bluuebunny/crossref_metadata_2025 huggingface dataset:
Postpartum thyroid dysfunction in women with normal thyroid function during pregnancy
Authors: Sakaihara Mitsuo , Yamada Hideto , Kato Emi Hirayama , Ebina Yasuhiko , Shimada Shigeki , Kobashi Gen , Fukushi Masaru , Fujimoto Seiichiro
Published: March 2003

OBJECTIVE

The aim of this study was to establish the risk of postpartum thyroid dysfunction (PPTD) in women who had normal thyroid function during pregnancy and no history of thyroid disease.

DESIGN

Four thousand and twenty‐two consecutive pregnant women were screened for thyroid function and antithyroid antibody. Among women with normal thyroid function during pregnancy and no history of thyroid disease, thyroid function were assessed in 131 of 388 antithyroid antibody positive (Group I) and 1030 of 3503 antibody negative (Group II) women at 1 and 3 months postpartum. In Group I women who experienced PPTD, the frequency of later manifestation of Hashimoto's disease was compared according to titres of antithyroid antibodies.

MEASUREMENTS

Blood samples in early pregnancy, and at 1 month and 3 months postpartum were obtained using the dried blood spot method. Levels of fT4 were measured by RIA, TSH by fluoroimmunoassay or ELISA, antimicrosome antibody (AMC) and antithyroglobulin antibody (ATG) by indirect agglutination reactions.

RESULTS

The prevalence of PPTD at 1 month and 3 months postpartum were found to be 6.9% and 21.3% in Group I, and 5.3% and 4.7% in Group II, respectively. The prevalence of PPTD was significantly higher at 3 months postpartum in Group I (P < 0.05). 27.3% of women with PPTD in Group I were later found to have Hashimoto's disease and 9.1% manifested hypothyroidism without goitre. A high AMC titre (≥ 25 600) at 3 months postpartum in women with PPTD was related to the manifestation of Hashimoto's disease. AMC titres of PPTD women and women who developed Hashimoto's disease were significantly higher than those of control women who did not experience PPTD.

CONCLUSION

A high prevalence of PPTD was found in women with antithyroid antibodies who were euthyroid during pregnancy. Prolonged follow‐up of the subsequent thyroid function may be needed in women who experience PPTD and/or show a high titre of antithyroid antibody.
Ectopic ACTH syndrome caused by pulmonary carcinoid tumourlets
Authors: Povedano S. Tofé , Pastor C. Villar , Seoane C. Pérez , Reina L. Jiménez , Moreno M. A. Gálvez , Ortega R. Palomares , López‐Rubio F. , López P. Benito
Published: March 2003

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3‐cm lung nodule became apparent on routine chest X‐ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.
The effect of the menopause on prolactin levels in patients with hyperprolactinaemia
Authors: Karunakaran S. , Page R. C. L. , Wass J. A. H.
Published: March 2003

Microprolactinomas have been reported to resolve spontaneously after pregnancy and there have been suggestions that oestrogen therapy increases the size of microprolactinomas. Little is known, however, about the effect of the menopause in patients previously known to be hyperpro‐lactinaemic. The aim of this study was to find out if pregnancy or the menopause leads to an alteration in prolactin levels.

We conducted a retrospective study of 148 case notes of patients with hyperprolactinaemia and microprolactinomas treated at the Radcliffe Infirmary during the period 1976–96.

Sixty‐nine female patients who had not had pituitary surgery as treatment for microprolactinoma were used as a control group. None of this group became pregnant or reached the menopause. They were compared with 25 female patients who became pregnant, 11 who became menopausal and 11 who were male. Subjects were excluded from the analysis if there were no follow‐up data off dopamine agonist treatment or if they were surgically cured. Data were gathered on demographic parameters, treatment given, scan abnormalities, prolactin levels at diagnosis and last follow up, prolactin levels pre‐ and postpregnancy as well as pre‐ and postmenopause. The pregnancy, postmenopausal and male patient groups were compared with the control group and each other to see if they had a higher frequency of normalization of their prolactin levels during follow up. Various factors were examined as possible variables for the normalization of prolactin, including the detection of scan abnormalities at diagnosis, prolactin levels at diagnosis as well as treatment with dopamine agonists and duration of follow up.

Forty‐five percent of the menopausal group, 24% of the pregnancy group and 18% of the male group subsequently normalized their prolactin levels during the period of the study in comparison with 7% of the control group. The menopausal groups had a significantly higher chance of normalizing their prolactin compared to the control group (P < 0·005), whilst the pregnancy group showed a non‐significant trend towards normalizing their prolactin (P = 0·06). The detection of scan abnormalities, treatment with dopamine agonist therapy and duration of follow up were not associated with normalization of prolactin levels.

