bluuebunny/crossref_metadata_2025 huggingface dataset:
BREAST STIMULATION IN CYCLING WOMEN, PREGNANT WOMEN AND A WOMAN WITH INDUCED LACTATION: PATTERN OF RELEASE OF OXYTOCIN, PROLACTIN AND LUTEINIZING HORMONE
Authors: AMICO JANET A. , FINLEY B. E.
Published: March 2008

Levels of oxytocin (OT) and PRL were measured in plasma drawn before and during intermittent mechanical pump and tactile stimulation of the breast in five normal cycling women and 19 women in the third trimester of pregnancy. OT was significantly increased above baseline in response to breast stimulation in two of five cycling women and PRL increased in one of the two OT responders. In pregnant women, mean OT post nipple stimulation was significantly higher than pre nipple stimulation whereas PRL did not increase significantly. The response of OT to nipple stimulation occurred in 18 of 19 pregnant women compared to only two of five normal cycling women but the magnitude of the OT response in pregnant women was less than in cycling women or post‐partum lactating women previously studied in this laboratory. In one non post‐partum woman who induced lactation for the purpose of breast‐feeding an adopted infant, OT and PRL were measured before and during mechanical pump and tactile stimulation before initiation of breast‐feeding. OT increased during mechanical pump and tactile stimulation of the breast, as well as suckling, whereas PRL increased only in response to suckling. Levels of LH were measured in plasma every 20 min for 160 min at the following times: before initiation of breast‐feeding, during induced lactation while breast‐feeding, and 30 d after discontinuation of breast‐feeding. Despite the development of oligomenorrhoea during the period of breast‐feeding, levels of progesterone were not suppressed and LH was released in a normal pulsatile fashion.
HUMAN FETAL HYPOTHALAMIC GnRH NEUROSECRETION: DOPAMINERGIC REGULATION IN VITRO
Authors: RASMUSSEN D. D. , LIU J. H. , SWARTZ W. H. , TUEROS V. S. , YEN S. S. C.
Published: March 2008

An in‐vitro perifusion system was used to investigate GnRH release from fetal (21–23 weeks gestation) human hypothalami in response to dopamine (DA) and the DA receptor antagonist haloperidol. Administration of 1 μmol/l DA during five perifusions in which 1 μmol/l haloperidol was added to the medium failed to alter basal GnRH release. In contrast DA evoked a rapid and sustained 95·8 ± 20·3% increase (P > 0·01) in GnRH release during five matching perifusions with medium containing the α‐adrenergic antagonist phentolamine. While exposure to 0·01 μmol/l DA failed to alter basal GnRH release during three perifusions, 0·1 μmol/l DA elicited a 145·7 ± 65·2% increase (P > 0·05) in GnRH release in three matching perifusions, indicating a dose‐dependent effect. These studies demonstrate that DA can stimulate in‐vitro release of GnRH from the mid‐gestation fetal human hypothalamus by a DA receptor mediated mechanism.
THE ABILITY OF THE SERUM THYROTROPHIN RECEPTOR ANTIBODY (TRAb) INDEX AND HLA STATUS TO PREDICT LONG‐TERM REMISSION OF THYROTOXICOSIS FOLLOWING MEDICAL THERAPY FOR GRAVEs' DISEASE
Authors: WILSON R. , McKILLOP J. H. , HENDERSON N. , PEARSON D. W. , THOMSON J. A.
Published: March 2008

In agreement with previous authors we found patients with Graves' disease to have an increased incidence of the DR 3 antigen. We could find no association, however, between the presence of the antigen and relapse after carbimazole treatment. A concordant HLA status and thyrotrophin receptor antibody (TRAb) index, obtained at either 6 or 12 months after the start of treatment could only predict cases of relapse and remission in a minority of patients making this of very limited clinical use. The TRAb index obtained at 12 months after the start of medical therapy could accurately predict cases of relapse and remission for the next 3 years in 24/30 patients studied.
NOCTURNAL URINARY MELATONIN EXCRETION AND PLASMA CORTISOL LEVELS IN CHILDREN AND ADOLESCENTS AFTER A SINGLE ORAL DOSE OF DEXAMETHASONE
Authors: LANG U. , THEINTZ G. , RIVEST R. W. , SIZONENKO P. C.
Published: March 2008

In the present study, the possible relationship between melatonin secretion as reflected by nocturnal melatonin excretion (2000 h‐0800 h) and the pituitary‐adrenocortical axis was investigated. Nocturnal urinary melatonin excretion and plasma cortisol levels were determined in 41 children with weight problems before and after a single oral dose of dexamethasone. A first group of 15 individuals with normal cortisol cycle (12·2 ± 1·4 at 0800 h and 3·1 ± 0·5 μg/100 ml at 1700 h), and levels below 1·0 μg/100 ml after dexamethasone, showed a highly significant increase in melatonin excretion during the night following dexamethasone treatment (63·5 ± 5·5 ng/12 h vs 33·6 ± 3·0 for the control night, P > 0·001). This increase was observed from prepuberty to young adulthood (pubertal stages PI—PV). In a second group of 16 subjects with mean cortisol levels similar at 0800 h and 1700 h (10·7 ± 1·3 and 9·3 ± 1·5 μg/100 ml respectively), but with a normal cortisol suppression after dexamethasone administration, nocturnal melatonin excretion increased from 21·2 ± 2·1 to 33·4 ± 3·0 ng/12 h (P > 0·01). A significant increase was found in prepubertal children (PI) whereas no change was observed at the end of pubertal development (stages PIV‐PV). A third group of 10 patients with both low amplitude cortisol cycles (16·2 ± 2·5 and 10·8 ± 2·4 μg/100 ml) and abnormal cortisol suppression after dexamethasone administration (9·1 ± 2·4 μg/100 ml), showed no increase in melatonin excretion (24·2 ± 2·7 and 24·9 ± 3·7 ng/12 h). However, one patient with delayed puberty had increased melatonin excretion after dexamethasone. No relationship was found between body weight and melatonin excretion. Six subjects with delayed puberty had high melatonin excretion before dexamethasone and showed a marked increase after dexamethasone treatment (76·1 ± 7·2 ng/12 h vs 38·6 ± 6·9 for the control night, P > 0·001), whatever the cortisol cycles and levels of suppression. Our results suggest a relationship between the patterns of cortisol and melatonin secretion. However, further studies are necessary to prove whether there exist interactions between the pituitary‐adrenal axis and the pineal gland and whether the response of melatonin to dexamethasone is also related to the stage of sexual maturation.
THE EFFECT OF OXANDROLONE ON THE GROWTH HORMONE RESPONSE TO GROWTH HORMONE RELEASING HORMONE IN CHILDREN WITH CONSTITUTIONAL GROWTH DELAY
Authors: LOCHE S. , CORDA R. , LAMPIS A. , PUGGIONI R. , CELLA S. G. , MULLER E. E. , PINTOR C.
Published: March 2008

