bluuebunny/crossref_metadata_2025 huggingface dataset:
BROMOCRIPTINE SUPPRESSES ACTH SECRETION FROM HUMAN PITUITARY TUMOUR CELLS IN CULTURE BY A DOPAMINERGIC MECHANISM
Authors: ADAMS E. F. , ASHBY M. J. , BROWN SUSAN M. , WHITE M. C. , MASHITER K.
Published: March 2008

Bromocriptine (0·13–13 μM) significantly inhibited ACTH secretion in a dose‐dependent manner when added to cell cultures of a human corticotrophic adenoma for 24 h. Haloperidol (13 μM), but not serotonin (13 μM), blocked this inhibition but had no significant effect when added alone. In addition, dopamine (10 μM) reduced ACTH secretion during a 4‐h incubation, whereas serotonin (0·01–10 μM) was ineffective. An ectopic ACTH secreting lung carcinoid was non‐responsive to doses of bromocriptine up to 13 μM. These results demonstrate a direct suppressive action of bromocriptine on a human pituitary corticotrophic adenoma through dopaminergic rather than sero‐toninergic mechanisms.
THYROXINE AND TRIIODOTHYRONINE LEVELS IN THYROID VEIN BLOOD AND IN THYROID TISSUE OF PATIENTS WITH AUTONOMOUS ADENOMAS
Authors: GHERI R. G. , BORRELLI D. , CICCHI P. , LEGNAIOLI M. , FABBRONI S. , MODIGLIANI U. , GHERI G. , SERIO M.
Published: March 2008

Thyroxine (T4) and triiodothyronine (T3) concentrations were measured in peripheral and thyroid vein blood and in nodular and extranodular thyroid tissue from twenty‐four patients with autonomous thyroid nodules (AFTN); fifteen of these patients showed clinical signs of hyperthyroidism and nine were euthyroid. Thirteen patients with solitary non‐functioning thyroid adenomas who were clinically euthyroid, served as controls; samples of thyroid vein blood and normal thyroid tissue being obtained from the contralateral lobe.

T4 (189·4 ± 27·2 nmol/l) and T3 (7·05 ± 2·03 nmol/l) concentrations were significantly higher in the thyroid vein blood of patients with AFTN compared with controls (T4 = 119 ± 9·1 nmol/l, P < 0·05; T3 = 2·3 ± 0·21 nmol/l, P < 0·01) whereas peripheral levels in the two groups were similar.

The T3 concentrations (10·56 ± 4·12 nmol/g wet tissue) in autonomously‐functioning thyroid nodular tissue were significantly higher than those of extranodular (1·9 ± 0·62 nmol/g wet tissue, P < 0·01) and normal thyroid tissue (2·63 ± 0·43 nmol/g wet tissue, P < 0·05). The T4 levels were not different in the tissues examined. The concentrations of T4 and T3 in thyroid vein blood did not show any significant correlation with the hormone levels in thyroid tissue.
RECOVERY OF HYPOPHYSEAL‐TESTICULAR FUNCTION FROM SEX STEROID TREATMENT AND THE PITUITARY RESPONSE TO CASTRATION IN MALE TRANSSEXUALS
Authors: GOH H. H. , KARIM S. M. M. , RATNAM S. S.
Published: March 2008

Twenty‐one male transsexuals who had been on steroid hormone therapy for at least 1 year volunteered for this investigation. Their hormone profiles after stopping sex steroid hormone treatment for periods ranging from 2 to 70 days were examined. Based on their testosterone levels before the sex‐reassignment operation which includes castration, penectomy and the construction of an artificial vagina, two separate groups can be distinguished; those with low (group A) and the other with normal (group B) levels. The gonadotrophins levels in group A and group B were (respectively) significantly (P < 0·05) lower and higher than corresponding levels in a group of normal males. Castration had caused elevations of FSH and LH in both groups. Although the increment rates were different, both groups attained the same maximum levels of FSH and LH. Within each group, the patterns of FSH and LH responses to castration were similar. However, differences in rates and time of significant elevation of FSH and LH were noted. These observations indicate that there is a delay between the cessation of steroid treatment and the recovery of testicular and hypophyseal functions. Testicular function seems to be altered by steroid treatment since excessive secretions of FSH and LH are needed to produce normal testosterone levels. The secretions of FSH and LH are controlled in some ways by the same mechanisms, while they, in other respects, are controlled by different factors.
TESTICULAR TESTOSTERONE LEVELS DURING PUBERTY IN CRYPTORCHIDISM
Authors: PASQUALINI TITANIA , CHEMES H. , RIVAROLA M. A.
Published: March 2008

Serum and testicular concentrations of testosterone were determined by radioimmunoassay in four prepubertal patients (Tanner's genital stage G1) with unilateral cryptorchidism and in ten pubertal patients with different degrees of genital development (stages G2‐G5), five with unilateral and five with bilateral cryptorchidism. In every case, testicular testosterone concentration was determined in the cryptorchid gonad. Two prepubertal autopsy cases were also studied. Results were compared with scrotal testes of adult subjects. Pubertal development resulted in a gradual increase in tubule diameter on microscopic examination notwithstanding the abnormal position of the gonad. As expected, serum testosterone also increased gradually throughout sexual development. Testicular testosterone concentration however increased to adult levels at early stages of puberty. Mean concentrations and ranges were: G1, 26 ng/g (range 7–49, n= 6); G2 + G3, 660 (range 37–1357, n= 6); G4 + G5, 438 (range 272–702, n= 4) and adults 520 (range 356–663, n= 4). This resulted in similar testicular: serum testosterone ratios in G1, G4 + G5 and adults but a high ratio in G2 + G3. Patients of groups G2 + G3 did not have elevation of serum gonadotrophins and did not show Leydig cell hyperplasia. Therefore, in early puberty, when peripheral tissues are exposed to low testosterone levels, seminiferous tubules of cryptorchid gonads might already receive high androgen stimulation.
IMPAIRMENT OF INSULIN SECRETION DURING EXPERIMENTAL POTASSIUM DEPLETION IS NOT CORRECTED BY THE PROSTAGLANDIN SYNTHESIS INHIBITOR, INDOMETHACIN
Authors: DÜSING R. , HARRISON L. C. , BHATHENA S. , RECANT LILLIAN , BARTTER F. C.
Published: March 2008

