bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spironolactone as a single agent for long‐term therapy of hirsute patients
Authors: Spritzer Poli Mara , Lisboa Karen O. , Mattiello Simone , Lhullier Francisco 
Published: March 2003

OBJECTIVETo assess the androgen‐suppressing effect of spironolactone, and the use of this drug as a single agent in the long‐term therapy of hirsute patients with either polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). Standard cyproterone acetate (CPA) treatment was used to evaluate the results obtained with spironolactone.DESIGNProspective randomized study.PATIENTSForty‐six hirsute women were separated randomly into two groups, stratified for polycystic ovary syndrome. For 12 months, Group 1 (21 patients, 10 PCOS) received spironolactone only (200 mg/day). Group 2 (23 patients, nine PCOS) received CPA (50 mg/day) with ethinyl oestradiol (35 μg/day).MEASUREMENTSFerriman–Gallwey clinical score for hirsutism and serum testosterone, androstenedione, and LH levels.RESULTSIn IH patients, hirsutism regressed equally with spironolactone (21 ± 2–14.5 ± 2) and CPA (23 ± 2–13 ± 2). In PCOS patients, the mean score for hirsutism after 12 months was significantly lower with CPA (12 ± 1) than with spironolactone (16 ± 1). Testosterone levels did not change with spironolactone; with CPA there was a decrease from baseline in PCOS (47% and 51%, 6 and 12 months) and IH patients (31% and 30%). Androstenedione levels also declined from baseline in CPA‐treated PCOS patients (38% and 39%, 6 and 12 months). Androgen levels were significantly different between the groups after 6 and 12 months. LH levels decreased with CPA (72%) but not with spironolactone.CONCLUSIONOur results suggest that spironolactone used as a single agent is as effective as cyproterone acetate combined with oestradiol for long‐term treatment of patients with idiopathic hirsutism. In PCOS patients, spironolactone is still effective for reducing hirsutism; however, for treatment of the hormonal or metabolic manifestations associated with PCOS, it may be necessary to combine spironolactone with either an antigonadotrophic agent or a drug that improves peripheral insulin sensitivity.
Inhibitory action on GHRH‐induced GH secretion of chronic tamoxifen treatment in breast cancer
Authors: De Marinis  , Mancini  , Izzi  , Bianchi  , Giampietro  , Fusco  , Liberale  , Rossi  , Valle  
Published: March 2003

OBJECTIVEPrevious in vitro and in vivo studies on animal models have demonstrated that tamoxifen (TAM) inhibits GH secretion. Studies in humans are conflicting. The aim of this study was to evaluate the effect of chronic TAM treatment on GH secretory dynamics in the presence of negligible endogenous oestrogens, in postmenopausal women with breast cancer.PATIENTSTen female patients were studied over a 6–12‐month period after surgical therapy, before medical therapy, and during chronic treatment with TAM (20 mg/day p.o.).MEASUREMENTSIn all subjects we performed a standard GHRH‐test (50 mg i.v. as a bolus) and compared the single time points, the peak response and the areas under the curves (AUC), before and during treatment. In basal samples, we evaluated the circulating levels of IGF‐1, IGF‐BP3 and their ratio, SHBG, FSH, LH, Oestradiol (E2) and PRL. GH was assayed by Immunoradiometric assay (IRMA). Insulin‐like growth factor type I (IGF‐I), Insulin‐like growth factor‐binding protein‐3 (IGF‐BP3), FSH, LH and PRL were measured by Radioimmunoassay (RIA). SHBG was measured by a noncompetitive liquid phase immunoradiometric assay, while E2 was measured directly in plasma by a liquid phase technique.RESULTSTAM chronic treatment significantly reduced GH response to GHRH at single time point evaluations, GH peak response (mean decrease: 59.8 ± 7.3%) and GH‐AUC (mean decrease 53.8 ± 8.9%). TAM also significantly reduced plasma IGF‐1 levels. No significant variations were found in IGF‐BP3 levels or in the IGF‐1/IGF‐BP3 ratio. A significant inverse correlation between SHBG and IGF‐1 circulating levels was noticed during TAM treatment.CONCLUSIONSOur data show that long‐term tamoxifen treatment blocks the response of GH to exogenous GHRH and reduces IGF‐1 levels, possibly by a central mechanism other than the demonstrated peripheral action. The results of this study, keeping in mind the demonstrated mitogenic role of IGF‐1 in cancer proliferation, can contribute to clarify the mechanism by which TAM exerts its antiproliferative effect.
The combined pituitary function test in children: an evaluation of the clinical usefulness of TRH and LHRH stimulation tests through a retrospective analysis of one hundred and twenty six cases
Authors: Westwood  , Butler  , McLellan  , Barth  
Published: March 2003

