bluuebunny/crossref_metadata_2025 huggingface dataset:
DEFECTIVE THYROGLOBULIN EXPORT AS A CAUSE OF CONGENITAL GOITRE
Authors: LISSITZKY S. , TORRESANI J. , BURROW G. N. , BOUCHILLOUX S. , CHABAUD O.
Published: March 2008

The thyroids of two brothers aged 13 and 15 with congenital goitre, butanolinsoluble iodine in blood and which had pronounced decrease of immunoreactive thyroglobulin content in the thyroid were studied. Two types of thyroglobulin were identified. The first amounted to only about 200‐300 μg/g wet tissue and was fully immunoreactive with anti normal human thyroglobulin antiserum (iTG‐G). It was purified by affinity chromatography. The other was mainly associated with intracytoplasmic membranes, amounted to about 8 mg/g wet tissue and was only partially immunoreactive (piTG‐G). Both had abnormal amino acid compositions but only iTG‐G showed a decreased carbohydrate content. Surprisingly, piTG‐G showed a normal iodination level (0.5%) and a normal iodoamino acid composition. Immunochemical studies performed on slices or cell‐free fractions incubated in the presence of labelled amino acids and /or monosaccharides showed that: (1) thyroglobulin peptide chains were being synthesized and almost normally discharged into the cisternae of the rough endoplasmic reticulum; (2) incorporation of sugars into iTG‐G was decreased; (3) sialyl‐ and galactosyltranserase activities were normal and the enzymes normally located, and (4) albumin which is present in the thyroid as the iodinated protein was probably not synthesized by the goitrous tissues. Two major abnormalities were detected by light and electron microscopy: absence or pronounced scarcity of colloid in the follicular lumina and over distended endoplasmic reticulum cisternae. These observations are compatible with a defect in TG transport from the cell into the lumen as the cause of the goitre. Whether defective thyroglobulin export is basically related to abnormality of the protein structure or to another cause is discussed.
HYPOGLYCAEMIA ASSOCIATED WITH AN INTRATHORACIC FIBROSARCOMA
Authors: WALSH C. H. , WRIGHT A. D. , COORE H. G.
Published: March 2008

A patient with an intrathoracic fibrosarcoma in whom disabling hypoglycaemic episodes occurred is reported. No further hypoglycaemic episodes occurred following removal of the tumour. The mechanism of the hypoglycaemia associated with non‐pancreatic tumours is discussed. It seems that inadequate hepatic glucose output was an important factor in contributing to the hypoglycaemia in this patient.
PLASMA GLUCAGON RESPONSE TO ARGININE INFUSION IN CHILDREN AND ADOLESCENTS WITH DIABETES MELLITUS
Authors: JOSEFSBERG Z. , LARON Z. , DORON M. , KERET R. , BELINSKI YOAV , WEISMANN I.
Published: March 2008

Plasma glucagon response to an arginine infusion was studied in children and adolescents belonging to the following groups: (I) twenty‐two controls; (II) six subjects with delayed insulin peak during oral GTT; (III) ten diabetics on diet and/or oral therapy; (IV) six newly diagnosed uncompensated diabetics; and (V) eight diabetics on insulin therapy. The fasting glucagon concentrations and rise of glucagon in response to arginine in the patients of Groups II, III and V were similar to those of the controls (Group I).

The basal levels and rise of glucagon in the newly diagnosed, uncompensated diabetic children (Group IV) was elevated compared to the other groups but the difference was statistically not significant.

The results of this investigation favour the hypothesis that the hyperglucagonaemia in diabetes is a secondary effect to the metabolic derangement, bearing a direct relationship to the degree of homeostastic decompensation.
RESPONSE OF PLASMA ALDOSTERONE TO FLUDROCORTISONE IN PRIMARY HYPERALDOSTERONISM AND OTHER FORMS OF HYPERTENSION
Authors: PADFIELD P. L. , ALLISON M. E. M. , BROWN J. J. , FERRISS J. B. , FRASER R. , LEVER A. F. , LUKE R. G. , ROBERTSON J. I. S.
Published: March 2008

The response of plasma aldosterone to fludrocortisone administration (400 μg 12‐hourly for 3 days) was studied in twenty‐two patients with primary hyperaldosteronism. No difference was observed in the response between those patients with an adrenal adenoma and those with bilateral adrenocortical hyperplasia, there being no significant change in plasma aldosterone levels across the test period. No separation between the groups was seen when basal plasma renin concentration was related to the aldosterone level following fludrocortisone. It is concluded that the test is of little value in the pre‐operative differentiation of these conditions.

Twenty‐three patients with no demonstrable cause for their hypertension and four with elevated levels of plasma deoxycorticosterone were similarly studied for comparison. These groups demonstrated a normal fall in plasma aldosterone levels following fludrocortisone.
SECRETION OF ALPHA AND BETA SUBUNITS OF TSH BY THE ANTERIOR PITUITARY
Authors: EDMONDS M. , MOLITCH M. , PIERCE J. , ODELL W. D.
Published: March 2008

We have attempted to determine whether blood concentrations of the α chains of TSH arise by direct pituitary secretion of α chain or by degratation of the intact hormone after secretion. Highly purified human TSH was administered by infusion to euthyroid volunteers; blood TSH concentrations were raised to 36 μu/ml. After TSH infusion, circulating blood α chain concentrations did not change. The same volunteers received an infusion of TRH which stimulated pituitary secretion of TSH, raising blood concentrations to 15 μ/ml in one series of subjects and to 23 μu/ml in a second series. After TRH, blood concentrations of α chain increased from undetectable to over 400 pg/ml. We conclude that α subunits of TSH are directly secreted by the pituitary gland and are not formed by degradation of intact TSH in the peripheral circulation.
PLASMA TESTOSTERONE AND PROLACTIN IN THE MENSTRUAL CYCLE
Authors: EPSTEIN M. T. , McNEILLY A. S. , MURRAY M. A. F. , HOCKADAY T. D. R.
Published: March 2008

Daily hormonal studies during nine ovulatory menstrual cycles showed that plasma prolactin and testosterone concentrations fluctuated randomly and independently.