The effect of treatment with oxandrolone, an anabolic steroid, on GH response to GH‐releasing hormone (GHRH) has been evaluated in children with constitutional growth delay. Five subjects, four males and one female, aged 11·0–17·1 years were given oxandrolone 0·1 mg/kg p.o. daily for 2 months, and underwent acute administration of GHRH (GRF 1–40, 1 μg/kg i.v.) before and after withdrawal of oxandrolone therapy. GHRH administration induced a much greater GH response, evaluated either as a peak plasma GH levels or plasma GH integrated area, after than it did before oxandrolone treatment. These findings indicate that in children with constitutional growth delay oxandrolone increases the sensitivity of somatotrophs to exogenous GHRH and, likely, to the endogenously‐released neurohormone.
ASSESSMENT OF THYROXINE SUPPRESSION IN THYROID CARCINOMA PATIENTS WITH A SENSITIVE IMMUNORADIOMETRIC TSH ASSAY
Authors: LAMBERG B.‐A. , HELENIUS T. , LIEWENDAHL K.
Published: March 2008

Serum TSH was determined with a sensitive radioimmunometric method (TSH IRMA) in 57 patients on suppression therapy with T4 after operation for differentiated thyroid carcinoma. When using a conventional RIA technique basal TSH was not detectable and remained so even after stimulation with TRH. With the TSH IRMA method 46 patients had a basal TSH below the detection limit (0·02 mU/l) (81 %) and in seven patients the values were between 0·02 and 0·05 mU/l (12%). In 23 of these patients there was a small increment of 0·01–0·15 mU/l. In two patients the basal TSH was 0·08 and 0·09 mU/l, and the increment after TRH was less than 0·7 mU/l. In two other patients with basal values close to 0·2 mU/l the increment after TRH was more than 1·0 mU/l. An undetectable basal TSH value did not thus predict an absent response to TRH. The responses were, however, in all but two cases, so small that they could be regarded as clinically insignificant. Therefore, the authors conclude that a basal TSH of 0·1 mU/l, as measured with a TSH IRMA method with a detection limit of 0·05, is a sufficient indication of TSH suppression in carcinoma patients on T4 therapy and that further testing with the TRH‐stimulation test is unnecessary.
THE ASSESSMENT OF DIMINISHED TESTICULAR FUNCTION IN BOYS OF PUBERTAL AGE
Authors: KULIN H. E. , SANTNER S. J.
Published: March 2008

Nine boys with anorchia and 9 individuals with diminished testicular function were followed between ages 10 and 18 with serial determinations of urine gonadotrophins and serum testosterone. Ten hCG stimulation tests were performed in eight of these patients. Adult levels of LH (> 500 mIU/h) and low measurements of serum testosterone (> 54 ng/dl) confirmed the anorchic state. Boys with diminished testicular reserve exhibited urinary gonadotrophin changes similar to peripubertal anorchic patients but testosterone levels increased progressively with age (90–715 ng/dl). FSH attained adult castrate levels (> 1700 mIU/h) by age 13 in these boys and served to distinguish them from normal controls. The longitudinal assessment of basal hormone levels can separate anorchia from diminished testicular reserve in boys of pubertal age and testing with hCG is not required for evaluation.
ATROPINE SELECTIVELY BLOCKS GHRH‐INDUCED GH SECRETION WITHOUT ALTERING LH, FSH, TSH, PRL AND ACTH/CORTISOL SECRETION ELICITED BY THEIR SPECIFIC HYPOTHALAMIC RELEASING FACTORS
Authors: CASANUEVA F. F. , VILLANUEVA L. , DIAZ Y. , DEVESA J. , FERNANDEZ‐CRUZ A. , SCHALLY A. V.
Published: March 2008

The role of acetylcholine in the regulation of the hypothalamo‐pituitary system in man was assessed using atropine, which selectively blocks cholinergic muscarinic receptors. Paired tests were performed in 10 normal men using either GHRH (1 μg/kg i.v.), or TRH (300 μg i.v.) plus LHRH (100 μg i.v.) plus corticotrophin releasing hormone (CRH) (1 μg/kg i.v.) with or without atropine given 30 min previously (1 mg i.m.). The GHRH‐induced GH secretory peak (17·8 ± 3·0 ng/ml) was completely blocked by atropine administration (2·8 ± 0·6 ng/ml) (P>0·05). Atropine did not, however, modify TRH‐induced TSH and PRL secretion, nor FSH and LH release induced by the LHRH pulse. ACTH/ cortisol secretion elicited by CRH was also unaffected by atropine. These results suggest that atropine blockade of GHRH‐induced GH secretion is highly specific, and constitutes an indication of the importance of cholinergic control of GH function. Furthermore, atropine's lack of action on the other pituitary hormones rules out the possibility that it acts non‐specifically, i.e. via blood flow changes or toxic effects.
RELATIONSHIPS BETWEEN THE CHARACTERISTICS OF ENDOGENOUS LUTEINIZING HORMONE SURGE AND THE DEGREE OF OVARIAN HYPERSTIMULATION DURING SUPEROVULATION INDUCTION IN WOMEN
Authors: MESSINIS I. E. , TEMPLETON A. , BAIRD D. T.
Published: March 2008

