bluuebunny/crossref_metadata_2025 huggingface dataset:
GnRH AGONIST ADMINISTRATION IN POLYCYSTIC OVARY SYNDROME
Authors: BUCKLER H. M. , PHILLIPS S. E. , KOVACS G. T. , BURGER H. G. , HEALY D. L.
Published: March 2008

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary—ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 μg, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co‐administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH‐RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH‐IRMA). Following buserelin administration there was an initial rise in LH‐RIA, FSH, oestradiol (E2) and inhibin (P < 0.01). Fourteen days were needed for LH‐RIA to return to the normal range, with both protocols resulting in a fall in LH‐RIA and FSH (P < 0.01) before hMG was co‐administered. Twenty‐eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P < 0.01). There was failure to respond to an intravenous bolus of 100 μg of GnRH from 7 days of buserelin administration onwards, despite the serum LH‐RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P < 0.01). There was no difference in the proportion of ovulations (52%vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (> 3 follicles > 15 mm diameter; 41%vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P < 0.01). This study demonstrates that (a) 28 days of buserelin administration in a dose of 200 μg, six times daily intranasally is needed to achieve suppression of ovarian function; (b) the GnRH stimulation test is unsatisfactory as an indicator of whether inhibition of pituitary secretion has occurred; (c) following a rise in endogenous and exogenous gonadotrophin levels, E2 and inhibin are stimulated and are closely correlated; (d) there was no benefit of pituitary—ovarian suppression with a GnRH agonist on subsequent ovulation induction, and multiple follicle development was not prevented.
FAMILIAL CUSHING'S SYNDROME DUE TO NODULAR ADRENOCORTICAL DYSPLASIA IS AN INHERITED DISEASE OF IMMUNOLOGICAL ORIGIN
Authors: VAN BERKHOUT F. TEDING , CROUGHS R. J. M. , WULFFRAAT N. M. , DREXHAGE H. A.
Published: March 2008

Circulating immunoglobulins may be involved in the pathogenesis of familial Cushing's syndrome due to nodular adrenocortical dysplasia. The disease may also be part of a complex including cutaneous and cardiac myxomas, spotty pigmentation of the skin, and other signs of endocrine overactivity. In the present study of two sisters treated by complete adrenalectomy for Cushing's syndrome due to nodular adrenocortical dysplasia, and of their first‐degree relatives, no evidence of associated disorders was present. However, the serum of both girls and of their mother contained immunoglobulins capable of stimulating adrenal DNA synthesis and cortisol production in vitro. The study supports the theory that familial Cushing's syndrome due to adrenocortical dysplasia is an inherited disease of immunological origin.
EFFECTS OF HYPERTHYROIDISM ON BINDING PROTEINS FOR STEROID HORMONES
Authors: CARON PH. , BENNET A. , BAROUSSE C. , NISULA B. C. , LOUVET J. P.
Published: March 2008

Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) binding capacities were examined weekly in eight normally cycling women and three women taking birth control pills during a 5‐week baseline period and after daily ingestion of 75 μg of L‐triiodothyronine (T3) for 30 days. The SHBG binding capacity increased whereas the CBG binding capacity decreased after T3 therapy. The binding capacities of proteins for steroid hormones were measured in 18 hyperthyroid subjects (Graves' disease) prior to and after 3 months of antithyroid drug therapy. SHBG binding capacity in hyperthyroid men or women was higher, and CBG binding capacity lower than those in euthyroid subjects. Thus, during hyperthyroidism, binding capacities of sex hormone binding globulin and corticosteroid binding globulin vary in opposite directions. A statistically significant correlation between the ratio of the sex hormone binding globulin to the corticosteroid binding globulin and triiodothyronine levels was found (P < 0.01). Therefore the ratio of the sex hormone binding globulin to the corticosteroid binding globulin might be potentially useful as a biochemical index of thyroid hormone action in peripheral tissues.
STIMULATION OF CYCLIC AMP PRODUCTION IN FRTL‐5 THYROID CELLS BY CRUDE IMMUNOGLOBULIN FRACTIONS OF SERUM FROM PREGNANT WOMEN
Authors: KASAGI K. , HIDAKA A. , HATABU H. , TOKUDA Y. , MISAKI T. , IIDA Y. , YOSHIDA M. , FUJII S. , TAII S. , TAMAI H. , KONISHI J.
Published: March 2008

In an assay for thyroid‐stimulating antibodies, in which FRTL‐5 thyroid cells were incubated with crude immunoglobulin (Ig) fractions precipitated from serum with 15|X% polyethylene glycol, significant increase in cAMP production was elicited by the samples from 25 (35·7%) out of 70 pregnant women. The highest value was 529·5%. There was a close correlation between thyroid stimulating activities and serum hCG concentrations (r= 0‐708, P < 0·001). When 125I‐hCG was added to serum from pregnant women, about 20% of the radioactivity was incorporated into the Ig fractions. hCG preparations within a range of concentrations of 30‐300 IU/m elicited 2·3–16·5 times increase in cAMP in a dose‐dependent manner.

