bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF OESTROGEN PRETREATMENT ON SUBSEQUENT RESPONSE TO LUTEINIZING HORMONE RELEASING HORMONE IN NORMAL WOMEN
Authors: SHAW R. W. , BUTT W. R. , LONDON D. R.
Published: March 2008

Twenty‐two normal, regularly menstruating female subjects had an LHRH test performed before and after pretreatment with 0.5 mg, 1 mg or 2.5 mg of oestradiol benzoate during the follicular phase of their menstrual cycles (days 4–8). Two further women acted as controls and received no oestrogen; they showed identical responses for both LH and FSH release when LHRH tests were performed at intervals of 48 h. Oestrogen pretreatment induced a biphasic effect upon subsequent LHRH response. Four subjects retested 20 h after 0.5 mg oestradiol benzoate showed either no change or a slight suppression of LH and FSH release. Fifteen of the eighteen women pretreated with oestradiol benzoate and retested 44 h later showed significantly increased LH release and fourteen significantly increased FSH release when compared to their control responses. The responses appeared to be dose related with a positive correlation between sum of LH increments and basal oestradiol levels (r= 0.61; P<0.001) and a similar correlation (r= 0.67; P<0.001) between sum of FSH increments and basal oestradiol levels. The physiological significance of this biphasic action of oestrogen upon pituitary sensitivity is discussed in relation to the control of the menstrual cycle.
SERUM TRIIODOTHYRONINE IN SOLITARY AUTONOMOUS NODULES OF THE THYROID
Authors: MARSDEN PHILIP , FACER PAUL , ACOSTA MANUEL , McKERRON C. G.
Published: March 2008

Seventeen patients with solitary autonomous nodules of the thyroid were studied. Eight had clinical features of hyperthyroidism though in some the clinical manifestations were mild. The serum T3 concentration was elevated in all patients with hyperthyroidism but the serum T4 and free thyroxine index were within the normal range in five. All patients with hyperthyroidism subsequently responded to treatment. These findings suggest a high incidence of preferential T3 hypersecretion in hyperthyoidism associated with solitary autonomous thyroid nodules. A further nine patients with single autonomous nodules were clinically euthyroid with normal serum T3 and T4 concentrations and remained euthyroid from 6 to 24 months on serial review.
STUDIES OF IN VITRO STEROID METABOLISM BY TESTIS TISSUE FROM ‘COMPLETE’ AND ‘INCOMPLETE’ FORMS OF TESTICULAR FEMINIZATION
Authors: BELL JANET B. G.
Published: March 2008

The in vitro steroid metabolism of testicular tissue from seven cases of testicular feminization was studied. Using radioactive steroid substrates of both C21 and C19 configurations, kinetic studies of these tissues showed that the major pathway of testosterone production was via the Δ5 pathway, i.e. pregnenolone → 17α‐hydroxy‐pregneolone → dehydroepiandrosterone → androstenedione and androstenediol → testosterone, with the accumulation of dehydroepiandrosterone and androstenediol. This accumulation of dehydroepiandrosterone and androstenediol does not occur in similar incubations of normal human testis tissue.

The seven cases of testicular feminization were classified as ‘complete’ or ‘incomplete’ forms of the syndrome by reference to clinical data and the histology of the testicular tissue. It was concluded that the biochemical differences between the two forms of the syndrome were the greater production and accumulation of C21 and C19Δ4 steroids from the C21 and C19Δ5 steroid precursors indicating the relatively greater activity of the C21‐3β‐hydroxysteroid dehydrogenase‐isomerase enzyme in the ‘incomplete’ form.
HORMONAL STUDIES IN KLINEFELTER'S SYNDROME
Authors: WANG C. , BAKER H. W. G. , de KRETSER D. M. , HUDSON B.
Published: March 2008

Some aspects of the hormonal abnormalities of Klinefelter's syndrome have been studied in nineteen patients. As a group the plasma production rate, the total and free levels of testosterone, and the metabolic clearance rates of testosterone and oestradiol were low. Plasma oestradiol, LH and FSH levels were elevated and there was increased peripheral conversion of testosterone to oestradiol. The production rates of oestradiol and the binding capacities of the sex steroid binding globulin were normal. There were fluctuations in the blood levels of LH, FSH, testosterone and oestradiol, but these appeared to be less marked than in healthy men. Both LH and FSH levels were suppressed by acute or prolonged testosterone administration and there was no evidence for a differential effect on LH. It is suggested that the threshold for suppression of LH and FSH is increased in hyper‐gonadotrophic states. Although no statistically significant relationships were found between the hormonal and clinical abnormalities of the syndrome it is probable that the hyperoestrogenism and androgen deficiency are linked to the development of the signs of feminization and hypogonadism.
SERUM GONADOTROPHINS IN YOUNG CHILDREN
Authors: RYLE MARGARET , STEPHENSON JUDITH , WILLIAMS J. , STUART J.
Published: March 2008

LH and FSH were assayed in serum samples from children ranging from newborn to 13 years. In boys, LH was found in most samples up to 4 months of age, in many up to 10 months, but in only 38% between 1 and 8 years. In girls, it was found in only 29% of the samples under 1 year and the frequency and concentration changed little thereafter until 8‐10 years. FSH was detected in all samples from boys up to 4 months and in most of those from girls up to 2 years. After these ages the frequency declined in each sex and there was little further change until 8‐10 years. Between 1 and 8 years the proportion of samples containing either FSH or LH was similar for the two sexes, but whereas in boys high LH tended to be associated with high FSH, and vice versa, there was no such correlation in girls. The results are discussed in relation to gonadal development and steroid synthesis.
CLEARANCE AND IDENTIFICATION OF THYROTROPHIN RELEASING HORMONE IN HUMAN URINE AFTER INTRAVENOUS INJECTIONS
Authors: JEFFCOATE S. L. , WHITE NICKI
Published: March 2008

