bluuebunny/crossref_metadata_2025 huggingface dataset:
PHARMACOLOGICAL‘RESCUE’OF THE CORPUS LUTEUM RESULTS IN INCREASED INHIBIN PRODUCTION
Authors: IL LINGWORTH P. J. , REDDI K. , SMITH K. , BAIRD D. T.
Published: March 2008

Inhibin production by the corpus luteum was investigated by undertaking pharmacological rescue of the corpus luteum with hCG in four healthy women. Blood samples were collected daily for two menstrual cycles. Starting 7 days after the LH surge in the second cycle, incremental doses of hCG (125–8000 IU) were administered daily for 7 days resulting in hCG levels comparable to those seen in normal pregnancy. Following hCG, the luteal phase was prolonged and there were significant increases in the plasma concentrations of inhibin (P < 0.05), and oestradiol (P<0.05). The progesterone concentration was maintained at the mid‐luteal phase peak and as a result was significantly higher than those on the equivalent days of the control cycle (P< 0.05). It was concluded that rescue of the corpus luteum with physiological levels of hCG resulted in a significant output of inhibin, thus suggesting that the corpus luteum is a significant source of inhibin in early pregnancy.
LUTEINIZING HORMONE AND FOLLICLE STIMULATING HORMONE SECRETION PATTERNS IN GIRLS 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 36 healthy girls by measuring every 10 min and applying immunoradiometric assays (IRMA). Different stages of puberty were associated with significant changes in the plasma LH and FSH levels, pulse numbers (Pno) and pulse amplitudes (pA). Plasma LH was not detectable by day or night in young prepubertal girls (B 1), neither was plasma oestradiol (E2); however, plasma FSH was detectable in a pulsatile pattern. In the older prepubertal girls (B1‐onset) a discrete pulsatile LH pattern became detectable only during the night; plasma FSH tended to rise, while E2 became just detectable. In the early pubertal girls (B2) most daytime LH values were above the detection limit, in some with low‐amplitude pulses. At night, pulses with a wide range of pulse amplitudes were detected. Plasma FSH increased further, plasma E2 only slightly. With the progression of puberty the plasma LH and FSH levels, Pno and pA increased significantly from stage B2 to B3 during the day (P |Ml 0.05) and close to significance during the night (0‐05 |Ml P |Ml 0.1). However, in stage B4 the secretory characteristics tended to decline, while from stage B3 onwards plasma E2 started to rise rapidly (P 0.05, during the night from stage B2 to B3, during the day from B3 to B4m —). Simultaneous LH and FSH pulses were observed throughout puberty, usually during the night. Using these IRMA methods nocturnal LH in older prepubertal girls and both diurnal and nocturnal FSH pulsatility could be demonstrated in young prepubertal girls. From this study we conclude that (1) puberty in girls, as in boys, may be brought about by an increasing GnRH secretion both in frequency and amplitude, first appearing during the night. This increased GnRH stimulation results in LH secretion only during the night; (2) a cyclical pulsatile LH pattern including an LH surge can be established before the menarche; the capacity for positive feedback activity is not the final maturation characteristic to achieve an ovulatory menstrual cycle.
COMPOSITION OF INTACT HORMONE AND FREE SUBUNITS IN THE HUMAN CHORIONIC GONADOTROPHIN‐LIKE MATERIAL FOUND IN SERUM AND URINE OF PATIENTS WITH CARCINOMA OF THE BLADDER
Authors: ILES R. K. , LEE C. L. , OLIVER R. T. D. , CHARD T.
Published: March 2008

Ectopic‐hCG production occurs in approximately 30% of urothelial cancers. However, the clinical features which might be expected to result from elevated hCG levels are rare. We now show that in six of seven metastatic and 20 of 21 localized (Ta‐T4) positive hCG bladder cancer patients, only the free β‐subunit of hCG and its respective urinary breakdown product, β‐core, could be detected in clinical samples. Since only intact hCG is biologically active, this explains the discrepancy between biochemical and clinical findings.
DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN‐LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP‐1) IN EXTREME OBESITY
Authors: WEAVER J. U. , HOLLY J. M. P. , KOPELMAN P. G. , NOONAN K. , GIADOM C. G. , WHITE N. , VIRDEE S. , WASS J. A. H.
Published: March 2008

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in‐vitro and in‐vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin‐like growth factor small binding protein (IGFBP‐1). IGFBP‐1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF‐1, IGFBP‐1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 |Mp 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean |Mp SEM; 21 |Mp 2 μmo1/1), a normal IGF‐1, but reduced IGFBP‐1 (14.6 |Mp 2, μg/1); in 15 women IGFBP‐1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24|Mp2 nmol/1) but total testosterone values (1.9 |Mp 0.1 nmo1/1) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/I‐1 ratio (P < 0.01, r2=0.306) and inversely correlated with SHBG (P <0.01, r2= 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P < 0.001, r2= 0.383). No correlation was found between IGFBP‐1 and W/H ratio but a strong positive correlation was seen between IGFBP‐1 and SHBG (P < 0.001, r2=0.466). Furthermore, an equally significant inverse correlation was found between IGFBP‐1 and insulin levels (P <0.001, r2=0.474). Testosterone and fasting IGF‐1 did not show any correlation with the studied variables. Multivariate analysis suggested that insulin was the strongest factor involved in the regulation of IGFBP‐1 levels, whereas the level of SHBG was primarily determined by IGFBP‐1 concentration and W/H ratio. We conclude that reduced SHBG and IGFBP‐1 found in extreme obesity are inversely correlated to the prevailing hyperinsulinaemia and to increasing upper segment obesity. These findings provide further evidence to support the hypothesis for insulin being an important regulator of both binding proteins, SHBG and IGFBP‐1.
CONTINUOUS SUBCUTANEOUS GHRH(1‐29)NH2 PROMOTES GROWTH OVER 1 YEAR IN SHORT, SLOWLY GROWING CHILDREN
Authors: BRAIN C. E. , HINDMARSH P. C. , BROOK C. G. D.
Published: March 2008