Female patients with hyperpro‐lactinaemia who pass through the menopause have a significant chance of normalizing their prolactin levels. Females who pass through pregnancy may have a higher chance of normalizing their prolactin levels. The menopause is an indication for reassess‐ment of the need to continue to treat hyperpro‐lactinaemia and microprolactinoma.
Growth restriction in dexamethasone‐treated preterm infants may be mediated by reduced IGF‐I and IGFBP‐3 plasma concentrations
Authors: Bloomfield Frank H. , Knight David B. , Breier Bernhard H. , Harding Jane E.
Published: March 2003

OBJECTIVE

Preterm infants receiving dexamethasone for respiratory morbidity frequently suffer restricted growth. The aim of this study was to investigate the interactions between dexamethasone treatment regimen and circulating IGFBP‐3 and IGF‐I levels, and the associations between these variables and linear growth rate in preterm babies receiving dexamethasone for chronic lung disease of prematurity.

DESIGN

A randomised, unblinded, clinical trial of two different courses of dexamethasone: a 42‐day tapering course (the long course) and a repeatable 3 day pulse course.

PATIENTS

Forty preterm infants (19 in the pulse group, 21 in the long group) with a birthweight ≤ 1250 g who were ventilated at 7 days of age.

MEASUREMENTS

Lower leg length was measured thrice weekly by knemometry, and IGFBP‐3 and IGF‐I levels were measured prior to commencing treatment, at 14 and 42 days of treatment and at 36 weeks postmenstrual age (PMA). Interactions between variables were analysed by stepwise regression analysis and analysis of covariance (ancova). Associations between variables were assessed by correlation coefficients.

RESULTS

In an ancova, mean daily dose of dexamethasone/kg (MDDD) and treatment group both significantly influenced IGFBP‐3 levels (P = 0·0009 and P = 0·017, respectively), and tended to influence IGF‐I levels similarly (P = 0·098 and P = 0·07). MDDD also significantly influenced mean daily increase in lower leg length (MDILL; P < 0·01). IGFBP‐3 and IGF‐I levels were significantly related to MDILL (ancova: P < 0·01).

The correlation coefficients for IGFBP‐3 and IGF‐I levels and MDILL were 0·2 and 0·3 (both P < 0·0001), respectively. IGFBP‐3 and IGF‐I levels were highly correlated (r2 = 0·52, P < 0·0001) and both increased significantly with increasing PMA (P < 0·0001). IGF‐I levels were higher in females (P = 0·036).

CONCLUSION

This study provides evidence that the growth‐restricting effects of dexamethasone may be mediated, at least in part, via suppression of the IGF axis. Both dexamethasone dose and treatment regimen influence circulating IGF‐I and IGFBP‐3 levels, and both are important in inducing growth restriction.
Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight
Authors: Phoojaroenchanachai Meta , Sriussadaporn Sutin , Peerapatdit Thavatchai , Vannasaeng Sathit , Nitiyanant Wannee , Boonnamsiri Vipa , Vichayanrat Apichati
Published: March 2003

Hyperthyroidism in pregnancy occurs with a prevalence of 0·05–0·2% and has been shown to affect neonatal outcomes. Fetal weight increases markedly during the third trimester of pregnancy. This retrospective study was performed to examine the effect of maternal hyperthyroidism during late pregnancy on neonatal birth weight (NBW).

Medical and obstetric records of 293 pregnant women with present and past history of hyperthyroidism were retrospectively reviewed.

There were 188 records of 181 patients with adequate data for inclusion in the analysis. The patients were divided into two groups according to the maternal thyroid function during the third trimester of pregnancy: hyperthyroidism (HT; 35 cases) and euthyroidism (ET; 153 cases).

Maternal thyroid function tests were periodically evaluated before and during the third trimester of pregnancy. Neonatal thyroid function tests and birth weight of the newborn infants were also assessed.

There was no significant difference of maternal age between HT and ET groups mean ± SD (27·6 ± 5·5 vs. 29·2 ± 5·4 years). The NBW of the HT group was not significantly different from that of the ET group (2880 ± 590 vs. 3019 ± 426 g). However, the prevalence of infants with low birth weight (LBW) defined as NBW of lower than 2500 g in HT group was 22·9% which was significantly higher than the 9·8% in the ET group (P = 0·039, OR = 2·7, 95%CI = 1·1–7·1) and 9·7% of infants born to healthy mothers at Siriraj Hospital (control group) between 1991 and 1995 (P = 0·01, OR = 2·7, 95%CI = 1·3–6·1). The 90% CI for the true difference between the prevalence of LBW infants born to ET and HT mothers was 0·7–25·4. There was no significant difference in the prevalence of LBW infants in ET and control groups. Multiple logistic regression analyses showed that maternal hyperthyroidism during the third trimester of pregnancy was an independent factor associated with increased prevalence of LBW infants (P = 0·037, OR = 4·1, 95%CI = 1·1–15·0).

