bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pit‐1 gene expression in human pituitary adenomas using the reverse transcription polymerase chain reaction method
Authors: Yamada Shozo , Takahashi Michie , Hara Masayuki , Hattori Atsuhiko , Sano Toshiaki , Ozawa Yasunori , Shishiba Yoshimasa , Hirata Kazuaki , Usui Masaaki 
Published: November 2003

OBJECTIVE Previous studies of Pit‐1 expression in human pituitary tumours have produced conflicting results. We have studied expression of Pit‐1 mRNA in human pituitary adenomas, as well as in normal human and rat pituitaries, and results were compared with clinical, histological, and immunohistochemical features. In addition, expression of GH, PRL, and TSH‐β mRNA was also studied and compared with Pit‐1 gene expression. MATERIAL AND METHODS The adenomas consisted of 13 GH cell adenomas, 7 PRL cell adenomas, 3 TSH cell adenomas, 4 ACTH cell adenomas, and 10 clinically non‐functioning adenomas. Expression of the Pit‐1, its isoforms, and each hormone, was studied using the reverse transcription polymerase chain reaction. RESULTS Pit‐1 mRNA was expressed not only in normal human and rat pituitaries, but also in all GH, PRL and TSH cell adenomas. There was no correlation between Pit‐1 transcripts and biological behaviour or histological findings in these three types of adenoma, suggesting that Pit‐1 is generally required for the determination of cell phenotype but is insufficient for the regulation of hormonal activity and tumour growth in these pituitary adenomas. In addition, Pit‐1 was also expressed in some ACTH cell (2/4) and non‐functioning adenomas (7/10). Although there were no GH, PRL or TSH‐β transcripts in Pit‐1 mRNA‐negative ACTH cell and non‐functioning adenomas, PRL mRNA was detected in all Pit‐1 mRNA‐positive ACTH cell adenomas and GH, PRL and/or TSH‐β mRNA were found in four of seven Pit‐1 mRNA‐positive non‐functioning adenomas. In contrast, Pit‐1 mRNA was expressed without any GH, PRL, or TSH‐β transcripts in only three non‐functioning adenomas. These data suggest that expression of Pit‐1 mRNA in these two types of adenomas can be mainly attributed to the presence of GH, PRL and/or TSH‐β mRNA expressing cells and that true Pit‐1 transcripts found in non‐functioning adenomas may be a rare event. Moreover, there were two cases which expressed Pit‐1α mRNA, but failed to show other Pit‐1 isoform mRNA. There were, however, no clinical or histological differences between these two adenomas showing only Pit‐1α mRNA and the others expressing both Pit‐1α mRNA and other Pit‐1 isoform mRNA. CONCLUSIONS Pit‐1 mRNA was expressed not only in GH, PRL and TSH cell adenomas but also in other types of adenoma. However, it is suggested that expression of Pit‐1 mRNA in most ACTH cell and non‐functioning adenomas can be attributed to GH, PRL and/or TSH‐β mRNA expressing cells. Further studies are necessary to elucidate the role of Pit‐1 transcripts in the three non‐functioning adenomas without GH, PRL and/or TSH‐β mRNA expression.
