bluuebunny/crossref_metadata_2025 huggingface dataset:
LACK OF EFFECT OF OESTROGENS ON ADRENAL ANDROGEN SECRETION IN CHILDREN AND ADOLESCENTS WITH A COMMENT ON OESTROGENS AND PUBIC HAIR GROWTH
Authors: SKLAR C. A. , KAPLAN S. L. , GRUMBACH M. M.
Published: March 2008

To study the effect of oestrogen on adrenarche and adrenal androgen secretion we measured plasma concentrations of dehydroepiandrosterone‐sulphate (DHEA‐S), androstenedione (Δ4A) and oestradiol (E2) in the following groups: children with premature adrenarche; agonadal patients before and after initiation of oestrogen replacement therapy; and, children exposed to increased concentrations of endogenous oestrogen at a precocious age.

Fourteen of fifteen patients with premature adrenarche had plasma E2 levels in the normal prepubertal range (> 10 pg/ml), despite a mean DHEA‐S concentration that was significantly elevated for age (6–8 years: 72·5 ± 12·6 μg/dl v. 11·4 ± 2·9 μg/dl, P 0·002). DHEA‐S and Δ4 A concentrations in fifteen patients with gonadal dysgenesis before and 2–14 months after initiation of oestrogen replacement therapy were not significantly different despite the appearance of oestrogen‐induced secondary sex characteristics. Six of fifteen patients developed increased pubic hair during oestrogen therapy but had no increase in the concentrations of plasma DHEA‐S. Two patients (aged 1 year 4 months and 4 years 10 months) with oestradrol secreting ovarian follicular cysts (plasma E2 11–796 pg/ml) and one patient (aged 6 years 10 months) who had had a granulosa cell tumour of the ovary maintained preadrenarchal DHEA‐S levels (> 6·2 μg/dl) despite exposure to concentrations of circulating oestrogen that were high for their chronological age.

We interpret the results as follows: (1) Initiation of premature adrenarche occurs without an increase into the early pubertal range of E2 levels. (2) Administration of replacement doses of oestrogen does not increase adrenal androgen concentrations in adolescent patients with gonadal dysgenesis. (3) Elevated plasma concentrations of endogenous ovarian oestrogens at a precocious age did not increase adrenal androgen secretion in childhood. Thus, it appears that circulating oestrogens are either required for the activation or maintenance of adrenarche nor do they significantly affect the plasma concentrations of adrenal androgens in children and adolescents. (4) The pubic hair growth associated with the institution of oestrogen replacement in adolescent patients with gonadal dysgenesis is not mediated by an increase in adrenal androgen secretion and may result from a specific effect of oestrogen on androgen action at the target tissue (pubic skin).
CLINICAL RESPONSE TO METYRAPONE AS INDICATED BY MEASUREMENT OF MINERALOCORTICOIDS AND GLUCOCORTICOIDS IN NORMAL CHILDREN
Authors: SONINO NICOLETTA , CHOW DIANE , LEVINE LENORE S. , NEW MARIA I.
Published: March 2008

The effect of 24‐h metyrapone administration on adrenal mineralocorticoid and glucocorticoid pathways has been studied in normal children. Urine and serum steroid concentrations were evaluated. Simultaneous determinations of deoxycorticosterone (DOC), corticosterone (B), cortisol (F), and aldosterone (aldo), in both urine and serum, were carried out by celite column chromatography and radioimmunoassay. 11‐deoxycortisol (Compound S) in serum and urine, urinary free 18‐hydroxydeoxycorticosterone (18‐OH‐DOC), urinary free 18‐hydroxycorticosterone (18‐OH‐B), and urinary aldosterone‐18‐glucuronide (pH 1 aldo) were measured separately by specific methods. Conclusions drawn were that (1) Useful indices of metyrapone effect were the marked rise of 11‐deoxysteroids (DOC and S), and the fall of aldo and 18‐OH‐B; no changes occurred in 18‐OH‐DOC and the 11‐hydroxylated steroids (B, F); (2) Serum and urine values were significantly correlated, indicating that both were equally reliable in the evaluation of the metyrapone test; (3) Hormonal ratios indicate that metyrapone inhibition affected the 11‐hydroxylation of DOC and Compound S, and the 18‐hydroxylation of DOC and B; and (4) The correlation between DOC/B and S/F ratios was highly significant (r = 0·86; P < 0·0001), showing the same degree of inhibition of 11‐hydroxylase functions for both 17‐hydroxy (17‐OHS) and 17‐deoxysteroids.
THE OPIOID CONTROL OF LH AND FSH RELEASE: EFFECTS OF A MET‐ENKEPHALIN ANALOGUE AND NALOXONE
Authors: GROSSMAN A. , MOULT P. J. A. , GAILLARD R. C. , DELITALA G. , TOFF W. D. , REES LESLEY H. , BESSER G. M.
Published: March 2008

The effect of a long‐acting analogue of met‐enkephalin (DAMME) and naloxone on gonadotrophin secretion has been investigated in man. In menopausal women DAMME induced a progressive fall in LH to approximately 60% of basal levels at 3 h, which was blocked by naloxone; there was a smaller fall in FSH that did not attain statistical significance. However, the LHRH‐induced rise in LH and FSH in young male volunteers was unaffected by pretreatment with a high‐dose DAMME infusion. Naloxone infusion in young male and female normal subjects produced a significant rise in both LH and FSH. Long‐term infusion of naloxone appeared to increase the rate, and possibly the amplitude, of LH pulsatility. These results suggest that met‐enkephalin‐like opioid peptides exert a tonic inhibitory control of LH release in both menopausal and young subjects of both sexes. This control is most likely to be at the level of the hypothalamus, and involves modulation of pulsatile LHRH release.
ORBITAL PSEUDOTUMOUR AND LACRIMAL INVOLVEMENT DEVELOPING IN A PATIENT WITH RIEDEL'S STRUMA RECEIVING STEROIDS
Authors: WILMSHURST P. , MELSOM R. , GOSTELOW B.
Published: March 2008