The urine clearance of TRH after intravenous injection in man has been measured by radioimmunoassay. Between 4.4% and 10.7% of the dose was excreted within 90 min, the majority within 30 min. The TRH excreted was immunochemically and chromatographically indistiguishable from synthetic TRH and was inactivated by plasma enzymes with the same kinetic characteristics. The immunoreactive TRH‐like material in basal urine samples was not TRH however: chromato‐graphically and enzymatically it behaved differently from the synthetic tripeptide.
EARLY DIAGNOSIS OF CONGENITAL ADRENAL HYPERLASIA BY MEASUREMENT OF 17‐HYDROXYPROGESTERONE
Authors: YOUSSEFNEJADIAN E. , DAVID R.
Published: March 2008

Plasma 17‐hydroxyprogesterone was measured by a simple radioimmunoassay technique in six infants, aged 3 days to 3 months, with congental adrenal hyperplasia due to 21‐hydroxylases defiviencey. Hormonal levels in this gruup were compared to those of twnety normal newborns and to those found inh sixty samples of umbilical vein blood from normal delivers. Plasma 17‐hydroxyprogenterone concentrations were markedly elevated in all congenital adrenal hyperplasia infants (range 544.7–1837 nmol/1, normal 3.03–19.06) at a time when urinary studies in some of these were either not diagnostic or inconclusive. In one infant whose cord blood was analysed, the level was also greatly reised. The data suggest that early definitive diagnosis of congenital sadrenal hyperplasia can be established by measurment of plasma 17‐hydroxyprogesterone.
MALIGNANT METASTATIC INSULINOMA TREATED WITH STREPTOZOTOCIN
Authors: GEFEL A. , FLATAU E. , AYALON D. , PAPO J. , LOEWENTHAL M.
Published: March 2008

A patient with metastatic insulinoma who suffered from severe hypoglycaemic attacks was treated with 7.5 of streptozotocin (Upjohn). Shortly after the start of treatment, the hypoglycaemic attacks ceased; fasting blood glucose levels and serum immunoreactive insulin values returned to normal upon completion of the treatment. Two years after treatment, the patient is well and active and has not had any attacks. The oral glucose tolerance test and tolbutamide stimulation test now show serum immunoreactive insulin excertion patterns similar to those seen in diabetics.
THE INFLUENCE OF PREOPERATIVE DRUG TREATMENT ON THE HISTOLOGICAL APPEARANCES AND IN VITRO131I UPTAKE OF HUMAN HYPERPLASTIC THYROID GLAND
Authors: BECK J. SWANSON , ELMSLIE WANDA H. , HARBITZ Th. B. , MICHIE W. , NICOL A. G. , PEGG C. A. S. , YOUNG R. J.
Published: March 2008

The specimen of thyroid resected at partial thyroidectomy from 103 patients with primary thyrotoxicosis was studied with histometric and organ culture techniques. Twenty‐seven patients had been prepared for operation with propranolol and seventy‐six with carbimazole: all received Lugol's iodine for 10 days before operation.

The resected specimen and deduced total thyroid weight was greater in the patients prepared with carbimazole. There was no absolute qualitative histopathological difference in the appearance of the glands of the two groups of patients, but histometry showed that the volume percentage of colloid and total gland colloid weight was significantly greater in the patients prepared with carbimazole: the volume percentage of epithelial cells and the total gland epithelial cell weight was similar in the two groups.

The iodide concentrating capacity per g wet weight thyroid tissue or per unit volume of colloid did not differ significantly between the two groups. However, the iodide concentration capacity per unit volume of epithelial cells was significantly higher in the carbimazole prepared patients than in those prepared with propranolol.
A RAPID RADIOIMMUNOASSAY FOR DETERMINATION OF DEHYDROEPIANDROSTERONE SULPHATE IN HUMAN PLASMA
Authors: CATTANEO S. , FORTI G. , FIORELLI G. , BARBIERI U. , SERIO M.
Published: March 2008

A rapid radioimmunoassay for the determination of dehydroepiandrosterone sulphate (DHEA‐S) in diluted human plasma is described. The radioimmunoassay is performed using an antiserum to DHEA‐3‐hemisuccinate‐BSA. A charcoaldextran mixture is used for separation of the bound from the free fraction. The reliability criteria of the method in terms of precision, accuracy, sensitivity and specificity have been evaluated.

The mean level of DHEA‐S in plasma samples from normal men (age range 24‐37) is 241.5±72.5 μg/dl. In normal premenopausal women the highest values are in the second third of the menstrual cycle (corresponding to the ovulatory phase). In normal old men (age range 64‐86) and in post‐menopausal women (age range 55‐88) the mean values are, respectively, 51.9±33.8 and 53.8±34.0.

The DHEA‐S levels found in several cases of adreno‐cortical disorders are reported. In primary adrenal insufficiency and in Cushing's syndrome due to adrenal adenoma or bilateral multinodular hyperplasia low values are found; in Cushing's syndrome due to bilateral adrenal hyperplasia normal values are usually found.
RADIOIMMUNOASSAY OF PLASMA DIHYDROTESTOSTERONE IN NORMAL AND HYPOGONODAL MEN
Authors: PAZZAGLI M. , FORTI G. , CAPPELLINI A. , SERIO M.
Published: March 2008

A radioimmunoassay for determination of dihydrotestosterone (DHT) in man is described. After extraction from plasma, DHT is separated by paper chromatography.