Ovarian hyperstimulation was induced in 17 normally cycling women undergoing in‐vitro fertilization (IVF) and embryo transfer with clomiphene (9 cycles), clomiphene followed by pulsatile hMG (12 cycles) or clomiphene followed by pulsatile FSH (11 cycles). Hyperstimulation was greater with the combined treatments than with clomiphene alone. In all 32 cycles an endogenous LH surge occurred. The peak values and the duration of the LH surge showed significant negative correlations with the plasma oestradiol levels, the number of the follicles and the total follicular fluid volume aspirated at laparoscopy. We suggest that during superovulation induction for IVF, the endogenous LH surge is attenuated by factors which are related to the degree of ovarian hyperstimulation.
FAMILIAL DYSALBUMINAEMIC HYPERTHYROXINAEMIA: STUDIES OF ALBUMIN BINDING AND IMPLICATIONS FOR HORMONE ACTION
Authors: BARLOW J. W. , CSICSMANN J. M. , MEINHOLD H. , LIM C.‐F. , STOCKIGT J. R.
Published: March 2008

The abnormal intermediate‐affinity T4 binding to albumin which is characteristic of familial dysalbuminaemic hyperthyroxinaemia (FDH) is dependent on buffer, temperature, and ionic composition. Scatchard analysis of T4‐binding to isolated albumin preparations from FDH subjects showed that half the circulating albumin showed the higher‐affinity T4 binding site, assuming one site per molecule. Using dextran‐charcoal separation at 40C the T4 affinity (Ka) of purified albumin from FDH subjects was 7.5 nmol/l in phosphate and 17 nmol/l in Tris‐CI‐ buffer. T4 binding to FDH albumin was inhibited by a range of substances in the order: 8‐anilino‐l‐naphthalene sulphonic acid > merthiolate>propylthiouracil> methyl‐thiouracil > carbimazole > salicylate > barbitone. Binding of T4 was competitively inhibited by low concentrations of dithiothreitol (DTT). The effect of DTT 0.1–0.5 mmol/l was reversed by removal of DTT by dialysis. Competition with a range of iodothyronines indicated that the 3′, 5′‐iodine atoms are most important for binding to this site. Serum binding of salicylate. frusemide. fenclofenac and barbituric acid, and a range of steroid hormones was similar in FDH and normal sera. Serum levels of sex hormone binding globulin (SHBG), were not significantly different from sex‐matched controls. Nuclear [125I]‐T3 binding sites in circulating lymphocytes from two FDH subjects showed affinities (Kd) of 59 and 79 pmol/l (normal 67±7 pmol/l, n= 6. These findings suggest that the highly specific binding anomaly of FDH is due to a disulphide‐dependent structural change in albumin. The normal T3 affinity of lymphocytic receptors and normal SHBG levels are consistent with a normal relationship between free hormone and tissue response in FDH.
ABSORPTION OF ORAL DIPHOSPHONATE IN NORMAL SUBJECTS
Authors: FOGELMAN I. , SMITH L. , MAZESSS R. , WILSON M. A. , BEVAN J. A.
Published: March 2008

Absorption of the diphosphonate etidronaEe (HEDP) was measured in 20 volunteer subjects at two centres (Glasgow and Madison) using a new method based on simultaneous administration of HEDP and intravenous 99Tc‐HEDP (Osteoscan). The mean absorption of HEDP in fasting subjects in Glasgow was 3.5% (range 1–8.9%) and in Madison 1.5% (0.7–2.8%) (P<0.035). In four subjects studies were repeated with good agreement between results (mean 3.9 cf. 3.5%). Six subjects had studies repeated when drug was ingested with food and in all cases absorption was effectively reduced to zero. We conclude that absorption of HEDP is significantly higher in normal subjects in Glasgow than in Madison. This may be of importance with regard to the finding of histological osteomalacia and fracture associated with HEDP use in Glasgow.
FAMILIAL HYPOPITUITARISM ASSOCIATED WITH AN ENLARGED PITUITARY FOSSA AND AN EMPTY SELLA
Authors: WHITE M. C. , CHAHAL P. , BANKS L. , JOPLIN G. F.
Published: March 2008

We report an 8‐year follow‐up of three sisters born of a consanguineous marriage and who originally presented with short stature and enlarged pituitary fossa. All have shown progressive failure of anterior pituitary hormone function. In addition, the two eldest sisters were eventually found to have an empty sella while the youngest, who initially showed an enhancing intrasellar mass consistent with a tumour, later showed an empty sella. A familial pituitary tumour developing early in childhood but subsequently undergoing involution could account for these findings.
AUTONOMOUS OVARIAN HYPERFUNCTION FOLLOWED BY GONADOTROPHIN‐DEPENDENT PUBERTY IN McCUNE‐ALBRIGHT SYNDROME
Authors: KAUFMAN FRANCINE RATNER , COSTIN GERTRUDE , REID BARBARA S.
Published: March 2008

A 5‐year‐old girl with the McCune‐Albright syndrome presented with precocious puberty secondary to autonomously functioning ovarian cysts, followed by true central puberty. Progression from gonadotrophin‐independent to gonadotrophin‐dependent precocious puberty may occur from elevated sex steroid levels leading to the early maturation of the hypothalamic‐pituitary axis.
MANAGEMENT OF CRANIAL DIABETES INSIPIDUS WITH ORAL DESMOPRESSIN (DDAVP)
Authors: CUNNAH D. , ROSS G. , BESSER G. M.
Published: March 2008

