bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECTS OF CHRONIC TREATMENT WITH LHRH ON GONADOTROPHIN SECRETION AND PITUITARY RESPONSIVENESS TO LHRH IN WOMEN WITH SECONDARY HYPOGONADISM
Authors: WILLIAMS C. A. VAUGHAN , McNEILLY A. S. , BAIRD D. T.
Published: March 2008

Twenty women with secondary hypogonadism and four normal women in the early follicular phase of the cycle were treated for 7 days with 10, 50 or 100 μg synthetic LHRH administered intramuscularly at 4 h intervals. Concentrations of pituitary and ovarian hormones in plasma were measured at intervals during the treatment period. The episodic pattern of LH secretion and the gonadotrophin responses to acute stimulation with LHRH were evaluated before and after treatment.

In normal women the concentrations of gonadotrophins and the LH response to LHRH remained unchanged, whilst the FSH response to LHRH was reduced after treatment. Concentrations of oestradiol rose progressively in response to treatment, indicating follicular development.

In hypogonadal subjects with unimpaired pituitary function, treatment with LHRH induced a marked but transient increase in the concentrations of LH and FSH in plasma and a progressive rise in that of oestradiol. The concentration of progesterone was increased in four of the 11 subjects. However, the amplitude of LH pulses and the responses of FSH and LH to LHRH after treatment were suppressed below pretreatment values.

Women with hypogonadotrophic hypogonadism and diminished pituitary responses to LHRH exhibited a sustained increase in the concentrations of LH, FSH and oestradiol in plasma to normal follicular phase levels. The amplitude of LH pulses and the LH response to LHRH were increased after treatment but did not reach normal values. The FSH response to LHRH was further reduced after treatment. Treatment of similar subjects with 10 μg LHRH induced a small increase in the concentration of gonadotrophins but not of ovarian steroids.
HYPERTHYROIDISM DUE TO A THYROTROPHIN‐SECRETING MICROADENOMA
Authors: KELLETT HILARY A. , WYLLIE A. H. , DALE B. A. B. , BEST J. J. K. , TOFT A. D.
Published: March 2008

We report a 63‐year‐old female with a TSH‐secreting pituitary adenoma causing hyperthyroidism. This case is apparently unique, and challenges the present concept of dividing patients with inappropriate TSH secretion into tumour and non‐tumour groups on the basis of conventional pituitary fossa radiology.
EVIDENCE THAT THYROID HORMONES REGULATE GLUCONEOGENESIS FROM GLYCEROL IN MAN
Authors: McCULLOCH A. J. , JOHNSTON D. G. , BAYLIS P. H. , KENDALL‐TAYLOR P. , CLARK F. , YOUNG E.T. , ALBERTI K. G. M. M.
Published: March 2008

We have previously reported that glucose production assessed using radioiso‐topic methods is 50% increased in hyperthyroidism but 30% decreased in hypothyroidism. These studies, however, do not distinguish between glycogenolysis and gluconeogenesis. In fasting man more than 80% of circulating glycerol is cleared by the liver and enters the gluconeogenic pathway. We have therefore measured glycerol clearance following bolus intravenous glycerol administration as an indirect assessment of gluconeogenic capacity. Hyperthyroid and hypothyroid subjects were compared with separate matched controls after an overnight fast. In hyperthyroid subjects blood glucose and blood glycerol were increased but lactate, pyruvate, and alanine concentrations were normal. Glycerol clearance was increased in hyperthyroidism and followed a double exponential decay with a shortened second component half‐time. Endogenous glycerol production was increased three‐fold. In hypothyroidism fasting circulating levels of glucose, lactate, pyruvate, alanine, and glycerol were normal but glycerol clearance was diminished. Both first and second component half‐times were prolonged in hypothyroidism and endogenous glycerol production was decreased by 50%. Thus in hyperthyroidism glycerol clearance is greatly enhanced whilst in hypothyroidism glycerol clearance is diminished. The magnitude of the changes suggests that alterations in gluconeogenesis are probably the major factors concerned in the reported increase and decrease in glucose production in hyperthyroidism and hypothyroidism respectively.
A CASE OF MULTIPLE ENDOCRINE ADENOMATOSIS (TYPE 1) WITH NESIDIOBLASTOSIS, TERMINATING WITH AN EXOCRINE PANCREATIC CARCINOMA
Authors: OLIVER M. H. , DRURY P. L. , VAN'T HOFF W.
Published: March 2008

We describe a patient with multiple endocrine adenomatosis Type I, characterized by pituitary‐dependent Cushing's Syndrome, marked hyperprolactinaemia, primary hyperparathyroidism and hyperinsulinism leading to hypoglycaemia. The patient subsequently developed an exocrine pancreatic carcinoma at the age of 32 years from which she died. An additional finding was the demonstration by immunocytochemistry of nesidioblastosis in the pancreas.
MALIGNANT HYPERTENSION IN CONGENITAL ADRENAL HYPERPLASIA DUE TO 11β‐HYDROXYLASE DEFICIENCY
Authors: HAGUE W. M. , HONOUR J. W.
Published: March 2008

Two brothers, aged 20 and 12, with the 11β‐hydroxylase deficient form of congenital adrenal hyperplasia, are presented. They had refused treatment for the previous four years until the younger was admitted with malignant hypertension, partial blindness and evidence of myocardial damage. The elder was therefore admitted for assessment and found to have less severe hypertension. Gas liquid chromatographic analysis of the steroids in urine from each revealed a possible difference in the enzyme defect between the two brothers—the younger having a complete, while the elder had only a partial block. Family studies have confirmed no association with the HLA locus.
INHIBITION OF PROLACTIN SECRETION BY LOW‐DOSE DOPAMINE INFUSION IN PATIENTS WITH HYPERPROLACTINAEMIA
Authors: CONNELL J. M. C. , PADFIELD P. L. , BUNTING E. A. , BALL S. G. , INGLIS G. C. , BEASTALL G. H. , TEASDALE G. M. , DAVIES D. L.
Published: March 2008