We have treated eight pre‐pubertal children with partial GH insufficiency with continuous subcutaneous infusions of GHRH(1‐29)NH2 at a dose of 60 ng/kg/ min for periods of up to 1 year. In five children treated for 1 year, mean growth velocity increased from 4.6 cm/year (range 4.4‐5.2) to 7.0 cm/year (5.7‐8.7) (P = 0.04). Three children treated for 3‐6 months showed similar height velocity increases. A return to pretreatment growth rates was seen after cessation of treatment in all children. Twenty‐four‐hour GH profiles performed at intervals of 3 months showed sustained augmentation of pulsatile GH secretion without evidence of desensitization. The presence of pulsatile GH secretion during continuous GHRH administration provides strong evidence in man for the role of somatostatin in determining GH pulse frequency. The ability of the pituitary to respond to a supramaximal bolus of GHRH remained constant during the treatment. Continuous administration of GHRH(l‐29)NH2 will become a practicable treatment when formulated into a sustained release or depot preparation. We have shown this to be an effective therapy for some short, slowly growing children. Further studies are required to establish the optimal dosage regimen.
THE EFFECT OF CYPROHEPTADINE AND/OR BROMOCRIPTINE ON PLASMA ACTH LEVELS IN PATIENTS CURED OF CUSHING'S DISEASE BY BILATERAL ADRENALECTOMY
Authors: WHITEHEAD HELEN M. , BEACOM R. , SHERIDAN B. , ATKINSON A. B.
Published: March 2008

Cyproheptadine and bromocriptine have been reported to be therapeutic in suppressing ACTH levels in Cushing's disease and Nelson's syndrome. However, there have been only scattered reports of their effect in suppressing raised ACTH levels found in patients cured of Cushing's disease by bilateral adrenalectomy. In order to assess whether these agents could prove beneficial in such patients we studied 12 patients previously treated with bilateral adrenalectomy alone for Cushing's disease before and after 3 weeks of cyproheptadine and/or bromocroptine therapy. All had raised plasma ACTH values but no patient had evidence of a pituitary macroadenoma. Plasma ACTH and cortisol were sampled 2‐hourly for 24 h. Neither drug regime led to any change in plasma levels of cortisol for 24 h after a 20 mg dose of oral hydrocortisone. Plasma ACTH (mean±SEM) showed a small but significant overall reduction (523±45 vs 392±34 ng/1; P < 0.05) while on bromocriptine alone (5 mg given at 0800 and 1800 h, n=5). When each time point was analysed individually this reduction was significant at only five out of 13 time points. At 0400 h plasma ACTH (mean±SEM) was 7584±298.1 vs 380.2±166.6; 0600 h, 795±288.7 vs 477.8±191.7; 1200 h, 266.8±106.2 vs 187.0±80.3; 1400 h, 470.0±239.0 vs 302.0±135.9; 1600 h, 548.6±262.5 vs 394.2±178.5 ng/1 (P < 0.05). There was no significant change in plasma ACTH during treatment with the combination of bromocriptine and cyproheptadine. These results do not support the routine use of these agents for patients with raised ACTH levels after bilateral adrenalectomy for Cushing's disease.
DQA2 U ALLELE: A GENETIC MARKER FOR RELAPSE OF Graves'DISEASE
Authors: RATANACHAIYAVONG SUVINA , GUNN CATHERINE A. , BIDWELL ELIZABETH A. , DARKE C. , HALL R. , McGREGOR A. M.
Published: March 2008

The association of HLA‐DR3 with Graves'disease in Caucasoids is well established but its significance is unclear and its clinical value as a predictive parameter for relapse after a course of antithyroid drug therapy is controversial. We have further investigated the predictive value at the genomic level in 51 patients with Graves'disease who were treated with a 6‐month course of carbimazole and followed up for 2 years. Using DNA‐restriction fragment length polymorphism (DNA‐RFLP) allogenotyping, (i) complete concordance of HLA‐DR assignment was observed between serological and DNA‐RFLP analysis of all but one of 51 patients with Graves'disease; (ii) the DRβ171‐DQα2‐DQβ2a (a DNA‐RFLP allogenotype of the classical Northern European haplotype of HLA‐B8 DR3) was significantly (corrected P = Pcorr <0.02) associated with Graves'disease particularly in patients who relapsed (Pcorr<0.005); (iii) HLA‐DR3 was highly associated with DQA2 U allele (X2=18.53, d.f.2, P< 0.0005); (iv) a strong correlation between the DQA2 U allele and the outcome of the disease was observed. Relapse occurred in 91% (10/11) of the patients who were homozygous for the DQA2 U allele whilst only 65% (15/23) and 41% (7/17) of patients who were hetero or homo‐zygous for the DQA2 L allele (DQA2 U/L and DQA2 L/L) relapsed within the same period of follow‐up (X2= 7.18, d.f.2, P< 0.05). Though the relapse rate in patients with the DQA2 U/U genotype was not significantly higher than the relapse rate in patients with the DQA2 U/L genotype, it was significantly higher than the relapse rate in patients with DQA2 L/L genotype (P< 0.0001) with a relative risk of 14.3.
TREATMENT OF CUSHING'S SYNDROME WITH THE LONG‐ACTING SOMATOSTATIN ANALOGUE SMS 201‐995 (SANDOSTATIN)
Authors: INVITTI C. , DE MARTIN M. , BRUNANI A. , PIOLINI M. , CAVAGNINI F.
Published: March 2008

