bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF CIMETIDINE ON PITUITARY FUNCTION: ALTERATIONS IN HORMONE SECRETION PROFILES
Authors: VALK T. W. , ENGLAND B. G. , MARSHALL J. C. 
Published: March 2008

SUMMARYCimetidine, an H2 receptor antagonist, was given for 6 weeks to six normal male volunteers to study the effects on pituitary, adrenal, thyroid, and testicular hormone secretion. Patients were studied before (day 1) and after (day 42) cimetidine (300 mg four times daily) therapy, and four of the six were restudied after discontinuing cimetidine for 1 month (day 72). Basal TSH concentrations and responses to TRH administration as well as T3 RIA and T4 resin uptakes did not change during or after cimetidine therapy. The diurnal rhythm of plasma cortisol and maximum cortisol response to insulin (0·15 u/kg) were similar on days 1 and 42, but urinary free cortisol excretion fell 31% (P < 0·01). Response of GH to exercise, 100 g carbohydrate ingestion and insulin were unchanged, but mean nocturnal GH secretion decreased 33% (P < 0·025) on cimetidine, and returned to baseline on day 72. The 24‐h plasma prolactin profile was unchanged as was the prolactin response to insulin and TRH stimulation. Plasma FSH was not altered, but mean LH concentrations decreased 20% on cimetidine and continued to decline (45% of day 1 levels) after discontinuation of cimetidine (P < 0·01). Spontaneous LH pulse amplitude declined slightly on day 42, but became significantly lower on day 72 (P < 0·01) while pulse frequency increased modestly on day 72 (P < 0·05). Peak LH responses to gonadotropin‐releasing hormone were also reduced on cimetidine therapy (P < 0·02). Plasma testosterone concentrations did not change but plasma oestradiol concentrations were 38% lower (P < 0·025) after cimetidine was discontinued.H2 histamine receptors are involved in the control of multiple hormone secretory patterns and blockade of these receptors by cimetidine alters hormone profiles. These changed patterns have to be considered in the interpretation of hormone measurements in patients receiving cimetidine therapy.
INDICES OF SERUM ANDROGENS IN NORMAL PUBERTY: CORRELATIONS OF TWO INDICES WITH CHRONOLOGICAL AGE, BONE AGE AND PUBERTAL DEVELOPMENT IN BOYS AND GIRLS*
Authors: PENFOLD J. L. , SMEATON T. C. , GILLILAND J. M. , BOULTON T. J. C. , THOMSETT M. J. , PREECE M. A. , VIMPANI A. 
Published: March 2008

SUMMARYTwo indices of free serum androgenic activity, the normalized androgen ratio (NAR) and the free androgen index (FAI) were determined in 218 normal children aged 8–17·9 years. Before the onset of puberty and between chronological age 8 and 11·9 years, NAR and FAI were similar in both sexes, the NAR being < 0·8 and FAI < 0·1. In boys mean NAR value increased from 0·87 to 1·39 between 12·5 and 17·5 years, and mean FAI from 0·14 to 1·85, between 12·5 and 17·5 years. In girls mean NAR increased from 0·79 to 0·85 between 12·5 and 15·5 years, and mean FAI from 0·11 to 0·23, between 12·5 and 15·5 years. Both indices did not change significantly between 15·5 and 17·5 years in girls. A rapid increase in NAR and FAI occurred in boys from a mean testicular volume of 4·1 to >20 ml and from genital stage G2+ to 5+. In girls a gradual increase in NAR and FAI occurred from breast stage B2 + to 5+. Although the androgen indices increased in both sexes between pubic hair stages PH2 + and 6 +, the values in girls were always less than in boys at corresponding stages suggesting an increased androgen sensitivity of the female pubic hair follicle during adolescence.The peak rise in NAR and FAI in boys between 13 and 15 years correlated closely with the timing of the pubertal growth spurt in this sex. A similar rise was not seen in girls at the time of their peak growth velocity between 11 and 13 years and suggested that androgens play only a minor or complementary part in the female growth spurt.
DEVELOPMENT OF A RADIOIMMUNOASSAY FOR AN AMINO‐TERMINAL PEPTIDE OF PRO‐OPIOCORTIN CONTAINING THE γ‐MSH REGION: MEASUREMENT AND CHARACTERIZATION IN HUMAN PLASMA
Authors: HOPE J. , RATTER SALLY J. , ESTIVARIZ F. E. , McLOUGHLIN LORRAINE , LOWRY P. J. 
Published: March 2008