Nine pregnant women with serum TSH concentrations less than the lower limit of the normal range (< 0·25 mU/1) displayed significantly higher values for both thyroid stimulating activities and serum hCG concentrations (P < 0·001, respectively) compared with those who had normal TSH levels in serum. These data suggest that hCG or its variant may stimulate the thyroid sufficiently to suppress secretion of TSH from the pituitary in some pregnant women.
ENHANCEMENT OF THE ACTIVITY OF THYROID‐STIMULATING ANTIBODIES BY ANTI‐HUMAN IgG ANTIBODIES IN VITRO
Authors: SAITO T. , SHIMURA H. , ENDO T. , ONAYA T.
Published: March 2008

In an attempt to determine whether or not anti‐human IgG antibodies could influence the activity of thyroid‐stimulating antibodies (TSAb), we investigated the effects of anti‐human Fc antibody (anti‐Fc antibody) and IgG from rheumatoid arthritis patients (RA‐IgG) on TSAb activity using FRTL‐5 cells. It was found that these anti‐human IgG antibodies enhanced the TSAb activity in vitro. FRTL‐5 cells were first incubated with Graves' disease IgG for 30 min at 37|MoC, then washed and incubated in Hanks’balanced salt solution with anti‐human IgG antibodies for 60 min at 4|MoC, and then for a further 120 min at 37|MoC. The level of cAMP accumulated in the medium was determined by RIA. Anti‐Fc antibody significantly augmented the cAMP formation stimulated by 16 out of 24 Graves' IgGs, whereas anti‐F(ab')2 antibody did not potentiate cAMP accumulation. Three of five RA‐IgGs, which are usually defined as specific antibodies for the Fc fragment of human IgG, mimicked these stimulatory effects. Protein A also potentiated the cAMP formation stimulated by Graves' IgGs. Furthermore, there was a significant correlation between the TSAb titres of these Graves' IgGs and the potentiating effects of anti‐Fe antibody (r= 0.495, P < 0.05, n= 21). These results suggest that the interaction of TSH receptor antibody with anti‐human IgG antibodies might modulate thyroid function in Graves' disease.
RADIATION‐INDUCED HYPOPITUITARISM IS DOSE‐DEPENDENT
Authors: LITTLEY M. D. , SHALET S. M. , BEARDWELL C. G. , ROBINSON E. L. , SUTTON M. L.
Published: March 2008

Radiation‐induced hypopituitarism has been studied prospectively for up to 12 years in 251 adult patients treated for pituitary disease with external radiotherapy, ranging in dose from 20 Gy in eight fractions over 11 days to 45 Gy in 15 fractions over 21 days. Ten further patients were studied 2–4 years after whole‐body irradiation for haematological malignancies using 12 Gy in six fractions over 3 days and seven patients were studied 3–11 years after whole‐brain radiotherapy for a primary brain tumour (30 Gy, eight fractions, 11 days). Five years after treatment, patients who received 20 Gy had an incidence of TSH deficiency of 9|X% and in patients treated with 35–37 Gy, 40 Gy and 42–45 Gy, the incidence of TSH deficiency (22, 35 and 52% respectively) increased significantly (P < 0.001) with increasing dose. A similar relationship was observed for both ACTH and gonadotrophin deficiencies when the 20 Gy group was compared to patients treated with 35–45 Gy (P < 0.01 and P < 0.05 respectively). Growth hormone deficiency was universal by 5 years over the dose range 35–45 Gy. In seven patients who were treated with 30 Gy in eight fractions over 11 days, deficiencies were observed at a similar frequency to the 40 Gy group (15 fractions, 21 days). No evidence of pituitary dysfunction was detected in the ten patients who received 12 Gy (six fractions, 3 days). Both total radiation dose and fractionation schedule may determine the incidence of pituitary hormone deficiencies. The dose below which deficiencies do not occur is probably irrelevant to therapeutic irradiation of pituitary and other intracranial neoplasms.
PLASMA ANDROSTANEDIOL GLUCURONIDE LEVELS DURING PREGNANCY
Authors: VAN DROOGENBROECK J. , VERMEULEN A.
Published: March 2008

In distinction to Braunstein and Horton (1985) who reported an increase in maternal 5α‐androstane‐3α, 17β‐diol glucuronide (ADG) plasma levels during pregnancy, we observed a decrease of these levels from the 10th week of pregnancy; the decrease parallels the decrease in dehydroepiandrosterone sulphate (DHEA‐S) concentration. As the latter is a major precursor of ADG, the decrease in ADG levels during pregnancy is not unexpected and in line with the concept that ADG is a parameter of androgenicity.
THYROID AUTOIMMUNITY IN ENDEMIC GOITRE CAUSED BY EXCESSIVE IODINE INTAKE*
Authors: BOYAGES STEVEN C. , BLOOT ANDRE M. , MABERLY GLEN F. , EASTMAN CRESWELL J. , MU LI , QIDONG QIAN , DERUN LIU , VAN DER GAAG REINDERT D. , DREXHAGE HEMMO A.
Published: March 2008

The pathophysiology of endemic goitre caused by excessive iodine intake is not well defined. By interacting with the immune system, iodine excess may trigger the development of autoimmune thyroid disease such as lymphocytic Hashimoto's thyroiditis (LT). In an attempt to examine this further, we compared the presence of thyroid autoantibodies in 29 goitrous children, from an iodine excess area, and in 26 healthy children, from an iodine sufficient area, of north central China. Serum was tested for antimicrosomal (MAb), anti‐thyroglobulin (TgAb), second colloid antigen antibodies (CA2‐Ab) and TSH binding inhibitory immunoglobulins (TBII). Affinity chromatographically purified IgG was tested for thyroid growth‐stimulating activity (TGI) by two different methods: a sensitive cytochemical bioassay (CBA) using guinea‐pig thyroid explants and a mitotic arrest assay (MAA) employing a continuous rat thyroid cell line (FRTL‐5). We found no increased prevalence of LT in patients with endemic iodine goitre. The levels of MAb, TgAb and CA2‐Ab did not differ significantly between the two groups of children. Further, TBII were not present in either group. Thyroid growth‐stimulating immunoglobulins (TGI) were the major autoantibodies found in children with goitres caused by iodine excess. In the CBA, 12 of 20 (60%) goitrous children and 0 of 12 (0% P<0.05) healthy children were positive for TGI. Similar results were found in the MAA, and a good correlation between results of the CBA and MAA was found (P = 0.003). Maximal TGI activity in dose‐response CBA showed a good relation with clinical goitre size (r = 0.63; P < 0.05) indicating a possible pathophysiological role for these antibodies. We conclude that endemic iodine goitre is not associated with Hashimoto's lymphocytic thyroiditis. Nevertheless, autoimmune growth factors such as TGI may play a primary role in the pathogenesis of thyroid growth in this condition.
MELATONIN SECRETION IN TURNER'S SYNDROME: LACK OF EFFECT OF OESTROGEN ADMINISTRATION
Authors: SCHOBER E. , WALDHAUSER F. , FRISCH H. , SCHUSTER E. , BIEGLMAYER CH.
Published: March 2008

