bluuebunny/crossref_metadata_2025 huggingface dataset:
THYROIDAL HORMONE METABOLISM IN OBESITY DURING SEMI‐STARVATION
Authors: GRANT A. M. , EDWARDS O. M. , HOWARD A. N. , CHALLAND G. S. , WRAIGHT E. P. , MILLS I. H.
Published: March 2008

Six obese subjects were studied over a period of 12 weeks whilst on a 1260 kJ (300 kcal) formula diet. Weight loss was initially rapid, but later slowed markedly despite good patient compliance. The basal metabolic rate (BMR) fell in all patients during the study. Plasma triiodothyronine fell in all patients, whilst the plasma half‐life of thyroxine increased. Plasma thyroxine, reverse triiodothyronine (reverse T3) and the serum prolactin and thyrotropin response to thyroliberin all showed no significant change.
HYPERPROLACTINAEMIA IN RENAL DISEASE
Authors: COWDEN E. A. , RATCLIFFE W. A. , RATCLIFFE J. G. , DOBBIE J. W. , KENNEDY A. C.
Published: March 2008

Basal prolactin concentrations in 357 patients with renal disease of defined pathology have been compared with those in 210 control subjects. Elevated prolactin concentrations were found in 113 renal patients (32%) including 53 patients in whom elevated concentrations were possibly attributable to drug therapy. In the remaining 60 patients who had hyperprolactinaemia not attributable to drugs, elevated concentrations (P < 0.005) were found exclusively in patients with impaired renal function. A significant correlation was observed between prolactin and creatinine concentrations in these patients (r= 0.45 P < 0.005) and prolactin reverted towards normal after successful renal transplantation. A significant arteriovenous prolactin concentration difference across the kidney (mean 16% range 8–29%P < 0.02) was found in seven patients with non‐renal non‐endocrine disease.

It is concluded that the hyperprolactinaemia found commonly in patients with impaired renal function is only partly attributable to drug therapy. The positive correlation between prolactin and creatinine reversion of prolactin towards normal after successful transplantation and arteriovenous hormone concentration differences across the normal kidney suggests that the kidney has a important role in prolactin metabolism. Abnormal regulation of prolactin secretion in renal failure may also be involved.
EFFECT OF SURGICAL STRESS ON PITUITARY‐TESTICULAR FUNCTION
Authors: WANG CHRISTINA , CHAN VIVIAN , YEUNG ROSE T. T.
Published: March 2008

The effect of surgical stress on the secretions of LH, FSH, testosterone (T) and oestradiol (E2) were studied in twelve male patients. During surgery LH rose significantly; post‐operatively, LH fell but remained persistently elevated a week after operation. However, T and E2 fell progressively to a nadir on the second and fifth post‐operative day respectively and remained suppressed. Serum FSH showed no significant change. Despite a post‐operative decrease in sex hormone binding globulin (SHBG) binding capacity, non‐SHBG bound T showed a decrease parallel to T. Multiple sampling studies showed that the secretions of LH were increased and that of T were decreased post‐operatively. Following surgery, LH responses to LHRH were magnified, FSH and T responses showed no significant change when compared with the pre‐operative responses. These data suggest that secretions of LH were increased during surgery. Following surgical stress, T and E2 concentrations were suppressed resulting in a compensatory elevation of LH concentrations.
URINARY EXCRETION OF 3,3′,5′‐TRIIODOTHYRONINE (REVERSE T3)
Authors: FABER J. , KIRKEGAARD B. C. , ROGOWSKI P. , SIERSBÆK‐NIELSEN K. , FRIIS TH.
Published: March 2008

A simple and sensitive radioimmunoassay for reverse T3 in urine using small Sephadex G25 fine columns is described. The recovery of rT3 added to urine was on average 101.0 ± 4.2% (mean ± SEM). Detection limit was 4 pg/column. Urine excretion of rT3 (mean ± SD) was 72.0 ± 32.1 ng/24 hin 61 healthy euthyroid subjects with a slight increase with age (P < 0.05), 28.8 ± 18.2 ng/24 h in 12 hypothyroid patients and 183.6 ± 79.7 ng/24 h in 25 hyperthyroid patients.
SERUM GROWTH HORMONE AND ULTRASTRUCTURAL STUDIES OF ADENOHYPOPHYSIAL TISSUE IN BROMOCRIPTINE TREATED ACROMEGALIC PATIENTS
Authors: FANGHANEL‐S. G. , LARRAZA O. , ARAUCO R. , ESQUIVEL R. , CAMPOS A. MARTINEZ , VALVERDE‐R. C.
Published: March 2008

The therapeutic effectiveness of bromocriptine as well as the post‐operative ultra‐structural aspects of treated pituitary adenomas were investigated in five acromegalic patients. Although concentrations of GH basal decreased and the glucose tolerance test and the TSH responses were significantly improved, the release of GH induced by TRH was not prevented by the dopaminergic agonist. Adenomatous cells were densely granulated and contained a dilated endoplasmic reticulum. Misplaced exocytosis was frequently observed. These findings clearly indicate that bromocriptine inhibits the spontaneous release of GH but does not interfere with the abnormal GH response to TRH. This suggests a separate site of action. The drug seems not to block the synthesizing activity of the adenomatous cell, a finding in accordance with clinical observations that warns against its use as a single therapeutic agent.
EFFECT OF PIPERAZINE OESTRONE SULPHATE ON SERUM OESTROGEN AND GONADOTROPHIN LEVELS IN POST‐MENOPAUSAL WOMEN
Authors: ISAACS A. J. , HAVARD C. W. H.
Published: March 2008

