERACTION OF THYROTROPHIN RELEASING HORMONE AND THE ENKEPHALIN ANALOGUE DAMME ON PITUITARY HORMONE SECRETION
Authors: PICÓ A. , CACICEDO L. , VARELA C. , SáNCHEZ‐FRANCO F.
Published: March 2008

Because TRH counteracts the inhibitory effect of opiate peptides on LH secretion in cultured cells from normal pituitaries, six normal postmenopausal women were studied to determine whether TRH interacts in vivo with opioid peptides in the regulation of pituitary hormone secretion. At two different times a constant 3 h infusion of either saline or TRH (5 μg/min) was initiated. At 60 min a 250 μg bolus of the opiate agonist peptide D‐AIa2‐MePhe4‐metenkephalin‐0‐ol (DAMME) was injected in one of the two saline and TRH infusion tests. The four treatments, i.e. saline infusion alone, saline infusion with a DAMME bolus, TRH infusion alone; and TRH infusion with DAMME bolus were given at random with an interval of at least 7 d. Blood samples were taken every 15 min during the 3 h study. DAMME induced a significant fall (P < 0.05) in serum LH (from 35±8.5 to 18.3±5.1 mlU/ml) (mean±SEM) without significantly affecting FSH levels (from 29 ± 11.2 to 26.9 ± 12.4 mlU/ml). These changes were not antagonized by the continuous infusion of TRH. PRL had a monophasic response pattern to continuous isolated TRH infusion; the basal levels increased from 4.2 ± 1.2 to 24.5 ± 6.8 ng/ml at 30 min and then slowly decreased with a plateau from 90 min until the end of the study. DAMME administration at 60 min induced a significant second peak of PRL secretion (44±6.5 ng/ml) 30 min later (P < 005). Basal serum TSH levels increased progressively during the first 135 min of TRH infusion (from 2.4 ± 0.5 to 18.5 ± 5.2 μU/ml), and then remained stable until the end of treatment. DAMME induced an even more striking TSH response 30 min after its administration at 60 min (P < 0.05), which was later maintained. In the absence of TRH infusion, DAMME administration did not modify either PRL or TSH basal levels. GH values did not significantly change during saline or TRH infusion alone, nor after DAMME i.v. administration at 60 min in either test. These findings are against an antagonistic effect of TRH and opioid peptides on the regulation of pituitary hormones in postmenopausal women. DAMME potentiating activity on PRL and TSH stimulatory action of continuous TRH infusion is shown. Also confirmed is the inhibitory effect of DAMME on LH secretion in postmenopausal women. Some of these effects may at least partially be mediated by the opiate inhibition of dopamine secretion.
CHANGES IN THYROID‐STIMULATING AND TSH‐BINDING INHIBITORY ACTIVITIES IN A PATIENT WHO DEVELOPED HYPERTHYROIDISM DUE TO GRAVES' DISEASE FOLLOWING PRIMARY HYPOTHYROIDISM
Authors: KASAGI K. , KONISHI J. , IIDA Y. , MORI T. , TORIZUKA K.
Published: March 2008

A 23‐year‐oid female who developed thyrotoxic Graves' disease following primary hypothyroidism was reported. She presented with symptoms of hypothyroidism and slight exophthalmos. After primary hypothyroidism was confirmed, she was treated with T4 in a dose of 50 μg/d. Two months after delivery, 1 year after the initial diagnosis of hypothyroidism, hyperthyroidism developed while she was taking T4. Graves' disease was confirmed by persistent thyrotoxicosis, high 99mTc thyroidal uptake, negative T3 suppressibility and detection of TSH‐receptor antibodies. During the hypothyroid phase, TSH‐binding inhibitory immunoglobulins (TBII) could not be detected, while thyroid stimulating antibodies (TSAb) were positive showing between 5.8 and 90 fold increases in the amount of cAMP produced in cultured porcine thyroid cells. Her IgG did not inhibit TSH‐induced cAMP increase in vitro. When she developed hyperthyroidism, TSAb activity became more potent (31.7 fold increase in cAMP) and TBII became positive (+61.3%).
PROLONGED LOW‐INTENSITY EXERCISE RAISES THE SERUM PARATHYROID HORMONE LEVELS
Authors: LJUNGHALL S. , JOBORN H. , ROXIN L.‐E. , RASTAD J. , WIDE L. , ÅKERSTRÖM G.
Published: March 2008