Mean plasma testosterone levels were found to be higher during the 7 days before and after the mid‐cycle LH peak when compared to the premenstrual phase (P<0.01). No correlation was found between daily levels of prolactin and those of LH, FSH, oestrogen or progesterone and no correlation was seen between peaks of prolactin and testosterone or mean prolactin and testosterone levels. The lack of correlation between blood levels of prolactin and testosterone during the menstrual cycle suggests that prolactin is unlikely to have any direct controlling influence on the cyclical nature of testosterone production observed during ovulatory menstrual cycles.
THE EFFECT OF PROGESTERONE ON FSH AND LH RESPONSE TO LHRH IN NORMAL WOMEN
Authors: SHAW R. W. , BUTT W. R. , LONDON D. R.
Published: March 2008

An LHRH test was performed on twenty‐eight regularly menstruating females dur‐the follicular phase of their cycles. Twenty‐four were then given an intramuscular injection of progesterone in oil and retested with LHRH 20 or 44 h later, the remaining four received no pretreatment and acted as controls.

The twelve subjects retested 20 h after the progesterone injection showed marked changes in response. The greatest increase in gonadotrophin release after LHRH was seen when subjects were tested between days 8 and 10 of the menstrual cycle. In contrast, the twelve studied 44 h after receiving the steroid showed no change in release.
TRIIODOTHYRONINE RESPONSE TO THYROTROPHIN RELEASING HORMONE IN PATIENTS WITH HYPOTHALAMIC‐PITUITARY DISORDERS
Authors: FAGLIA G. , FERRARI C. , PARACCHI ALESSANDRA , SPADA ANNA , BECK‐PECCOZ P.
Published: March 2008

The serum triiodothyronine concentration was evaluated before and after thyrotrophin releasing hormone in fifty‐six patients with hypothalamic‐pituitary disorders (thirty‐four had secondary hypothyroidism, twenty‐two were euthyroid) and in twenty‐four normal controls.

Basal serum T3 was low in fifteen hypothyroid subjects and normal in the remainders. After TRH, serum T3 did not increase normally in twenty‐five hypothyroid and in ten euthyroid patients; even the patients with normal or supranormal plasma TSH increase had significantly lower T3 responses than normal controls (P<0.0001 for hypothyroid, P<0.01 for euthyroid subjects).

The finding of low T3 response to TRH in some euthyroid patients with hypothalamic‐pituitary disorders can perhaps identify cases of preclinical secondary hypothyroidism, probably due to low biological activity of released TSH.
THE ROLE OF PROLACTIN IN THE RESTORATION OF OVARIAN FUNCTION DURING THE EARLY POST‐PARTUM PERIOD IN THE HUMAN FEMALE
Authors: ROLLAND RUNE , LEQUIN RUDOLF M. , SCHELLEKENS LOUIS A. , JONG FRANK H. DE
Published: March 2008

Serial plasma levels of prolactin, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), 17β‐oestradiol (E) and progesterone (P) were determined by radioimmunoassay in ten healthy women during late pregnancy and puerperium until the occurrence of the first menstruation, at which moment an endometrial biopsy was taken. Prolactin concentrations, which were high during late pregnancy and the early post‐partum period, declined thereafter but remained above 30 ng/ml plasma during the period of breast‐feeding. FSH was nearly undetectable during late pregnancy and the first week post‐partum but returned to normal levels between days 7 and 18. Thereafter relatively high FSH levels were found during the period of hyperprolactinaemia. Following clearance of human chorionic gonadotrophin (HCG) during the first 2 weeks post‐partum, LH remained below the normal cyclic range in all cases for at least 28 days. Placental E and P were fully cleared within 7 days. In spite of relatively high levels of FSH, E remained low as did LH during the period of hyperprolactinaemia. Thereafter E increased followed by an increase of LH, suggesting a positive feedback of E on LH release. The first menses observed in five subjects during the study were preceded by (subnormal P levels for a relatively short period although the endometrial biopsies showed only late proliferative changes.
PLASMA PREGNENOLONE, PROGESTERONE, 17‐HYDROXYPROGESTERONE, TESTOSTERONE AND 5α‐DIHYDROTESTOSTERONE IN DIFFERENT TYPES OF CONGENITAL ADRENAL HYPERPLASIA
Authors: JÄNNE O. , PERHEENTUPA J. , VIINIKKA L. , VIHKO R.
Published: March 2008

Unconjugated pregnenolone, progesterone, 17‐hydroxyprogesterone, testosterone and 5a‐dihydrotestosterone were simultaneously measured by radioimmunoassay in plasma from children with congenital adrenal hyperplasia (CAH) due to a deficiency of 21‐hydroxylase (21‐OHase), 11 β‐hydroxylase (11β‐OHase) or 3β‐hydroxysteroid dehydrogenase (3β‐HSD). These steroids were also measured in a reference group of children of similar age.

The following concentrations of these five steroids were observed in the prepubertal children aged 0‐4‐10‐9 years: pregnenolone <0‐2‐0‐85 ng/ml; progesterone 0‐17‐0‐68 ng/ml; 17‐hydroxyprogesterone 0‐10‐0‐53 ng/ml; testosterone <0‐05‐0‐14 ng/ml, and 5α‐dihydrotestosterone <0‐05 ng/ml (detection limit of the method).