The radioimmunoassay is performed using an antiserum to dihydrotestosterone‐3‐oxime‐BSA and a charcoal‐dextran mixture is used to separate the free from the bound fraction. The reliability criteria of the method in terms of precision, accuracy, sensitivity and specificity have been evaluated.

The mean level of DHT in plasma samples from young (age 21‐37) and old (age 65‐90) normal men is respectively (mean ± SD) 54.7 ± 19 ng/dl (n= 17) and 39.1 ± 19 ng/dl (n= 14). The difference is statistically significant (P<0.01). The values found in seven patients with Klinefelter's syndrome (21.0 ± 6 ng/dl) are significantly lower than normal young subjects (P<0.01).

Lastly, the DHT levels found in a mixed group of male hypogonadism (azoospermia, due to tubular failure, germinal cell aplasia and anorchia) are reported.
FETAL HYPOTHYROIDISM COMPLICATING MEDICAL TREATMENT OF THYROTOXICOSIS IN PREGNANCY
Authors: IBBERTSON H. K. , SEDDON R. J. , CROXSON M. S.
Published: March 2008

Two women with thyrotoxicosis were treated with antithyroid drugs during pregnancy. One women had inadvertently received a therapeutic dose of radioiodine at 21 weeks gestation and the other suffered from severe thyrotoxicosis with a serum LATS level of 1850%. In both patients, the serum triiodothyronine was maintained above 500 ng/dl by the concurrent oral administration of this hormone. Despite this precaution, cord serum thyrotrophin levels were markedly elevated and both infants showed clinical signs of hypothyroidism at birth. This experience indicates that triiodothyronine does not prevent fetal hypothyroidism when given to the mother in pharmacological amounts.
METABOLIC RESPONSES TO MONOCOMPONENT HUMAN INSULIN INFUSIONS IN NORMAL SUBJECTS AND PATIENTS WITH LIVER AND ENDOCRINE DISEASE
Authors: WEST T. E. T. , OWENS D. , SÖNKSEN P. H. , SRIVASTAVA M. C. , TOMPKINS C. V. , NABARRO J. D. N.
Published: March 2008

Hypoglycaemic and growth hormone responses were studied at different steady‐state plasma insulin concentrations during a graded infusion of monocomponent human insulin. The control group consisted of ten volunteer subjects. The other groups studied included women taking oral contraceptives and patients with obesity, thyrotoxicosis, myxoedema, acromegaly, diabetes mellitus (moderate and severe) and liver disease.

The hypoglycaemic response was measured in two ways: (i) the percentage reduction in plasma glucose below basal, and (ii) the rate of fall of plasma glucose (Kg‐%/min). Insulin sensitivity was greatest in the normal subjects and in the other groups decreased in the order thyrotoxicosis>oral contraceptive>obesity>myxoedema>acromegaly>liver disease. Insulin sensitivity was difficult to assess in the diabetic patients because basal plasma glucose concentrations were elevated. At any given insulin concentration, the diabetics metabolized approximately the same amount of glucose as the normal subjects but the fact that this rate of glucose turnover occurred at higher plasma glucose concentrations probably indicated insulin resistance. Within each group Kg at each dose level of insulin correlated with the steady state plasma insulin concentration during the same infusion period. Diminishing sensitivity to insulin was reflected in an increasing fasting plasma insulin and insulin/glucose ratio except in patients with diabetes.

GH responses to insulin infusion in normal subjects reflected the pattern of fall of plasma glucose. In the diabetic patients GH secretion appeared to be related to the infusion of insulin and occurred before plasma glucose had fallen to hypoglycaemic levels. GH secretory patterns were within normal limits in women taking oral contraceptives and in seven of eleven patients with liver disease but were impaired in three of seven patients with thyrotoxicosis and four of five patients with myxoedema. Four obese patients had a markedly delayed but eventually normal GH response.
THE HCG STIMULATION TEST IN MEN WITH TESTICULAR DISORDERS
Authors: DEKRETSER D. M. , BURGER H. G. , HUDSON B. , KEOGH E. J.
Published: March 2008

The rise in plasma testosterone levels following stimulation with human chorionic gonadotrophin (3000 i.u./day for 4 days) has been used as a test of interstitial cell function in normal men and men with testicular disorders. The large majority of patients with testicular disorders resulting in infertility, showed a subnormal testosterone response to stimulation. The most marked impairment was noted in those patients with the biopsy appearance of germinal cell arrest and Sertoli cell only syndrome.
INCIDENCE AND SIGNIFICANCE OF HYPERPROLACTINAEMIA IN WOMEN WITH AMENORRHOEA
Authors: FRANKS S. , MURRAY M. A. F. , JEQUIER A. M. , STEELE S. J. , NABARRO J. D. N. , JACOBS H. S.
Published: March 2008

Serum prolactin and gonadotrophin concentrations were measured by radio‐immunoassay in 106 women with amenorrhoea. Prolactin was normal in those with weight related disorders, primary ovarian failure, those with a variety of systemic diseases and in those in whom amenorrhoea followed treatment with the oral contraceptive and in unexplained primary amenorrhoea. Gonadotrophin concentrations in the above patients were normal except in those with primary ovarian failure. Prolactin was elevated in eight of forty patients (20%) with functional secondary amenorrhoea and was greatly raised in all but one of the thirteen women in this series with pituitary tumours (five of whom were studied only after treatment). Only three patients in each of the last two groups had galactorrhoea. Gonadotrophin levels were normal or slightly raised in all of the hyperprolactinaemic patients apart from those studied after hypophysectomy. Four hyperprolactinaemic patients (three with pituitary tumours and one with functional amenorrhoea) who did not have galactorrhoea have been treated with bromocriptine. Prolactin secretion was reduced in all patients and, in the two with normal gonadotrophins, ovulatory menstruation was resumed. One became pregnant in the second ovulation cycle after starting treatment.