OBJECTIVEThe combined pituitary function test is routinely used in the endocrine investigation of short children. The TRH and luteinising hormone‐releasing hormone (LHRH) response tests have been shown to be of minimal value in adults. We have evaluated the clinical utility of these tests in the context of combined pituitary function testing in children.DESIGNA retrospective analysis of basal hormone measurements and pituitary stimulation tests in relation to clinical assessment of pituitary function.PATIENTSOne hundred and twenty‐six children, 82 boys and 44 girls, aged 2–17 years, who had undergone pituitary function testing were studied.RESULTSThe TSH response to TRH stimulation correlated directly with basal plasma TSH but not basal plasma total T4. In patients with an impaired response to stimulation, basal TSH concentrations were <2.0 mIU/l and significantly lower than in patients with a normal response (P < 0.0001). An impaired response to TRH stimulation had a positive predictive value of 0.43 and a negative predictive value of 0.90 for the diagnosis of hypopituitarism. A basal TSH concentration of <2.0 mIU/l had a positive predictive value of 0.22 and a negative predictive value of 0.92. A low basal T4 (normal range 60–140 nmol/l) in combination with an inappropriately low or normal basal TSH was always associated with a diagnosis of hypopituitarism.The responses of plasma LH and FSH to LHRH stimulation correlated directly with basal plasma LH and FSH concentrations. Basal gonadotrophin concentrations, basal sex hormone concentrations or response to LHRH stimulation could not distinguish patients with constitutional delay of growth and puberty from those with hypopituitarism. There was no apparent relationship between either basal gonadotrophin concentrations or response to LHRH stimulation and clinical assessment of pituitary function. In patients ≥13 years with constitutional delay of growth and puberty the median and interquartile ranges of basal LH and FSH were 1.4 IU/l (0.7–3.6) and 2.6 IU/l (2.2–5.2) respectively. The three hypopituitary patients in this study with chronological age ≥13 years had undetectable concentrations of both gonadotrophins. The response of LH and FSH to LHRH stimulation was significantly lower in patients ≥13 years with clinical hypopituitarism than in those with intact pituitary function (P <0.02).CONCLUSIONTRH and LHRH tests in children with short stature appear to have little value over and above the baseline hormone measurements. An abnormal response to hormone stimulation is not diagnostic of hypothalamic‐pituitary disease. We have demonstrated that neither TRH nor LHRH stimulation tests should be routinely used in the investigation of children with short stature.
Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome
Authors: Moorkens Greta , Berwaerts Joris , Wynants Herlindis , Abs Roger 
Published: March 2003