Melatonin secretion was investigated in 13 girls with Turner's syndrome before and after long‐term oestrogen administration. Oestrogen treatment resulted in an increase in the serum levels of the hormone and a decrease in blood progesterone concentration. No change, however, was observed in the melatonin secretion pattern (in terms of peak values, time of peak level and total melatonin secretion) after oestrogen therapy. A distinct circadian rhythm in serum melatonin was evident in all subjects with peak occurring around 0200 h and concentration similar to those of normal subjects.
BODY COMPOSITION IN ACROMEGALY: THE EFFECT OF TREATMENT
Authors: BENGTSSON BENGT‐ÅKE , BRUMMER ROBERT‐JAN , EDÉN STAFFAN , BOSAEUS INGVAR , LINDSTEDT GÖRAN
Published: March 2008

Total body water (TBW) and total potassium (TBK) were measured in patients participating in a follow‐up investigation of all acromegalic patients seen between 1956 and 1984. The results were compared with population‐based estimates of TBK and TBW calculated from height (BH), weight (BW) age and sex, using data from a large number of healthy subjects (n=476). The findings were compared with values obtained at diagnosis and were also related to growth hormone (GH) and IGF‐I/SmC concentrations at follow‐up. BW at follow‐up was unchanged compared to BW at diagnosis and was 9.7 and 10.0 kg higher in males and females, respectively, than in healthy subjects of the same BH (BWnorm). Growth hormone concentration at follow‐up correlated directly with excess extracellular fluid volume (ECW%) (P < 0.001) and inversely with the ratio observed/predicted body fat (BF%) (P < 0.001) as well as with BW/BWnorm (P < 0.05). On the other hand, GH concentration did not correlate with excess body cell mass (BCM%) estimated from TBK. IGF‐I/SmC concentration correlated with GH concentration at follow‐up (P<0.001) and with ECW % (P< 0.01) but not with BCM% or BF%. In 39 patients, data on body composition were also available at diagnosis. Of these, three males had developed gonadal insufficiency and their BCM had decreased markedly. One patient had suffered from hemiplegia. Five patients had not received any treatment. In the remaining 30 treated patients, those with a post‐treatment GH concentration below 5 mU/1 were normalized with respect to ECW and BF. BCM, however, was unchanged. In contrast, patients with GH concentration |Mg 10 mU/1 displayed unchanged body composition. Furthermore, BH decreased significantly in successfully treated patients.
MUSCARINIC CHOLINERGIC, BUT NOT SEROTONINERGIC MEDIATION OF ARGININE VASOPRESSIN RESPONSE TO METOCLOPRAMIDE IN MAN
Authors: COIRO V. , CAPRETTI L. , SPERONI G. , VOLPI R. , FAGNONI F. , BIANCONI L. , SCHIANCHI L. , CAIAZZA A. , CHIODERA P.
Published: March 2008

Y

The possibility that metoclopramide (MCP) stimulates arginine vasopressin (AVP) secretion in man through a serotoninergic and/or a cholinergic muscarinic pathway was studied. Twenty normal male subjects were tested with MCP (10 mg in an i. v. bolus) alone or in the presence of the 5HT1 serotoninergic antagonist metergoline (10 mg/day p. o. in five divided doses for 4 days), the 5HT2 receptor blocker ketanserin (10 mg i. v. 5 min before MCP) (n= 10), the M1 and M2 muscarinic antagonist atropine (1.2 mg i. v. just before MCP administration) or the M1 muscarinic receptor blocker pirenzepine (40 mg i. v. 10 min before MCP) (n= 10). AVP doubled in response to MCP. The MCP‐induced AVP rise did not change after metergoline, ketanserin or pirenzepine administration, whereas it was abolished by atropine. Additional experiments were performed in order to evaluate the effect of 1.2 mg atropine, given alone, on circulating AVP levels and whether the effect of atropine on the AVP response to MCP depends on the amount of the muscarinic antagonist (dose—response study). For these purposes, atropine was given alone to the same subjects previously tested with MCP plus atropine; furthermore, eight additional male subjects were tested with MCP plus atropine given in doses ranging from 0.8 to 1–4 mg. The results of these additional studies failed to show an effect of atropine alone on AVP secretion and demonstrated a dose‐related inhibition of MCP‐induced AVP rise by increasing atropine administration from 0.8 mg to 1.2 mg. The results of the present study did not show an involvement of 5HT1 and 5HT2 serotoninergic receptors in the AVP response to MCP. On the other hand, the data indicated that atropine‐sensitive muscarinic receptors mediate the AVP response to MCP. Since atropine, but not pirenzepine, crosses the blood‐brain barrier (BBB), the present results might indicate that the AVP releasing effect of MCP is mediated by M2 receptors at places located inside and/or outside the BBB or by M1 receptors in structures located inside the BBB.
SEX HORMONE BINDING GLOBULIN IN POSTMENOPAUSAL WOMEN: A PREDICTOR OF OSTEOPOROSIS SUPERIOR TO ENDOGENOUS OESTROGENS
Authors: VAN HEMERT ALBERT M. , BIRKENHÄGER JAN C. , DE JONG FRANK H. , VANDENBROUCKE JAN P. , VALKENBURG HANS A.
Published: March 2008