SUMMARYA radioimmunoassay has been developed for the N‐terminal region of human pituitary pro‐opiocortin (N‐POC), the common precursor protein of ACTH and β‐LPH, using an antiserum which recognizes residues near the γ‐MSH region. The concentrations of greater than 300 ng/l of immunoreactive peptide were determined in unextracted human plasma, the relative molecular mass of the reacting fragments corresponding to a seventy‐seven amino acid glycoprotein. The concentrations of immunoreactive N‐POC peptides were correlated with those of ACTH in plasma obtained from patients with various disorders of the hypothalamic‐pituitary‐adrenal axis.
A POSSIBLE DIRECT EFFECT OF 24,25‐DIHYDROXYCHOLECALCIFEROL ON THE PARATHYROID GLAND IN PATIENTS WITH CHRONIC RENAL FAILURE
Authors: CHRISTIANSEN C. , Rødbro P. , NÆSTOFT J. , CHRISTENSEN MERETE S. 
Published: March 2008

SUMMARYSeventeen undialysed adult patients with chronic renal failure took part in a controlled study of the effects of 1,25(OH)2D3 and D3. After a 6‐month observation period the patients were allocated at random to two groups for 6 months of treatment with either 1,25(OH)2D3 (mean dose 0·5 μg daily) or D3 (dose 100 μg daily). The treatment was then discontinued and the patients were studied for a further 3 months.In the 1,25(OH)2D3 group the mean serum concentration of 1,25(OH)2D rose significantly during treatment, whereas serum concentrations of 25OHD and 24,25(OH)2D remained unchanged. In the D3 group there was a highly significant increase in serum concentrations of 25OHD and 24,25(OH)2D, whereas serum 1,25(OH)2D remained unchanged.There was a significant fall in serum iPTH in both treatment groups. This fall was unrelated to serum calcium in the D3 group unlike the findings in the 1,25(OH)2D3 group. The data support previous experimental evidence that serum iPTH can be suppressed by 24,25(OH)2D3 and suggest that this analogue may be of clinical importance in the treatment of chronic renal failure without inducing hypercalcaemia.
THE INFLUENCE OF CARBAMAZEPINE ON THYROID HORMONES AND THYROXINE BINDING GLOBULIN IN HYPOTHYROID PATIENTS SUBSTITUTED WITH THYROXINE
Authors: AANDERUD SYLVI , MYKING O. L. , STRANDJORD R. E. 
Published: March 2008

SUMMARYCarbamazepine (CBZ) decreases the serum concentration of thyroid hormones. It is proposed that CBZ increases the extra‐thyroidal metabolism of thyroid hormones. In order to test this hypothesis CBZ was given to nine hypothyroid patients substituted with thyroxine (T4). A significant decrease in serum concentrations of T4, calculated free T4 (FT4), triiodothyronine (T3), and calculated free T3 (FT3) was found after 3 weeks of CBZ medication. The serum concentrations of TSH and the T4:T3 ratios were unaltered, while the serum concentrations of T4‐binding globulin (TBG) increased markedly in eight of the nine patients. These findings support the hypothesis of a CBZ induced increase in the extra‐thyroidal metabolism of thyroid hormones.
LIMITATIONS OF A NEW FREE THYROXINE ASSAY (AMERLEX® FREE T4)
Authors: STOCKIGT J. R. , GARIS M. De , CSICSMANN J. , BARLOW J. W. , WHITE E. L. , HURLEY D. M. 
Published: March 2008