The effect of oral administration of desmopressin (DDAVP) solution was investigated in six patients with cranial diabetes insipidus of varying aetiology. All patients experienced a prompt and prolonged antidiuresis. Nine patients have been managed with oral DDAVP tablets for up to 5 months and all preferred this route of administration to intranasal application using a rhinyle. Oral DDAVP gives excellent and convenient control in cranial diabetes insipidus.
BIOACTIVE LUTEINIZING HORMONE IN PLASMA OF URAEMIC MEN AND MEN WITH PRIMARY TESTICULAR DAMAGE
Authors: HANDELSMAN D. J. , JENNIFER A. , SPALIVIERO  , TURTLE J. R.
Published: March 2008

Elevation of immunoreactive LH and reduced testosterone production are consistent features of Leydig cell dysfunction in uraemic hypogonadism. To investigate further Leydig cell regulation in uraemia, we measured plasma bioactive LH (B‐LH) and immunoreactive LH (I‐LH), as well as FSH, testosterone, creatinine, urea and albumin in seven uraemic men before and after haemodialysis and compared them to levels both in eugonadal controls (n = 10) and in men with primary testicular damage (n= 10). Plasma B‐LH was increased in uraemic men compared with both nonuraemic control groups. Plasma I‐LH and FSH were increased and testosterone decreased in uraemic men compared to eugonadal controls. In comparison with nonuraemic men with primary testicular damage, plasma I‐LH levels were similar but FSH and testosterone lower in uraemic men. As a consequence, the ratio of B‐LH to I‐LH (LH:B/I ratio) was decreased in men with primary testicular damage but normal in uraemic men. A single session of haemodialysis decreased creatinine (50–5%) and urea (58.5%) and increased B‐LH (47.7%), I‐LH (32.9%), FSH (24.4%), testosterone (15.8%) and albumin (17.8%) levels, but the LH:B/I ratio was unchanged. Increases in gonadotrophin levels were greater than could be accounted for by haemoconcentration suggesting that dialysis may also ameliorate uraemic suppression of the hypothalamus and pituitary. Ultrafiltrates of human uraemic plasma (mol wt < 25000) had no inhibitory effect on in‐vitro steroidogenesis by isolated rat Leydig cells making circulating uraemic‘middle‐molecule’‐type toxins unlikely to be involved in causing lowered testosterone levels in uraemic men. These qualitative abnormalities of plasma LH in uraemia indicate that the pathogenesis of uraemic testicular dysfunction involves additional defects in regulation of Leydig cell function beyond that of primary testicular damage.
ACTH AND CRF‐PRODUCING BRONCHIAL CARCINOID ASSOCIATED WITH CUSHING'S SYNDROME
Authors: ZÁRATE A. , KOVACS K. , FLORES M. , MORÁN C. , FÉLIX I.
Published: March 2008

A young female patient, with clinical and biochemical manifestations of severe hypercorticism and with the presence of a pituitary adenoma shown by computerized tomography, was thought to have Cushing's syndrome of hypophysial origin. However, the surgically‐removed pituitary adenoma contained no ACTH, by immunocytology, and hypercorticism persisted after transsphenoidal adenomectomy. The patient died and autopsy demonstrated an ACTH and corticotrophin releasing factor (CRF)‐containing bronchial carcinoid. It can be concluded that bronchial carcinoids can produce ACTH and CRF and can mimic the clinical and biochemical manifestations of pituitary Cushing's syndrome. Thus, the localization of the primary site of hypercorticism can be extremely difficult in patients who have an insidious, occult extrapituitary tumour. Further work is required to establish whether CRF plays a role in the causation of Cushing's syndrome and whether the simultaneous secretion of this peptide can modify the clinical and biochemical manifestations of the ectopic ACTH syndrome.
OVULATION AND NORMAL LUTEAL FUNCTION DURING LHRH TREATMENT OF WOMEN WITH HYPERPROLACTINAEMIC AMENORRHOEA
Authors: POLSON D. W. , SAGLE M. , MASON H. D. , ADAMS J. , JACOBS H. S. , FRANKS S.
Published: March 2008

Five patients with hyperprolactinaemic amenorrhoea who had been resistant to, or intolerant of bromocriptine were treated with pulsatile LHRH therapy. Ovulation was induced in 9 of 12 treatment cycles. In one patient hyperstimulation occured in the first cycle of treatment but subsequently she ovulated normally on a reduced dose of LHRH. The gonadotrophin and ovarian responses to treatment in ovulatory cycles were normal despite prolactin concentrations that remained elevated throughout treatment and rose still further with resumption of ovarian activity. The length of the luteal phase and the mid‐luteal serum progesterone concentrations were also normal. Pulsatile secretion of progesterone in response to LHRH pulses was observed. These data show that ovulation and normal luteal function can be induced by physiological LHRH replacement in women with persistent hyperprolactinaemia. This confirms that the mechanism of anovulation in hyperprolactinaemic amenorrhoea is disordered LHRH secretion.
NOCTURNAL PULSATILE GROWTH HORMONE RELEASING HORMONE TREATMENT IN GROWTH HORMONE DEFICIENCY
Authors: SMITH P. J. , BROOK C. G. D. , RIVIER J. , VALE W. , THORNER M. O.
Published: March 2008

We have treated five GH‐deficient prepubertal children (4 M, 1 F) with GH releasing hormone1–40 (GHRH1–40) in two dosage regimens over 9 months. Profiles of serum GH concentrations were obtained over 24 hours before treatment and nocturnal profiles were obtained serially throughout the study. GHRH was administered subcutaneously at night for four pulses using 1 μg/kg/pulse in the first 3 months and 2 μg/kg/pulse for a further 6 months. All subjects demonstrated pituitary responsiveness to i.v. GHRH before treatment and at 3 and 6 months. GH secretion was induced in a pulsatile fashion in response to subcutaneous GHRH in three children from the first night of treatment. A self priming effect to successive GHRH pulses was evident and the response augmented with time and with the higher dose regimen. The growth velocity of these three children increased from a mean of 3.7 cm/year (range 3.7–3.8) before treatment to 5.5 cm/year (range 4.1–7.2) over the first 3 months and to 7.2 cm/ year (range 4.8–9.2) over the following 6 months. In one subject entrainment of GH secretion to GHRH did not occur until the higher dose regimen and this was associated with a modest increase in growth velocity. One subject did not respond to treatment. Pulsatile administration of GHRH1–40 is effective in inducing GH secretion and promoting growth acceleration in some children with idiopathic GH deficiency. The optimal dose and mode of administration of GHRH have yet to be established.
ALTERATIONS IN THE HYPOTHALAMIC‐PITUITARY‐THYROID AXIS AFTER PROLONGED RESIDENCE IN ANTARCTICA
Authors: REED H. L. , BURMAN K. D. , SHAKIR K. M. M. , O'BRIAN J. T.
Published: March 2008