To quantify the role of endogenous oestrogen activity in osteoporosis we measured relative metacarpal cortical area (RCA), body mass, serum oestrone, oestradiol, androstenedione, and sex hormone binding globulin (SHBG) in 746 postmenopausal women aged 53 to 76 years, sampled from the general population. The occurrence of fractures and the rate of loss of RCA (delta‐RCA) were determined over the previous 9 years. Both RCA and delta‐RCA were significantly related to body mass, serum oestrone, oestradiol, and SHBG. The influence of the first three variables appeared to be bone preserving, whereas the latter appeared to be bone wasting. Serum oestradiol, SHBG and body mass proved to have an independent relationship with RCA in multivariate regression analysis. The relationship to delta‐RCA was statistically independent for serum SHBG only. Serum androstenedione was unrelated to either RCA or delta‐RCA. In the total study population, body mass, serum oestrone, oestradiol and SHBG were not related to the occurrence of fractures over the previous 9 years. In the subgroup of 249 elderly women, aged 65‐76 years, SHBG levels were significantly higher for women with type I osteoporotic fractures (vertebral and forearm fractures) as compared to controls. The results suggest a bone wasting influence of SHBG in postmenopausal women, possibly resulting in an increased risk of type I osteoporotic fractures in elderly women.
LUTEINIZING HORMONE AND FOLLICLE STIMULATING HORMONE SECRETION PATTERNS IN BOYS THROUGHOUT PUBERTY MEASURED USING HIGHLY SENSITIVE IMMUNORADIOMETRIC ASSAYS
Authors: WENNINK JOHANNA M. B. , VAN DE WAAL HENRIETTE A. DELEMARRE‐ , SCHOEMAKER RIK , SCHOEMAKER HELGA , SCHOEMAKER JOOP
Published: March 2008

Pulsatile gonadotrophin secretion patterns were studied in 32 normal boys (chronological age, CA 7.2‐14.6 years) at different stages of pubertal development (5 in stage G1, 11 in G2, 5 in G3, 4 in G4, 7 in G5). Plasma LH and FSH concentrations were measured at 10 min intervals from 1200 to 1800 h and from 2400 to 0600 h using an immunoradiometric assay with a lower limit of detection of 0.15 IU/1 for both LH and FSH. Plasma testosterone (T) was measured hourly. In the young prepubertal boys plasma LH was not detectable during day or night. In contrast, plasma FSH ranged from 0.7 to 1.4 IU/1. Plasma T was not detectable either (< 0.25 nmol/1). In the older prepubertal boys a discrete pulsatile LH pattern (2 per 6 h) became discernible only during the night (range 0.1‐0.4 IU/1). Plasma FSH also revealed a pulsatile pattern only during the night (2 per 6 h), while plasma T still remained undetectable. In the early pubertal boys (G2) a median daytime LH value of 0.37 IU/1 was determined with 1 pulse per 6 h and at night definite LH pulses (4 per 6 h) were found in all boys (range 0.4‐4.7 IU/1). Plasma FSH increased considerably to a median level of 2.50 IU/1 during the day; most boys had a pulsatile FSH pattern (one per 6 h). Plasma T became detectable during the day (median 0.54 nmol/l) and night (median 1.16 nmol/1). With the progression of puberty the mean plasma level of LH and FSH, the LH/FSH pulse number and the LH/FSH pulse amplitude increased; plasma T rose as well, more obviously during the night. In G5, however, the LH pulse number decreased, while the LH level and pulse amplitude still increased, presumably as a result of the increased negative feedback action of sex steroids. Simultaneous LH/FSH pulses developed during the night at onset of puberty but during the day only towards the end of pubertal development. The use of these novel highly sensitive IRMA methods demonstrated nocturnal LH and both diurnal and nocturnal FSH pulsatility to be present in older prepubertal boys. The early detectable FSH level plus the existence of solitary FSH pulses throughout puberty as well as in adult men support the hypothesis of the existence of a GnRH‐independent FSH secretion in men. Our results are in accordance with the following hypotheses: (1) puberty is brought about by GnRH secretion increasing with time, both in frequency and amplitude, and first appearing during the night. (2) GnRH secretion decreases in frequency at the end of puberty due to the development of a negative feedback action by a testicular factor or factors. (3) FSH secretion in puberty is only partly dependent on GnRH secretion.
MATURATION OF THYROID FUNCTION IN NORMAL HUMAN FOETUSES
Authors: BALLABIO M. , NICOLINI U. , JOWETT T. , DE ELVIRA M. C. RUIZ , EKINS R. P. , RODECK C. H.
Published: March 2008

The functional maturation of an independent foetal thyroid activity was investigated in the present study. Serum concentrations of total T4, free T4, TSH and TBG were measured in 23 foetuses between 18 and 31 weeks' gestational age. Foetal samples were collected by transabdominal needling from the placental cord insertion. TT4, FT4, TBG and TSH levels significantly increased with gestational age. FT4 levels were comparable with the adult range by 28 weeks' gestation; TBG levels reached adult values at approximately 30 weeks, while TT4 was lower than adult levels throughout the whole period studied. TSH values were, in all cases, higher than the normal adult range. A significant positive correlation was present between TT4 and TBG, TT4 and TSH, and TBG and TSH levels; on the contrary, no correlation was demonstrated between FT4 and TSH levels. The TSH/TT4 ratio significantly decreased with gestational age. The results suggest an incomplete responsiveness of the foetal thyroid gland to TSH, while the feedback control system between pituitary and thyroid is operating at a different set point from that in post‐natal life. The normal range of thyroid parameters established is of clinical relevance for the antenatal diagnosis, and eventual treatment, of thyroid disorders that may seriously damage foetal development and maturation.
hCG TEST IN GYNAECOMASTIA: FURTHER STUDY
Authors: KUHN J. M. , REZNIK Y. , MAHOUDEAU J. A. , COURTOIS H. , LEFEBVRE H. , WOLF L. M. , LUTON J. P.
Published: March 2008