Dopamine inhibits the secretion of prolactin from the pituitary. We have examined the relation between plasma dopamine and serum prolactin in 12 patients with hyperprolactinaemia during the infusion of dopamine at low doses (0·01, 0·1 and 1 μg/kg/min). Plasma dopamine levels were raised from less than 100 pg/ml at the lowest rate of infusion to more than 20 000 pg/ml at the highest. Suppression of prolactin secretion was seen in some patients even at the lowest rate of infusion (0·01 μg/kg/min); marked suppression of prolactin secretion (60%; 17–83%) was found at the intermediate dose (0·1 μg/kg/min) in 11 of the 12 subjects with little further decrease in serum prolactin (70%; 50–87%) in those in whom the rate of dopamine infusion was increased ten‐fold. One patient with the highest serum prolactin (82 500 mu/l) showed no decrease in prolactin either at the lowest or intermediate rates of dopamine infusion. Serum prolactin levels returned to values similar to or greater than basal on cessation of dopamine infusion. Infusion of dopamine at doses much lower than previously used in man exposes the pituitary to a concentration of dopamine sufficient to suppress prolactin secretion. These observations have important implications in understanding the pathophysiology of prolactin secretion from the pituitary gland and for future investigations of the control of hormone release by dopamine.
FERTILITY AFTER CHILDBIRTH: PREGNANCY ASSOCIATED WITH BREAST FEEDING
Authors: McNEILLY A. S. , GLASIER A. F. , HOWIE P. W. , HOUSTON M. J. , COOK A. , BOYLE H.
Published: March 2008

During studies on the resumption of fertility postpartum in 12 breast feeding mothers who were using no contraception, eight pregnancies occurred. In seven cases these pregnancies occurred while the mothers continued to breast feed while in one it occurred within 2 weeks of weaning. In two cases pregnancy occurred prior to first postpartum menstruation but followed an abrupt decline in suckling frequency and duration resulting in resumption of follicular development and ovulation. In the remaining six cases, pregnancy was preceded by between 1 and 7 menstrual cycles, the majority of which (13/19) had deficient luteal phases or were anovular (4/19).

In all mothers a significant decrease in the suckling frequency and duration observed during lactational amenorrhoea had occurred prior to the resumption of ovulation and conception. No mother conceived with a suckling frequency of greater than three times per day although some mothers ovulated without conceiving when suckling four times per day.

The results suggests that if a breast feeding mother wishes to rely upon the infertility associated with lactational amenorrhoea, she must suckle at least five times per day with a total suckling duration of more than 65 min per day (more than 10 min per feed). Any reduction below either of these limits may result in a return of fertility.
ANDROGEN RECEPTOR CHARACTERISTICS IN SKIN FIBROBLASTS FROM MEN WITH PUBERTAL MACROMASTIA
Authors: EIL C. , LIPPMAN M. E. , DE MOSS E. V. , LORIAUX D. LYNN
Published: March 2008

Endocrine studies in men with pubertal macromastia (PM) have failed to reveal a hormonal abnormality to account for the disorder. As a result, it has been hypothesized that this form of gynecomastia may be a manifestation of a target organ abnormality.

Because the syndromes of apparent androgen resistance, such as testicular feminization and Reifenstein's Syndrome, are associated with gynaecomastia, we examined skin fibroblasts cultured from men with pubertal macromastia for androgen receptor defects. We studied 12 men with PM and confirmed that plasma concentrations of testosterone, oestradiol, gonadotrophins, and prolactin, were all within the normal range; findings identical to those of a similar series of patients previously reported. Androgen receptor content (Ro) and binding affinity (Kd) in cultured areolar and pubic skin fibroblasts were measured using a dispersed, whole cell assay. Nineteen areolar cell lines from the 12 patients with PM were compared with 4 areolar cell lines from three normal men and 9 areolar cell lines from nine normal women. There was no difference in the mean androgen receptor content (approximately 10 000 sites/cell) or binding affinity (approximately 1 nM) between the patients' fibroblasts and those of the normal subjects. Similarly, there were no differences in these parameters when pubic skin fibroblast androgen receptors were used for the comparison.

We conclude that, although PM may yet be due to a defect in breast tissue sensitivity to androgen, the disorder cannot be explained by abnormalities in fibroblast androgen receptor number or affinity.
FREE THYROID HORMONE CONCENTRATIONS IN SUBJECTS WITH VARIOUS ABNORMALITIES OF BINDING PROTEINS: EXPERIENCE WITH AMERLEX FREE‐T4 AND FREE‐T3 ASSAYS
Authors: BYFIELD P. G. H. , LALLOZ M. R. A. , PEARCE C. J. , HIMSWORTH R. L.
Published: March 2008

Free thyroid hormone concentrations measured by Amerlex assays were studied in subjects with inherited disorders of thyroxine‐binding globulin (TBG) synthesis, variant albumins with a high avidity for T4, and iodothyronine‐binding autoantibodies. Free T4 (fT4) and free T3 (fT3) levels were normal in euthyroid subjects with TBG deficiency and excess. Free T3 concentration was in the low normal range in subjects having a variant albumin but f T4 (Amerlex) was erroneously elevated because of the enhanced affinity of the 125I‐T4 analogue employed in the assay for the abnormal albumin. The 125I‐T3 analogue used in the f T3 assay does not bind more strongly to this variant albumin than to normal albumin. Amerlex assays for fT4 and fT3 in patients with iodothyronine‐binding autoantibodies to thyroglobulin give variable results according to the specificity of the autoantibodies: non‐specific antibodies cause extraordinarily high values even in hypothyroid patients; fT3 measurements may be appropriate in patients with T4‐specific antibodies and even in some with T3‐specific antibodies. The presence of such antibodies should be suspected if the results of Amerlex assays for fT4 and f T3 are discordant or are inconsistent with the clinical picture or TSH levels.
THYROID HORMONE SECRETION RATES: RESPONSE TO ENDOGENOUS AND EXOGENOUS TSH IN MAN DURING SURGERY*
Authors: TEGLER L. , GILLQUIST J. , LINDVALL R. , ALMQVIST S. , ROOS P.
Published: March 2008

