bluuebunny/crossref_metadata_2025 huggingface dataset:
PROLONGED TREATMENT OF HYPERTHYROIDISM WITH SODIUM TYROPANOATE, AN ORAL CHOLECYSTOGRAPHIC AGENT: A RE‐EVALUATION OF ITS CLINICAL UTILITY
Authors: NOGUCHI K. , SUZUKI H. , NAKAHATA M. , KUROSAWA S. , NAKAGAWA S.
Published: March 2008

To re‐evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1·5 g daily) alone for 14 weeks, and six patients (TP+MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an ‘escape’ occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment.

In the TP+MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4–14 weeks (7·3±5·0 weeks on the average), TP was withdrawn and replaced by MMI. A rebound of TI and serum T3 occurred within a week. These data suggest that, in the chronic treatment of hyperthyroidism, doses of combined TP and thionamide drug may have the advantage over those of TP alone both for achieving a more significant improvement of thyrotoxicosis and for precluding the recurrence of hyperthyroidism after cessation of TP therapy.
SERUM IODOTHYRONINE CONCENTRATIONS DURING INTRODUCTION OF THYROXINE REPLACEMENT THERAPY IN HYPOTHYROIDISM
Authors: PEARCE C. J. , HIMSWORTH R. L.
Published: March 2008

Serum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 μg at intervals of 4 weeks to a total of 200 μg daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1·35 + 0·23FT4, r = 0·916, P> 0·001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0·195 TT4, (r=0·936, P>0·001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 μg of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = ‐ 0·022 + 0·0027TT4, r= 0·921, P > 0·001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r= 0·927, −0·917 and −0·900 respectively). These correlations were significantly better (P > 0·05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised. During incremental treatment with T4 there was no disproportionate increase in rT3 as TT4 and FT4 rose, nor was there evidence of a changing relation between the concentrations of FT3 and FT4 over the range of concentrations encountered. The findings suggest that the deioidination of T4 does not change with the availability of T3.
MEASUREMENT OF TSH IN HUMAN AMNIOTIC FLUID: DIAGNOSIS OF FETAL THYROID ABNORMALITY IN UTERO
Authors: YOSHIDA K. , SAKURADA T. , TAKAHASHI T. , FURUHASHI N. , KAISE K. , YOSHINAGA K.
Published: March 2008

Using a highly sensitive immunoradiometric assay kit for human TSH, we measured TSH concentrations in unconcentrated amniotic fluids in normal pregnancies and those complicated for example by maternal hyper‐ and hypothyroidism, and compared them with those in maternal and cord sera. In normal pregnancies the mean concentration of TSH in amniotic fluid samples was 0·129 μU/ml, ranging from 0·065 to 0·278 μU/ml. In patients with premature delivery, the amniotic fluid TSH concentration was higher at 0·218 μU/ml. In four patients with abnormal thyroid function, TSH in amniotic fluid changed in parallel to that in cord serum, and there was a significant positive correlation between the two. No such correlation was observed between the concentrations of TSH in amniotic fluid and maternal serum. These results suggest that TSH in human amniotic fluid reflects fetal rather than maternal thyroid function and that the determination of TSH levels in amniotic fluid is useful in the diagnosis of abnormal thyroid function in fetuses.
THE LEUCOCYTE SODIUM PUMP IN HEALTHY AND OBESE SUBJECTS: THE ASSOCIATION OF INSULIN WITH ITS ACTIVITY
Authors: NG L. L. , HOCKADAY T. D. R.
Published: March 2008

Leucocyte ouabain‐sensitive 22Na+ efflux was studied in 35 normal and 12 obese subjects. This efflux rate constant was raised in the obese (2·72 ± SEM 0·13 vs 2·31 ± 0·08 h‐1, P>0·006), indicating a higher activity of the sodium pump in vivo. There was a significant correlation between this efflux rate constant and fasting insulin level in both the whole population and in the normals alone (rs= 0·36, P > 0·007, and rs= 0·40, P > 0·009 respectively). A hyperinsulinaemiceuglycaemic clamp was performed on seven normal volunteers. After 2 h, there was a significant stimulation of the leucocyte efflux rate constant (from 2·86 ± 0·17 to 3·33 ± 0·18 h‐1, P> 0.01). In‐vitro incubation of leucocytes with insulin produced a maximal stimulation of the Na+‐K+‐ATPase activity of about 35% at 2 h with half‐maximal stimulation achieved at 46 mU/1. Insulin (100 mU/1) also stimulated the leucocyte ouabain‐sensitive 22Na+ efflux rate constant in vitro by about 11 % with or without 1 h of preincubation with the insulin. These findings may explain the hypokalaemic and sodium retaining effects of insulin in man; they may also partially explain the raised Na+ efflux rate constants in obesity.
AUTOIMMUNE CRANIAL DIABETES INSIPIDUS: ITS ASSOCIATION WITH OTHER ENDOCRINE DISEASES AND WITH HISTIOCYTOSIS X
Authors: SCHERBAUM W. A. , WASS J. A. H. , BESSER G. M. , BOTTAZZO G. F. , DONIACH DEBORAH
Published: March 2008