The human population which lives and works in polar environments has been increasing steadily over the last 15 years. Very little is known about how these residents adjust to their environment. Cold adaptation in man is a poorly understood phenomenon. Euthermic mammals maintain body temperature during cold exposure via non‐shivering thermogenesis, a process which is hormonally mediated. We studied prospectively the response of the hypothalamic‐pituitary‐thyroid axis in 17 euthyroid men before, during and after assignment to duty in the Antarctic. Serum total and free T4 levels fell slightly but not significantly after very prolonged Antarctic residence. Serum total and free T3 decreased significantly from basal levels of 170 ± 3 ng/dl and 388 ± 19 pg/ dl to 155 ±5 ng/dl and 319±14 pg/dl respectively after Antarctic duty. Serum T3 levels increased after 42 weeks of polar living, the end of the observation period, but the change did not attain statistical significance. The integrated TSH response to TRH administration increased by 50% to 734 ± 58 μIU.min/ml over warm climate basal response levels of 456 ± 33 μIU.min/ml by the end of the study. The daily circadian rhythm of serum Cortisol was maintained throughout the study period. The alterations in thyroid hormones which we describe, are apparently related to the chronic cold exposure which our subjects experienced in this polar environment.
THE EFFECT OF TRANSDERMAL OESTROGEN ON BONE, CALCIUM‐REGULATING HORMONES AND LIVER IN POSTMENOPAUSAL WOMEN
Authors: SELBY P. L. , PEACOCK M.
Published: March 2008

Transdermal oestradiol, 100 μg/d, was used to treat 11 women suffering from postmenopausal symptoms. After 3 weeks therapy there was a significant rise in the plasma oestradiol into the premenopausal range and a significant fall in plasma FSH level and symptom score. Bone resorption, assessed by urinary excretion of calcium and hydroxyproline, decreased significantly while plasma alkaline phosphatase activity remained constant. There was a significant fall in plasma calcium and phosphate but the plasma concentrations of PTH, calcitonin and calcitriol and the urinary excretion of cAMP were unchanged. Plasma levels of vitamin D binding protein, albumin and globulin were unaltered, and blood pressure did not rise. These effects were similar to those found in postmenopausal women with oral ethinyloestradiol, 30 μg/d, (Selby et al., 1985), apart from those on plasma vitamin D binding protein, total calcitriol, albumin, globulin, tubular reabsorption of phosphate and blood pressure, changes which probably arise from a direct action of oral oestrogen on the liver.
ROLE OF ENDOGENOUS OPIOIDS IN REDUCING THE FREQUENCY OF PULSATILE LUTEINIZING HORMONE SECRETION INDUCED BY PROGESTERONE IN NORMAL WOMEN
Authors: STEELE P. A. , JUDD S. J.
Published: March 2008

It is well‐established that the frequency of LH pulses varies during the normal menstrual cycle with a significant reduction in frequency in the luteal phase. Previous studies have indicated that both progesterone and opioids are able to reduce the frequency of LH pulses and in this study we sought to clarify the possible interaction between progesterone, endogenous opioids and GnRH neurons. Sixteen normal women in the mid‐follicular phase (days 8–12) were randomly allocated to a control or treatment group and LH pulsatility assessed on one or two occasions by taking blood samples at 15 min intervals over 8 h. For the control women, LH pulsatility was assessed on one occasion during a saline infusion. The treated women received progesterone (50–100 mg/d for 7 d) at the end of which LH pulsatility was assessed before and after a naloxone infusion (2 mg/h for 8 h). Mean±SEM LH pulse frequency in the control women was 4.9 ± 0.5 pulses/8 h which was significantly decreased to 3.0 ± 0.3 pulses/8 h (P < 0.01) in the progesterone treated women but not different from 5.5 ± 0.3 pulses/8 h in those also treated with naloxone. Mean ± SEM LH pulse amplitude in the control women was 2.3 ± 0.3 IU/l, which was significantly increased to 4.8 ± 0.7 IU/l (P < 005) in the progesterone treated group, and to 3.7 ± 0.4 IU/l (P < 005) in the progesterone‐treated women after naloxone. We conclude that progesterone slows the frequency of LH pulsatility by increasing endogenous opioid activity in the hypothalamus which may in turn inhibit the firing rate of the GnRH neurons.
BASAL AND STIMULATED RELEASE OF CALCITONIN GENE‐RELATED PEPTIDE (CGRP) IN PATIENTS WITH MEDULLARY THYROID CARCINOMA
Authors: MASON R. T. , SHULKES A. , ZAJAC J. D. , FLETCHER A. E. , HARDY K. J. , MARTIN T. J.
Published: March 2008