We conclude that, despite the rarity of galactorrhoea, hyperprolactinaemia is common in patients with functional amenorrhoea and in those with pituitary tumours. Treatment with bromocriptine in patients with normal gonadotrophins restores ovulation when the infertility is due to prolactin excess.
THE ROLE OF PROLACTIN IN THE RESTORATION OF OVARIAN FUNCTION DURING THE EARLY POST‐PARTUM PERIOD IN THE HUMAN FEMALE
Authors: ROLLAND RUNE , JONG FRANK H. DE , SCHELLEKENS LOUIS A. , LEQUIN RUDOLF M.
Published: March 2008

Serial plasma levels of prolactin, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), 17β‐oestradiol (E) and progesterone (P) were determined by radioimmunoassay in ten healthy women during late pregnancy and the puerperium during inhibition of lactation by Bromergocryptine. This medication was continued until the occurrence of the first menstruation, at which point an endometrial biopsy was taken. Prolactin was very effectively suppressed by Bromergocryptine in all patients, as was lactation. FSH was nearly undetectable during late pregnancy and the first week post‐partum with an increase back to normal levels between day 7 and day 12. Thereafter FSH levels were within the normal cyclic range. Following clearance of human chorionic gonadotrophin (HCG) during the first 2 weeks post‐partum, LH was found within the normal cyclic range in all patients. From day 7 E increased in nine of ten patients to reach levels during the fourth week which are seen normally at the moment of the pre‐ovulatory E‐surge in cycling women. In eight of the ten cases this was concomitant with high levels of LH. The tenth patient showed a high E level at day 36. P was fully excreted within 7 days and remained low until approximately day 20. Thereafter an increase was demonstrated with levels as found during the luteal stage of the menstrual cycle in nine patients within 33 days and within 40 days in all ten patients. The endometrial biopsies showed clear signs of secretory activity. The probable action of prolactin on ovarian function is discussed. It is suggested that during the puerperium the ovaries are the more refractory part of the hypothalamic‐pituitary‐ovarian axis, due probably to an influence of prolactin on the ovarian steroid synthesis.
CYPROTERONE ACETATE: A STUDY INVOLVING TWO VOLUNTEERS WITH IDIOPATHIC HIRSUTISM
Authors: BARNES E. W. , IRVINE W. J. , HUNTER W. M. , ISMAIL A. A. A.
Published: March 2008

Two female volunteers, of menstrual age, with severe idiopathic hirsutism were treated for eight cycles and fifteen cycles respectively with cyproterone acetate 50 mg twice daily on days 5‐14 of the cycle. In all but one cycle, ethinyl oestradiol in a dose of 50 μg daily from day 5 to day 21 was given in addition. Cyproterone acetate when given alone abolished the mid‐cycle LH surge. Combined therapy with cyproterone acetate and ethinyl oestradiol produced a significant improvement in both patients’hirsutism and was accompanied by a marked reduction in the urinary excretion of LH, FSH and androgens and by a fall in plasma testosterone. However, the clinical benefit derived from this drug was due principally to its action as a peripheral antiandrogen.
PLASMA FREE FATTY ACID TURNOVER IN TOTAL LIPODYSTROPHY
Authors: BOUCHER B. J. , COHEN R. D. , FRANCE M. W. , MASON A. STUART
Published: March 2008

Basal free fatty acid (FFA) turnover was found to be elevated or at the upper limit of normal in a patient with total lipodystrophy. The decrease in plasma FFA concentration which occurred after intravenous administration of insulin was shown to be primarily due to a fall in the inflow of FFA into the circulation. These results provide support for the suggestion that adipocytes in total lipodystrophy are able to synthesize triglyceride, but that they are unable to store it because of rapid lipolysis.
OESTROGEN INDUCED HYPERTRIGLYCERIDAMIA: ROLE OF THE ADRENAL CORTEX
Authors: AFOLABI S. K. , TULLOCH B. R. , KISSEBAH A. H. , VYDELINGUM N. , FRASER T. R.
Published: March 2008

The role of the adrenal cortex in the pathogenesis of hypertriglyceridaemia associated with the intake of oral contraceptive agents containing oestrogen has been investigated in rats.

Bilateral adrenalectomy reduced the activity of hepatic enzymes regulating lipogenesis (acetyl CoA carboxylase, fatty acid synthetase) and decreased plasma triglyceride concentrations. On the other hand, the administration of high dosage corticosterone induced the activity of hepatic enzymes with consequent elevation in serum triglyceride levels.

In animals with intact adrenals the administration of oestradiol: (a) raised plasma triglyceride levels, (b) enhanced the activity of hepatic enzymes, and (c) increased the adrenal cortex: body weight ratio. The effects (a) and (b) were not observed when both adrenals were removed prior to oestrogen therapy. High dosage corticosterone replacement was found to be essential for the oestradiol to produce its effects on hepatic enzymes and plasma triglyceride levels.