The thyroid hormone secretory response to TSH was studied in twenty‐eight patients undergoing thyroid and parathyroid surgery. Eighteen patients received bovine or human exogenous TSH by injection into a thyroid artery, and 10 received TRH to stimulate endogenous TSH secretion. Thyroid secretion rates of T4, T3, and rT3 were determined directly from measurement of blood flow and the hormone gradient across the gland. A significant secretory response was seen for all three hormones following TSH increase. T3 secretion accelerated more rapidly than that of T4 and rT3, thus reducing the T4/T3 and rT3/T3 ratios. The T4/rT3 ratio fell during the first 30 min but then increased. The responses correlated with the area under the curve of the TSH serum concentration, and were similar after administration of bovine and human exogenous TSH, and TRH. Conclusions regarding preferential secretion ought to be made by comparing ratios of thyroid hormone secretion with those of the hormone content of the gland, but our results indicate that TSH induces preferential secretion of triiodothyronines in man.
SEASONAL VARIATION OF PLASMA DEHYDROEPIANDROSTERONE SULPHATE AND URINARY ANDROGEN EXCRETION IN POST‐MENOPAUSAL WOMEN
Authors: DESLYPERE J. P. , DE BISCOP G. , VERMEULEN A.
Published: March 2008

Urinary levels of the glucuronides of androsterone, aetiocholanolone, 5α‐androstane‐3α, 17β‐diol and 5β‐androstane‐3α, 17β‐diol, were determined in twenty‐two‐post menopausal women both in spring and in autumn–winter. In sixteen women dehydroepiandrosterone sulphate plasma levels were also measured. Plasma DHAS levels as well as urinary metabolite excretion values were significantly higher in autumn–winter than in spring. This seasonal variability should be taken into account in long‐term studies involving adrenal hormone levels, excretion or metabolism. Moreover this seasonal variability might be of relevance for the cyclical growth rate of hormone dependent tumours such as breast cancer.
RESPONSE OF PANCREATIC POLYPEPTIDE TO HYPOGLYCAEMIA IN INSULIN‐DEPENDENT DIABETICS WITH AND WITHOUT RESIDUAL β‐CELL FUNCTION
Authors: KRARUP T. , MADSBAD S. , HILSTED J. , CHRISTENSEN N.J. , SESTOFT L. , SCHWARTZ T.W.
Published: March 2008

To investigate a possible association between the β‐cells and the cells secreting pancreatic polypeptide (PP), the response of PP to insulin‐induced hypoglycaemia was investigated in seven insulin‐dependent diabetics with and seven without residual β‐cell function, all without signs of autonomic neuropathy. The mean concentrations of PP was significantly greater from 15 to 60 min after symptoms of hypoglycaemia in patients with residual β‐cell function than in patients without (P < 0·05) despite similar blood glucose concentrations in the two groups. Also the total integrated areas beneath the response curves as well as the incremental integrated areas were significantly greater in patients with β‐cell function (216 + 36 pmol/l × min and 188 ± 34 pmol/l X min, respectively) than in patients without β‐cell function (125 ± 26 pmol/1 × min and 102 ± 26 pmol/l × min) (P < 0·05 for both). The mean maximal concentrations of adrenaline (1±53 ± 0·28 ng/ml v. 1·29 ± 0·12 ng/ml) and noradrenaline (0·56 ± 0·16 ng/ml v. 0·45 ± 0·04 ng/ml) were not statistically different in the two groups. No well established explanation for an association between residual insulin secretion and capacity for PP‐response to hypoglycaemia in type 1 diabetics exists.
THYROTOXICOSIS IN PREGNANCY: RESULTS OF TREATMENT BY ANTITHYROID DRUGS COMBINED WITH T4
Authors: RAMSAY IAN , KAUR S. , KRASSAS G.
Published: March 2008

Treatment of thyrotoxicosis in pregnancy with antithyroid drugs plus supplementary T4 is controversial. Data are presented on twenty consecutive pregnancies treated by this method. The mean birth weights of the babies and their gestation did not differ from those of normal controls. Cord blood mean T4 and free T4 index (FT4I) were not significantly different from controls and total T3 and free T3 index (FT3I), though significantly lower than the controls, were all within the normal range. In five babies in whom they were measured, FT3, FT4 and rT3 levels were not significantly different from controls. Cord TSH was significantly higher in the babies of thyrotoxic mothers than in the control babies. One baby had a goitre at birth which disappeared after a few days. Another baby, born euthyroid, developed neonatal thyrotoxicosis the day after birth. Data collected from the literature on this method of treatment are compared with similar data from women treated with antithyroid drugs alone.
ENTEROGLUCAGON AND GIP AFTER ORAL GLUCOSE IN PATIENTS WITH PROLACTINOMA AND ACROMEGALY
Authors: CASSAR J. , GHATEI M. A. , SARSON D. L. , JOPLIN G. F. , MASHITER K. , BLOOM S. R.
Published: March 2008

We have performed oral glucose tolerance tests (OGTT) in nine patients with prolactinomas, eight patients with active acromegaly, five patients with acromegaly in remission and nine normal controls, and measured blood glucose, plasma insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide (GIP) and GH during the test. Patients with prolactinomas and with active acromegaly were hyperinsulinaemic and five of the nine patients with prolactinomas had impaired glucose tolerance, with blood glucose levels that were significantly higher than the normal controls. Prolactinoma patients had higher GIP levels than those with active acromegaly and both showed a failure of suppression of pancreatic glucagon. Of particular interest was the finding that enteroglucagon, a putative gut growth factor, was low in active acromegaly when compared with acromegaly in remission, but similar to normal in the rest of the patients.
RECIPROCAL PATTERN OF THE TSH AND PRL RESPONSES TO DOPAMINE RECEPTOR BLOCKADE IN WOMEN WITH PHYSIOLOGICAL OR PATHOLOGICAL HYPERPROLACTINAEMIA
Authors: MASSARA F. , CAMANNI F. , MARTRA M. , DOLFIN G. C. , MÜLLER E. E. , MOLINATTI G. M.
Published: March 2008