The concentrations were clearly elevated in the plasma of children with CAH. A very high plasma concentration of 17‐hydroxyprogesterone differentiates a 21‐OHase deficiency from the two other types: children with this defect had levels mostly in excess of 100‐fold that of normal. Plasma progesterone concentrations in these patients were also high being in the range found during the luteal phase level in the adult. Their plasma testosterone concentrations showed a scatter from normal values to high adult male levels being mostly at the level of adult females. The concentrations of 5a‐dihydrotestosterone were at or above those of adult males. A high plasma concentration of pregnenolone with at most slightly elevated progesterone and 17‐hydroxyprogesterone levels differentiated the 3β‐HSD defect from the other two forms of CAH. The plasma profile of the five steroids determined in a patient with an 11 β‐OHase deficiency was close to normal, but slightly elevated pregnenolone, progesterone and 17‐hydroxyprogesterone levels were found to be characteristic of this enzyme deficiency.
ENDOCRINE EFFECTS OF VASECTOMY
Authors: PURVIS K. , SAKSENA S. K. , CEKAN Z. , DICZFALUSY E. , GINER J.
Published: March 2008

In order to provide information on the endocrine effects of vasectomy, unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were analysed in the blood plasma of twenty Mexican men on two occasions before and 1, 3, 6 and 12 months after vasectomy. Vasectomy appeared to be associated with a significant decrease in the plasma levels of pregnenolone, dehydroepiandrosterone and androstenedione and a significant increase in the levels of dihydrotostrone and oestrone. A probably significant increase in oestradiol levels took place 12 months after vasectomy but not before. No consistent changes were found in testosterone (up to 12 months) or in FSH and LH levels (up to 6 months) after vasectomy.

The unconjugated steroids indicated above, except oestrone, were also estimated, whenever possible, in seminal plasma specimens obtained from thirty‐nine subjects (including the twenty indicated above) on the same occasions. Vasectomy was associated with a highly significant decrease of seminal plasma dihydrotestosterone levels on all occassions and a significant decrease in androstenedione levels after 6 and 12 months. After 12 months there was a decrease in dehydroepiandro‐sterone and an increase in oestradiol; these changes were both probably significant.

In another preliminary study, the levels of pregnenolone sulphate, dehydroepiandrosterone sulphate, testosterone glucuronide, testosterone sulphate and dihydrotestosterone sulphate were estimated before and 1 month after vasectomy in the seminal plasma of fourteen to seventeen subjects. Testosterone glucuronide fell, probably significantly, but other conjugates were unchanged.

The data indicate that vasectomy may be associated with significant changes in the circulating and in seminal plasma levels of several steroids. The gradual nature of some of the changes observed suggests the necessity of conducting in several centres large‐scale, long‐term studies on vasectomized subjects and on a carefully matched control group.
EFFECT OF ACUTE AND CHRONIC NEUROLEPTIC THERAPY ON SERUM PROLACTIN LEVELS IN MEN AND WOMEN OF DIFFERENT AGE GROUPS
Authors: DE RIVERA JOSE LUIS , LAL SAMARTHJI , ETTIGI PRAKASH , HONTELA SLAVOJ , MULLER HERBERT F. , FRIESEN HENRY G.
Published: March 2008

A single fasting level of serum prolactin was measured in each of sixty control subjects and eighty‐three psychiatric patients of both sexes who had been on neuroleptic therapy for 2‐4 weeks (acute treatment) or at least 5 years (chronic treatment) and who were aged either 17‐45 or 48‐85 years. All groups of patients had significantly higher mean prolactin levels than controls. Gender, age group of women, and exposure to acute or chronic treatment were significant variables determining the magnitude of neuroleptic‐induced elevation of prolactin. In some of the groups, dose, duration of chronic therapy, and concomitant administration of anticholinergic drugs also influenced prolactin levels.

Whereas all acutely treated women had prolactin values above the control range, one out of twelve (8.3%) of the women aged 17‐45 years and six out of fourteen (42.9%) of the women aged 48‐85 years who were under chronic treatment had normal values. Normal prolactin levels were also found in five out of sixteen (31.2%) of the acutely treated and nine out of twenty‐four (37.5%) of the chronically treated men aged 17‐85 years.
THE EFFECT OF VARYING DOSES OF CEREBRAL IRRADIATION ON GROWTH HORMONE PRODUCTION IN CHILDHOOD
Authors: SHALET S. M. , BEARDWELL C. G. , PEARSON D. , JONES P. H. MORRIS
Published: March 2008

The radiation dose, delivered to the hypothalamic‐pituitary region, has been calculated in thirty‐nine children irradiated for brain tumours and in seventeen children who had received prophylactic cranial irradiation for acute leukaemia. All subjects had an insulin tolerance test at least 2 years after their radiotherapy. There is a significant inverse correlation between radiation dose and peak GH response. Thirty‐seven of the fifty‐six patients showed an impaired GH response and thirty‐six of these received more than 2900 rads. Only five patients who received such a dose showed normal GH responses and four of these were aged over 13 years when treated.