Thirty‐nine patients with idiopathic cranial diabetes insipidus (DI) and 81 secondary to hypothalamic lesions were investigated for the presence both of associated autoimmune diseases and autoantibodies. Eleven (28%) of the idiopathic but none of the secondary DI cases had an overt autoimmune disease. A further two patients with idiopathic DI had associated organ‐specific autoantibodies. Autoantibodies to vasopressin (AVP)‐secreting hypothalamic cells were detected in 12 patients with idiopathic DI (31 %). Seven out of 13 cases of DI secondary to histiocytosis X (HX) were also positive (54%), whereas only two (3%) of the other 68 sera from patients with secondary DI reacted with AVP cells. Of the 13 patients with DI associated with frank organ‐specific autoimmune diseases or autoantibodies alone, eight (62%) were positive for AVP‐cell antibodies. The finding of associated autoimmune diseases in a patient with idiopathic DI is therefore suggestive of an autoimmune origin of DI, and this can be supported by the detection in the serum of AVP cell antibodies. In cases of HX, the new finding of the presence of AVP‐cell antibodies reflects hypothalamic infiltration by HX cells, and suggests that these DR+‘Langer‐hans‐like’ cells play more than a passive role in the hypothalamic lesion.
AN ANALOGUE OF MET‐ENKEPHALIN ATTENUATES THE PITUITARY‐ADRENAL RESPONSE TO OVINE CORTICOTROPHIN RELEASING FACTOR
Authors: GROSSMAN A. , DELITALA G. , MANNELLI M. , AL‐DAMLUJI S. , COY D. H. , BESSER G. M.
Published: March 2008

The met‐enkephalin analogue, DAMME, suppresses the pituitary‐adrenal axis in normal subjects; it is not clear whether this occurs at the level of the pituitary or above. We therefore administered synthetic ovine corticotrophin releasing factor (CRF‐41) 100 μg i.v. to a group of normal male subjects, with or without pretreatment with DAMME 250 μg i.v., and monitored the response of plasma ACTH and serum cortisol. CRF‐41 caused a marked stimulation of ACTH and cortisol release, but this was significantly attenuated by pretreatment with DAMME. It is therefore concluded that DAMME either directly inhibits the corticotroph at the level of the pituitary, or that it suppresses release of an additional factor which normally potentiates the action of CRF‐41 on the pituitary.
DOPAMINE EFFECTS ON 11‐DEOXYCORTICOSTERONE CONCENTRATIONS IN PATIENTS WITH CUSHING'S SYNDROME AND IN VITRO
Authors: CONNELL J. M. C. , DAVIES D. L. , FRASER R. , KENYON C. J.
Published: March 2008

The effect of dopamine (1 μg/kg /min by i.v. infusion) on corticosteroid levels was studied in five patients with cortisol excess caused by increased ACTH secretion. In four of the five subjects dopamine, when compared with placebo infusion, caused plasma concentrations of 11‐deoxycorticosterone to rise without affecting levels of cortisol, corticosterone or aldosterone. In a parallel in‐vitro study using incubations of bovine adrenal zona glomerulosa cells, dopamine (10‐9 mol/1–10‐5 mol/l) had no effect on basal or ACTH stimulated secretion of aldosterone, cortisol or 11‐deoxycorticosterone. However, dopamine (10‐5 mol/l) partially inhibited angiotensin II (10‐7 mol/l) stimulated secretion of aldosterone (4.36 ng/106 cells/h ± 0·28 vs 2·90 ± 0·20, P>0·05) but did not alter 11‐deoxycorticosterone secretion in the same incubations. These data suggest that the effect of dopamine on 11–deoxycorticosterone secretion in vivo may not be due to its direct action on the adrenal to inhibit corticosteroidogenesis. An alternative explanation is that dopamine may alter extra‐adrenal synthesis of 11‐deoxycorticosterone, possibly by increasing substrate availability to tissues capable of 11‐hydroxylation reactions.
THYROID FUNCTION IN PATIENTS WITH HYPERPROLACTINAEMIA: RELATIONSHIP TO DOPAMINERGIC INHIBITION OF TSH RELEASE
Authors: DIEGUEZ C. , PETERS J. R. , PAGE M. D. , JOHN R. , HALL R. , SCANLON M. F.
Published: March 2008

It has been reported recently that patients with hyperprolactinaemia may develop hypothyroidism as a consequence of the increased inhibition of TSH release by dopamine which occurs in the majority of such patients. In this study we have evaluated thyroid function in a large number of hyperprolactinaemic patients in order to delineate more precisely the relationship between thyroid status, free thyroid hormone levels and the control of TSH release by dopamine. Biochemical euthyroidism was present in the majority of the hyperprolactinaemic patients. Our data indicate that the increased dopaminergic inhibition of TSH release does not lead to hypothyroidism. Instead, the slightly elevated basal TSH levels and TSH responses to TRH (within the normal range) may reflect the operation of a compensatory mechanism to maintain euthyroidism in the face of the increased inhibition of TSH release by hypothalamic dopamine.
PROTEIN‐A PURIFIED HUMAN IMMUNOGLOBULINS: A COMPARISON OF THYROID STIMULATING AND THYROTROPHIN RECEPTOR BINDING ACTIVITIES IN THYROTOXICOSIS
Authors: READER S. C. J. , DAVISON B. , BEARDWELL C. , RATCLIFFE J. G. , ROBERTSON W. R.
Published: March 2008

Protein‐A purified human thyroid stimulating immunoglobulins (TSIg) and thyrotrophin binding inhibiting immunoglobulins (TBIIg) were measured in euthyroid subjects and thyrotoxic patients by bioassay and TSH radioligand receptor assay respectively. Unextracted sera from euthyroid and thyrotoxic subjects inhibited both basal and TSH stimulated iodide uptake in the bioassay, which was based on iodide uptake in porcine thyrocytes. Similar effects were seen with Ig and TSIg extracted from sera using either polyethylene glycol or ammonium sulphate. However IgG and TSIg prepared using Protein‐A Sepharose CL‐4B from sera of euthyroid subjects had little effect in this system. The majority of Protein‐A purified TSIg preparations from sera of thyrotoxic patients stimulated iodide uptake in porcine thyrocytes in a dose‐dependent manner and most (85%) diluted parallel to both bovine and human TSH. TSIg and TBIIg from 73 patients with thyrotoxicosis were assessed using the bioassay and receptor assay and compared to a control group of 35 euthyroid subjects. The median (and range) values for TSIg and TBIIg in the euthyroid group were 4·35 (0·8 to 7·5, % stimulation over control) and 2·7 (–9·3 to 8·6, TBII index) for the bioassay and radioreceptor assay respectively. A value of < 10·0 in both assays was taken as a positive result. Of the thyrotoxic patients 61 out of 73 were positive in the bioassay (83·6%) compared to 60 in the radioreceptor assay (82·2%). There was a positive correlation between the two assays (r = 0·821, P>0·001). Of the 73 thyrotoxic patients 40 were untreated, 18 had received carbimazole and 15 had been previously treated with iodine‐131. TSIg levels in the untreated thyrotoxics were similar to those in either group of treated patients. However they were higher (P>0·05) in the iodine‐131 group than in the patients treated with carbimazole.