SUMMARYWe have assessed a new method of free T4 measurement (Amerlex®) which uses a novel unidentified T4‐labelled analogue, said to be unreactive with T4 binding proteins in serum, together with an antibody that binds both analogue and T4. Free T4 is assessed by competition with analogue for antibody binding‐sites. The test method has been compared with free T4 measured by equilibrium dialysis and with a technique using an immobilized T4 antibody. All methods gave the expected free T4 levels in normal, hyperthyroid and hypothyroid subjects and normal free T4 levels with high or low levels of T4 binding globulin. However, in autosomal dominant familial euthyroid T4‐excess, where T4 is abnormally bound to albumin, the test method gave apparent high free T4 levels suggestive of hyperthyroidism. In a selected group of severely‐ill euthyroid patients the new method gave apparent low free T4 levels. In view of these discrepancies, binding of labelled analogue was evaluated by dextran‐charcoal separation at 4°C. Familial euthyroid T4‐excess sera showed greater analogue binding and samples with low prealbumin concentration showed less binding than did normal sera. Despite its validity with variations in TBG, it appears that Amerlex® Free T4 is influenced by lower‐affinity, high‐capacity T4 binding sites in serum, so that apparent free T4 concentration may vary with changes in the concentration of such sites.
AUTORADIOGRAPHIC COMPARISON OF GROWTH FACTORS: INFLUENCE OF GROWTH HORMONE AND SOMATOMEDIN B ON PATTERNS OF PROLINE INCORPORATION
Authors: RUDMAN C. G. , PARSONS J. A. 
Published: March 2008

SUMMARYPatterns of incorporation of 14C proline have been compared by whole body autoradiography to study the action of growth factors, infused for 1 week to hypophysectomized rats by subcutaneously implanted minipumps. Human growth hormone (hGH) caused dose‐related increases in the width of the tibial epiphyseal cartilage and obvious weight gain, whereas only at 640 μg/week did Somatomedin B have a barely significant effect on these two parameters. Samples of tissues showing significant proline uptake by autoradiography were burned for direct measurement of 14C content. Both hGH (80–160 μg/week) and SMB (160–640 μg/week) significantly enhanced proline uptake in skin, tibia, liver and kidney. Whereas the Somatomedin was less active than hGH on skin it showed a greater effect on bone, significantly exceeding the apparently maximal response to hGH. The autoradiographic technique can be used not only to compare different growth factors but also to study the growth process by use of appropriate tracers.
THE METABOLIC EFFECTS OF CHRONIC HYPERGLUCAGONAEMIA
Authors: NANKERVIS ALISON , PROIETTO J. , NG K. W. , ALFORD F. P. , LARKINS R. 
Published: March 2008

A subject with a benign glucagonoma was studied before and after complete resection of his pancreatic tumour. Studies were undertaken pre‐and post‐operatively to determine the effects of chronic hyperglucagonaemia on glucose tolerance and glucose kinetics both in the fasting state and during physiological insulin infusions, employing the [3H]‐3‐glucose technique. In addition the plasma cyclic AMP response to an acute infusion of glucagon was studied pre‐and post‐operatively.The basal immunoreactive glucagon levels pre‐and post‐operatively were 10492 ± 1296 and 149 ± 15 pg/ml respectively. Pre‐and post‐operative oral glucose tolerance tests did not differ but were abnormal. Pre‐operatively basal hepatic glucose production was normal and it was suppressed rapidly by the low dose insulin infusion, despite continuing hyperglucagonaemia. The metabolic clearance rate of glucose was slightly reduced. There was no plasma cyclic AMP response to a glucagon infusion, suggesting down‐regulation of the glucagon receptor by the chronic hyperglucagonaemia. Post‐operatively the hepatic glucose production and clearance rate of glucose fell, whereas the plasma cyclic AMP responses to the glucagon infusion reverted to a normal pattern.It is concluded that chronic hyperglucagonaemia is not a major factor in the development of the glucose intolerance, but it may lead to down‐regulation of the biological action of glucagon.
LACK OF SUPPRESSION OF INSULIN SECRETION BY EXERCISE IN PATIENTS WITH INSULINOMA
Authors: JARHULT J. , ERICSSON M. , HOLST J. , INGEMANSSON S. 
Published: March 2008