The TSH and PRL responses to administration of the two dopamine (DA) receptor antagonists sulpiride and domperidone, were studied in fifteen normoprolactinaemic subjects, twenty‐two post‐partum women and sixteen subjects with presumptive evidence of (six subjects) or surgically confirmed (ten subjects) prolactinomas. Sulpiride (100 mg i.m.) or domperidone (10 mg i.v.) elicited a slight increase in basal TSH levels in both normoprolactinaemic and post‐partum women, but induced a clear‐cut TSH rise in subjects with a tumour. Conversely, sulpiride and domperidone strikingly stimulated PRL secretion in normoprolactinaemic and post‐partum women, but only slightly enhanced base‐line PRL levels in women with prolactinomas. The reason for the reciprocal pattern of TSH and PRL responsiveness to DA receptor blockade of post‐partum women and subjects with prolactinomas is presently obscure. Since baseline PRL levels in the two hyperprolactinaemic states overlapped widely, it would appear that hyperprolactinaemia per se is not responsible for such behaviour.
A TEST OF 1,25‐DIHYDROXYVITAMIN D3 SECRETORY CAPACITY IN NORMAL SUBJECTS FOR APPLICATION IN METABOLIC BONE DISEASES
Authors: PRINCE R. L. , WARK J. D. , OMOND S. , OPIE J. M. , EISMAN J. A.
Published: March 2008

The circulating concentration of 1,25‐dihydroxyvitamin D3 [1,25‐(OH)2D3] varies in man in response to a variety of physiological stimuli. In pathological states, random plasma 1,25‐(OH)2D3 levels reflect the sum of the underlying pathological process and the homeostatic corrections to those perturbations. Hence random 1,25‐(OH)2D3 levels do not allow differentiation as to whether changes in 1,25‐(OH)2D3 production or metabolism are primary or secondary to other changes. Similarly random levels do not provide much insight into the reserve of 1,25‐(OH)2D3 secretory capacity. We have developed a single infusion of parathyroid extract (PTE) as a test of 1,25‐(OH)2D3 secretory capacity. Normal responses in twelve males and six females consisted of an increase in plasma 1,25‐(OH)2D3 levels of 78% over basal in the male and 77% over basal in the female subjects. The peak response occurred 18–22 h after the PTE was administered. This test of 1,25‐(OH)2D3 secretory capacity should prove useful in the evaluation of patients with metabolic bone disease. As part of this study, the diurnal plasma 1,25‐(OH)2D3 level was examined in six males and seven females. There was no significant diurnal rhythm between 8.00 and 22.00 h.
NALOXONE INHIBITS EXERCISE‐INDUCED RELEASE OF PRL AND GH IN ATHLETES
Authors: MORETTI C. , FABBRI A. , GNESSI L. , CAPPA M. , CALZOLARI A. , FRAIOLI F. , GROSSMAN A. , BESSER G. M.
Published: March 2008

Opiate peptides stimulate the release of GH and PRL, and such changes have also been reported following physical exercise. To investigate opiate involvement in the exercise‐induced release of these hormones, eight professional athletes were exercised to 80% of their maximal heart rate on a bicycle ergometer. This exercise alone induced an increase in circulating mean GH (basal to maximal level, 3·1 ± 0·9 ng/ml–27·3 ± 5·9 ng/ml) and mean PRL level (6·1 ± 11 ng/ml–19·5 ± 1·9 ng/ml). Infusion of naloxone (0·3 mg/min) antagonized these responses in mean serum GH (5·6 ± 1·0 ng/ml to 8·6 ± 1·1 ng/ml) and PRL levels (6·4 ± 1·1 ng/ml–8·1 ± 1·2 ng/ml), which were both significantly less than during the control infusions (P < 0·01). It is suggested that certain forms of stress stimulate the release of PRL and GH via endogenous opiate peptides.
DIFFERENT EFFECTS OF PROPRANOLOL, ALPRENOLOL, SOTALOL, ATENOLOL AND METOPROLOL ON SERUM T3 AND SERUM rT3 IN HYPERTHYROIDISM
Authors: PERRILD H. , HANSEN J. MØLHOLM , SKOVSTED L. , CHRISTENSEN L. KORSGAARD
Published: March 2008

Serum T4, T3, rT3 and T3 resin uptake (T3 RU) were measured before and after 7 days of treatment with either propranolol, alprenolol, sotalol, atenolol or metoprolol in hyperthyroid patients. We found a significant decrease in serum T3 after propranolol, alprenolol, atenolol and metoprolol but no change in the sotalol treated group. A significant increase in rT3 was found in the propranolol and alprenolol treated groups whereas a significant fall in rT3 was found in the atenolol and metoprolol treated groups. No change was found in the sotalol treated group. The changes observed in serum T3 and in rT3 could be explained by an inhibition of the 5′deiodinase enzyme by propranolol and alprenolol and an inhibition of both the 5′deiodinase and 5 deiodinase enzymes caused by atenolol and metoprolol.
AN ADRENAL ADENOMA CAUSING VIRILIZATION OF MOTHER AND INFANT
Authors: FULLER P. J. , PETTIGREW I. G. , PIKE J. W. , STOCKIGT J. R.
Published: March 2008