Three patients with Cushing's disease and one patient with paraneoplastic hypercortisolism were treated for 24‐49 days with the long‐acting analogue of somatostatin, SMS 201‐995, Sandoz (SMS), administered in increasing doses up to 400‐1200 μg daily. In the three Cushing's patients during SMS treatment plasma ACTH displayed an initial rise and a subsequent decrease. The pattern of urinary free cortisol (UFC) tended to be opposite to that of ACTH. In one of these patients, UFC continued to decrease throughout the treatment, without becoming normal. In the patient with paraneoplastic hypercortisolism, SMS was associated with a progressive decrease, though not the normalization, of UFC and of ACTH and cortisol levels. The reciprocal changes of the ACTH and UFC levels observed in the three Cushing's patients receiving SMS suggest that the peptide may act temporarily by inhibiting glucocorticoid secretion. In view of the marked reduction of UFC recorded in 1 of the 3 Cushing's patients and in the patient with paraneoplastic Cushing's syndrome, administration of SMS seems worth trying in cases of ACTH‐dependent hypercortisolism requiring medical treatment.
ISOLATED HYPOGONADOTROPHIC HYPOGONADISM: A FAMILY WITH AUTOSOMAL DOMINANT INHERITANCE
Authors: DEAN JOHN C. S. , JOHNSTON ALAN W. , KLOPPER ARNOLD I.
Published: March 2008

A family is reported in which isolated hypogonadotrophic hypogonadism is inherited as air autosomal dominant condition with variable expression. In previous familial cases, inheritance was autosomal recessive. Comparison is made with the endocrine and genetic findings in Kallmann's syndrome, which should be considered a separate disorder. There is difficulty in drawing a sharp distinction between hypogonadotrophic hypogonadism and constitutional delay in puberty in this family
NEUROENDOCRINE ALTERATIONS IN NUDE MICE WITH A HUMAN LUNG CARCINOMA PRODUCING PRO‐OPIOMELANOCORTIN, CORTICOTROPHIN‐RELEASING HORMONE AND ARGININE VASOPRESSIN
Authors: MORANO M. I. , DE ANTUENO R. J. , NIEDFELD G. , ESTIVARIZ F. E.
Published: March 2008

A mucoepidermoid carcinoma of the lung (ICD classification 8430/3) resected from a patient with no clinical signs of pituitary—adrenal alterations was transplanted into 2‐month‐old athymic nu/nu nude mice, with the purpose of studying the effects exerted by the human tumour on the host hypothalamo—pituitary—adrenal axis. The tumour produces peptides derived from different regions of pro‐opiomelanocortin (POMC: ACTH, 7.6±0.7; N‐terminal POMC, 6.6±0.6; β‐LPH/endorphin, 7.3±0.7; and α‐MSH, 3.8±0.5 pmol/g wet tissue) and the neuropeptides corticotrophin‐releasing hormone and arginine vasopressin (CRH: 3.6±0.4 and AVP: 1‐1±0.2 pmol/g wet tissue). Immunohistochemical staining of consecutive sections of the tumour indicated that staining of tumour cells for the different peptides was not uniform and although some cells co‐stained with CRH and AVP, POMC‐positive cells appeared to be distinct from CRH and AVP cells. Tumour extracts were chromatographed on Sephadex G‐75 and fractions monitored for POMC derived peptides. A single peak with characteristics of α‐MSH was detected. The ACTH, N‐POMC and β‐LPH/endorphin radioimmunoassays (RIA) detected a peak at large molecular weight, eluting at the position expected for POMC. These RIA systems also revealed an ACTH(1‐39) peak and another peak which probably correspond to 13 kDa ACTH, a peak eluting at the position of hN‐POMC(1‐48), a β‐LPH‐like peak, and a smaller sized peak which may represent α or γ‐endorphin. The ACTH, N‐POMC and β‐LPH/endorphin contents of anterior lobe (AL) extracts, but not neutrointermediate lobe (NIL) extracts, showed a striking decrease in tumour‐bearing (TB) nude mice. However, while no difference was seen in the α‐MSH content of AL extract between TB and control (C) nude mice, it decreased in NIL extracts of TB animals. The contents of CRH and AVP in stalk—median eminence extracts of TB nude mice was significantly lower than that of C nude mice. Basal plasma corticosteroids were raised in TB nude mice at levels comparable to those in stressed C nude mice, and although adrenal weights did not vary between TB and C nude mice, morphological changes indicating hypertrophy were found in the adrenal glands of the host animals. It was concluded that the tumour dramatically alters the hypothalamo—pituitary—adrenal axis of the host, and that it may be a useful model for studying tumour—host interactions in ectopic hormone‐producing tumours.
THE EFFECT OFD‐ VERSUSL‐ PROPRANOLOL IN THE TREATMENT OF HYPERTHYROIDISM
Authors: EBER OTTO , BUCHINGER WOLFGANG , LINDNER WOLFGANG , LIND RATH PETER, MONIKA , KLIMA GERT , LANGSTEGER WERNER , KÕLTRINGER PETER
Published: March 2008

