bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF CALORIE RESTRICTION ON SERUM THYROID HORMONE BINDING PROTEINS AND FREE HORMONE IN OBESE PATIENTS
Authors: MOREIRA‐ANDRES M. N. , BLACK E. G. , RAMSDEN D. B. , HOFFENBERG R.
Published: March 2008

In ten obese euthyroid subjects the concentration of thyroxine (T4), tri‐iodothyronine (T3) and reverse T3 (rT3) were assayed in serum and of T4 and T3 in urine before and after 2 weeks of 2·1 MJ (500 Kcal) per day diet. Mean serum T4 was unchanged, while T3 decreased and rT3 increased. Urinary excretion of both T4 and T3 decreased after diet. In six subjects the concentrations of serum thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA) and albumin were measured before and after diet. Free T4 and T3 were calculated using a formula based on measured concentration of hormones and their binding proteins. Calorie restriction resulted in a significant decrease in TBG and a greater decrease in TBPA, while albumin was unchanged. Calculation of free hormones showed a fall in absolute free T3 and rise in percentage free T3, but a rise in both absolute and per cent free T4. Our data indicate a selective effect of calorie restriction on the concentrations of TBPA and to a lesser extent TBG and confirm previous reports of altered peripheral monodeiodination of T4. Decreased urinary excretion of T4, despite a calculated increase of free T4 in serum, suggests intrarenal metabolic adjustment, the mechanism of which awaits elucidation.
11‐DEOXYCORTISOL IN AMNIOTIC FLUID: PRENATAL DIAGNOSIS OF CONGENITAL ADRENAL HYPERPLASIA DUE TO 11 β‐HYDROXYLASE DEFICIENCY
Authors: SCHUMERT ZEWIJAH , ROSENMANN ADA , LANDAU HEDI , RÖSLER ARIEL
Published: March 2008

The mean control level of 11‐deoxycortisol as determined by radioimmunoassay in eighty‐one human amniotic fluid samples was 1·20 ± 0·07 ng/ml. Markedly elevated levels were found at term in amniotic fluid of two pregnancies with fetuses affected with 11 β‐hydroxylase deficiency, congenital adrenal hyperplasia (135·0 and 64·0 ng/ml respectively) as well as in the maternal serum of one of these cases (28·0 ng/ml). It is suggested that the determination of 11‐deoxycortisol in amniotic fluid be a prenatal diagnostic test for 11 β‐hydroxylase deficiency congenital adrenal hyperplasia.
INTRA‐AMNIOTIC OR INTRAVENOUS INJECTION OF DEHYDROEPIANDROSTERONE SULPHATE: SIMULTANEOUS CHANGES IN STEROID LEVELS IN AMNIOTIC FLUID AND MATERNAL SERUM
Authors: YLIKORKALA O. , KAUPPILA A. , REINILÄ M. , TUIMALA R.
Published: March 2008

Levels of unconjugated oestradiol‐17β (E2) and testosterone (T) and total oestriol (E3) were measured hourly for 6 h after intra‐amniotic (i.a.) (100–200 mg) or intravenous (i.v.) (100 mg) injection of dehydroepiandrosterone sulphate (DHEA‐S) in a series of twenty‐six women with mid‐trimester abortion. Amniotic fluid E2 and T levels were elevated significantly 1–6 h after the i.a. injection of DHEA‐S, while the E3 level in amniotic fluid did not change. The i.a. administration also induced significant rises in serum E2 and T levels between 1 and 6 h and in the serum E3 level between 2–6 h. The i.v. injection of DHEA‐S was accompanied by significantly elevated serum levels of E2 and T, while the E3 concentration remained unchanged. It appears that following maternal i.v. administration or an amniotic fluid injection, DHEA‐S is rapidly converted to E2 and T, and these accumulate in both the maternal circulation and the amniotic fluid. E3, however, is formed only after i.a. administration of DHEA‐S, and is selectively transported to the maternal blood.
IMMUNOREACTIVE SOMATOSTATIN CHANGES DURING INSULIN‐INDUCED HYPOGLYCAEMIA AND OPERATIVE STRESS IN MAN
Authors: WASS J. A. H. , PENMAN ERICA , MEDBAK S. , DAWSON A. M. , TSIOLAKIS D. , MARKS V. , BESSER G. M. , REES LESLEY H.
Published: March 2008

Little is currently known about the factors controlling somatostatin secretion. A radioimmunoassay has been developed that is sufficiently specific and sensitive to be used for physiological studies of circulating levels in man. During insulin‐induced hypoglycaemia a rise in plasma somatostatin was seen in each of ten subjects studied. Although this paralleled the rise in circulating glucagon and growth hormone, no individual relationships were found either between these variables or to any change in cortisol or insulin C‐peptide. In contrast no rise in somatostatin was seen during surgical stress. Thus, contrary to expectation, circulating somatostatin levels can be altered by metabolic stimuli. It seems likely that this peptide may serve an endocrine as well as a paracrine role since its modulating effects may occur not only near to but also at a distance from the site of secretion. It is not yet clear whether the somatostatin measured comes from the hypothalamus, any other part of the central nervous system or the gastrointestinal tract.
TWENTY‐FOUR HOUR PROFILES OF SERUM PROLACTIN DURING MALE PUBERTY WITH AND WITHOUT GYNAECOMASTIA
Authors: LARGE D. M. , ANDERSON D. C. , LAING I.
Published: March 2008

Twenty‐four hour profiles of circulating prolactin have been documented in eight boys with simple delayed puberty, eleven with gynaecomastia, three of whom were retested following its spontaneous resolution, and two normal adult men. Mean 24 h prolactin levels in four boys with delayed puberty and ten with gynaecomastia exceeded the mean levels for the two adult men. A sleep‐associated rise in prolactin levels occurred at all stages of puberty irrespective of the presence or absence of gynaecomastia, and in some subjects peaks also occurred during the daytime. Boys with gynaecomastia had higher 24 h mean levels of prolactin (P < 0·05), higher daytime levels (P < 0·05) and higher sleep‐associated levels (P < 0·05) than did control subjects. These were not related to the degree or duration of the gynaecomastia, but 24 h mean levels of prolactin and oestradiol were positively correlated. In one subject who had had transient galactorrhoea, high levels of circulating prolactin, oestrone and oestradiol fell following spontaneous resolution of the gynaecomastia. We believe that oestrogen: androgen imbalance during the daytime is the major cause of pubertal gynaecomastia, with hyperprolactinaemia (which may cause galactorrhoea) sometimes occurring as a response to relative hyperoestrogenaemia.
PITUITARY AND TESTICULAR FIBROSIS IN ASSOCIATION WITH RETROPERITONEAL FIBROSIS
Authors: GROSSMAN A. , GIBSON J. , STANSFELD A. G. , BESSER G. M.
Published: March 2008