A right adrenal androgen‐producing adenoma was identified by CT scanning in a 33‐year‐old woman after delivery of an otherwise‐normal, virilized female infant. Despite clinical evidence of mild chronic androgen excess, maternal reproductive function was normal. Post‐partum studies showed 2–5‐fold excess in maternal plasma testosterone, androstenedione and dehydroepiandrosterone‐sulphate; urinary androgen metabolites were increased 3–10‐fold. Androgen production from the tumour increased acutely in response to hCG administration; after removal of the tumour, androgen levels were normal and showed negligible responses to hCG. These findings lead us to speculate that endogenous chorionic gonadotrophin may have led to augmented androgen production from the adrenal tumour during pregnancy, causing fetal virilization as previously described in patients with ovarian tumours. This study demonstrates that CT scanning can be valuable in distinguishing between adrenal and ovarian androgen‐producing tumours, a distinction which is often unreliable when based on physiological manipulations of hormone secretion.
THE ENDOCRINE AND METABOLIC EFFECTS OF CIMETIDINE
Authors: STUBBS W. A. , DELITALA G. , BESSER G. M. , EDWARDS C. R. W. , LABROOY S. , TAYLOR R. , MISIEWICZ J. J. , ALBERTI K. G. M. M.
Published: March 2008

Serial blood sampling in nine patients treated with cimetidine (1 g/day) showed that PRL values were within the normal range apart from a stress‐induced initial rise. Hormonal and metabolic profiles from 08.30 to 18.30 h were performed in six patients before and after 1 month's treatment with cimetidine (1 g/day). Circulating PRL, LH, FSH, GH, TSH T3, T4 and testosterone were similar before and after treatment. The mean blood glucose fell from 5·4 ± 0·3 mmol/l to 4·8 ± 0·2 mmol/l on cimetidine (P<0·02). Small changes were also observed in blood pyruvate, lactate, 3‐hydroxybutyrate and the (lactate)/(pyruvate) ratio. The effects of oral or i.v. cimetidine on the circulating concentrations of insulin, glucose and intermediary metabolites were investigated in normal subjects. Intravenous cimetidine (100 mg/h for 4 h) given to fasting subjects decreased blood glucose and serum insulin by 15 and 34% respectively at 150 min. During an oral GTT, i.v. cimetidine caused a striking decline in blood glucose, lactate and pyruvate responses compared with control studies, although the serum insulin was similar to control values. When given for 48 h before the study, oral cimetidine did not alter basal serum insulin and blood glucose, lactate, pyruvate, alanine, glycerol and 3‐hydroxybutyrate levels. However, 150 min after an oral GTT the serum insulin was increased by 47% by oral cimetidine although the blood glucose was not significantly changed compared with the control day. Oral cimetidine had no effect on the blood glucose or serum insulin during an i.v. GTT. These results show that oral cimetidine given at therapeutic doses to patients with peptic ulcers does not produce consistent changes in circulating anterior pituitary hormones. Oral cimetidine given to patients for 1 month and i.v. cimetidine given to normal subjects have mild hypoglycaemic effects. Oral cimetidine administered over 48 h to normal subjects has little effect on blood glucose concentration.
PLASMA CONTAMINATION ACCOUNTS FOR THYROID HORMONE BINDING IN NUCLEAR PROTEIN EXTRACTS FROM HUMAN MONONUCLEAR CELLS
Authors: MABERLY G. F. , EASTMAN C. J. , SMITH H. C. , WAITE K.
Published: March 2008

Plasma protein contamination accounted for high affinity thyroid hormone binding to a nuclear protein extract from human blood mononuclear cells. The degree of contamination was directly related to the number of times the cells were washed before the nuclear protein was extracted. After three washes, no specific binding was detected. Plasma contamination was estimated to be 0·3–0·5 μl/assay tube. The TBG concentration in this volume of plasma was consistent with the concentration of 0·2 μg/ml measured by RIA in the nuclear extract. Total specific binding of [125I] T4 and [125I] T3 can be attributed to plasma contamination, as 0·3 μl of plasma gave identical binding. Furthermore, a TBG antiserum abolished specific T4 and T3 binding to the nuclear protein extract. These data are consistent with TBG being the major plasma contaminant. In fourteen normal, euthyroid subjects, the higher mean maximum binding capacity (MBC) for T4 (1·63 ± 0·27 SD) compared to T3 (0·25 ± 0·21 pmol/mg protein; P < 0·001) and the same binding affinity (Ka, 2·0 ± 0·7 × 109/mol) for both T4 and T3 are the same as found in plasma. The higher MBC for T4 (5·8 ± 1·0) and T3 (0·69 ± 0·2 pmol/mg protein) in two hypothyroid subjects are consistent with the higher mean TBG concentration of 28 ± 5 μg/ml compared to the level in ten normal subjects (19·2 ± 1·8 μg/ml; P < 0.001). In two subjects with low normal TBG concentrations of 15 μg/ml, the T4 maximum specific binding of 9% was lower than found in normal subjects 16·6 ± 7·6%. We conclude that the methodology described previously and used in this study is invalid for measuring thyroid hormone nuclear receptor status in humans.
NUCLEAR BINDING AND CELLULAR METABOLISM OF THYROXINE IN A EUTHYROID PATIENT WITH HYPERTHYROXINAEMIA
Authors: KVETNY J.
Published: March 2008

The receptor mechanism and intracellular T4 deiodination were studied in a patient, who was euthyroid despite high T4 levels. Serum T3 and serum reverse T3 levels were normal and the TRH tests produced a normal rise in TSH. Protein binding capacities for T4 in serum were found to be normal. The T4 bound to a single set of binding sites in the patient's lymphocyte nuclei with a Ka which was depressed as compared with that of normals (Ka= 2·8 × 1010 l/mol) and a maximum specific binding capacity (MSBC = 1·9 fmol T4/10 μg DNA) which was increased as compared with normals (msbc = 1 × 10−16 mol/l T4/10 μg DNA). The cellular deiodination of T4 was found to be normal, whereas T3 accumulation was increased and the nuclear T3 concentration raised. In conclusion, these results suggest that in this patient the syndrome of peripheral tissue resistance to thyroid hormone action is due to a defect at the level of the nuclear receptor and not to a defective intracellular T4 to T3 conversion.
AN INTRACRANIAL METASTASIS FROM A PRL SECRETING PITUITARY TUMOUR
Authors: COHEN D. L. , DIENGDOH J. V. , THOMAS D. G. T. , HIMSWORTH R. L.
Published: March 2008