Thirty‐three post‐menopausal women were treated with piperazine oestrone sulphate 1.5–3.0 mg daily on a cyclical basis for 3–6 months. Serum luteinising hormone (LH), follicle‐stimulating hormone (FSH), oestrone and oestradiol were measured on two occasions prior to starting treatment, and several times during the course of therapy. Initial mean concentrations of oestrone and oestradiol of 59 and 14 pg/ml rose to 528 and 83 pg/ml, respectively, and this was associated with a dose‐related suppression of LH (from 57.1 to 50.3 u/1) and more particularly FSH (from 25.8 to 16.5 u/1). There was a highly significant correlation between the decrease in FSH and the oestradiol concentration during treatment, but no correlation with oestrone.
DISCREPANCY BETWEEN ACTH AND CORTISOL RESPONSES TO INSULIN INDUCED HYPOGLYCAEMIA
Authors: LINDHOLM JÖRGEN , KEHLET HENRIK , BLICHERT‐TOFT MOGENS , RIISHEDE JOHN , HUMMER LOTTE , DINESEN BO
Published: March 2008

The purpose of this study was to assess the normal relationship between plasma ACTH and cortisol during insulin induced hypoglycaemia. Twenty‐six healthy persons were studied. Peak plasma concentration and the amounts of ACTH and cortisol secreted during hypoglycaemia were compared. There was no significant correlation between the ACTH and cortisol values. The ACTH responses varied significantly more than those of cortisol. This probably signifies an overcapacity of ACTH secretion in comparison to the secretory capacity of the adrenal cortex.
SOMATOSTATIN INHIBITS THE PENTAGASTRIN‐INDUCED RELEASE OF SERUM CALCITONIN IN MEDULLARY CARCINOMA OF THE THYROID
Authors: GORDIN A. , LAMBERG B.‐A. , PELKONEN R. , ALMQVIST S.
Published: March 2008

The effect of somatostatin on the secretion of calcitonin was studied in four patients with medullary carcinoma of the thyroid (MCT). The basal serum calcitonin level was markedly elevated in all cases. A bolus injection (100 μg) of somatostatin followed by an intravenous infusion (5 μg/min) for 60 min suppressed the basal calcitonin level in three of the four patients by 24–42%, while it had no inhibitory effect in one case. In another experiment, the pentagastrin‐stimulated (6 μg/kg s.c.) calcitonin release was partially blocked by a simultaneous i.v. injection of somatostatin (200 μg) in all four patients studied. These experiments add human calcitonin to the list of hormones whose release is inhibited by somatostatin.
PROLACTIN AND ADRENAL ANDROGEN SECRETION
Authors: VERMEULEN A. , ANDO S.
Published: March 2008

The aim of this study was to investigate the role of prolactin in the secretion by the adrenal of dehydroepiandrosterone (DHA) and its sulphate (DHA‐S). Therefore prolactin and DHA‐S levels were determined in different groups of subjects under various physiological and pathological conditions. In patients with prolactinomas, or with pharmacologically induced hyperprolactinaemia, plasma DHA‐S and, to lesser extend, DHA concentrations were elevated, and the DHA‐S blood production rate greatly increased. ACTH stimulation which did not influence DHA‐S concentrations in normals, caused a significant increase in patients with prolactinomas; the increase in DHA concentrations was similar in normal subjects and in prolactinoma patients. Bromocriptine treatment of prolactinaemia patients normalized both prolactin and DHA‐S concentrations. Acute elevation of prolactin in normal subjects by TRH stimulation or by short term administration of sulpiride, in contrast to long term treatment, did not influence DHA‐S levels. During pregnancy, notwithstanding high prolactin concentrations, DHA‐S concentrations were lower than during the menstrual cycle. In patients with prolactinomas, given glucocorticoid replacement with cortisol, DHA‐S concentrations were low (normal) notwithstanding persistently high prolactin concentrations. It is concluded that only prolonged elevation of prolactin induces increased DHA‐S secretion by the adrenal cortex and that normal ACTH secretion is a prerequisite for this effect. The absence of elevated DHA‐S concentrations in pregnancy might be explained by the rapid rate of metabolism, as the DHA‐S production rate is increased. The intimate mechanism of prolactin and ACTH interaction at the adrenal cortex remains however unknown.
DISCRIMINANT ANALYSIS IN THE DIFFERENTIAL DIAGNOSIS OF HYPERCALCAEMIA
Authors: CASCIO V. LO , VALLAPERTA P. , ADAMI S. , COMINACINI L. , GALVANINI G. , BIANCHI I. , FERRARI M. , SCURO L. A.
Published: March 2008

Linear discriminant analysis, a multivariate statistical procedure, applied to serum calcium, phosphate, alkaline phosphatase, bicarbonate, chloride, creatinine and tubular reabsorption of phosphate, proved to be effective in distinguishing patients with Primary Hyperparathyroidism from other hypercalcaemic patients in eighty‐four retrospective cases. The application of the model to thirty‐four prospective cases enabled us to separate correctly, hyperparathyroid patients from non‐parathyroid hypercalcaemic patients.
CUSHING'S SYNDROME, NODULAR ADRENAL HYPERPLASIA AND VIRILIZING CARCINOMA
Authors: ANDERSON D. C. , CHILD D. F. , SUTCLIFFE C. H. , BUCKLEY C. H. , DAVIES D. , LONGSON D.
Published: March 2008

A 48‐year‐old hypertensive diabetic woman rapidly became virilized. Urine 17‐oxo‐and oxogenic steroids and plasma testosterone, androstenedione, DHEA, DHEA‐sulphate and androstenediol were greatly elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18–24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumour of 17α‐hydroxypregnenolone, 17α‐hydroxyprogesterone and five C‐19 steroids, but very little prenenolone, progesterone or cortisol, was shown by blood sampling, tumour culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing's syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 months later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there had been an indentation in the fossa floor for at least 7 years. The left adrenal gland showed nodular hyperplasia. Therefore we conclude that mild pituitary‐dependent Cushing's syndrome may have been present for many years before development of a virilizing carcinoma. This case demonstrates that adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may in turn be due to long‐standing trophic hyper‐stimulation.
SEX HORMONE CONCENTRATIONS IN POST‐MENOPAUSAL WOMEN RELATION TO OBESITY, FAT MASS, AGE AND YEARS POST‐MENOPAUSE
Authors: And A. VERMEULEN , VERDONCK L.
Published: March 2008

