bluuebunny/crossref_metadata_2025 huggingface dataset:
The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF‐I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population
Authors: Janssen J. A. M. J. L. , Huizenga N. A. T. M. , Stolk R. P. , Grobbee D. E. , Pols H. A. P. , De Jong F. H. , Attanasio A. M. F. , Blum W. F. , Lamberts S. W. J.
Published: March 2003

OBJECTIVE

To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF‐I/IGFBP system and leptin levels in healthy elderly humans.

METHODS

In 209 healthy elderly individuals (95 men, 114 women, aged 55–80 years) measurements were made in the fasting state (0800 h) and after an overnight dexamethasone suppression test (1 mg p.o. at 2300 h.

RESULTS

Mean leptin levels increased from 6.2 ± 0.4 (SE) μg/l to 7.3 ± 0.5 (SE) μg/l in men and from 18.9 ± 1.4 (SE) μg/l to 23.9 ± 1.8 (SE) μg/l in women after 1 mg dexamethasone overnight (‘post treatment’) (P < 0.001 for both sexes). There was a significant relationship between post‐treatment leptin and dexamethasone levels (men: P = 0.002; women: P < 0.001). The increase in leptin levels after dexamethasone administration was only partially related to the increase in plasma insulin concentrations. Cortisol levels were not related to leptin. In multivariate analyses the relationship between post‐treatment leptin and dexamethasone levels remained after adjustment for post‐treatment insulin levels, BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women: P = 0.001). Plasma (free and total) IGF‐I and IGFBP‐3 levels were not related to leptin levels in men or women. IGFBP‐1 levels were inversely related to leptin levels (P = 0.02), but this relationship was lost after adjustment for insulin, and/or BMI. In multivariate analyses the relationship between leptin and DHEAS was inverse in women (P = 0.04) (after adjustment for BMI, WHR, insulin and glucose), while there was no relationship between leptin and DHEAS in men.

CONCLUSIONS

Administration of dexamethasone acutely increased leptin levels within 9 h in this elderly population. This increase was only partly related to changes in circulating insulin concentrations, but was independent of BMI and waist:hip ratio. No relation existed between leptin and (free or total) IGF‐I and IGFBP‐3 in men or women. Dehydroepiandrosterone was inversely related to leptin in women. These findings suggest a contributory regulatory role for corticosteroids in modulating circulating leptin concentrations in elderly healthy individuals of both sexes, which is at least in part independent of insulin, BMI and waist:hip ratio. Dehydroepiandrosterone might play a role in the gender‐specific differences in serum leptin levels.
Reduced serum dehydroepiandrosterone levels in diabetic patients with hyperinsulinaemia
Authors: Yamaguchi Yumiko , Tanaka Shun‐ichi , Yamakawa Tadashi , Kimura Mari , Ukawa Kunio , Yamada Yoshihiko , Ishihara Manabu , Sekihara Hisahiko
Published: March 2003

OBJECTIVE

To elucidate the interaction between insulin and dehydroepi‐androsterone (DHEA) concentrations, we evaluated serum DHEA and DHEA‐sulphate (DHEA‐S) levels in diabetic patients with hyperinsulinaemia.

PATIENTS AND DESIGN

Twenty‐four subjects with non‐insulin dependent diabetes mellitus, 12 hyperinsulinaemic subjects (fasting serum insulin concentrations 10 mU/ml (71.8 pmol/l)) and 12 non‐hyperinsulinaemic subjects, and 10 normal control subjects were studied. Serum DHEA, DHEA‐S, cortisol and ACTH levels were investigated in these subjects. Moreover, their serum DHEA levels were compared during hyperinsulinaemic–euglycaemic clamp and after ACTH stimulation.

MEASUREMENTS

Serum insulin, cortisol, ACTH, DHEA and DHEA‐S concentrations were evaluated by RIA. Serum glucose was determined by the glucose oxidase method.

RESULTS

Diabetic patients with hyperinsulinaemia showed significantly lower levels of serum DHEA and DHEA‐S than controls. After ACTH stimulation, these patients also showed significantly lower DHEA levels. During the hyperinsulinaemic–euglycaemic clamp, serum DHEA concentrations of diabetic patients with hyperinsulinaemia remained low and did not decline further, although those of control subjects and non‐hyperinsulinaemic diabetic patients showed a significant decline of serum DHEA levels. Even after ACTH stimulation during the clamp, serum DHEA in hyperinsulinaemic patients was still significantly lower than in controls.