Similar results were obtained for TBIIg. The coupling of a specific extraction method for human serum IgG with a bioassay for TSIg has demonstrated a high prevalence of these immunoglobulins in patients with thyrotoxicosis. The agreement between this assay and a radioreceptor assay was good, indicating that TSH displacing and thyroid stimulating activities of these immunoglobulins are closely related.
IS SALT‐WASTING IN CONGENITAL ADRENAL HYPERPLASIA DUE TO THE SAME GENE AS THE FASCICULATA DEFECT?
Authors: STONER ELIZABETH , DIMARTINO‐NARDI JOAN , KUHNLE URSULA , LEVINE LENORE S. , OBERFIELD SHARON E. , NEW MARIA I.
Published: March 2008

Clinical studies in patients with 21‐hydroxylase deficiency congenital adrenal hyperplasia (CAH) were designed to ascertain the genetics of the salt‐wasting component of the disorder. The gene controlling aldosterone biosynthesis may not be the same gene that controls 21‐hydroxylase in the adrenal zona fasciculata. This we infer from the following clinical observations: (1) concordance for salt‐wasting is not observed in all HLA‐identical sibs with CAH; (2) the defect in aldosterone biosynthesis does not persist throughout life as does the fasciculate defect; (3) there is a significantly increased gene frequency of B40 and Bw47 in salt‐wasting CAH; (4) obligate heterozygote parents of patients with salt‐wasting CAH do not express a partial defect in aldosterone biosynthesis, as they do in the fasciculata. These observations cast doubt on the accepted concept of the autosomal recessive transmission of the glomerulosa 21‐hydroxylase deficiency.
PROLACTIN LEVELS IN HYPOTHYROID AND EUTHYROID INFANTS DURING THE FIRST WEEK OF LIFE
Authors: MITCHELL M. L. , HERMOS ROSALIE J. , BENNETT ANN J. E. , McKENNA J. J. , MITCHELL ELIZABETH L.
Published: March 2008

A radioimmunoassay (RIA) procedure was devised for the estimation of PRL in eluates of dried whole blood from filter paper. Levels of PRL were measured in newborn blood obtained during the first week of life from 530 infants of normal birthweight (>2500 g) with normal T4 values, 114 infants of normal birthweight with low T4 values (T4<6.0 μg/dl), 47 infants with congenital hypothyroidism, 57 infants of low birthweight (<2500 g) with normal T4 values, and 114 infants of low birthweight with low T4 values. Examination of PRL concentrations among comparably aged infants from the various groups revealed that the mean PRL values of the hypothyroid group were consistently greater than those of any of the other groups of infants regardless of the mean T4 levels. With the exception of the hypothyroid infants. the groups with both the lowest mean T4 concentrations and mean body weights also had the lowest mean PRL values.
INDUCTION OF OVARIAN ACTIVITY BY PULSATILE INFUSION OF LHRH IN WOMEN WITH LACTATIONAL AMENORRHOEA
Authors: GLASIER A. , McNEILLY A. S. , BAIRD D. T.
Published: March 2008

Four fully breast‐feeding women at 6 weeks post partum were injected with LHRH (0.1 μg/kg) every 94 min by pulsatile infusion pump. While follicular development occurred in all women, and evidence of luteinization was apparent in three out of four, normal ovulation and luteal function did not occur. This suggests that a simple disturbance in the pulsatile pattern of LHRH secretion may not, in itself, be enough to explain the suppression of ovarian activity during lactation.
MEASUREMENT OF INSULIN‐LIKE GROWTH FACTOR‐II BY RADIORECEPTOR ASSAY USING OVINE PLACENTAL MEMBRANES
Authors: BAXTER R. C. , DE MELLOW J. S. M.
Published: March 2008

A new radioreceptor assay for insulin‐like growth factor‐II (IGF‐II), using receptors on ovine placental membranes, is described. Half‐maximal displacement of specifically bound radioiodinated human IGF‐II tracer was seen at 1.0 ng/tube of unlabelled IGF‐II. The cross‐reactivity of IGF‐I was 1%, and insulin was entirely without effect. Measured on serum samples from 100 healthy adults, the mean IGF‐II concentration (±SD) was 576 ± 160 ng/ml. Identical mean values were seen for all adult age groups up to 65 years. The mean value for 10 acromegalic adults was 583 ± 155 ng/ml, and for 9 GH‐deficient subjects, 161 ± 26 ng/ml (P < 0.001 compared to normals). Of eight patients with chronic renal failure, none had an IGF‐II level less than 2SD above the normal mean. No significant effect of renal dialysis was seen. In groups of patients with gastric, breast, lung, testicular, oat cell, ovarian, colonic and prostatic carcinoma, Hodgkin's lymphoma, non‐Hodgkin's lymphoma, sarcoma and teratoma (5–12 patients per group), mean IGF‐II levels were in the lower part of the normal range. Thus this study does not provide evidence supporting a role for excessive IGF‐II production in the growth of any of these tumour types.
A DIVERGENCE OF PLASMA GROWTH HORMONE RESPONSE BETWEEN GROWTH HORMONE‐RELEASING FACTOR AND INSULIN‐INDUCED HYPOGLYCAEMIA AMONG MIDDLE‐AGED HEALTHY MALE SUBJECTS
Authors: WAKABAYASHI I. , SHIBASAKI T. , LING† N.
Published: March 2008