Plasma sex hormone concentrations (testosterone, (T), androstenedione (A), oestrone (El) and oestradiol (E2)) were measured in forty post‐menopausal women more than 4 years post‐normal menopause. Correlations between these and age, years post‐menopause (YPM), degree of obesity and fat mass respectively were studied. T and A, as well as El and E2 were positively correlated (P<0.0l), but no statistically significant correlation between A and El was observed. Sex hormone concentrations in this group of postmenopausal women (>4YPM) did not show any variation as a function of age, with the possible exception of E2 which showed a tendency to decrease in the late post‐menopause. El and to a lesser extent E2 as well as the El/A ratio were significantly correlated with degree of obesity or fat mass, suggesting a possible role of fat tissue in the aromatization of androgens. Neither the T/A nor the E2/E1 ratios were correlated with fat mass, suggesting that the reduction of 17 oxo‐group does not occur in fat tissue. The El/A ratio was significantly higher than the reported conversion rate of A in El. This might suggest the existence of an additional precursor of plasma El.
THE RELATION BETWEEN PLASMA AND ROSTENEDIONE AND OESTRONE LEVELS IN UNTREATED AND CORTICOSTEROID‐TREATED POST‐MENOPAUSAL WOMEN
Authors: MARSHALL D. H. , CRILLY R. , NORDIN B. E. C.
Published: March 2008

Plasma oestrone (E,) and androstenedione (A) were measured in 96 untreated and 18 corticosteroid‐treated post‐menopausal women. Levels of both hormones were consistently lower in the steroid‐treated cases, presumably due to suppression of ACTH secretion. There was a clear relationship between A and Ei levels in both groups and when the data were pooled they formed a continuous series with a curvilinear relationship going through the origin. This relationship could be described by an equation based on Michaelis‐Menten kinetics, suggesting that the rate of A to E! conversion is an inverse function of the plasma androstenedione level. The main determinant of plasma E] was plasma A; body weight and age were of subsidiary importance. Secondary oestrogen deficiency may be a factor in the genesis of steroid‐induced osteoporosis in post‐menopausal women and oestrogen therapy may be indicated in this group of patients.
OESTROGEN AMPLIFICATION OF LH‐RH RESPONSE IN THE POLYCYSTIC OVARY SYNDROME AND RESPONSE TO CLOMIPHENE
Authors: KANDEEL F. R. , BUTT W. R. , LONDON D. R. , LYNCH S. S. , EDWARDS R. LOGAN , RUDD B. T.
Published: March 2008

An LH‐RH test was performed before and 44 and 92 h after treatment with 2.5 mg oestradiol benzoate in 17 patients with a diagnosis of polycystic ovarian (PCO) disease. The responses were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4–6). Patients were divided into two groups on the basis of their LH responses to LH‐RH. In Group A (seven patients) the response at 92 h was greater than at 44 h as in the normal subjects, but in Group B (ten patients) the response at 44 h was greater than at 92 h. Basal serum hormone values were similar in the two groups except for androgens and oestrone, which were significantly (P<0.01) higher in Group B patients. There was a negative correlation between the basal androgen and oestrone concentrations and the LH and FSH amplifications at 92 h in all PCO patients.

The ratios of the basal concentrations of LH to FSH and the ratios of the highest levels of each achieved during the basal LH‐RH test, were significantly higher in the two groups of patients when compared to controls (P< 0.01).

The test is of value in predicting the subsequent responsiveness to clomiphene. All patients in Group A showed evidence of ovulation following treatment with 100 mg clomiphene for 5 days, but only one of Group B responded in this way.
THE EFFECT OF HEROIN ADDICTION ON PITUITARY‐TESTICULAR FUNCTION
Authors: WANG CHRISTINA , CHAN VIVIAN , YEUNG ROSE T. T.
Published: March 2008

The effect of heroin addiction on pituitary‐testicular function was studied in 54 active and 19 abstinent addicts and their results were compared with those of 43 age‐matched controls. Abnormal sexual function was frequently found in heroin addicts and this persisted after drug withdrawal. The mean total (mean ± SE, 18.1 ± 1.0 nmol/l) and free (0.17 ± 0.03 nmol/l) testosterone (T) levels in heroin addicts were significantly lower than those in healthy controls (total T 22.8 ± 1.1 nmol/l, P < 0.005; free T 0.30 ± 0.03 nmol/l, P < 0.005). The mean sex hormone binding globulin binding capacity was higher in heroin addicts (60.1 ± 5.2 nM) than in healthy controls (35.5 ± 2.1 nM). These hormonal changes returned promptly to normal after withdrawal. The basal LH and FSH and the responses to LHRH were comparable in the three groups studied.

The finding of significantly lower total and free T together with higher SHBG indicates an abnormal testicular function in heroin addiction. Normal basal and LHRH‐stimulated LH and FSH levels suggest that chronic heroin abuse depressed testicular function via the hypothalamus or higher centres.
PARTIAL HYPOPITUITARISM IN A PATIENT WITH A PITUITARY STONE
Authors: MROUEH ADNAN , SALTI IBRAHIM
Published: March 2008

A case of sexual infantilism was found to have calcification within the sella turcica. Endocrine evaluation revealed partial hypopituitarism involving gona‐dotrophm and growth hormone secretion.
SUPPRESSION OF PLASMA ACTH CONCENTRATION BY ANGIOTENSIN II INFUSION IN NORMAL HUMANS AND IN A SUBJECT WITH A STEROID 17α‐HYDROXYLASE DEFECT
Authors: SEMPLE PETER F. , BUCKINGHAM JULIA C. , MASON PETER A. , FRASER ROBERT
Published: March 2008