OBJECTIVEPrevious studies have revealed that hormonal disturbances may accompany the chronic fatigue syndrome (CFS). Changes in the secretion of the pituitary–adrenal axis have been demonstrated, as well as abnormalities in the GH‐IGF‐I axis. However, data have not always been well characterized and were sometimes conflicting. The small number of CFS patients investigated in earlier studies may have played a role in the interpretation of the results.SUBJECTS AND DESIGNHormonal testing was performed in 73 nonobese CFS patients and nonobese 21 age‐and gender‐matched healthy controls. We investigated GH, ACTH and cortisol responses to insulin‐induced hypoglycaemia. In a subgroup of patients arginine and clonidine stimulation for GH was also performed. Nocturnal secretion of GH, ACTH and cortisol were determined. Serum levels of IGF‐I, prolactin, TSH, and free thyroxine were also measured. Visceral fat mass was assessed by CT scanning.RESULTSGH response to insulin induced hypoglycaemia assessed by peak value (17.0 ± 13.1 μg/l vs. 22.1 ± 9.8 μg/l; P = 0.01) and by AUC (450.0 ± 361.3 μg/l vs. 672.3 ± 393.0 μg/l; P = 0.002) was significantly decreased in CFS patients vs. controls. Nocturnal GH secretion assessed by GH peak value (5.4 ± 3.7 vs. 9.0 ± 5.1 μg/l; P = 0.44) and by AUC (34.4 ± 20.2 vs. 67.4 ± 43.1; P = 0.045) was also significantly impaired in CFS patients. Arginine and clonidine administration showed no differences in GH secretion between CFS patients and controls. In the CFS group, GH peak values were significantly higher after ITT than after arginine (P = 0.017) or clonidine (P = 0.001). No differences in serum IGF‐I levels were found between CFS patients and controls. Except for a significantly lower nocturnal cortisol peak value, no differences were found in ACTH and cortisol secretion between CFS patients and controls. Significantly higher serum prolactin levels (7.4 ± 4.7 μg/l vs. 4.4 ± 1.3 μg/l; P = 0.004) and significantly higher serum TSH levels (1.6 ± 1.0 mU/l vs. 1.0 ± 0.4 mU/l; P = 0.011) were found in CFS patients. Serum free thyroxine was comparable in both groups. Visceral fat mass was significantly higher in CFS patients (86.6 ± 34.9 cm2vs. 51.5 ± 15.7 cm2; P < 0.001).CONCLUSIONSWe observed a significant impairment of GH response during insulin‐induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however, not lead to different concentrations in serum IGF‐I. The clinical expression of this inadequate GH secretion can thus be questioned, although the alteration in body composition may be related to this relative GH deficiency. Significantly increased prolactin and TSH levels were found when compared to controls. These findings give support to the hypothesis of a decreased dopaminergic tone in CFS. Further investigations are required in order to identify specific adaptations within the neurotransmitter system in CFS and to determine the clinical importance of the impaired GH homeostasis.
Effects of normalization of GH hypersecretion on lipoprotein(a) and other lipoprotein serum levels in acromegaly
Authors: Maldonado Castro Gonzalo F. , Escobar‐Morreale Héctor F. , Ortega Henar , Gómez‐Coronado Diego , Balsa Barro José A. , Varela César , Lasunción Miguel A. 
Published: March 2003

BACKGROUND & AIMSLipoprotein(a) has been recognized as an important risk factor for cardiovascular disease. Lipoprotein(a) has been found to be elevated in sera of acromegalic patients, possibly contributing to the increased incidence of coronary heart disease found in these patients. In the present study we sought to determine the effects of GH hormonal status on lipoprotein(a) and other lipid parameters, including lipoprotein lipase (LPL) activity.DESIGNCross‐sectional study.PATIENTSTwenty acromegalic patients, with either active (n = 12) or controlled (n = 8) acromegaly, were studied. Twenty‐nine healthy subjects served as control group for serum lipid measurements.MEASUREMENTSSerum GH, IGF‐1, IGF binding protein‐3 (IGFBP‐3) and insulin levels were measured in patients. Insulin resistance was measured by the homeostatic model assessment (HOMA). Plasma total cholesterol, triglycerides, HDL‐lipids, apolipoproteins A‐I and B, lipoprotein(a) and lipoprotein lipase activity were also measured.RESULTSThe highest lipoprotein(a) levels were observed in patients with active acromegaly, followed by patients with controlled acromegaly, whose lipoprotein(a) concentrations were still significantly higher than those of the control group (means ± SEM: active acromegaly, 0.67 ± 0.13 g/l; controlled acromegaly, 0.41 ± 0.12 g/l; controls 0.17 ± 0.02 g/l; P < 0.05). There were no differences in other lipid and lipoprotein values among the groups. In patients, significant correlations were observed between lipoprotein(a) and basal GH levels (r = 0.56, P < 0.02), mean GH levels (r = 0.48, P < 0.05) and with insulin resistance estimated by HOMA (r = 0.62, P < 0.01). No correlations were found between lipoprotein(a) and IGF‐1 or IGFBP‐3 levels.CONCLUSIONSOur present results demonstrate that both active acromegalic patients and those with controlled disease have elevated serum lipoprotein(a) concentrations. The findings might suggest that the present biochemical criteria for cure of acromegaly are not strict enough to result in the normalization of all the undesirable metabolic changes found in this disease, and also that significant cardiovascular risk may persist despite successful treatment of acromegaly.
Potential of norethisterone enanthate for male contraception: pharmacokinetics and suppression of pituitary and gonadal function
Authors: Kamischke Axel , Diebäcker Julia , Nieschlag Eberhard 
Published: March 2003