The effect of potassium depletion on glucose tolerance, plasma insulin and plasma glucagon was studied in six normal young female subjects. Negative potassium balance was induced by a diet low in potassium, together with frusemide (40 mg/day), for 3 days. Studies were performed during a period of potassium depletion and were repeated during potassium depletion in five subjects taking indomethacin (150 mg/day), an inhibitor of prostaglandin biosynthesis. Mean plasma potassium concentration was reduced from 4·2 ± 0·1 mmol/l to 3·3 ± 0·1 mmol/l, and was 3·2 ± 0·1 mmol/l during administration of indomethacin. Potassium depletion had no significant effect on the levels of plasma glucose, either fasting or following a 100 g oral glucose load, although the peak rise in plasma glucose after oral glucose was delayed (from 30 to 60 min). There was a decrease in the fasting plasma insulin concentration from 10·0 ± 1·3 mu/l to 6·7 ± 0·6 mu/l and a significant suppression of the early (30 min) insulin response to oral glucose from 126·0 ± 23·5 mu/l to 74·0 ± 19·2 mu/l. The insulin: glucose ratio during the first 60 min following oral glucose was significantly decreased from 43·7 ± 7·3 mu insulin/mmol glucose to 30·6 ± 7·3 mu insulin/mmol glucose. Furthermore, the suppression of plasma glucagon secretion that normally follows oral glucose was not observed. Administration of indomethacin during potassium depletion had no significant effect on plasma glucose, insulin or glucagon concentrations. These data indicate that short‐term potassium depletion in normal young females impairs the early insulin response to oral glucose but does not significantly alter overall glucose tolerance. Failure of an indomethacin effect suggests that the defect in insulin secretion may not be mediated by an increased synthesis of prostaglandins.
ANGIOTENSIN II STIMULATES THE RELEASE OF ACTH FROM DISPERSED RAT ANTERIOR PITUITARY CELLS
Authors: GAILLARD R. C. , GROSSMAN A. , GILLIES GLENDA , REES LESLEY H. , BESSER G. M.
Published: March 2008

In a rat anterior pituitary dispersed cell system, angiotensin II was found to stimulate the release of ACTH at concentrations ranging from 100 pmol/l to l μmol/l, with a maximal response being given by 10 nmol/l. The angiotensin II antagonist, saralasin, was able to block completely at a concentration of l μmol/l the stimulation of ACTH induced by 10 nmol/l angiotensin II, but had no effect on the basal release. The log dose‐response curve for ACTH release by angiotensin II was shifted to the right in a parallel fashion by saralasin 10 nmol/l, suggesting competitive antagonism. The stimulation of ACTH release by a rat stalk‐median eminence extract or by arginine vasopressin was unaffected by saralasin. The data are interpreted as suggesting that rat corticotrophs contain angiotensin II receptors, and that these may be involved in ACTH release in response to hypovolaemic stress.
RAPID ADAPTATION OF PITUITARY RESPONSIVENESS TO TRH IN THE POST‐SURGICAL STATE. THE ROLE OF FREE T3
Authors: WOLFSON M. S. , RAOUF A. A. , O'GORMAN P. , MARSDEN P.
Published: March 2008

In eight clinically and biochemically euthyroid patients undergoing routine major non‐thyroidal surgery preoperative and daily postoperative serum concentrations of total and free thyroid hormones were measured. Thyrotro‐phin‐releasing hormone (TRH) tests were performed preoperatively and on the first 3 postoperative days. There was a significant fall in mean serum total and free triiodothyronine (T3) concentrations on the postoperative days and mean reverse T3 concentrations rose reciprocally. There was no significant change in mean basal thyroid‐stimulating hormone (TSH) values, but there was a significant increase in the mean TSH response to TRH on the first postoperative day. The mean TSH response then declined sequentially until day 3 while mean free T3 concentrations remained significantly depressed. Mean serum free thyroxine (T4) concentrations remained normal during the study. Intrapituitary conversion of T4 to T3 or other down regulatory mechanisms could explain this rapid adaptation of the pituitary axis.
SOTALOL IN HYPERTHYROIDISM
Authors: KAUR S. , KRASSAS G. , RAMSAY I.
Published: March 2008

Ten hyperthyroid patients were studied before and after 2 weeks' β‐adrenoceptor blockade with sotalol. The following variables were measured: resting pulse rate, blood pressure, weight, thyroid hormone levels, plasma lipids, alkaline phosphatase, plasma glucose and insulin responses to oral glucose, bromsulph‐thalein retention and the 24‐h urinary excretion of calcium, hydroxyproline, creatine and creatinine. Sotalol produced a significant fall in pulse and blood pressure. Weight loss continued during treatment. No metabolic changes of any consequence were found. It is concluded that sotalol should not be used as the sole treatment of a patient with hyperthyroidism.
PROLONGED GALACTORRHOEA IN A 6‐YEAR‐OLD GIRL WITH ISOSEXUAL PRECOCIOUS PUBERTY DUE TO A FEMINIZING ADRENAL TUMOUR
Authors: DROP S. L. S. , BRUINING G. J. , VISSER H. K. A. , SIPPELL W. G.
Published: March 2008

A large cystic adrenal carcinoma was removed in toto from a 6½‐year‐old girl with isosexual precocious puberty treated with cyproterone‐acetate. Immediately following surgery, severe galactorrhoea developed, but was successfully treated with bromocriptine. The tumour fluid and pre‐operative plasma samples contained highly elevated levels of both oestrogens and androgens. In addition prolactin values were high. One year after adrenalectomy all plasma hormonal values were normal for age, but galactorrhoea could still be elicited. The prolonged galactorrhoea is most likely the result of excessive oestrogen‘priming’, whereas the hyperprolactinaemic effect of cyproterone acetate therapy remains uncertain.
STUDIES ON THE RESPONSES OF PLASMA RENIN ACTIVITY AND ALDOSTERONE AND CORTISOL LEVELS TO DOPAMINERGIC AND OPIATE STIMULI IN MAN
Authors: LIGHTMAN S. L.
Published: March 2008

