bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone treatment affects plasma LH pulsatile release in women with secondary amenorrhoea
Authors: Genazzani Alessandro D , Petraglia Felice , Volpogni Cristina , Pianazzi Francesco , Montanini Vanna , D'Ambrogio Gerardo , Genazzani Andrea R. 
Published: March 2008

SummaryOBJECTIVE Since growth hormone (GH) is administered as a co‐gonadotrophic factor in ovulation induction, this study aimed to assess the action of GH on the episodic pulsatile release of LH and FSH in amenorrhoeic patients. PATIENTS AND DESIGN Nineteen patients affected by hypothalamic amenorrhoea were enrolled for this study: group A, 9 patients with normal gonadotrophins; group B, 10 patients with low gonadotrophins. Both groups were studied during GH infusion (0015 IU/min for 4 hours) and after 7 days of GH administration (0 1 IU/kg/day). Patients underwent a 4‐hour pulsatility study, with blood sampling every 10 minutes. A standard GnRH test (10 μ g i.v. bolus) was performed immediately after the pulsatility evaluation.MEASUREMENTS LH and FSH were assayed with an IFMA method; oestradiol and IGF‐I were assayed by RIA and IRMA, respectively.PULSE DETECTION Time series were analysed with Detect program.RESULTS All patients showed similar LH and FSH pulsatile characteristics both under baseline conditions and during GH infusion. After 7 days of GH administration, episodic FSH release showed no change in either group. On the contrary, LH pulse frequency (mean ± SE) significantly increased in group A (4 0±0 2 peaks/4h, P&kt;0 05), while putse amplitude (baseline, 3.9± 0 6 IU/I; after 7 days, 2.9±0.3 IU/I, P<0 05), and integrated LH plasma concentrations (baseline, 7.6 ±1–1 IU/I; after 7 days, 5±0 8 IU/I, P<0 05) were significantly decreased. No significant changes were observed for LH pulse frequency, amplitude or integrated LH plasma concentrations in hypogonado‐trophinaemic patients (group B). Plasma oestradiol levels were significantly increased only in group A (baseline, 154 18±23 8 pmoI/I; after 7 days, 380 3±110 1 pmoI/I, P < 005), while IGF‐I levels were significantly increased in both groups after 7 days of GH administration (P<0 05). No significant differences were observed in the gonadotropin responses to GnRH test before and after GH administration.CONCLUSIONS The present study showed that the administration of GH in amenorrhoeic patients determines the significant changes in episodic LH release in those subjects with normal LH plasma levels and suggests that the action of GH may be dependent upon the ovarian‐pituitary feedback action.
Recombinant human growth hormone therapy does not increase microalbuminuria in children with short stature
Authors: Levine Daniel , Kreitzer Paula , Freedman Samuel , Trachtman Howard 
Published: March 2008

SummaryOBJECTIVE Concerns have been raised about possible adverse effects of growth hormone on renal function. We measured microalbuminuria as a sensitive index of early glomerular damage in children being treated with recombinant human growth hormone.DESIGN AND PATIENTS Microalbuminuria was measured in a group of 17 children with short stature being treated with recombinant human growth hormone and in a group of 13 patients with idiopathic short stature not receiving therapy.MEASUREMENTS Microalbuminuria was measured by a commercially available ELISA and urinary creatinines were determined using a Beckman creatinine analyser.RESULTS The level of microalbuminuria was 0 484 ± 0 275 g albumin/mol creatinine (mean ± SD) in the patients receiving growth hormone and 0 681 ±0 574 g albumin/mol creatinine in the untreated controls. There was no statistically significant difference between these values.CONCLUSIONS Treatment with recombinant human growth hormone does not cause an increase in microalbuminuria in children with normal renal function. This supports the safety of this medication in growth hormone deficient children with normal renal function.
Preliminary observations using endocrine markers of pituitary venous dilution during bilateral simultaneous inferior petrosal sinus catheterization in Cushing's syndrome: Is combined CRF and TRH stimulation of value?
Authors: McNally Paul G. , Bolia Amman , Absalom Steve R. , Falconer‐Smith James , Howlett Trevor A. 
Published: March 2008