The results suggest a regulatory role for the adrenal cortex in the homeostasis of plasma triglyceride concentration and that the hypertriglyceridaemia induced by the oestrogen containing preparations might be secondary to alterations in adrenocortical function.
THE ASSESSMENT OF 125I TREATMENT OF THYROTOXICOSIS
Authors: BREMNER W. F. , SPENCER CAROLE A. , RATCLIFFE WENDY A. , GREIG W. R. , RATCLIFFE J. G.
Published: March 2008

257 patients have been reviewed 1‐5 years (mean 3 years 2 months) after receiving one of five dose regimes of 125I for thyrotoxicosis. The cumulative incidence of hypothyroidism was 34% and of persistent thyrotoxicosis 17%. The group receiving doses between 351 and 500 μCi/g had the highest proportion of euthyroid patients (65%) with the lowest requirement for repeat therapy (46%). In the euthyroid patients, increasing dose of 125I was associated with progressive decline in mean thyroxine (T4) level and free thyroxine index (FTI) within the respective normal ranges, and increase in mean thyroid stimulating hormone (TSH) level to above the normal range. Euthyroid patients with elevated TSH levels had significantly lower T4 and FTI values compared with those with normal TSH, and showed a 3‐4‐fold increased rate of development of hypothyroidism over 1 year. Euthyroid patients with elevated T3 levels remained euthyroid during the subsequent year and mean T3 levels declined significantly, suggesting that abnormally elevated T3 levels after 125I do not generally indicate impending relapse of thyrotoxicosis.

It is concluded that the potential advantages of 125I therapy for thyrotoxicosis in reducing the incidence of hypothyroidism have not been realized in practice.
GALACTORRHOEA, HYPERPROLACTINAEMIA AND PITUITARY TUMOURS IN THE FEMALE
Authors: NADER S. , MASHITER K. , DOYLE F. H. , JOPLIN G. F.
Published: March 2008

A series of sixty‐two women with pituitary tumours, but having neither acromegaly nor Cushing's disease, has been analysed with respect to mode of presentation. Thirty‐six (58%) presented with amenorrhoea and galactorrhoea and a further fifteen (24%) presented with amenorrhoea only. Pretreatment prolactin levels were available in thirty‐four of these patients and in twenty‐seven (79%) hyperprolactinaemia was found, this occurring in the absence of a history of galactorrhoea in four out of ten cases.

In addition, among a series of twenty‐five unselected women with unexplained galactorrhoea, we have found twelve pituitary tumours, amenorrhoea being a feature of all twelve cases.

We conclude that the incidence of hyperprolactinaemia in women with apparently functionless pituitary tumours is much higher than previously estimated and suggest that serum prolactin should be assayed in all patients with such tumours even in the absence of a history of galactorrhoea. All patients with unexplained galactorrhoea should have careful radiological investigation for a possible pituitary tumour.
STERIOD CONJUGATES IN HUMAN SEMINAL PLASMA*
Authors: PURVIS K. , SAKSENA S. K. , LANDGREN B.‐M. , CEKAN Z. , DICZFALUSY E.
Published: March 2008

A technique for the measurement of five conjugated steroids (dehydroepiandrosterone sulphate, pregnenolone sulphate, testosterone sulphate, dihydrotestosterone sulphate and testosterone glucuronide) in human seminal plasma is described. The steroid sulphates and testosterone glucuronide were measured by radioimmunoassay after solvolysis and enzyme hydrolysis, respectively. In all cases the recognized criteria of assay reliability were fulfilled.

In a group of men with established fertility, dehydroepiandrosterone sulphate had the highest concentration and testosterone sulphate had the lowest (mean levels of 1.04 μmoles/l and 1.52 nmoles/l, respectively). The levels of pregnenolone sulphate, dihydrotestosterone sulphate and testosterone glucuronide were 30.3, 4.37 and 38.8 nmoles/l, respectively. In all cases the levels of conjugated steroid exceeded the levels of the corresponding unconjugated compound.
CLINICAL USE OF GLYCINE INTRAVENOUS LOAD FOR DIAGNOSIS OF GROWTH HORMONE DEFICIENCY
Authors: FLOREA ION , POPA MIRCEA , SIMIONESCU LIGIA , DINULESCU ELENA , JUVINÂ ELENA
Published: March 2008

Intravenous glycine injection (250 mg/kg of body weight) resulted in growth hormone release in normal children but not in those with growth hormone deficiency diagnosed by insulin‐induced hypoglycaemia. In the latter significantly higher peak concentrations of serum α‐amino nitrogen were also found. False negative responses to glycine (no GH release) were observed in two patients of short stature but normal pituitary function. In them the peak levels of serum α‐amino nitrogen were lower than in those with hypopituitarism. We propose the clinical use of glycine as an inexpensive and innocuous procedure for the detection of GH deficiency in children. A post‐glycine GH peak greater than 10.0 mu/1 seems to be a good index of an intact GH reserve.
RECURRENT HORMONE DEPENDENT CHOREA: EFFECTS OF OESTROGENS AND PROGESTOGENS
Authors: BARBER P. V. , ARNOLD A. G. , EVANS G.
Published: March 2008

Summary

A case of hemi‐chorea is described in a young woman, initially following administration of an oral contraceptive pill and recurring in a subsequent early pregnancy. The chorea ceased with the removal of the aetiological factor on each occasion. Subsequent challenge with a combined oestrogen/progestogen pill resulted in recurrence of the chorea, but the patient has been successfully maintained on a progestogen without any further symptoms. Thus it would appear that oestrogen component was the precipitating factor for the chorea.
DISSOCIATION BETWEEN TSH AND PROLACTIN DYNAMICS IN TREATED THYROTOXICOSIS
Authors: KANNAN C. , AKBAR M. , BEGUM F. , DWARAKANATHAN A. , BURKE G.
Published: March 2008

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 μg) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I‐treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4.5 years (χ= 17.1±4.1 months). Based on maximal TSH increment (ΔTSH), three patient groups were identified: Group 1 [normal ΔTSH, n = 6]: Δ prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): Δ prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): Δ prolactin was normal in five, blunted in three, and exaggerated in five.

Eleven patients (three men, eight women) were studied after 6 months antithyroid‐drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH‐TSH response. All three men showed an exaggerated Δ prolactin as did four of eight women. Three women showed a blunted Δ prolactin and in one, Δ prolactin was normal.

