bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone secretion after the administration of GHRP‐6 or GHRH combined with GHRP‐6 does not decline in late adulthood
Authors: Micle Dragan , Popovic Vera , Kendereski Aleksandra , Macut Djura , Casanueva Fellpe F. , Dieguez Carlos 
Published: March 2008

SummaryOBJECTIVE Growth hormone (GH) secretion in middle and late adulthood declines with age. However, the precise mechanisms causing this impairment in OH release are unknown. HIs‐D‐Trp‐Ala‐Trp‐D‐Phe‐Lys‐NH2(GHRP‐6) Is a synthetic compound that releases OH in a dose related and specific manner in several species, including man. In order to gain a further Insight Into disrupted GH secretion in late adulthood, we evaluated GH responses to GHRP‐6 or GHRH, administered either alone or in combination, in healthy young and late adulthood groups of subjects.DESIGN All subjects underwent three different tests carried out in random order and separated by at least one week. Tests were performed at 0900 h after an overnight fast. GHRH (100 μg), GHRP‐6 (90 μg) either alone or In combination were administered as an I.v. bolus.SUBJECTS Groups of healthy young (mean ± SEM 22 ± 1·1 years, n= 9) and older adult subjects (59·5 ± 1·7 years, n= 9) were studied.MEASUREMENTS Serum GH levels were measured by radioimmunoassay.RESULTS In the group of young adult subjects the combined administration of GHRH and GHRP‐6 elicited a greater GH increase than GHRH alone (F= 21·9, P < 0·001) or GHRP‐6 alone (F= 6·2, P= 0·01). Similarly, the response to the combined stimuli was also greater than with GHRH alone (F= 21·8, P < 0·001) or GHRP‐6 alone (F= 23·9, P < 0·001) In the late adulthood group of subjects. OH responses to GHRH were greater in younger than in older subjects (F= 3·45, P= 0·03). In contrast, OH responses to either GHRP‐6 (F= 0·71, P= NS) or combined GHRH plus GHRP‐6 administration (F= 0·68, P= NS) were not significantly different between the two groups.CONCLUSIONS These data show that OH responses to GHRP‐6 are much greater than to GHRH In late adulthood. The marked Increase of plasma GH levels observed after administration of GHRP‐6 alone or in combination with GHRH Indicates that Impaired GH secretion in late adulthood is a functional and potentially reversible state.
Human chorionic gonadotrophin immunoactivity in cystic intracranial tumours
Authors: Honegger Jürgen , Mann Klaus , Thlerauf Paul , Zrinzo Anthony , Fahlbusch Rudolf 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE With regard to intracranial tumours, elevated hCG in CSF or serum has been considered to be specific for germ‐cell tumours. Recently however, elevated hCG has also been shown to be present In cyst fluid and CSF of patients with craniopharyngiomas. While germ‐cell tumours are generally non‐cystic, the aim of our study was to determine the significance of hCG In cystic intracranial lesions.DESIGN in a prospective study, hCG Immunoactivity and subunits of hCG were measured in cyst fluid, CSF, and serum of patients harbouring intracranial cyst lesions.PATIENTS AND MEASUREMENTS hCG immunoactivity was measured in cyst fluid and serum samples of 42 patients. CSF samples were available from 12 patients with craniopharyngiomas. In order to fully characterize the hCG immunoactivity, we used immunoradiometric assays for total hCG activity (measuring both intact hCG and the free β‐subunit of hCG), and those specific for intact, dimeric hCG (hCG), free β‐subunit of hCG (hCGP) and free α‐subunit. Furthermore, immunostaining of tumour tissue was performed using monoclonal antibodies directed against the free β‐subunit of hCG.RESULTS Total hCG immunoactivity was markedly elevated in cyst fluid of all 17 craniopharyngiomas (range 36·7–4558 IU/I; normal <5IU/I). Moderately elevated levels of hCG in cyst fluid were detected In three of four pituitary adenomas, in two metastases from lung cancer and in two arachnoid cysts. hCGβ was detected in cyst fluid from all hCG positive cysts, while specific determination of intact (dimer) hCG and α‐subunit mostly yielded negative results. No hCG immunoactivity was found in cystic giiomas, meningiomas or haemangioblastomas. hCG was elevated in CSF of two patients with craniopharyngiomas, but no hCG immunoactivity was detected in any serum sample. Subtle immunostaining of epithelial cell groups was shown in five of ten craniopharynglomas. Clear immunostaining for hCGβ was also found in scattered epithelial cells of one pituitary adenoma.CONCLUSIONS hCG immunoactivity in cystic intracranial lesions is due mainly to hCGβ. Measurement of hCG immunoactivity in cyst fluid can be helpful in the differential diagnosis of intracranial cystic lesions, if surgery is restricted to cyst decompression and no histology is available. High levels suggest a craniopharyngioma.
Short‐term effects of octreotide on blood pressure and plasma catecholamines and neuropeptide Y levels in patients with phaeochromocytoma: a placebo‐controlled trial
Authors: Plouin P.‐F. , Bertherat J. , Chateiller O. , Billaud E. , Azizi M. , Grouzmann E. , Epelbaum J. 
Published: March 2008