In adult men referred with gynaecomastia, the prolonged plasma oestradiol (E2) response to hCG appears to be a useful tool in the diagnosis of feminizing Leydig cell tumour (LCT) of the testis. However, its specificity is uncertain. The hormonal status was therefore studied in 85 men with gynaecomastia including 17 with LCT, 52 with clinically isolated gynaecomastia and 16 hypogonadal men (13 with Klinefelter's syndrome and three with hypogonadotrophic hypogonadism). The data obtained after hCG (5000 IU i.m., n= 85) or GnRH (100 μg i.v., n= 70) administration were compared to those of a group of control men. Means of basal gonadotrophin and of gonadotrophin responses to GnRH were similar in LCT and controls but were significantly (P< 0.001) higher than controls in patients with either Klinefelter's syndrome or isolated gynaecomastia. Half the patients with isolated gynaecomastia had normal gonadotrophin parameters (NGG) while half had significantly (P < 0.001) higher levels (EGG) than controls, suggesting either primary testicular failure or androgen resistance. The T responses to hCG did not differentiate patients with LCT from either isolated gynaecomastia or controls. A prolonged E2 response (> 300 pmol/1 on day 3 following hCG) was observed in all patients with LCT, in 10/21 EGG patients and in 3/13 patients with Klinefelter's syndrome. Such a response was observed in only one NGG patient. We conclude that a prolonged E2 response to hCG does not appear to be specific to LCT but that specificity is greatly improved (from 80 to 98|X%) when the gonadotrophin pattern (basal and/ or responses to GnRH) is also taken into account.
RECOVERY FROM FOETAL HYPOTHYROIDISM: EVIDENCE FOR THE SAFETY OF BREAST‐FEEDING WHILE TAKING PROPYLTHIOURACIL
Authors: MOMOTANI NAOKO , YAMASHITA RYOKO , YOSHIMOTO MIDORI , NOH JAEDUK , ISHIKAWA NAOFUMI , ITO KUNIHIKO
Published: March 2008

We assessed the post‐natal thyroid function in eight infants of mothers with Graves' disease whose thyroid function at birth was suppressed by maternal ingestion of propylthiouracil during pregnancy. These mothers continued taking propylthiouracil after delivery and breast‐fed exclusively (two mothers supplemented their breast milk with a small amount of baby food). The cord free T4 level was slightly but uniformly below the normal range in all eight infants, and the cord TSH level was above the normal in seven infants. The dose of propylthiouracil after delivery ranged from 50 to 300 mg daily, which was equal to, or higher than, that before delivery. All these abnormal values normalized in the infant after birth. Serum samples, from seven of the eight mothers, taken at delivery were examined for TSH receptor antibodies; all were positive. The antibody titre, however, was too low, and/or free T4 and TSH levels were examined too long after delivery, for the antibodies to be the cause of the restoration of the infants’thyroid function. These results assure the safety of breast‐feeding for the infants of mothers with Graves' disease taking propylthiouracil.
EFFECTS OF TREATMENT WITH OESTRADIOL/LEVONORGESTREL ON BONE, LIPOPROTEINS AND HORMONE STATUS IN POSTMENOPAUSAL WOMEN
Authors: FARISH ELIZABETH , HART DAVID M. , GRAY CHRISTINA E. , BEASTALL GRAHAM , FLETCHER COLIN D. , LINDSAY ROBERT
Published: March 2008

The aim of the study was to investigate the effects of an oestradiol/ levonorgestrel regimen, administered parenterally, on bone metabolism, bone density, lipoprotein metabolism and hormone status. Twenty‐five women who had undergone a surgical menopause had an oestradiol/levonorgestrel‐containing vaginal ring pessary in situ for 6 months. Within the first month there were sustained changes in the biochemical indices of bone metabolism in keeping with a marked reduction in bone turnover and decrease in bone resorption. Bone mineral content in the distal forearm was measured in 14 patients and a small increase was noted in every patient. Levonorgestrel was well absorbed and the serum levels remained almost constant throughout treatment. There was a gradual increase in serum total oestradiol which became significant at 6 months. Dialysable oestradiol levels rose from 26% of total oestradiol at 0 time to 3.3% at 1 month with no further change thereafter. SHBG levels were 23% of pretreatment levels at 6 months. There were sustained decreases in triglyceride, VLDL and HDL cholesterol levels and a transient fall in LDL cholesterol. Total HDL, HDL2 and HDL3 cholesterol levels were reduced by 25, 40 and 21% respectively. The results suggest that levonorgestrel exerts a protective influence on bone either directly or by its effect on the proportion of oestradiol circulating in the free, physiologically active form. The effects on lipoproteins were predominately those of the progestogen component, the lipoprotein risk factors for coronary heart disease being adversely affected.
EFFECT OF PORCINE BRAIN NATRIURETIC PEPTIDE (pBNP) ON HUMAN ADRENOCORTICAL STEROIDOGENESIS
Authors: HASHIGUCHI TAKASHI , HIGUCHI KAZUMI , OHASHI MASAO , TAKAYANAGI RYOICHI , MATSUO HISAYUKI , NAWATA HAJIME
Published: March 2008

Porcine brain natriuretic peptide (pBNP), purified from porcine brain, had a significant suppressive effect on aldosterone and cortisol secretions in ACTH‐treated cultured human adrenal cells. Concomitantly, the intracellular cGMP formation was enhanced by pBNP treatment. A specific pBNP receptor was identified in the human adrenal tissues. Affinity labelling of 125I‐BNP showed two separate molecular weights of specific binding sites for pBNP of 140 and 67 kDa. A 125I‐BNP binding study of the human adrenal membrane fraction demonstrated the presence of high‐affinity and low‐capacity binding sites for pBNP. Moreover, these binding sites for 125I‐pBNP were displaced by unlabelled α‐rANP as well as pBNP. From these studies, we concluded that pBNP had suppressive effects on human adrenocortical steroidogensis, possibly via a receptor which may be shared with ANP.
ELEVATED SERUM INTACT PARATHYROID HORMONE LEVELS IN ELDERLY PATIENTS WITH HIP FRACTURE
Authors: COMPSTON J. E. , SILVER A. C. , CROUCHER P. I. , BROWN R. C. , WOODHEAD J. S.
Published: March 2008