In conclusion, cerebral irradiation is a potent cause of GH deficiency in children.
HYPOTHALAMIC‐PITUITARY FUNCTION FOLLOWING SUCCESSFUL TREATMENT OF INTRACRANIAL TUMOURS
Authors: HARROP J. S. , DAVIES T. J. , CAPRA L. G. , MARKS V.
Published: March 2008

Hypothalamic‐pituitary function was examined in seventeen patients treated in the past for extrasellar intracranial tumours. All patients had received a course of external cranial irradiation. Biochemical abnormalities of endocrine function were present in almost all of the patients. In particular, the growth hormone response to insulin induced hypoglycaemic stress was impaired in eleven out of fifteen patients. Preliminary data from a group of seven patients with intracranial tumours prior to radiotherapy are also presented. The possibility that cranial irradiation causes hypothalamic‐pituitary dysfunction is discussed. The results suggest that endocrine assessment should be considered in patients who have been treated for intracranial tumours, even in the absence of direct pituitary involvement.
HYPOTHALAMIC HYPOPITUITARISM FOLLOWING EXTERNAL RADIOTHERAPY FOR TUMOURS DISTANT FROM THE ADENOHYPOPHYSIS
Authors: PERRY‐KEENE D. A. , CONNELLY J. F. , YOUNG R. A. , WETTENHALL H. N. B. , MARTIN F. I. R.
Published: March 2008

Three cases of panhypopituitarism and five of isolated growth hormone dificiency which occurred following previous external irradiation of tumours distant from the adenohypphysis are described. The hypothalamic pituitary region received between 2800 and 12000 rads in each case, 1‐9 years before endocrine deficiency was recognized. Evidence is presented that th esite of damage is in the region of the hypothalamus rather than the pituitary gland itself.

Individuals treated with X‐ray therapy in whom the hypothalamic‐pituitary region is exposed to irradiation would appear to be at risk of developing some degree of delayed hypothalamic‐pituitary dysfunction.

Early reports of the effects of external radiotherapy on hypothalamo‐hypophyseal function suggested that the pituitary gland was resistant to damage from irradiation, but that the hypothalamus and adjacent neural tissues were more sensitive (Kelly et al., 1951; Arnold, 1954). Radiotherapy to malignant tumours distant from the pituitary has not been thought to result in endocrine dysfunction even when the hypothalamo‐hypophyseal region was included in the field of irradiation (de Schryver et al., 1973). Only three reports of documented hypopituitarism following external radiotherapy in such circumstances have been recorded (Tan & Kunaratnam, 1966; Larkins & Martin, 1973; et al., 1975).

This paper details the endocrine status of eight patients treated by radiotherapy for malignant disease distant from the pituitary, in whom the hypothalamus was also irradiated. Two of these patients have been reported previously (Larkins & Martin, 1973) and all were found to have severe or partial hypopituitarism.
EFFECTS OF OESTROGENS ON PROLACTIN AND THYROTROPHIN RESPONSES TO TRH IN WOMEN DURING THE MENSTRUAL CYCLE AND UNDER ORAL CONTRACEPTIVE TREATMENT
Authors: REYMOND M. , LEMARCHAND‐BÉRAUD TH.
Published: March 2008

The effects of physiological and pharmacological variations of oestrogens on prolactin and thyrotrophin (TSH) secretion have been studied during the menstrual cycle and under oral contraceptive treatment.

Ten women were tested for prolactin and TSH responses to 200 μg TRH in the early follicular (days 4‐6), periovulatory (days 14‐15) and luteal phases (days 22‐26) of the same menstrual cycle. Circulating plasma prolactin levels did not significantly vary in three phases, but TSH basal levels were lower in the luteal than in the follicular and periovulatory periods. The prolactin response to TRH was significantly enhanced in the periovulatory phase, while the TSH response was slightly decreased.

Seven women on sequential contraceptives exhibited increased basal and TRH‐induced prolactin secretion during the oestrogen treatment, with an unaltered TSH secretion throughout therapy. Treatment with combined contraceptives did not alter either basal or TRH‐induced prolactin secretion in eight women, but basal TSH secretion and its response to TRH were both reduced.

These data show that oestrogens may produce different regulatory effects on prolactin and TSH secretion, particularly in the pituitary sensitivity to TRH stimulation. Physiological variations of oestrogen secretion such as those observed during the menstrual cycle can likewise modify prolactin levels. These results could provide some support for a regulatory role for prolactin in the menstrual cycle.
MODIFICATION BY SEX STEROIDS OF LHRH RESPONSE IN THE POLYCYSTIC OVARY SYNDROME
Authors: SHAW R. W. , DUIGNAN N. M. , BUTT W. R. , LOGAN‐EDWARDS R. , LONDON D. R.
Published: March 2008

Exogenously administered oestradiol or progesterone was found to induce augmentation of LH and FSH release in response to LHRH administration in patients with the polycystic ovary (PCO) syndrome. The effect of oestradiol upon LH release in the patients was significantly less than the augmented release induced in normal women (P < 0.02). In contrast, progesterone induced a significantly greater LH release in PCO patients than normal women studied during the early follicular phase (P < 0.001) but less than that in normal women studied during the mid‐follicular phase of the cycle (P < 0.01). The effects on FSH release in the PCO patients were less marked but similar to those in normal women with comparable basal steroid levels.

The results suggest that both oestradiol and progesterone can modify the hypothalamic‐pituitary axis in the PCO syndrome in a manner similar to that observed in normal women and a failure of these ‘positive feedback’ mechanisms does not appear to be the cause of the ovulatory deficiency in this syndrome.
THE CONTROL OF GONADOTROPHIN RELEASE IN WOMEN WITH HYPERPROLACTINAEMIC AMENORRHOEA: EFFECT OF OESTROGEN AND PROGESTERONE ON THE LH AND FSH RESPONSE TO LHRH
Authors: GLASS M. R. , SHAW R. W. , WILLIAMS J. W. , BUTT W. R. , LOGAN‐EDWARDS R. , LONDON D. R.
Published: March 2008

The effect of the administration of oestradiol benzoate and of progesterone on the subsequent response to LHRH has been investigated in women with hyperprolactinaemia. There was an amplification in the release of LH in four out of ten patients and of FSH in one out of ten patients at 44 h after the administration of 2·5 mg oestradiol benzoate. The average amount of LH released before and after oestrogen did not change, but there was a significant decrease in the amount of FSH released. There was no correlation between the LH released and the oestradiol concentration in serum at the time of the LHRH tests but there was a negative correlation between the FSH released and the oestradiol concentration (r= 0.507; P < 0.05). These results contrast with those obtained in normal subjects in the follicular phase of the cycle when there is a positive correlation of oestrogen concentrations and the amount of LH and FSH released. As in normal subjects, bowever, a significant suppression of basal FSH concentrations, persisting until 44 h, was produced by the oestrogen (P < 0.01).