SummaryOBJECTIVE The observation that phaeochromocytoma possess specific somatostatin binding sites led us to test the hypothesis that octreotide may have antisecretory potential in patients with phaeochromocytoma. We therefore compared the effects of octreotide and placebo on blood pressure and plasma catecholamines and neuropeptide Y. PATIENTS Ten consecutive patients referred to a tertiary care centre for the diagnosis and treatment of a phaeochromocytoma.DESIGN AND MEASUREMENTS We performed a crossover comparison of either three 100 μg subcutaneous injections of octreotide over one day or 3 injections of octreotide vehicle over another. Blood pressure was measured over 24 hours on each test day using an automatic ambulatory recorder. Blood samples were collected before (at 0800 and 0900 h) and after (at 1000, 1100, 1200, 1300 and 1500h) placebo or octreotide injection. Plasma catecholamines were assayed by high‐performance liquid chromatography and neuropeptide Y was determined using a two‐site amplified enzyme immunoassay. All patients then underwent surgery and tumoral somatostatin binding site density was determined by quantitative autoradiography.RESULTS Compared to placebo, octreotide did not alter mean 24‐hour ambulatory blood pressure or plasma neuropeptide Y, or plasma or urinary catecholamine, levels. Although a moderate reduction in plasma noradrenaline was found in the two patients with the highest tumoral somatostatin binding site densities, overall octreotide induced variations in plasma noradrenaline did not correlate with somatostatin binding site density. Blood glucose increased from 5·4 ± 0·3 on placebo to 7·8 ± 0·5 mmol/l on octreotide (P< 0·01).CONCLUSION In the present controlled conditions, short‐term administration of octreotide had no antisecretory effect in patients with phaeochromocytoma.
Benzodiazepines attenuate the pituitary‐adrenal responses to corticotrophin‐releasing hormone in healthy volunteers, but not in patients with Cushing's syndrome
Authors: Korbonits M. , Trainer P. J. , Edwards R. , Besser G. M. , Grossman A. B. 
Published: March 2008

SummaryOBJECTIVE The corticotrophin‐releasing hormone (CRH) stimulation test has become established as a powerful tool in differentiating the source of ACTH In patients with Cushing's syndrome. Psychiatric symptoms are common In patients with Cushing's syndrome, and many patients with psychiatric illnesses may show disturbances of function of the pituitary‐adrenal axis; both of these groups of patients may be receiving benzodiazepine drugs when presenting for evaluation of their possible endocrine problems. Both animal and human studies suggest that Interactions occur between benzodiazepines and the hypothalamopituitary‐adrenal axis. We have therefore evaluated the effects of a benzodiazepine drug on the pituitary‐adrenal response to CRH.DESIGN We have Investigated the effects of 20 mg oral temazepam or placebo on serum Cortisol and plasma ACTH after the administration of 100μg i.v. human CRH in 12 healthy volunteers and In 9 patients with Cushing's syndrome.RESULTS Temazepam significantly inhibited the peak serum/plasma levels and area under the curve for circulating Cortisol and ACTH in normal subjects after CRH, but there was no such difference after temazepam in patients with Cushing's syndrome.CONCLUSIONS Our results have shown that temazepam Inhibits the pituitary‐adrenal responses to human CRH in normal subjects, but not in those with Cushing's syndrome. We believe that Inhibition of endogenous AVP by temazepam is the most likely explanation for our findings in healthy volunteers: the hypercortisolaemia in Cushing's syndrome suppresses the release of both endogenous CRH and AVP In portal blood which then results in abolition of the temazepam induced reduction In the pituitary‐adrenal response to exogenous CRH, as seen in our patients. These effects of benzodiazepines should clearly be taken Into account in patients using these compounds while undergoing endocrine assessment.
Oestrogen formation from androstenedione in human bone
Authors: Schweikert Hans‐Udo , Wolf Lutz , Romalo Gabriela 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Peripheral aromatization of testosterone and androstenedione Is the principal source for circulating oestrogens In men and In castrated and post‐menopausal women. Since human bone is a target organ for androgens and oestrogens, aromatase activity was assessed In human sponglosa obtained from patients who were undergoing orthopaedic surgery.DESIGN AND PATIENTS In Initial experiments for assessing aromatization, oestrogen formation from 1,2,6,7‐3H‐androstenedlone was compared with the release of trltlated water from 1β‐3H‐androstenedlone. Since the rates of enzyme activity were similar with the two methods, rates of oestrogen formation were determined under standardized conditions with the trltlated water generation technique In bone specimens obtained from 4 men and 11 post‐menopausal women.RESULTS The apparent Km of the aromatase ranged between 6 and 50 nm (20.4 ± 3.9; mean ± SEM), values In the range of those reported for human placental mlcrosomes. The maximum velocity (Vmax) of the aromatase activity ranged between 0‐14 and 1.23 nmol/g DNA/h.CONCLUSIONS Oestrogens formed in human bone may play a physiological role In steroid hormone action in this tissue.
High dose testosterone therapy for reduction of final height in constitutionally tall boys: does it influence testicular function in adulthood?
Authors: de Waal W. J. , Vreeburg J. T. M. , Bekkering F. , de Jong F. H. , de Muinck Keizer‐Schrama S. M. P. F. , Drop S. L. S. , Weber R. F. A. 
Published: March 2008