SummaryOBJECTIVE We determined whether the measurement of hormones in pituitary blood permits correction for dilution by non‐pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome. DESIGN Bilateral simultaneous inferior petrosal sinus blood sampling was performed after combined hCRF and TRH stimulation. Peak ACTH concentrations were corrected for the TSH and PRL inter‐sinus ratio, assuming uniform secretion of both hormones into each inferior petrosal sinus.PATIENTS Eight patients with clinical and biochemical features of Cushing's syndrome.MEASUREMENTS Basal and stimulated ACTH, TSH and PRL concentrations were measured after bilateral simultaneous inferior petrosal sinus blood sampling and simultaneously from a peripheral forearm vein.RESULTS Basal central peripheral ACTH ratio misdiagnosed four of eight patients as having non‐pituitary disease. Peak uncorrected ACTH central:peripheral ratio erroneously suggested two of eight patients had non‐pituitary disease. ACTH central: peripheral ratio corrected by TSH and PRL correctly predicted pituitary‐dependent disease in all eight cases and provided correct lateralization data in four of five patients with a unilateral pituitary microadenoma.CONCLUSION This study suggests that measuring other hormones in pituitary blood after TRH stimulation can offer a simple and reliable method for correcting for dilution by non‐pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome.
Modulation of IGF‐I receptors by exogenous hGH treatment in constitutionally short children
Authors: Eshet R. , Klinger B. , Silbergeld A. , Laron Z. 
Published: March 2008

SummaryOBJECTIVE To study the in‐vivo regulation of IGF‐I binding sites on erythrocytes (RBC) following administration of growth hormone (hGH) to constitutionally short children. Recently, owing to biosynthetic techniques, treatment with hGH has been administered not only to children with GH deficiency but also to children with constitutional growth delay and with familiaf short stature.PATIENTS AND DESIGN Growth hormone (rhGH‐Norditropin, Novo/Nordisk) was administered at a dose of 0 1 U/kg/ day s.c. to 11 children with constitutional short stature. Before and at 1–2 months after initiation of treatment IGF‐I binding sites and serum IGF‐I were determined. Erythrocytes were separated from whole blood by centrifugation over Ficoll Hypaque and used to assess IGF‐I binding sites.RESULTS Serum IGF‐I levels increased from 14 93 ±1 50 nmoI/I (mean±SEM) to 30 29 ±2 32 nmoI/I, with a mean difference of 15 38 + 2 21 (P= 0 00001). Concomitantly, the number of binding sites per cell decreased from 5 77 ±0.81 sites per celt (m±SEM) to 2 10 ±0 36, with a mean difference of ‐ 3 67 ± 0 76 (P= 0.0003). The dissociation constant (Kd) also decreased from 0 47±016 MM (m±SEM) to 0.10±0 02 with a mean difference of 0 37±0.16 (P=0.02), indicating an increase in the affinity of the receptors.CONCLUSION Treatment of children with constitutional short stature with hGH raises the circulating IGF‐I levels and down‐regulates the IGF‐I receptors: This study shows that IGF‐I is capable of regulating its homologous receptor concentrations in vivo and it is suggested that the measurement of IGF‐I binding sites on RBC may be used for the diagnosis of subtle states of resistance to IGF‐I.
Luteinizing hormone secretion and hypoandrogenaemia in critically ill men: effect of dopamine
Authors: Van den Berghe Greet , de Zegher Francis , Lauwers Peter , Veldhuls Johannes D. 
Published: March 2008