SUMMARYSerum glucose, insulin and glucagon concentrations were measured in three patients with insulin‐producing tumours of the pancreas while performing an exercise test. In contrast to the normal adrenergic inhibition of insulin release in response to exercise, plasma insulin concentration remained at a constant and high level during exercise in patients with insulinomas. Their plasma glucose concentrations fell during exercise and in the post‐exercise period. No significant changes occurred in plasma glucagon concentration. An exercise test may be a useful new diagnostic tool in organic hyperinsulinism.
EVIDENCE AGAINST AN INTERACTION OF ANGIOTENSIN II WITH THE SYMPATHETIC NERVOUS SYSTEM IN MAN
Authors: NICHOLLS M. G. , ESPINER E. A. , MILES K. D. , ZWEIFLER A. J. , JULIUS S. 
Published: March 2008

SUMMARYAnimal experiments indicate that angiotensin II can, under some circumstances stimulate the sympathetic nervous system at a number of different sites. In order to determine whether such a relationship of the renin‐angiotensin and sympathetic nervous system exists in man, we increased (by intravenous infusion), or decreased (by administering the oral converting enzyme inhibitor captopril) circulating angiotensin II levels and monitored plasma adrenaline and nor‐adrenaline responses. Angiotensin II infusions did not increase plasma catechol‐amines, and lowering of angiotensin II by captopril treatment in patients with severe hypertension or congestive heart failure failed to alter plasma adrenaline or nor‐adrenaline levels. Whether physiological levels of angiotensin II are capable of interacting directly with the sympathetic nervous system in man remains to be demonstrated.
COMPARISON BETWEEN DOSE‐RESPONSES OF PROLACTIN, THYROID STIMULATING HORMONE AND GROWTH HORMONE TO TWO DIFFERENT HISTAMINE H2‐RECEPTOR ANTAGONISTS IN NORMAL MEN
Authors: KNIGGE U. , WOLLESEN F. , DEJGARRD A. , THUESEN B. , CHRISTIANSEN P. M. 
Published: March 2008

SUMMARYThe effects of the histamine H2‐receptor antagonists, ranitidine and cimetidine on prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) were studied in six normal males. Intravenous bolus injections of saline and of 50, 100, and 200 mg ranitidine and 300 mg cimetidine were tested. Ranitidine (100 and 200 mg) and cimetidine (300 mg) caused a significant increase in PRL secretion, whereas saline and ranitidine (50 mg) did not. TSH and GH secretion were unaffected by all doses. A dose‐response relationship between ranitidine and PRL was established, and a dose of 65 mg ranitidine was found to be the minimal effective PRL‐releasing dose. Plasma ranitidine concentration was measured by specific RIA. The results indicate an effect of H2‐receptor antagonists on physiological functions in the control of PRL secretion. Histamine, therefore, may play a role in the regulation of PRL secretion.
PRE‐OPERATIVE LOCALIZATION OF ALDOSTERONE‐SECRETING ADRENAL ADENOMAS
Authors: MCAREAVEY D. , BROWN J. J. , CUMMING A. M. M. , DAVIDSON J. K. , DUNCAN J.G. , FRASER R. , LEVER A. F. , MEEK D. , ROBERTSON J. I. S. 
Published: March 2008