The purpose of this study is to determine whether there is a difference in treatment of hyperthyroidism using either the D‐ or L‐isomer of propranolol. Two groups of 20 patients with overt hyperthyroidism received either 120 mg L‐or D‐propranolol each for a period of 5 days. In the D‐propranolol administered group there was a significant decrease in TT3 and f T3 plasma levels and in the ratio of TT3 to TT4; however, a significant increase occurred in rT3 values up to day 5. On the other hand, L‐propranolol treatment resulted in a less pronounced decrease in TT4 and TT3 values, while all other thyroid hormone levels remained unchanged as, above all, did the T3/T4 ratio. The well known effect of D,L‐propranolol upon peripheral conversion of T4 to T3 is thus not due to the beta‐blocking action of L‐propranolol but is mainly conditioned by the D‐isomer which has no beta‐blocking action itself.
HLA ASSOCIATIONS IN PATIENTS WITH POLYCYSTIC OVARIES AND IN PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA CAUSED BY 21‐HYDROXYLASE DEFICIENCY
Authors: HAGUE WILLIAM M. , ADAMS JUDITH , ALGAR VIVIENNE , DRUMMOND VARINA , SCHWARZ GISELE , BOTTAZZO GIAN‐FRANCO , JACOBS HOWARD S.
Published: March 2008

Ninety‐nine Caucasian patients with ultrasonically detected polycystic ovaries (PCO) were typed for human leucocyte (HLA) antigens. Fifty patients with congenital adrenal hyperplasia (CAH) caused by 21‐hydroxylase deficiency were similarly typed. Among the patients with PCO, there was a significant increase in the frequency of HLA DRW6 (P = 0‐0027) compared with that found in a control population, which remained significant (P = 0.027) when corrected for the number of antigens tested. This difference was reduced, but remained significant (P = 0.006), when the patients with CAH and PCO were added. There was also a significant decrease in the frequency of HLA DR7 (P = 0.017) among the patients with PCO compared with a control population, but there was no distortion of the frequencies of HLA A, B or Cw antigens. Among the patients with CAH, previously well documented associations of HLA B14 and DR1 with non‐classical disease were confirmed. The frequency of HLA Bw47 was increased among the whole group of CAH patients (P = 0.05) but was not increased among those with classical salt‐wasting (SW) or simple virilizing (SV) disease. Family studies were performed in close female relatives of 16 of the PCO patients and 21 of the CAH patients but no evidence for genetic linkage between HLA and PCO status could be found. These data suggest that there is no significant component of disturbed adrenal steroid 21‐hydroxylase activity to account for the PCO morphology, although there may be some other genetic factor, more proximal to the centromere on chromosome 6, affecting the development of polycystic ovaries.
IMPAIRED GROWTH HORMONE RESPONSE TO INSULIN‐INDUCED HYPOGLYCAEMIA IN OBESE PATIENTS: RESTORATION BLOCKED BY RITANSERIN AFTER FENFLURAMINE ADMINISTRATION
Authors: BERNINI G. P. , ARGENIO G. F. , VIVALDI M. S. , CORSO C. DEL , BIRINDELLI R. , LUISI M. , FRANCHI F.
Published: March 2008

The aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin‐induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal‐weight control women underwent three IIH tests, at 14‐day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5‐HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2‐2 mmol/1. In the controls, the expected GH increase to IIH (peak value 56±13.4 mU/1, AUC 234.4±55 mU/min/m1) was unaffected by FF administration (peak value 43±11.4;AUC 216.8±34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak value 21.4±4.6 mU/1, P<0.02; AUC 93.2±18.6, P<0.02). However, in comparison with the basal test, FF administration significantly (P < 0.001) enhanced GH response to insulin hypoglycaemia (peak value 33.4±4; AUC 150±14.6), reaching values not significantly different from those of the controls. This effect was completely antagonized by RIT administration (peak value 18±5; AUC 85.6±21). In conclusion, the reduced GH response to insulin hypoglycaemia in obese women has been confirmed in the present study. However, the restoration of the hormonal response obtained after FF administration in obese patients only, which is effectively antagonized by RIT, strongly suggests the involvement of the serotoninergic system in this impaired secretary pattern and provides indirect evidence of the failure of this system in human obesity.
THE HYPOTHALAMIC‐PITUITARY‐ADRENAL AXIS IN INFANTILE MALNUTRITION
Authors: MALOZOWSKI SAUL , MUZZO SANTIAGO , BURROWS RAQUEL , LEIVA LAURA , LORIAUX LYNN , CHROUSOS GEORGE , WINTERER JORG , CASSORLA FERNANDO
Published: March 2008