Calcitonin gene‐related peptide (CGRP) is a recently discovered peptide whose existence was first predicted following sequence analysis of the rat calcitonin gene. In the present study, plasma levels of CGRP were measured in patients with medullary thyroid carcinoma, both basally and following calcium or pentagastrin stimulation. Using a sensitive radioimmunoassay for CGRP, 19 of 21 patients with medullary thyroid carcinoma had elevated plasma levels of immunoreactive CGRP (median value 114 pmol/l) while 23 normal subjects had plasma CGRP levels below the detection limit of the assay (< 10 pmol/l). Calcium or pentagastrin infusion in medullary thyroid carcinoma patients were potent stimuli to CGRP release, increasing plasma levels two‐to five‐fold. Chromatographic characterization using high pressure liquid chromatography of the CGRP immunoreactivity in plasma from two patients with medullary carcinoma of the thyroid demonstrated the presence of two molecular forms, neither of which co‐eluted with synthetic human CGRP. The role of CGRP in the pathophysiology of medullary thyroid carcinoma is not clear but it may contribute to some of the clinical features associated with the disease. Furthermore, measurement of CGRP in conjunction with calcitonin could help in determining the prognosis of these patients.
CORTICOTROPHIN‐RELEASING FACTOR‐TEST USED WITH BILATERAL, SIMULTANEOUS INFERIOR PETROSAL SINUS BLOOD‐SAMPLING FOR THE DIAGONOSIS OF PITUITARY‐DEPENDENT CUSHING'S DISEASE
Authors: LANDOLT A. M. , VALAVANIS A. , GIRARD J. , EBERLE A. N.
Published: March 2008

Bilateral, simultaneous inferior petrosal sinus blood‐sampling for determinations of ACTH levels has improved the ability to establish a differential diagnosis of Cushing's disease, particularly in patients whose endocrinological studies show equivocal results and whose computed tomography scans yield negative or inconclusive findings. Individual anatomical variations in the configuration of the sinus and insignificant differences between the ACTH levels obtained from its two sides may be a problem. Seven patients with clinically and biochemically typical Cushing's disease and one with atypical Cushing's disease were examined. An alternative approach for catheterization of the inferior petrosal sinus through the deep vertebral venous plexus was used in those patients who did not have direct connections between the sinus and the internal jugular vein. In two of the eight patients, only ACTH secretion stimulated with corticotrophin‐releasing factor could unmask a significant difference between the ACTH levels on the two sides which was not obvious from the basal ACTH levels. Beta‐lipotrophin values showed a behaviour similar to that of ACTH values, but because of a slower turn‐over rate, the CRF‐induced peaks were better visible. The aetiology of Cushing's disease was established from the results of this examination and corresponded with the surgical findings in this series, with the exception of one in which the patient had a highly atypical form of the disease. The abnormal ACTH source was found later to be a thymus carcinoid.
GONADOTROPHIN‐SECRETING PITUITARY ADENOMAS MASQUERADING AS PRIMARY OVARIAN FAILURE
Authors: COOK D. M. , WATKINS S. , SNYDER P. J.
Published: March 2008

Three women, 20–35 years old, appeared on initial presentation to have primary ovarian failure, because each had amenorrhoea or oligomenorrhoea and markedly supranormal serum concentrations of gonadotrophins. On further evaluation, however, each had ovaries that could secrete oestradiol normally, and one had normal oestradiol secretion without any treatment. Another secreted oestradiol normally only after reduction of her gonadotrophins following partial excision of a pituitary adenoma. The third secreted oestradiol normally only after exogenous oestrogens were administered to reduce her gonadotrophins and were then withdrawn. Each had an enlarged, contrast‐enhancing pituitary gland by computed tomographic scan and a markedly supranormal serum concentration of glycoprotein alpha subunit. We conclude that each of these women had a gonadotrophin‐secreting pituitary adenoma that masqueraded as primary ovarian failure. Their persistently supranormal serum gonadotrophins appear to have inhibited ovarian function.
METOCLOPRAMIDE‐INDUCED HYPERPROLACTINAEMIA: EFFECTS ON CORPUS LUTEUM FUNCTION, ENDOMETRIAL STEROID RECEPTOR CONCENTRATIONS AND 17β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITY
Authors: KAUPPILA A. , ISOTALO H. , KIRKINEN P. , MÄKILÄ U.‐M. , ORAVA M. , VIHKO R.
Published: March 2008

Induced hyperprolactinaemia impairs ovarian follicular development, especially during the recruitment period. The consequences of hyperprolactinaemia during the luteal phase alone on corpus luteum. function have not been characterized, nor have the actions of excessive circulating PRL on the endometrium. In this study, postovulatory 5‐d administration of metoclopramide (MC) increased serum concentrations of PRL and decreased those of pregnenolone and progesterone indicating inhibition of steroidogenesis in the corpus luteum. This effect may partly explain the relatively common failure of implantation in association with induced ovulation using regimens leading to transient hyperprolactinaemia. In contrast to this, MC‐induced hyperprolactinaemia during the mid‐follicular (4 d) or early luteal phase of the cycle did not alter the concentrations of cytosol or nuclear oestrogen and progestin receptors or the activity of 17β‐hydroxysteroid dehydrogenase in endometrial tissue. Thus, transiently elevated circulating PRL does not seem to have direct effects on female sex steroid receptors or their function in the proliferative or secretory endometrium.
EFFECTS OF NALOXONE ON THE PITUITARY‐ADRENAL AXIS IN PATIENTS WITH DEXAMETHASONE‐SUPPRESSIBLE HYPERALDOSTERONISM
Authors: FALLO F. , BOSCARO M. , SONINO N. , MANTERO F.
Published: March 2008