SummaryOBJECTIVE We have studied the effect of treatment with high doses of androgens during puberty on testicular function In adult men with constitutionally tall stature, taking Into account confounding factors interfering with sperm quality, since existing published data do not include whether testicular function is impaired by such treatment.DESIGN Historical cohort study.PATIENTS Forty‐three previously androgen treated tall men (cases) and 30 non‐treated tall men (controls).MEASUREMENTS Physical examination, semen analysis and plasma levels of LH, FSH, testosterone (T), sex hormone binding globulin (SHBG) and Inhlbin.RESULTS Sperm quality and testis volume were comparable between cases and controls. Mean sperm concentration was 66.4 ± 106/ml in cases and 66.2 ± 106/ml in controls. A left‐sided varicocele was found In 45% of the cases and 37% of the controls. In cases we observed a significant effect of the age at start of androgen therapy on sperm motility (regr. coeff. (SE): 4.92 (2.41)%,P= 0.048). In addition, testicular size at start of therapy had a significant effect on sperm concentration (regr. coeff. (SE): 5.57 (1.54) ± 106/ml,P= 0.0012) and on total sperm count (regr. coeff. (SE): 43.1 (7.73) ± 106,P= 0.0001). Plasma levels of T, SHBG and Inhibin were not statistically different between the groups. Cases had significantly higher FSH levels (mean (SD) 3.3 (2.2)vs2.1 (0‐8) IU/I,P= 0.004) and significantly lower LH levels (mean (SD) 2.3 (0.9)vs3.1 (1.4) IU/I,P= 0.019). We found a significant effect of age at start of therapy on plasma FSH level In the treated men (regr. coeff. (SE): −0.73 (0.18) IU/I,P= 0.0003).CONCLUSIONS Treatment with high doses of androgens for reduction of final height in constitutionally tall stature has no long‐term side‐effect on sperm quality, testicular volume or plasma testosterone levels. However, treated men had significantly higher plasma levels of FSH compared with controls. The meaning of this difference remains to be established. Varicocele was present in 42% of the adult tall men.
Investigation of delayed puberty
Authors: Albanese A. , Stanhope R. 
Published: March 2008

SummaryDelayed puberty is defined arbitrarily on the basis of statistical consideration, when no signs of puberty have occurred at 2.0 SD (13.4 years in girls and 13.8 in boys) above the mean chronological age for the onset of puberty. The vast majority of these patients have no endocrine abnormality and their pubertal development and growth spurt are simply consequences of primary delay (constitutional delay of growth and puberty (CDGP)) or secondary delay due to a chronic disease of childhood, such as asthma. However, a small proportion may have pathological causes of delayed puberty which must be careful Identified as specific management may be required. Associated with delayed puberty, the growth spurt is always delayed which is why the condition Is described as delayed growth and puberty. Short stature and lack of sexual development may lead to emotional and social difficulties and In some patients their consequences can persist when ‘normal’ height and full sexual maturation are attained. Recent data also suggest that a delay in the ‘tempo’ of pubertal maturation may Interfere with the normal bone accretion occurring during puberty, later causing osteoporosis. Such findings suggest that a new approach In delayed puberty may be necessary not only for psychological reasons but also for optimizing bone mass accretion.
A new deletion of the 5α‐reductase type 2 gene in a Turkish family with 5α‐reductase deficiency
Authors: Boudon Christel , Lobaccaro Jean Marc , Lumbroso Serge , Ösgur Gönül , Öcal Gönül , Belon Charles , Sultan Charles 
Published: March 2008