We present a patient with hypothyroidism secondary to Riedel's struma, treated with thyroxine and prednisolone, who developed clinical and radiological features of a unilateral orbital pseudotumour with lacrimal gland involvement; the histology of which was indistinguishable from that of the thyroid gland.
PREVALENCE OF VARIOUS DEGREES OF HYPOTHYROIDISM AMONG PATIENTS OF A GENERAL MEDICAL DEPARTMENT
Authors: RINIKER M. , TIÈCHE M. , LUPI G. A. , GROB P. , STUDER H. , BÜRGI H.
Published: March 2008

We have measured basal thyrotropin (TSH) in 945 consecutive patients of a general medical department. Additional thyroid tests were carried out in patients with elevated TSH. Thirty patients (3·1%) had subclinical hypothyroidism, i.e. an elevated TSH with no clinical signs and with a normal free thyroxine index. A cause was found in only fifteen of these thirty patients. Thirteen additional patients (1·37%) had mild or overt primary hypothyroidism, three of which were already diagnosed. This prevalence is three times higher than that found in a retrospective survey at the same hospital. Of the ten newly‐detected cases five were discharged on thyroid hormone replacement. In two patients the antithyroid drugs which were the cause of hypothyroidism were discontinued. The remaining three patients had severe non‐thyroidal illnesses and thyroid hormone was not prescribed. A cause for the hypothyroidism (autoimmune thyroid disease, post‐radioiodine, post‐thyroidectomy or antithyroid drugs) was established in all but two cases. The data suggest that thyroid function tests (preferably a TSH) should be performed on any patient with prior treatment to the thyroid and, in addition with very broad indications, perhaps even routinely, in all women over 50 years of age.
HUMAN POST‐MORTEM PINEAL ENZYME ACTIVITY
Authors: SMITH J. A. , MEE T. J. X. , PADWICK D. J. , SPOKES E. G.
Published: March 2008

The synthetic enzymes for melatonin production, serotonin‐N‐acetyltransferase (SNAT) and hydroxy‐indole‐O‐methyltransferase (HIOMT) were measured in post‐mortem pineal organs from eighty‐eight men and women. The activity of each enzyme was correlated with age and sex. No difference was seen in either parameter when the maximum or minimum activities were measured in the death time periods of the diurnal rhythm established earlier. However, an annual bimodal rhythm was seen in HIOMT activity with maximal values occurring in January and July and minimum activities in March and October. The SNAT and HIOMT enzymes have previously been shown to be stable when measured in pineal organs held under the usual post‐mortem conditions. Pineal HIOMT has also been measured in twenty‐one psychotic individuals. Whilst the schizophrenic group showed significantly increased values, the schizophrenic‐like group had normal values. The results were not affected by ante‐mortem or post‐mortem states or by drug treatment. Any clinical interpretation of pineal dysfunction in disease states need not, therefore, take into consideration age, or possibly sex, but should be aware of the normal diurnal rhythm as well as the bimodal annual rhythm.
A SENSITIVE TECHNIQUE FOR DETERMINATION OF THYROID‐STIMULATING IMMUNOGLOBULIN (TSI) IN UNFRACTIONATED SERUM*
Authors: ETIENNE‐DECERF J. , WINAND R. J.
Published: March 2008

A new sensitive and reproducible technique for the determination of thyroid stimulating immunoglobulins is described. This procedure employs cells obtained from primary culture of human thyroid gland. We measured the increase of cyclic AMP after addition of patient sera. The major advantages of this procedure are the improved sampling throughout with the ability to measure eighty samples simultaneously without fractionation of serum. This large sample allows us to test forty sera together and to assay in duplicate, thus increasing the validity of the results. The TSI activity is associated with the immunoglobulins G (IgG) fraction and we obtained a linear dose response curve with IgG as well as with whole serum. The results obtained in various thyroid diseases are discussed.
THE GONADOTROPHIN RESISTANT OVARY SYNDROME: A CURABLE DISEASE?
Authors: EVERS J. L. H. , ROLLAND R.
Published: March 2008

SUMMARY. A patient with the resistant ovary syndrome is reported. It is suggested that lack of synchronization between steroidogenesis in the granulosa and theca cells is responsible for the (acquired) occurrence of this syndrome. Feedback inhibition of pituitary gonadotrophin secretion was achieved by exogenously administered ovarian steroid hormones. All protein and steroid hormone levels returned to normal and spontaneous ovulatory cycles returned after withdrawal of medication. It is concluded that the so called‘resistant ovary syndrome’is not an irreversible process.
COMBINED CAPTOPRIL AND SPIRONOLACTONE TREATMENT IN CONN'S SYNDROME WITH RENAL IMPAIRMENT AND REFRACTORY HYPERTENSION
Authors: ATKINSON A. B. , BROWN J. J. , DAVIES D. L. , LEVER A. F. , ROBERTSON J. I. S.
Published: March 2008

SUMMARY. Spironolactone alone in full dosage failed to correct hypertension in a patient with Conn's syndrome and renal impairment, although the previously increased total exchangeable sodium fell to normal and the previously suppressed plasma angiotensin II did not rise above the normal range. Addition of the converting enzyme inhibitor captopril reduced plasma angiotensin II to very low levels, with a slight further fall in exchangeable sodium. Blood pressure was well controlled. Because hypertension in Conn's syndrome resistant to spironolactone usually also responds poorly to removal of the adenoma, and is difficult to treat with conventional hypotensive agents, the combination of a converting enzyme inhibitor with a potassium conserving diuretic is worthy of trial in such cases.
ALTERATIONS IN CIRCULATING THYROID HORMONES AND THYROXINE BINDING GLOBULIN IN CHRONIC ALCOHOLISM
Authors: GEURTS J. , DEMEESTER‐MIRKINE N. , GLINOER D. , PRIGOGINE T. , FERNANDEZ‐DEVILLE M. , CORVILAIN J.
Published: March 2008