A patient is discussed who originally presented with retroperitoneal fibrosis, and subsequently developed both pituitary fibrosis and testicular fibrosis. Replacement of testicular tissue by fibrosis has not previously been described in this condition, while we have only been able to find a single previous report of pituitary fibrosis. Fibrous replacement of testis and pituitary should be considered as a further manifestation of the midline fibrosing syndrome.
FAMILIAL MALE PSEUDOHERMAPHRODITISM DUE TO DEFICIENCY OF 5α‐REDUCTASE
Authors: SAVAGE M. O. , PREECE M. A. , JEFFCOATE S. L. , RANSLEY P. G. , RUMSBY G. , MANSFIELD M. D. , WILLIAMS D. I.
Published: March 2008

Two brothers of Greek Cypriot origin, karyotype 46 XY, aged 17 and 19 years were brought up as females because of predominantly female external genitalia with clitoromegaly and urogenital sinus. At puberty there was genital masculinization with testicular enlargment and descent and development of male musculature and body habitus without gynaecomastia. Both subjects acquired male gender identity and changed from a female to a male gender role. The internal genitalia were normally formed with an ejaculate containing mature spermatozoa. In both subjects plasma testosterone levels were slightly elevated, dihydrotestosterone was in the low normal range and the plasma testosterone to dihydrotestosterone ratio was markedly elevated. Plasma oestrogens were normal whereas SHBG binding capacity was elevated. The urinary 5β‐aetiocholanolone to 5α‐androsterone ratios were elevated compared with normal subjects. Basal plasma LH was normal but, the LH response to LHRH was exaggerated and basal and peak plasma levels of FSH were elevated. 5α‐reductase activity in genital skin homogenates was higher when androstenedione was used as a substrate, compared with testosterone, suggesting a decreased affinity of the enzyme for testosterone. The clinical and hormonal features in the two siblings are consistent with an impaired peripheral conversion of testosterone to dihydrotestosterone due to deficiency of the enzyme 5α‐reductase.
IMMUNOHISTOCHEMICAL DEMONSTRATION OF LUTEINIZING HORMONE‐RELEASING FACTOR‐LIKE MATERIAL IN HUMAN SYNCYTIOTROPHOBLAST AND TROPHOBLASTIC TUMOURS
Authors: SEPPÄLÄ M. , WAHLSTRÖM T. , LEHTOVIRTA P. , LEE J.N. , LEPPÄLOUTO J.
Published: March 2008

Luteinizing hormone‐releasing factor (LRF)‐like immunoreactivity was demonstrated by a three layer bridge immunoperoxidase technique in the syncytiotrophoblast of early human placenta, hydatidiform mole and choriocarcinoma. Anti‐LRF antiserum was prepared by immunizing rabbits with synthetic LRF coupled to bovine serum albumin (BSA). The immunoreactive site of LRF reacting with the antiserum resided between residues Tyr5 and Gly10‐NH2. Syncytiotrophoblast cells of the normal placenta from the first half of pregnancy and trophoblastic tumours, showed staining with anti‐LRF antiserum after solid phase immuno‐adsorption with Sepharose‐coupled BSA. Adjacent control sections showed no staining when prepared with anti‐LRF antiserum after immunoadsorption with a Sepharose‐coupled LRF‐BSA conjugate. The finding of LRF‐like material in the placenta prompted us to examine the effect of exogenous LRF on the circulating levels of placental proteins and protein hormones synthesized by the syncytiotrophoblast. Serum levels of chorionic gonadotrophin, pregnancy‐specific beta‐l‐glycoprotein, placental protein five, and placental lactogen remained unaltered for 2 h after an intravenous bolus of LRF (100–300 μg) to ten pregnant volunteers admitted for legal abortion between 8 and 18 weeks of gestation. The significance of LRF‐like material for the endocrinology of the normal and malignant trophoblast remains to be elucidated.
THE CAUSES OF LOW OESTROGEN EXCRETION IN PREGNANCY: THE DEVELOPMENT OF DIAGNOSTIC METHODS FOR THE ANTENATAL DETECTION OF FAMILIAL CONGENITAL ADRENOCORTICAL HYPOPLASIA
Authors: HARKNESS R. A. , TAYLOR N. F. , BOWMAN P. R. , GORDON H. , CUMMINS M. , VALMAN H. B.
Published: March 2008

A pregnancy producing a boy with congenital adrenocortical hypoplasia is described. Consistently low oestrogen excretion, less than 10 μmol/24 h, was not associated with any anatomical abnormality or diminished growth of the fetus as judged by ultrasound examination. Fetoplacental steroid sulphatase deficiency was excluded by finding normal maternal excretion of oestrogen precursors, the 3β‐hydroxy‐5‐ene steroid sulphates. Generalized adrenocortical hypoplasia was proven in the baby boy by analysis of steroid metabolites excreted in his urine. He suffered from salt loss and progressive jaundice. Both were responsive to gluco‐ and mineralo‐corticoid replacement therapy. It is suggested that amniocentesis may be required for the antenatal diagnosis of congenital adrenocortical hypoplasia.
DECREASED LH RESPONSE TO THE SECOND OF CONSECUTIVE DAY LUTEINIZING HORMONE RELEASING HORMONE (LHRH) INFUSIONS AMONG PATIENTS WITH CONSTITUTIONAL DELAY OF PUBERTY: A PHENOMENON OF PUBERTAL MATURATION?
Authors: SCHNEIDER JILL , LEE PETER A.
Published: March 2008