The role of plasma renin activity in evaluating the adequacy of mineralocorticoid replacement in primary adrenal insufficiency
Authors: Fiad Tarek M. , Conway J. Donald , Cunningham Sean K. , McKenna T. Joseph 
Published: November 2003

BACKGROUND Elevation of plasma renin activity (PRA) is a feature of mineralocorticoid deficiency in patients with primary adrenal insufficiency. This study was designed to assess the usefulness of PRA as an index of adequacy of fludrocortisone (FC) replacement in patients with primary adrenal failure, paying particular attention to the variability in PRA levels during FC and glucocorticoid treatment. METHODS Twenty‐two patients with mineralocorticoid deficiency due to primary adrenal disease were studied at 3 time points: 8, 24 and 32 hours following the administration of FC replacement. Body weight, blood pressure while supine and erect, PRA, and plasma or serum levels of aldosterone, urea, sodium and potassium were measured at each time. The clinical and biochemical consequences of adjusting the FC dose were monitored in 5 patients with PRA levels above the range seen in normal subjects and in one hypokalaemic patient with normal PRA levels. RESULTS At 8 and 32 hours following FC administration, PRA levels were not significantly different. PRA levels were significantly higher at 32 hours following FC administration (4.7 ±1.1 nmol/l/h) than at 24 hours (4.2 ±1.1 nmol/l/h, mean ± SEM, P <0.05). At 8 and 32 hours following FC administration, potassium levels were similar. Potassium levels were significantly higher at 32 hours following FC administration (3.9 ± 0.1 mmol/l) than at 24 hours (3.6 ±0.1 mmol/l, P < 0.05). No changes in measurements of sodium, urea, mean supine and erect arterial pressure or body mass index were noted at the different study points. Attempted lowering of elevated PRA in 5 normokalaemic subjects by raising the dose of FC led to normalization of PRA in all of these patients but 2 developed hypokalaemia and oedema. Lowering of FC dose in one hypokalaemic patient with normal PRA levels led to the PRA levels rising to a supranormal value while the hypokalaemia was corrected. CONCLUSIONS These results indicate that when plasma renin activity is estimated in patients with primary adrenal insufficiency replaced with daily doses of fludrocortisone, the time of day of blood sampling is not critical. Lowering elevated plasma renin activity levels to normal in patients who were considered to be otherwise normal may lead to over‐treatment in some patients. Therefore, optimal fludrocortisone replacement may be associated with mildly elevated plasma renin activity levels. The information obtained by monitoring plasma renin activity adds little to the assessment of patients based on clinical evaluation and measurement of urea and electrolyte levels in blood.
Undiagnosed morbidity in adult women with Turner's syndrome
Authors: Garden Anne S. , Diver Michael J. , Fraser William D. 
Published: November 2003

OBJECTIVE Adult patients with Turner's syndrome are rarely followed up at specialist clinics after discharge from paediatric care but do have a predisposition to several long‐term medical problems. We have assessed the undiagnosed morbidity that exists among adult women with Turner's syndrome. PATIENTS A group of 32 women (age range 17–52 years; mean 25 years) attending a specialist out‐patient clinic. MEASUREMENTS Blood samples were obtained at the initial visit for lipid assessment, thyroid function, gonadal status and routine biochemical profile. Bone mineral density (BMD) was measured in 31 of the women. RESULTS Thirty‐one women were receiving some form of oestrogen replacement. Two were receiving T4 therapy. In 50%, total cholesterol was greater than 5.2 mmol/l (range 3.4–9.3 mmol/l, mean 5.8 mmol/l) and 28% had an abnormality of thyroid function tests. Two women were newly diagnosed as hypothyroid, 6 had compensated hypothyroidism and one was under‐replaced with T4. Lumbar spine BMD was below 100% of age matched reference range in 84% and below 75% in 26% of patients. Femoral neck BMD was below 100% of age matched reference range in 90% and below 75% in 10% of patients. CONCLUSIONS There is a high incidence of undiagnosed lipid, thyroid and bone mineral density abnormalities in the adult population with Turner's syndrome. Doctors caring for these women need to be aware of and look for the potential problems. Appropriate long‐term treatment should be commenced to help prevent the development of lipid, skeletal and thyroid abnormalities which may cause these patients major problems in the future.
Normal growth hormone secretion in growth hormone insufficient children retested after completion of linear growth
Authors: Wacharasindhu S. , Cotterill A.M. , Camacho‐Hübner C. , Besser G.M. , Savage M.O. 