CONCLUSIONS

In diabetic patients with hyperinsulinaemia, baseline DHEA levels are chronically and maximally suppressed compared to control subjects and non‐hyperinsulinaemic diabetic patients, and thus not decreased further by exogenous insulin infusion during hyperinsulinaemic–euglycaemic clamp.
A study of patients with Nelson's syndrome
Authors: Pereira Maria A. Albergaria , Halpern Alfredo , Salgado Luiz Roberto , Mendonça Berenice B. , Nery Marcia , Liberman Bernardo , Streeten David H. P. , Wajchenberg Bernardo L.
Published: March 2003

OBJECTIVE

The prevalence of Nelson's syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelson's syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushing's disease after bilateral adrenalectomy. We have compared patients with Cushing's disease who developed Nelson's syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelson's syndrome.

PATIENTS AND METHODS

We have reviewed the records of 30 patients with Cushing's disease after adrenalectomy, and divided them into two groups; I: 14 who developed Nelson's syndrome and II, 16 who did not. The two groups of patients were compared in their clinical, laboratory and imaging data as well as in the therapeutic procedures that preceeded the adrenalectomy.

RESULTS

The comparison between the two groups of patients demonstrated a highly significant difference in relation to the development of cutaneous hyperpigmentation (100% in group I and 19% in group II) and neuro‐ophthalmological symptoms (21% in group I and 0% in group II) after adrenalectomy. There were no significant differences in laboratory data before adrenalectomy. After adrenalectomy, plasma ACTH levels increased significantly in the patients of both groups, but to much higher levels in those who developed Nelson's syndrome. Plasma ACTH concentrations above 154 pmol/l occurred only in the subjects with Nelson's syndrome. Before adrenalectomy, a pituitary tumour was more frequent in the patients who developed Nelson's syndrome (55% vs. 33% at transsphenoidal pituitary exploration). Pituitary surgery and irradiation were undertaken before adrenalectomy in approximately equal numbers of patients in each group.

DISCUSSION

The prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.
A cytotoxic T lymphocyte antigen‐4 (CTLA‐4) gene polymorphism is associated with autoimmune Addison's disease in English patients
Authors: Kemp  , Ajjan  , Husebye  , Peterson  , Uibo  , Imrie  , Pearce  , Watson  , Weetman
Published: March 2003

OBJECTIVE

Recent studies have demonstrated an association between a microsatellite polymorphism of the CTLA‐4 gene, specifically a 106 base pair allele, and both Graves' disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA‐4 gene was associated with autoimmune Addison's disease.

DESIGN AND PATIENTS

We analysed a microsatellite polymorphism (variant lengths of a dinucleotide (AT)n repeat) within exon 3 of the CTLA‐4 gene in the following groups: 21 English patients with non‐associated Addison's disease, 18 with autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients with non‐associated Addison's disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non‐associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients with non‐associated Addison's disease, 2 with APS2 and 45 controls.

MEASUREMENTS

The CTLA‐4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels.

RESULTS

The frequency of the 106 base pair allele was significantly increased in the groups of English patients with either non‐associated Addison's disease or APS2 (P = 0.02 and 0.04, respectively), when compared to healthy controls with no clinical evidence or family history of either Addison's disease or any other autoimmune disorder. For Norwegian patients with either non‐associated Addison's disease, APS1 or APS2, there was no association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for Finnish patients with either non‐associated Addison's disease or APS2 (P = 0.23 and 0.28, respectively) and for Estonian patients with either non‐associated Addison's disease or APS2 (P = 0.34 and 0.29, respectively).

CONCLUSIONS

These results indicate that differences exist in the frequency of the 106 base pair allele in different population groups and in only the English population was the 106 base pair allele associated with Addison's disease.
HDL‐cholesterol reductions associated with adult growth hormone replacement
Authors: Leese  , Wallymahmed  , VanHeyningen  , Tames  , Wieringa  , MacFarlane
Published: March 2003

OBJECTIVE

To study the effects of human growth hormone (hGH) replacement on serum lipids and lipoprotein (a) (Lp(a)) concentrations.

DESIGN

A randomized double blind placebo controlled trial for 6 months followed by an open trial where all patients were treated with hGH for a further 6 months. Treatment was with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk.

PATIENTS

Thirty two patients with growth hormone deficiency were recruited, but two withdrew because of side effects. Of the thirty patients (age 35.1 ± 11.8 year; mean ±SD) completing the study 13 of were assigned to the placebo group for six months and 17 to active treatment from the start.