It has been postulated that secondary hyperparathyroidism contributes to bone loss and the high incidence of hip fractures in the elderly population, but there are no data on serum intact parathyroid hormone concentrations in these patients. In this study, serum intact parathyroid hormone (PTH) levels have been measured in 39 elderly patients with hip fracture; in addition, serum 25‐hydroxyvitamin D3 and 1,25‐dihydroxyvitamin D3 concentrations have been measured. Twenty patients (51.3%) had elevated serum intact PTH concentrations whilst five (12.8%) had abnormally low serum 25‐hydroxyvitamin D3 levels and serum 1,25‐dihydroxyvitamin D3 was reduced in only two. These results provide the first direct evidence for secondary hyperparathyroidism in elderly patients with hip fracture. Vitamin D deficiency is unlikely to be the sole cause of secondary hyperparathyroidism in these subjects and calcium deficiency by itself may also contribute.
EFFECTIVENESS OF COMPUTER‐ASSISTED PERIMETRY IN THE DIAGNOSIS OF PITUITARY ADENOMAS
Authors: CANNAVÓ S. , DE NATALE R. , PRINCI P. , LI CALZI L. , ARAGONA A. , TRIMARCHI F.
Published: March 2008

Computer‐assisted perimetry (CP) is a new method which quantifies the differential light sensitivity threshold and allows the statistical analysis of the data. It offers advantages as compared with manual methods. This study has been carried out in 27 patients with pituitary adenomas (four males and 23 females; 13 with prolactinomas; six with acromegaly, four with Cushing's disease and four with non‐secreting adenomas). A skull X‐ray and a computed tomodensitometry (CT), a manual Goldman perimeter and a computer assisted visual field examination were performed in all cases. The presence of a pituitary tumour was suggested by the X‐ray and by the CT in 12 and 23 patients respectively out of the 27: the CT scan revealed a suprasellar extension in seven cases. Visual field defects were detected by means of the Goldman perimeter in six patients and by means of the computer‐assisted technique in 25/27. The effectiveness of this new technique was proved by the concordance with the CT scan results in 21 cases and by the histological examination of the four adenomas which were not apparent at CT scan. A significant difference was found for both eyes (right eye, chi squared = 258, P < 0.001; left eye, chi squared = 295.0, P < 0.001) between patients and controls. No correlation existed between visual defects and the pituitary size apparent at CT scan. Six patients were evaluated with the CT and CP after 1 year of bromocriptine treatment; a slight reduction of size was documented with the CT in four cases, whereas a significant positive change in visual acuity was observed in five patients. In conclusion, the computer‐assisted perimetry gives useful information about the optic chiasma region, increasing the chance of recognizing the changes in visual fields in the follow‐up of patients with pituitary adenomas.
CORTICOTROPHIN‐LIKE INTERMEDIARY LOBE PEPTIDE AS A MARKER OF ALTERNATE PRO‐OPIOMELANOCORTIN PROCESSING IN ACTH‐PRODUCING NON‐PITUITARY TUMOURS
Authors: VIEAU DIDIER , MASSIAS JEAN‐FRANCIS , GIRARD FRANÇOIS , LUTON JEAN‐PIERRE , BERTAGNA XAVIER
Published: March 2008

In order to evaluate which of human (h) corticotrophin‐like intermediary lobe peptide (CLIP) or hβ‐melanocyte stimulating hormone5–22 (hβMSH5–22) was the better marker of alternate pro‐opiomelanocortin (POMC) processing, both peptides were simultaneously sought in the same tissue extracts from a normal human pituitary, six corticotrophic adenomas, and four non‐pituitary tumours responsible for an ectopic ACTH syndrome. Human CLIP was detected using a combination of gel exclusion chromatography and two different radioimmunoassays (RIAs): a mid‐ACTH RIA which recognized ACTH but not CLIP, and a COOH‐ACTH RIA which recognized both molecules. Human βMSH5–22 had been measured previously. Neither hCLIP nor hβMSH5–22 were detected in the normal or tumoural pituitaries. The four non‐pituitary tumours, in contrast, contained both peptides; the hCLIP and hβMSH5–22 ratios (CLIP/ CLIP + ACTH and hβMSH5–22/ hβMSH5–22+ hγLPH) ranged from 40 to 94% and from 24 to 46%, respectively. In a given tissue the hCLIP ratio was always higher than the hβMSH5–22 ratio. hCLIP is therefore the better marker of alternate POMC processing.
DIET‐INDUCED CHANGES IN SEX HORMONE BINDING GLOBULIN AND FREE TESTOSTERONE IN WOMEN WITH NORMAL OR POLYCYSTIC OVARIES: CORRELATION WITH SERUM INSULIN AND INSULIN‐LIKE GROWTH FACTOR‐I
Authors: KIDDY D. S. , HAMILTON‐FAIRLEY D. , SEPPÄLÄ M. , KOISTINEN R. , JAMES V. H. T. , REED M. J. , FRANKS S.
Published: March 2008

The purpose of this study was to investigate the effect of calorie restriction on serum concentrations of sex hormone binding globulin (SHBG) in women with normal or polycystic ovaries (PCO) and to examine the possible role of insulin and insulin‐like growth factor‐I (IGF‐I) in mediating changes in SHBG levels. Six normal subjects with mean (SD) body mass index (BMI) 25.5 (2.2) and five subjects with PCO (BMI 36.1 (3.7)) were studied before and after 2 or (PCO only) 4 weeks of a very low calorie diet (330 kcal/day; Cambridge Diet). In both normal women and patients with PCO there was a twofold increase in SHBG concentrations after 2 weeks and this was sustained in the PCO subjects for a further 2 weeks. The rise in SHBG was accompanied by a fall in free testosterone concentrations. There were parallel changes in serum insulin and IGF‐I concentrations which decreased during the diet and there were significant negative correlations of SHBG with insulin in both normal subjects (r =−0.62) and women with PCO (r =−0.60). In addition, serum concentrations of an insulin‐dependent small molecular weight (34 kDa) binding protein for IGF‐I (IGF‐BPI) increased significantly during dieting in both groups and were negatively correlated with serum insulin (controls, r =−0.56; PCO, r =−0.68) and positively correlated with serum SHBG levels (controls, r = 0.69; PCO, r = 0.63).