The present study concerns eighteen chronic alcoholics with minimal liver damage. A significant reduction in total serum T4 with an accompanying drop in circulating TBG was observed in these otherwise euthyroid patients. During alcohol withdrawal, we observed a rapid increase in T4 and TBG into the normal range. We suggest that the fall in the level of circulating thyroxine‐binding globulin is related to a defect in its synthesis or secretion by the liver due to ethanol consumption. Caution is recommended in the interpretation of thyroid function tests in chronic alcoholics.
FAMILIAL HYPERCHOLESTEROLAEMIA AND PRIMARY HYPOTHYROIDISM: COEXISTENCE OF BOTH DISORDERS IN A YOUNG WOMAN WITH SEVERE HYPERCHOLESTEROLAEMIA
Authors: ILLINGWORTH D. R. , McCLUNG M. R. , CONNOR W. E. , ALAUPOVIC P.
Published: March 2008

Severe hypercholesterolaemia in a 17‐year‐old girl was found to be due to the coexistence of heterozygous familial hypercholesterolaemia and chronic lymphocytic thyroiditis with primary hypothyroidism. Her cultured skin fibroblasts showed a 70–75% reduction in the binding, internalization and degradation of 125I‐labelled low density lipoprotein and several other family members were hypercholesterolaemic. Replacement therapy with L‐thyroxine reduced the concentrations of total and low density lipoprotein cholesterol and apoprotein B in the patient's plasma to values similar to those in other sibs with only heterozygous familial hypercholesterolaemia. Severe hypercholesterolaemia attributable to coexistent heterozygous familial hypercholesterolaemia and hypothyroidism in teenage girls may be estimated to occur with a frequency of between 1 in 500 000 and 1 in 106. This value is similar to the gene frequency for homozygous familial hypercholesterolaemia.
FAILURE OF HAEMAGGLUTINATION AND IMMUNOFLUORESCENCE METHODS TO DETECT SERUM ORBITAL ANTIBODIES IN PATIENTS WITH GRAVES' OPHTHALMOPATHY
Authors: HENDERSON JANICE , WALL J. R.
Published: March 2008

Serum antibodies against human, bovine, and guinea‐pig, orbital antigens were tested for in patients with Graves' ophthalmopathy using haemagglutination and immunofluorescence techniques. Although low titres of antibodies were demonstrated in a small proportion of patients with Graves' ophthalmopathy, the prevalence was similar to that for normal subjects using both tests. The significance of these findings and the evidence for a role of autoantibodies in the pathogenesis of Graves' ophthalmopathy are discussed.
A RADIOIMMUNOASSAY FOR NEUROTENSIN
Authors: KRONHEIM S. , SHEPPARD M. C. , MILLER J.
Published: March 2008

A specific radioimmunoassay for neurotensin has been developed with a sensitivity of 40 pg/ml. Neurotensin‐like immunoreactivity in human plasma shows characteristics similar to synthetic neurotensin on Sephadex G‐25 (f) gel chromatography.
EFFECT OF EXOGENOUS INSULIN ON FASTING SERUM LEVELS OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) IN JUVENILE DIABETES
Authors: TALAULICAR M. , EBERT R. , WILLMS B. , CREUTZFELDT W.
Published: March 2008

The effect of insulin on fasting levels of immunoreactive gastric inhibitory polypeptide (IR‐GIP) has been examined in insulin‐dependent, juvenile‐type diabetics who were well‐controlled with two doses of an intermediate insulin. After withdrawal of the evening insulin injection the fasting blood glucose and serum IR‐GIP levels were elevated and decreased significantly following intravenous insulin towards normal values. There was a significant positive correlation between levels of blood glucose and serum IR‐GIP before and during insulin application. It is suggested that fasting serum GIP levels increase in case of insulin deficiency because basal GIP secretion is suppressed by normal insulin levels.
GROWTH HORMONE (GH) SECRETION IN HEPATIC ENCEPHALOPATHY
Authors: LANGER MARIA , MASALA A. , ALAGNA S. , RASSU S. , MADEDDU G. , SOLINAS A. , CHIANDUSSI L.
Published: March 2008

Elevated plasma concentrations and abnormal secretory patterns of GH have been found in patients with cirrhosis of the liver. Displacement of brain dopaminergic monoamines by false ‘neurotransmitters’ produced in the gut has been postulated as a cause of encephalopathy. In this study basal GH plasma levels and their response to TRH and l‐DOPA were determined in thirty‐nine cirrhotic patients and fifteen controls. Eleven patients had evidence of encephalopathy (Group 1), twenty‐eight did not (Group 2). Both basal levels and the mean peak response to TRH were significantly higher in the cirrhotic patients than in the controls (Group 3). Peak values were moderately, but not significantly, higher in Group 1 than in Group 2. The response to l‐DOPA was considerably lower in the encephalopathic patients in comparison with the subjects of both Group 2 and Group 3. This finding is consistent with depletion of active ‘neurotransmitters’ in CNS. Our data fail to demonstrate clearly whether the paradoxical response to TRH can also be related to these abnormalities of monoamine metabolism in cirrhotics.
FACTORS RELATING TO ALDOSTERONE SECRETION RATE, THE EXCRETION OF ALDOSTERONE 18‐GLUCURONIDE, AND THE PLASMA ALDOSTERONE CONCENTRATION IN CIRRHOSIS
Authors: WILKINSON S. P. , WHEELER P. G. , JOWETT T. P. , SMITH I. K. , KEENAN J. , SLATER J. D. H. , WILLIAMS R.
Published: March 2008

In a group of eight patients with cirrhosis the rate of renal excretion of the 18‐glucuronide metabolite of aldosterone (UAldoV) was found to be closely related to the aldosterone secretion rate (ASR). UAldoV was therefore used as an index of ASR in a further group of fifty patients in order to evaluate the possible importance of factors known to regulate aldosterone secretion. UAldoV showed statistically significant relationships to both plasma renin activity (PRA) and the plasma sodium concentration (PNa), but not to the plasma potassium concentration (PK) or the renal excretion of cortisol (UCortV), the latter used as an index of adrencorticotrophic hormone activity. The plasma aldosterone concentration (PAido) was determined in fifty‐eight patients and also found to show statistically significant relationships to PRA and PNa. PAldo showed a weak, though statistically significant, relationship to PK, but not to UCortV. These findings are in keeping with a role for the renin‐angiotensin system in the control of aldosterone secretion in cirrhosis although evidence from other studies suggest other factors to be involved also. Whether PNa was another determinant of ASR, or whether aldosterone was a determinant of PNa through regulating sodium reabsorption by the proximal tubule of the nephron, is uncertain.
PROLACTIN RESPONSE TO METOCLOPRAMIDE AND CHLORPROMAZINE IN PRIMARY TESTICULAR FAILURE AND ISOLATED GONADOTROPHIN DEFICIENCY
Authors: SPITZ I. M. , HALPERIN Y. , ZYLBER‐HARAN E. , SHILO S. , LEROITH D. , LIEL Y. , LIVSHIN J. , LAUFER N. , SCHENKER J.
Published: March 2008