MEASUREMENTS

Fasting serum samples were analysed for total cholesterol, High density lipoprotein (HDL)‐cholesterol, HDL‐subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF‐1. LDL‐cholesterol was calculated using the Friedewald formula.

RESULTS

Compared to placebo, 6 months treatment with hGH therapy resulted in increased IGF‐1 (37.6 ± 4.1 vs. 14.0 ± 2.2 nmol/l, P < 0.01), but there was no significant difference in any of the lipid parameters measured between placebo and active treatment groups at 6 months. hGH was associated with a decrease in HDL‐cholesterol concentration from baseline to 6 months (0.97 ± 0.08 to 0.76 ± 0.10 mmol/l P < 0.01), especially within the HDL2 subfraction. This reduction was maintained at 12 months. There was no change in Lp(a) concentrations from 0 to 6 months (placebo −26 (−340 to 82), median and range, active −4 (−586 to 212) mg/l). There was no change in total cholesterol, LDL‐cholesterol, triglycerides or proportion of HDL subfractions.

CONCLUSIONS

Treatment with hGH can reduce serum HDL‐cholesterol concentrations. Further investigation of this is required.
No overrepresentation of congenital adrenal hyperplasia in patients with adrenocortical tumours
Authors: Kjellman Magnus , Holst Mikael , Bäckdahl Martin , Larsson Catharina , Farnebo Lars‐Ove , Wedell Anna
Published: March 2003

OBJECTIVE

The development and progression of sporadic adrenocortical tumours are poorly understood. In autopsy studies adrenocortical tumours are found in between 2 and 9% of the general population. In congenital adrenal hyperplasia (CAH), decreased production of cortisol leads to increased secretion of ACTH from the pituitary, resulting in hyperplasia of the adrenals. More than 95% of all cases of CAH are due to steroid 21‐hydroxylase deficiency, resulting from mutations in the CYP21 gene. In subjects homozygous and heterozygous for CYP21 mutations, adrenocortical tumours have been found in a high frequency compared to the general population, suggesting that chronic ACTH stimulation may play a role in the development of this tumour form. In order to test whether mild undiagnosed CAH is a common predisposing factor, we screened 27 patients with sporadic adrenocortical tumours for CYP21 mutations.

DESIGN

A retrospective study.

PATIENTS

We screened 27 patients with sporadic adrenocortical tumours, representing both benign and malignant as well as hormonally active and silent lesions.

MEASUREMENTS

Mutation analyses of the CYP21 gene was performed by allele‐specific PCR on high molecular weight DNA. The method used detects the nine CYP21 mutations that are responsible for 95% of all disease‐causing alleles in CAH.

RESULTS

No mutations were detected in any of the 23 DNA samples that were prepared from leucocytes. In 4 cases where no leucocyte DNA was available, tumour tissue was analysed. In one of these tumours, two CYP21 mutations, V281 L and L307insT, were found in heterozygous form.

CONCLUSION

Our data indicate that mild undiagnosed congenital adrenal hyperplasia is not a common underlying factor predisposing to adrenocortical tumours, at least not in the Swedish population.
Inhibin forms in serum from postmenopausal women with ovarian cancers
Authors: Robertson David M. , Cahir Nicholas , Burger Henry G. , Mamers Pamela , Groome Nigel
Published: March 2003

BACKGROUND AND OBJECTIVE

Previous studies have shown that serum inhibin as measured by α subunit‐directed radioimmunoassay (RIA) and inhibin A ELISA was elevated in postmenopausal women with mucinous and granulosa cell cancers, with the RIA showing a more frequent elevation than the inhibin A ELISA. It was thus hypothesised that these cancers may also produce inhibin B or the free α subunit. The aim of the study was to identify the forms of inhibin found in a range of ovarian cancers using a range of inhibin assays with varying specificities.

DESIGN

Serum samples obtained from women with ovarian cancer were assayed by inhibin B ELISA and Pro‐αC subunit ELISA and compared with inhibin RIA and inhibin A ELISA.

PATIENTS

Blood samples were obtained from 34 postmenopausal women (>55 years) with no history of endocrine disease and from women with ovarian serous cystadenocarcinomas (n = 66), mucinous cystadenocarcinomas (n = 20), granulosa cell tumours (n = 9 − 11), miscellaneous ovarian cancers (n = 46) and non ovarian cancers (n = 23).