The capability of the anterior pituitary gland to secrete GH in response to an intravenous injection of growth hormone‐releasing factor (GRF) and insulin‐induced hypoglycaemia was evaluated in 9 healthy male subjects ranging in age between 37 and 52 years old. Plasma GH response to 100 /μg human GRF showed considerable intersubject variation and the increment of the peak value from the basal did not exceed 5 ng/ml in four out of 9 subjects. In contrast, insulin‐induced hypoglycaemia resulted in a consistent stimulation of GH that exceeded 21 ng/ml in all subjects. The mean peak GH response after insulin‐induced hypoglycaemia was significantly higher than that after GRF (27·4±1·6 vs 10·6±1·9 ng/ml). These results demonstrate that a significant divergence exists in plasma GH responses between the two provocative tests in the middle‐aged subjects and suggest that the stimulation of GH following insulin‐induced hypoglycaemia is not mediated solely by endogenous GRF.
DOES MELATONIN DEFICIENCY CAUSE THE ENLARGED GENITALIA OF THE FRAGILE‐X SYNDROME?
Authors: O'HARE J. P. , O'BRIEN I. A. D. , ARENDT J. , ASTLEY P. , RATCLIFFE W. , ANDREWS H. , WALTERS R. , CORRALL R. J. M.
Published: March 2008

Melatonin profiles were studied in five males with cytogenetic and clinical features of the fragile‐X syndrome including megalo‐orchidia and macrogenitosomia. In comparison with age‐matched normal controls, the fragile‐X group showed lower melatonin values and a significant impairment of the nocturnal rise in this hormone. Melatonin deficiency may thus be responsible for some of the phenotypic features of this disorder.
LOPERAMIDE, AN OPIATE ANALOGUE, INHIBITS PLASMA ACTH LEVELS IN PATIENTS WITH ADDISON'S DISEASE
Authors: AMBROSI B. , BOCHICCHIO D. , FAGLIA G.
Published: March 2008

The effects of loperamide, an opiate analogue of the piperidine class on pituitary hormone secretion were evaluated in eight patients with Addison's disease. In all patients loperamide administration (16 mg orally) induced a marked fall in plasma ACTH levels (P<0.01), without affecting GH, PRL and LH levels. Plasma ACTH concentration fell significantly from 854±167 pg/ml (mean±SEM) to 460±123 pg/ml at 60 min (P±0.01). The inhibition persisted throughout the whole test period, the nadir being reached at 300 min. Low dose naloxone infusion 180 min after loperamide administration caused plasma ACTH to rise from 181±61 pg/ml to 539±99 pg/ml (P±0.01). The present data suggest that the opiate analogue loperamide is a potent inhibitor of ACTH secretion in patients with Addison's disease, which may be acting on μ receptors, since its effect is blocked by low doses of naloxone.
INTERACTIONS OF OESTRADIOL BENZOATE AND PROMEGESTONE UPON BASAL AND TRH‐INDUCED PROLACTIN SECRETION IN POSTMENOPAUSAL WOMEN
Authors: JOSEPH P. JEAN , COUZINET B. , BRAILLY S. , RIGAUD C. , RAYNAUD J. P. , SCHAISON G.
Published: March 2008

The interactions of ovarian steroids with PRL secretion in women are still controversial. Ten healthy postmenopausal women, on no medication, received during the first period or 2 months later in a cross‐over design study, i.m. injections of 0.625 mg of oestradiol benzoate (EB) alone for 10 d or in combination with 750 μg/d of a pure progestin promegestone for 10 d. A TRH (200 μg i.v.) stimulation test was performed before the start and at the completion of each treatment period. Basal plasma gonadotrophins, PRL and oestradiol were measured every day by radioimmunoassay. The EB‐induced rise in oestradiol levels was similar during the two periods. In response to EB treatment serum PRL levels increased from 6·1±0·9 ng/ml to 22·9±3·4 ng/ml. With the addition of promegestone, the increase in PRL, from 6·7±1·3 ng/ml to 13·8±2·5 ng/ml, was significantly diminished (P<0.001). The PRL release induced by TRH was significantly greater with EB treatment than was the response with the combined treatment (P<0·05, Wilcoxon test to compare the areas under the curves). These data suggest that in postmenopausal women (1) oestrogens act as stimulators of PRL release and (2) promegestone is able to partially counteract the stimulatory effect of oestradiol benzoate upon basal and TRH‐stimulated PRL secretion.
DOES TESTOSTERONE AFFECT THE NORMAL MENSTRUAL CYCLE?
Authors: DEWIS P. , NEWMAN M. , RATCLIFFE W. A. , ANDERSON D. C.
Published: March 2008

In order to throw further light on the role of androgens in the aetiology of the polycystic ovary syndrome (PCO) we have examined the effect of artificially increasing serum testosterone levels on menstrual function in a group of ovulating women. Six women were studied who had either severe premenstrual syndrome or loss of libido for which they were treated with 100 mg testosterone by s.c. implantation. All had regular menstrual cycles. For 1 month before implantation serum LH, FSH, oestradiol (E2), progesterone and testosterone were measured three times per week. All women showed normal cyclical variation of LH, FSH, E2 and progesterone. Following implantation, three times weekly blood samples were taken during the first and third cycles. No patient had any disturbance of menstrual pattern. All continued to show cyclical changes of LH, FSH, E2 and progesterone. Serum E2 and progesterone were lower but not significantly so in the luteal phase of the treated cycles. This was despite a mean serum testosterone which rose from 1.3 to 7.1 nmol/1 at the end of the third week following implantation and to 4.1 nmol/1 at the end of the third month. Sex hormone binding globulin levels fell as expected by 18.5% during the first cycle. The lack of significant effect of a markedly elevated serum testosterone level on cyclical hormone changes is indirect evidence that in PCO the primary cause of the menstrual disturbance is not excessive production of ovarian or adrenal testosterone.
EFFECT OF LHRH TREATMENT ON TESTICULAR DESCENT AND HORMONAL RESPONSE IN CRYPTORCHIDISM
Authors: WIT J. M. , DELEMARRE‐VAN DE WAAL H. A. , BAX N. M. A. , VAN DEN BRANDE J. L.
Published: March 2008