The aim of the present study was to measure the PRL response to metoclopramide (MET) and chlorpromazine (CPZ) in seventeen patients with primary testicular failure and eight patients with isolated gonadotrophin deficiency (IGD). The responses were compared with those to TRH. Basal gonadotrophins and peak responses to LHRH were increased in testicular failure and reduced in IGD. Basal PRL levels were normal in both groups of patients. However, when compared with controls, the PRL response to both MET and CPZ as well as to TRH was exaggerated in primary testicular failure, whereas the responses were decreased in IGD. In both patient groups, as well as in the controls, the PRL response to MET exceeded that to TRH and CPZ. It is suggested that alterations in the steroid milieu are responsible for the exaggerated PRL response to MET, CPZ and TRH in primary testicular failure and the reduced response observed in IGD.
PROLACTIN PULSATILITY IN PATIENTS WITH GONADAL DYSFUNCTION
Authors: MOULT P.J.A. , DACIE JANET E. , REES LESLEY H. , BESSER G.M.
Published: March 2008

Serum prolactin concentrations have been measured at 15 min intervals for 2 h on 240 occasions in 227 patients with symptoms which could have been due to hyperprolactinaemic gonadal dysfunction. Of the 227, 138 had at least one elevated random prolactin level. Overall, 22% showed no significant fluctuation in prolactin. In 38% the levels fell progressively from the start of the sampling period, this pattern being found most commonly in patients complaining of infertility. The sampling method yielded a basal or unstressed prolactin concentration which was, on average, 27% lower than random prolactin concentrations. However, a comparison with clinical data, the radiological appearances of the pituitary fossa, and the response to bromocriptine therapy, has shown that there is no predictive information in the multiple sampling results that could not have been obtained from two or three random prolactin levels.
LACK OF RESPONSE OF 1,25‐DIHYDROXYCHOLECALCIFEROL TO EXOGENOUS PARATHYROID HORMONE IN A PATIENT WITH TREATED PSEUDOHYPOPARATHYROIDISM
Authors: BRAUN J. J. , BIRKENHÄGER J. C. , VISSER T. J. , JUTTMANN J. R.
Published: March 2008

The response of serum 1,25‐dihydroxycholecalciferol (1,25‐OH2CC) concentration to the administration of parathyroid extract (PTE) was studied in a patient with pseudohypoparathyroidism (PHP) type I, 3 days after withdrawal of dihydrotachysterol (DHT) treatment. The patient had had a normal serum calcium (Ca), phosphorus (P) and immunoreactive parathyroid hormone (iPTH) level on DHT for 6 years. After PTE administration no rise of the 1,25‐OH2CC concentration and no response of urinary cAMP and P were seen.
ADDISON'S DISEASE PRESENTING AS A HYPERCALCAEMIC CRISIS IN A PATIENT WITH IDIOPATHIC HYPOPARATHYROIDISM
Authors: WALKER D. A. , DAVIES M.
Published: March 2008

A patient with idiopathic hypoparathyroidism complicated by Addison's disease is described. The development of adrenal insufficiency was accompanied by a hypercalcaemic crisis. The hypercalcaemia appeared to result from a reduction in the filtered load and enhanced renal tubular reabsorption of calcium. Cortisone therapy was followed by the characteristic renal tubular leak of calcium associated with hypoparathyroidism and a return of the serum calcium to normal. The possible mechanisms for these changes in calcium homeostatis are discussed.
DIFFERENT ASPECTS OF 5α‐REDUCTASE DEFICIENCY IN MALE PSEUDOHERMAPHRODITISM AND HYPOTHYROIDISM
Authors: MAUVAIS‐JARVIS P. , KUTTENN F. , MOWSZOWICZ IRÈNE , WRIGHT FRANÇOISE
Published: March 2008

The 5α‐reductase activity that mediates the transformation of testosterone to dihydrotestosterone in various anatomical sites of human beings, has been studied in different pathological conditions related to 5α‐reductase deficiency. We have studied two patients with male pseudohermaphroditism due to 5α‐reductase deficiency, four patients with the complete form of testicular feminization syndrome and four men with primary hypothyroidism. Results were compared with those obtained in seven normal men. In vivo: radioactive tracers of testosterone were administered to each subject by different routes: intravenous, oral and subcutaneous. The urinary metabolites of these labelled precursors were measured. The 5β: 5α ratios of 17‐ketosteroids (aetiocholanolone: 5α‐androsterone) and androstanediols (5β‐androstane‐3α, 17β‐diol: 5α‐androstane‐3α, 17β‐diol) were calculated in the urine recovered after each mode of administration of radioactive testosterone. When testosterone was administered subcutaneously these ratios were highly increased in one patient with male pseudohermaphroditism due to 5α‐reductase deficiency. In all the other patients, the ratios were found to be in the normal range for men. After oral administration of radioactive testosterone, both 5β: 5α ratios were very high in hypothyroid and in 5α‐reductase deficient patients. These results suggest that the defective 5α‐reductase activity observed in hypothyroid patients is only localized in the hepatic compartment. Conversely, in male pseudohermaphroditism, the 5α‐reductase defect might affect both hepatic and extra‐hepatic compartments. In vitro: the diagnosis of 5α‐reductase deficiency was confirmed in the two male pseudohermaphrodite patients after incubation with 3H testosterone of skin homogenates from the external genital area. No 5α‐reduction of testosterone occurred in the two skin specimens studied. In contrast, 5α‐reductase activity was normal in genital skin from hypothyroid and testicular feminization syndrome patients. In pubic skin, 5α‐reductase activity was absent in patients with testicular feminization syndrome. It was in the normal range in homogenates from hypothyroid patients and varied in the 5α‐reductase deficient patients. Based on these data, it may be postulated that the programming of hepatic and extrahepatic 5α‐reductase enzymes is fundamentally different. In addition, the enzyme that mediates the appearance of secondary sex characteristics seems to be androgen dependent, while the 5α‐reductases present in the external genital area and the liver are not androgen dependent.
THE EFFECTS OF A MET‐ENKEPHALIN ANALOGUE ON ACTH, β‐LPH, β‐ENDORPHIN AND MET‐ENKEPHALIN IN PATIENTS WITH ADRENOCORTICAL DISEASE
Authors: GAILLARD R. C. , GROSSMAN A. , SMITH R. , REES LESLEY H. , BESSER G. M.
Published: March 2008