Six healthy subjects were infused with angiotensin II and plasma concentrations of angiotensin, ACTH and cortisol were measured before, during and after the infusion. In all cases the plasma ACTH concentration fell as plasma angiotensin increased and rose again, sometimes to higher than basal levels, when the angiotensin infusion was terminated. These effects were most marked at the highest rate of infusion (8 pmol/kg/min) and, at the lower rates (2 and 4 pmol/kg/min), there was some recovery of ACTH levels during the infusion period in some subjects. Plasma ACTH concentrations also fell when angiotensin was infused into a patient with high ACTH levels due to a steroid 17α‐hydroxylation defect. The inhibition of ACTH secretion is not due to a rise in plasma cortisol operating a negative feedback inhibition. It could be a direct effect of the infused angiotensin on the brain‐hypothalamus‐pituitary complex or an effect on the metabolism of ACTH.
BROMOCRIPTINE TREATMENT OF SEVEN WOMEN WITH PRIMARY AMENORRHOEA AND PROLACTIN‐SECRETING PITUITARY TUMOURS
Authors: BERGH T. , NILLIUS S. J. , WIDE L.
Published: March 2008

Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pituitary tumour was diagnosed, four women had been given longterm cyclical oestrogen replacement therapy. Three women had received primary tumour therapy with surgery and/or irradiation but had persistent hyperprolactinaemia. The basal luteinizing hormone (LH) levels were low in four of the women while all the women had normal basal levels of follicle‐stimulating hormone (FSH) and normal or exaggerated gonadotrophin responses to luteinizing hormone‐releasing hormone (LHRH). None of the women had evidence of endogenous oestrogen production before treatment. Bromocriptine treatment normalized the raised serum prolactin levels (46–2900 μg/1) in all but one woman, in whom the prolactin level decreased from 160 to 38 μg/1. Regular ovulatory menstrual cycles appeared in four women, one of whom had previously been treated by transsphenoidal adenomectomy followed by external irradiation. Two other women with persistent hyperprolactinaemia after previous surgical and/or irradiation treatment of large pituitary tumours did not menstruate after more than one year of treatment with bromocriptine. One infertile patient with a microadenoma conceived at the first ovulation on therapy and developed symptoms and signs of tumour growth during pregnancy.
ETHANOLINDUCED SECRETION OF CALCITONIN IN CHRONIC RENAL DISEASE
Authors: KANIS J. A. , ADAMS N. D. , CECCHETTIN M. , LUIZETTO G. , GASPAR S. , HEYNEN G.
Published: March 2008

Whisky (25–50 ml) increased plasma levels of immunoreactive calcitonin (iCT) in seventeen of nineteen patients with chronic renal failure. The effect was greater in patients with high levels of iCT than in those with normal levels. Changes in plasma iCT were not related to changes in calcium, phosphate or immunoreactive gastrin, but were inhibited by the prior administration of propranolol.
LIPODYSTROPHY WITH HYPERLIPIDAEMIA: THE ROLE OF INSULIN IN VERY LOW DENSITY LIPOPROTEIN OVER‐SYNTHESIS
Authors: CHAIT ALAN , JANUS EDWARD , MASON A. STUART , LEWIS BARRY
Published: March 2008

A patient with partial lipodystrophy is described in whom hypertriglyceridaemia was accompanied by marked hyperinsulinaemia. The hyperlipidaemia was due to increased plasma levels of very low density lipoprotein (VLDL). Kinetic studies, performed after injection of autologous radioiodinated VLDL, indicated that the raised VLDL levels were associated with over‐production of this lipoprotein. Administration of diazoxide led to a substantial fall in serum insulin levels, accompanied by reduction in VLDL production and in serum triglyceride concentration. The possible role of insulin in inducing hyperlipidaemia by causing over‐production of VLDL is discussed.
THE RELATIONSHIP BETWEEN ENDOGENOUS HYPERPROLACTINAEMIA AND PLASMA ALDOSTERONE
Authors: RE R. N. , KOURIDES I. A. , WEIHL A. C. , MALOOF F.
Published: March 2008

It has been suggested that prolactin is a regulator of aldosterone secretion. In order to test this hypothesis, we measured prolactin, thyrotrophin and aldosterone by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in eight normal women before and after the intravenous injection of 200 μg of thyrotrophin releasing hormone (TRH). Prolactin increased from 4.1 ± 1.1 ng/ml (mean ± SE) to a peak of 27.4 ± 3.8 (P > 0.005) at 15 min following TRH. Plasma renin activity was not different from control levels (1.0 ± 0.2 ng/ml/h) during the first hour following the administration of TRH, nor did the plasma aldosterone concentration differ significantly from the control levels (39 ± 7 pg/ml) during this period. However, with upright posture, an increase in aldosterone (from 31 ± 3 pg/ ml at 1 h to 68 ± 9 at 2 h, P > 0.005) and in plasma renin activity (from 0.9 ± 0.2 ng/ml/h at 1 h to 2.0 ± 0.5 at 2 h, P > 0.05) was noted, demonstrating a normal capacity to secrete aldosterone in these subjects. Similarly, no change in aldosterone was seen in nine patients with primary hypothyroidism given TRH, despite the fact that the increase in prolactin was greater than normal. Chronic hyperpro‐lactinaemia was not associated with hyperaldosteronism in six patients with pituitary tumour. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.
GROWTH HORMONE RELEASE INHIBITORY HORMONE‐LIKE IMMUNOREACTIVITY IN PANCREAS AND GUT IN STREPTOZOTOCIN DIABETES IN THE RAT AND RESPONSE TO INSULIN ADMINISTRATION
Authors: BERELOWITZ M. , SHAPIRO B. , PIMSTONE B. , KRONHEIM S.
Published: March 2008