In a double‐blind placebo‐controlled study in 49 boys with cryptorchidism the effect of intranasal synthetic LHRH was studied. After 8 weeks improvement in testicular location was found in 13 testes (37%), but this improvement was considered sufficient of only six testes. Placebo resulted in an improved location in 18% of the testes. The mean change in testicular position (expressed in cm) after LHRH therapy was slightly greater than after placebo but only in the squatting position did this difference reach significance. Aggressive behaviour was reported in 23% of the children treated with LHRH. A second LHRH course did not result in significant improvement in any of the patients. At follow‐up reascent was frequently seen. The final results in unilateral cryptorchidism are poorer than those in bilateral cryptorchidism. LHRH therapy leads to higher plasma LH levels and a lower FSH in response to an intravenous LHRH test. In 15 boys plasma testosterone levels rose above 0.4 nmol/1. We conclude that intranasal LHRH application has a limited value for the treatment of cryptorchidism but may be suitable as a diagnostic test.
A COMPARISON OF THE EFFECTS OF DANAZOL AND GESTRINONE ON TESTOSTERONE BINDING TO SEX HORMONE BINDING GLOBULIN IN VITRO AND IN VIVO
Authors: DOWSETT M. , FORBES K. L. , ROSE GILLIAN L. , MUDGE JOANNE E. , JEFFCOATE S. L.
Published: March 2008

Danazol and gestrinone are both effective agents in the treatment of endometriosis. Their mechanism of action is unknown but may be related to their androgenic activity, which is at least partly dependent on increases in the proportion of testosterone which circulates unbound to plasma protein. We have quantified these increases in patients on treatment, and by experimentation in vitro have demonstrated the relative importance of (i) the reduction of sex hormone binding globulin (SHBG) binding capacity and (ii) competition with testosterone for SHBG binding sites by the drugs and some of their metabolites. The mean SHBG binding capacity in patients treated with danazol (400 mg/d, n = 7) and gestrinone (5 mg/week, n = 7) fell from 66.9 and 56.4 nmol/1 to 36.1 and 28.1 nmol/1, after 1 week's treatment and to 11.1 and 7.1 nmol/1 after 4 weeks respectively. Despite the similarity between the falls in SHBG binding capacity there was a significantly greater increase in % free testosterone in plasma samples from patients treated with danazol than in those from patients treated with gestrinone at 1 week. Experiments in vitro suggest that this was largely due to ethisterone (a major metabolite of danazol) competing with testosterone for SHBG binding sites. After 4 weeks on treatment there was a similar, near maximal reduction in SHBG binding of testosterone in both treatment groups. At the low levels of SHBG binding capacity reached by this time the extra effect of any competition for binding sites was much reduced.
EFFECT OF A CALCIUM ENTRY BLOCKER ON BLOOD PRESSURE, PLASMA RENIN ACTIVITY, ALDOSTERONE AND CATECHOLAMINES IN NORMOTENSIVE SUBJECTS
Authors: SAITO IKUO , TAKESHITA EIKO , SARUTA TAKAO , NAGANO SHIRO , SEKIHARA TOSHIO
Published: March 2008

The effects of the calcium entry blocker nifedipine on blood pressure, heart rate, plasma renin activity, aldosterone, noradrenaline and adrenaline were studied in 23 normotensive subjects in the supine and upright positions. Nifedipine, 10 mg administered sublingually, lowered mean blood pressure and increased heart rate, plasma noradrenaline and renin activity without increasing plasma aldosterone in the supine position. The increase in plasma aldosterone in response to upright posture was inhibited by nifedipine, whereas the rise in plasma noradrenaline was augmented. These results suggest that intracellular calcium is important as a regulator of aldosterone secretion as well as of vascular tone in normotensive subjects.
SEX HORMONE BINDING GLOBULIN IN WOMEN WITH ANOREXIA NERVOSA
Authors: ESTOUR B. , PUGEAT M. , LANG F. , DECHAUD H. , PELLET J. , ROUSSET H.
Published: March 2008

In 29 women with anorexia nervosa, on a blood sample withdrawn at 0900 h before and during weight gain, the binding parameters of serum sex hormone binding globulin (SHBG) were measured by a solid phase method and the levels of testosterone, oestradiol and thyroid hormones were measured by radioimmunoassay. The binding capacity of SHBG was higher than the upper limit for normally menstruating women in 23 patients whilst its affinity for binding testosterone at 37°C was normal (0.32–0.53 × 10−9mol/l). The mean levels of testosterone, oestradiol and free thyroxine were normal and the mean level of triiodothyronine was significantly (P< 0·005) decreased. The binding capacity of SHBG did not correlate significantly with body mass index, percent weight lost, thyroid hormone or sex hormone levels. In 9 patients, an i.v. infusion providing 1200–1400 calories daily was given for 1 week. In these patients a significant decrease (P< 0.005) in the binding capacity of SHBG (from 74·7±26·7 to 52·9±21·8 nmol/l) and a significant increase (P<0.001) in T3 levels (from 0·69±0·21 to 0·95±0·13 nmol/l) was observed. In 14 patients, when a weight gain of at least 5% was obtained, the binding capacity of SHBG fell into the normal range (25.6–62.9 nmol/l) while T3 levels rose to normal (0.85–2.30 nmol/l). These findings suggested that variations of calorie intake and/or body weight may influence the binding capacity of SHBG in the human.
THE IMMUNOSUPPRESSIVE EFFECT OF METHIMAZOLE ON CELL‐MEDIATED IMMUNITY IS MEDIATED BY ITS CAPACITY TO INHIBIT PEROXIDASE AND TO SCAVENGE FREE OXYGEN RADICALS
Authors: BALAZS CSABA , KISS E. , LEÖVEY A. , FARID N. R.
Published: March 2008