Endogenous opioids may normally modulate the function of the hypothalamopituitary‐adrenal axis. We investigated whether opioid peptides play any role on aldosterone secretion in dexamethasone‐suppressible hyperaldosteronism (DSH). Clinical and hormonal effects of i.v. administration of naloxone (10 mg as a bolus) in two siblings affected by this disease and in eight normal volunteers were studied. In normals, naloxone caused a significant increase in plasma Cortisol compared with placebo, an insignificant increase in ACTH and no change in plasma renin activity (PRA) and aldosterone level. In DSH patients there was a slight increase in plasma Cortisol, no change in PRA and a marked rise of aldosterone level. In five normals retested after dexamethasone 2 mg, baseline ACTH and Cortisol were reduced and no response to naloxone was observed compared to naloxone alone. After dexamethasone, aldosterone levels were suppressed in DSH patients and unchanged in normals, and did not respond to naloxone in any case. In conclusion, naloxone may increase the responsiveness of adrenal zona fasciculata to physiological levels of ACTH in normals, since the slight increase in ACTH seems inadequate to explain per se the marked Cortisol elevation. The marked aldosterone rise after naloxone indicates an underlying adrenal rather than pituitary abnormality in patients with DSH, and possibly implicates endogenous opioids.
NORMAL GROWTH AND PUBERTAL DEVELOPMENT DURING BROMOCRIPTINE TREATMENT FOR A PROLACTIN‐SECRETING PITUITARY MACROADENOMA
Authors: DALZELL G. W. , ATKINSON A. B. , CARSON D. J. , SHERIDAN B.
Published: March 2008

An 11 ‐year‐old male presented with a 2‐year history of headache and lethargy. Serum PRL was elevated at 14 000 mU/1 and computerized tomography showed a pituitary macroadenoma. Visual fields and fundi were normal and the testes showed early pubertal changes. There was normal responsiveness of serum Cortisol but absence of GH response to hypoglycaemia. After bromocriptine therapy for 4 months serum PRL had fallen to 90 mU/1 and the tumour was not visible on repeat computerized tomography. After 7 months treatment, repeat pituitary function testing showed restoration of GH response to hypoglycaemia. Treatment with bromocriptine was continued and there was spontaneous progression of normal puberty; the serum testosterone continued to rise, and height maintained the 50th centile. Bromocriptine therapy should be considered as initial therapy in the management of prolactinomas in prepubertal patients.
PLASMA OXYTOCIN, ARGININE VASOPRESSIN AND ATRIAL NATRIURETIC PEPTIDE RESPONSES TO INSULIN‐INDUCED HYPOGLYCAEMIA IN MAN
Authors: FISHER B. M. , BAYLIS P. H. , FRIER B. M.
Published: March 2008

The changes in blood glucose, plasma oxytocin, plasma vasopressin, plasma atrial natriuretic peptide, serum osmolality, haematocrit and blood pressure were measured in response to acute insulin‐induced hypoglycaemia in six normal male subjects. After the i.v. administration of insulin (015 U/kg), plasma concentrations of oxytocin and vasopressin increased rapidly in all subjects and were maximal 15 min after the acute hypoglycaemic reaction (R). Haematocrit increased at the time of the hypoglycaemic reaction, but there was no change in serum osmolality. Systolic blood pressure rose and diastolic blood pressure fell, but mean arterial blood pressure remained unchanged. No changes were demonstrated in plasma concentrations of atrial natriuretic peptide. The release of oxytocin and vasopressin in response to acute hypoglycaemia in man is probably caused by stimulation of the posterior pituitary gland via hypothalamic activation, and not by stimulation of osmoreceptors or baroreceptors.
OVULATION OF A SINGLE DOMINANT FOLLICLE DURING TREATMENT WITH LOW‐DOSE PULSATILE FOLLICLE STIMULATING HORMONE IN WOMEN WITH POLYCYSTIC OVARY SYNDROME
Authors: POLSON D. W. , MASON H. D. , SALDAHNA M. B. Y. , FRANKS S.
Published: March 2008

Ten women with clomiphene‐resistant chronic anovulation associated with polycystic ovary syndrome were treated with purified urinary FSH (urofollitro‐phin). The gonadotrophin was given s.c. by pulsatile infusion pump starting at a low dose (1 ampoule or 75 U/d) and increasing by 37‐5 U/d at weekly stages in an attempt to induce ovulation of a single follicle. Seventy percent of the 33 cycles were ovulatory and in 18 of these (78%) a single dominant follicle developed and ovulated. Each of the 10 women ovulated when the optimum dose was reached and five of these women became pregnant. The maximum dose of FSH in uniovulatory cycles was 150 U/d or less. Endogenous LH concentrations which were raised at the onset of treatment were suppressed in the late follicular phase. The rate of follicular growth and gonadal steroid concentrations were consistent with those observed in spontaneous ovulatory cycles. This study demonstrates that by using low‐dose gonadotrophin therapy it is possible to find the‘threshold’ dose of FSH to promote maturation of a single dominant follicle. The high rate of ovulation and pregnancy suggest that this approach is of practical importance in treatment of infertile patients with polycystic ovaries.
SUPPRESSION OF OVARIAN ACTIVITY BY ZOLADEX DEPOT (ICI 118630), A LONG‐ACTING LUTEINIZING HORMONE RELEASING HORMONE AGONIST ANALOGUE
Authors: WEST C. P. , BAIRD D. T.
Published: March 2008

A long‐acting LHRH agonist, Zoladex depot 3–6 mg, was administered as a monthly s.c. injection to seven premenopausal volunteers for a maximum of 6 months, starting in the luteal phase of the cycle. Transient stimulation of gonadotrophin release was observed 24 h after the initial depot, followed by sustained suppression of plasma LH, while FSH levels returned to the normal range. Plasma oestradiol concentrations fell to early follicular phase values within 14 d. Twice‐weekly monitoring of urinary oestrone‐3‐glucuronide and pregnanediol demonstrated inhibition of ovulation and almost complete suppression of ovarian follicular activity throughout therapy. All the subjects became amenorrhoeic. Mean plasma testosterone concentrations were also significantly reduced while androstenedione remained within the pretreatment range. SHBG concentrations were not significantly reduced. After cessation of therapy, postovulatory menstruation occurred within 80 d of administration of the last depot.
VALUE OF BASAL PLASMA CORTISOL ASSAYS IN THE ASSESSMENT OF PITUITARY‐ADRENAL INSUFFICIENCY
Authors: HÄGG E. , ASPLUND K. , LITHNER F.
Published: March 2008