Evidence for a role of dopamine and endogenous opioids in the control of the secretion of renin and adrenal steroids was sought in man. The effects of l‐dopa, l‐dopa plus carbidopa, dopamine, domperidone and naloxone were studied on the renin and aldosterone responses to head‐up tilt. l‐dopa diminished the rise in renin following tilt and this effect of l‐dopa was abolished by carbidopa. Aldosterone was not significantly affected by any of the compounds. Cortisol secretion was stimulated by carbidopa plus l‐dopa more than l‐dopa alone, and was also increased by both dopamine and naloxone. The significance of these findings is discussed.
BASAL GANGLIA CALCIFICATION IN PSEUDOHYPOPARATHYROIDISM TYPE II
Authors: WINDECK R. , MENKEN U. , BENKER G. , REINWEIN D.
Published: March 2008

The case history of a patient with basal ganglia calcifications found by computerised tomography is presented. Calcium and phosphorus metabolism showed a pattern suggesting lack of parathyroid hormone (PTH). Further studies revealed increased endogenous PTH levels and urinary cAMP excretion. However, endogenous and exogenous PTH could not elicit the cAMP‐mediated phosphaturic response, indicating pseudohypoparathyroidism type II. The responses of prolactin to TRH and chlorpromazine was impaired. Basal ganglia calcification in pseudohypoparathyroidism type II may represent the only somatic abnormality in this disease apart from the biochemical abnormalities.
THE SHORT METYRAPONE TEST: COMPARISON OF THE PLASMA ACTH RESPONSE TO METYRAPONE WITH THE CORTISOL RESPONSE TO INSULIN‐INDUCED HYPOGLYCAEMIA IN PATIENTS WITH PITUITARY DISEASE
Authors: FEEK C. M. , BEVAN J. S. , RATCLIFFE J. G. , GRAY C. E. , BLUNDELL G.
Published: March 2008

After a single dose of 2 g metyrapone given with a snack at 2300 h, blood was taken for estimation of plasma adrenocorticotrophin hormone (ACTH) concentrations at 0800 h the next morning from normal individuals and from patients with pituitary disease. Plasma ACTH concentrations following metyrapone were significantly lower in patients with pituitary disease with no evidence of anterior pituitary hormone deficiency (mean 90·0±SD 63·9 ng/l) when compared with normal individuals (mean 182·5±SD 14·1 ng/l, P < 0·01) but significantly greater than in patients with pituitary disease in whom a deficiency of one or more anterior pituitary hormones was demonstrated (mean 50·8±SD 14·1 ng/l, P < 0·01). It is concluded that the short metyrapone test is a sensitive method of detecting minor degrees of impairment of the negative feedback control of ACTH secretion that would be unrecognized by conventional assessment by insulin‐induced hypoglycaemia. The clinical relevance of impaired ACTH release in response to a single dose of metyrapone in patients with pituitary tumours, in whom pituitary function is otherwise shown to be adequate, needs to be determined.
CALCITONIN SECRETION AND BONE DISEASE SEVERITY IN HYPERCALCAEMIC HYPERPARATHYROIDISM
Authors: MAZZUOLI G. F. , D'ERASMO E. , SCARDA A. , MANCINI D. , MINISOLA S. , ALBERTI L. MALAGUTI , VALTORTA C.
Published: March 2008

Calcitonin (CT) plasma levels and urinary hydroxyproline (OHPr) excretion were studied in twenty‐eight patients (eleven males and seventeen females) with primary hyperparathyroidism in order to ascertain the effect of CT secretion on the severity of bone disease. The results show that in primary hyperparathyroidism plasma CT levels are increased in about 50% of patients independent of sex. Plasma CT levels were correlated with serum calcium values in males but not in females. Urinary OHPr excretion values appeared higher in those patients which showed lower CT plasma levels. In this latter group the incidence of undetectable CT plasma values was higher in females. The results suggest that in patients with primary hyperparathyroidism the persistent challenge of CT secreting parafollicular cells due to chronic hypercalcemia, may induce a decrease in their functional reserve, and that the bone involvement may have a greater incidence and more severe course in females, due at least in part, for their inability to increase CT secretion as much as males, due to an intrinsic sex‐related lower CT secretory reserve.
REDUCED SEX HORMONE BINDING GLOBULIN AND DERIVED FREE TESTOSTERONE LEVELS IN WOMEN WITH SEVERE ACNE
Authors: LAWRENCE DAPHNE M. , KATZ M. , ROBINSON T. W. E. , NEWMAN MAUREEN C. , McGARRIGLE H. H. G. , SHAW MARCIA , LACHELIN GILLIAN C. L.
Published: March 2008

Reduced circulating sex hormone binding globulin (SHBG) levels were found in 54% of a group of women with moderate to severe acne and in 60% of another group of twenty‐three women who had acne complicated by hirsutism and/or irregular menstrual cycles. The concentrations of SHBG for the women with acne alone (mean 48 ± 24 nmol/l) and for those with acne and hirsutes (mean 39 ± 18 nmol/l) were compared with the SHBG concentrations of fifteen unaffected women with normal menstrual cycles (mean 70 ± 19 nmol/l). The differences in mean SHBG values for both groups of women with acne were significant (P < 0·001) on comparison with the mean for the unaffected women.

Twenty‐nine per cent of the women with acne had elevated testosterone values (mean testosterone concentration for the group 1·5 ± 0·3 nmol/l) and 41% had elevated‘derived’free testosterone levels (mean 21 ± 6 pmol/l). Of the women with acne and hirsutes 65% had elevated plasma testosterone levels (mean 2·1 ± 0·6 nmol/l) and 89% had elevated free testosterone concentrations (mean 31 ± 10 pmol/l). The mean values for testosterone and free testosterone in the plasma of unaffected women (mean testosterone concentration 1·1 ± 0·3 nmol/l and free testosterone 13 ± 4 pmol/l) were significantly lower than in women with acne alone (P < 0·01 and P < 0·001) and in women with acne and hirsutism (P < 0·001).