SUMMARYTechniques for pre‐operative localization of aldosterone‐secreting adrenal adenomas were studied in thirty‐seven patients, each with hypertension and biochemical evidence of primary hyperaldosteronism and each later having adrenal surgery (thirty‐two adenomas, five bilateral adrenal hyperplasia).Bilateral adrenal vein catheterization was attempted in all cases; it was successful on the left side in all patients and in 92% of cases on the right. Adrenal vein plasma samples were obtained from the left side in 92% and from the right in 73% of cases. Adrenal vein plasma aldosterone measurements correctly indicated the presence of tumour in twenty‐eight cases but falsely predicted unilateral adenoma in two cases of bilateral adrenal hyperplasia. Adrenal venography also correctly predicted unilateral adrenal adenomas in twenty‐six cases but falsely suggested the presence of tumour in three cases of bilateral adrenal hyperplasia.Computed tomography (CT) was used in the last eight cases. In seven instances the predictions (six adenomas, one bilateral adrenal hyperplasia) were confirmed at surgery. However, the remaining patient harboured an adenoma 20 mm in diameter which was not detected by CT although diagnosed both by adrenal venography and adrenal vein aldosterone measurements.Ultrasound detected adenoma in only three of twenty‐two cases examined. Although further comparative studies of the type described here are required, the results of computed tomography are promising and suggest that this non‐invasive technique might well become the first choice procedure in localizing aldosterone‐secreting adenomas.
DIURNAL HORMONE‐METABOLITE PROFILES IN HYPOTHYROIDISM
Authors: McCULLOCH A. J. , JOHNSTON D. G. , BURRIN J. M. , HODSON A. W. , CLARK F. , WAUGH C. , ØRSKOV H. , ALBERTI K. G. M. M. 
Published: March 2008

SUMMARYTo investigate the influence of thyroid hormones on intermediary metabolism in man, hormone and metabolite profiles were obtained over a 12‐h period of normal meals and activity in eight hypothyroid subjects before and during thyroxine replacement therapy, and in sixteen matched controls.The fasting blood glucose concentration and the mean 12‐h blood glucose concentration were normal in hypothyroid subjects but the blood glucose response to breakfast was exaggerated. Fasting blood lactate and pyruvate levels were normal but post‐prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1·08 ± 0·06 v. control 0·77 ± 0·03 mmol/l, P<0·01) and pyruvate (0·10 ± 0·01 v. 0·08 ± 0·003 mmol/l, P < 0·01) were elevated. Blood alanine concentrations were elevated only in the evening. Although plasma non‐esterified fatty acid levels were normal, fasting blood glycerol levels were decreased (0·06 ± 0·01 v. 0·08 ± 0·01 mmol/l, P <0·001) and this decrease persisted throughout the 12‐h period. Blood total ketone body concentrations did not differ from controls, but, as for plasma NEFA and blood glycerol, the normal preprandial rise in concentration was absent. Serum insulin, glucagon and growth hormone concentrations did not differ from control values at any time.Six months of thyroxine (T4) treatment produced a rise in blood glycerol concentrations (mean 12 h value during T4 therapy, 0·06 ± 0·01; before T4 therapy, 0·04 ± 0·005 mmol/l; P<0·01) but not to control values (0·08 ± 0·01 mmol/l). Concentrations of glucose and other gluconeogenic precursors were unaltered by therapy but the insulin response to meals and the mean 12 h serum insulin concentration were increased.
LONG‐TERM EVALUATION OF THYROIDAL RESPONSE TO PARTIAL CALORIE RESTRICTION IN OBESITY
Authors: MOREIRA‐ANDRÉS M. N. , DEL CAÑIZO‐GÓMEZ F. J. , BLACK E. G. , HOFFENBERG R. 
Published: March 2008