Thus, TRH‐induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.
CLINICAL AND ENDOCRINE FEATURES OF HYPERPROLACTINAEMIC AMENORRHOEA
Authors: JACOBS H. S. , FRANKS S. , MURRAY M. A. F. , HULL M. G. R. , STEELE S. J. , NABARRO J. D. N.
Published: March 2008

The clinical, radiological and endocrine findings in thirty‐five women with hyperprolactinaemia and amenorrhoea are described. Twelve patients had radiological evidence of a pituitary tumour and six were tested after pituitary ablation. Seventeen patients with hyperprolactinaemia and normal pituitary X‐rays were also studied. None was on any drug known to increase prolactin secretion and all patients were euthyroid when tested.

Basal serum prolactin concentrations were high in the group with untreated pituitary tumours and in those with normal X‐rays. The levels were variable in the post‐ablation cases. The increase of prolactin after TRH was subnormal in all of the groups. Serum oestradiol concentrations were low in most patients and nineteen of twenty‐one patients tested had no withdrawal bleeding after treatment with a progestogen. Mean serum gonadotrophin concentrations (basal and after LHRH) were normal in twenty‐nine patients but subnormal in four post‐ablative cases. Anovulatory responses to clomiphene were obtained in nineteen of twenty patients tested. Fifteen patients were treated with bromocriptine; twelve ovulated and eight became pregnant; two not responding had impaired LH and FSH production.

Hyperprolactinaemic amenorrhoea is a common disorder with characteristic endocrine features. Galactorrhoea is unusual (30%). Treatment with bromocriptine lowers prolactin concentrations and rapidly repairs the reproductive defect.
THE CHARACTERIZATION OF THE ACTH PRODUCED BY A PRIMARY PITUITARY TUMOUR IN A PATIENT WITH CUSHING'S DISEASE
Authors: KRIENGER DOROTHY T. , CHOI HO‐SOON H. , ANDERSON PAUL J.
Published: March 2008

The nature of ACTH present in pitutary tumours associated with Cushing's disease has not been previously characterized nor correlated with the electron microscopic appearance. The present report describes the culture of tumour tissue obtained from a patient with a pituitary tumour associated with Cushing's disease, and the characterization of the ACTH content of tumour and media by bioassay, immunoassay, and Sephadex G‐50 gel filtration. Electron microscopic studies were also performed. The pathological diagnosis was pituitary adenoma with basophilic PAS‐positive granules. Electron microscopy showed uniformity of size and shape of the tumour cells, the presence of secretory granules of varying size and density, and disorganized tubular and vacuolar arrays of endoplasmic reticulum.

The bioreactive ACTH content of the tumour was 0.29 μ/g, Which is markedly below that seen in the normal pituitary, but within the range reported for ecotopic ACTH‐producing tumours. Immunoreactive ACTH when measured by a C‐terminal antibody was five‐fold higher than when measured by an N‐terminal antibody; the latter gave a value of 1.24 μ/g. On Sephadex G‐50 gel filtration, 9% of the N‐terminal immunoreactivity was present in the V0 fraction (‘big’ ACTH). This latter fraction had a greater percentage of bioreactivity (28%) than previously reported for this molecular species. Analysis of the tumour culture medium revealed a variation in molecular size similar to that seen in the tumour, although the percentage of ACTH of large molecular size was greater, suggesting increased secretion of a possible ‘prohormone’ by the tumour. Plasma ACTH was characterized by a 2:1 ratio of immunoreactivity (N‐terminal) to bioreactivity, and a 4:1 ratio of C‐terminal/N‐terminal immunoreactivity.

This report also appears to be the first of successful short‐term tissue culture of a primary ACTH‐producing tumour. The granule size was considerably larger than that reported for normal pituitary ACTH‐containing cells.
AN IMPROVED MATHEMATICAL MODEL OF HUMAN THYROID HORMONE REGULATION
Authors: SARATCHANDRAN P. , CARSON E. R. , REEVE J.
Published: March 2008

1. A mathematical model has been constructed of human thyroid hormone regulation by the anterior pituitary gland, which takes account of most of the currently available experimental data.

2. Successful simulation of data on the stimulation of thyrotrophin (TSH) secretion by thyrotrophin releasing hormone (TRH) was achieved assuming that the TSH secretion rate is proportional to the logarithm of the concurrent blood TRH level.

3. Data on the regulation of triiodothyronine (T3) secretion by TSH and the inhibition of TSH secretion by thyroid hormones in contrast could not be simulated on the assumption of instantaneous proportional responses. A mixture of proportional and integral control—the latter taking account of the past history of plasma levels of the regulatory hormone—appeared to be operating at both levels.

4. The pituitary gland appears to be more sensitive to a given fractional change in TRH secretion rate than to the same fractional change in T3 plasma concentration.
RETARDED INCORPORATION OF [14C] MANNOSE INTO THYROGLOBULIN OF HUMAN THYROTOXIC THYROID GLANDS
Authors: THOMSON JOHN A. , BAIRD SHEILA G.
Published: March 2008

In vitro studies using thyroid slices from human non‐toxic goitres and from thyrotoxic glands show retarded incorporation of [14C] mannose into the 19S protein of thyrotoxic glands. This was not found using [14C]galactose with thyrotoxic glands or using either labelled sugar with slices from non‐toxic goitres.