In streptozotocin diabetes in the rat, growth hormone release‐inhibitory hormone‐like immunoreactivity (GHRIH‐LI) content of pancreas, gastric antrum and colon was increased. Insulin therapy significantly lowered the increased pancreatic GHRIH‐LI content but did not affect that of the gastric antrum and colon at the dosage used. The relevance of these findings in relation to pancreatic and gastrointestinal function in diabetes awaits clarification.
EFFECT OF AGE ON PLASMA ANDROSTENEDIONE CONCENTRATION IN OOPHORECTOMIZED WOMEN
Authors: CRILLY R. G. , MARSHALL D. H. , NORDIN B. E. C.
Published: March 2008

Plasma androstenedione concentration was measured in 92 oophorectomized women in the age range 33 to 76 years. Although this concentration was significantly inversely correlated with age, the data suggest a discrete change in the first half of the sixth decade rather than a continuous fall.
THE EFFECT OF CYPROHEPTADINE ON THE RELEASE OF CORTICOTROPHIN RELEASING FACTOR
Authors: JONES M. T. , BIRMINGHAM M. , GILLHAM B. , HOLMES M. , SMITH T.
Published: March 2008

The effect of cyproheptadine was tested on the neurotransmitter‐induced release of corticotrophin releasing factor (CRF) from the rat hypothalamus in vitro. It was found that cyproheptadine inhibited both acetylcholine and 5‐hydroxytryptamine‐induced release of CRF. Cyproheptadine did not interfere with the ACTH releasing ability of CRF. These results suggest that cyproheptadine reduces the high circulating levels of ACTH in some patients suffering from Cushing's disease and Nelson's syndrome by inhibiting CRF secretion.
PRESENCE OF POSITIVE FEEDBACK BETWEEN OESTROGEN AND LH IN PATIENTS WITH KLINEFELTER'S SYNDROME, AND SERTOLI‐CELL‐ONLY SYNDROME
Authors: BARBARINO A. , DE MARINIS L. , LAFUENTI G. , MUSCATELLO P. , MATTEUCCI B. R.
Published: March 2008

In five adult patients with Klinefelter's syndrome and two with Sertoli‐cell‐only syndrome, exogenous administration of 17β‐oestradiol, resulting in a sustained and prolonged elevation of circulating oestrogen levels, had a biphasic effect on LH release. After an initial decrease, a dramatic rise in peripheral levels of LH (positive feedback) was observed in all patients. The timing and magnitude of the induced LH surge was similar to that observed in postmenopausal women after administration of large doses of Ethinyloestradiol. A similar positive feedback effect on the secretion of FSH could not be demonstrated. In two patients with the Sertoli‐cell‐only syndrome, oestrogen treatment induced marked variations in serum testosterone levels, which appeared to be related to the LH changes. Similar changes were not present in patients with Klinefelter's syndrome, indicating a decrease in the sensitivity of the testicular Leydig cell. These experiments demonstrate that positive feedback between oestrogen and luteinizing hormone is present in the adult hum an male.
THYROTROPHIN‐RELEASING HORMONE INHIBITS THE PENTAGASTRIN STIMULATED GASTRIC SECRETION IN MAN. A DOSE RESPONSE STUDY
Authors: DOLVA L. Ø. , HANSSEN K. F. , BERSTAD A. , FREY H. M. M.
Published: March 2008

Actions of thyrotrophin‐releasing hormone (TRH) have generally been confined to the central nervous system (CNS). We have studied the effect of increasing doses of TRH i.v. (8, 40, 200 and 1000 μg/h) on pentagastrin‐stimulated gastric secretion in ten normal individuals. All doses caused stepwise inhibition of gastric juice (volume), acid and pepsin output. When employing the largest dose of i.v. TRH (1000 μg/h) the inhibition was 44% for gastric volume, 51% for acid output and 57% for pepsin output. This study shows that TRH inhibits gastric secretion, and indicates that TRH has actions outside the CNS in man.
EXCHANGE OF TRIIODOTHYRONINE DERIVED FROM THYROXINE WITH CIRCULATING TRIIODOTHYRONINE AS STUDIED IN THE RAT*
Authors: OBREGON MARIA JESUS , ROELFSEMA FERDINAND , DE ESCOBAR GABRIELLA MORREALE , ESCOBAR DEL REY FRANCISCO , QUERIDO ANDRIES
Published: March 2008

At present it is widely assumed that T3 derived from T4 is rapidly and totally exchangeable within the volume of distribution of T3 secreted by the thyroid into the bloodstream. This concept is implied when conclusions are drawn from comparisons between a biological effect in a responsive tissue and circulating T3 and T4 levels. Such conclusions are often in conflict with those derived by comparing the biological effect with the concentrations of T3 and T4 in the responsive tissue itself. Thus, it appeared important to test the above assumption directly. Thyroidectomized rats have been treated for 4–4° days with a mixture of 131I labelled T4 (131T4) and 125I labelled T3 (125T3), which was either injected twice daily or administered by continuous i.v. infusion. The rats were bled, perfused, and their plasma and tissues submitted to extraction and paper chromatography. If the tested assumption were correct, the ratio between the T3 derived from T4 and the T3 injected as such (namely, the 131T3/125T3 ratio) should be the same in plasma, liver, kidney, heart, muscle, etc. It was evident that the 131T3/125T3 ratio was not the same for different tissues. The differences were not merely due to artefactual deiodinations. The presence of small amounts of 131I and 125I containing compounds in the T3 spot was considered as highly unlikely, though not totally excluded. The data thus suggest that T3 derived from T4 and the injected (or thyroidally secreted) T3 might not be totally exchangeable within an observation period which is considerably longer than the one for which complete equilibrium was previously assumed. If so, changes in the size of the T4 pool, or in the rate of T4 conversion to T3, might affect the con centration of T3 in a given tissue to an extent not disclosed from the circulating T3 levels alone. Several possible consequences of the present findings are discussed.
BOOK REVIEWS
Authors: LONDON D. R. , ROBERTSON W. G. , HEATH D. A.
Published: March 2008

Reproductive Endocrinology, Physiology, Pathophysiology and Clinical Management. Ed. by S. S. C. YEN & R. B. JAFFE. W. B. Saunders

Calcium Urolithiasis‐Pathogenesis, Diagnosis and Management. By C. Y. C. PAK.