We studied the circadian rhythm and the response of the hypothalamic‐pituitary‐adrenal (HPA) axis to ovine corticotrophin releasing hormone (oCRH) stimulation and dexamethasone suppression in 32 children with grade II‐III marasmus. Children were studied prior to and after nutritional rehabilitation. Mean baseline plasma cortisol concentrations were elevated at admission and decreased significantly after nutritional rehabilitation. Mean±SEM plasma cortisol response to oCRH increased from a basal of 480 ±41 to a peak of 582 ± 58 nmol/1 at the time of admission, and from a basal of 234±27 to a peak of 532±41 nmol/1 after caloric rehabilitation. Dexamethasone suppression in the malnourished group was associated with a decrease in the mean±SEM basal plasma cortisol concentration from 397±44 to 171 ±44 nmol/1. After caloric rehabilitation, basal cortisol levels decreased from 259±27 to 22±5 nmol/l following dexamethasone. Our results support the concept that malnutrition is associated with decreased responsiveness to oCRH and incomplete dexamethasone suppression, and that these abnormalities are restored after nutritional rehabilitation.
THYROID FUNCTION IN PATIENTS WITH MYOTONIC DYSTROPHY
Authors: FUKAZAWA HIROSHI , SAKURADA TOSHIRO , YOSHIDA KATSUMI , KAISE NOBUKO , KAISE KAZURO , NOMURA TAKASHI , YAMAMOTO MAKIKO , SAITO SHINTARO , TAKASE SADAO , YOSHINAGA KAORU
Published: March 2008

In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean±SD) of T4 (114.7±26.8 vs 129.9± 28.3 nmol/l), FT4 (16.6±4.5 vs 18.4±3.8 pmol/l), T3 (1.61±0.29 vs 1.86±0.33 pmol/l), TSH (2.7±1.3 vs 2.4±1.4 mU/l), TBG (26.7±5.5 vs 27.6±4.9 mg/l), T4/T3 (84.3±18.4 vs 82.1±15.3), and FT4/FT3 (0.28±0.05 vs 0.33±0.08). Serum FT3 (4.3±1.4 pmol/l) in patients were significantly lower than those (5.3±0.9 pmol/l) in normal controls (P<0.02). Thyroidal131 I‐uptakes (8.7±4.3%) in patients were significantly lower than those (25.8±7.4%) in controls (P<0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4±4.5 vs 17.0±6.2 mU/l; P<0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy.
RELEASE OF ATRIAL NATRIURETIC PEPTIDE DURING HYPERTONIC SALINE INFUSION: THE IMPORTANCE OF POSTURE
Authors: BURRELL LOUISE M. , BAYLIS P. H.
Published: March 2008

It is well known that atrial distension is an important stimulus for atrial natriuretic peptide (ANP) release, but conflicting evidence exists as to whether hyperosmolality also stimulates the release of atrial natriuretic peptide (ANP) in man. As infusion of hypertonic saline causes an increase in both blood volume and plasma osmolality, we have employed this stimulus to investigate:

(i) whether hyperosmolality increases plasma ANP concentrations;

(ii) the importance of posture in ANP release.

Normal male volunteers (n=6) were infused with hypertonic saline at a rate of 0.06 ml/kg/min for 2 h on two different occasions separated by 1 month. Infusion was performed with subjects in the seated and supine positions in random order. Hypertonic saline infusion induced increases in plasma osmolality (P<0.001), plasma sodium (P<0.01) and blood volume (P<0.001) in both seated and supine position. The increase in plasma osmolality was accompanied by an increase in plasma ANP during the supine infusion (2.7±1.0 to 9.0±2.4 pmol/l (mean±SEM; P <0.01)) but no significant change in plasma ANP concentration occurred during the seated infusion. A positive linear correlation was obtained between increase in plasma osmolality and plasma ANP in the supine but not in the seated hypertonic saline infusion. There was a positive linear correlation between estimated increase in blood volume and plasma ANP in the supine but not the seated infusion of hypertonic saline. We suggest that the increase in ANP during hypertonic saline infusion reported by some workers was due to atrial distension, secondary to increased blood volume and is dependent on the position in which the subjects were studied. We conclude that the release of ANP in normal subjects is not influenced by hyperosmolality but is stimulated by atrial distension.
A LONG‐TERM FOLLOW‐UP OF POSTPARTUM THYROIDITIS
Authors: OTHMAN SAKINAH , PHILLIPS D. I. W. , PARKES A. B. , RICHARDS C. J. , HARRIS B. , FUNG H. , DARKE C. , JOHN R. , HALL R. , LAZARUS J. H.
Published: March 2008

To investigate the long‐term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2‐4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P<0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P < 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long‐term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.
HUMAN GRANULOSA CELLS CONTAIN INSULIN‐LIKE GROWTH FACTOR‐BINDING PROTEIN (IGF BP‐1) mRNA
Authors: KOISTINEN RIITTA , SUIKKARI ANNE‐MARIA , TIITINEN AILA , KONTULA KIMMO , SEPPÄLÄ MARKKU
Published: March 2008

Previous studies have demonstrated expression of insulin‐like growth factor‐binding protein (IGF BP‐1) in secretory and decidualized endometrium, in adult and fetal liver, and in HepG2 liver cancer cells. We have studied the expression of IGF BP‐1 in various types of ovarian neoplasias, normal ovary, and granulosa cells from hyperstimulated human ovarian follicles by RNA blot hybridization. A single 1.6 kb mRNA species, similar to that present in human decidua, was identified in poly(A)RNA‐containing preparations of granulosa cells and of a borderline malignant ovarian cystadenoma. This finding verifies the postulated production of IGF BP‐1 by the human ovary.
IMPAIRED PROLACTIN SECRETION AND BODY FAT DISTRIBUTION IN OBESITY
Authors: WEAVER J. U. , NOONAN K. , KOPELMAN P. G. , COSTE M.
Published: March 2008