A 70‐year‐old man developed panhypopituitarism and was found to have hyperprolactinaemia and a locally invasive pituitary tumour. The visual fields were unaffected and therefore the patient was treated with hormone replacement only. After 3±5 years during which time the pituitary tumour had not enlarged further, the patient developed a mass in the left cerebello‐pontine angle. This mass was subsequently shown to be entirely separate from, but histologically identical to, the pituitary tumour and the cells of both contained PRL. Evidence was obtained to show that the tumour had spread by a vascular route. This is the second reported case of a malignant prolactinoma.
DOPAMINERGIC MODULATION OF TSH AND ITS SUBUNITS: IN VIVO AND IN VITRO STUDIES
Authors: COOPER D. S. , KLIBANSKI ANNE , RIDGWAY E. CHESTER
Published: March 2008

We have studied the effects of dopamine on the secretion of TSH and its subunits in vivo and in vitro. Four normal controls, seven patients with primary hypothyroidism, two patients with peripheral resistance to thyroid hormone (PRTH), and two patients with α‐secreting pituitary tumours underwent a 3‐h dopamine infusion (4 μg/kg/min). Serial blood samples were drawn for TSH, PRL, α, and TSH‐β subunit. In normal subjects, TSH fell from 2·1 ± 0·9 (±SE) to 0·7 ± 0·1 μU/ml (P < 0·05), and α declined from 1·5 ± 0·4 to 1·0 ± 0·1 ng/ml (P < 0·01). TSH‐β was at or slightly above the detection limits of the assay before and after dopamine. In hypothyroidism, basal serum TSH was 81 ± 14 μ/ml. With dopamine, TSH fell to 35 ± 8 μU/ml (P < 0·001), while α decreased from 3·2 ± 0·4 to 2·0 ± 0·3 ng/ml (P < 0·001). Serum TSH‐β also declined from 0·97 ± 0·06 to 0·57 ± 0·05 ng/ml (P 0·001). A similar fall in TSH and α was seen in the two patients with PRTH. In normals and hypothyroid patients, the percentage change in α concentration was significantly less than that observed for intact TSH. This is due presumably to the contribution of the gonadotrophs to the circulating α pool. TSH and TSH‐β were undetectable in the two pituitary tumour patients, and α declined only slightly in each patient after dopamine. The in vitro effects of dopamine were studied using cultured bovine anterior pituitary cells. Dopamine (10−4‐10−8 mol/l) did not change basal TSH, α, or TSH‐β release. However, dopamine at all doses significantly blunted TRH (10−7 mol/l)‐stimulated TSH and TSH‐β release, and blunted TRH‐mediated α release at the two highest dopamine doses. These data suggest that dopamine modulates both TSH and TSH subunit secretion. These effects may be exerted directly at the level of the thyrotroph.
THE PLACE OF PRL IN HUMAN LACTATION
Authors: MARTIN R. H.
Published: March 2008

Plasma PRL levels were measured during an episode of breast feeding in fourteen women on the eighth and 42nd post‐partum days. The results show that as lactation continues so the importance of absolute values of PRL diminishes, but the capability to secrete PRL in response to the suckling stimulus is maintained.
THE ACUTE AND LONG TERM EFFECT OF THE H2‐RECEPTOR ANTAGONISTS CIMETIDINE AND RANITIDINE ON THE PITUITARY‐GONADAL AXIS IN MEN
Authors: KNIGGE U. , DEJGAARD A. , WOLLESEN F. , INGERSLEV O. , BENNETT P. , CHRISTIANSEN P. M.
Published: March 2008

We have investigated the effect on the human pituitary–gonadal axis of the H2‐receptor antagonists cimetidine 300 mg and ranitidine 50, 100, and 200 mg by i.v. bolus, or treatment for 6 months with either cimetidine (1000 mg/day for 1·5 months followed by 400 mg/day for 4·5 months) or ranitidine (200–400 mg/day for 1·5 months followed by 100–200 mg/day for 4·5 months). Administration of the H2‐antagonists (i.v.) to normal men did not cause any release of LH, FSH, or testosterone. Long‐term treatment with cimetidine of duodenal ulcer patients caused a significant rise in basal LH (6 weeks) and FSH secretion (11 weeks). Following reduction of the cimetidine dose LH and later FSH returned to pre‐treatment values. However, despite reduction of the cimetidine dose, the LH and FSH responses to LHRH stimulation were still significantly higher after 6 months of treatment compared with pre‐treatment responses. No changes were found in basal or in LHRH stimulated testosterone or dihydrotestosterone secretion. Treatment with the more potent H2‐antagonist ranitidine did not cause any change in basal or in LHRH stimulated LH and FSH secretion. The effects on LH and FSH secretion observed during cimetidine treatment might therefore be caused by other mechanisms than blockade of H2‐receptors. It is possible that cimetidine, having anti‐androgen properties, blocks pituitary or hypothalamic androgen receptors.
CYCLE INITIATION IN AMENORRHOEA; THE EFFECT OF PROGESTERONE AND OESTROGEN ADMINISTRATION ON THE PULSATILE RELEASE OF GONADOTROPHINS
Authors: EL SHEIKH M. A. A. , MOLLOY B. G. , CHAPMAN C. , OAKEY R. E. , HANCOCK K. W. , GLASS M. R.
Published: March 2008

The modulation of pulsatile gonadotrophin release by endogenous ovarian steroids during the normal menstrual cycle may be involved in the initiation of the following menstrual cycle. The absence of this cyclical variation may, in some cases, be the cause of, or contribute to the cause of, amenorrhoea. To assess this the modulatory effect of gonadal steroid administration on the pulsatile release of gonadotrophins was studied in fourteen amenorrhoeic and four oligomenorrhoeic women. Pulsatility was assessed by samples collected at 10 min intervals during a 4 h morning period before and after treatment with either progesterone or micronized oestradiol or a sequential combination of both.