Seven out of eleven patients showed an amplification of LH response and six out of eleven an FSH response 20 h after the administration of 25 mg progesterone. The mean amplifications are not significantly different from those of normal subjects tested in the early follicular phase of the cycle, but are significantly less than those tested in the mid follicular phase of the cycle (LH P < 0.001; FSH P < 0.01). This may be related to the serum concentrations of oestradiol which in patients with hyperprolactinaemia are significantly less than those found in the mid follicular phase of the cycle (P < 0.05).

These results indicate that in women with hyperprolactinaemia oestrogen negative feedback, necessary for cycle initiation, is normal: failure of ovulation may be related to failure of positive feedback to oestrogen. Oestrogen‐negative feedback is unopposed and this may explain the follicullar development and lack of oestrogen in the mid‐follicular phase.
HORMONAL VARIATIONS IN SECONDARY AMENORRHOEA DURING THE METYRAPONE TEST
Authors: MAZZI C. , RIVA L. P. , BERNASCONI D.
Published: March 2008

The occurrence of uterine bleeding following administration of Metyrapone in cases of secondary amenorrhoea and oligomenorrhoea led the authors to measure pituitary, gonadal and adrenal hormone levels, before and after the oral administration of this drug in sixteen patients, in an attempt to provide an interpretation of this phenomenon. There were expected changes in plasma ACTH and urinary 17‐hydroxycorticosteroids, but no variations were noted in serum FSH and LH, plasma oestradiol and urinary oestrogens; the most important alterations occurred in plasma progesterone and urinary pregnanetriol levels. It is suggested that bleeding occurs because of the changes which are induced in plasma progesterone levels.
1‐ALPHA‐HYDROXYCHOLECALCIFEROL IN THE TREATMENT OF HYPOCALCAEMIC PSYCHOSIS
Authors: GERTNER J. M. , HODSMAN A. B. , NEUBERGER J. N.
Published: March 2008

Two patients with profound hypocalcaemia due to uraemia and hypopara‐thyroidism respectively presented with alterations of mental state as their dominant symptom. 1‐Alpha‐hydroxycholecalciferol (1‐α‐OHD3) was chosen as the principal therapy because of its potency and rapid action. In both patients the plasma calcium was restored towards normal and the symptoms relieved within a very short period. The cases illustrate the role of 1‐α‐OHD3 in severe hypocalcaemia due to two different causes and provide experience on which to base treatment regimes for future patients similarly afflicted.
EFFECT OF EPIDURAL ANALGESIA ON THE GLYCOREGULATORY ENDOCRINE RESPONSE TO SURGERY
Authors: BRANDT M. , KEHLET H. , BINDER C. , HAGEN C. , McNELLY A.S.
Published: March 2008

Plasma concentrations of glucose, insulin, glucagon, cortisol, growth hormone and prolactin were measured repeatedly in ten females undergoing abdominal hysterectomy during general anesthesia. In addition to general anesthesia five of the patients had continuous epidural analgesia effective for the 26 post‐operative hours. Plasma glucose was elevated during surgery and postoperatively, but not in patients having epidural analgesia. Insulin was low and unchanged in both groups. Glucagon was unchanged and similar in both groups. Cortisol was lower during surgery in the epidural group, but not postoperatively. Growth hormone increased during surgery in four of five patients receiving general anaesthesia alone, but not changes were observed in the epidural group. Prolactin was greatly elevated in all patients immediately after induction of anesthesia and then fell rapidly during surgery, similarly in both groups. It is concluded that epidural analgesia can inhibit the hyperglycaemic response to surgical stress, but this effect cannot be uniformly correlated to changes in peripheral plasma levels of insulin, glucagon, cortisol, growth hormone or prolactin.
MATERNAL THYROID FUNCTION, IODINE DEFICIENCY AND FETAL DEVELOPMENT
Authors: PHAROAH P. O. D. , ELLIS SHEILA M. , EKINS ROGER P. , WILLIAMS EDWARD S.
Published: March 2008

In an area of New Guinea where there is dietary iodine deficiency, measurements of thyroid function have been made on women of child‐bearing age, several of whom were pregnant at the time. The outcome of these pregnancies, and also of those occurring in the four preceding years, were examined in relation to indices of thyroid function. More stillbirths, infant deaths and endemic cretins occurred among the offspring of women who showed biochemical evidence of iodine deficiency, without clinical evidence of hypothyroidism. This situation differs from that of untreated myxoedema or congenital hypothyroidism in women, which is usually associated with altered menstrual function, infertility or repeated abortion. Mechanisms that may account for these differences and the possible implications are discussed.
SUBCELLULAR PROGESTERONE IN HUMAN MYOMETRIUM DURING LATE PREGNANCY
Authors: HAUKKAMAA M. , WICHMANN K.
Published: March 2008

Samples of myometrium were obtained from twenty‐two patients undergoing caesarian sections for various obstetric indications. The myometrium was homogenized and divided into four subcellular fractions (crude nuclear, mitochondrial, microsomal and cytosol). The concentration of endogenous progesterone in these fractions was determined by radioimmunoassay. In addition the concentration of oestrone and oestradiol of fifteen cytosolic fractions was determined.