Twelve healthy males performed 5 h exercise on a bicycle ergometer at a constant work load of approximately 50% of their maximum capacity. The serum concentrations of parathyroid hormone (PTH) increased after the first hour and were continuously elevated throughout the exercise period. The rise in PTH was 5–7% above pre‐exercise levels, corresponding to 20–30% of the maximal increase obtained by the same assay during prolonged hypocalcaemia. The probable cause for the rise in PTH was that the plasma ionized calcium tended to be lowered during exercise. Since the total serum calcium concentrations were raised (by 3–5%) during exercise the reduction of the free, ionized, fraction was presumably largely due to increased complex‐binding although an outward transport from plasma was not excluded. The serum concentrations of magnesium were gradually reduced during exercise while those of phosphate and potassium were raised throughout, probably as a result of leakage from the working muscle.
ASYMPTOMATIC HYPERPROLACTINAEMIA AND PROLACTINOMA IN THE GENERAL POPULATION—MASS SCREENING BY PAIRED ASSAYS OF SERUM PROLACTIN
Authors: MIYAI K. , ICHIHARA K. , KONDO K. , MORI S.
Published: March 2008

A total of 10 550 ‘normal’ adults (8450 men and 2100 women) in the general population were screened by a paired assay method for serum PRL and 40 subjects with hyperprolactinaemia (>75 μg/1) were detected. Of these, five patients (three men and two women) with pituitary prolactinoma, one man with empty sella syndrome, 10 cases of ‘big’ prolactinaemia, seven pregnant women and 13 subjects with drug‐induced hyperprolactinaemia were found. The patients with prolactinoma had few if any complaints (asymptomatic prolactinoma).
NON‐FUNCTIONING PITUITARY ADENOMAS DO NOT REGRESS DURING BROMOCRIPTINE THERAPY BUT POSSESS MEMBRANE‐BOUND DOPAMINE RECEPTORS WHICH BIND BROMOCRIPTINE
Authors: BEVAN J. S. , BURKE C. W.
Published: March 2008

Dopaminergic binding to membranes from 20 well‐characterized non‐functioning pituitary tumours was investigated using the radioligand [3H]spiperone; nine had failed to regress during pre‐operative bromocriptine therapy. Five macro‐prolactinomas and six normal pituitaries were similarly investigated. High affinity dopaminergic binding sites were defined in all tissues studied. Mean dissociation constants were similar for the three groups (0.92, 0.55 and 0.51 nmol/l, respectively) but mean site numbers were greater in the prolactinomas (698) than in non‐functioning tumours (131) or normal pituitaries (136 fmol/mg protein). In a pool of non‐functioning tumour membranes ligand competition experiments confirmed that binding was dopaminergic. Stereospecificity was demonstrated using the (+) and (−) isomers of butaclamol. Bromocriptine was present in three non‐functioning tumours that had been exposed to the drug within 24 h of surgery and it largely prevented [3H]spiperone binding; membrane washing restored [3H]spiperone binding to control values. We conclude that non‐functioning tumours possess high affinity membrane‐bound dopaminergic binding sites similar to those in normal pituitary and macroprolactinomas, but apparently fewer in number than in the latter. Though bromocriptine binds to dopamine receptors on non‐functioning tumours in vivo, this does not result in tumour regression.
EFFECT OF INJECTION SITE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF SUBCUTANEOUSLY ADMINISTERED LUTEINIZING HORMONE RELEASING HORMONE
Authors: BLUNT S. M. , CLAYTON R. N. , BUTT W. R.
Published: March 2008

Serum concentrations of LHRH and the subsequent LH responses were compared following s.c. injections of 20 μg LHRH into the upper arm and the lower abdominal wall, in 9 hypogonadal women responsive to pulsatile LHRH therapy. Tests were carried out at the two sites in random order. Peak LHRH concentrations were reached by 5 min after upper arm and by 20 min after lower abdominal wall injections, the maximum concentrations being significantly greater following injections into the former. There was no increase in LH until 10 min and then maximum concentrations were reached at 30 min following injection into both sites. There was no significant correlation between the LHRH increments and the LH response but there was a negative correlation between the Ponderal Index of the patients and the LHRH increments following injections into the lower abdominal wall only. There was no significant overall difference between the LH increments related to the site of injection, but the order of injections affected the responses. When upper arm injections were given first the LH responses were significantly greater, but when lower abdominal wall was injected first the subsequent responses to upper arm injections were impaired. A possible reason for this is that the absorption from the lower abdominal wall was delayed so prolonging the exposure of the pituitary gonadotrophs to LHRH, resulting in pituitary desensitization at the time of the second test.
DOSAGE‐RELATED EFFECTS OF DANAZOL ON SEX HORMONE BINDING GLOBULIN AND FREE AND TOTAL ANDROGEN LEVELS
Authors: FORBES K. L. , DOWSETT M. , ROSE GILLIAN L. , MUDGE JOANNE E. , JEFFCOATE S. L.
Published: March 2008