Vitamin D. Ed. by D. E. M. LAWSON.
KINETICS OF PLASMA CORTICOSTEROIDS DURING METYRAPONE INFUSION IN MAN
Authors: LEJEUNE‐LENAIN C. , WOLTER R. , FRANCKSON J. R. M.
Published: March 2008

The effect of metyrapone on plasma kinetics of cortisol (F), 11‐deoxycortisol (S), corticosterone (B), 11‐deoxycorticosterone (DOC), aldosterone (Aldo) and 17 hydroxyprogesterone (17 OHP) was studied in ten normal prepubertal children intravenously infused with the drug (1 gm/1.73 m2 body surface area in 4 h).

Similar falls in F, B and Aldo were observed during the first hour expressing similar sensitivity of the 11 hydroxylases to the drug. The effect of the compensatory increase of endogenous ACTH could be detected after 1 hour by the rise in 17 OHP. However the concentrations of the 11‐hydroxy compounds, F, B and Aldo, remained low throughout the infusion period.

From the second hour onwards, facilitation of the synthesis of DOC was noticed.

After the end of infusion, the levels of the precursors decreased and F and B were restored to initial values. Aldo remained low probably due to the inhibitory effect of the elevated DOC on the renin‐angiotensin system.
NON‐PROTEIN‐BOUND OESTROGENS IN PLASMA AND URINARY EXCRETION OF UNCONJUGATED OESTROGENS IN MEN
Authors: SPEIGHT ALISON C. , HANCOCK K. W. , OAKEY R. E.
Published: March 2008

Unconjugated oestrone and unconjugated oestradiol‐17β were measured in 24 h urine specimens from twenty normal men. The concentrations of non‐protein‐bound oestrone and non‐protein‐bound oestradiol‐17β, in samples of blood obtained from these subjects during the time in which the urine was collected, were measured by equilibrium dialysis (using a correction for plasma dilution). The mean excretion of unconjugated oestrone (0.44 ± 0.36 nmol/24 h, mean ± SD) was significantly greater (P < 0.01) than that of unconjugated oestradiol‐17β (0.20 ± 0.13 nmol/24 h). The concentrations of non‐protein‐bound oestrone and non‐protein‐bound oestradiol‐17β in plasma were 5.52 ± 2.69 pmol/1 and 2.42 + 0.73 pmol/l, respectively.

There was no correlation between the quantity of unconjugated oestrone excreted and the concentration of non‐protein‐bound oestrone in plasma (r= 0.27) nor between the quantity of unconjugated oestradiol‐17β in the urine and the concentration of non‐protein‐bound oestradiol‐17β in plasma (r= 0.05). Therefore in normal men, estimation of unconjugated oestrone or oestradiol‐17β in urine provides no guide to the concentration of the corresponding non‐protein‐bound oestrogen in plasma.
AMNIOTIC FLUID CONCENTRATIONS OF 3,3′,5′‐TRI‐IODOTHYRONINE (REVERSE T3), 3,3′‐DI‐IODOTHYRONINE, 3,5,3′‐TRI‐IODOTHYRONINE (T3) AND THYROXINE (T4) IN NORMAL AND COMPLICATED PREGNANCY
Authors: MEINHOLD H. , DUDENHAUSEN J. W. , WENZEL K. W. , SALING E.
Published: March 2008

Amniotic fluid concentrations of 3,3′,5′‐tri‐iodothyronine (rT3), 3,3′‐di‐iodothyronine (3,3′‐T2), 3,5,3′‐tri‐iodothyronine (T3) and T4 were studied in 384 women during normal and complicated pregnancy. An inverse correlation was observed between decreasing rT3 and increasing 3,3′‐T2 concentrations in amniotic fluid with gestational age. The mean rT3 level in normal pregnancy was 2.81 nmol/l at 12–20 weeks and decreased significantly to 1.06 nmol/l at 36–42 weeks of gestation. The mean 3,3′‐T2 concentration was 49.1 pmol/l at 12–20 weeks increasing to 119 pmol/l at 36–42 weeks. The mean T4 value of 3.83 nmol/l at 12–20 weeks was about half that of later periods. The T3 concentration in a random sample of 45 amniotic fluids ranged from <28 to 370 pmol/1 (mean 102 pmol/l). The mean rT3, 3,3′‐T2 and T4 values measured in patients with intra‐uterine malnutrition, gestation diabetes, tocolysis, placental insufficiency and rhesus incompatibility at 31–40 weeks of gestation were not significantly different from those in uncomplicated pregnancy. Significantly decreased rT3 and T4 concentrations were found in toxaemia. From the results obtained in complicated pregnancy it may be concluded that measurements of iodothyronines, especially rT3, in amniotic fluid have insignificant diagnostic value in the recognition of intra‐uterine lesions with the probable exception of fetal hypothyroidism. The analysis of the dependence of iodothyronine concentrations on the gestational age showed a maximum of rT3 and T4 levels between 20 and 30 weeks of pregnancy. This marked rise of iodothyronine concentrations in amniotic fluid at mid‐gestation may be due to the onsetting maturation of the hypothalamic‐pituitary‐thyroid control system of the fetus.
RAPID ASSAY OF PLASMA 21‐DEOXYCORTISOL AND 11‐DEOXYCORTISOLIN CONGENITAL ADRENAL HYPERPLASIA
Authors: FUKUSHIMA D. K. , NISHINA T. , WU R. H. K. , HELLMAN L. , FINKELSTEIN J. W.
Published: March 2008