Maternal hyperthyroidism during the third trimester of pregnancy independently increases the risk of low birth weight by 4·1‐fold. Appropriate management of hyperthyroidism throughout pregnancy is essential in the prevention of this undesirable neonatal outcome.
Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism
Authors: Homsanit Mayuree , Sriussadaporn Sutin , Vannasaeng Sathit , Peerapatdit Thavatchai , Nitiyanant Wannee , Vichayanrat Apichati
Published: March 2003

Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease.

Seventy‐one patients with newly diagnosed Graves' disease were studied.

Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period.

There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3·54 ± 0·72 vs. 5·49 ± 2·74 nmol/l, P < 0·05) through the end of the study (2·22 ± 1·42 vs. 4·30 ± 1·78 nmol/l, P < 0·05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101·67 ± 54·05 vs. 176·32 ± 66·92 nmol/l, P < 0·05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77·1% vs. 19·4%). Hypothyroidism was observed in 31·4% of the patients in the MMI group but not in the PTU group.

During 12‐weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once‐daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.
Increased serum inhibin B levels after varicocele treatment
Authors: Pierik Frank H. , Abdesselam Salem Aït , Vreeburg Jan T. M. , Dohle G. R. , De Jong Frank H. , Weber Robertus F. A.
Published: March 2003

OBJECTIVE Inhibin B is secreted by Sertoli cells in response to FSH and is the major feedback regulator of FSH secretion in man. The serum inhibin B level has emerged as a good marker of spermatogenesis and Sertoli cell function. Varicocele has been associated with infertility and disturbed spermatogenesis. We have studied the effect of varicocele treatment on serum inhibin B levels, with the aim of investigating the effect on spermatogenesis and the involvement of the Sertoli cell in varicocele pathophysiology.

DESIGN AND PATIENTS In a pre–post test design, the effect of varicocele surgery on inhibin B levels was studied in 30 infertile men.

MEASUREMENTS Endocrinology (inhibin B, FSH, LH, SHBG and testosterone) and semen analysis (sperm concentration, motility and morphology).

RESULTS In men receiving varicocele treatment, a significant increase in serum inhibin B levels was observed from 133·9 ± 13·4 pretreatment to 167·8 ± 16·1 ng/l after treatment (mean ± SEM, P < 0·0001). No significant changes were observed in serum levels of FSH, LH and testosterone. The serum SHBG level decreased from 32·9 ± 3·5 to 28·6 ± 3·4 nmol/l (mean ± SEM, P = 0·04) and the free androgen index was significantly increased from 66 ± 5·9 pretreatment to 85 ± 6·8 after treatment (P = 0·02, mean ± SEM). Semen analysis showed a significant improvement in sperm concentration, from 6·5 ± 1·9 pretreatment to 19·3 ± 4·9 × 106/ml after treatment (P = 0·003, mean ± SEM), and in sperm motility from the baseline level of 17 ± 3 to 32 ± 4% after treatment (P = 0·001, mean ± SEM).

CONCLUSIONS Varicocele treatment can increase serum inhibin B levels, indicating improvement of spermatogenesis and Sertoli cell function. This finding suggests that the pathophysiology of varicocele involves impairment of Sertoli cell function or a different distribution of germ cell stages.
Tissue insulin sensitivity and body weight in polycystic ovary syndrome
Authors: Marsden Philippa J. , Murdoch Alison P. , Taylor Roy
Published: March 2003

OBJECTIVE Polycystic ovarian syndrome (PCOS) and obesity both affect insulin sensitivity. This study was designed to investigate the biochemical indices of PCOS and tissue insulin sensitivity in groups of lean and obese women with clinically equivalent degrees of the syndrome, relative to control subjects.

DESIGN A prospective study of in vivo parameters and in vitro study of adipocytes to assess insulin sensitivity.

PATIENTS Six lean and 14 overweight patients fulfilling formal diagnostic criteria for PCOS were studied. The degree of hirsutism and amenorrhoea was similar in each group. Eight control subjects were also studied.

MEASUREMENTS Endocrine and metabolic parameters were measured in lean and overweight patients with PCOS and control subjects. In vitro studies of adipocyte insulin receptor binding and adipocyte insulin action were performed.