Thirteen patients with either Addison's disease, or Cushing's disease treated by bilateral adrenalectomy, were infused with the long‐acting met‐enkephalin analogue DAMME. In patients with Addison's disease significant and pronounced falls in ACTH and N‐ and C‐terminal β‐LPH were seen; chromatography suggested that β‐endorphin fell concomitantly. Three out of four patients with Cushing's disease who had not received pituitary irradiation, also showed a decrease in plasma ACTH and N‐ and C‐terminal β‐LPH; however, no change was seen in any of the irradiated patients. The changes were naloxone reversible. The levels of plasma met‐enkephalin were normal and did not change after DAMME in any group of patients. These results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, β‐LPH, and β‐endorphin.
DOPAMINERGIC CONTROL OF KETOGENESIS IN FASTING
Authors: BLESA‐MALPICA G. , JOHNSTON D. G. , BURRIN JACKY M. , ØRSKOV H. , HEATH A. B. , ALBERTI K. G. M. M.
Published: March 2008

The role of dopamine in starvation ketonaemia was investigated in male Wistar rats by administration of a specific dopamine receptor antagonist, metoclopramide (4 mg.kg−1.24h−1), or placebo, intragastrically during a 48‐h fast. Starvation alone caused a fall in blood glucose and gluconeogenic precursor concentrations, which was unaffected by metoclopramide administration. Circulating 3‐hydroxybutyrate and acetoacetate levels rose with fasting alone but metoclopramide impaired this ketonaemic response. After 48‐h starvation, total ketone body concentrations (mean±SEM) were 2·28 ± 0·19 mmol/l with metoclopramide therapy, 3·49 ± 0·21 mmol/l with placebo, P < 0·001. Plasma non‐esterified fatty acid levels were similar in metoclopramide‐ and placebo‐treated animals, as were circulating concentrations of insulin, glucagon and growth hormone. Metoclopramide thus decreased the ketonaemic response to starvation without an apparent change in lipolysis or circulating hormone levels, suggesting a direct role for dopamine in production of starvation ketonaemia.
FAMILIAL CONGENITAL CUSHING'S SYNDROME DUE TO BILATERAL NODULAR ADRENAL HYPERPLASIA
Authors: DONALDSON M. D. C. , GRANT D. B. , O'HARE M. J. , SHACKLETON C. H. L.
Published: March 2008

Two siblings with congenital Cushing's syndrome due to bilateral nodular adrenal hyperplasia are described. The older, a boy, presented with severe hypertension and died soon after subtotal adrenalectomy. His sister, who had clitoral enlargement and showed persistent hyponatraemia, had a two‐stage total adrenalectomy and is still alive. Investigations in the second case showed grossly elevated urinary cortisol metabolites, 17‐oxosteroids and 3β‐hydroxy‐5‐ene‐steroids. These were not suppressed by dexamethasone, and plasma ACTH was undetectable, indicating that the disorder was not due to excessive ACTH secretion. Cell culture studies on the resected adrenals failed to demonstrate an abnormal pattern of steroid synthesis in vitro, and normal trophic responses were obtained with 1–24 ACTH and monobutyryl cyclic AMP. No stimulation of steroid synthesis was obtained with a range of polypeptide hormones, and the cause of the adrenal hyperplasia remains unknown.
THE EFFECT OF WEIGHT LOSS ON SEX STEROID SECRETION AND BINDING IN MASSIVELY OBESE WOMEN
Authors: KOPELMAN P. G. , WHITE N. , PILKINGTON T. R. E. , JEFFCOATE S. L.
Published: March 2008

We have previously reported increased testosterone and androstenedione concentrations and decreased sex hormone binding globulin (SHBG) concentrations in the plasma of massively obese women. We now report that these plasma hormone concentrations return to normal in twelve of the same women after substantial weight reduction and these changes are associated with more normal menstrual cycles. We conclude that body weight and fat are important determinants of sex steroid secretion and binding and thus influence menstrual function.
BROMOCRIPTINE AND OESTROGEN MODULATION OF GONADOTROPHIN RELEASE IN NORMO‐AND HYPERPROLACTINAEMIC PATIENTS WITH AMENORRHOEA
Authors: DJURSING H. , HAGEN C. , CHRISTENSEN F. , NICKELSEN C.
Published: March 2008

Effects of oestradiol, bromocriptine, and bromocriptine plus oestradiol, on basal and GnRH stimulated gonadotrophin concentrations were studied in normo‐(group 1, n= 7) and hyperprolactinaemic (group 2, n= 6) patients with secondary amenorrhoea. Before drug administration, hyper‐responsiveness of LH, but normal FSH responses to GnRH were observed in most patients. Oral administration of 2 mg oestradiol for 4 days resulted in increased 17β‐oestradiol levels in plasma in normal women (n= 6) in the early follicular phase of the cycle, and in groups 1 and 2. During oestradiol administration plasma LH concentration increased significantly and there was an increase of LH and FSH responses to GnRH in normal subjects, but not in amenorrhoeic women. In groups 1 and 2 basal FSH levels were suppressed but no change in GnRH stimulated gonadotrophin responses was seen. Bromocriptine (5 mg per day for 5 days) significantly decreased prolactin concentrations and increased 17β‐oestradiol levels in plasma in group 2 but not in group 1. The mean plasma 17β‐oestradiol concentration had increased to levels similar to those obtained during oestradiol administration alone. The mean LH response to GnRH was suppressed in group 2, but not in group 1. Basal and GnRH‐stimulated plasma FSH concentrations were not changed by bromocriptine treatment. Compared with the GnRH induced LH response during bromocriptine alone, bromocriptine treatment plus oestradiol administration resulted in a significantly increased LH response in group 2. This was not found in group 1.