We have investigated the effect of methimazole (MMI) on cell‐mediated immunity and ascertained the mechanisms of immunosuppression produced by the drug. Methimazole (≥ 10−5m) produced a dose‐dependent inhibition in ‘active’ (early) rosette formation with sheep red cells and in phytohaemagglutinin (PHA)‐induced lymphocyte transformation. A concentration of 10−4 M MMI inhibited the immediate rise in intracellular cAMP triggered by PHA and the subsequent time dependent decrement over 24 h. The drug (10−3 M) also exerted a significant inhibitory effect on antibody‐dependent cell‐mediated cytotoxicity (ADCC) over six‐fold difference in target/effector cell ratios. At a concentration of 10−5 M, MMI inhibited zymosan‐induced respiratory burst (determined by change in the chemiluminescence of oxidized luminol) in polymorphonuclear and mononuclear cell preparations. Ninety‐five per cent of the chemiluminescence in the latter preparation was due to monocytes. At concentrations between 10−7 and 10−6 M, MMI significantly inhibited (in cell‐free systems) horseradish peroxidase‐dependent generation of chemiluminescence as well as the oxidation of luminol by hydrogen peroxide. Methimazole exerts its inhibitory effects on measures of cell‐mediated immunity by at least two mechanisms: inhibition of peroxidase and scavenging free oxygen radicals. Insensitivity of the test systems or poor access of MMI to leucocytes may account for the need for ≥ 10−5m MMI to inhibit cell‐mediated immunity significantly.
INTERACTION OF IgG HEAVY‐CHAIN ALLOTYPES (GM) AND HLA IN CONFERRING SUSCEPTIBILITY TO THYROID CARCINOMA
Authors: JUHASZ F. , BALAZS GY. , KOZMA L. , KRASZITS E. , STENSZKY VALERIA , FARID N. R.
Published: March 2008

We have recently reported an increase in HLA‐DR1 in 52 patients with thyroid epithelial cancer from Eastern Hungary (Juhasz et al., 1986). We have now investigated the association of IgG heavy chain markers (Gm) in 50 patients with this disease and explored possible interaction between Gm and HLA in modifying the risk for thyroid cancer. No Gm phenotype showed significant increases in the patients compared to 168 local controls. When both Gm and HLA, however, were considered, a marked heterogeneity in risk was noted. The odds ratio for DR1 +fb+ homozygotes was 37.5, for DR1 +fb− individuals 60 and for DR1−fb+ individuals 2.6 (DR1−fb−= 1.0). Thus Gm and HLA interact to enhance greatly the risk of thyroid cancer.
SUBACUTE THYROIDITIS: ACTIVATED HLA‐DR AND INTERFERON‐γ EXPRESSING T CYTOTOXIC/SUPPRESSOR CELLS IN THYROID TISSUE AND PERIPHERAL BLOOD
Authors: KARLSSON F. A. , TÖTTERMAN T. H. , JANSSON R.
Published: March 2008

Using a two‐colour direct immunofluorescence staining technique, we investigated activated HLA‐DR‐expressing T helper and T cytotoxic/suppressor cells in peripheral blood of six patients with subacute thyroiditis at referral and at follow‐up and in blood from 20 controls. In three of the patients, thyroid fine‐needle aspirates were examined as well. At referral, all patients had elevated blood levels of activated T helper and T cytotoxic/suppressor cells 2 (2–4)%, median and range, vs 0 (0–2)%, P < 0.001 and 12.5 (2–24)%, vs 0 (0–1)%P < 0001). At follow‐up, the activated proportion of T helper cells had become normal whereas some activated T cytotoxic/suppressor cells remained, 7 (0–8)%. No significant changes in total T cell number were detected when data at referral and at follow‐up were compared. In thyroid aspirates, HLA‐DR expressing thyrocytes were observed; the total proportion of T cytotoxic/suppressor cells was elevated (70% compared with 35% in blood) and 70% of the T cytotoxic/suppressor cells were HLA‐DR+. Furthermore, 55% of the thyroid‐infiltrating lymphoid cells were positive for interferon (IFN‐γ+). The finding of activated T cytotoxic/suppressor cells in the blood and thyroid tissue in subacute thyroiditis is consistent with a viral aetiology. Furthermore, intrathyroidal IFN‐γ+ lymphocytes are likely to contribute to expression of major histocompatibility complex (MHC) class II antigens on thyrocytes. No autoantibodies, however, were detected, which suggests that aberrant expression of MHC class II molecules alone is not sufficient to provoke an autoimmune response.
TESTICULAR FOLLICLE STIMULATING HORMONE RECEPTORS AND EFFECTIVENESS OF HUMAN MENOPAUSAL GONADOTROPHIN‐HUMAN CHORIONIC GONADOTROPHIN TREATMENT IN INFERTILE MEN
Authors: NAMIKI M. , NAKAMURA M. , OKUYAMA A. , ITATANI H. , SONODA T. , MATSUMOTO K.
Published: March 2008