MEASUREMENTS

Inhibin B and inhibin Pro‐αC subunit levels were determined by ELISA and compared to values obtained by RIA and inhibin A ELISA. Cancers were discriminated from controls based on values obtained 2SD above the geometric mean of the control values.

RESULTS

Granulosa cell tumours were detected by RIA and inhibin B ELISA (100%), Pro‐αC ELISA (90%) and inhibin A ELISA (77%). Mucinous tumours were detected by RIA (70%), inhibin B ELISA (60%), Pro‐αC ELISA (55%) and inhibin A (20%). Serous tumours were detected by RIA (35%) and the other assays (<15%). Miscellaneous tumours were detected by RIA (41%) and other assays <30%.

CONCLUSIONS

Ovarian neoplasms may produce a variety of peptides related to the inhibins, including dimeric inhibin A and B. Inhibin B is detected in more ovarian cancers than inhibin A but does not discriminate as well as the α subunit directed assays. The higher discrimination index obtained with the RIA compared to the Pro‐αC ELISA suggests that assays detecting all inhibin forms containing the α subunit and not just those detecting the Pro‐αC subunit will provide the most useful detection method.
High prevalence of osteoporosis in cardiac transplant recipients and discordance between biochemical turnover markers and bone histomorphometry
Authors: Glendenning Paul , Neil Kent G. , Adler Brendan D. , Matz Leonard , Watson Ian , O'Driscoll Gerry J. , Hurley David M.
Published: March 2003

OBJECTIVE

All patients attending the cardiac trans‐plantation clinic at the Royal Perth Hospital were investigated to determine the prevalence of osteoporosis and to assess changes in bone metabolism and histomorphometry in a cohort of cardiac transplant recipients.

DESIGN

Retrospective cross‐sectional study.

PATIENTS

Thirty‐two patients (27 male; 5 female) who had received a cardiac transplant during the past 10 years and who were receiving immunosuppressive therapy with cyclosporin, azathioprine and prednisolone were studied.

MEASUREMENTS

All patients had bone densitometry by DEXA of the lumbar spine and femoral neck and X‐rays of the thoracolumbar spine. Fasting serum ionized calcium, intact PTH, creatinine, 25 hydroxy‐vitamin D, alkaline phosphatase, osteocalcin, testosterone and free thyroxine and urine calcium, creatinine, hydroxyproline and deoxypyridinoline were measured. Six osteoporotic patients consented to transiliac bone biopsy following double tetracycline labelling.

RESULTS

Osteoporosis was present at the lumbar spine in eight patients, femoral neck in seven patients and was present at one or more sites in 13 patients (41%). Seven patients (22%) had vertebral fractures which were asymptomatic in five patients. Secondary hyperparathyroidism was present in 16 patients (53%) but significant renal failure (creatinine clearance < 70 ml/min) was only found in 8 (50%). Levels of biochemical markers of bone turnover were increased in 23 patients (72%). Serum osteocalcin (P = 0.02) and alkaline phosphatase (P = 0.04) were significantly higher in osteoporotic patients than in nonosteoporotic patients. Histomorphometric findings varied markedly between patients. Microscopic features of hyperparathyroidism were not observed.

CONCLUSIONS

Osteoporosis and asymptomatic vertebral fractures are common following cardiac transplantation. Biochemical markers of bone turnover were increased in the majority of patients. Many had biochemical evidence of secondary hyperparathyroidism but this could be attributable to significant renal failure in only 50% of cases. Osteocalcin and alkaline phosphatase correlated inversely with bone density. Histomorphometric findings did not correlate with these biochemical changes in most cases. These results suggest that multiple factors are responsible for osteoporosis in cardiac transplant recipients. Osteocalcin and alkaline phosphatase may be useful biochemical markers, predicting patients at highest risk of fracture.
The HLA–DQ associations with Graves' disease in Chinese children
Authors: K. Wong Gary W. , Cheng  , Dorman
Published: March 2003

OBJECTIVE

Graves' disease has been documented to be associated with different HLA genes in Caucasians and Chinese adults. The incidence of childhood Graves' disease has been reported to be high in Hong Kong Chinese. The aims of this study were to examine the HLA‐DQA1 and DQB1 associations with Graves' disease in Chinese children.

PATIENTS AND DESIGN

Sixty‐seven Chinese children with Graves' disease (59 girls and 8 boys) and 51 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. HLA‐DQ typings were determined by sequence‐specific oligonucleotide probing of the respective enzymatically amplified gene. Frequencies of HLA‐DQ alleles at each locus were compared between patients and controls using the χ2‐test.