The present results suggest that there is an increased dopamine activity and inhibition of GnRH at the hypothalamic level and a relative dopamine deficiency at the pituitary level in hyperprolactinaemic patients. Normoprolac‐tinaemic patients with hypothalamic amenorrhoea have increased dopaminergic activity at the hypothalamic, as well as the, pituitary level, or alternatively that the LH release is not influenced by dopamine in these patients. Finally bromocriptine sensitizes LH‐secreting cells to GnRH in hyperprolactinaemic, but not in normoprolactinaemic, patients.
NON‐SUPPRESSIBLE INSULIN‐LIKE ACTIVITY DURING PREGNANCY IN WOMEN WITH DIABETES MELLITUS
Authors: HERINGTON A. C. , MARTIN F. I. R. , McBAIN J. C.
Published: March 2008

Serum levels of the growth factor non‐suppressible insulin‐like activity (NSILA‐S) have been measured in eleven pregnant women with diabetes mellitus during pregnancy and immediately (2 days) after birth. A significant increase in mean levels was observed with increasing gestation, reaching a peak at the time of delivery and subsequently returning to non‐pregnant levels within 2 days. The NSILA‐S levels in diabetic pregnancies were not different from those in non‐diabetic pregnancies and there were no significant correlations between NSILA‐S and birth weight, maternal diabetic control, age or duration of diabetes or the treatment required. The physiological role of high NSILA‐S levels during pregnancy still requires elucidation.
STUDIES ON OESTROGEN STIMULATED NEUROPHYSIN IN WOMEN WITH ANOVULATION
Authors: McHUGH ROSEMARY E. , MARVIN SUSAN C. , SHIRLEY ANNE , BUTT W. R. , LYNCH S. S. , SHAW R. W.
Published: March 2008

The effects of endogenous and exogenous oestrogen on serum concentrations of oestrogen stimulated neurophysin (ESN) were studied in women with regular menstrual cycles and patients with anovulation. In ten menstrual cycles serum ESN concentrations rose steadily from 305 ± 16 ng/l (mean ± SEM) in the early follicular phase to reach maximum concentrations at about the time of ovulation (601 ± 106 ng/l). There were significant correlations between ESN and oestradiol concentrations in nine of the ten cycles (P < 0·05). The concentration in the mid luteal phase (386 ± 43 ng/l) was also significantly greater than at the beginning of the cycle (P < 0·05).

Stimulation of endogenous oestrogens by treatment with clomiphene was accompanied by a release of ESN. Oestrogen concentrations were significantly lower in 5 months in which ovulation did not occur than in ten treatments in which ovulation did occur (P < 0·05). The amount of ESN produced however, was similar in the two groups.

The basal concentration of ESN was within the range found in the early follicular phase of the cycle in twenty of the thirty‐seven patients with anovulation in whom it was measured. Concentrations tended to be low in patients with anorexia nervosa or hyperprolactinaemia and oestrogen concentrations were also low. Levels were high in oligomenorrhoea but oestradiol concentrations were normal.

Serum ESN concentrations in oestrogen provocation and amplification tests reached maximum values in normal subjects 48 h after the administration of oestradiol benzoate: LH concentrations continued to rise until 72 h. In twenty‐one of forty‐one provocation tests on anovular patients the amount of ESN released was within the range for normal controls: twelve released less and eight released more. There was no correlation between the basal ESN values and the ESN released.

There was intact positive LH feedback in sixteen of the forty‐one tests performed. In all except two tests with positive LH feedback, ESN was also released, but in the twenty‐five tests with no evidence of LH positive feedback there was normal release of ESN in twelve, reduced release in ten and excessive release in three. In the amplification tests LHRH was without effect on the ESN concentrations before or after oestrogen administration.

It is concluded that either the release of LH stimulated by oestrogen is independent of the release of ESN, or it is stimulated at different threshold levels of oestrogen. ESN is more readily released than LH and the mechanism is probably less involved.
LHRH TEST IN BARTTER'S SYNDROME BEFORE AND DURING TREATMENT WITH PROSTAGLANDIN SYNTHESIS INHIBITORS
Authors: LARIZZA DANIELA , LORINI RENATA , CISTERNINO MARIANGELA , SALVATONI A. , SEVERI FRANCESCA
Published: March 2008

LHRH tests were performed in two children with Bartter's syndrome before and during treatment with prostaglandin synthesis inhibitors. Before treatment, in patient 1 both basal and peak FSH and LH levels were elevated; in patient 2 basal and peak FSH levels were above the normal range, while basal and peak LH levels were normal. During treatment with an inhibitor of prostaglandin synthesis, abnormal values decreased into the normal range. These results support a possible role of endogenous prostaglandins in regulating gonadotrophin secretion in humans.
RELATION OF hCG‐STIMULATED STEROIDOGENESIS TO SERUM FSH, LH AND PROLACTIN IN MAN
Authors: MARTIKAINEN H.
Published: March 2008

Nine adult healthy male volunteers were given a single intramuscular injection of 5000 iu of human chorionic gonadotrophin (hCG). Peripheral blood samples were collected up to 7 days after the injection, the sera were analysed for LH, FSH and prolactin and the results were related to changes in the concentrations of testosterone and oestradiol.

Serum LH concentrations tended to decrease for 4 days after the hCG injection (to 65% of the 0 h value) but returned to the starting level during the 7‐day observation period. FSH was suppressed throughout the experiment and correlated inversely with serum prolactin (r = ‐0·74, P < 0·01). The first significant decrease was seen at 48 h and the minimum concentration (28 ± 4%, SEM) at 7 days. Prolactin levels changed only slightly during the first 48 h after the injection but increased thereafter, being significantly elevated at 4 days, and reached a maximum (183 ± 22%) at 6 days after hCG adminstration, coinciding with the late phase of the testosterone response to hCG. Between testosterone and prolactin a positive correlation (r = 0·70. P < 0·01) was found during hCG stimulation.