SummaryThe molecular basis for male pseudohermaphroditism produced by the 5α‐reductase deficiency is becomining Increasingly understood.OBJECTIVE We have performed biochemical and molecular analyses of the 5α‐reductase type 2 gene In a Turkish family with a 5α‐reductase deficiency.PATIENT A 46,XY prepubertal Turkish patient with female phenotype showing clltoral hypertrophy, high plasma testosterone and dihydrotestosterone, and normally differentiated and developed testosterone‐dependent internal genitalia.MEASUREMENTS 5α‐Reductase activity, measured by the conversion of 3H‐T Into 5α‐reduced compounds, was determined from cultured genital skin fibroblasts by both Intact monolayer assay and cell‐free extracts at various pH values. The five exons of the 5α‐reductase type 2 gene were sequenced after enzymatic amplification (PCR) of the patient's genomic DNA. Labelled PCR of the consanguineous parents’DNA was submitted to electrophoresis on a sequencing gel.RESULTS A marked decrease In the transformation of T into 5α‐reduced compounds by Intact cells and a diminished 5α‐reductase activity at acidic pH by sonicated cell extracts strongly suggested a 5α‐reductase type 2 deficiency. Molecular analysis of the 5α‐reductase type 2 gene showed a trinucleotide deletion straddling codons 156 and 157, responsible for a methionine residue deletion at position 157 of the protein. The parents’DNA contained both normal and deleted alleles.CONCLUSIONS This Is the third deletion described in the 5α‐reductase type 2 gene. The deleted methionine 157 Is conserved in both types 1 and 2 of human and rat 5α‐reductase, which suggests Its crucial role In the functioning of the enzyme. This gene rearrangement was thus clearly responsible for the reduced 5α‐reductase activity and abnormal genital development in this patient.
Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance
Authors: Mantzoros Chrlstos S. , Moses Alan C. 
Published: March 2008

SummaryA 47‐year‐old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemla with pancreatitis, and overt diabetes mellltus associated with severe Insulin resistance requiring 2.5‐3 units of Insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotropins, very low IGF‐I concentrations and GH concentrations unresponsive to Insulin or l‐dopa administration. Prolactin, pituitary‐adrenal and pituitary‐thyroid axes were normal. Dynamic testing with GnRH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapltultary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of Insulin resistance and hyperlipidaemla.
Thirst induced by a suckling episode during breast feeding and its relation with plasma vasopressin, oxytocin and osmoregulation
Authors: James R. J. A. , Irons D. W. , Holmes C. , Charlton A. L. , Drewett R. F. , Baylis P. H. 
Published: March 2008

SummaryOBJECTIVE There have been anecdotal reports of increased maternal thirst during breast feeding, but the physiological mechanisms remain obscure. We have assessed and quantified the stimulation of maternal thirst during breast feeding (suckling), and Correlated the changes with plasma oxytocin and vasopressin levels.DESIGN A within subject design was used with each subJect acting as her own control. Each subject participated in a suckling period and a control non‐suckling period the order of which was counterbalanced.SUBJECTS Ten healthy breastfeeding women ranging from 28 to 52 days post partum.MEASUREMENTS Thirst (assessed by a visual analogue scale), plasma vasopressin, plasma oxytocin (POT), plasma osmoiality and haematocrit, blood pressure, volume of milk transferred to baby, volume of water drunk immediately following each experimental period. RESULTS Thirst increased significantly more over a suckling period than over a comparable control period (P=0.013). The peak level of thirst correlated with the volume of water consumed to satiety following the suckling period (r=0.7, P=0.024). As expected, POT levels rose significantly in response to suckling (P <0.001). Six women demonstrated a close relation between thirst and oxytocin response during the suckling period. Despite significant changes in thirst during suckling there was no increase in plasma vasopressin or in osmoregulatory parameters.CONCLUSIONS This study confirms that suckling is a potent stimulus to thirst in the mother, and is not associated with vasopressin release or dependent on any measurable alterations In osmoregulation. What actually stimulates thirst during breast feeding remains unknown, but there are two potential explanations for these observations: (i) suckling sends nerve impulses to the para‐ventricular and supraoptic nuclei In the hypothalamus which may have afferents within the central nervous system which stimulates a thirst response simultaneous with oxytocin release; (ii) a learned anticipation of thirst may be occurring in a situation associated with expectant fluid loss to preserve homeostasis.
Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects
Authors: Daidoh H. , Morita H. , Mune T. , Murayama M. , Hanafusa J. , NI H. , Shibata H. , Yasuda K. 
Published: March 2008