In summary, these data indicate that in both normal subjects and those subjects with PCO, calorie restriction results in a highly significant increase in SHBG concentrations. Data from this study and related experiments in vitro suggest that the changes in SHBG may be mediated by a fall in insulin and/or IGF‐I.
DIFFERENT HEPATIC RESPONSES TO THYROXINE REPLACEMENT IN SPONTANEOUS AND 131I‐INDUCED PRIMARY HYPOTHYROIDISM
Authors: GOW S. M. , CALDWELL G. , TOFT A. D. , BECKETT G. J.
Published: March 2008

The serum levels of a range of analytes known to change with thyroid status were measured in two groups of patients with primary hypothyroidism commencing T4 replacement therapy. One group (group 1; n= 9) had spontaneous hypothyroidism whilst in the second (group 2; n= 10), hypothyroidism had resulted from radioiodine therapy. The replacement dose was increased in 50 μg increments each month to 200 μg/day; this produced similar serum concentrations of thyroid hormones and TSH in the two groups at each dose. Dose‐dependent increases in glutathione S‐transferase (GST) were seen in both groups but changes in alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) activities occurred only in group 1 patients. Group 1 patients had significantly higher levels of GST than group 2 at the 150 μg (P > 0.01) and the 200 μg (P > 0.005) doses of T4, and they had higher activities of ALT (P > 0.01) and GGT (P > 0.02) at the 200 μg dose. Seven patients in group 1 had abnormalities in GST and four had high levels of ALT, whereas three patients from group 2 had high GST concentrations and all had ALT activities within reference limits. The concentrations of the other analytes measured in serum showed the same response to T4 in the two groups, particularly the concentrations of certain transport proteins whose serum concentrations depend on hepatic protein synthesis. These data suggest that patients with spontaneous primary hypothyroidism are more susceptible to hepatocellular damage than patients who have radioiodine‐induced primary hypothyroidism when given oral doses of thyroxine < 150 μg/day.
VASOPRESSIN AND OXYTOCIN RESPONSES TO HYPERTONIC SALINE INFUSION: EFFECT OF THE OPIOID ANTAGONIST NALOXONE
Authors: SECKL J. R. , JOHNSON M. R. , LIGHTMAN S. L.
Published: March 2008

Endogenous opioids inhibit the release of oxytocin (OT) when vasopressin (AVP) is secreted in response to acute pharmacological stimuli in man and to a variety of physiological and pharmacological stimuli to animals. We have investigated the effect of naloxone on the AVP and OT responses to hypertonic saline in man. In two separate studies, six male subjects were infused with hypertonic saline (675 mmol/l, 0.05 ml/kg/min for 2 h) and either naloxone (4 mg bolus and 6 mg/h) or normal saline in random order. Hypertonic saline resulted in similar significant rises of plasma osmolality and AVP in both groups and a small but significant decrease in OT. Thirst sensation was not altered by naloxone. Endogenous opioids do not play an important role in the suppression of OT release when AVP is secreted in response to an osmotic stimulus in man.
CHOLINERGIC BLOCKADE WITH PIRENZEPINE IMPROVES CARBOHYDRATE TOLERANCE AND ABOLISHES THE GH RESPONSE TO MEALS IN NORMAL SUBJECTS
Authors: PAGE M. D. , BEVAN J. S. , DIEGUEZ C. , PETERS J. R. , SCANLON M. F
Published: March 2008

Pretreatment of normal male volunteers with the cholinergic muscarinic receptor‐blocking drug pirenzepine (200 mg p.o.) abolishes the delayed GH response to a meal stimulus. In addition, the glycaemic and insulin responses to meals are significantly reduced following this dose of pirenzepine. The data suggest that the effect of pirenzepine on the glucose response to meals is at least partly independent of the inhibition of GH release. Our findings are of relevance to the further investigation of cholinergic muscarinic antagonist in diabetes mellitus.
PULSATILE GnRH‐THERAPY IN OLIGOZOOSPERMIC MEN DOES NOT IMPROVE SEMINAL PARAMETERS DESPITE DECREASED FSH LEVELS
Authors: BALS‐PRATSCH M. , KNUTH U. A. , HÖNIGL W. , KLEIN H. M. , BERGMANN M. , NIESCHLAG E.
Published: March 2008

In order to evaluate GnRH administration for the treatment of infertile men with elevated serum FSH levels we administered GnRH in pulses via portable electronic infusion pumps initially to seven patients with low sperm counts and high FSH values over 12 weeks and later to nine further patients over 24 weeks who also underwent testicular biopsies. Fifty microlitres containing 5 pg GnRH were infused subcutaneously for 1 min every 120 min in the short‐term study and every 90 min in the long‐term study. Although FSH levels could be lowered in both groups of patients, none showed any improvement in sperm count or other seminal parameters. Therefore, pulsatile GnRH treatment cannot be recommended for therapy of severe oligozoospermia with elevated FSH levels.
PLASMA ACTH RESPONSES TO CORTISOL INFUSION ARE SIMILAR IN PATIENTS WITH PRIMARY HYPOADRENALISM AND PATIENTS STUDIED SOME YEARS AFTER BILATERAL ADRENALECTOMY FOR CUSHING'S SYNDROME
Authors: ATKINSON A. B. , BEACOM R. , KENNEDY A. L. , HADDEN D. R. , SHERIDAN B.
Published: March 2008