Consecutive day LHRH stimulation by continuous infusion has been used to evaluate pituitary reserve. Different responses on the 2 days were not present among non‐pubertal hypopituitary patients, pubertal growth hormone deficient patients or adult males. However, patients with constitutionally delayed puberty demonstrated a greater serum LH response on day 1 than day 2. Urinary LH responses suggest a similar but not statistically significant pattern. This response may be a normal phenomenon of puberty or may represent part of the reason for constitutionally delayed puberty.
EVIDENCE FOR DOPAMINE AS AN INHIBITOR OF VASOPROTEIN RELEASE IN MAN
Authors: LIGHTMAN S. L. , FORSLING MARY
Published: March 2008

The effect of dopamine on vasopressin release was studied by the infusion of L‐Dopa, a dopamine precursor that crosses the blood‐brain barrier. L‐Dopa suppressed resting levels of vasopressin and inhibited the rise of vasopressin produced by head‐up tilt. Carbidopa, a decarboxylase inhibitor that does not cross the blood‐brain barrier blocked the action of L‐Dopa. These results suggest that dopamine inhibits the release of vasopressin, either by an action at pituitary level or at the median eminence of the hypothalamus.
AN ASSESSMENT OF GLUCOSE INTOLERANCE IN ACROMEGALY AND ITS RESPONSE TO MEDICAL TREATMENT
Authors: WASS J. A. H. , CUDWORTH A. G. , BOTTAZZO G. F. , WOODROW J. C. , BESSER G. M.
Published: March 2008

The prevalence of abnormal carbohydrate tolerance has been assessed in sixty‐nine acromegalic patients using six different criteria for the definition of diabetes mellitus. Family history, HLA status and the incidence of pancreatic islet cell antibodies have been documented and the effect of 3 months therapy with bromocriptine on oral glucose tolerance has been assessed in sixty‐one patients.

Thirteen patients (18–8%) had clinical diabetes and a total of twenty‐six patients (377%) had asymptomatic diabetes as defined by the British Diabetic Association criteria of 1964. Implementing the 1978 recommendations of the British Diabetic Association, 130% were defined as diabetic. The incidence of a positive family history of diabetes was the same in the diabetic and non‐diabetic acromegalics. There was no disturbance in respect of any of the HLA antigens when this was considered for the number of specificities tested for, and no patient had pancreatic islet cell antibodies.

On treatment with bromocriptine, there was a highly significant improvement in the glucose tolerance of both the diabetic (P <0.0001) and the non‐diabetic (P < 0.005) acromegalics. However, in the group of eleven patients with no reduction of serum growth hormone on treatment, no improvement in glucose tolerance was seen.

It is concluded that bromocriptine, by directly reducing serum growth hormone, has a significant effect on carbohydrate metabolism in acromegaly, irrespective of the initial level of glucose tolerance.
ANTIDIURETIC HORMONE IMMUNOACTIVITY IN TUMOUR TISSUE FROM PATIENTS WITH BRONCHOGENIC CARCINOMA: WITH AND WITHOUT HYPONATRAEMIA
Authors: KELLY P. , MORTON J. J.
Published: March 2008

Antidiuretic hormone (ADH) immunoactivity (28–164 pg/mg wet weight) was detected in the tumour tissue of only three out of thirty‐two patients with carcinoma of the bronchus. All three patients had small oat‐cell tumours and two had persistent hyponatraemia prior to death. Serum sodium was not obtained in the third patient. Serum sodium was normal in the remaining twenty‐nine patients with undetectable ADH immunoactivity.
PLASMA ALDOSTERONE RESPONSE TO ANGIOTENSIN 11 AND POTASSIUM CHLORIDE INFUSIONS IN HYPOPITUITARY PATIENTS
Authors: LÓPEZ J. M. , RODRIGUEZ J. A. , MARUSIC ELISA T.
Published: March 2008

The acute adrenal response to potassium chloride and angiotensin II (A II) infusions was studied in hypopituitary patients and compared with normal subjects. The peripheral plasma levels of aldosterone (PAC), cortisol (F), potassium (K), and plasma renin activity (PRA), were measured at 09.00 h and after 60 and 120 min of infusion. All subjects were recumbent and under balance conditions, receiving a daily dietary intake of 180 mmol of sodium and 80 mmol of potassium. Basal PAC in hypopituitary patients was not significantly different from that observed in the control group. Both normal and hypopituitary patients respond to A II infusion with significant increments. Under potassium chloride stimulus the PAC response in hypopituitary patients was only observed when cortisol (20 mg) was given 2 h prior to the infusion. When cortisol replacement was omitted the response to KCl was not detected. These results suggest a permissive role of cortisol on glomerulosa response to potassium.
THE EFFECT OF OXPRENOLOL, ACEBUTOLOL AND PROPRANOLOL ON THYROID HORMONES IN HYPERTHYROID SUBJECTS
Authors: JONES M. K. , JOHN R. , JONES G. R.
Published: March 2008

Serum thyroid hormone levels were measured before and during 10 days treatment with acebutolol (400 mg/day), oxprenolol (160 mg/day) and propranolol (160 mg/day) in eighteen hyperthyroid patients. A significant change in thyroid hormone concentrations was seen only in the group treated with propranolol. Propranolol should be used in preference to beta‐adrenoreceptor blocking drugs with partial agonist activity, in the treatment of hyperthyroidism.
PERICARDIAL EFFUSION IN HYPOTHYROIDISM
Authors: HARDISTY C. A. , NAIK D. R. , MUNRO D. S.
Published: March 2008

Thirty‐nine patients with untreated hypothyroidism have been examined using echocardiography for the presence of a pericardial effusion. Effusions were present in twelve patients who tended to be more severely hypothyroid. Plasma creatine phosphokinase and lactate dehydrogenase levels were higher in the presence of an effusion. Nine were reinvestigated during thyroxine replacement therapy and the effusions did not disappear until thyroid function tests had returned to normal. There were no specific electrocardiographic changes associated with the presence of an effusion which could be associated with a normal cardiac silhouette on a standard P.A. chest X‐ray.
FAILURE OF BOMBESIN TO ALTER ANTERIOR PITUITARY HORMONE SECRETION IN MAN
Authors: MORLEY J. E. , VARNER A. A. , MODLIN I. M. , CARLSON H. E. , BRAUNSTEIN G. D. , WALSH J. H. , HERSHMAN J. M.
Published: March 2008