Published: November 2003

OBJECTIVE The recognition of the syndrome of adult GH deficiency suggests that young GH deficient adults, deprived of GH replacement at completion of linear growth, may suffer effects of GH deficiency. We assessed GH reserve in young adults previously diagnosed as having idiopathic GH insufficiency, who were treated with hGH replacement (14 IU/m2/week) in childhood. DESIGN Eight patients (7 males, 1 female) diagnosed as having GH insufficiency by insulin tolerance test (ITT) in childhood (ages 8.5–15.6 years) were retested by ITT at completion of linear growth (ages 15.1–19.6 years), 3 months after discontinuation of hGH therapy. MEASUREMENTS GH reserve was measured during ITT at diagnosis and at retesting. Height velocity (HV) and HV SDS were calculated before and during GH therapy. RESULTS At diagnosis, the mean peak GH response to ITT was 10.5 ± 2.0 mU/l (range 7.7–13.6). At retesting, mean GH was 52.4 ± 33.2 mU/l (range 10.4–100), 7/8 subjects having peak GH levels greater than 15 mU/l. During hGH therapy mean HV increased from 4.0 ± 1.5 cm/year at diagnosis to 7.3 ± 1.9 cm/year during the 1st year (P = 0.004) and 6.9 ± 2.3 cm/year during the 2nd year (P = 0.02). Mean HVSDS increased from −1.6 ± 2.1 at diagnosis to 3.1 ± 2.9 during the 1st year (P = 0.004) and 2.2 ± 4.2 during the 2nd year (P = 0.05, NS) of treatment. CONCLUSIONS Seven out of 8 children diagnosed as having idiopathic GH insufficiency had normal GH secretion at completion of linear growth. Children with GH insufficiency cannot be assumed to become GH deficient adults and should not continue on GH therapy into adult life without reinvestigation. All who were GH insufficient children should be retested at completion of linear growth to identify those who are truly GH insufficient adults and may benefit from replacement therapy.
Sleep apnoea in treated acromegaly: relative frequency and predisposing factors
Authors: Rosenow Felix , Reuter Stefan , Deuß Ulrich , Szelies Brigitte , Hilgers Ralf‐Dieter , Winkelmann Werner , Heiss Wolf‐Dieter 
Published: November 2003

OBJECTIVES Sleep apnoea is common in active acromegaly. It is associated with increased morbidity and mortality but can be treated effectively. The objective of this study was to determine the largely unknown relative frequency of, and the predictive factors for, sleep apnoea in treated acromegalic patients. DESIGN Retrospective cohort study. SETTING Tertiary referral hospital. PATIENTS Fifty‐four of 100 patients with treated acromegaly. If sleep apnoea had been diagnosed before acromegaly, the patient was excluded. MEASUREMENTS Sleep studies (using the MESAM‐4 device measuring oxyhaemoglobin saturation, heart rate, snoring sounds and body position to determine presence and severity of sleep apnoea); GH and IGF‐I levels; body mass index, neck and index‐finger circumference; daytime symptoms of sleep apnoea, duration of acromegaly before treatment, shoe and neck‐size difference since beginning of acromegaly; age, sex and treatment modes of acromegaly. RESULTS The relative frequency of sleep apnoea was 39% in the 54 patients with sleep studies and at least 21% in the entire study population of 100 patients. In patients with sleep apnoea, statistically significant higher values were observed for GH (P = 0.002), IGF‐I (P = 0.029), age (P = 0.014) and neck circumference (P = 0.016). An index‐finger circumference of ≥8.5 cm was associated with a significantly higher desaturation index (P = 0.012, Mann–Whitney Itest). Adenomectomy had been performed significantly less frequently in patients with sleep apnoea (P < 0.001, χ2 test). The body mass index was non‐significantly higher in the patients with sleep apnoea. CONCLUSIONS The relative frequency of sleep apnoea in patients with treated acromegaly is at least 21%. Parameters of predictive value for the presence of sleep apnoea in this population are neck and index‐finger circumference as measures of soft tissue hypertrophy, age, GH and IGF‐I levels, and whether or not operative therapy was applied.
Urinary free cortisone and the assessment of 11β‐hydroxysteroid dehydrogenase activity in man
Authors: Palermo Mario , Shackleton Cedric H. L. , Mantero Franco , Stewart Paul M. 