This study indicates that a deficiency in SHBG and an elevation in‘derived’free testosterone is a frequent finding in women with severe acne and may be a significant factor in the aetiology and/or perpetuation of this condition.
RAPID COMMUNICATION: ABNORMAL SUPPRESSION OF PLASMA CORTISOL DURING THE INTRAVENOUS INFUSION OF DEXAMETHASONE TO ALCOHOLIC PATIENTS
Authors: FINK R. S. , SHORT FRANCES , MARJOT D. H. , JAMES V. H. T.
Published: March 2008

. In some cases the oral administration of dexamethasone to alcoholic patients has failed to cause a normal depression of plasma cortisol levels. Although alcoholics often show signs of intestinal malabsorption, the possibility that the dexamethasone was not fully absorbed has not previously been considered. To eliminate any question of malabsorption, ten male alcoholic patients were infused intravenously with dexamethasone (1mg/h). The plasma cortisol levels in blood samples withdrawn at half‐hourly intervals during a 2‐h infusion were compared with the values found in ten normal subjects similarly infused. Four of the alcoholics failed to show normal suppression of plasma cortisol levels, thus confirming that in some alcoholics there is a disturbance of pituitary‐adrenal function similar to that found in Cushing's disease. In only one of the four cases was failure to suppress normally associated with the presence of clinical signs of Cushing's disease.
BLOOD‐SPOT 17α‐HYDROXYPROGESTERONE RADIOIMMUNOASSAY IN THE FOLLOW‐UP OF CONGENITAL ADRENAL HYPERPLASIA
Authors: SÓLYOM J.
Published: March 2008

The value of plasma 17α‐hydroxyprogesterone (17α‐OHP) concentration in monitoring the treatment of congenital adrenal hyperplasia (CAH) was studied by using a capillary blood micromethod. The blood‐spot 17‐OHP radioim‐ munoassay method involves serial sampling throughout the day and sending the samples into a centre by mail. Follow‐up of seven children treated for CAH due to 21‐hydroxylase deficiency showed that a single measurement of plasma 17‐OHP concentration cannot be relied upon to determine adequacy of control, since circadian variation and timing of the sample in relation to the last dose of glucocorticoid may influence the plasma level of 17α‐OHP. Our data confirm the value of sequential 17α‐OHP assays throughout the day in the follow‐up of CAH. With the blood‐spot method the 17α‐OHP determinations can be used on a wide scale for monitoring therapy.
STUDIES OF THYROID HORMONE AND METHIMAZOLE LEVELS IN PATIENTS WITH GRAVES' DISEASE ON A STANDARDIZED ANTI‐THYROID DRUG REGIMEN
Authors: DAHLBERG P. A. , KARLSSON F. A. , LINDSTROM B. , WIDE L.
Published: March 2008

The outcome of a standardized carbimazole (CMI) regimen was evaluated in fifty‐four patients with Graves' disease. Triiodothyronine (T3) and thyroxine (T4) serum values were determined before and throughout the first 6–8 months of therapy. Before therapy, decreasing T4/T3 ratios were found with increasing T3 levels, reflecting a relative increase in T3 production compared with T4 in thyrotoxicosis. High pretreatment T3 values were comparatively common among patients in whom a fixed CMI dosage had an insufficient effect. T4 levels were less informative in this respect. Serum levels of methimazole (MMI), the active metabolite of CMI, were dose‐dependent. A 50% reduction in dosage resulted in a similar decrease in the serum values. For a given dose, the MMI levels differed considerably among individuals. The variation was not related to thyroid hormone values. It appears that the response to the anti‐thyroid drug is primarily dependent upon the severity of the disease, which is clearly reflected in serum T3 levels, rather than individual differences in drug handling. A routine CMI regimen for the treatment of thyrotoxicosis is suggested.
REVERSIBLE MALE INFERTILITY DUE TO CONGENITAL ADRENAL HYPERPLASIA
Authors: WISCHUSEN JANE , BAKER H. W. G. , HUDSON B.
Published: March 2008

We have studied a patient who was azoospermic and infertile. The cause of his infertility was unusual and curable: untreated congenital adrenal hyperplasia resulting from a partial 21‐hydroxylase deficiency. The diagnosis was suggested by the combination of small testes, elevated levels of testosterone and suppressed levels of gonadotrophins.
GROWTH HORMONE TREATMENT IN CHILDREN WITH CRANIOPHARYNGIOMA: FINAL GROWTH STATUS
Authors: BURNS E. C. , TANNER J. M. , PREECE M. A. , CAMERON N.
Published: March 2008

Twenty‐seven out of thirty craniopharyngioma patients treated with human growth hormone (hGH) for 2 years or more (average 4·5 years) reached final adult heights above the population third centile, though none was above the fiftieth centile. However, only twelve of twenty‐eight patients had final heights above the lower limits to be expected from their parents' heights. All patients eventually had long legs relative to sitting height (final mean subischial leg length SDS =+ 0·2, final mean sitting height SDS = ‐3·0).

Twenty‐nine patients were TSH‐deficient, twenty‐two were ACTH‐deficient, thirteen were deficient in ADH and all had total (85%) or partial (15%) gonado‐trophin deficiency. Following the administration of testosterone or hCG the boys had, on average, only half the normal adolescent growth spurt. This may have been due to the lateness of starting androgens in these patients and we recommend, when considering height, that testosterone or hCG should be started when a bone age of 13·0 ‘years’ is reached or when a lower bone age has remained unchanged for a year. The girls showed no adolescent height spurt; the average increase after oestrogen treatment commenced was 1·7 cm.
ACROMEGALY AND PITUITARY ADENOMA WITH PHAEOCHROMOCYTOMA: A VARIANT OF MULTIPLE ENDOCRINE NEOPLASIA
Authors: ANDERSON R. J. , LUFKIN E. G. , SIZEMORE G. W. , CARNEY J. A. , SHEPS S. G. , SILLIMAN Y. E.
Published: March 2008