Ten patients with intact positive oestrogen‐gonadotrophin feedback responded to progesterone treatment by both a significant reduction in LH pulse frequency, from a mean of 4·1 to a mean of 2·1 pulses within the 4 h study period and an increase in pulse amplitude. Progesterone therapy did not affect mean LH concentrations but there was a significant reduction in mean FSH concentrations. In the eight patients with absence of positive feedback, none of the treatment regimes elicited significant changes in LH release. No definable FSH pulses were detected before or after treatment in either group.

Both the changes in LH and FSH concentrations and their release observed in this study, support the concept that cycle initiation may be related to a reduced pituitary exposure to LHRH associated with elevated progesterone concentration in the luteal phase of the cycle. This selectively induces FSH synthesis and storage. Release of this stored FSH may occur as a result of failure of the corpus luteum and falling progesterone concentrations.
SUPPRESSION OF RESIDUAL OESTROGEN PRODUCTION WITH AMINOGLUTETHIMIDE IN WOMEN FOLLOWING SURGICAL HYPOPHYSECTOMY OR ADRENALECTOMY
Authors: SAMOJLIK E. , SANTEN R. J. , WORGUL T. J.
Published: March 2008

In postmenopausal women with breast carcinoma, plasma and urinary oestrogens remain detectable following surgical adrenalectomy or hypophysectomy. These residual oestrogens could result from absorption of exogenous steroids, from endogenous production, or from a combination of these two sources. To determine whether endogenous production contributes to this oestrogen pool, we administered a potent steroidogenesis inhibitor, aminoglutethimide (AG), to women with breast carcinoma following hypophysectomy or adrenalectomy. Plasma and urinary oestrogens were measured with radioimmunoassays developed to provide appropriate sensitivity. In five women treated after initial hypophysectomy (hypox), plasma oestrone fell from 66·28 pg/ml (hypox) to 9·1 ± 2·4 pg/ml (hypox and AG) and oestradiol decreased from 8·3 ± 1·8 pg/ml to 2·5 ± 0·69 pg/ml. Similar decrements in urine oestrone (U‐E1) and ostradiol (U‐E2) were observed (U‐E1 hypox: 2·25 ± 0·71 μg/24 h and 0·071·0±015 μg/24 h hypox and AG; U‐E2 0·47 ± 0·12 μg/24 h hypox to 0·124 ± 0·015 hypox and AG, P<0·05 for all). Similar significant reductions in plasma oestrone and oestradiol were observed in four women treated with aminoglutethimide following surgical adrenalectomy. While the levels of urinary oestrogens also fell in these patients, the differences were not statistically significant. In response to the decrements in oestrogen levels induced by AG, 2/5 women in the post‐hypophysectomy group and 2/4 in the post‐adrenalectomy group experienced partial objective tumour regression. These observations indicated that the residual oestrogens produced after surgical adrenalectomy or hypophysectomy, even though made in small quantities, were nonetheless biologically active. We conclude that endogenous production of oestrogens in extragonadal and extra‐adrenal sites occurs after major surgical endocrine
CORTICOTROPHIN RELEASING FACTOR: RESPONSES IN NORMAL SUBJECTS AND PATIENTS WITH DISORDERS OF THE HYPOTHALAMUS AND PITUITARY
Authors: LYTRAS N. , GROSSMAN A. , PERRY L. , TOMLIN S. , WASS J. A. H. , COY D. H. , SCHALLY A. V. , REES L. H. , BESSER G. M.
Published: March 2008

Synthetic CRF‐41 has been given to 43 patients with hypothalamic, pituitary or adrenal diseases and contrasted with the responses in 20 normal subjects. In the normal subjects the mean increment in serum cortisol (± SE) was 276 ± 38 nmol/l; the increments showed a significant negative correlation with the basal serum cortisol levels (r= ‐0·56; P<0·02). The mean peak serum cortisol was 662 ± 34 nmol/1 and the mean peak corticosterone was 28·6 ± 3·8 nmol/1. There was a significant positive correlation between the peak serum corticosterone and cortisol concentrations (r= 0·84; P<0·0001). Dexamethasone pretreatment abolished the rise in cortisol in response to CRF‐41. The peak serum cortisol following CRF‐41 was not significantly different between the normal subjects and those patients with pituitary disease who had normal cortisol responses to insulin‐induced hypoglycaemia. However, in individual patients the peak cortisol levels induced by hypoglycaemia were greater than, but significantly correlated with, those induced by 100 μg of CRF‐41. Seven patients were ACTH deficient in response to hypoglycaemia, and of these six responded normally to CRF‐41. Only one of these patients had a lesion clearly originating in the hypothalamus; four had pituitary tumours with suprasellar extensions and the remaining patient had idiopathic GH and ACTH deficiency. Our data suggest that these patients have a functional defect of ACTH secretion due to the failure of CRF to reach the corticotroph. Of the four patients with pituitary‐dependent Cushing's disease who were on no treatment at the time of testing, three showed an exaggerated and one a normal response to CRF‐41. These normal or enhanced responses of hypercortisolaemic patients with Cushing's syndrome contrast with the complete inhibition of the responses to CRF‐41 in normal subjects given dexamethasone. In the treated patients with Cushing's syndrome
STUDIES OF THE ANDROGEN RECEPTOR IN DISPERSED FIBROBLASTS: INVESTIGATION OF PATIENTS WITH ANDROGEN INSENSITIVITY
Authors: EVANS B. A. J. , JONES T. R. , HUGHES I. A.
Published: March 2008