Published: November 2003

OBJECTIVE Two isoforms of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) catalyse the interconversion of cortisol to hormonally inactive cortisone; defects in the 11β‐HSD2 isoform result in hypertension. The kidney, expressing high levels of 11β‐HSD2, is the principal source of cortisone in man. We have validated the measurement of urinary free cortisone (UFE) excretion in normals and in patients with disorders of the pituitary‐adrenal axis in an attempt to more accurately measure the activity of 11β‐HSD2 in vivo. SUBJECTS Forty‐one normal adults, 12 normal children <12 years of age, 15 patients with Cushing’s syndrome, 12 with hypopituitarism on replacement hydrocortisone, 12 with the syndrome of apparent mineralocorticoid excess (AME) and 7 volunteers consuming liquorice. MEASUREMENTS A complete 24‐hour urine collection was analysed by gas chromatography/mass spectrometry for ‘A‐ring’ reduced cortisol and cortisone metabolites, i.e. tetrahydrocortisols (THF and allo‐THF) and tetrahydrocortisone (THE). In addition, urinary free cortisol (UFF) and urinary free cortisone were quantified using deuterium‐labelled internal standards. RESULTS In normal adults and children, UFE excretion exceeded that of UFF (UFF 30.4 ± 2.4 μg/24h (mean ± SE), UFE 54.6 ±4.1 μg/24h, adults) (for conversion to nmol/24h multiply E by 2.78 and F by 2.76 respectively). Thus the normal UFF/UFE ratio was 0.54 ± 0.05 in contrast to the (THF+allo‐THF)/THE ratio of 1.21 ± 0.06. UFE excretion was normal in hypopituitary patients on replacement hydrocortisone. Although UFE was elevated in all forms of Cushing’s syndrome, the UFF/UFE ratio was grossly elevated in patients with the ectopic ACTH syndrome (14.0 ± 6.7, n=6). UFE was below the lower limit of the assay (<1 μg/24h) in most patients with the so‐called type 1 variant of AME and significantly reduced in 4 patients described as having the type 2 variant of AME (10.5 ± 3.5 μg/h, P<0.05) and in 7 volunteers consuming liquorice (26.8 ± 10.0 μg/24h, P<0.01). In ectopic ACTH syndrome, AME, and liquorice ingestion the UFF/UFE ratio was more deranged than the (THF+ allo‐THF)/THE ratio. CONCLUSION In normals the discrepant THF + allo‐THF/THE and UFF/UFE ratio suggests that much more of the UFE is derived from the kidney. Reduction in UFE excretion is seen following liquorice ingestion and in both variants of AME, though it is more profound in AME1. The high UFF/UFE ratio in the mineralocorticoid excess state seen in the ectopic ACTH syndrome is compatible with substrate‐saturation of renal 11β‐HSD2. The measurement of UFE and the UFF/UFE ratio is a significant advance in the analysis of human 11β‐HSD activity in vivo; in particular, the UFF/UFE ratio appears to be a more sensitive index than the (THF+allo‐THF)/THE ratio of renal 11β‐HSD2 activity.
HLA DRB1/DQA1/DQB1 haplotype determines thyroid autoimmunity in patients with insulin‐dependent diabetes mellitus
Authors: Chuang L.‐M. , Wu H.‐P. , Chang C.‐C. , Tsai W.‐Y. , Chang H.‐M. , Tai T.‐Y. , Lin B. J. 