RESULTS

The frequency of HLA‐DQB1*0303 was increased in the combined male and female patient group [53.7%; relative risk (RR) = 4.22; Pc = 0.005] and female patients (50.8%; RR = 3.76; Pc = 0.018) compared with that in the entire control group (21.2%). HLA‐DQB1*201 was protective for Graves' disease (10.4%; RR = 0.20; Pc = 0.006). In contrast to studies in Caucasians, DQA1*0501 was not associated with susceptibility for Graves' disease in Chinese children.

CONCLUSIONS

This study confirms that DQB1*0303 is a race‐specific susceptible allele for Graves' disease in Chinese. Both susceptible and protective HLA‐DQ alleles for Graves' disease in Chinese children are different from those in Caucasians.
Evaluation of adrenal function in patients with hypothalamic and pituitary disorders: comparison of serum cortisol, urinary free cortisol and the human‐corticotrophin releasing hormone test with the insulin tolerance test
Authors: Dullaart Robin P. F. , Pasterkamp Susanne H. , Beentjes John A. M. , Sluiter Wim J.
Published: March 2003

OBJECTIVE

This study aimed to evaluate the performance of screening tests (serum cortisol and 24‐h urinary free cortisol) and the human‐corticotrophin releasing hormone (h‐CRH) test in the assessment of adrenal function in patients with hypothalamic‐pituitary disorders.

DESIGN

Summary receiver operating characteristics (SROC) curve analysis was applied with the insulin tolerance test (ITT) as reference test. A peak serum cortisol response to ITT ≥ 500 nmol/l indicated adrenal sufficiency. The sensitivity at the intersect of the diagonal between sensitivity = 1 and (1 − specificity) = 1 with the SROC curve, where sensitivity and specificity are equal, and the corresponding weighted kappa, an estimate of agreement with the ITT, served as parameters of test performance. The diagnostic yield, representing the proportion of tests obviating the need for an ITT, was also calculated.

MEASUREMENTS

Serum cortisol at 0800 h (n = 122), at 1600 h (n = 116), 24‐h urinary free cortisol (n = 115) and the peak serum cortisol to h‐CRH (n = 129) were compared with the peak serum cortisol to ITT.

PATIENTS

Eighty patients with hypothalamic‐pituitary disorders in whom 75 ITT's were performed pre‐ and 57 post‐operatively.

RESULTS

Sensitivity at the intersect and weighted kappa were higher for 0800 h serum cortisol (0.873 and 0.763 respectively) than for 1600 h serum cortisol (0.769 and 0.561) and 24‐h urinary free cortisol (0.777 and 0.576). These parameters were 0.868 and 0.756 for the h‐CRH test. The diagnostic yield was 63.9% for 0800 h serum cortisol compared to 25.9% for 1600 h serum cortisol (P<10−8), 23.5% for 24‐h urinary free cortisol (P<10−8) and 60.5% for the h‐CRH test (NS).

CONCLUSIONS

Serum cortisol measurement at 0800 h is better than 1600 h and 24‐h urinary free cortisol to evaluate adrenal function in this patient category. The diagnostic applicability of the h‐CRH test is not superior to 0800 h serum cortisol measurement.
Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome
Authors: Conway Gerard S. , Conway Emily , Walker Caroline , Hoppner  , Gromoll  , Simoni
Published: March 2003

OBJECTIVE

To determine whether mutations in the FSH receptor gene are associated with premature ovarian failure (POF) or resistant ovary syndrome (ROS) in women in the UK. To determine whether an allelic variant of the FSH receptor gene affects fertility parameters in women with polycystic ovary syndrome (PCOS).

DESIGN

A mutation screen using DNA from women with POF and ROS. Restriction digest of amplified DNA from women with POF, ROS, PCOS and controls to determine allelic variant status. Fertility parameters were compared between allelic variant subgroups of women with PCOS.

PATIENTS

The study population comprised 49 women with POF, 5 with ROS, 93 with PCOS and 51 controls.

MEASUREMENTS

In women with PCOS, fertility and menstrual status was recorded and serum FSH and ovarian volume were measured.

RESULTS

No mutation of the FSH receptor gene was found in women with POF or ROS. The allelic variant Thr307/Ser680 was found to be similarly prevalent in all study groups. The Thr307/Ser680 variant was found to have no phenotype in terms of fertility parameters in women with PCOS.