In order to investigate the relationship between testicular FSH receptors and the effectiveness of hMG‐hCG treatment in idiopathic male infertility, 36 infertile men were examined. None of the 13 patients without detectable testicular high affinity FSH receptors showed any increase in motile sperm count after the hMG‐hCG treatment, whereas 11 of the 23 patients with FSH receptors responded to the treatment. In patients with FSH receptors, patients with a middle or high Johnsen's score count responded more than those with a low score count did. From the above results, it seems that both the presence or absence of testicular FSH receptors and the histological appearance of spermatogenesis predict responsiveness to hMG‐hCG treatment in infertile men.
CONTINUOUS INFUSION OF GROWTH HORMONE RELEASING HORMONE DOES NOT ALTER THE GROWTH HORMONE RESPONSE TO DIFFERENT STRESS STIMULI
Authors: SCHULTE H. M. , ALLOLIO B. , FROHWEIN U. S. , BENKER G. , REINWEIN D.
Published: March 2008

Continuous infusion of GHRH, as well as a bolus injection of GHRH, specifically stimulates the release of GH by the anterior pituitary. However, repetitive bolus injections of GHRH result in diminished responses of GH, while a constant infusion of GHRH cannot maintain high serum GH levels. To investigate whether different GH‐releasing stimuli are able further to challenge the somatotroph being exposed to continuous infusion of GHRH, we determined the GH response to insulin‐induced hypoglycaemia and bicycle exercise. Six normal volunteers received a bolus of 50 μg GHRH or vehicle followed by a continuous infusions of GHRH 1–29 amide (lμg/kg/h) or vehicle for 2.5 h. GHRH bolus and infusion resulted in elevated GH levels, but GH levels fell to values not significantly different from baseline levels after 150 min, GH plasma levels rose again, however, in response to insulin hypoglycaemia and bicycle exercise after both GHRH or vehicle infusion. Thus, the somatotroph's responsiveness to GHRH remains intact to respond to stress stimuli after continuous GHRH infusion.
THE COMPLEX OF MYXOMAS, SPOTTY PIGMENTATION AND ENDOCRINE OVERACTIVITY
Authors: LEEDMAN P. J. , COHEN A. K. , MATZ L. R.
Published: March 2008

We describe a 40‐year‐old male with acromegaly, multiple and recurrent cutaneous myxomas, spotty cutaneous pigmentation, a mammary myxoma, a large‐cell calcifying Sertoli cell tumour of the testis, and an unusual calcifying pigmented neuroectodermal tumour. He presented a combination of clinical and histological features not previously documented within the complex of myxomas, spotty pigmentation and endocrine overactivity, and therefore the findings broaden the spectrum of the syndrome.
ON THE USE OF A NEW SOMATOSTATIN ANALOGUE IN THE TREATMENT OF HYPOGLYCAEMIA IN PATIENTS WITH INSULINOMA
Authors: VERSCHOOR L. , UITTERLINDEN P. , LAMBERTS S. W. J. , DEL POZO E.
Published: March 2008

A novel potent analogue of somatostatin, the octapepide SMS 201–995 was tested as a therapeutic manoeuvre to prevent hypoglycaemia in patients with insulinoma. We investigated the acute effects of a single 50 μg dose of the analogue administered s.c. in three patients, comparing the results in two of them with those obtained after administration of saline (control) and native somatostatin. In addition two patients were treated for up to 5 d with two or three daily s.c. injections (daily dose of analogue ranging from 100 to 300 μg). In two of the three patients SMS 201–995 suppressed circulating insulin levels by more than 50% and increased plasma glucose to hyperglycaemic levels for 6–8 h after a single injection. No undesirable effects of the administration of the analogue were observed. As opposed to insulin suppression obtained with native somatostatin, no rebound increase in insulin levels was observed after administration of the analogue. We conclude that SMS 201–995 prevented hypoglycaemia in two out of three patients with insulinoma. The advantage of s.c. administration, the long duration of action and the absence of a rebound phenomenon give this analogue a place in the pre‐operative management of patients with insulinoma.
EVIDENCE FOR SEROTONINERGIC SYSTEM INVOLVEMENT IN OPIOID CONTROL OF LUTEINIZING HORMONE SECRETION IN MAN
Authors: FORESTA C. , MIONI R. , SCANDELLARI C.
Published: March 2008

Endogenous opioid peptides tonically inhibit LH by acting on hypothalamic mechanisms which regulate LHRH secretion. Opiates increase hypothalamic serotonin turnover but the involvement of the serotoninergic system in the opioid mechanisms regulating LH secretion in man is not clear at present. This study was designed to evaluate whether the tonic inhibitory effect on LH secretion induced by opiates involves the serotoninergic system. We have studied 10 healthy young men (aged 20–28 years). Five subjects were infused with naloxone (10 mg/h for 3 h) before and 120 min after fenfluramine administration (60 mg orally) on two different occasions. In five other subjects naloxone was infused before and after metergoline pretreatment (8 mg on first and second day and 4 mg on the third day, orally, at 0 time of naloxone infusion). After fenfluramine, naloxone infusion failed to induce any increase in LH plasma levels; metergoline pretreatment significantly enhanced the nalox‐one‐induced LH increase. These data suggest that in man a hypothalamic serotoninergic system may be involved in the opioid mechanisms regulating LH secretion.
CHARACTERISTICS OF PATIENTS WITH NORMAL T3 AND T4 AND A LOW TSH RESPONSE TO TRH
Authors: BOUTIN J. M. , MATTE R. , D'AMOUR P. , GILBERT F. , HAVRANKOVA J. , BÉLANGER R. , CHARTRAND R. , ZAKARIJA M.
Published: March 2008