Published: November 2003

OBJECTIVE Thyroid autoimmunity is frequently associated with insulin‐dependent diabetes mellitus (IDDM). The genetic factors which contribute to thyroid autoimmunity and IDDM have been described but vary between different races. We have therefore investigated the effect of class II HLA genes at both loci and the HLA haplotypes on the presence of autoimmunity in patients with IDDM in Taiwan. SUBJECTS AND MEASUREMENTS Eighty‐three patients with IDDM and 105 unrelated normal controls were recruited for the measurement of thyroid autoantibodies and for genotyping of HLA DRB1, DQA1 and DQB1 by polymerase chain reaction‐based DNA typing techniques. RESULTS Among 83 patients with IDDM, 23 (27.7%) were positive for antithyroid autoantibodies. Compared to those without thyroid autoimmunity, there was a female preponderance for IDDM with thyroid autoimmunity (female: male, 3:20 vs 29:31). Among the DR specificities, DR6 was associated with a weak protective effect against thyroid autoimmunity in IDDM patients. Upon detailed analysis of class II HLA haplotypes, the DRB1*0301/DQA1*0501/DQB1*0201 haplotype was found to be associated with an increased risk of IDDM regardless of thyroid autoimmunity, while DRB1*0405/DQA1*0301/DQB1*0401 was significantly increased only in the IDDM patients with thyroid autoimmunity. IDDM individuals with the HLA DRB1*0405/DQA1*0301/DQB1*0302 haplotype were not at risk of thyroid autoimmunity. CONCLUSIONS Our data indicated that there was a generalized genetic factor within or associated with the DRB1*0301/DQA1*0501/DQB1*0201 haplotype, and a more restricted effect with the DRB1*0405/DQA1*0301/DQB1*0401 haplotype which led to thyroid autoimmunity in patients with insulin‐dependent diabetes mellitus.
Growth hormone, insulin‐like growth factor I and its binding proteins 1 and 3 in last trimester intrauterine growth retardation with increased pulsatility index in the umbilical artery
Authors: Larsen Torben , Main Katharina , Andersson Anne Marie , Juul Anders , Greisen Gorm , Skakkebæk Niels Erik 
Published: November 2003

OBJECTIVE The interrelationships between maternal hormone levels and placental dysfunction in mothers bearing children with intrauterine growth retardation remain unclear. We have examined some endocrinological aspects of intrauterine growth retardation and, in particular, tested whether low levels of GH and IGF‐ I in maternal serum are associated with direct evidence of placental dysfunction. DESIGN Prospective, descriptive and comparative. PATIENTS Women with singleton pregnancies: 48 with a small for gestation fetus (SGA) (estimated fetal weight less than −1.5 standard deviation scores) and 28 with an appropriate for gestation fetus (AGA). MEASUREMENTS Maternal serum GH, IGF‐I, IGFBP‐1 and 3 were determined, and fetal weight and umbilical artery pulsatility index (PI) was estimated by ultrasonography and Doppler ultrasound at 33 weeks gestational age. RESULTS Serum IGF‐I was lower in the SGA group (246  vs 297 μg/l, P = 0.03) but GH and IGFBP‐1 and ‐3 did not differ between the groups. In the 16 SGA pregnancies with increased PI, IGF‐I concentration was low (218 μg/l, quartiles 149–265), whereas in the 32 with normal PI, IGF‐I was 269 μg/l, quartiles 219–382. Serum IGFBP‐1 was increased in the high PI group compared to the normal PI group (161 μg/l vs 113, P = 0.05). CONCLUSION M aternal serum IGF‐I concentration was lower in small for gestational age pregnancieswith increased pulsatility of the umbilical artery blood flow, compared to small for gestational age pregnancies with normal umbilical blood flow, which in turn was close to the IGF‐I concentration in appropriate for gestational age pregnancies. Growth hormone concentrations did not differ among the groups.