Experiments with thyroid tissue from rats on a variety of treatment regimes such as iodine supplements, carbimazole alone or with iodine supplements did not show this differential delay of [14C]mannose incorporation. This suggests that there may be some abnormality of carbohydrate incorporation into thyroglobulin in thyrotoxicosis.
ACROMEGALY CAUSED BY PULMONARY CARCINOID TUMOURS
Authors: SÖNKSEN P. H. , AYRES A. B. , BRAIMBRIDGE M. , CORRIN B. , DAVIES D. R. , JEREMIAH G. M. , OATEN S. W. , LOWY C. , WEST T. E. T.
Published: March 2008

Two patients are described whose acromegaly was cured by removal of a bronchial carcinoid tumour. One had an enlarged pituitary fossa and evidence is presented that in this patient the tumour was not secreting growth hormone. The evidence available suggests that the tumour was producing a growth hormone releasing substance. It is suggested that some cases of the pluriglandular syndrome may be secondary to small bronchial carcinoid tumours that produce substances as yet unidentified, that stimulate the growth and hyperactivity of other endocrine tissue.
STUDIES ON THE CONTROL OF THYROTROPHIN SECRETION IN NORMAL MAN
Authors: VICE P. A. , CLARK F. , SCHARDT W. , EVERED DAVID
Published: March 2008

The effect of graded doses of thyroxine (T4) and triiodothyronine (T3) separately on the pituitary‐thyroid axis has been studied in normal subjects. It has been demonstrated that small doses (50 μg T4 or 20 μg T3) cause significant suppression of the pituitary‐thyroid axis. There was a strong negative correlation between the TSH value 20 min after TRH and the does of thyroid hormone. T4 supplements led to a progressive dose‐related rise in serum T4 and no significant change in T3 until high daily doses (> 200 μg) were administered. T3 supplements led to a progressive reduction in serum T4 and there was no change in T3 until substantial supplements were given (7gt; 50 μg/day). Concurrent administration of 6 PTU had no effect on the pattern of pituitary suppression or thyroid hormone concentrations in contrast to its reported effect in hypothyroid subjects.
PROLACTIN AND SOMATOMEDIN STUDIES IN THE SYNDROME OF GROWTH HORMONE‐INDEPENDENT GROWTH
Authors: GLUCKMAN P. D. , HOLDAWAY I. M.
Published: March 2008

Three children with hypothalamic mass lesions and continued linear growth in the absence of circulating growth hormone are presented. Serum growth hormone levels were either undetectable or very low both basally and following insulin‐induced hypoglycaemia, whereas serum somatomedin levels were normal. Two subjects had elevated serum levels of prolactin, and in one of these prolactin suppression with bromoergocryptine failed to influence either somatomedin levels or urinary excretion of nitrogen, hydroxyproline and calcium. Although only one case was studied in detail these data suggest that maintenance of serum somatomedin and of normal growth in these children was not dependent upon prolactin secretion.
EFFECT OF TWO SEROTONIN ANTAGONISTS ON PROLACTIN AND THYROTROPHIN SECRETION IN MAN
Authors: FERRARI C. , PARACCHI ALESSANDRA , RONDENA M. , BECK‐PECCOZ P. , FAGLIA G.
Published: March 2008

The effects of serotoninergic blockade on prolactin and thyrotrophin secretion in man was evaluated by determining the basal and TRH‐stimulated serum prolactin and TSH concentrations in normal volunteers before and after a 3 days course of cyproheptadine or methergoline administration. Cyproheptadine, a serotonin antagonist with antihistaminic, anticholinergic and antidopaminergic properties as well, did not affect prolactin secretion, while it reduced the serum TSH response to TRH; methergoline, a specific blocker of central serotonin receptors, decreased basal and TRH‐induced serum prolactin levels, without affecting TSH secretion. These results support the existence of serotoninergic stimulatory influences on human prolactin release, while suggesting that human TSH secretion is not modulated by serotoninergic inputs.
MEASURMENT OF CIRCULATING THYROID MICROSOMAL ANTIBODIES BY THE TANNED RED CELL HAEMAGGLUTINATION TECHNIQUE: ITS USEFULNESS IN THE DIAGNOSIS OF AUTOIMMUNE THYROID DISEASES
Authors: AMINO NOBUYUKI , HAGEN SWEN R. , YAMADA NOBORU , REFETOFF SAMUEL
Published: March 2008

Thyroid‐microsomal antibodies were quantitated by a new technique utilizing tanned sheep red blood cells coated with human thyroid microsomal antigens. This haemagglutination assay (MCHA) correlated with the immunofluorescent antibody (FAB) but not with the thyroglobulin haemagglutination antibodies (TGHA) assay.

Of forth‐one patients with Hasmimoto's thyroiditis, Thirty‐nine (95%) were MCHA but only twenty‐four (59%) TGHA positive. Titres were similar for the hypothyroid and euthyroid patients. Patients less than 20 years of age had either negative (50%) or low titre (less than 1:160) TGHA but 100% positive MCHA at titres greater than 1:1280. Of twenty‐one patients with Graves’diseases eighteen (86%) were MCHA and six (29%) TGHA positive. Of thirty‐two patients without thyroid diseases eleven (34%) were MCHA and/or TGHA positive. On the basis of family history and associated abnormalities, in eight of eleven, positive antibodies may have been due to subclinical Hashimoto's thyroiditis.

Fourteen subjects of a control group (10%) were MCHA postivie. Seven of ten examined had goitres.