The practical application of a simple, reproducible androgen receptor assay using dispersed fibroblasts is described for the investigation of patients with the androgen insensitivity syndrome (AIS). The concentration of androgen receptors (Bmax) in genital skin fibroblasts derived from normal subjects is 814 ± 168 ×−18 moles/μg DNA (mean ± SD) and the binding affinity (Kd) is 0·91 ± 0·26 × 10±10M at 37°C, using [3H]‐5α‐dihydrotestosterone (DHT) as the labelled ligand. Studies in patients with phenotypic signs of complete or partial AIS showed either absent (receptor‐negative), decreased (receptor‐deficient) or normal/increased (receptor‐positive) specific binding of DHT to the receptor. In some mutant cell lines, there was evidence of thermolability and increased rate constant of dissociation of the androgen‐receptor complex, suggesting a possible structural abnormality of the receptor protein. This simple receptor assay can be used to delineate quantitative and qualitative defects of the androgen receptor in a significant number of patients with a wide spectrum of phenotypic abnormalities associated with androgen resistance.
MEASUREMENT OF FREE THYROXINE AND FREE TRIIODOTHYRONINE IN THYROTOXICOSIS AND HYPOTHYROIDISM
Authors: FRANKLYN J. A. , SHEPPARD M. C. , RAMSDEN D. B. , WILKINSON R. , HOFFENBERG R.
Published: March 2008

Free T4 and free T3 concentrations in thyrotoxic and hypothyroid patients at presentation differentiated those with thyroid disease from euthyroid control subjects and were closely correlated with T4/TBG ratio. A further group of thyrotoxic patients was followed serially during treatment with carbimazole. Measurements of free T4 and free T3 against closely reflected thyroid status with changes in the hormone measurements being paralleled by changes in T4/TBG ratio.
PLASMA SOMATOMEDIN ACTIVITY AFTER INJURY IN MAN AND ITS RELATIONSHIP TO OTHER HORMONAL AND METABOLIC CHANGES
Authors: FRAYN K. N. , PRICE D. A. , MAYCOCK P. F. , CARROLL S. M.
Published: March 2008

Plasma somatomedin activity was measured in 12 patients who had sustained non‐fatal musculo‐skeletal injuries. It was depressed for 2‐3 d after injury, but this depression bore no relationship to the catabolic response to injury which, as judged by urinary nitrogen excretion, was maximal at about one week. The depression of somatomedin activity may have been related to the high plasma cortisol concentrations observed during the first few days after injury. Plasma growth hormone concentrations were high acutely after injury but rapidly returned to normal. The changes in plasma somatomedin activity were thus unrelated to those in growth hormone, but were very similar to those in plasma insulin concentrations. A marked positive relationship was observed between plasma insulin concentrations and urinary nitrogen excretion, indicating unresponsiveness of protein metabolism to the normal anabolic effects of insulin. The study showed, however, that this was not as a result of low somatomedin activity.
ELEVATED SERUM THYROGLOBULIN AS A MANIFESTATION OF ACUTE HAEMORRHAGE INTO THE THYROID GLAND
Authors: KAWAMURA S. , KISHINO B. , TAJIMA K. , MASHITA K. , TARUI S.
Published: March 2008

Clinical observations and serial determinations of serum thyroglobulin (Tg) were made in five patients with acute haemorrhage into the thyroid gland. Fever, local pain and acceleration of erythrocyte sedimentation rate were minimal or were not observed, and serum T4 and T3 were normal. Although all patients showed an increase in serum Tg, this was most obvious in three subjects and it gradually decreased as the nodule became smaller. There was no correlation between the serum Tg concentration and the nodular size. Acute haemorrhage into the thyroid gland should be added as one of the causes to increase serum Tg concentrations.
EFFECTS OF THE GABAERGIC DRUG, SODIUM VALPROATE, ON THE PROLACTIN RELEASE EVOKED BY PHARMACOLOGICAL STIMULI IN NORMAL WOMEN
Authors: MELIS G. B. , FRUZZETTI F. , PAOLETTI A. M. , MAIS V. , BENEVENTI F. , TRIMARCHI G. , FIORETTI P.
Published: March 2008

Sodium valproate (DPA or Na‐dipropylacetate), an anticonvulsant drug activating the endogenous GABAergic system, was administered orally at the dose of 400 mg to seventeen normal women 1 h before intravenous injections with three drugs which stimulate prolactin (PRL) release: TRH (200 ųg bolus; six subjects); domperidone (5 mg bolus; six subjects); and sulpiride (5 mg bolus; five subjects). DPA pretreatment significantly blunted PRL response to both domperidone and sulpiride injections without affecting the PRL response to TRH. In particular, the quantitative PRL secretion (areas under curves) following domperidone and sulpiride tests appeared significantly reduced after DPA treatment in comparison to placebo (P < 0·02 and P <0·01 for domperidone and sulpiride respectively). These results indicate that the pharmacological enhancement of the endogenous GABAergic system by DPA may blunt PRL response to both central and peripheral dopamine receptor blockade. These observations suggest that a GABAergic pathway inhibiting PRL secretion at the hypothalamic level competes, at least in part, with the dopaminergic system. Conversely, the lack of any effect of DPA on PRL response to TRH seems to suggest that pituitary TRH receptors are independent of any GABAergic control.
SALMON AND HUMAN CALCITONIN‐LIKE PEPTIDES IN MAN
Authors: TOBLER P. H. , TSCHOPP F. A. , DAMBACHER M. A. , FISCHER J. A.
Published: March 2008

Calcitonin‐like peptides have been identified in the serum of normal subjects and of medullary thyroid carcinoma (MTC) patients. Using specific homologous radioimmunoassays (RIA) in combination with reversed‐phase high performance liquid chromatography and gel permeation chromatography under denaturing conditions, we have recognized major components which coeluted with human calcitonin‐(1–32), PDN‐21, a carboxyl‐terminal flanking peptide derived from the calcitonin mRNA sequence, and salmon calcitonin‐(1–32). An additional 12000 molecular weight peak possibly represents a human calcitonin‐PDN‐21 polyprotein. In both the human calcitonin‐(1–32) (normal value < 0·043 ngEq/ml; MTC 140·80 ngEq/ml, mean value±SEM) and the PDN‐21 (normal value <0·050 ngEq/ml; MTC 33·6±16·5 ngEq/ml) RIAs, serum levels were increased in MTC patients. Circulating levels of the salmon calcitonin‐like peptide were indistiguishable between normal subjects (0·038 ± 0·006 ngEq/ml) and MTC patients (0·037 ± 0·011 ngEq/ml).