Two women had acromegaly due to a pituitary adenoma associated with phaeochromocytoma. Eight additional patients with this combination of tumours have been described by others. Our first patient had sustained hypertension, mild hypercalcaemia, and elevated basal levels of parathyroid hormone and calcitonin associated with malignant phaeochromocytoma and parathyroid hyperplasia. The second patient had episodic hypertension and normal basal serum calcium, parathyroid hormone, and calcitonin levels with a benign cystic phaeochromocytoma. Four of the ten patients died from causes related to the phaeochromocytoma. Three patients had parathyroid hyperplasia. A separate group of four patients with phaeochromocytoma and pituitary adenoma without acromegaly has also been reported. These fourteen patients probably represent a non‐familial variant of the multiple endocrine neoplasia syndrome. Our findings suggest that acromegalic patients with hypertension should be screened for phaeochromocytoma.
CLINICAL EFFICACY OF TESTOSTERONE UNDECANOATE IN MALE HYPOGONADISM
Authors: MAISEY N. M. , BINGHAM J. , MARKS V. , ENGLISH J. , CHAKRABORTY J.
Published: March 2008

Testosterone undecanoate (Restandol, Organon Laboratories Ltd *) dissolved in oleic acid, was administered orally to seventy‐six hypogonadal males for three consecutive 3‐week periods and the subjective clinical response assessed by a standard interview. Plasma testosterone and testosterone undecanoate levels were determined by radioimmunoassay before the study and after 3, 6 and 9 weeks treatment. The treatment was effective in sixty of the sixty‐six patients who completed the trial. Ten patients did not complete the trial; two for reasons unrelated to the drug and eight because of side effects, mainly gastro‐intestinal. There was a significant rise in plasma testosterone levels during treatment and a positive correlation between plasma testosterone and testosterone undecanoate levels. Testosterone undecanoate is a potentially valuable drug for the oral treatment of male hypogonadism.
LONG‐ACTING THYROID STIMULATOR (LATS) AND LONG ACTING THYROID STIMULATOR PROTECTOR (LATS‐P) IN UNTREATED THYROTOXICOSIS
Authors: HARDISTY C. A. , HANFORD LINDA , HUMPHRIES HAZEL , MUNRO D. S.
Published: March 2008

The prevalance of serum LATS and LATS‐P in untreated Graves' disease has been studied in eighty‐three patients with thyroid overactivity; twelve (14%) were found to have significant levels of LATS and LATS‐P whilst fifty‐nine (72%) had significant levels of LATS‐P alone. Twelve (14%) had neither activity. There was a very wide range in both activities. LATS was invariably found in association with a significantly greater concentration of LATS‐P. There was no correlation between LATS‐P and thyroid mass, as estimated from scintiscanning, thyroidal radioiodine uptake at 4 and 48 h, total serum T4 and total serum T3. Neither LATS nor LATS‐P were detected in eleven patients with toxic multinodular goitre nor four with solitary toxic adenoma.
PROLACTIN RESPONSIVENESS TO TRH AND METOCLOPRAMIDE IN THALASSAEMIA
Authors: SPITZ I. M. , LANDAU H. , GROSS V. , TRESTIAN S. , PALTI Z. , RACHMILEWITZ E.
Published: March 2008

PRL and gonadotrophin secretion has been evaluated in six prepubertal male thalassaemic patients and nine females. Four of the latter were sexually immature (group 1) and the remainder had more advanced sexual development (group 2). Subjects were challenged with LHRH (100 μg), TRH (200 ug) as well as the dopaminergic antagonist, metoclopramide (10 mg) and their responses compared with normal adult controls. The male patients had low testosterone, oestradiol and basal and peak LH responses to LHRH. FSH values were intact. Basal PRL levels, as well as PRL responses to TRH and metodopramide were normal. There was a further increase in PRL response to TRH after the administration of a long acting testosterone preparation. In group 1 females, basal and peak gonadotrophins and oestradiol were decreased. Basal PRL was normal, but there was a markedly impaired PRL response to both TRH and metoclopramide. Oestradiol valerate administration restored the impaired PRL response to TRH, but not to metoclopramide in group 1 female subjects, although conjugated oestrogens had no effect. Group 2 females had normal gonadotrophin profiles, but low oestradiol levels. Their PRL response to TRH was normal, but they also demonstrated an impaired PRL response to metoclopramide. It is concluded that the impaired PRL reserve in female thalassaemic patients could be due to iron infiltration in the pituitary, or to oestradiol deficiency. It may also be related to the low LH levels or, alternatively, it may represent some alteration in dopamine tone.
THE ROLE OF OPIATE PEPTIDES IN THE CONTROL OF PROLACTIN IN THE PUERPERIUM, AND TSH IN PRIMARY HYPOTHYROIDISM
Authors: GROSSMAN A. , WEST S. , WILLIAMS J. , EVANS J. , REES L. H. , BESSER G. M.
Published: March 2008

The role of endogenous opiate peptides in puerperal hyperpro‐lactinaemia, and in the control of TSH in hypothyroidism, has been investigated. Although exogenous opioids raise prolactin and TSH levels, 16 mg naloxone administered to women on days 2–4 of the puerperium produced no significant change in serum prolactin and the same dose of naloxone had no significant effect on serum TSH in six primary hypothyroid patients. There is little evidence that endogenous opioid peptides are major modulators of prolactin or TSH in man under these conditions.
CALCIUM AND PARATHYROID HORMONE BEHAVIOUR AFTER EXOGENOUS SECRETIN INFUSION IN MAN
Authors: LO CASCIO V. , PIUBELLO W. , COMINACINI L. , VANTINI I. , GALVANINI G. , EDERLE A. , CAVALLINI G. , SCURO L. A.
Published: March 2008

The response of serum calcium, PTH, CT and gastrin to an infusion of secretin (3 CU/kg/h) over a period of 90 min was studied in ten healthy males and two female patients with hypoparathyroidism.

In the healthy males serum calcium, after a transient fall, significantly increased at 45 min after the onset of the infusion (P < 0·001). Serum iPTH rose significantly within 5 min whereas serum CT and gastrin concentrations did not change. The two hypoparathyroid patients did not show any variations in either serum iPTH or calcium.