RESULTS The mean plasma LH level was elevated in both groups of PCOS but was significantly higher in the lean group (LH levels were 25·1 ± 3·1 and 14·5 ± 1·6 iu/l in lean PCOS and obese PCOS, respectively (P = 0·01)). There was a strong inverse correlation between BMI and LH levels (R = − 0·70, P = 0·001). Fasting insulin levels were elevated in both lean and obese groups (11·5 ± 2·8 and 26·8 ± 8·1 mU/l, respectively; P = 0·068). Mean serum testosterone and serum androstenedione levels were also elevated in PCOS compared to control subjects but there was no difference between the two groups of PCOS subjects. Insulin receptor binding in amenorrhoeic subjects with PCOS was low in both lean and obese patients with PCOS but was not significantly different between the two groups (0·79 ± 0·17% and 0·66 ± 0·07% per 10 cm2 cell membrane, respectively). Maximally insulin‐stimulated rates of 3‐O‐methylglucose transport were low in both groups compared to previously studied normal subjects (0·96 ± 0·21 and 0·64 ± 0·07 pmol per 10 cm2 membrane in lean and obese PCOS subjects, respectively; P = NS).

CONCLUSIONS  Lean subjects with a given phenotypic expression of PCOS have an equivalent degree of tissue insulin resistance compared to obese PCOS subjects. This implies that the insulin resistance may be a primary feature of PCOS. If this is so, a similar clinical degree of the syndrome may be brought about by genetically determined insulin resistance in lean subjects or by insulin resistance which is secondary to obesity.
Gonadotrophin releasing hormone agonist treatment with or without recombinant human GH in adopted children with early puberty
Authors: Mul D. , Oostdijk W. , Waelkens J. J. J. , Schulpen T. W. J. , Drop S. L. S.
Published: March 2003

BACKGROUND Early onset of puberty is frequently observed in adopted children. During treatment with a gonadotrophin releasing hormone agonist (GnRHa), a decrease in height velocity (HV) precludes height gain.

OBJECTIVE AND DESIGN We studied the effect of the addition of GH to GnRHa treatment in a 3‐year prospective randomized trial in 30 adopted children with early puberty.

PATIENTS Mean age (SD) at start of treatment was 9·6 (0·9) years in girls and predicted adult height (PAH) using a segmented bone age (BA) assessment method was 148·0 (5·3) cm.

RESULTS HV decreased gradually in both groups with a higher HV in the group with GH addition (group B). No significant difference between the rates of bone maturation [change in bone age (ΔBA)/change in chronological age (ΔCA)] of both treatment groups was observed. After 3 years of treatment, PAH increase was 5·7 (3·8) cm in group A (GnRHa alone) and 10·1 (3·8) cm in group B (P < 0·01). IGF‐I levels were higher in group B. HV decreased slowly in both groups during treatment, unlike stabilization of IGF‐I levels.

CONCLUSION We conclude that, after 3 years of treatment, the addition of GH to GnRHa results in higher HV and a significant increase in PAH compared to GnRHa alone.
Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF‐I and IGFBP‐1 in type 1 diabetes
Authors: Hedman C.A. , Orre‐Pettersson A.‐C. , Lindström T. , Arnqvist H.J.
Published: March 2003

OBJECTIVE IGF‐I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF‐I and IGFBP‐1 than that seen during treatment with conventional human insulin (regular insulin).

DESIGN AND PATIENTS Twelve patients with type 1 diabetes, age 47·8 ± 2·4 years (mean ± SEM), body mass index 26·5 ± 1·0 kg/m2, diabetes duration 30·5 ± 3·2 years participated in this open label randomized cross‐over study. IGF‐I and IGFBP‐1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF‐I was measured fasting while IGFBP‐1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.

RESULTS Lispro gave a marked insulin peak of 135 ± 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0·01). Plasma IGF‐I concentration was 78·8 ± 10·9 µg/l on lispro and 82·3 ± 10·5 µg/l on human regular insulin (not significant). AUC for IGFBP‐1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0·006) but glycosylated haemoglobin (HbA1c) was 6·4 ± 0·2% on both therapies.

CONCLUSIONS Our results indicate that the effect of lispro on IGF‐I and IGFBP‐1 in patients with type 1 diabetes does not differ from that of human regular insulin.
Currently used growth‐promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents‡
Authors: Fors Hans , Bjarnason Ragnar , Wirén Lena , Albertsson‐Wikland Kerstin , Bosaeus Ingvar , Bengtsson Bengt‐Åke , Johannsson Gudmundur
Published: March 2003

BACKGROUND AND AIMS The need for continued GH replacement in patients with childhood‐onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years.

PATIENTS Forty adolescents (aged 16–21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re‐examined with the same protocol after 1 and 2 years. Twenty‐one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS).

RESULTS At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2–L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy‐terminal cross‐linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy‐terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls.