MCHA is a simple and quantitative test, useful in the diagnosis of autoinnune thyroid diseases.
A COMPARISON OF THE EFFECT OF LEVODOPA AND SOMATOSTATIN ON THE PLASMA LEVELS OF GROWTH HORMONE, INSULIN, GLUCAGON AND PROLACTIN IN ACROMEGALY
Authors: DUNN P. J. , DONALD R. A. , ESPINER E. A.
Published: March 2008

The acute suppressive effects of l‐dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 μg) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). l‐Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P<0.025; P<0.05 respectively). Plasma glucose concentrations did not change. l‐Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but l‐Dopa suppressed basal values to <2 ng/ml in five patients. This study shows that the plasma GH change after the administration of l‐dopa and somatostatin in acromegaly is commparable and confirms the pancreatic effects of somatostatin.
MODULATION OF PITUITARY RESPONSIVENESS TO EXOGENOUS LHRH BY AN OESTROGENIC AND AN ANTI‐OESTROGENIC COMPOUND IN THE NORMAL MALE
Authors: DHONT M. , DE GEZELLE H. , VANDEKERCKHOVE D.
Published: March 2008

The effect of clomiphene (100 mg daily for 10 days) and ethinyl oestradiol (100 μg daily for 10 days) on the gonadotrophin response to synthetic LHRH has been investigated in two groups of five normal males. A third group of five men served as control group. LHRH, 25 μg, was injected intravenously on days 0, 4, 7 and 10 and the response of serum LH and FSH was monitored by radioimmunoassay. In contrast to the wide inter‐individual variation of the response pattern, the intraindividual variation of the response to LHRH in the control group was small. Clomiphene induced a significant elevation of the baseline levels of LH and FSH after a few days of treatment; the pituitary responsiveness to LHRH, however, was significantly reduced. Oestrogen treatment resulted in a uniform suppression of both basal gonadotrophin levels and pituitary responsiveness. The decreased gonadotrophin response to LHRH during clomiphene treatment is thought to be caused by a relative and temporary pituitary depletion of the releasable gonadotrophin content. Although the suppression of LH and FSH response during oestrogen treatment may point to a direct inhibitory effect of oestrogen on pituitary gonadotrophin release, an indirect hypothalamic pathway, through suppression of endogenous LHRH, cannot be ruled out.
EFFECTS OF GROWTH HORMONE RELEASE‐INHIBITING HORMONE AND BROMOCRYPTINE (CB 154) IN STATES OF ABNORMAL PITUITARY‐ADRENAL FUNCTION
Authors: BENKER G. , HACKENBERG K. , HAMBURGER B. , REINWEIN D.
Published: March 2008

Growth hormone release‐inhibiting hormone (GHR‐IH) was administered to five patients with abnormal pituitary‐adrenal function. There was immediate suppression by about 50% of ACTH levels in two patients who had undergone bilateral adrenalectomy because of Cushing's disease; one of them had Nelson's syndrome. Bromocryptine (2.5 mg) suppressed ACTH levels by 62‐67% for more than 6 h in these patients GHR‐IH did not significantly influence cortisol secretion by an adrenal carcinoma and only slight changes were seen in two patients with Addison's disease. The possible therapeutic implications are discussed.
INCREASED SOMATOSTATIN CONTENT OF ISLETS FROM STREPTOZOTOCIN‐DIABETIC RATS
Authors: PATEL YOGESH C. , WEIR GORDON C.
Published: March 2008

Pancreatic islets were isolated from control and streptozotocin‐diabetic rats. Somatostatin content as determined by radioimmunoassay was strikingly increased in the diabetic group. Immunoreactive insulin content was markedly reduced and glucagon was moderately increased. The mechanisms responsible for the somatostatin changes are unknown.
ASSESSMENT BY CONTINUOUS CARDIAC MONITORING OF MINIMUM DURATION OF PREOPERATIVE PROPRANOLOL TREATMENT IN THYROTOXIC PATIENTS
Authors: TOFT A. D. , IRVINE W. J. , CAMPBELL R. W. F.
Published: March 2008

The effect of the beta‐blocker, propranolol (40 mg 6‐hourly orally) has been studied on the tachycardia of six patients with untreated thyrotoxicosis. Heart rate was monitored continuously using a light portable ECG recorder which allowed the patients to undertake normal activities during the recording periods. The most marked reduction in heart rate was evident at 24 h after starting propranolol treatment. In three of the patients there was only a minor further fall in heart rate despite continued propranolol administration, but in the remaining patients the reduction in heart rate with each successive day of treatment was more marked. These results suggest that if propranolol were to be used alone in the preparation of patients before partial thyroidectomy for thyrotoxicosis, a dose of 40 mg 6‐hourly for 3‐4 days might be sufficient.
SUPRANORMAL FSH RESPONSE TO GONADOTROPHIN‐RELEASING HORMONE IN OLIGOSPERMIC MEN WITH A NORMAL BASAL SERUM FSH CONCENTRATION
Authors: LIPSHULTZ LARRY I. , GREENBERG STANLEY H. , CAMINOS‐TORRES RAUL , SNYDER PETER J.
Published: March 2008

Twenty‐six men with severe oligospermia (sperm density <10×106/ml, but >0), but normal serum concentration of FSH, as well as normal serum concentrations of LH and testosterone, were given a 250 μg i.v. bolus dose of synthetic gonadotrophinreleasing hormone (LHRH). The serum FSH and LH responses were compared to those of a group of normal men and a group of men with oligospermia or azoospermia and elevated basal serum FSH concentration.

The mean FSH response to LHRH of the men with oligospermia but normal basal serum FSH concentration was 911 miu min/ml, nearly three times that of the normal men, 322 miu min/ml (P < 0.001), though not so great as that of the men with oligo/azoospermia and elevated basal FSH concentration (2890 miu min/ml). Ten of the twenty‐six men with oligospermia and normal basal serum FSH had a supranormal FSH response to LHRH. The mean LH response to LHRH of the men with oligospermia and normal basal serum FSH levels was not significantly different from that of the normal men.

We conclude that LHRH stimulation can often elicit a deficiency of feedback inhibition of FSH secretion not readily recognizable by measurement of the basal serum FSH concentration.