Plasma assays using highly specific antisera to 21‐deoxycortisol, 21‐deoxycortisone and 11‐deoxycortisol were developed to provide a rapid means of diagnosis in patients with congenital adrenal hyperplasia (CAH). The assays were done on plasma extracts with and without Celite chromatography to compare the results of direct assays on plasma extracts and assays on purified plasma extracts. Both methods showed elevations of metabolites that permitted the correct diagnosis of the specific enzyme deficiency. Untreated patients with 21‐hydroxylase deficiency had elevated levels of 21‐deoxycortisol, 21‐deoxycortisone and 17‐hydroxyprogesterone. One of the untreated patients with 21‐hydroxylase deficiency had elevated levels of these metabolites due to inadequate glucocorticoid treatment. In one newborn patient, who developed a salt‐losing syndrome, a combined deficiency of 11‐ and 21‐hydroxylase appeared to be present based on elevations of plasma concentrations of 11‐deoxycortisol (2.7 μg/dl), 21‐deoxycortisol (10.3 μg/dl), 21‐deoxycortisone (8.6 μg/dl), and 17‐hydroxyprogesterone (> 20 μg/dl). After treatment was begun the levels of all four metabolites returned to normal. This patient had XX/XO karyotype and ambiguous genitalia. Fourteen normal neonates were studied as controls for this subject. Normal neonates all had low plasma levels of these compounds. Their 21‐deoxycortisol concentrations were all less than 0.5 μg/dl and their 11‐deoxycortisol concentrations were all less than 0.1 μg/dl. The study shows that accurate, rapid plasma diagnosis is possible in patients with congenital adrenal hyperplasia, using specific radioimmunoassay procedures.
SELECTIVE INHIBITORY EFFECT OF PORCINE FOLLICULAR FLUID ON FOLLICLE STIMULATING HORMONE SECRETION IN ANTERIOR PITUITARY CELLS IN CULTURE
Authors: LAGACÉ LISETTE , LABRIE FERNAND , LORENZEN JANICE , SCHWARTZ NEENA B. , CHANNING CORNELIA P.
Published: March 2008

Incubation of rat anterior pituitary cells in culture with porcine follicular fluid (treated with charcoal to remove steroids) led to a marked inhibition of spontaneous FSH release while no effect was observed on basal LH secretion. The inhibitory effect of follicular fluid was, however, less specific on LHRH‐induced gonadotropin release. Although more potent on FSH than LH release, a significant inhibition of LH release induced by the neurohormone was also observed. This inhibitory activity is mainly associated with material of MW 10000 daltons.
DISTURBED MINERAL METABOLISM IN HYPERTHYROIDISM: GOOD CORRELATION WITH TRMODOTHYRONINE
Authors: MANICOURT D. , DEMEESTER‐MIRKINE N. , BRAUMAN H. , CORVILAIN J.
Published: March 2008

Mineral metabolism is frequently disturbed in hyperthyroidism. In a group of seventy‐two patients with hyperthyroidism, we observed an increase in serum diffusible calcium in 50% of the cases, elevated inorganic phosphorus in 30% and elevated alkaline phosphatase in 44% of the cases. Correlations existed between the values of diffusible calcium, inorganic phosphorus, alkaline phosphatase and certain indices of thyroid function (T4, FT4I, T3, FT3I), of which that with T3 was the best (P < 0.001). Our results suggest that the magnitude of the disturbances of mineral metabolism depends on the severity of the hyperthyroidism and that it is the T3 level that constitutes the best index of that seventy.
COMPARISON OF LONG‐ACTING ANALOGUES OF LUTEINIZING HORMONE RELEASING HORMONE IN MAN
Authors: WASS J. A. H. , BESSER G. M. , GOMEZ‐PAN A. , SCANLON M. F. , HALL R. , KASTIN A. J. , COY D. H. , SCHALLY A. V.
Published: March 2008

Currently, LHRH, when used therapeutically, is given by parenteral injection every 8 h. We have looked at the release of LH and FSH induced by five analogues of LHRH and compared this with gonadotrophin release after synthetic LHRH. The analogues were substituted in position 6 or in positions 6 and 10 and were given intravenously, intranasally or subcutaneously in three separate studies. After intravenous administration of 100μg, all analogues caused greater release of LH and FSH than did synthetic LHRH. Given intranasally in a dose of 500 μg, three of the four analogues tested caused greater LH and FSH release than did LHRH. With tryptophan substitution in position 6 (D‐TRP6‐LHRH), mean LH levels in five subjects were still above the normal range 24 h after a single intranasal dose. The intranasal administration of selected analogues of LHRH has great potential in the treatment of conditions associated with deficient gonadotrophin secretion, provided that pituitary overstimulation, which may eventually lead to a decrease in LH and FSH output by the anterior pituitary, is avoided.
PROPRANOLOL, TRIIODOTHYRONINE, REVERSE TRIIODOTHYRONINE AND THYROID DISEASE
Authors: FEELY JOHN , ISLES T. E. , RATCLIFFE W. A. , CROOKS J.
Published: March 2008

Propranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1–2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranolol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.
THE HORMONAL STATUS OF PATIENTS WITH BENIGN PROSTATIC HYPERTROPHY: FSH, LH, TSH AND PROLACTIN RESPONSES TO RELEASING HORMONES*
Authors: HAMMOND G. L. , LUKKARINEN O. , VIHKO P. , KONTTURI M. , VIHKO R.
Published: March 2008