SummaryOBJECTIVE Critical Illness has been associated with decreased LH secretion and lowering of testosterone. Dopamine is often used for vasoactive support in these patients. We therefore aimed to Investigate LH secretion during severe illness and particularly the effect exerted by dopamine on LH in such patients.PATIENTS AND DESIGN In a randomized, controlled study of critically 111 adult male polytrauma patients (n= 8), we evaluated the effect of prolonged (83‐298 hours) dopamine infusion (5μg/kg/mln I.v.) on the dynamics of LH secretion and on serum testosterone Concentrations. The effect of brief (15‐21 hours) dopamine administration was documented in an additional randomized, controlled, crossover study involving 6 patients.MEASUREMENTS Serum LH concentrations were measured by IRMA. The LH profiles, obtained by blood sampling every 20 minutes for 9 hours during two consecutive nights, were examined by deconvolution analysis. Serum testosterone concentrations were measured by RIA once per study night. RESULTS We found that before dopamine initiation and within 24 hours of dopamine withdrawal, the mean serum LH concentrations, the LH secretory amplitude, the amount of LH secreted per burst, the mean LH secretion rate and the number of LH pulses were higher than during dopamine infusion, being increased by a median of 161 % (P= 0·006), 98% (P= 0·03), 106% (P= 0·03). 164% (P= 0·01) and 25% (P= 0·008) respectively. However, without dopamine administration the amplitude and mass of the LH secretory bursts still appeared to be low, whereas the pulse frequency remained elevated. After dopamine withdrawal, LH secretion increased significantly within 3 hours. Serum testosterone levels were very low and dopamine infusion appeared not to affect them within 24 hours.CONCLUSION We documented decreased LH secretory pulse amplitude and mass with Increased pulse frequency, as well as very low serum testosterone concentrations in critically ill men. Dopamine Infusion further suppressed LH release by decreasing secretory burst amplitude, mass and frequency, possibly through an inhibitory action at both the pituitary and the hypothalamic level.
Inhibition of growth hormone release after the combined administration of CHRH and GHRP‐6 in patients with Cushing's syndrome
Authors: Leal‐Cerro Alfonso , Pumar Alfonso , Garcia‐Garcia Emlllo , Dieguez Carlos , Casanueva Felipe F. 
Published: March 2008

SummaryOBJECTIVE In patients with Cushing's syndrome there is a blunted OH response to all types of stimuli. Although Inferential data point towards a direct perturbation in the pituitary exerted by glucocorticoids, the bask mechanism is unknown. His‐d‐TRP‐ALA‐TRP‐d‐Phe‐Lys‐NH2 (GHRP‐6) is a synthetic hexapeptlde which releases GH by a direct pituitary effect through receptors other than GHRH receptors. Furthermore, the combined administration of GHRH and GHRP‐6 is able to induce a large OH discharge even in some pathological states such as obesity, associated with GH blockade.To gain further insight into the disrupted mechanisms of GH secretion, Cushing's syndrome patients were challenged with either GHRH, GHRP‐6 or GHRH together with GHRP‐6. A group of normal subjects was included for control purposes.DESIGN Three different tests were undertaken: (a) GHRH 100 μg I.v.; (b) GHRP‐6 100 μg I.v. and (c) GHRH plus GHRP‐6 100 μg I.v. of each; administered to each subject on different days, at least 4 days apart.PATIENTS Ten patients (8 women, 2 men) with untreated Cushing's syndrome, 9 Cushing's disease and 1 adrenal adenoma. Five healthy volunteers (3 women, 2 men) of similar ages served as a control group.MEASUREMENTS Plasma OH levels were measured by immunoradiometric assay.RESULTS The areas under the curve (AUC) of OH secretion (mean ± SEM In μ/1/120 mi) in the control subjects after each test were: GHRH, 1420 ± 330; GHRP‐6, 2278 ± 290 and GHRH plus GHRP‐6,7332 ± 592 (P < 0·05 vs each compound alone). The AUCs for Cushing's syndrome patients were: GHRH, 248 ± 165; GHRP‐6 530 ±170 and for GHRH plus GHRP‐6, 870 ± 258 (P < 0·05 vs GHRH alone). After the combined stimulus only one out of the ten patients with hypercortisolism showed a GH peak over 20 μ/l, while ail the controls had a peak over 04mU/l.CONCLUSIONS GHRP‐6 induced OH secretion as well as the OH discharge elicited by GHRH and GHRP‐6 are considerably reduced in Cushing's syndrome patients. This suggests that the main impairment of GH secretion in that pathological state resides at pituitary level.
Abnormal response of luteinizing hormone beta subunit to thyrotrophin‐releasing hormone in patients with non‐functioning pituitary adenoma
Authors: Gil‐dei‐Alamo Paloma , Pettersson Kim S. I. , Saccomanno Katia , Spada Anna , Faglia Giovanni , Beck‐Peccoz Paoio 
Published: March 2008