The nature of the thyroid disorder presented by patients with normal T4 and T3 but blunted TSH response to TRH has not been clarified. In this study, we compared thyroid function tests in 16 such patients with those of 14 controls and 10 hyperthyroid patients. Basal total T4, free T4. total T3, iodine uptake and cholesterol of the study group were similar to controls but significantly (P < 0.001) lower than in hyperthyroid patients, except for cholesterol which was higher. In contrast, the basal TSH, increase in TSH after TRH stimulation, and decrease of T4 during T3 suppression tests were similar to data obtained in hyperthyroid patients but significantly (P < 0001) lower than in controls. Pulse rate was mid‐way between the control and the hyperthyroid group. Thyroid stimulating antibody (TSAb) was measured with human thyroid cells in culture; the assay was positive in four subjects in the 16‐patient group and in all hyperthyroid patients tested. TSH stimulation test showed a hyporesponse in iodine uptake in the four patients with positive TSAb (26±29%), as well as in hyperthyroid patients (6+5%). However, there was a hyper‐response to TSH (213 ± 52%) in the remaining 12 patients in the group, none of whom had TSAb. Thus TSAb is not seen as responsible for the thyroid disorder in the majority of patients with normal T3 and T4 and absent or blunted TSH response to TRH; surprisingly, most of these patients have thyroid hypersensitivity to TSH. These two characteristics, absence of TSAb and hypersensitivity to TSH, delineate a thyroid disorder clearly different from Graves' disease.
COMPLEMENT COMPONENT C9 IN GRAVES' DISEASE
Authors: OLEESKY D. A. , RATANACHAIYAVONG S. , LUDGATE M. , MORGAN B. P. , CAMPBELL A. K. , MCGREGOR A. M.
Published: March 2008

C9, the terminal component of complement, is the key part of the membrane attack complex formed as a result of complement activation; it has also been reported to be an acute phase protein. Its potential role in Graves' disease has been studied by measuring plasma C9 concentrations using an automated two‐site immunoradiometric assay employing monoclonal antibodies, whose binding to thyroid tissue has also been investigated. The plasma C9 concentration in patients with hyperthyroid Graves' disease (86.3 ± 21.6 mg/L mean±SD; n= 49) was significantly increased (P < 0.001) compared with normal subjects (60.4 ± 13.4 mg/l; n= 48). In contrast, the plasma concentration of C‐reactive protein, a marker of the acute phase response, was not significantly different between the two groups. The plasma C9 concentration in patients with hyperthyroid Graves' disease decreased significantly (P < 0.01) after treatment with antithyroid drugs (carbimazole or methimazole; n= 14), but not after radioactive iodine (131I) treatment (n = 18). Immunohistochemical staining demonstrated that monoclonal antibody to C9 bound to the basement membranes of thyroid follicular cells of Graves' thyroid tissue but not to normal thyroid tissue. Radiolabeled monoclonal antibody to C9 bound to membrane fragments prepared from thyroid glands from two patients with Graves' disease. We conclude that C9, and by implication the membrane attack complex, may be involved in the pathogenesis of Graves' disease.
THE EFFECT OF PULSATILE FOLLICLE STIMULATING HORMONE ON THE. ENDOGENOUS LUTEINIZING HORMONE SURGE IN WOMEN
Authors: MESSINIS I. E. , TEMPLETON A.
Published: March 2008

The effect of pulsatile administration of ‘pure’ FSH on the endogenous LH surge was investigated in 10 infertile but otherwise normal women. In each woman the LH surge in the spontaneous cycle preceding the treatment cycle was characterized in blood samples taken every 6 h. FSH was injected s.c. via a pump (28 IU every 3 h) starting on cycle day 2. Only five of the FSH‐treated women displayed an endogenous LH surge, and this was markedly attenuated in four of them. The LH surge occurred significantly earlier in the FSH‐treated than in the corresponding spontaneous cycle (cycle day 10.2 ± 0.5 vs 13.6 ± 0.8 mean‐± SEM, P < 005), although it tended to occur later in the FSH‐treated cycles with a higher total follicular fluid volume of follicles 12–15 mm in diameter. This volume was even greater in the FSH‐treated cycles without an endogenous LH surge. Serum progesterone levels increased significantly in all five FSH‐treated cycles after the onset of the LH surge and ovulation was confirmed by ultrasound in four of them. These results suggest that the LH surge during superovulation induction with pulsatile FSH in normally cycling women is a variable event. We postulate that unknown inhibitory substances secreted be small growing follicles antagonize the positive feedback effect of E2 on LH secretion.
EFFECTS OF MEDROXYPROGESTERONE ACETATE IN WOMEN WITH POLYCYSTIC OVARY SYNDROME
Authors: PETSOS P. , RATCLIFFE WENDY A. , ANDERSON D. C.
Published: March 2008

LH levels are inappropriately elevated in women with polycystic ovary syndrome (PCO). Regardless of whether this LH elevation is primary or secondary it may be involved in the establishment of chronic anovulation. We have therefore tried selectively to suppress LH by giving medroxyprogesterone acetate (MPA) 5 mg twice daily for 14 d to 13 women with PCO (14 studies) and have examined their pituitary and ovarian response to assess whether follicular development and ovulation would be triggered post‐treatment as a result of secretion of endogenous gonadotropins in a more nearly physiological ratio. Blood samples were obtained before and two to three times weekly during and after treatment for 35–50 d. In two of these cycles MPA was started fortuitously during the luteal phase of a spontaneous cycle. In the remainder, three patterns of response were seen. In 9 cycles, after an initial rise, there was a progressive fall in gonadotropin levels, LH (mean 48% of basal) more than FSH (mean 68% of basal); after MPA was stopped FSH levels recovered more rapidly than LH. In two cycles (one subject) MPA administration was associated with a progressive rise in serum oestradiol and progesterone. In a further cycle, treatment was also accompanied by an oestradiol rise and was followed by establishment of regular ovulatory cycles. The observed differential suppressive effect on LH and FSH levels suggests that MPA might be of therapeutic value if followed by treatment with anti‐oestrogens or exogenous gonadotrophins in PCO.