The subcellular concentration of progesterone (pg/mg protein) in human myometrium was higher in samples taken during labour than in samples taken at elective caesarian sections. This finding was statistically significant in the crude nuclear (P < 0.005) and the microsomal (P < 0.05) fractions. The absolute concentration of progesterone was lowest in the nuclear and highest in the microsomal fraction. The relative progesterone concentrations in the four subcellular fractions were the same in both groups. The data show that there is no significant decrease in myometrial progesterone associated with labour in man.

The mean concentration of oestrone was higher than the mean oestradiol concentration in the cytosol fraction of human myometrium in late pregnancy. This study shows that a completely different oestrogen ratio exists in myometrium than in plasma.
TRIGLYCERIDE FATTY ACIDS CONFIRM A CHANGE IN DIETARY FAT
Authors: MOORE R. A. , OPPERT S. , EATON P. , MANN J. I.
Published: March 2008

The pattern of triglyceride fatty acids has been shown to alter rapidly when normolipaemic individuals eating a normal‘western’diet rich in saturated fats were changed to a diet low in cholesterol and high in polyunsaturated fats. The proportion of triglyceride linoleate was used to monitor the adherence to dietary advice of eleven primary hypercholesterolaemic patients (Type II) presenting to a lipid clinic. Patients adhering to diet showed a fall in serum cholesterol and a rise in triglyceride linoleate; recalcitrant patients showed little change. The estimation of triglyceride linoleate may be an important adjunct to clinical judgement in assessing dietary resistance before resource to drug therapy in hypercholesterolaemic patients.
THE PITUITARY‐THYROID AXIS FOLLOWING SURGERY FOR THYROTOXICOSIS: THYROTROPHIN‐RELEASING HORMONE TESTS IN DIFFUSE THYROID HYPERPLASIA AND TOXIC UNINODULAR GOITRE
Authors: BROWNLIE B. E. W. , JENSEN C. A. , TURNER J. G. , MACBETH W. A. A. G. , DONALD R. A.
Published: March 2008

The pituitary‐thyroid axis was assessed 1 month after surgery by thyrotrophinreleasing hormone (TRH) testing in thirty thyrotoxic patients treated by subtotal thyroidectomy and eleven patients with toxic uninodular goitre. All toxic nodule patients gave essentially normal TRH responses and have remained clinically and biochemically euthyroid at follow‐up. Only seven of the thirty subtotal thyroidectomy patients had normal TRH tests when assessed 1 month post thyroidectomy —sixteen patients showed increased response, six gave flat responses, and one showed an anomalous minimal response. Follow‐up TRH tests 12 months postthyroidectomy have shown a tendency for TRH responsiveness to return towards normal, but two patients with flat TRH tests have required radioiodine for relapse and four TRH hyperresponders are currently receiving thyroxine replacement therapy.
INCREASED PROLACTIN AND THYROTROPHIN SECRETION FOLLOWING ORAL METOCLOPRAMIDE: DOSE‐RESPONSE RELATIONSHIPS
Authors: HEALY D. L. , BURGER H. G.
Published: March 2008

Four normal men received 1, 5, 10 and 20 mg doses of oral metoclopramide, a dopamine receptor antagonist, or placebo to determine the effect of this drug on anterior pituitary hormone secretion. Increases in serum prolactin (PRL) occurred even after the 1 mg tablet (P < 0.01) while maximal responses were observed 60 min after ingestion of the 20 mg tablet (mean 27.8 ng/ml; range 25.6–30.3 ng/ml). Serum PRL levels peaked 60–90 min after ingestion of any dose of metoclopramide and values remained significantly elevated (P< 0.05) for up to 8 h after the tablet.

Increases in serum thyrotrophin (TSH) also occurred after the 10 and 20 mg doses of metoclopramide. Peak responses were seen at 120–180 min, with significant elevation (P < 0.05) persisting from 60 to 240 min after ingestion. No consistent changes in serum FSH, LH or GH were observed and no side‐effects were reported.

It was concluded that metoclopramide elevated serum PRL and TSH. The threshold dose of metoclopramide required for these effects was different for the two hormones; their peak responses occurred at different times and the duration of the elevation was dissimilar, suggesting a mechanism other than the release of hypothalamic thyrotrophin‐releasing hormone (TRH).
ENDOGENOUS ADRENERGIC REGULATION OF RENIN RELEASE IN NORMOTENSIVE MAN
Authors: HSU L. , LILLEY J. J. , STONE R. A.
Published: March 2008

Exogenous infusion of catecholamines in man and electrical stimulation of renal nerves in anaesthetized animals have suggested the importance of adrenergic influence on renin release. We have studied the effect of endogenous adrenergic stimulation on renin release in seventeen apparently healthy, unanaesthetized normotensive men (mean arterial pressure < 100 mmHg). All subjects were ingesting an unrestricted salt diet, excreting > 100 mEq sodium per 24 h. Plasma renin activity (PRA), expressed as nanograms angiotensin I per millilitre per hour, increased 4.1±0.76 ng/ml (range 0.3–9.7 ng/ml) in all subjects 5 h after ingestion of 80 mg frusemide. Amyl nitrite inhalation and cold pressor testing produced the appropriate haemodynamic alterations but failed to increase PRA significantly (P>0.05). The alpha agonist, phenylephrine, decreased PRA from an average basal level of 1.21±0.16 ng/ml to 0.83±0.13 ng/ml, and the alpha blocker, phentolamine, increased PRA from an average initial level of 1.26±0.3 ng/ml to 3.61±0.6 ng/ml. Repeat inhalation of amyl nitrite with alpha blockade further elevated PRA to 4.36±0.97 ng/ml in contrast to the effect of amyl nitrite alone. These data suggest that endogenous stimulation of sympathetic nerves with amyl nitrite inhalation or cold pressor testing is not associated with measurable increase in PRA. Alpha adrenergic stimulation with phenylephrine causes a significant decrement in PRA, and alpha blockade with phentolamine significantly increases PRA. Amyl nitrite inhalation in the presence of alpha blockade further elevated PRA in direct contrast to the effect of amyl nitrite alone. Haemodynamic correlates, the elevation of PRA with alpha blockade, and the decrement of PRA with alpha stimulation suggest that alpha adrenergic receptor inhibition may account for the lack of PRA increase with endogenous sympathetic stimulation.
ALTERATIONS IN SERUM PROLACTIN HETEROGENEITY BY PROVOCATIVE TESTS IN A PATIENT WITH A PITUITARY TUMOUR
Authors: GALA R. R. , VAN DE WALLE CYNTHIA , HOFFMAN W. H.
Published: March 2008