Because of the stimulating effects of bombesin on growth hormone and prolactin secretion in the rat, we have studied the effects of bombesin infusions on anterior pituitary hormone secretion in man. Biological activity of the infused bombesin was confirmed by observing a brisk increase in serum gastrin concentrations and in gastric acid secretion during the lowest dose of bombesin infused. We could demonstrate no effect of bombesin in doses from 200 to 600 pmol.kg−1.h−1 on growth hormone, prolactin, thyrotrophin, luteinizing hormone and follicle stimulating hormone.
PLASMA ANGIOTENSIN II AND THE CONTROL OF DIABETES MELLITUS
Authors: SULLIVAN P. A. , GONGGRIJP HELGA , CROWLEY M. J. , FERRISS J. B. , O'SULLIVAN D. J.
Published: March 2008

Plasma angiotensin II was measured in twenty patients with poorly controlled non‐ketotic diabetes mellitus, and again when blood glucose control improved. Plasma angiotensin II fell significantly with improved control, both when patients were supine and fasting overnight, and when studied after 4 h ambulation. The change occurred with improved short‐term and longer‐term control. It is concluded that the degree of blood glucose control is important when assessing the renin‐angiotensin system in diabetic patients.
OESTROGEN DYNAMICS IN ADRENAL VENOUS EFFLUENTS IN CONGENITAL VIRILIZING ADRENAL HYPERPLASIA
Authors: WAJCHENBERG B. L. , GOLDMAN J. , KYAN T. S. , ACHANDO S. S. , THOMSEN Y. L. , LIMA S. S.
Published: March 2008

Four patients with untreated congenital virilizing adrenal hyper‐plasia (partial 21‐hydroxylase deficiency) were studied by bilateral adrenal vein catheterization. Simultaneous right and left adrenal and peripheral blood samples were collected for determination of oestrone (E1) and oestradiol (E2. The concentrations of both were higher in the adrenal effluents than in the peripheral blood samples, indicating their secretion by the adrenals. All patients were also studied during a sequential test of suppression (0.5 h after i.v. administration of 4 mg dexamethasone) and stimulation (5 min after i.v. administration of 250 μg ACTH 1–24; Synacthen). Mean peripheral E2 concentrations did not change significantly whereas E1 increased above control levels after stimulation. In contrast, suppression of adrenal venous blood concentrations with dexamethasone, and stimulation with ACTH, was demonstrated for every patient. The results indicate that in congenital adrenal hyperplasia the adrenal glands secrete significant amounts of E1 and E2.
FAILURE OF NALOXONE TO ALTER EXERCISE‐INDUCED GROWTH HORMONE AND PROLACTIN RELEASE IN NORMAL MEN
Authors: MAYER G. , WESSEL J. , KÖBBERLING J.
Published: March 2008

Growth hormone and prolactin levels during standardized exercise tests were measured in ten normal male volunteers, with and without previous intravenous administration of 4 mg naloxone. No significant influence of naloxone on hormone release could be observed. The lack of effect indicates that an opioid pathway is not involved in exercise‐induced growth hormone and prolactin release in humans, in contrast to that in rats.
ABNORMAL PANCREATIC POLYPEPTIDE RESPONSE TO ORAL GLUCOSE LOADING IN DIABETES MELLITUS
Authors: TSUDA K. , SAKURAI H. , SEINO Y. , SEINO S. , TANIGAWA K. , KUZUYA H. , MORI K. , IMURA H.
Published: March 2008

In order to elucidate the abnormality of pancreatic polypeptide (PP) secretion in diabetes mellitus, basal plasma PP levels and their response to oral glucose loading were measured in normal subjects and diabetic patients. Fasting plasma PP levels were significantly elevated in patients with diabetes mellitus. Oral administration of 50g of glucose elicited an exaggerated rise in plasma PP in diabetic patients as compared with the response in normal subjects. This exaggerated PP response to oral glucose loading was partially but significantly improved after the treatment, with an augmented response of plasma insulin. These results indicate the existence of abnormal PP secretion in diabetes mellitus which is possibly caused by metabolic or endocrine derangements.
URINARY PROSTAGLANDINS FOLLOWING FRUSEMIDE TREATMENT AND SALT DEPLETION IN NORMAL SUBJECTS AND SUBJECTS WITH DIABETIC HYPORENINAEMIC HYPOALDOSTERONISM
Authors: FARESE R. V. , RODRIGUEZ‐COLOMÉ M. , O'MALLEY B. C.
Published: March 2008

Urinary immunoreactive PGA and PGE, plasma and urinary aldosterone, and plasma renin activity (PRA) were determined in eleven control subjects and four patients with diabetic hyporeninaemic hypoaldosteronism (HH) before and during 4 days of sodium chloride restriction and frusemide administration. Aldosterone and PRA increased steadily in control subjects, but not in patients with HH. Increases in urinary PGA and PGE were observed during volume depletion. The basal levels and increases observed were comparable in both groups. The apparently normal stimulation of PGA and PGE in subjects with diabetic HH suggests that this syndrome is not associated with abnormal prostaglandin metabolism, despite the fact that drug‐induced abnormalities of the latter may precipitate or aggravate the clinical syndrome in susceptible individuals. The increase in PGA and PGE following frusemide treatment and salt depletion supports the possibility of a relationship between renal prostaglandin metabolism, frusemide‐induced natriuresis and/or renin secretion. While the nature of this relationship remains obscure, the increases in PGA and PGE in the absence of increases in renin‐angiotensin levels in subjects with HH suggests that these changes are not due to activation of the renin‐angiotensin system.
PITUITARY FUNCTION IN NORMOPROLACTINAEMIC INFERTILE MEN RECEIVING BROMOCRIPTINE
Authors: GLATTHAAR C. , DONALD R. A. , SMITH R. , McRAE C. U.
Published: March 2008