Human obesity shows clustering within families. The hypothesis for the presence of a major gene or genes acting in human obesity is supported by recent evidence from studies of obesity in adoptees and their biological parents and siblings. The heterogeneity of obesity may be demonstrated by the shape of fat distribution and the prolactin response to insulin hypoglycaemia. Fat distribution has been shown to have a genetic background whereas a primary disorder of hypothalamic function is suspected in obese women who show an impaired prolactin response to insulin‐induced hypoglycaemia. We have investigated the possible association between fat distribution and hypothalamic function in 23 extremely obese, nondiabetic premenopausal women who have been characterized using their absolute body weight, body mass index (BMI), fat distribution (expressed as waist to hip ratio), fasting insulin, basal prolactin and prolactin response to hypoglycaemia. Fasting insulin values showed a significant correlation (P < 0‐05, R = 0.604) with increasing waist to hip ratio (upper body segment obesity), whereas the graded prolactin response to hypoglycaemia of the obese women showed a negative association with increasing upper body segment obesity (P < 0‐05; R=‐0.446). No relationship was observed between fasting insulin and the prolactin response to hypoglycaemia. We suggest that this previously unrecognized association of an impaired prolactin response to hypoglycaemia and upper body segment fatness may be useful for the investigation of the genetics of obesity.
BASIC FIBROBLAST GROWTH FACTOR IN HUMAN PITUITARY TUMOURS
Authors: SILVERLIGHT J. J. , PRYSOR‐JONES R. A. , JENKINS J. S.
Published: March 2008

Immunoreactive (ir) basic fibroblast growth factor (FGF) has been measured in normal human pituitary glands and in 41 pituitary tumours of various types using a radioimmunoassay. Normal pituitary glands contained ir basic FGF ranging from 29.4 to 355 fmol/mg wet weight whereas 87.5% of pituitary tumours contained amounts of the growth factor which were less than normal. There was no relationship between the type of tumour and the FGF content. Normal and tumorous pituitary FGF had an affinity for heparin which was similar to that of basic FGF. Gel column chromatography revealed that the pituitary ir FGF was present mainly as high molecular weight forms, with only a small proportion as the basic 146 amino‐acid peptide. Because of our previous observation that basic FGF inhibits the growth of human pituitary tumour cells, it is suggested that the reduction in basic FGF of many pituitary tumours may favour the stimulation of pituitary growth.
HORMONAL CHANGES IN PATIENTS WITH POLYCYSTIC OVARIAN DISEASE AFTER OVARIAN ELECTROCAUTERY OR PITUITARY DESENSITIZATION
Authors: GADIR AHMED ABDEL , KHATIM MOHAMED S. , MOWAFI RAOUF S. , ALNASER HUDA M. I. , ALZAID HUSSEIN G. N. , SHAW ROBERT W.
Published: March 2008

Eleven patients with polycystic ovarian disease (PCO) were treated by laparoscopic ovarian electrocautery and nine with a long‐acting luteinizing hormone releasing agonist (LHRH‐A) for 8 weeks. Both groups showed equivalent significant decreases in their 6‐h mean values of luteinizing hormone (LH) and testosterone (T) measured in 25 samples collected every 15 min. Patients treated with ovarian electrocautery showed significant increases in their 6‐h mean values of follicle stimulating hormone (FSH) and insulin with variable oestradiol (E2) responses. The magnitude of change following treatment was significantly greater for LH than for FSH. Buserelin medication did not cause persistent significant changes in the levels of insulin or FSH but it did cause a significant reduction in the 6‐h mean values of E2. We conclude that LH is the gonadotrophin primarily affected after pituitary desensitization and ovarian electrocautery. Furthermore, there is no direct correlation between the levels of circulating insulin and testosterone in patients with PCO.
A COMPARATIVE STUDY OF SINGLE‐DOSE GROWTH HORMONE THERAPY AS AN ADJUVANT TO GONADOTROPHIN TREATMENT FOR OVULATION INDUCTION
Authors: HOMBURG R. , WEST C. , TORRESANI T. , JACOBS H. S.
Published: March 2008

One intramuscular injection of biosynthetic human growth hormone (24 IU), administered on the first day of gonadotrophin treatment for ovulation induction, significantly augmented the ovarian response to gonadotrophic stimulation in seven patients. Compared with a protocol involving six injections of 24 IU of GH given on alternate days to the same patients, the smaller dose had an intermediate but highly significant effect in reducing the amount, duration of treatment and daily effective dose of hMG needed to induce ovulation. The difference between the effect of the one‐dose and six‐dose protocols was small. The action of growth hormone on the human ovary, probably mediated by insulin‐like growth factor‐1 (IGF‐1), appears effective in enhancing the response to gonadotrophin therapy even when given in a single dose.
EFFECTS OF IMPROVED BLOOD GLUCOSE ON INSULIN‐INDUCED HYPOGLYCAEMIA, TRH, GnRH AND EXERCISE TESTS IN INSULIN‐DEPENDENT DIABETES
Authors: WÜRZBURGER M. I. , PRELEVIC G. M. , SÖNKSEN P. H. , PERIC L. A. , TILL S. , MORRIS R. W.
Published: March 2008