These findings suggest that infusion of pharmacological doses of secretin into normal subjects modifies serum calcium, and that this change is due to PTH release.
DEVELOPMENT OF ADRENOCORTICAL FAILURE IN NON‐ADDISONIAN PATIENTS WITH ANTIBODIES TO ADRENAL CORTEX A CLINICAL FOLLOW‐UP STUDY
Authors: SCHERBAUM W. A. , BERG P. A.
Published: March 2008

Out of 1036 sera tested for the presence of antibodies to adrenal cortex using the indirect immunofluorescence (IFL) method, fifteen out of 323 patients with Graves' thyrotoxicosis, 6/105 Hashimoto's thyroiditis, 3/29 myxoedema, 2/49 asymptomatic autoimmune thyroiditis, 1/12 subacute thyroiditis, and 4/130 with myasthenia gravis were positive. Thirty antibody‐positive non‐addisonian patients were tested for subclinical adrenocortical failure and followed up over a period of 1–3–5 years. Three women with Graves' disease had biochemical signs of early Addison's disease at the first Synacthen test. Two young women with controlled Graves' thyrotoxicosis developed a diminished adrenocortical reserve within 2 and 3 years, respectively; one of them developed anovulatory cycles which did not respond to clomiphene treatment. Both patients had high titres of complement‐fixing adrenal antibodies before the adrenal failure could be recognized by functional tests. One elderly female patient in whom a euthyroid goitre with adrenal and thyroid antibodies was detected in 1977, developed Graves' thyrotoxicosis in 1980. These observations indicate that antibodies to adrenal cortex have a high clinical significance and may allow the early diagnosis of Addison's disease even in the absence of specific clinical symptoms.
NALOXONE INCREASES THE NICOTINE‐STIMULATED RISE OF VASOPRESSIN SECRETION IN MAN
Authors: LIGHTMAN STAFFORD , LANGDON NICOLA , TODD KATHRYN , FORSLING MARY
Published: March 2008

Intravenous nicotine was administered to a group of six subjects during the concurrent intravenous infusion of either the opiate antagonist naloxone, or of saline. Nicotine stimulated vasopressin secretion in all subjects. Naloxone infusion increased both the plasma vasopressin response to nicotine and the resulting rise in urine osmolality.
BIOCHEMICAL AND CLINICAL EFFECTS OF FENCLOFENAC IN THYROTOXICOSIS
Authors: PEARSON D. W. M , RATCLIFFE WENDY A. , THOMSON J. A. , RATCLIFFE J. G.
Published: March 2008

Administration of the anti‐inflammatory drug fenclofenac (600 mg bd) for 28 days to four females with thyrotoxicosis resulted in a rapid decline in thyroid hormone levels. The mean total thyroxine (T4) level of 173 ± 8·6 (SEM) nmol/l before therapy was normalized to 70 ± 6·4 nmol/l after administration of the drug for 7 days. Free T4 levels also decreased significantly but not to within the reference range in all subjects. Mean total triiodothyronine (T3) and reverse T3 levels declined from 6·2 ± 0·9 nmol/l and 0·63 ± 0·2 nmol/l respectively before therapy to 3·8 ± 0·5 nmol/l and 0·52 ± 0·1 nmol/l after 7 days' treatment but remained consistently elevated in all subjects.

Clinical thyroid status remained unchanged despite these marked reductions in circulating thyroid hormone levels, suggesting that fenclofenac was of no therapeutic benefit.
DEXAMETHASONE SUPPRESSION TESTS: USEFULNESS OF SIMULTANEOUS MEASUREMENT OF PLASMA CORTISOL AND DEXAMETHASONE
Authors: MEIKLE A. WAYNE
Published: March 2008

The effect of oral dexamethasone on the plasma content of cortisol and dexa‐methasone was investigated in 175 patients suspected of having Cushing's syndrome. Plasma concentrations of cortisol and dexamethasone were measured by specific radioimmunoassays at 08.00 h following administration of either a low‐low (0·5 mg), low (1·0 mg), high (4·0 mg) or high‐high (8·0 or more mg) dose of dexamethasone at midnight. All seventeen patients with documented Cushing's syndrome exhibited resistance to the action of low‐low and/or low dose dexamethasone on suppression of 08.00 h plasma cortisol content. Nine of twelve patients with pituitary dependent Cushing's syndrome had plasma cortisol values of less than 166 nmol/l following high‐high dose testing. In 157 patients with suspected Cushing's syndrome, standard dexamethasone testing was considered unsatisfactory in at least 20%. After low‐low or low dose tests 11% had supranormal cortisol values, but plasma cortisol content overlapped with values observed in patients with Cushing's syndrome only when plasma dexamethasone content was less than 5·6 nmol/l. Twelve per cent of patients suspected of having Cushing's syndrome had sufficient elevation of plasma dexamethasone values after low dose testing so that marked reduction of plasma cortisol might be expected even in patients with pituitary dependent Cushing's syndrome. Four patients receiving anticonvulsants had subnormal plasma levels of dexamethasone for the dose administered, but all exhibited normal suppression when plasma levels of dexamethasone and cortisol were correlated simultaneously. In summary, there is considerable variation in the plasma content of dexamethasone following oral doses. Simultaneous measurement of both plasma levels of dexamethasone and cortisol has proved most useful in identifying patients with unsatisfactory dexamethasone suppression tests.
CORTICOSTEROID‐INDUCED OSTEOPENIA AND VITAMIN D METABOLISM. EFFECT OF VITAMIN D2, CALCIUM PHOSPHATE AND SODIUM FLUORIDE ADMINISTRATION
Authors: RICKERS H. , DEDING Å. , CHRISTIANSEN C. , RØDBRO P. , NÆSTOFT J.
Published: March 2008

Thirty‐one patients scheduled for long‐term (24 weeks) treatment with prednisone in comparatively high doses were randomly allocated to two further treatment groups.

Group A received prednisone plus ‘triple‐treatment’ (vitamin D2 45 000 iu twice weekly, sodium fluoride 50 mg and calcium phosphate 4·5 g daily), group B received only prednisone. The study was undertaken in order to evaluate the effect of prednisone‐ and triple‐treatment upon bone mineral content (BMC) and vitamin D metabolism. The groups were comparable with regard to age, sex and prednisone dose. BMC fell rapidly and similarly in both groups, demonstrating that the triple‐treatment has no preventive effect on corti‐costeroid induced osteopenia.