The proportion of serum prolactin heterogeneity were investigated in a patient with a pituitary adenoma producing both prolactin and growth hormone. Glucose tolerance (GTT) and insulin tolerance (ITT) tests were performed alone and in combination with chlorpromazine both before and after hypophysectomy. Serum prolactin multiple forms were separated by Sephadex G‐100 column chromatography at 3°C. None of the provocative tests altered the already elevated serum prolactin either before (300 ng/ml) or after (100 ng/ml) hypophysectomy. Chlorpromazine or ITT did not alter the proportion of prolactin heterogeneity; GTT, whether in conjunction with chlorpromazine or alone and both before and after hypophysectomy, increased the proportions of the larger molecular species. In five tests in which the GTT was not performed the prolactin heterogeneity was as follows: ‘void volume’, 4.9%; ‘big’, 13.1%; ‘little’, 82.1%; in those experiments in which the GTT was performed the proportions of prolactin heterogeneity were: ‘void volume’, 13.5%, ‘big’, 19.2%; ‘little’, 67.3%.
COEXISTING PRIMARY EMPTY SELLA SYNDROME AND ACROMEGALY*
Authors: MOLITCH M. E. , HIESHIMA G. B. , MARCOVITZ S. , JACKSON I. M. D. , WOLPERT S.
Published: March 2008

SUMMARY The‘empty’sella syndrome is now a more frequent diagnosis due to the increased use of pneumoencephalography in the evaluation of the enlarged pituitary fossa. This syndrome has also been classified into a‘primary’form in which there has been no prior pituitary irradiation or surgery, and a ‘secondary’ form in which the empty sella is found after such procedures. Most patients with the primary empty sella syndrome are found to have normal pituitary function while about 30% have varying degrees of hypopituitarism (Neelon et al., 1973).

It is not widely appreciated, however, that the primary empty sella may harbour a pituitary tumour with resultant acromegaly. In this report we describe two such patients who presented with active acromegaly. This entity of pituitary tumour in a primary empty sella merits careful consideration since the coexistence of these two findings may influence the therapeutic approach that might otherwise be appropriate for the pituitary tumour.
IS THE GROWTH‐HORMONE RESPONSE TO INSULIN DUE TO HYPOGLYCAEMIA, HYPERINSULINAEMIA OR A FALL IN PLASMA FREE FATTY ACIDS?
Authors: WEST T. E. T. , SÖNKSEN P. H.
Published: March 2008

Seven normal male volunteers were given a 2 h intravenous infusion of insulin (2 mu kg‐1 min‐1). During the first hour, in which normoglycaemia was maintained by glucose infusion, no detectable increase in growth hormone (GH) secretion occurred. When controlled symptomatic hypoglycaemia was produced during the second hour of the insulin infusion a brisk rise in plasma GH concentration was observed in all the subjects studied. Since it was possible that the falls in the concentration of plasma free fatty acids (FFA) occurring during infusion of insulin also acted as a stimulus to GH release the study was repeated in four subjects but normoglycaemia was maintained throughout the entire 2 h period of insulin infusion. In these experiments there was no rise in plasma GH concentration although a similar fall in plasma FFA was produced. These results clearly indicate that hypoglycaemia per se was the important stimulus to GH secretion and not hyperinsulinaemia or a lowering of plasma FFA. Furthermore there appeared to be a threshold hypoglycaemic stimulus to GH secretion. In no subject was a rise in plasma GH seen without a fall in plasma glucose greater than 1.4 mmol/l. Prolonged mild hypoglycaemia did not stimulate GH secretion.
SERUM PROLACTIN AND OESTRADIOL LEVELS AT DIFFERENT STAGES OF PUBERTY
Authors: THORNER M. O. , ROUND JOAN , JONES ANN , FAHMY D. , GROOM G. V. , BUTCHER SUSAN , THOMPSON K.
Published: March 2008

Serum prolactin and oestradiol levels were measured in 183 children who were staged for pubertal development. Mean serum prolactin levels are higher in girls than in boys at stage 3 of pubertal development. In girls prolactin levels rise at stage 2, and are higher after menarche; in boys there is no change in prolactin levels. In this study serum oestradiol correlates with prolactin in the girls, but not in the boys.
EFFECT OF STILBOESTEROL THERAPY ON THYROTROPHIN‐RELEASING HORMONE (TRH) RESPONSIVENESS IN MALES
Authors: SMYTH P. P. A. , TURNER J. J. , O'DONOVAN D. K.
Published: March 2008

TRH responsiveness was investigated in twenty‐four males (aged 66‐83 years) undergoing stilboesterol therapy for carcinoma of the prostrate. Twelve were taking 2‐6 mg daily by mouth for periods of 5 days to 12 months (mean 5 months) (Group A) and the remainder were on daily i.v. doses of 250‐500 mg for periods of 3‐10 days (mean 8 days) (Group B). In the former group TRH responsiveness was enhanced compared to age matched controls. A contrary effect was observed in the latter group in that the group mean TRH response was significantly lower than that of Group A or of the control group. Basal serum TSH values were unchanged in Group A compared to controls, but a significant elevation in the basal mean value was observed in Group B.