CONCLUSIONS After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH‐deficient children to final height results in normal BMD.
Elevation of soluble E‐selectin levels following gestational diabetes is restricted to women with persistent abnormalities of glucose regulation
Authors: Lawrence Natasha J. , Kousta Eleni , Penny Anna , Millauer Barbara , Robinson Stephen , Johnston Desmond G. , McCarthy Mark I.
Published: March 2003

objective Increased levels of the soluble adhesion molecule sE‐selectin have been reported in normoglycaemic women with previous gestational diabetes but not in other groups at increased risk of future type 2 diabetes. To explore the basis for these discrepant findings, we studied the relationship between sE‐selectin and glucose regulation in a large group of women with previous gestational diabetes.

design Comparison of sE‐selectin levels between a study cohort ascertained on the basis of recent gestational diabetes and suitable control subjects.

patients One hundred and forty women with recent gestational diabetes (104 European, 20 South Asian and 16 Afro‐Caribbean) and 125 normoglycaemic control women (90 European, 19 South Asian and 16 Afro‐Caribbean).

measurements sE‐selectin, fasting lipids, insulin and current glucose regulation status.

results There was no overall difference in sE‐selectin levels between women with a history of gestational diabetes and control women among the 3 ethnic groups. European post‐GDM women with abnormal glucose regulation postpartum (n = 30) had higher sE‐selectin than control women (67 (54–91) ng/ml vs. 57 (43–75) ng/ml, P= 0·049). There was no difference in sE‐selectin between normoglycaemic European women with a history of gestational diabetes (n = 74) and control women, even though the former displayed metabolic abnormalities predictive of diabetes. In those European post‐GDM women with normal glucose regulation postpartum, sE‐selectin levels were negatively correlated with time since delivery (r = –0·25, P= 0·04), suggesting that the previously described elevation of sE‐selectin following GDM pregnancies slowly resolves postpartum. There was no correlation between sE‐selectin levels and features of insulin resistance.

conclusions In contrast to previous findings, this larger study does not support a role for sE‐selectin as a marker, independent of prevailing glucose levels, of early metabolic abnormalities or future diabetes risk in women with previous gestational diabetes.
Galanin in human pituitary adenomas: frequency and clinical significance
Authors: Leung Betty , Lismaa Tiina P. , Leung Kin‐Chuen , Hort Yvonne J. , Turner Jennifer , Sheehy John P. , Ho Ken K. Y.
Published: March 2003

objectives Galanin (GAL) is a neuropeptide widely expressed in the central and peripheral nervous system and in neuroendocrine tissue, including the adenohypophysis where, in humans, it is expressed in corticotrophs and in ACTH‐producing adenomas. Previous analyses of human tissue have used antiserum against porcine GAL for detection of GAL immunoreactivity (GAL‐IR) and no pathophysiological correlates have been reported. Given significant differences between the sequence of porcine and human GAL peptides, the aim of this study was to use antiserum raised against synthetic human GAL to investigate GAL‐IR in non tumorous pituitaries and in pituitary adenomas, and to correlate GAL‐IR with the clinical and hormonal characteristics of patients with Cushing’s disease.

patients Six nontumorous pituitaries were obtained from autopsy and 151 pituitary adenomas, comprising 62 functioning (16 corticotroph, 26 somatotroph, 19 lactotroph and one thyrotroph) and 89 nonfunctioning adenomas, were obtained by surgery.

results All non tumorous pituitary glands showed GAL‐IR in corticotrophs, in basophil cells within the neurohypophysis and in nerve fibres of the neurohypophysis. GAL‐IR was found in a subset (10 of 16) of patients with ACTH‐secreting tumours causing Cushing’s syndrome. GAL‐IR was rarely expressed in somatotroph adenomas and prolactinomas, but was expressed in approximately one‐third of nonfunctioning tumours. GAL‐IR was found in almost 90% of nonfunctioning tumours that were positive for ACTH. There were no significant differences in sex ratio, age at presentation or 24‐h urinary free cortisol secretion in the subset of patients with Cushing’s disease positive (n = 10) or negative (n = 6) for GAL‐IR. However, Cushing’s patients positive for GAL‐IR tended to have smaller tumours and achieved a higher cure rate than those without (100 vs. 50%, P = 0·017).

conclusions Galanin is present in normal and tumorous human pituitaries. In addition, GAL colocalizes exclusively in corticotrophs of normal pituitaries and is coexpressed almost exclusively in corticotrophs from functioning and nonfunctioning tumours. The finding that corticotroph adenomas can function irrespective of the presence of GAL suggests that GAL may not play a pathophysiological role in Cushing’s disease. However, the better surgical outcome observed in patients with Cushing’s disease who had tumours positive for GAL‐IR suggests that the expression of GAL confers a less aggressive tumour phenotype.
Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys
Authors: Kauschansky Arieh , Dickerman Zvi , Phillip Moshe , Weintrob Naomi , Strich David
Published: March 2003

objectives The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH‐a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests.