A double blind trial of bromocriptine 7–5 mg daily versus placebo was carried out in ten infertile men. Pretreatment basal plasma prolactin, thyroid stimulating hormone (TSH) testosterone and luteinizing hormone (LH) concentrations were normal, but plasma follicle‐stimulating‐hormone (FSH) was raised in four individuals. After 4 months treatment with bromocriptine a significant fall in plasma prolactin was observed (P<0.01), both under basal conditions and following thyroid stimulating hormone releasing hormone (TRH). Basal plasma gonadotrophin, testosterone and thyroid stimulating hormone (TSH) concentrations did not alter. No change in sperm density, volume or motility was noted. However an apparent fall in the peak plasma LH (but not FSH) response to gonadotrophin releasing hormone (LHRH) was observed in patients receiving bromocriptine. This reduction in plasma LH responsiveness was significant when compared with the baseline response (P < 0.05) but failed to reach significance when compared with the placebo response. It is concluded that prolonged bromocriptine therapy in normoprolactinaemic men does not suppress FSH secretion, and any reduction in plasma LH responsiveness to LHRH is not accompanied by a significant fall in plasma testosterone.
OESTRONE SULPHATE IN PLASMA FROM POSTMENOPAUSAL WOMEN AND THE EFFECTS OF OESTROGEN AND ANDROGEN THERAPY
Authors: TOWOBOLA O. A. , CRILLY R. C. , OAKEY R. E.
Published: March 2008

The concentration of oestrone sulphate in peripheral plasma from postmeno‐pausal women was investigated using a method which involved extraction of the conjugate, which was then hydrolysed with acid, and determination (by radioimmunoassay) of the purified oestrone fraction obtained. The concentration of unconjugated oestrone in the same plasma samples was also measured. Postmenopausal women had concentrations of oestrone sulphate in plasma (1.1 ± 0.36 nmol/1, mean ± SD, n = 39) similar to those found in women in the follicular phase of the menstrual cycle and less than those found in males (3.2 ± 0.61 nmol/1, n= 21). The mean ratio of the concentration of oestrone sulphate to that of oestrone in plasma from postmenopausal women (7.9 ± 3.3) was significantly lower (P < 0.001, t test) than the mean ratio in men (19.8 ± 3.8). Treatment with conjugated oestrogens, oestradiol in a cream, oestradiol valerate or ethinyl oestradiol, increased the concentration of oestrone sulphate in the peripheral circulation. In contrast, chronic corticosteroid therapy reduced the level of oestrone sulphate (0.5 ± 0.11 nmol/1, n = 10) but this was partly restored (to 0.7 ± 0.13 nmol/1) by concomitant oral dehydroepiandrosterone. Ingestion of piperazine oestrone sulphate (Harmogen, 1.5 mg) by three fasting postmenopausal women was followed 4 h later by oestrone sulphate concentrations five to ten times those found at midcycle.
THERAPY OF PRIMARY HYPOTHYROIDISM WITH L‐TRIIODOTHYRONINE: DISCORDANT CARDIAC AND PITUITARY RESPONSES
Authors: RIDGWAY E. C. , COOPER D. S. , WALKER HARRIET , DANIELS G. H. , CHIN W. W. , MYERS G. , MALOOF FARAHE
Published: March 2008

Cardiac systolic time intervals were studied in ten patients with primary hypo‐thyroidism before and during therapy with increasing doses of oral L‐triiodo‐thyronine (L‐T3). Therapy was increased sequentially from 10, 20, 25 to 50 μg of L‐T3 daily on a monthly basis. On L‐T3, 20 to 25 μg/day, cardiac systolic time intervals and other peripheral responses to thyroid hormone including serum cholesterol concentration, serum creatine phosphokinase (CPK) activity, and basal metabolic rate had normalized. However, serum thyrotrophin (TSH) levels and peak TSH responses to thyrotrophin‐releasing hormone (TRH) remained elevated on these doses of L‐T3. As the dose of L‐T3 was increased from 20 to 50 μg/day, mean basal serum TSH levels decreased from 55 to 16 μu/ml, and the peak TSH response to TRH decreased from 243 to 58 μu/ml (P < 0.001) while systolic time intervals did not decrease further. Changing to L‐thyroxine (L‐T4) therapy at this point resulted in further suppression of TSH secretion, without significantly altering systolic time intervals or the other peripheral responses to thyroid hormone. These data suggest (a) that some biological responses to thyroid hormone were normalized on lower doses of L‐T3 than were required to normalize TSH secretion, and (b) that higher doses of L‐T3 or substituting L‐T4 therapy could suppress TSH secretion further without altering the other peripheral responses to thyroid hormone.
METABOLIC ASPECTS OF THE CALORIGENIC EFFECT OF THYROID HORMONE IN MAMMALS
Authors: SESTOFT L.
Published: March 2008

The increased BMR in hyperthyroidism may be accounted for by the use of chemical energy for metabolic processes and work. Major contributors are the heart work and futile cycling of FFA into triglyceride in adipose tissue, whereas gluconeogenesis in liver and the maintenance of sodium and potassium concentration gradients across the plasma membranes are unlikely to play any significant role. Information on the use of energy for protein turnover and urea production is lacking. The rate of oxygen uptake is not increased in the brain, spleen and testis. The main metabolic fuel seems to be free fatty acid.