The mechanism of action of stilboesterol in the subjects studied remains to be elucidated. Our data are in keeping with either a hypothalamic or pituitary locus for such actions.
THYROID FUNCTION AND ANTIBODY STUDIES IN PERNICIOUS ANAEMIA
Authors: KRASSAS G. , McHARDY‐YOUNG S. , RAMSAY IAN , FLORIN‐CHRISTENSEN A.
Published: March 2008

Thyroid antibodies were demonstrated in 57% of thirty pernicious anaemia patients without overt thyroid disease. Elevated basal thyroid stimulating hormone (TSH) levels and an enhanced TSH response to thyrotrophin releasing hormone (TRH) only occurred in thyroid antibody positive subjects; by contrast the thyroid antibody negative subjects in the older age group frequently had undetectable basal TSH levels and an impaired TRH response. Thyroid hormone concentrations provided no absolute evidence of hypothyroidism in any of the patients.
GLUCAGON AND DIABETES
Authors: WARNE G. L. , ALFORD F. P. , CHISHOLM D. J. , COURT J.
Published: March 2008

In order to determine whether glucagon levels of diabetic subjects are suppressible, alpha cell responsiveness to acute insulin administration (0.1 units/kg intravenously) was determined in fourteen juvenile onset, healthy diabetic and eight control subjects. In the diabetics, insulin produced a significant but slow fall in blood glucose over 60 min (P<0.01). On the other hand, glucagon levels fell dramatically in all diabetics to undetectable levels (P<0.001). Only one diabetic became hypoglycaemic and he alone showed a rebound rise of glucagon at 60 min. The rate of fall of blood glucose in the diabetic subjects was not influenced by the basal glucagon level (r= 0.13) or the rate of fall of plasma glucagon (r= 0.04). The glucose and glucagon responses of control subjects to insulin administration were in sharp contrast to the diabetics: blood glucose levels fell rapidly to hypoglycaemic levels and were associated with a major rise in glucagon levels (mean rise 116 pmol/1, P<0.001).

We conclude that alpha cell hyperfunction in human diabetes can be completely suppressed by insulin administrtion and is therefore not autonomous, and that the slow rate of fall of blood glucose following insulin administration in diabetics is not secondary to glucagon excess.
HORMONAL CHANGES ASSOCIATED WITH TESTICULAR ATROPHY AND GYNAECOMASTIA IN PATIENTS WITH LEPROSY
Authors: MORLEY JOHN E. , DISTILLER LARRY A. , SAGEL JULIUS , KOK S. H. , KAY GRAHAM , CARR PETER , KATZ MAURICE
Published: March 2008

Basal LH, FSH, 17ß‐oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty‐four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration.

The mean basal testosterone and 17ß‐oestradiol values of the lepromatous group were significantly lower than those of the tuberculoid and control groups.

The abnormal gonadotrophin and sex steroid values in the lepromatous group are in keeping with the testicular atrophy and gynaecomastia accompanying this form of leprosy. However, the lack of a significant correlation between basal FSH and testicular atrophy should be noted. In addition, no correlation between any of these hormonal values and gynaecomastia could be demonstrated.

The patients with tuberculoid leprosy had essentially normal hormonal profiles (except for two who had raised 17ß‐oestradiol values). This is compatible with the lack of gonadal involvement in these patients.
ACUTE EFFECT OF INORGANIC IODIDE AFTER 131I THERAPY FOR HYPERTHYROIDISM
Authors: SCHIMMEL MARTIN , UTIGER ROBERT D.
Published: March 2008

Patients treated with inorganic iodide weeks to years following 131I therapy for hyperthyroidism do not adapt to its antithyroid effect. To determine whether such adaptation occurs soon after 131I therapy, serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured daily for 9‐14 days following 131I therapy in seventeen hyperthyroid patients. Nine patients received 150 mg KI daily starting 48 h after 131I administration; eight received only 131I. Serum T4 and T3 concentrations did not change significantly in the patients who received only 131I. In the patients who received 131I and KI, serum T4 and T3 concentrations fell promptly, reaching nadir values 2‐10 days after initiation of iodide, and then increased despite continuation of KI therapy. The mean maximal fall in serum T4 was 34% and in serum T3 42%. These results show that ‘escape’ from the acute antithyroid effect of iodide occurs when it is given immediately after 131I therapy, thus limiting the utility of iodide as a therapeutic agent at this time.

131I‐iodide is a widely used and effective form of therapy for hyperthyroidism. Reduction in thyroid hormone does not occur within the first weeks after 131I therapy. Exacerbation of hyperthyroidism may occur shortly after 131I administration, with frequency ranging from 0 to 11% in several large species (Chapman et al., 1954; Cassidy & Astwood, 1959; Lamberg et al., 1959; Green & Wilson, 1964). Such exacerbations are thought to reflect acute thyroid radiation necrosis and subsequent hormone release, and may limit the use of 131I therapeutically.

Inorganic iodide is a rapidly, but usually transiently, effective antithyroid agent when used alone. No reports are available concerning the efficacy of iodide when given immediately following 131I therapy. Since some hormone release after 131I therapy may reflect thyroid destruction, rather than secretion, it is possible iodide might be less effective in this setting. On the other hand, if iodine is effective immediately after 131I therapy, especially if its action is sustained (as occurs in patients treated with 131I months or years previously; Hagen et al., 1967; Braverman et al., 1969), it might be a useful adjunct for certain hyperthyroid patients treated with 131I. This report describes the result of a study of patients so treated.