Serum levels of insulin‐like growth factor I and insulin‐like growth factor‐binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle‐aged men
Authors: Erfurth Eva Marie , Hagm ar Lars , Sääf Maria , Hall Kerstin 
Published: November 2003

OBJECTIVE Administration of testosterone has been reported to increase serum levels of IGF‐I in men with isolated hypogonadotrophic hypogonadism. An inverse relation between serum IGF‐I and sex hormone binding globulin (SHBG) is seen in GH deficient children. The biological action of IGF‐I is thought to be influenced by binding proteins, one of which is insulin‐like growth factor‐binding protein‐1 (IGFBP‐1), which is not only a carrier protein but also actively regulates the cellular actions of IGF‐I. These observations suggest associations between IGF‐I, IGFBP‐1, testosterone and SHBG in serum. The aim of the present study was to investigate these associations in normal healthy men. DESIGN AND PATIENTS The associations between the serum levels of IGF‐I and IGFBP‐1 on one hand, and testosterone and SHBG on the other were investigated in 38 normal healthy young and middle‐aged men. RESULTS Serum levels of IGF‐I decreased both with increasing age (r = − 0.66, P < 0.001) and increasing SHBG levels (r = − 0.46, P = 0.002), but increased with increasing free testosterone (f‐testosterone) (r = 0.42, P = 0.005). These associations remained after mutual simultaneous adjustments in a multiple regression analysis. IGFBP‐1 did not display any significant univariate correlation with age (r = − 0.25, P = 0.06) or SHBG (r = 0.18, P = 0.14), but showed a significant positive correlation with both f‐testosterone (r = 0.42, P = 0.004), and total testosterone (t‐testosterone) (r = 0.39, P = 0.008). In a multiple regression analysis IGFBP‐1 was positively correlated with both SHBG and f‐testosterone, but not with t‐testosterone. CONCLUSION The present study suggests that among healthy young and middle‐aged men, there is an association between serum levels of free‐testosterone and SHBG on the one hand, and serum IGF‐I and IGFBP‐1 on the other.
Predicting the growth response to growth hormone in patients with intrauterine growth retardation
Authors: Frank Graeme R. , Cheung Pik‐To , Horn Jo Ann , Alfaro Mary Pat , Smith Eric P. , Chernausek Steven D. 
Published: November 2003

OBJECTIVE Human GH treatment of short children who had intrauterine growth retardation (IUGR) results in a highly variable growth response. The object of this study was to test the hypothesis that differences in responsiveness to exogenously administered GH might reflect differences in endogenous GH secretion or sensitivity. DESIGN Prospective study evaluating the growth response to GH therapy in short individuals with prior IUGR. PATIENTS Ten short, prepubertal children with prior IUGR were studied. Mean age was 6 years (3.39–8.61). Mean bone age was 4.6 years (2.3–8.3). Mean body mass index was 13.2 kg/m2 (9.9–14.0; normal 13.5–19.0). MEASUREMENTS  Overnight spontaneous GH release was measured using a constant withdrawal pump and stimulated GH release was measured following clonidine (0.15 mg/m2) administration. IGF‐I concentrations were measured at baseline and 12, 24, 36 and 48 hours after sequential doses of GH (0.05 and 0.2 mg/kg/dose) given 48 hour apart. Patients were treated with GH (0.125 mg/kg three times a week) and growth response was assessed. In the second and third year, attempts were made to improve the growth rate by nutritional supplementation and increasing the dose of GH to 0.25 mg/kg three times a week. RESULTS All patients had normal integrated nocturnal GH secretion (>3 μg/l, 6mU/l) and normal peak GH secretion in response to clonidine (>7 μg/l). In the first year of the trial, mean growth velocity (GV) increased from 5.39 cm/year ± 0.29 to 7.32 cm/year ± 0.39 (P = 0.004). Changes in GV correlated inversely with integrated GH (r = − 0.69; P = 0038), baseline IGF‐I concentration (r =  − 0.88; P = 0.002) and baseline GV‐SDS (r =  − 0.68; P =  0.043). There was no correlation between change in GV and GH binding protein, baseline height SDS or age. The effect of GH waned in the second year, but tended to remain greater than the pretreatment growth rate (6.54 ± 0.49 vs 5.53 cm/year ± 0.29; P  = 0.09). No significant advancement of bone age over chronological age was observed over the first 2 years. Increasing nutritional intake by 17% did not result in significant weight gain nor increase in height velocity. Doubling the dose of GH in the second or third year did not result in a significant increase in GV. CONCLUSION  The variable response to GH therapy in short children with a history of intrauterine growth retardation may partly reflect relative sufficiency or insufficiency of GH. Baseline IGF‐I levels and baseline growth velocity appear to be useful and practical predictors of response to GH.