The results suggest that endogenous steroid production of the human testis after hCG administration is sufficient to induce changes in gonadotrophin and prolactin secretion. It is further concluded that the feedback mechanism of FSH is more sensitive to increased testicular steroid output following hCG injection than that of LH. It is hypothesized that pituitary prolactin secretion is stimulated by the elevated serum oestradiol concentration at 24–48 h, and the long term testosterone response, observed 2–6 days after the hCG injection, may be partly due to increased prolactin concentrations.
STUDIES ON CIRCULATING MET‐ENKEPHALIN AND β‐ENDORPHIN: NORMAL SUBJECTS AND PATIENTS WITH RENAL AND ADRENAL DISEASE
Authors: SMITH R. , GROSSMAN A. , GAILLARD R. , CLEMENT‐JONES VICKY , RATTER SALLY , MALLINSON J. , LOWRY P. J. , BESSER G. M. , REES LESLEY H.
Published: March 2008

Studies were performed to define the responses of plasma met‐enkephalin to various endocrine and pathological stimuli and to determine the relationship between plasma β‐endorphin and met‐enkephalin. During insulin‐induced hypoglycaemia ACTH, β‐LPH and β‐endorphin immunoreactivity rose in parallel, but plasma met‐enkephalin did not change significantly. Sephadex G75 chromatography of samples taken at the time of the peak response (45 min) confirmed the rise in both β‐LPH and β‐endorphin. During administration of dexamethasone, 0·5mg 6 hourly for 48 h, plasma cortisol and ACTH became undetectable at 24 h, and β‐LPH and β‐endorphin fell significantly by 24 h and were undetectable by 48 h; plasma met‐enkephalin, however, showed no significant change. Nine adrenalectomized patients with Cushing's disease and four patients with Addison's disease had elevated plasma ACTH, β‐LPH and β‐endorphin but normal plasma met‐enkephalin levels. Each of ten patients with renal failure had markedly elevated plasma met‐enkephalin immunoreactivity which co‐eluted with synthetic met‐enkephalin on BioGel P4 chromatography. Trypsin and carboxypeptidase‐B digestion of the P4 chromatography fractions generated met‐enkephalin immunoreactivity in earlier fractions, indicating the presence of a potential high molecular weight met‐enkephalin precursor.

The results imply that different control mechanisms govern β‐endorphin and met‐enkephalin plasma levels and that the adrenal is not the only source of plasma met‐enkephalin. The elevated levels of met‐enkephalin in renal failure may be due to impaired clearance of met‐enkephalin or of its precursor or to increased met‐enkephalin production.
Γ‐MELANOTROPHIN‐LIKE IMMUNOREACTIVITIES IN HUMAN PITUITARIES, ACTH‐PRODUCING PITUITARY ADENOMAS, AND ECTOPIC ACTH‐PRODUCING TUMOURS: EVIDENCE FOR AN ABNORMALITY IN GLYCOSYLATION IN ECTOPIC ACTH‐PRODUCING TUMOURS
Authors: TANAKA I. , NAKAI Y. , NAKAO K. , OKI S. , FUKATA J. , IMURA H.
Published: March 2008

Using gel exclusion chromatography on Bio‐Gel P‐60, γ‐melanotropin‐like immunoreactivity (γ‐MSH‐LI) in three human pituitary glands, two ACTH‐producing pituitary adenomas, and three ectopic ACTH‐producing tumours (two medullary thyroid carcinomas and one thymoma) was divided into one or two molecular weight classes. The largest component eluted near the position of mouse 16K fragment and was designated big γ‐MSH‐LI. This big γ‐MSH‐LI was present in all samples. The second one, designated intermediate γ‐MSH‐LI, eluted between the position of mouse 16K fragment and human ACTH, and was demonstrated only in two ectopic ACTH‐producing tumours. No γ‐MSH‐LI emerged at the elution position of synthetic γ3‐MSH.

Affinity chromatography on concanavalin A‐agarose revealed that a significant fraction (52–68%) of γ‐MSH‐LI from human pituitary glands, ACTH‐producing pituitary adenomas, and one ectopic ACTH‐producing tumour bound to the column and was eluted with α‐methyl‐D‐mannopyranoside. In two ectopic ACTH‐producing tumours which contained big and intermediate γ‐MSH‐LI, a relatively small fraction (27–35%) of γ‐MSH‐LI bound to the column and was similarly eluted. These observations suggest that human γ‐MSH‐LI is glycosylated and that there is an abnormality in the glycosylation of γ‐MSH‐LI in some ectopic ACTH‐producing tumours.
INHERITED THYROXINE EXCESS: A SERUM ABNORMALITY DUE TO AN INCREASED AFFINITY FOR MODIFIED ALBUMIN
Authors: DOCTER R. , BOS G. , KRENNING E. P. , FEKKES D. , VISSER T. J. , HENNEMANN G.
Published: March 2008

Further analysis of sera from euthyroid subjects with dominantly‐inherited, elevated serum total thyroxine (T4) and free T4 index but with normal free T4 levels was performed as an extension of a previous study (Hennemann et al., 1979a). Scatchard analysis and isoelectric focusing of whole sera and purified serum fractions suggest that this T4 excess is due to increased T4 binding by modified serum albumin.

Recognition of this syndrome and appreciation that the free T4 index does not reflect the free T4 levels is important to protect patients from the consequences of an incorrect diagnosis of thyrotoxicosis.
EVIDENCE FOR SECONDARY HYPERPARATHYROIDISM IN THE OSTEOMALACIA ASSOCIATED WITH CHRONIC LIVER DISEASE
Authors: DIBBLE J. B. , SHERIDAN P. , HAMPSHIRE R. , HARDY G. J. , LOSOWSKY M. S.
Published: March 2008

Previous reports have suggested that secondary hyperparathyroidism is extremely uncommon in hepatic osteomalacia. This, together with other findings, has led to suggestions that in chronic liver disease there may be selective resistance of bone to vitamin D or a specific bone mineralization defect unrelated to Vitamin D.