SummaryOBJECTIVE it has been suggested that the response of free β‐subunit of LH (LHβ) to TRH Is the most useful in‐vivo marker of gonadotroph adenomas in patients with non‐functioning pituitary adenomas (NFPA). The aim of the present study was to investigate LHβ secretion in patients with NFPA in whom other markers of gonadotroph adenomas, such as supranormal basal concentrations or responses of intact gonadotrophins to TRH, were absent.DESIGN AND PATIENTS Serum basal levels Of LHβ, LH and FSH were evaluated in 80 patients with NFPA showing normal levels of intact gonadotrophin, 20 with PRL‐secreting adenomas, 25 with OH‐secreting adenomas and 58 healthy subjects. Moreover, LHβ, LH, FSH and alpha‐subunit (α‐SU) were evaluated in 27 patients with NFPA In whom intact gonadotrophin responses to TRH were absent, 8 with PRL‐oma, 7 with GH‐oma and 17 healthy subjects before and 20,30 and 60 minutes after the intravenous administration of either 200 μg TRH or placebo. A response was considered present when serum LHβ increased by at least 50% above basal levels.MEASUREMENTS LHβ was evaluated using a new assay based on the sequestration of the combined and free α‐SU by an anti α‐SU blotinylated monoclonal antibody (MAb) and the subsequent measurement of the LHβ by an IFMA method employing two MAbs directed towards two different epitopes on LHβ. intact LH and FSH were assayed with an IFMA method and α‐SU with an IRMA method.RESULTS in basal conditions, no significant difference in the mean values of LHβ was observed among patients with different types of tumour and normal controls. In 9 of 27 (33%) patients with NFPA, TRH caused an abnormal elevation of serum LHβ (net increase 410 ± 403%, range 71‐1300) which was completely dissociated from changes in intact gonadotrophins. Of the 5 patients who had a TRH test repeated after transsphenoidal surgery, abnormal LHβ responses disappeared in 2 and were maintained in 3. Disappearance of LHβ response occurred only in patients in whom improvement of visual field and radiological imaging after adenomectomy was observed. in contrast, in ail patients with pituitary tumours other than NFPA and healthy subjects a response to TRH was absent (net increase ranging from 0 to 23%). immunofluorescence, performed on 14 NFPA removed from patients either responsive or unresponsive to TRH, showed a variable proportion of cells positive for LHβ, without a significant difference between the two groups.CONCLUSIONS These results indicate that measurement of basal LHβ is of poor value in the diagnosis of non‐functioning pituitary adenomas and the identification of gonadotroph adenomas among non‐functioning pituitary adenomas. Conversely, an abnormal response of free LHβ to TRH occurs in about a third of patients with low/normal basal gonadotrophins unresponsive to TRH stimulation.
Turner's syndrome with X‐isochromosome and Hashimoto's thyroiditis
Authors: de Kerdanet M. , Lucas J. , Lemee F. , Lecornu M. 
Published: March 2008

SummaryOBJECTIVE The higher frequency Of Hashimoto's thyroiditis in Turner's syndrome compared with the general population is well known. We have attempted to establish clearly the more frequent association of thyroiditis with the X‐isochromosome, since previous reports of this aspect have included only small numbers of patients.DESIGN Retrospective study of patients with Turner's syndrome investigated within the past 12 years.PATIENTS Sixty‐seven cases of Turner's syndrome were reviewed.MEASUREMENTS Peripheral blood leucocyte karyotype and screening for thyroid disturbances on the basis of clinical examination and laboratory evaluation (anti‐thyroglobulin and anti‐microsomal antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for each patient.RESULTS A diagnosis of thyroiditis, based on the association of positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical examinatlon, was established in 20·9% (14/67) of cases. A significantly higher frequency of thyroiditis was found among the patients presenting with an X‐isochromosome (57·3%, 9/16), compared to patients with other karyotypes (9·8%, 5/51) (P = 0·0001).CONCLUSIONS Our results, obtained by Investigation of a larger number of patients with an X‐isochromosome karyotype than in previous reports, confirm conclusively that patients with X‐isochromosome Turner's syndrome have an increased risk of developing thyroiditis.
Hyperthyroidism associated with metastatic thyroid carcinoma
Authors: Steffensen F. H. , Aunsholt N. Aa. 
Published: March 2008

SummaryWe report a patient with unilateral thyroid carcinoma, who developed hyperfunction of the thyroid gland during the metastatic progression of the thyroid carcinoma. Concurrently with this event, TSI increased and it is suggested that the differentiated aggressive metastatic thyroid neoplasm had initiated the autoimmune disorder leading to TSI production and thus to hyperplasia and hyperfunction of the thyroid resulting in hyperthyroidism.
Insulin sensitivity in non‐diabetic relatives of patients with non‐insulin‐dependent diabetes from two ethnic groups
Authors: Gelding Susan V. , Niththyananthan Ratnam , Chan Siew‐Pheng , Skinner Elizabeth , Robinson Stephen , Gray I. Peter , Mather Hugh , Johnston Desmond G. 
Published: March 2008