The mechanism which enables the hyperthyroid tissue to maintain normal concentrations of ATP, ADP and inorganic phosphate, (Pi) despite an increased turnover of energy‐rich phosphates, is not fully elucidated. However, ultimately the increased rate of oxygen uptake in hyperthyroidism seems to rely upon an increased capacity for the transport of cytosolic ADP and Piinto mitochondria. The transport capacity is increased by an increased area of the mitochondrial membrane per g tissue and by a change in the kinetics of translocation of substrates for oxidative phosphorylation. Other transport processes across the mitochondrial membrane are also changed by hyperthyroidism, e.g. long chain fatty acid transport via carnitine acyl transferase, and oxaloacetate transport via substrate shuttles.
EFFECT OF DOPAMINE INFUSION ON SERUM PROLACTIN CONCENTRATION IN NORMAL AND HYPERPROLACTINAEMIC SUBJECTS
Authors: RESCHINI E. , FERRARI C. , PERACCHI M. , FADINI R. , MESCHIA M. , CROSIGNANI P. G.
Published: March 2008

The serum prolactin response to intravenous dopamine infusion (5μg.kg−1 min−1) was measured in twenty‐one healthy subjects, in seven hyperprolactinaemic patients without evidence of a pituitary tumour, and in twenty‐one patients with prolactinomas. Mean serum prolactin values were significantly suppressed in all three groups, without any significant difference between the degree of suppression. A decrease of serum prolactin to below 50% of basal values occurred in fifteen healthy subjects, in four patients without evidence of pituitary tumour, and in fourteen patients with prolactinomas. These findings demonstrate that most human prolactin‐secreting pituitary adenomas are normally suppressible by exogenously administered dopamine and that dopamine infusion is not able to distinguish between tumorous and non‐tumorous hyper‐prolactinaemia. Since intravenously infused dopamine is believed to inhibit prolactin secretion by acting at pituitary level, it is suggested that a normal functioning of pituitary dopamine receptors is maintained in most human prolactinomas.
EVALUATION OF TWO INHIBITORY TESTS (NOMIFENSINE AND L‐DOPA + CARBIDOPA) FOR THE DIAGNOSIS OF HYPERPROLACTINAEMIC STATES
Authors: MORIONDO PAOLA , TRAVAGLINI P. , NISSIM MARINA , FAGLIA G.
Published: March 2008

It has been reported that administration of nomifensine (Nom) or of L‐dopa + carbidopa (L‐dopa + Carb) potentiates central dopaminergic tonus, resulting in decreased prolactin (PRL) secretion. It has been proposed that these drugs would help to discriminate patients with PRL‐secreting pituitary tumours from those with so‐called ‘functional’ hyperprolactinaemia.

In this study, oral Nom (200 mg) was given to forty‐three hyperprolactinaemic patients and L‐dopa + Carb (50 mg Carb every 6 h for four doses followed by L‐dopa 100 mg and Carb 35 mg) to thirty of them and both treatments to ten normal subjects. The hyperprolactinaemic patients were divided into four clinical groups. Group A, twenty patients with proven PRL‐secreting pituitary tumours; Group B, thirteen women with elevated PRL levels (<100 ng/ml) without any radiological evidence of a pituitary tumour (hyperprolactinaemia of unknown aetiology or ‘functional’ hyperprolactinaemia); Group C, four women with polycystic ovarian disease and mildly elevated serum PRL; Group D, six patients with various other disorders associated with hyperprolactinaemia.

PRL levels decreased in the normal controls below the basal values by 61.3%±6.2 (SEM) after Nom and 77.6%± 4.2 after L‐dopa + Carb. Decreases in serum PRL of at least 50% (in three consecutive determinations) were found in group A in 20% of patients after Nom and in 25% after L‐dopa + Carb; in group B in 15% and 40% of cases; in most of the hyperprolactinaemic women in group C; and some in group D.

In conclusion, these two treatments did not discriminate between tumorous and non‐tumorous causes of PRL hypersecretion.
GRAVES' DISEASE AND HLA: CLINICAL AND EPIDEMIOLOGIC ASSOCIATIONS
Authors: FARID N. R. , STONE E. , JOHNSON G.
Published: March 2008

Correlation between clinical and epidemiological features of Graves' disease and HLA were sought in 175 patients, eighty‐three of whom were typed for HLA DR antigens. The relative risks (x) conferred by HLA‐B8 and DR3 were 3.1 and 5–7 respectively (P<0.0005 uncorrected). The disease occurred at an earlier age in HLA‐DR3 positive patients compared to negative patients (P<0.005 in females> and <30‐years‐old). Eighty‐four out of ninety‐two patients could specify the season of onset of hyperthyroidism; an excess of HLA‐B8 positive patients in the summer and a lack of these in the spring and autumn was found. No associations between B8 and exophthalmos and/or soft tissue eye changes were observed. However, significant associations between exophthalmos and either exophthalmos and/or soft tissue changes were found with DR3 (x=3.6 and 3.8 respectively). HLA‐DR3 positive patients were found to be more resistant to radioiodine therapy than patients negative for these antigens. No heterogeneity in the distribution of HLA antigens was found when the following indices were examined: sex, goitre size, severity of disease, pretibial myxoedema, antecedent psychological disorder, consumption of oral contraceptives, family history of Graves' disease or thyroid antibody titre. HLA does not appear to distinguish subvariants of Graves' disease, rather it influences the susceptibility to disease and its persistence once it becomes clinically manifest.
THE EFFECT OF FENCLOFENAC ON THYROID FUNCTION TESTS IN VIVO AND IN VITRO
Authors: RATCLIFFE WENDY A. , HAZELTON R. A. , THOMSON J. A. , RATCLIFFE J. G.
Published: March 2008

Clinically euthyroid patients on long term maintenance therapy with the non‐steroidal anti‐inflammatory drug fenclofenac (Flenac) show an unusual and abnormal pattern of serum thyroid function tests. In all twelve patients studied, total T4 concentrations were grossly subnormal (mean 28.4±9.9 (SD) nmol/1 and total T3 levels low‐normal (mean 1.4 ± 0.3 (SD) nmol/1), whereas rT3 (mean 0.36 ± 0.06 (SD) nmol/1) and basal TSH levels (mean 1.9 ± 0.5 (SD) mu/1) were within their respective normal ranges. Free T4 levels were low normal (mean 11.0 ± 1.0 (SD) pmol/1) while TSH, T4 and T3 responses to intravenous TRH were similar to those found in euthyroid subjects. These effects appear to be due predominantly to in vivo inhibition of binding of thyroid hormones to carrier proteins in serum, rather than in vitro drug interference in the radioimmunoassays employed. Fenclofenac does, however, interfere in those laboratory methods employing serum proteins as binding agents. Thus the Thyopac 4 method for serum total T4 grossly over‐estimates T4 levels, while thyroid hormone binding capacity (Thyopac 3) is low. Since fenclofenac is one of the most potent drugs interfering with routine indices of thyroid status, it is suggested that suspected thyroid dysfunction is excluded before commencing therapy with the drug.
THE FUNCTION OF THE PITUITARY‐THYROIDAL AXIS IN ACROMEGALIC PATIENTS V. PATIENTS WITH HYPERPROLACTINAEMIA AND A PITUITARY TUMOUR
Authors: KLIJN J. G. M. , LAMBERTS S. W. J. , DOCTER R. , JONG F. H. DE , VAN DONGEN K. J. , BIRKENHAGER J. C.
Published: March 2008