In order to evaluate effects of metabolic control on pituitary function in insulin‐dependent diabetes exercise, hypoglycaemia (insulin tolerance test), thyrotrophin releasing hormone and gonadotrophin releasing hormone, tests were performed on 25 patients before (Study 1) and after 2 weeks of improved metabolic control (Study 2). Patients were sub‐divided into C‐peptide negative (CpN, 10 patients with no residual C‐peptide secretion) and C‐peptide positive (CpP, 15 patients with residual beta‐cell function) groups for analysis of results. Exercise induced higher growth hormone responses in CpN patients independent of metabolic control (P < 0.001). Thyrotrophin releasing hormone induced higher growth hormone responses in CpN patients; this response was threefold greater after improved control (P < 0.005). Growth hormone and cortisol response to hypoglycaemia and thyroid stimulating hormone and prolactin secretion in response to thyrotrophin releasing hormone were unaffected by residual beta‐cell function or metabolic control. Luteinizing hormone response to gonadotrophin releasing hormone in CpN patients was impaired and lower after improved control (P < 0.002). The results indicate an association between residual pancreatic insulin secretory and hypothalamic/pituitary function, possibly reflecting central neurosecretion of insulin.
PLASMA C19 STEROID SULPHATE LEVELS AND INDICES OF ANDROGEN BIOAVAILABILITY IN FEMALE PATTERN ANDROGENIC ALOPECIA
Authors: MONTALTO J. , WHORWOOD C. B. , FUNDER J. W. , YONG A. B. W. , CALLAN A. , DAVIES H. E. , CONNELLY J. F.
Published: March 2008

Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA‐S), 5‐androstene‐3β, 17/β‐diol sulphate (5‐ADIOL‐S), 5α‐androstane‐3α, 17β‐diol sulphate (3α‐DIOL‐S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non‐SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 × T (nmol/1) ÷ SHBG (nmol/1), in premenopausal women with AA (n= 25‐45) and in normal premenopausal women (n= 17–73). While mean plasma concentrations of DHEA‐S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 ± 3 vs 64±3 nmol/1) and the mean free androgen index (4.4±0.4 vs 2.4±0–2), and mean concentrations of free testosterone (45 ± 5 vs 26 ± 1.4 pmol/ 1), non‐SHBG bound T (0.9 ±0.2 vs 0.6±0.1 nmol/1) and androstenedione (4.3±0.3 vs 3.4±0.2 nmol/1) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5‐ADIOL‐S (512±42 nmol/1) and 3a‐DIOL‐S (76±7 nmol/1) were significantly higher than levels found in normal women (272±12 nmol/1 and 52±2 nmol/1 respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5‐ADIOL‐S and 3α‐DIOL‐S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.
SECRETORY DYNAMICS OF OESTRADIOL (E2) AND PROGESTERONE (P4) DURING PERIODS OF RELATIVE PITUITARY LH QUIESCENCE IN THE MIDLUTEAL PHASE OF THE MENSTRUAL CYCLE
Authors: ROSSMANITH W. G. , LAUGHLIN G. A. , MORTOLA J. F. , YEN S. S. C.
Published: March 2008

Although the temporal relationship between pulsatile pituitary luteinizing hormone (LH) secretion and steroid hormone release from the corpus luteum has been investigated, the secretory profiles of oestradiol (E2) and progesterone (P4) during periods without any discernible LH pulsatile activity remain unknown. Consequently, blood was sampled at 15‐min intervals for 24 h from 16 women during the midluteal phases (6–8 days after midcycle LH surge) of their cycles. LH was measured in all samples and analysed for significant pulses by the Cluster pulse algorithm. Nine studies showing the lowest LH pulse frequencies and large LH pulse amplitudes were also assessed for E2 and P4 in all samples. All three hormones were released in pulsatile fashions. Pulses of E2 and P4 were found to be synchronous. While the release frequencies for E2 (mean±SEM: 8.9±0.7 pulses/24 h) and P4 (8.5±0.7 pulses/24 h) were comparable, the LH pulse frequency (4.6 ±0.4 pulses/ 24 h) was found to be significantly (P< 0.001) lower than the ovarian steroid pulse frequencies. Maximum (P<0.01) cross‐correlation coefficients were determined at positive time lags of 28.1 ± 7.7 min for LH/E2 and 31.7 ± 5.8 min for LH/P4, indicating that changes in E2 or P4 levels tended to occur within approximately 30 min following LH concentration changes. Further, the degree of concomitance between a steroid pulse and an LH peak was much higher (P< 0.001) than by chance. Maximum (P<0.01) cross‐correlation coefficients between E2 and P4 hormonal data series were found at zero time lag, suggesting that these sex steroids were secreted simultaneously. The pulse amplitudes, pulse durations and areas under the peaks of those E2 or P4 pulses preceded by large (> 5IU/1) amplitude LH pulse were significantly greater (P<0.05 or less for all comparisons) than for steroid pulses not associated with preceding LH pulses. Thus, two populations of steroid pulses were observed; one associated with preceding LH pulses and having greater magnitude of all pulse attributes (duration, amplitude, area under the peaks), and another, not associated with preceding LH pulses and having pulse characteristics of lower magnitude. This observation suggests that the pulsatile release of ovarian steroids is a result of the episodic modulating influence of LH and that pulsatile steroid hormone secretion pertains with smaller magnitude during periods of relative pituitary quiescence of LH pulsatility.
GONADOTROPHIN SECRETION IN THE SECOND HALF OF THE MENSTRUAL CYCLE: A COMPARISON OF WOMEN WITH NORMAL CYCLES, LUTEAL PHASE DEFECTS AND DISTURBED FOLLICULAR DEVELOPMENT
Authors: SCHWEIGER ULRICH , TUSCHL REINHARD , BROOCKS ANDREAS , PIRKE KARL‐MARTIN
Published: March 2008

