bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SUMMARYCyproheptadine 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

SUMMARYThe 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

SUMMARYThree 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

SUMMARYA 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

SUMMARYA 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

SUMMARYThe 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

SUMMARYNinety‐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

SUMMARYThe 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

SUMMARYWe 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

SUMMARYIn 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

SUMMARYIt 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

SUMMARYTo 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

SUMMARYPrevious 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

SUMMARYHuman 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

SUMMARYImmunoreactive (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.