SummaryOBJECTIVE Non‐insulin‐dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non‐insulin‐dependent diabetes from two different ethnic groups.DESIGN Subjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test.PATIENTS Twenty‐four glucose‐tolerant first‐degree relatives of patients with non‐insulin‐dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes.MEASUREMENTS Insulin, proinsulin, glucose and intermediary metabolites were measured during a 75‐g oral glucose tolerance test. Insulin sensitivity was assessed using a 15‐minute insulin tolerance test (0.05 units/kg).RESULTS Asian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 ± 17 vs 40 ± 6 pmol/l, P < 0 05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 ± 9 vs 51 ± 4 μmol/l, P < 0.005), but fasting glucose and non‐esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements.The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non‐significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 ± 7 vs 139 ± 12μmol/l/min, P < 0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 ± 11 vs 160 ± 11 μmol/l/min).CONCLUSIONS First‐degree relatives of non‐insulin‐dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non‐insulin‐dependent diabetes in the Asian population.
The effect of low and high sodium diets on plasma atrial natriuretic factor, the renin‐aldosterone system and blood pressure in subjects with essential hypertension
Authors: McKnight J. A. , Roberts G. , Sheridan B. , Atkinson A. B. 
Published: March 2008

SummaryOBJECTIVE Increasing dietary sodium intake increases blood pressure in some subjects with essential hypertension. Atrial natriuretic factor (ANF) has a potential role in modifying these changes. The purpose of this study was to observe the blood pressure and plasma ANF responses to low and high sodium diets in subjects with essential hypertension to see if the plasma ANF and blood pressure responses were related.DESIGN An in‐patient study of subjects taking their normal diet (day 1), a 12 mmol sodium diet for 6 days and a 250 mmol diet for 6 days.PATIENTS Seven men with essential hypertension.MEASUREMENTS Continuous 24 hour urine collections were analysed for sodium excretion. Blood pressure was recorded at 0900, 1205 and 1700 h on days 1, 7 and 13. Blood was taken at 0900 h (fasting supine overnight) and at 1200 h (after 2 hours erect posture) on the above days for plasma ANF, plasma renin activity (PRA) and serum aldosterone.RESULTS Urinary sodium excretion was (mean±SEM) 11 ±1 mmol on day 5 of the low sodium diet, and 294 ± 17 mmol during the fifth day of the high sodium diet. Plasma ANF (supine and erect) was significantly lower (2 8±0 6, 1 6 ± 0 2 pmoi/l) on the low sodium diet when compared to the high sodium diet (8 6 ± 2 4, 5 0 ± 1 6 pmol/l (P < 0 05)). Supine and erect PRA and serum aldosterone were significantly higher on the low compared to the high sodium diet. Blood pressure responses were heterogeneous rather than bimodal. Mean arterial blood pressure was 107 ±3 mmHg on the low sodium diet and 111 ±4 mmHg on the high sodium diet (P<0 05). Changes of blood pressure did not correlate with the changes of plasma ANF.CONCLUSIONS Failure of plasma atrial natriuretic factor to rise with increasing dietary sodium did not therefore determine the blood pressure reponse to the change in dietary sodium. No link was established between plasma atrial natriuretic factor response and sodium sensitivity.
Oncoprotein immunoreactivity in human pituitary tumours
Authors: Raghavan Ravi , Harrison David , Ince Paul G. , James R. A. , Daniels Mark , Birch Peter , Caldwell G. I. , Kendall‐Taylor P. 
Published: March 2008

SummaryOBJECTIVE and DESIGN The immediate early gene locus AP‐1, incorporating the cellular oncogenes c‐fos and c‐jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc‐gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in‐vivo characteristics (hormone secretion, size and invasiveness) and an in‐vitro index of cell proliferation (Ki‐67 immunoreactivity). Thirty‐three human pituitary adenomas and 16 normal pituitary glands were examined.MEASUREMENTS Oncoprotein immunoreactivity was recorded as present (+) or absent (‐), and Ki‐67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted.RESULTS Oncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH‐secreting tumour in the series (1/33). Ki‐67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%.CONCLUSIONS Oncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki‐67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance remains to be elucidated.