In order to determine whether the benign prostatic hypertrophy (BPH) adenoma is responsible for low serum LH levels in patients with this disease, we measured FSH, LH and prolactin in sera collected from patients before and 0.8–2.2 years after retro‐pubic prostatectomy, but found no change in their levels. Pituitary stimulation tests were therefore conducted to evaluate the pituitary hormone reserve in normal elderly men, and BPH patients before and after removal of the BPH adenoma. Blood was drawn 20 min before and during the administration of 100 μg LHRH and 200 μg TRH, as a single intravenous injection, and after 20, 60 and 120 min. Serum FSH, LH, TSH and prolactin were estimated by radioimmunoassays. Prior to prostatectomy, patients with BPH had significantly lower levels of serum LH, but not FSH, TSH or prolactin, as compared to normal men 20 min before the test. Serum LH in the BPH group after prostatectomy (1–2.75 years) was not statistically different from that of normal age‐matched men, but the mean level more closely resembled that of the untreated BPH group. Although there were no significant differences in serum levels of FSH or prolactin between subject groups during stimulation, levels of LH and TSH in untreated BPH patients' serum were significantly lower than those of normal men. The BPH patients after prostatectomy resembled the normal men under these circumstances, and the serum levels of TSH in these ex‐BPH patients were significantly higher than in untreated BPH patients. Similarly, the maximum LH and TSH responses to the hypothalamic releasing hormones were also significantly lower in the BPH patients as compared to normal age‐matched men, and evidently return to normal 1–2.75 years after prostatectomy. No statistically significant differences were observed in the FSH and prolactin responses to LHRH and TRH between groups. The results suggest that a factor originating from the BPH adenoma, such as 5α‐dihydrotestosterone, may be responsible for the suppression of pituitary LH and TSH responses to LHRH and TRH, respectively. It also appears that the pituitary of BPH patients does not regain its full secretory potential after the BPH adenoma has been removed, or that an additional factor may regulate pituitary LH secretion in the untreated and ex‐BPH patients at the hypothalamic level.
PLASMA CYCLIC‐AMP RESPONSE TO PARATHYROID HORMONE IN TURNER'S SYNDROME AND ALBRIGHT'S HEREDITARY OSTEODYSTROPHY
Authors: ASHBY J.P. , RENTON W. B. , MACPHERSON J.N. , PRICE W. H. , ABBOTT S. R.
Published: March 2008

Purified bovine parathyroid hormone (BPTH) given by injection to five patients with Turner's syndrome, and seven healthy volunteers produced a significant rise in plasma cyclic AMP reaching a maximum within 10 min. In a pseudohypoparathyroid patient there was no increase. Urinary excretion of cyclic AMP exceeded the normal in three out of four patients with Turner's syndrome. Thus, if there is a relationship between Turner's syndrome and Albright's osteodystrophy it is with the incomplete form known as pseudo‐pseudohypoparathyroidism.
PITUITARY MICROADENOMA: DIAGNOSTIC STUDIES
Authors: PINEDA GUSTAVO , VALDES MARIO , CASTRO MARIO , STEVENSON CARLOS
Published: March 2008

Forty‐one women with oligo‐menorrhoea and/or galactorrhoea were subjected to hypothalamic pituitary‐thyroid testing in an attempt to establish the presence or absence of an underlying pituitary microadenoma. They were divided into two groups in accordance with the serum level of prolactin (PRL): Group I (N = 25, mean ± SE 17.6 ± 1.5 ng/ml) and Group II (N = 16, 102.8 ± 29.7 ng/ml). The dynamic tests performed were a TRH test, a stimulation test with metoclopramide (MCP) and a suppression test with bromocriptine. The results of these tests were compared with those obtained in nine normal women and eleven patients with surgically proved pituitary microadenoma. Radiologically abnormal pituitary fossas were found in ten subjects from Group I and in fourteen from Group II. All patients were euthyroid.

A persistently elevated serum TSH in response to TRH was observed in patients of Group II suggesting an hypothalamic abnormality and a progressive decrease in the 120‐min use of serum T3 was noted with increasing evidence of the existence of a pituitary tumour. A negative correlation was found between the basal serum PRL and the rise of serum PRL with TRH.

Patients from Group II showed a lower PRL response to MCP when compared to Group I and again a negative correlation between basal level of serum PRL and the change after MCP was observed. No clear difference in the 4‐h response to bromocriptine was found between the different groups of subjects.

In conclusion, none of the three tests analysed permitted us to establish which of the patients had an underlying pituitary microadenoma.
FREE‐RUNNING CIRCADIAN PLASMA CORTISOL RHYTHM IN A BLIND HUMAN SUBJECT
Authors: ORTH D. N. , BESSER G. M. , KING P. H. , NICHOLSON W. E.
Published: March 2008

The plasma cortisol rhythm in man has been presumed to be an endogenous circadian rhythm, synchronized by some external stimulus to an exact 24‐h period. Sleep/wake and ‘social activity’ cycles have been considered as candidates for this synchronizer. Previous studies have suggested that the dark/light phase shifts associated with the sleep/wake cycle may be the external synchronizer, rather than the sleep/wake cycle itself. A totally blind, but otherwise normal subject was studied for a period of 50 days. Her hourly sleep/wake status and hourly integrated mean plasma cortisol concentrations were determined, and the data were subjected to non‐parametric mathematical analysis. The subject was found to have a free‐running rhythm in plasma cortisol with a period of approximately 24.5 h. Her sleep/wake rhythm, determined by similar analysis, had a period of exactly 24 h. In addition to the dominant 24.5‐h cortisol rhythm, there appeared to be a minor 24‐h cortisol rhythm with a peak that coincided approximately with the time of awakening. It was not possible to determine whether this sleep/wake‐related peak represented a minor component of the circadian rhythm, synchronized by some stimulus associated with sleep/wake activity, or merely an acute response to awakening itself. Nevertheless, the two rhythms exhibited ‘beating’ behaviour, resulting in maximal peak cortisol concentrations when they were in synchrony and minimal peak concentrations when they were not. It is concluded that environment dark/light phase shifts are the dominant synchronizer of the circadian rhythm in plasma cortisol concentrations in man, as they are for a variety of circadian rhythms in other living things.