patients, methods and design The study sample included 32 prepubertal boys aged 14 years or older. Thirteen entered spontaneous puberty within 1 year of referral (group A) and 19 remained prepubertal (group B). All underwent the GnRH test (Relefact, Hoechst AG, 0·1 mg/m2 i.v. in one bolus), GnRH‐a test (Decapeptyl, Ferring GmbH, 0·1 mg/m2 s.c.) and hCG stimulation (Chorigon, Teva, 1500 units i.m. on three alternate days) at 1‐week intervals. All tests were performed at referral at 0800 h. Blood samples were collected before testing and at 30 and 60 min (GnRH test) or 4 h (GnRH‐a) for LH and FSH determination, and before testing and at 4 h (GnRH‐a) or on the seventh day (hCG) after stimulation for serum testosterone measurement.

results The LH response to GnRH‐a and the testosterone response to hCG stimulation were significantly higher in group A (LH, mean ± SD 20·4 ± 7·5 mIU/ml, range 10·8–32·6; testosterone, mean ± SD 18·0 ± 5·9 nmol/l, range 9·4–26, P < 0·0001) than in group B (LH, mean ± SD 2·3 ± 2·0 mIU/ml, range 0·7–6·9; testosterone, mean ± SD 1·0 ± 0·7 nmol/l, range 0·7–3·2), with no overlap between the groups. The cut‐off for the LH response to GnRH‐a was 8·0 mIU/ml, and for the testosterone response to hCG, 8 nmol/l. There were also significant differences between the groups in mean basal serum LH and FSH (LH, 1·1 ± 0·5 vs. 0·6 ± 0·2 mIU/ml, P < 0·05; FSH, 2·2 ± 2·0 vs. 0·4 ± 0·3 mIU/ml, P < 0·02) and their response to GnRH (LH, 11·4 ± 4·4 vs. 2·7 ± 1·1 mIU/ml, P < 0·0001; FSH, 5·1 ± 3·4 vs. 2·5 ± 2·4 mIU/ml, P < 0·0001), and mean serum testosterone level at 4 h after GnRH‐a administration (1·9 ± 1·0 vs. 0·9 ± 0·4 nmol/l, P = 0·002), but all showed a great overlap in range. Mean age, testicular volume and basal serum testosterone levels were similar in the two groups at referral. One year later, the testicular volume of group A (5·0–12·0 ml) was significantly larger than that of group B (1·0–3·0 ml, P < 0·0001), which remained unchanged on re‐examination 3·0 ± 0·5 years later.

conclusions The GnRH‐agonist test and the repeated‐injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.
Long‐term effects of androgen deprivation therapy in prostate cancer patients
Authors: Basaria Shehzad , Lieb John , Tang Alice M. , DeWeese Theodore , Carducci Michael , Eisenberger Mario , Dobs Adrian S.
Published: March 2003

background Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long‐term ADT in men with PCa.

methods We conducted a cross‐sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age‐matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non‐ADT group); and (3) 20 age‐matched normal men who were healthy and ambulatory (control group).

results Men on ADT had castrate levels of serum total testosterone (P < 0·0001), free testosterone (P < 0·0001) and oestradiol (P < 0·0001), which were significantly lower than in the other groups. Total body (P = 0·03) and lumbar spine (P < 0·0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N‐telopeptide (P = 0·02). The ADT group had higher fat mass compared to the other groups (P = 0·0001) and significantly reduced upper body strength (P = 0·001) when compared to non‐ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0·0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0·001), role limitation (P = 0·02) and perception of physical health (P = 0·004).

conclusions This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy.
Growth hormone deficiency and vascular risk
Authors: McCallum Roland W. , Petrie John R. , Dominiczak Anna F. , Connell John M. C.
Published: March 2003