A basal plasma Cortisol value taken in a physically unstressed state in 68 patients with or without hypothalamic‐pituitary‐adrenocortical disease was compared with the maximal plasma Cortisol concentration during an insulin tolerance test. There was a strong positive correlation between the values. Basal Cortisol levels above 300 nmol/1 (RIA method) almost excluded ACTH‐cortisol insufficiency and those below 100 nmol/1 strongly suggested dysfunction. A repeated basal Cortisol estimation within a month was especially valuable in categorizing patients with levels between 100 and 200 nmol/1. We suggest that a basal Cortisol measurement may be used as a first laboratory test in patients evaluated for possible hypothalamic‐pituitary‐adrenocortical insufficiency; in many patients, this approach obviates more sophisticated and expensive testing.
DETERMINANTS OF THYROID VOLUME AS MEASURED BY ULTRASONOGRAPHY IN HEALTHY ADULTS IN A NON‐IODINE DEFICIENT AREA
Authors: BERGHOUT A. , WIERSINGA W. M. , SMITS N. J. , TOUBER J. L.
Published: March 2008

Thyroid volume was measured by ultrasonography in 50 healthy adults (25 males, 25 females, age 20‐70 years) living in the non‐iodine deficient area of Amsterdam. Thyroid volume was 10‐7 ± 4–6 ml (mean ± SD, range 2.7‐20.4 ml). No relation was found between thyroid volume and any of the following parameters: plasma TSH, T4, T3, thyroglobulin (Tg), urinary iodine excretion, tobacco and alcohol consumption. Thyroid volume in males (12.7 ± 4.4 ml) was greater than in females (8.7 ± 3.9 ml, p = 0.0014), but no sex difference was observed in the ratio of thyroid volume to body weight (males, 0.16 ± 005 ml/ kg; females 013 ± 0.06 ml/kg; NS). Thyroid volume was positively related to body weight, but not to age. We conclude that the sex difference in thyroid volume is due to the difference in body weight between males and females. Lean body mass is presumably the most important physiological determinant of thyroid size in subjects living in a non‐iodine deficient area.
COMPARISON OF INTESTINAL CALCIUM ABSORPTION AND CIRCULATING 1,25‐DIHYDROXYVITAMIN D LEVELS IN MALIGNANCY‐ASSOCIATED HYPERCALCAEMIA AND PRIMARY HYPERPARATHYROIDISM
Authors: RALSTON S. H. , COWAN R. A. , GARDNER M. D. , FRASER W. D. , MARSHALL E. , BOYLE I. T.
Published: March 2008

The relation between circulating 1,25‐dihydroxyvitamin D (l,25(OH)2D) levels and intestinal calcium absorption–as determined by an oral calcium load test–was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid‐like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid‐like features. It is postulated that in the former, the ‘inappropriately’ detectable or raised 1,25(OH)2D levels may have been due to enhanced renal la‐hydroxylase activity stimulated by the parathyroid hormone (PTH)‐like effect of a non‐PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is ‘end organ’ resistance to the effects of 1,25(OH)zD due to a generalized malabsorptive process.
IgG SUBCLASS DISTRIBUTION OF THYROID AUTOANTIBODIES: A ‘FINGERPRINT’ OF AN INDIVIDUAL'S RESPONSE TO THYROGLOBULIN AND THYROID MICROSOMAL ANTIGEN
Authors: McLACHLAN S. M. , FELDT‐RASMUSSEN U. , YOUNG E. T. , MIDDLETON S. L. , BLICHERT‐TOFT M. , SIERSBOEK‐NIELSEN K. , DATE J. , CLARK F. , SMITH B. REES
Published: March 2008

The IgG subclass distribution of autoantibodies to thyroglobulin and thyroid microsomal antigen was studied in 21 patients with Graves' disease during fluctuations in total IgG class autoantibody levels induced by various forms of therapy. In addition, changes in autoantibody subclass distributions were investigated during the natural course of Hashimoto's disease in seven patients taking thyroxine. The autoantibodies were principally of subclasses IgGl and/or IgG4 in Graves' patients although IgG2 contributed significantly to thyroglobulin antibodies in 5/7 Hashimoto sera. In Graves' disease the distribution of microsomal and thyroglobulin antibodies among the IgG subclasses remained essentially unchanged over periods of 6 months‐2 years whether autoantibody levels decreased during carbimazole therapy or increased transiently following 13lIodine treatment or subtotal thyroidectomy. Similar observations were made for thyroglobulin antibodies in Hashimoto patients studied over 2½‐4 years; furthermore, the IgG subclass distribution of microsomal antibodies was usually different from that of thyroglobulin antibodies in the same patient. These observations suggest that the microsomal and/or thyroglobulin antibody subclass distribution is characteristic for a particular individual and may be regarded as the ‘fingerprint’ of an individual's response to these thyroid autoantigens.
CHOLINERGIC MUSCARINIC RECEPTOR BLOCKADE WITH PIRENZEPINE ABOLISHES SLOW WAVE SLEEP‐RELATED GROWTH HORMONE RELEASE IN YOUNG PATIENTS WITH INSULIN‐DEPENDENT DIABETES MELLITUS
Authors: PAGE M. D. , KOPPESCHAAR H. P. F. , DIEGUEZ C. , GIBBS J. T. , HALL R. , PETERS J. R. , SCANLON M. F.
Published: March 2008

Cholinergic receptor blockade has been shown to abolish GH secretion in a variety of physiological and pharmacological situations in normal subjects. We have investigated the effect of pirenzepine on nocturnal GH secretion in young adult patients with Type I insulin‐dependent diabetes mellitus. Five patients (three male, two female; aged 20‐27 years) were studied in a randomized order on two days separated by at least 1 week. All patients showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 6–115 mU/1). In contrast, cholinergic muscarinic receptor blockade with pirenzepine (100 mg orally at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. Mean plasma glucose levels at each sampling time between each study did not differ significantly. The ability to abolish nocturnal GH secretion may be important in the field of diabetes, since excess GH secretion is implicated in several acute metabolic and chronic microvascular complications of the disease.