The function of the pituitary‐thyroidal axis was examined in fifty‐three of sixty‐two patients with hyperprolactinaemia and a pituitary tumour and in forty of forty‐four acromegalic patients, in whom one or more indices of the pituitary‐thyroid function were determined before treatment. In the patients with hyperprolactinaemia and a pituitary tumour, sellar + extrasellar tissue (EST) size showed a significant negative correlation with the response of TSH to TRH (ΔTSH) as well as with the circulating T4 and T3 levels. These correlations were not present in the acromegalic patients. In the prolactinoma group a sharp decrease in mean serum T4 and T3 levels was found at sellar + EST sizes exceeding 3 cm2. In twenty‐three patients with a sellar + EST size of 3 cm2 or more, thirteen (57%) showed a T4 level of less than 6 μg/dl against none of twenty‐eight patients with a sellar + EST size of less than 3 cm2. For T3, using a limit of 120 ng/dl, the corresponding numbers were eight out of thirteen (62%) and none of ten patients respectively. A positive correlation was observed between ΔTSH and the T3 levels but not between ΔTSH and T4, while in the acromegalic patients there was no correlation between TSH reserve and T3 or T4. In the patients with hyperprolactinaemia and a pituitary tumour positive correlations between basal TSH and ΔTSH as well as between T4 and T3 levels were observed. These correlations were not found in the acromegalic patients.

In conclusion: (1) Thyroid function appears to be independent of pituitary tumour size in patients with acromegaly but not in patients with hyperprolactinaemia and a pituitary tumour. (2) In acromegalic patients the high incidence of an impaired TSH response (without hypothyroidism and independent of tumour size) may be caused by suppression of TSH secretion rather than by destruction of thyrotrophic cells.
THE EFFECT OF INCREASING DOSES OF INGESTED GLUCOSE ON INSULIN AND GASTRIC INHIBITORY POLYPEPTIDE (GIP) CONCENTRATIONS IN MAN
Authors: FALKO J. M. , CROCKETT S. E. , CATALAND S. , O'DORISIO T. M. , KRAMER W. , MAZZAFERRI E. L.
Published: March 2008

Gastric inhibitory polypeptide (GIP) is insulinotropic in vivo and in vitro. It is released following glucose ingestion and is a leading candidate as a mediator of the enteroinsular axis. To investigate the GIP response to increasing amounts of oral glucose, and its relationship to glucose levels and insulin secretion, fourteen normal volunteers ingested 25, 50 and 75 g of glucose at random with 5–7 days between each test. Serum insulin, glucose and GIP concentrations were measured and total integrated incremental responses were determined. Peak mean responses to glucose, insulin and GIP occurred at 30 min following each glucose ingestion. There were no significant differences in glucose concentrations at any interval with the varying glucose doses. Mean peripheral insulin concentrations were significantly increased ater 50 or 75 g of glucose as compared with the 25 g dose (P<0.02). Mean GIP concentrations were significantly greater (P<0.03) between 15 and 180 min with both the 50 and 75 g glucose stimulus. Total integrated areas under the response curves for glucose, insulin and GIP showed a graded increase in circulating insulin and GIP (P<0.01) as the amount of ingested glucose was increased from 25 to 75 g. These findings show that increasing doses of glucose stimulated greater levels of GIP and insulin and further support the insulinotropic properties of endogenous GIP in man.
ADRENAL FUNCTION IN SUBGROUPS OF THE PCO SYNDROME ASSESSED BY A LONG ACTH TEST
Authors: KANDEEL F. R. , LONDON D. R. , BUTT W. R. , DAVILA N. , RUDD B. T. , SADEGHIAN S. , LYNCH S. S. , EDWARDS R. LOGAN , HORDER M.
Published: March 2008

Fifteen patients with the polycystic ovarian (PCO) syndrome were classified into Group A (n= 6) and Group B (n= 9) based on their LH responses to LHRH before and at 44 and 92h after administration of oestradiol benzoate. Adrenal function in both groups was assessed by comparing the hormone responses to ACTH (0.5mg twice daily for 4 days) with those obtained in nine normally ovulating women during the early follicular phase of their cycles. In Group A patients there was no significant difference from normals in the serum concentration of dehydroepiandrosterone sulphate (DHAS), 17α‐hydroxy‐progesterone (17‐OHP) or androgens (testosterone and dihydrotestosterone). In contrast, the serum concentrations in Group B were significantly higher (P<0.01) for each of these steroids before ACTH, and remained higher at 2 and 4 days for DHAS, but not for the other two steroids. The concentration of oestrone was significantly higher (P<0.05) in Group B patients before, and 2 days after, ACTH, while in Group A patients higher concentrations (P<0.02) were found only after 2 days. The concentrations of oestradiol, on the other hand, were not different from normal in either group before ACTH and became lower than normal in both groups at 2 days and remained lower at 4 days in Group B. The concentration of cortisol was within the normal range throughout in Group A, but was lower than normal after 4 days in Group B patients (P<0.05). The ratios between the sums of concentrations of DHAS to cortisol on days 2 and 4 (P<0.001) or 17‐OHP to cortisol (P<0.05) were elevated in Group B compared with normal subjects. LH, FSH and prolactin values were normal throughout in Group A, but in Group B patients the mean value for LH was significantly elevated before ACTH and at 4 days after ACTH (P<0.02).
SOMATOSTATIN SECRETION BY LUNG AND THYMIC TUMOURS
Authors: PENMAN ERICA , WASS J. A. H. , BESSER G. M. , REES LESLEY H.
Published: March 2008