In order to study the relationship between episodic gonadotrophin secretion and alterations of ovarian hormone secretion, we examined women with normal menstrual cycles (n= 26), luteal phase defects (n= 10) or disturbed follicular oestradiol secretion (n= 8) as established by daily (except weekends) determinations of oestradiol and progesterone. Pulsatile gonadotrophin secretion was studied during the luteal phase or the second half of the menstrual cycle sampling at IS min intervals for 12 h. LH and FSH mean concentrations and LH pulse frequency were significantly (P<0.01) increased in the group with disturbed follicular development in the presence of decreased oestradiol (E2) and progesterone (P4) levels. In women with luteal phase defects mean LH and FSH concentrations and pulsatile LH secretion showed a nonsignificant trend to lower values in the presence of significantly decreased P4 concentrations during the luteal phase.
LATE ONSET ADRENAL HYPERPLASIA IN A GROUP OF IRISH FEMALES WHO PRESENTED WITH HIRSUTISM, IRREGULAR MENSES AND/OR CYSTIC ACNE
Authors: MCLAUGHLIN B. , BARRETT P. , FINCH T. , DEVLIN J. G.
Published: March 2008

The aims of this study were to determine the frequency of late‐onset adrenal hyperplasia due specifically to 21‐hydroxylase deficiency in a group of Irish women who presented at a Dublin Clinic with symptoms of hyperandrogenism, including hirsutism, menstrual irregularities and/or cystic acne, and to determine if those with 21‐hydroxylase deficiency showed particular HLA associations. 119 women had blood samples taken basally and 1 h after an injection of 0.25 mg synacthen with the following hormones profiled: 17‐hydroxyprogester‐one, 11‐deoxycortisol, androstenedione, testosterone, DHEAS and Cortisol. Blood sampling was carried out between 0900 and 1000 h during the early follicular phase of the menstrual cycle (when applicable). Ninety‐six subjects were new referrals to the Clinic for investigation of hyperandrogenism and 23 were acting as controls. In this study, 6% of patients showed evidence of partial 21‐hydroxylase deficiency. In addition, 3 of the 6 with partial 21‐hydroxylase deficiency had normal baseline levels of 17‐hydroxyprogesterone, with the biochemical abnormality becoming manifest only on synacthen stimulation. Late‐onset adrenal hyperplasia due to partial deficiency of this enzyme should always be considered as a possible diagnosis in women who present with symptoms of hyperandrogenism. Synacthen stimulation is an important diagnostic tool in elucidating partial enzyme deficiency as baseline 17‐hydroxyprogesterone may be normal in such patients.
THE EFFECTS OF SUBMAXIMAL ENDURANCE EXERCISE UPON LH PULSATILITY
Authors: McARTHUR JANET W. , GILBERT IAN , HENERY ROBERT J. , QUINN JACQUELINE , PERRY LESLIE , CRAMER DEREK , KIRKLAND MARK , PEDOE DAN S. TUNSTALL , REES LESLEY H. , BESSER G. MICHAEL , TURNBULL BARRY A.
Published: March 2008

The acute effects of submaximal endurance exercise (three consecutive 20‐min runs on a treadmill at 50,60 and 70% of the subjects' maximum oxygen uptake) upon the pulsatile release of LH were compared with those accompanying leisurely strolling for a similar period in seven normally menstruating young women. All trials were conducted during the early to mid‐luteal phase, as determined by body temperature patterns, ultrasonic scans of the ovaries, detection of the LH surge in first morning urine specimens, and serial measurements of plasma progesterone. Blood was sampled every 10 min via an indwelling cannula for 8 h before and 12 h after exercise and serum LH measured by radioimmunoassay. LH pulsations were analysed by a time series method. Following cannulation, mean LH levels declined but then rose to reach a maximum 2 h before the beginning of the exercise bout. LH concentrations remained virtually unchanged during exercise itself, and exhibited a declining trend throughout the post‐exercise period. The findings in the two groups were similar in all respects, except that in the control study the rate of LH pulsatility was significantly diminished (P<0.05) during the first 2 h of sampling as compared with the subsequent 2‐h period. The approximate half‐life of LH varied from 27 to 57 min, with a mean of 41 min.
Gonadotrophin releasing hormone agonist suppressive treatment of ovarian function decreases serum LH‐β and bloactive LH but maintains elevated levels of LH‐α
Authors: Lemay Andre , Lourdusamy Mettllda
Published: March 2008

Ten patients with endometriosis were treated by a continuous subcutaneous infusion of the GnRH agonist buserelin for 6 months. Although serum oestradiol decreased into the menopausal range within 2 weeks after starting treatment, serum LH levels as measured by immunoassay remained elevated at least fivefold over baseline during the entire treatment. However, the bloactivity of LH as determined by mouse Leydlg cell assay was rapidly lost, changing the mean ± SEM bioactivity/Immunoassay ratio from 2·4 ± 0·5 before treatment to 0·4 ± 0·01 after only 1 week of medication. When LH‐α and LH‐β immunoreactlvities were assessed by specific antibodies, the serum LH‐α profile was parallel to immunoreactive LH whereas the LH‐β profile corresponded to the pattern of bioactive LH. LH‐α was elevated at least tenfold over baseline whereas LH‐β decreased to less than 35% of pretreatment level. The α/β ratio shifted from 1·3 ± 0·2 before treatment to 0·04·0 ± 06 after 2 weeks of buserelin infusion. Thus In response to continuous buserelin exposure, the gonadotrophin releases excessive amounts of LH having predominant LH‐α immunoreactivity. The effective loss of LH bloactivity would be related to decreased LH‐β submits. The significance of high levels of LH‐α or possibly modified LH molecules remains to be evaluated during GnRH agonist treatment using well characterized assays