Serum concentrations of 25OHD2, 25OHD3 and 1,25(OH)2D were unchanged in group B (without triple‐treatment), whereas in group A 25OHD2 increased enormously, 25OHD3 was suppressed possibly by substrate competition for hydroxylation in the liver and 1,25(OH)2D was halved. The suppression of 1,25(OH)2D may be an effect of raised 25OHD2 alone, or in combination with corticosteroid excess.
RECOVERY OF HYPOTHALAMO‐PITUITARY‐ADRENAL FUNCTION IN ASTHMATICS WHOSE ORAL STEROIDS HAVE BEEN STOPPED OR REDUCED
Authors: HARRISON B. D. W. , REES LESLEY H. , CAYTON RUTH M. , NABARRO J. D. N.
Published: March 2008

Hypothalamo‐pituitary‐adrenal (HPA) function was studied using tetracosactrin and insulin hypoglycaemia tests in eleven asthmatic patients who were receiving or had taken oral steroids. The patients had been on prednisone, 5–20 mg/day for 2–17 years. As the dose was reduced they used beclomethasone inhalation, up to 800 μg/day.

Seven insulin hypoglycaemia tests were performed when the patients had been off oral steroids for 15–37 months. Plasma cortisol responses were normal in all seven, three had subnormal responses of ACTH.

In five patients serial tetracosactrin and insulin hypoglycaemia tests were performed during reduction of steroid dose. Two patterns of recovery of HPA function were observed. In one, both hypothalamo‐pituitary and adrenal function seemed to return simultaneously, in the other normal response to tetracosactrin appeared before that to insulin hypoglycaemia. One patient had normal ACTH and cortisol responses to the stress of a vasovagal attack, but failed to respond to subsequent hypoglycaemia.

We conclude that a normal response to tetracosactrin does not indicate recovery of the HPA axis after stopping prolonged oral steroid therapy for asthma, and that patients should continue to carry steroid therapy cards for at least 5 years after such treatment has been discontinued.
SIMULTANEOUS STUDY OF SOMATOTROPHIC AND CORTICOTROPHIC PITUITARY SECRETIONS DURING ORNITHINE INFUSION TEST
Authors: EVAIN‐BRION D. , DONNADIEU M. , ROGER M. , JOB J. C.
Published: March 2008

An ornithine infusion test was performed in fifty‐four children with constitutional short stature. The ornithine infusion induced an elevated level of GH at 45 min (mean value = 873 pmol/1) and a similar rise of cortisol levels (mean value = 544 nmol/1). An important peak of ACTH appeared 15 min before the increase of cortisol. In three panhypopituitary dwarfs studied, no elevation of GH or cortisol was observed. The well tolerated ornithine infusion test allows the simultaneous study of the somatotropic and corticotropic pituitary secretions in children with delayed growth.
THE SPECIES SPECIFICITY OF TSH RECEPTOR BINDING ANTIBODIES AS MEASURED BY RADIORECEPTOR ASSAY
Authors: STRAKOSCH C. R. , JOYNER DIANNE , MANLEY S. W. W. , WALL J. R.
Published: March 2008

The species specificity of TSH binding inhibitory antibodies was compared for patients with untreated Graves' hyperthyroidism, past Graves' hyper‐thyroidism, active ophthalmopathy with past hyperthyroidism, and subacute thyroiditis, by measuring inhibition of TSH binding to plasma membranes prepared from human, guinea‐pig, calf, pig, and dog thyroid glands in a radioreceptor assay. Results were expressed as TSH binding inhibition indices (TBII). Broad species reactivity was demonstrated. This was greatest with pig and least with guinea‐pig thyroid membranes. Immunoglobulin (Ig) from patients in whom strongly positive tests with human thyroid preparations were demonstrated were usually strongly positive with all other species tested, whereas Ig from patients which were less strongly positive with human were, generally, also less positive with the other species. There was a tendency for greater species reactivity of TSH binding inhibiting antibodies from patients with treated Graves' hyperthyroidism (with or without eye disease) than of those from untreated patients with Graves' hyperthyroidism or subacute thyroiditis. Combining the data from all groups, correlation between TBII for human membranes and those of other species was best for dog and least for guinea‐pig. It is concluded that the TSH binding inhibiting antibody is a polyclonal antibody against a single antigen at or near the TSH receptor, and that the degree of reactivity with its antigen in other species depends, mainly, on the amount of antibody present in the serum.
PITUITARY GIGANTISM: A DISABLING CONDITION
Authors: WHITEHEAD E. M. , SHALET S. M. , DAVIES D. , ENOCH B. A. , PRICE D. A. , BEARDWELL C. G.
Published: March 2008

Ten pituitary giants have been seen in hospitals in the Manchester region between 1938 and 1980, nine of whom are still alive. We report the clinical and hormonal features in eight of these cases. Marked skeletal deformity and psychological problems were common. We draw attention to the importance of early diagnosis and treatment if the long‐term sequelae of pituitary gigantism are to be prevented.
HYPERPROLACTINAEMIA AFTER EXTERNAL IRRADIATION FOR ACROMEGALY
Authors: CLARK A. J. L. , MASHITER K. , GOOLDEN A. W. , JOPLIN G. F.
Published: March 2008

The progress of twelve patients who received external irradiation of the pituitary as sole treatment for acromegaly was reviewed. In all cases a fall in serum GH was achieved and no patient developed hypopituitarism. Three had mild hyperprolactinaemia before therapy. In all twelve cases, PRL levels rose after treatment, in five entering the hyperprolactinaemic range. It is suggested that the most likely cause is interference with the supply of prolactin release inhibiting factor (PIF) by the effects of irradiation on the hypothalamus.
EFFECTS OF CIMETIDINE ON THYROID HORMONES
Authors: HUGUES J. N. , PERRET G. , SEBAOUN J. , MODIGLIANI E.
Published: March 2008