It has been suggested that the first‐phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary‐directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first‐phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.
SALIVARY TESTOSTERONE LEVELS AND THE PROGRESS OF PUBERTY IN THE NORMAL BOY
Authors: BUTLER G. E. , WALKER R. F. , WALKER R. V. , TEAGUE P. , RIAD‐FAHMY D. , RATCLIFFE S. G.
Published: March 2008

Salivary testosterone (ST) levels were measured in 84 boys aged 7.3–16.2 from the Edinburgh Growth Study. The correlation coefficient between matched plasma/saliva samples was 0.88. Six samples were collected over the course of one day from 0900 to 2100 h each month in the majority of the children for 4 consecutive months. Mean daily ST levels showed a significant rise between each pubertal stage (genital (G) and pubic hair (PH)). The rise in ST became more rapid once a mean testicular volume (MTV) of 10 ml had been reached. The diurnal rhythm was assessed by individual curve fitting on the log scale and by cosinor analysis. A rhythm was present prepubertally and developed into a pattern similar to that of the adult rhythm by stage G3. The monthly rate of rise of ST was greatest at stage G4. A significant rise in ST levels was detectable immediately prior to an increase in MTV to 3 ml. This allowed earlier recognition of the clinical onset of puberty at testicular volume of 3 ml, which in this group occurred at 10.9 (SD 0.9) years. ST is a non‐invasive and sensitive method for the serial monitoring of gonadal function in the prepubertal and adolescent boy.
INTRASELLAR GANGLIOCYTOMA CONTAINING GASTRIN AND GROWTH HORMONE‐RELEASING HORMONE ASSOCIATED WITH A GROWTH HORMONE‐SECRETING PITUITARY ADENOMA
Authors: BEVAN J. S. , ASA S. L. , ROSSI M. L. , ESIRI M. M. , ADAMS C. B. T. , BURKE C. W.
Published: March 2008

A 74‐year‐old acromegalic found to have an intrasellar gangliocytocytoma and GH‐secreting pituitary adenoma is described. The gangliocytoma contained immunoreactive gastrin and, to a lesser extent, GHRH, and the adenoma immunostained for GH. Gastrin has not been previously reported in hypothalamic gangliocytomas. Since this peptide has been demonstrated in normal hypothalamus and pituitary, and provokes GH release when administered intraventricularly, it may have caused GHRH release from the gangliocytoma by a local paracrine action and led to adenoma formation and acromegaly.
TREATMENT OF ACROMEGALY BY EXTERNAL IRRADIATION
Authors: MACLEOD A. F. , CLARKE D. G. , PAMBAKIAN H. , LOWY C. , SONKSEN P. H. , COLLINS C. D.
Published: March 2008

Despite the place of hypophysectomy as the primary treatment in acromegaly, external radiotherapy maintains a role as a relatively slow but effective therapy for inadequately treated patients or those unsuitable for operation. Over the last 25 years our radiotherapy regimen has differed from the published series in that we give a larger dose per fraction, with fewer treatments. We have analysed the efficacy and side‐effects of this regimen in 27 subjects with acromegaly. Growth hormone levels have fallen by, on average, 27% per year in the first five years, 83% of subjects achieving a basal growth hormone of < 10mU/l. The acute and chronic side‐effects of irradiation are discussed, including the relevance of estimates of biological potency, for example the Time Dose Fraction (TDF). One patient suffered visual loss that was most likely to be secondary to the radiotherapy. We also report the histological appearances of the pituitary fossa in five subjects previously treated with radiotherapy.
EFFECT OF SUBACUTE CABERGOLINE TREATMENT ON PROLACTIN, THYROID STIMULATING HORMONE AND GROWTH HORMONE RESPONSE TO SIMULTANEOUS ADMINISTRATION OF THYROTROPHIN‐RELEASING HORMONE AND GROWTH HORMONE‐RELEASING HORMONE IN HYPERPROLACTINAEMIC WOMEN
Authors: GIUSTI M. , LOMEO A. , TORRE R. , SGHEDONI D. , MAZZOCCHI G. , DURANTE R. , GIORDANO G.
Published: March 2008

It is known that dopaminergic neurotransmission is involved in the control of PRL, TSH and GH secretion. Cabergoline (CAB) is a new ergolinic derivative with a long‐acting dopaminergic activity. We evaluated 11 women with pathological hyperprolactinaemia before and during sub‐acute CAB treatment (0.8–1.2 mg/p.o.; 8 weeks). Simultaneous administration of TRH (200 μg i.v.) and GHRH 1–44 (50 μg i.v.) were carried out before and after 4, 8 and 10 week intervals from the beginning of CAB treatment. Basal PRL levels (2453.5 ± S.E. 444.5 mU/l) were significantly reduced during CAB administration (week 4: 164.5 ± 66.5 mU/l; week 8: 168.0 ± 66.5 mU/l; P < 0.01) and no variations were observed 2 weeks after drug discontinuation (week 10: 210.0 ± 98.0 mU/l). PRL percentage change after TRH was increased by CAB (P < 0.05). No variation in basal and TRH‐stimulated TSH levels was found during CAB administration. A slight increase in GH basal levels (3.0 ± 0.6 mU/l) was found after weeks 4 (6.4 ± 2.0 mU/l) and 10 (5.8 ± 1.6 mU/l) (P < 0.05). GH response to GHRH was significantly enhanced (ANOVA: P < 0.01) during sub‐acute CAB treatment. A positive correlation was found between GH secretory area and weeks of CAB therapy (P < 0.01). Our data show that CAB is very effective in lowering PRL secretion in hyperprolactinaemia, and is able to modify PRL and GH responses after TRH and GHRH. The increasing trend in GH basal and GHRH‐stimulated GH levels seems to indicate that CAB can override the central dopaminergic tone which is operative in hyperprolactinaemia.