SUMMARYTwenty obese patients were treated as out‐patients with a 3·35 MJ (800 Kcal) per day diet, and, by the double‐blind method, ten of the patients were prescribed 40 μg of triiodothyronine (T3) daily and the other ten placebo. Body weight and serum thyroxine (T4), T3 and reverse T3 (rT3) concentrations were measured before treatment, then monthly over 6 months.No significant difference in mean weight loss was found between the patients receiving T3 and those on placebo. Serum T3 concentration decreased slightly in patients on placebo and increased in those on T3 but these changes were not statistically significant. However, patients on T3 maintained a significantly higher concentration of T3 in serum than those on placebo. Mean serum T4 and rT3 concentrations remained essentially unchanged in the patients on placebo, whereas both decreased significantly in patients receiving T3. We conclude that changes in serum T3 during dietary treatment of obesity are of minor significance in limiting the expected weight loss in the patients.
HORMONE BINDING GLOBULIN LEVELS IN PATIENTS WITH HEREDITARY ANGIOOEDEMA DURING TREATMENT WITH DANAZOL *
Authors: SCHWARZ S. , TAPPEINER G. , HINTNER H. 
Published: March 2008

SUMMARYFive patients with hereditary angiooedema were treated with Danazol for periods up to 10 months. This therapy resulted in normalization of serum levels of the inhibitor of the first complement component and disappearance of clinical disease symptoms in all patients. Although a variety of hormones were measured, only those of the pituitary‐gonadal axis altered during treatment: a moderate decrease in leuteinizing hormone levels and a sharp fall of testosterone in adult men were observed. In all patients, however, both sex hormone binding globulin and thyroxine binding globulin concentrations were considerably suppressed during Danazol therapy. However, levels of corticosterone binding globulin remained unchanged. The fraction of endogenous testosterone not bound to sex hormone binding globulin invariably increased. The possible relevance of these findings to the understanding of the mode of action of Danazol both in these patients and in general, are discussed.
THE EFFECT OF PROPRANOLOL ON THYROID HORMONES IN T3 TOXICOSIS
Authors: JONES M. K. , OWENS D. R. , JONES G. R. , BIRTWELL J. 
Published: March 2008

SUMMARYSerum thyroid hormone concentrations were measured before and during 6 months treatment with propranolol (160 mg/day) in eight patients with T3 (triiodothyronine) toxicosis. Serum total T3 concentrations showed a significant (P < 0·01) and sustained fall to approximately 80% of pre‐treatment values. Six of the patients, however, remained clinically and biochemically hyper‐ thyroid and our data do not support the use of propranolol as sole therapy in T3 toxicosis.
THE STEROID RESPONSE TO CONTROLLED ADRENAL STIMULATION IN CONGENITAL ADRENAL HYPERPLASIA
Authors: CONWAY D. I. , ANDERSON D. C. , BU'LOCK D. E. 
Published: March 2008

SUMMARYAdrenal steroidogenesis has been studied in vivo in eleven patients aged 13–68 years with 21‐hydroxylase deficiency, in one patient with 11β‐hydroxylase deficiency and in ten female control subjects. Serum levels of the Δ5 3β‐hydroxysteroids, pregnenolone (Pe), 17α‐hydroxypregnenolone (17Pe), dehydroepian‐drosterone (DHEA) and androstenediol (Adiol) and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxyprogesterone (17Po) androstenedione (Adione) and testosterone as well as of 11‐deoxycortisol and cortisol were measured during acute adrenal suppression with dexamethasone followed by stimulation with synthetic 1–24 ACTH.In the seven patients with 21‐hydroxylase deficiency who were on adequate glucocorticoid therapy, grossly exaggerated responses of 17Po and Po to ACTH were nevertheless preserved. In contrast, there was a grossly subnormal response of 17Pe, DHEA and Adiol to ACTH, and low basal levels of DHEA‐sulphate. In the untreated patients the response of 17Pe and DHEA was normal. The Adione response was exaggerated in untreated and normal in treated cases. Similar findings obtained in the patient with 11β‐hydroxylase deficiency who was studied after 6 weeks without replacement therapy. Our findings demonstrate that production of adrenal steroids that are associated with the adrenarche is not exaggerated in untreated CAH, and is grossly suppressed in treated cases. These findings are compatible with the hypothesis that intra‐adrenal cortisol may initiate and/or maintain production of the Δ5 steroids by the zona reticularis that occurs in the human adrenarche.