The importance of growth hormone deficiency (GHD) in adult life has become more apparent over the last decade. As well as a distinct clinical syndrome there is a significant excess risk of cardiovascular disease. Although it is difficult to ascertain what part is played by the original pituitary disorder and the concomitant replacement hormonal therapies, there is clear evidence that GHD is associated with known cardiovascular risk factors such as body shape, lipid profile, insulin resistance, blood pressure, vessel wall morphology and haemostatic factors. Novel means of assessing vascular risk such as pulse wave velocity and flow‐mediated dilatation can also estimate the risk without invasive procedures. The role of possible mediators of endothelial function such as nitric oxide and free radicals is being investigated further. Replacement of GH in GH‐deficient patients leads to many effects on the above indices, some but not all of which are associated with reduced vascular risk. Long‐term follow‐up studies of morbidity and mortality are required for an accurate assessment of the beneficial effects of therapy.
Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult‐onset GH deficiency: results from two 12‐month randomized studies
Authors: Abrahamsen B. , Hangaard J. , Horn H. C. , Hansen T. B. , Gregersen G. , Hansen‐Nord M. , Vahl N. , Junker P. , Andersen M. , Hagen C.
Published: March 2003

objective To establish the optimum GH dose for restoring bone mineral density (BMD) in adult‐onset GH deficiency (GHDA).

design Two separate randomized, controlled clinical trials.

patients Fifty‐eight adults aged 45·1 (20–64) years with severe GHDA were followed in two 12‐month studies. In the first study, patients were randomized to placebo or GH 1·7 IU/m2/day and in the second study GH 0·5 IU/m2/day or 1·0 IU/m2/day.

measurements BMD of the spine, hip, forearm and whole body was measured at 0 and 12 months. Alkaline phosphatase (AP) and collagen markers serum C‐terminal propeptide of type I collagen (PICP), type I collagen telopeptide (ICTP) and N‐terminal propeptide of type III collagen (PIIINP) were measured at baseline and every 3 months.

results Biochemical markers of skeletal and soft tissue collagen increased significantly and remained elevated throughout the study period. BMD changes depended on site, dose and gender. In placebo‐treated patients, spinal BMD declined by 2·5%. At the low and medium doses, BMD increased by 2·4 and 3·1%, respectively, while a nonsignificant 0·2% decrease was seen with high dose. Forearm BMD decreased by 4·9% (P < 0·05) with high‐dose treatment but remained unchanged at lower doses. Males showed larger gains in BMD, but the dose–response relationship was similar in males and females.

conclusion A GH dose of 0·5–1·0 IU/m2/day (4–9 µg/kg/day) stimulated bone remodelling and increased BMD over 12 months in patients with severe GHDA, irrespective of gender. A higher dose (1·7 IU/m2/day ≅ 15 µg/kg/day) was associated with initial declines in forearm and whole‐body BMD.
Neonatal thyrotoxicosis and maternal infertility in thyroid hormone resistance due to a mutation in the TRβ gene (M313T)
Authors: Blair J. C. , Mohan U. , Larcher V. F. , Rajanayagam O. , Burrin J. M. , Perry L. A. , Grossman A. B. , Chatterjee V. K. K. , Savage M. O.
Published: March 2003

We report two unusual cases of resistance to thyroid hormone (RTH) in one family. The first case, a male infant, had clinical features of thyrotoxicosis in the neonatal period. In the fourth week of life weight gain was poor despite a daily intake of standard infant formula almost double the infant's estimated requirements. At this time serum free T4 (fT4) was 60·7 pmol/l (Normal range [NR] 11–25 pmol/l) and TSH was inappropriately normal at 1·8 mU/l (NR 0·3–4·0 mU/l). The infant responded clinically and biochemically to propylthiouracil (PTU) at a dose of 10 mg/kg/day. Following 27 days of treatment serum fT4 was 22·6 pmol/l and TSH had risen to 24·9 mU/l. As the infant was thriving treatment was discontinued. The infant, now aged 6 months old, remains clinically euthyroid and developmentally normal off treatment.

The infant's mother, from whom he had inherited a mutation of the thyroid receptor β (TRβ) gene (M313T), presented earlier with secondary infertility and clinical features of thyrotoxicosis. Treatment with PTU restored her fertility and she spontaneously conceived. In the subsequent pregnancy, clinical and biochemical features of RTH improved, and she gave birth to a small but healthy female infant. In the next pregnancy, resulting in the birth of the affected male infant, clinical and biochemical features of RTH worsened, and high doses of PTU were required to maintain a clinically euthyroid state.