Ectopic secretion of somatostatin in one patient with a thymic tumour and in two patients with lung tumours is described. All three patients also had ectopic ACTH secretion. Gel filtration chromatography under dissociating conditions showed the two lung tumour extracts to contain predominantly 1600 MW somatostatin monomer while the thymic tumour contained predominantly a 3000–3500 MW form of somatostatin, 77% of which was not converted to 1600 MW somatostatin by dithiothreitol (an agent which reduces disulphide bridges). This form may therefore represent a covalently‐bound precursor of somatostatin rather than a dimer of two somatostatin monomers. Plasma from all three tumour patients and from normal subjects contained both 1600 and 3000–3500 MW somatostatin. It is suggested that somatostatin secretion may frequently be associated with multiple hormone producing tumours.
STUDIES OF DIURNAL CHANGES IN PLASMA RENIN ACTIVITY, AND PLASMA NORADRENALINE, ALDOSTERONE AND CORTISOL CONCENTRATIONS IN MAN
Authors: LIGHTMAN S. L. , JAMES V. H. T. , LINSELL C. , MULLEN P. E. , PEART W. S. , SEVER P.S.
Published: March 2008

Diurnal studies were performed on ten normal volunteers taking a normal sodium diet. Half‐hourly blood samples were taken throughout 25 h and assayed for plasma renin activity (PRA) and the plasma concentrations of noradrenaline, aldosterone and cortisol. Sleep was recorded polygraphically and scored by standard criteria. Circadian rhythms were demonstrated for plasma cortisol, aldosterone and noradrenaline concentrations, but not for plasma renin activity. The nadir of the rhythm for the noradrenaline concentration appeared to be related to sleep itself rather than to any chronological index. Only PRA was effected by the stage of sleep, falling sharply during periods of REM sleep. Plasma cortisol and aldosterone concentrations showed a positive correlation over the 24 h. There was, however, no correlation between PRA and plasma aldosterone concentrations, except when the subjects arose after their night's recumbency. Plasma noradrenaline concentration did not correlate with the concentration of any of the other hormones measured.
THE RELATIONSHIP OF ERYTHROCYTE INSULIN RECEPTORS TO RED CELL AGE AND TO MONOCYTE INSULIN RECEPTORS
Authors: WARD G. M. , REES A. R. , NAYLOR B. A. , TURNER R. C.
Published: March 2008

This study examines the degree to which erythrocyte insulin receptors might be used instead of monocyte insulin receptors to assess overall insulin receptor status. Red blood cells from eight normal subjects were fractionated into older and younger populations by high speed centrifugation. Fractionated red cells (3·5 ± 109/ml) were incubated with 0·14 ng/ml of ‘monoiodo’125I‐insulin for 2·5 h at 15°C. The high reticulocyte fractions (mean 2·1% reticulocytes) had greater insulin binding than the low reticulocyte fractions (mean 0·6%), −9·0% compared with 6·0% specific binding, respectively. The difference (P > 0·05) appeared to be predominantly due to a greater number of high affinity sites per cell in the high reticulocyte fractions. Culture of high and low reticulocyte fractions, from both normal subjects and patients with high reticulocyte counts, in vitro for 2·5 days at 37°C, markedly reduced reticulocyte count and insulin binding of the high reticulocyte fractions, but produced little change in the low reticulocyte fractions. It appeared the reticulocytes had a ten‐ to twenty‐fold increase in binding sites compared with erythrocytes.

There is little degradation of insulin by intact erythrocytes or reticulocytes at 37°C, with a dissociation between insulin binding and insulin degradation. The large degradative capacity of haemolysed red cells implies that insulin receptor assays would be invalid in the presence of haemolysis.

Monocyte and erythrocyte receptors were compared in the same blood samples from overnight fasted subjects, with a correlation between insulin binding (r = 0·62). The inexact correlation may be partly due to the non‐homogeneous insulin binding of red cells, but correction for differences between reticulocyte content of the assayed red cells only increased the correlation to r = 0.67. Whilst the non‐homogeneity of red cells means that erythrocyte binding must be interpreted with caution, we cannot exclude similar non‐homogeneity of monocyte populations.
A COMPARATIVE STUDY OF THE BINDING OF GRAVES’ IMMUNOGLOBULINS BY THE PATIENT'S OWN AND OTHER THYROID MEMBRANES
Authors: GOSSAGE A. A. R. , BYFIELD P. G. H. , COPPING SUSAN , HIMSWORTH R. L.
Published: March 2008

Thyroid membrane preparations from six patients with active Graves’ disease were tested in an assay which detects the thyroid interactive immunoglobulins of Graves’ disease by their inhibition of binding of [125I]‐thyroid stimulating hormone (TSH). With all preparations inhibition of binding of 125I‐TSH by excess TSH could be demonstrated (specific binding). The patients’ own immunoglobulins were assayed against their own thyroid membranes and against each other's under exactly comparable conditions. Inhibition of binding by IgGs from the patients varied between membrane preparations: with one preparation 5/6 IgGs were inhibitory but with another none were effective. Of the six patients, their own IgG inhibited binding of 125I‐TSH to their own thyroid membrane preparation in only four instances, and when interaction did occur this did not reliably predict that the membrane preparation would interact with IgGs from other patients with Graves’ disease. The selection of a membrane preparation for this assay cannot be made solely on ability to specifically bind TSH but the measure of the specific interaction with a Graves’ IgG of proven potency must also be considered. Moreover, because of the variability between different membrane preparations, sequential clinical studies on individual patients, of the changes in concentration of Graves’ IgG, must be performed using the same selected thyroid membrane preparation.

We infer from these observations that the membrane structure in the vicinity of the TSH binding site is an important determinant of the interaction of Graves’ IgGs with the TSH receptor, and that the configuration of this area is variable between individuals of the same species. The distinction between ‘human‐specific’ and ‘non‐species‐specific’ thyroid stimulating antibodies is therefore probably not valid. The observation that the patient's own IgG was not often the most potent IgG inhibitor of binding of TSH also suggests that the Graves’ IgG binding site is not identical or restricted to the TSH binding site; alternative explanations are discussed.