SummaryOBJECTIVE The standard ACTH test in clinical use employs a pharmacological dose of ACTH which assesses the maximum secretory capacity of the adrenal cortex. We have investigated the responses of plasma adrenocortical steroids including cortisol, aldosterone and dehydroepiandrosterone (DHEA) to physiological doses of ACTH (ACTH 1–24, tetracosactide, Cortrosyn) and determined the minimal dose which induces a response equivalent to that induced by a pharmacological dose of ACTH.DESIGN Rapid ACTH tests at various physiological (0.1, 0.5, 1 and 5μg) and standard pharmacological (250μg) intravenous doses.SUBJECTS Seven healthy normal volunteers.MEASUREMENTS Plasma cortisol, aldosterone and DHEA were measured. Peak value and the increment from basal value were used as indices of responses.RESULTS Each steroid responded to physiological doses of ACTH in a dose dependent manner. The minimum dose inducing an equivalent response to 250μg ACTH was 0.5μg for peak and incremental values in cortisol and DHEA, while that for aldosterone was 0.1μg. The time to peak for each steroid was delayed as the dose increased. Plasma aldosterone and DHEA peaked significantly earlier than plasma cortisol in 1–5μg and 0.5–5‐μg ACTH tests, respectively.CONCLUSIONS These results suggest that the sensitivity of secretion to physiological doses of ACTH in descending order is aldosterone > DHEA = cortisol. When peak and incremental values are used, sufficient doses of ACTH are 0.1μg for plasma aldosterone and 0.5μg for plasma cortisol and DHEA in the rapid ACTH test.
Combined treatment of growth hormone and the bisphosphonate pamidronate, versus treatment with GH alone, in GH‐deficient adults: the effects on renal phosphate handling, bone turnover and bone mineral mass
Authors: Valk N. K. , Erdtsieck R. J. , Algra D. , Lamberts S. W. J. , Pols H. A. P. 
Published: March 2008

SummaryOBJECTIVE A potential drawback of GH replacement therapy In GH deficient (GHD) patients is the Initial decrease in bone mass. The present study Investigates the effects of the addition of pamidronate to GH replacement therapy in adult GHD subjects, on serum PTH and 1,25‐dihydroxyvitamin D3 (1,25‐(OH)2D3) levels, renal phosphate handling, bone turnover and bone mineral content (BMC).DESIGN Six GHD adult patfents were studied for two periods of 6 months with a wash‐out period of 3 years. In the first period they were treated with conventional replacement therapy and GH. In the second study period GH treatment was Identical, whlle after 2 weeks 150 mg pamidronate per day was added.RESULTS In the first study period (GH only) there was a slgniflcant increase of phosphate reabsorption, without a change In serum PTH and 1,25‐(OH)2D3 levels. Thls suggests a specific effect of GH or IGF‐l on renal phosphate handling. This was supported by the close correlatlon between serum IGF‐I levels and TmPlGFR (r=0·75, P < 0.0001). When GH was administered together with pamldronate, this correlation was less, but remained signiflcant (r=0·44, P < 0001). The Increase In bone turnover and decrease in BMC, as Initially observed during GH replacement therapy alone, were attenuated by simultaneous pamidronate administration. The decline in lumbar spine BMC (measured with dual‐photon absorptiometry) at 6 months was −3.1 ± 1.5% during GH replacement therapy alone vs an increase of +3.8 ± 2.0% during the admlnistratlon of the comblnatlon of GH and pamldronate (measured with dual‐energy X‐ray absorptlometry). At the distal and proximal forearm the changes amounted to −0.5 ± 3.4% vs +4.5 ± 1.8% and −1 ± 1.2% vs +1.2 ± 1.1 % respectively.CONCLUSIONS This study shows that the addition of a bisphosphonate to GH replacement therapy in GHD adults counteracts the GH (or IGF‐I) Induced Increase In renal phosphate reabsorptlon. Furthermore, It reduces OH induced bone turnover and prevents the lnitlal decrease in bone mineral content seen during GH treatment alone, resultlng In a beneflclal effect on bone mlneral mass. Pamidronate might therefore be an important adjunct to GH replacement therapy in adults with GHD and severe osteopenia during the early phase of GH Induced stlmulation of bone turnover.