OBJECTIVEGestagens are known to suppress gonadotrophins in women and are currently also under investigation for the development of hormonal male contraceptives. The aim of the study was to assess the potential of norethisterone enanthate (NETE) for male contraception.DESIGN AND MEASUREMENTSThe suppressive effect of a single injection of 200 mg NETE on serum gonadotrophins, serum testosterone, lipids, spermatogenesis, well‐being and sexual function was evaluated in seven healthy men.RESULTSIn this single dose study treatment was well tolerated by all volunteers. NETE led to a rapid, profound and significant suppression of serum LH (day 6 − day 10), FSH (day 2 − day 29), testosterone (day 1 − day 29 and day 35) and SHBG (day 6 − day 35). At study end sperm counts were significantly suppressed. Numbers of spontaneous erections (day 17, 23 and 26), number of sexual fantasies (day 20 and 23) as well as libido (day 20 and 26) were significantly decreased compared to baseline. All other parameters including lipids, augmented glucose, testicular volume and well‐being showed no significant alterations.CONCLUSIONBecause of its strong, rapid and sustained suppression of serum FSH and testosterone norethisterone enanthate offers great potential for hormonal male contraception if combined with testosterone esters.
Functional characterization of five constitutively activating thyrotrophin receptor mutations
Authors: Wonerow Peter , Chey Soroth , Führer Dagmar , Holzapfel Hans‐Peter , Paschke Ralf 
Published: March 2003

OBJECTIVEGain of function mutations of the thyrotrophin receptor (TSHR) affect several functional characteristics, such as cAMP and inositol phosphate (IP) accumulation, cell surface expression and TSH affinity. In this study we compared five constitutively activating TSHR mutations, four receptors with a point mutation (S505N, L629F, I630L, V656F) and a nine amino acid (aa) deletion mutant (aa positions 613–621) for these functional parameters in parallel transfection experiments.METHODSThe wild‐type TSHR (wt) and TSHRs containing the mutations S505N, L629F, I630L, V656F and the deletion 613–621 (all cloned in the expression vector pSVL) were transiently expressed in COS‐7 cells in parallel experiments. Forty‐eight hours after transfection the basal and stimulated cAMP and inositol phosphate accumulation as well as the cell surface expression (by FACS and ELISA), KD‐values and TSHR down regulation by different stimuli were determined.RESULTSIn contrast to the very different values for specific constitutive activity (sca) (ranging from 7.5 to 100.3‐fold wt) and very different levels of receptor cell surface expression (11–94% wt level) the basal cAMP accumulation determined in transfected COS‐7 cells was surprisingly uniform (6.5–8.0 over wt basal). None of the point mutated receptors constitutively activates the phospholipase C cascade. In contrast the deletion 613–621 mutant showed constitutive activity for the IP pathway with a twofold increase in basal IP accumulation compared to the wild type TSHR. All investigated TSHR‐mutants showed a TSH‐stimulated receptor down‐regulation, which seems to be independent of the phospholipase C pathway.CONCLUSIONSThe uniform basal cAMP values in spite of the large variation in specific constitutive activity values suggest that the COS‐7 cell overexpression system used for the in vitro characterization is partly regulated. This regulation is most likely due to receptor down regulation. The TSHR deletion mutant (613–621) showed a constitutive activity for both the Gαs and the Gαq/11 pathways. The TSH‐mediated IP‐stimulation by this mutant contrasts with its unresponsiveness to TSH for cAMP accumulation and therefore supports the model of different active conformations of the TSHR.
Monosomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1
Authors: Kontogeorgos G. , Kapranos N. , Tzavara I. , Thalassinos N. , Rologis D. 
Published: March 2003

Multiple endocrine neoplasia type 1 (MEN 1) represents an endocrine syndrome characterized by complex pituitary, parathyroid and pancreatic neoplasia. Loss of heterozygosity of the specific region 11q13 has been reported in several tumours from patients with MEN 1 inherited disorder. We present a case of a young patient with familial MEN 1 syndrome with a pituitary adenoma exhibiting monosomy of chromosome 11. The patient presented with a large and rapidly growing pituitary adenoma associated with markedly elevated serum PRL levels, progressive bilateral visual loss and hydrocephalus. The resected adenoma was chromophobic, mainly PRL‐producing and to a lesser degree immunoreactive for GH. Fluorescence in situ hybridization (FISH) using an α‐satellite centromeric probe detected loss of one chromosome 11 copy in almost all pituitary adenoma cells. Clinical and biochemical studies revealed parathyroid hyperplasia and MRI studies detected a pancreatic tumour in addition to the pituitary adenoma. To our knowledge this is the first study reporting monosomy 11 in pituitary adenoma in a patient associated with familial MEN 1 syndrome.
Recurrent ACTH‐independent Cushing's syndrome in multiple pregnancies and its treatment with metyrapone
Authors: Hána V. , Dokoupilová M. , Marek J. , Plavka R. 
Published: March 2003