Short‐term administration of the H2‐antagonist cimetidine (400 mg three times/day for 5 days) was performed in eight healthy male volunteers and its effects on both thyroid hormone levels and on hypophyseal hormone release induced by acute hypoglycaemia and TRH were tested. Absolute values of basal and post‐TRH serum T3 were decreased by treatment, while basal and stimulated serum rT3 and T4 levels were not altered significantly. Cimetidine administration did not change the hormone release induced by acute hypoglycaemia but significantly enhanced the prolactin and TSH responses to TRH. Our results suggest that cimetidine administration can modify the peripheral metabolism rather than the secretion of thyroid hormones.
IS TESTICULAR ENDOCRINE FUNCTION ABNORMAL IN YOUNG MEN WITH SPINAL CORD INJURIES?
Authors: YOUNG R. J. , STRACHAN R. K. , SETH J. , NICOL K. , FRIER B. M. , CORRALL R. J. M.
Published: March 2008

Plasma concentrations of FSH, LH, testosterone and prolactin have been studied in seventeen men, aged 19 to 38 years, with traumatic paraplegia. Plasma testosterone, FSH and LH values were normal in all patients. The median LH concentration in patients was significantly higher (P < 0.05) than in controls but there was no difference for FSH or testosterone. Plasma prolactin was high in five patients and the median prolactin concentration in patients was significantly greater (P < 0.001) than in controls. It is concluded that there is no evidence of primary testicular failure in young paraplegics but it is possible that testicular hypofunction in some paraplegics may be related to increased prolactin production.
RAPID COMMUNICATION: A COMPARISON OF FREE T4 AND THE RATIO OF TOTAL T4 TO T4‐BINDING GLOBULIN IN SERUM THROUGH PREGNANCY
Authors: WHITWORTH A. S. , MIDGLEY J. E. M. , WILKINS T. A.
Published: March 2008

Serum free T4 concentrations have been variously reported as either constant or falling in pregnancy. In this study, 122 serum samples from apparently normal pregnancies were used to derive euthyroid ranges throughout pregnancy for T4 and free T 4 (measured by the Amerlex kits) and for T4‐binding globulin (TBG). The mean free T4 concentration fell with increasing gestational age, the range of values in the third trimester being narrower than the non‐pregnant normal range. Evidence is reviewed which shows that the Amerlex free T4 assay is unaffected by the elevation of TBG in non‐pregnant subjects. The decline in mean free T4 as pregnancy proceeds is in good agreement with the change in free T4 predicted by the falling T4/TBG ratio.
FERTILITY AFTER CHILDBIRTH: INFANT FEEDING PATTERNS, BASAL PRL LEVELS AND POST‐PARTUM OVULATION
Authors: HOWIE P. W. , McNEILLY A. S. , HOUSTON M. J. , COOK A. , BOYLE H.
Published: March 2008

The infant feeding patterns at the time of first ovulation after childbirth were determined in a longitudinal study of twenty‐seven mothers who chose to breast feed their babies. Fourteen mothers suppressed ovulation throughout lactation and thirteen ovulated while still breast feeding. Those who ovulated while breast feeding had all introduced two or more supplementary feeds/day, reduced suckling frequency to less than six times/day and reduced suckling duration to less than 60 min/day at the time of first ovulation. Basal PRL levels had fallen to below 600 μU/l in all but one of the mothers at first ovulation.

Those mothers who suppressed ovulation for more than 40 weeks post‐partum (late ovulation group) were compared with those who ovulated between 30 and 40 weeks post‐partum (middle group) and with those who ovulated before 30 weeks post‐partum (early group). The late ovulation group breast‐fed for longest, suckled most intensively, maintained night feeds for longest and introduced supplementary feeds most gradually.

This study suggests suckling may be the most important factor inhibiting the return of ovulation during lactation and that policies which encourage increased suckling frequency and duration will maximize the contraceptive effects of breast feeding.
PARATHYROID SUPPRESSIBILITY IN HYPERPARATHYROIDISM DUE TO CHRONIC RENAL FAILURE: STUDIES WITH AUTOTRANSPLANTED PARATHYROID TISSUE
Authors: BORN WALTER , DAMBACHER MAXIMILIAN A. , MEYRIER ALAIN , ARDAILLOU RAYMOND , FISCHER JAN A.
Published: March 2008

Suppressibility of parathyroid hormone (PTH) secretion by calcium was evaluated in six patients with chronic renal failure and parathyroid tissue autotransplanted into the forearm. One patient was reinvestigated after renal transplantation. Plasma PTH levels were measured in the venous effluent of transplanted parathyroid tissue (VE) and in peripheral blood (PB) with two radioimmunoassays (RIA). One of these detected predominantly the intact human parathyroid hormone‐(1–84) [PTH‐(1–84)] (N‐assay) and another in addition carboxyl (COOH)‐terminal fragments (C‐assay). At 5 min after the start of 12‐min calcium infusions, resulting in a mean increase of plasma calcium levels of 0±6 mmol/l (P < 0±01), PTH was lowered to 44±10% (mean ± SE) (P < 0±01) of preinfusion levels in the VE and to 88±4% (P < 0±05) in PB, when measured in the N‐assay; subsequently the plasma calcium level remained raised and PTH level lowered. When estimated in the C‐assay, PTH was significantly lowered to 82± 6% (P < 0–05) in the VE at 120 min, and to between 91 ± 2% and 96 ± 2% (P < 0±01‐ < 0±05) in the PB at 20 to 120 min after the start of the calcium infusions. The results were extended with gel permeation chromatography of representative plasma samples. After renal transplantation and restoration of renal function gel filtration analysis indicated that the levels of intact PTH‐(1–84) were 49±6 and of its COOH‐terminal fragments 3±5 higher in the VE than in PB. In response to i.v. calcium administration intact PTH and its COOH‐terminal fragments were lowered to 25% and 62% in the VE, and to 29% and 86% in PB, respectively. These findings demonstrate that the secretion of intact PTH‐(1–84) is suppressed within minutes in response to i.v. calcium administration; a slower fall of the secretion of COOH‐terminal PTH fragments was demonstrated only after restoration of near‐normal renal function.