Danazol is known to cause marked suppression of sex hormone binding globulin (SHBG) levels in plasma and to increase the proportion of plasma testosterone unbound to protein but the effect on the concentration of total and free testosterone is unclear. Twenty‐five patients with endometriosis were treated daily for 6 months with doses of danazol ranging from 50 to 600 mg. The fall in SHBG and rise in percent free testosterone was dose‐related during the early part of treatment. Suppression of total testosterone and 5α‐dihydrotestos‐terone levels occurred and was probably due to increases in metabolic clearance rates. The observed fall in androstenedione levels was related to the incidence of menstrual abnormality, suggesting that this might be due to reduced ovarian activity. The concentration of free testosterone increased by a factor of two in the first week but subsequently returned to levels of between 25 and 50% above pretreatment levels. This pattern of changes may be due to the rise in metabolic clearance rates being dependent on induction of enzymes of androgen metabolism.
INCREASED CIRCULATING RADIORECEPTOR‐ACTIVE GROWTH HORMONE IN INSULIN‐DEPENDENT DIABETICS
Authors: MACFARLANE I. A. , STAFFORD S. M. , WRIGHT A. D.
Published: March 2008

A radioreceptor assay (RRA) for GH, using pregnant rabbit liver membranes, was used to evaluate the receptor‐hormone interaction of circulating (serum) GH in diabetics. Multiple morning blood samples were taken from 18 fasted insulin‐dependent diabetics on three occasions and assayed for GH by the RRA and radioimmunoassay (RIA). Samples from 12 normal subjects (GH secretion stimulated by exercise and hypoglycaemia) and 11 acromegalics were also studied. The RRA/RIA ratio was higher in samples from the acromegalics than in normal subjects (0.85 vs 0.65, P < 0.01) and only a few samples had RRA values greater than RIA. All the samples from 14 of the diabetics had lower RRA values than RIA, but 40% (39 of 96) of samples from the remaining four diabetics had RRA concentrations markedly in excess of the levels measured by RIA. Sephadex chromatography (G100) of serum samples revealed similar proportions of immunoreactive GH forms in the diabetics with high RRA values compared with the diabetics with low RRA values. These findings may indicate intermittent secretion of highly bioactive GH in some insulin‐dependent diabetics. Further studies on the biological properties of circulating GH are needed to clarify the role of GH secretion in the development of diabetic microvascular complications.
VITAMIN D NUTRITION AND VITAMIN D METABOLISM IN THE PREMATURE HUMAN NEONATE
Authors: MAWER E. BARBARA , STANBURY S. W. , ROBINSON M. J. , JAMES J. , CLOSE C.
Published: March 2008

The effect of supplementation with daily doses of vitamin D2 (1000 IU or 3000 IU, 25–75 μg, 63–189 nmol) has been studied in 39 premature neonates, initial gestational age 25–32 weeks. The initial mean plasma 25‐hydroxyvitamin D was 25.8 nmol/l (10.3 ng/ml) but in 12 infants, most of whom were born in the winter months, the level was < 15 nmol/l (6 ng/ml), and in seven babies plasma 1,25‐dihydroxyvitamin D was <48 pmol/l (20 pg/ml). These findings suggest a considerable degree of maternal vitamin D‐deficiency. Maximum attained concentrations of 25‐hydroxyvitamin D on treatment were 77.3 nmol/l (30.9 ng/ ml), high dose and 86.8 nmol/l (34.7 ng/ml), low dose; the mean rate of increase was greatest during the first two weeks (2.2 nmol/l/d; 0.88 ng/ml/d) and declined over the next 4 weeks. Mean maximum concentrations of 1,25‐dihydroxyvitamin D2 were 283 pmol/l, (121 pg/ml), high dose and 309 pmol/l (129 pg/ml), low dose. Apart from a minor contribution to the initial plasma 1,25‐dihydroxyvitamin D concentration, no effect of gestational age could be discerned in any of the measured variables. The endogenous pool of 1,25‐dihydroxyvitamin D3 decayed with a T of 22.5 d, indicating that vitamin D supplementation of these infants was necessary to avoid vitamin D‐deficiency.
CALCITONIN GENE‐RELATED PEPTIDE AND CALCITONIN IN MEDULLARY THYROID CARCINOMA
Authors: SCHIFTER S. , WILLIAMS E. D. , CRAIG R. K. , HANSEN H. H.
Published: March 2008

We have investigated the levels of serum calcitonin and calcitonin‐gene related peptide (CGRP) in 35 patients with well‐documented medullary thyroid carcinoma (MTC). Immunohistochemical investigations for calcitonin and CGRP have been performed on tumour tissue from 9 patients to clarify the cellular pattern of production. In four patients with aggressive disease, serum calcitonin and CGRP values have been monitored in relation to progression of disease after surgery. All 35 patients with MTC have elevated calcitonin and 26 elevated CGRP levels. Generally calcitonin values were found to be higher than those of CGRP, although the ratio of the two peptides varied from patient to patient. The immunohistochemical investigations corresponded with these findings, generally showing diffuse staining for calcitonin in MTC tumour‐cells and only a small number of CGRP positive cells. Calcitonin and CGRP are produced by alternative processing of the common precursor gene transcript. Our results suggest that absolute values of either calcitonin or CGRP in serum have no direct relationship to aggressiveness of disease. Thus whilst serum CGRP measurements appear to be a useful additional marker for the disease, they can be considered to be only a useful adjunct to serum calcitonin as a marker for tumour progression.