A 17‐year‐old primigravid woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By week 17 of gestation, plasma cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma cortisol after a 1‐mg dexamethasone overnight suppression test. Basal urinary free cortisol was 10 times above the upper limit (in pregnancy) and ACTH levels were suppressed. The diagnosis of ACTH – independent Cushing's syndrome was established. MRI scans revealed normal adrenal and pituitary glands. To control hypercortisolism, the patient was treated with metyrapone. At 34 weeks of gestation, the patient developed preeclampsia and underwent caesarean section. A female infant weighing 1070 g was delivered. No apparent metyrapone‐induced teratogenic effects were observed. Cushing's syndrome in the patient resolved within three weeks of delivery. No corticosteroid replacement therapy either for child or mother was needed. Eight months after delivery the patient became pregnant again and rapidly developed Cushing's syndrome with typical clinical symptoms and signs and laboratory results (urinary free cortisol 6464 nmol/24 h). This second pregnancy was unwanted and terminated by artificial abortion that was followed by rapid resolution of hypercortisolism. A third pregnancy, 12 months after delivery was also accompanied by the rapid development of hypercortisolism which recovered after artificial termination.The mechanisms by which pregnancy‐induced Cushing's syndrome occurred in this patient are unclear. Aberrant responsiveness or hyperresponsiveness of adrenocortical cells to a non‐ACTH and non‐CRH substance produced in excess in pregnancy should be considered.Metyrapone suppression of hypercortisolism currently represents the best treatment for these rare cases.
In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non‐functioning pituitary adenomas
Authors: Andersen Marianne , Bjerre Per , Schrøder Henrik D. , Edal Anette , Høilund‐Carlsen Poul F. , Pedersen Per Hyltoft , Hagen Claus 
Published: March 2003

The secretory capacity, in vivo, of clinically non‐functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy.Ten patients (mean (range) 53 years (26–73)) with clinically non‐functioning macroadenomas, ≥ 10 mm were studied. The secretory capacity of the adenomas was examined using basal, NaCl and TRH‐stimulated LH, FSH and α‐subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 µg × 3/day and a dopamine‐D2‐agonist, cabergoline 0·5 mg × 1/day was studied. The basal LH, FSH and α‐subunit levels were determined before and during 6 months' therapy with octreotide and cabergoline, and MR scans were used to evaluate tumour volume before and during this period of therapy. Octopus‐perimetry was used to examine the visual fields.A reduction in tumour volume (mean ± SEM (range); 30% ± 4% (18–46%)) during 6 months of combination therapy with octreotide and cabergoline was recorded only in patients with in vivo secretory potential. Tumour volume was not reduced in four patients: in three of these patients it remained unchanged while in one patient it was observed to have increased (by 14%). Of the six patients with pretherapy secretory capacity, one displayed a very high basal level of α‐subunit (74 µg/l) despite unmeasurable levels of LH and TSH, and an FSH‐level of 1 IU/l. The other five patients presented paradoxical LH, FSH and/or α‐subunit responses to TRH. A reduction in basal levels of LH, FSH and/or α‐subunit was observed in all six patients, and the maximum reduction of at least one of the hormonal levels was 66% ± 7% (50–98%). The basal levels of LH, FSH and α‐subunit in the 10 patients were (mean ± SEM (range)), 3·0 IU/l ± 1·0 (0·0–7·4), 12·7 IU/l ± 5·0 (0·0–39·0) and 9·0 IU/l ± 7·0 (0·2–74·0). During six months of therapy with octreotide and cabergoline, the basal levels of LH, FSH and α‐subunit were reduced by ≥ 50% in seven patients – including the six patients with in vivo secretion prior to therapy. No new visual field defects were detected during therapy and no deterioration of existing visual field defects was recorded. The medical therapy was well tolerated.The in vivo basal and TRH‐stimulated secretory capacity of LH, FSH and α‐subunit predicted tumour reduction following intensive medical therapy in all of our patients with non‐functioning pituitary adenomas.