To our knowledge, these are the first case reports of RTH associated with added features of a hypermetabolic state in infancy and secondary infertility.
Individualized growth hormone substitution with normalized IGF‐I levels does not stimulate the renin–angiotensin–aldosterone system
Authors: Ekman Bertil , Öhman Peter K. , Arnqvist Hans J. , Lindström Torbjörn , Nyström Fredrik H.
Published: March 2003

objective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF‐I levels, in GH‐deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.

study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF‐I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF‐I levels at or slightly below the age‐related mean (Tend), and this maintenance dose was held constant for 6 months.

subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.

measurements Blood pressure and heart rate, circulating levels of IGF‐I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24‐h urine aldosterone and urine free cortisol levels.

results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24‐h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.

conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near‐normal IGF‐I levels.
Fasting plasma free fatty acid concentrations and Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor (PPAR) γ2 gene in healthy individuals
Authors: Vaccaro O. , Mancini F. P. , Ruffa G. , Sabatino L. , Iovine C. , Masulli M. , Colantuoni V. , Riccardi G.
Published: March 2003

background The Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor (PPAR) γ gene has been associated in some, but not all, studies with lower body mass index (BMI) and improved insulin sensitivity; how an altered transcriptional activity of PPARγ2 could influence insulin sensitivity is currently unclear. The free fatty acids (FFAs) released from adipose tissue triglycerides via lipolysis are key mediators of impaired insulin sensitivity; however, no study has described the relationship of the Pro12Ala mutation with circulating levels of FFAs under physiological conditions.

objective To investigate in a population‐based sample of Caucasians the relation of the Pro12Ala polymorphism with plasma concentrations of FFAs and other markers of lipid and glucose metabolism described as components of the insulin resistance syndrome.

subjects Four hundred and thirty‐eight nondiabetic employees of the Italian Telephone Company, aged 35–65 years, randomly selected from a total population of 3900 participants in a company‐sponsored health screening.

measurements The Pro12Ala polymorphism of the PPARγ was studied together with plasma FFAs, insulin, glucose, triglycerides, high density lipoprotein (HDL) cholesterol, blood pressure and anthropometry. The Homeostatic Model Assessment (HOMA) index was calculated as a measure of insulin resistance.

results Carriers and noncarriers of the Pro12Ala polymorphism showed very similar circulating levels of FFA (0·46 ± 0·2 vs. 0·47 ± 0·2, NS); plasma glucose, triglycerides, HDL cholesterol and blood pressure were also similar in the two groups with or without the polymorphism. To allow for the possible confounding effect of obesity, a separate analysis was conducted in overweight (BMI ≥ 25 kg/m2) and normal‐weight people (BMI < 25 kg/m2). Circulating plasma FFA concentrations, as well as triglycerides, blood pressure and HOMA, were significantly higher in overweight than normal‐weight, as expected, but no significant differences were detected between carriers and noncarriers of the Pro12Ala polymorphism within each BMI group (0·49 ± 0·2 vs. 0·48 ± 0·2, NS, and 0·44 ± 0·2 vs. 0·47 ± 0·2, NS, in overweight and normal‐weight, respectively). The Pro12Ala polymorphism was also analysed across increasing quartiles of FFA concentrations and no relationship was observed between the frequency of the polymorphism and FFA values (overall χ2 = 0·48, NS).

conclusion This study does not show any relationship between the Pro12Ala polymorphism of the PPARγ gene and fasting FFAs in the general population. The possibility of a different handling of FFAs under different conditions (i.e. postprandial) cannot be excluded and remains to be explored.
A mortality prediction model in diabetic ketoacidosis
Authors: Efstathiou Stamatis P. , Tsiakou Aphrodite G. , Tsioulos Dimitrios I. , Zacharos Ioannis D. , Mitromaras Athanasios G. , Mastorantonakis Stylianos E. , Panagiotou Themistoklis N. , Mountokalakis Theodore D.
Published: March 2003

aim To assess the value of clinical and laboratory parameters in predicting mortality in patients presenting with diabetic ketoacidosis (DKA).

methods The records of all DKA admissions within 10 years were reviewed. Eighteen variables were evaluated at initial presentation and 20 variables at 4, 12 and 24 h from admission. A scoring system derived from these variables was compared to the APACHE III scoring system.

results Among 154 patients (52 males, mean age 58 ± 12 years), 20 (13%) died in hospital. Multivariate analysis yielded six variables as significant independent predictors (P < 0·05) of mortality: severe coexisting diseases (SCD) and pH < 7·0, at presentation; units of regular insulin required in the first 12 h > 50 and serum glucose > 16·7 mmo/l, after 12 h; depressed mental state and fever, after 24 h. An integer‐based scoring system was derived, as follows: number of points = 6 (SCD at presentation) + 4 (pH < 7·0 at presentation) + 4 (regular insulin required > 50 IU after 12 h) + 4 (serum glucose > 16·7 mmo/l after 12 h) + 4 (depressed mental state after 24 h) + 3 (fever after 24 h). Patients with 0–14 points had 0·86% risk of death, whereas for those with 19–25 points the risk was 93·3%. Median APACHE III scores differed significantly (P < 0·001) among groups of patients stratified according to the above scoring system.

conclusions Risk stratification of patients with diabetic ketoacidosis is possible from simple clinical and laboratory variables available during the first day of hospitalization.