To examine these possibilities, twenty‐five patients with chronic liver disease have been studied by bone biopsy, serum calcium and inorganic phosphate, plasma 25‐hydroxyvitamin D, plasma immunoreactive parathormone (iPTH), fasting urine cAMP, fasting renal tubular maximal reabsorptive capacity for phosphate (TmP/GFR) and fine grain hand x‐rays. Nine of the patients had osteomalacia on bone biopsy, eight of these had subnormal levels of plasma 25‐hydroxyvitamin D and the other had a borderline result. Based on the concensus of all the tests, five of these had evidence of secondary hyperparathyroidism. Plasma iPTH was higher in patients with osteomalacia than in patients without osteomalacia (P < 0·01) or controls (P < 0·01). Urine cAMP was higher in patients with osteomalacia than in patients without osteomalacia (P < 0·001) or controls (P < 0·01). TmP/GFR was significantly lower in patients with osteomalacia than in controls (P < 0·05) but not significantly different from patients without osteomalacia.

The findings of this study indicate that hyperparathyroidism occurs in a substantial proportion of patients with the osteomalacia of chronic liver disease. Moreover, osteomalacia in chronic liver disease is clearly related to reduced levels of plasma 25‐hydroxyvitamin D. We conclude that hepatic osteomalacia is a vitamin D deficiency state and there is no need to suggest an unusual aetiology.
FAILURE OF 2‐HYDROXYOESTRONE TO LOWER PROLACTIN CONCENTRATIONS IN HYPERPROLACTINAEMIC WOMEN
Authors: FRANKS S. , LIGHTMAN S. L. , MACLUSKY N. J. , NAFTOLIN F. , LYNCH S. S. , BUTT W. R. , JACOBS H. S.
Published: March 2008

The catechol oestrogen 2‐hydroxyoestrone has been reported to lower serum prolactin concentrations acutely in normal women and it has been proposed that it may be effective in suppressing prolactin secretion in hyperprolactinaemic patients. Five women with hyperprolactinaemia and anovulation were studied. Following a control infusion, 2‐hydroxyoestrone was given at a rate of 80 μg/h for 4 h. In no patient was there a fall in prolactin levels and no changes were observed in gonadotrophin concentrations. We conclude that a short‐term infusion of 2‐hydroxyoestrone, at a dose which will produce high blood levels of the steroid, does not affect prolactin or gonadotrophin secretion in hyperprolac‐tinaemic states.
HYPERTHYROIDISM IN GESTATIONAL TROPHOBLASTIC NEOPLASIA
Authors: NORMAN R. J. , GREEN‐THOMPSON R. W. , JIALAL I. , SOUTTER W. P. , PILLAY N. L. , JOUBERT S. M.
Published: March 2008

The thyroid status of twenty‐seven African patients with gestational trophoblastic neoplasia (GTN) was studied. Fifteen patients were found to be biochemically hyperthyroid (eight patients with choriocarcinoma; seven with hydatidiform mole). Of these fifteen patients, nine were clinically thyrotoxic. The most serious complication of thyrotoxicosis was life‐threatening acute pulmonary oedema with associated cardiac failure. It was found that when serum levels of the human chorionic gonadotrophin (hCG) reached a level of about 0·1 ± 106 iu/l, thirteen of sixteen patients were biochemically hyper‐thyroid; at serum levels of 0·3 ± 106 iu/l of hCG most patients were clinically thyrotoxic. A feature of hyperthyroidism associated with GTN is that whereas T4 is invariably raised the T3:T4 ratio tends to be low (0·015 ± 005); rT3:T3 ratios were high in this group. TSH levels were not increased.
DEFECTIVE IODIDE TRANSPORT AND NORMAL ORGANIFICATION OF IODIDE IN COLD NODULES OF THE THYROID
Authors: SHIROOZU A. , INOUE K. , NAKASHIMA T. , OKAMURA K. , YOSHINARI M. , NISHITANI H. , OMAE T.
Published: March 2008

Eleven thyroid follicular adenomas, cold on scintigram were analysed to determine whether defect in iodide organification or iodide transport causes low iodide uptake in cold nodules of the thyroid. The results were compared with perinodular tissue samples used as controls.

In eight of eleven adenomas incubated in medium with 0·1 μm of iodide, newly organified iodide was 85·6 ± 8·6% of total trapped iodide, which was significantly higher than 52·3 ± 12·8% in controls. The remaining three adenomas showed a value as low as 4·0 ± 2·7%. These data suggest that follicular adenomas are of two different groups; one with high organic iodinating activity and the other with none. These two groups were denned as FA‐1 and FA‐2. Thyroid: medium ratios of iodide of both groups were significantly depressed, indicating that the essential alteration in the thyroid follicular adenoma is a disturbance of iodide transport.

In contrast to controls organification of iodide was not inhibited by the addition of 100 μm iodide to the medium in FA‐1 adenomas. In both FA‐1 and FA‐2, the degree of iodination of thyroglobulin (Tg) in equilibrium was significantly lower than that in controls. Therefore, in most cases with the follicular adenoma, the principal cause of decreased iodination of Tg was considered to be a depressed iodide transport, but not an impairment of organic iodination.
T3 KINETICS IN EUTHYROID GRAVES' DISEASE PATIENTS WHO EXHIBIT HYPER‐RESPONSIVENESS TO TRH AFTER RADIOIODINE TREATMENT
Authors: JAFFIOL C. , BALDET L. , MISSONNE C. LEMAIRE , PAPACHRISTOU C.
Published: March 2008

A major reduction in T3 turnover has been demonstrated previously in clinically hypothyroid patients. We have used non‐compartmental (NC) and mono‐compartmental (MC) analysis to study ten patients with Graves' disease who, following treatment with radioactive iodine (RAI), are now clinically euthyroid but who showed hyper‐responsiveness to TRH although serum T3 and T4 concentrations are within the normal range. T3 production rate (PR), metabolic clearance rate (MRC) and fractional‐turnover (K) were all significantly reduced in patients compared with seven controls (P < 0·01). T3, MCR and PR were consistently higher, and T3 K lower, when calculated by MC, than values calculated by NC analysis. The difference in T3 production rates between patients (mean 16·6 nmol/day) and controls (mean 38·9 nmol/day) raises the question of replacement therapy in patients who are apparently euthyroid but TRH hyper‐responsive.