CONCLUSIONS

Mutations of the FSH receptor gene are rare in women with premature ovarian failure or resistant ovary syndrome in the UK. Polymorphisms of the FSH receptor gene do not appear to have pathophysiological significance with regard to ovarian function.
Vitamin D insufficiency increases bone turnover markers and enhances bone loss at the hip in patients with established vertebral osteoporosis
Authors: Sahota O. , Masud T. , San P. , Hosking D. J.
Published: March 2003

AIM

The aim of this study was to determine whether the presence of vitamin D insufficiency increases bone turnover and enhances bone loss by examining the relationship between bone turnover markers and Bone mineral density (BMD) in vitamin D insufficient and vitamin D sufficient patients, with established vertebral osteoporosis.

SUBJECTS

119 consecutive, active, community dwelling, elderly women were assessed over a 7‐month period between the months of March to October.

RESULTS

There was a significant correlation between parathyroid hormone (PTH) and 25 hydroxyvitamin D (25(OH)D), r = − 0.42 (P < 0.01). The prevalence of vitamin D insufficiency was 26.9% (defined by a 25(OH)D ≥ 6.1 μg/l and ≤ 12 μg/l). This resulted in a statistically significant increase in bone turnover markers compared to the vitamin D sufficient group: bone alkaline phosphatase (P < 0.05), osteocalcin (P < 0.01), hydroxyproline (P < 0.05), free deoxypyridinoline (P < 0.05) and lower bone mineral density at the total hip (P < 0.01).

CONCLUSIONS

These results show that there is a high prevalence of vitamin D insufficiency in the active community dwelling elderly with established vertebral osteoporosis presenting to clinical attention, which leads to increased bone turnover, decreased BMD at the hip and thus enhanced risk of further osteoporotic fractures in comparison with vitamin D sufficient subjects.
Ovarian responses to hCG stimulation: insulin resistance/hyperinsulinaemia vs. insulin deficiency
Authors: Witchel Selma F. , Arslanian Silva
Published: March 2003

Polycystic ovary syndrome is a heterogeneous disorder characterized by signs and symptoms of hyperandrogenism and insulin resistance. We present the clinical and hormonal features in an adolescent girl who had distinct intervals of insulin deficiency and insulin resistance/hyperinsulinaemia. This case report confirms that insulin resistance/hyperinsulinaemia exacerbates ovarian hyperandrogenism.
Growth hormone (GH) status is an independent determinant of serum levels of cholesterol and triglycerides in healthy adults
Authors: Vahl Nina , Klausen Ib , Christiansen Jens S , Jørgensen Jens O. L.
Published: March 2003

OBJECTIVE

Both severe growth hormone (GH) deficiency in hypopituitary adults and physiological ageing are associated with an increase in fat mass, dyslipidaemia, and an increased incidence of cardiovascular disease. Ageing is also associated with a physiological decrease in spontaneous as well as stimulated GH secretion. We wished to evaluate the effects of endogenous GH status on circulating lipoproteins.

DESIGN

A cross‐sectional study.

SUBJECTS

Forty‐two healthy nonobese adults of both sexes (20 M + 22 F) aged 27–59 years.

MEASUREMENTS

Twenty‐four hour GH secretion, arginine‐stimulated GH secretion, and fasting values of lipoproteins and triglycerides. Body composition was measured by CT‐scan and whole body DXA‐scan. VO2‐max was measured on an ergometer bicycle.

RESULTS

GH secretion decreased with age and was lower in males. Older subjects had more total body fat, subcutaneous abdominal fat, and intra‐abdominal fat than younger ones, and their VO2‐max was decreased. Men had more intra‐abdominal and subcutaneous abdominal fat but less total body fat than women. There was no sex difference in VO2‐max. Total cholesterol (TC) and LDL‐C (mmol/l) were higher in older than in the younger subjects (TC: 5.32 (95% CI = 0.49) vs. 4.17 (95% CI = 0.28), P < 0.001; LDL‐C: 3.66 (95% CI = 0.52) vs. 2.54 (95% CI = 0.37), P = 0.001) without sex differences. HDL‐C did not show any difference with age or between sexes. Triglycerides (mmol/l) were higher in older subjects and in males (older: 1.36 (95% CI = 0.19) vs. younger: 1.02 (95% CI = 0.20), P = 0.015; M: 1.34 (95% CI = 0.24) vs. F: 1.03 (95% CI = 0.16), P = 0.03). There was no age‐difference in lipoprotein (a), but concentrations were higher in women (M: 4.35 (2.95–8.30) vs. F: 19.40 (4.10–32.80), P = 0.03). TC, LDL‐C, and triglycerides correlated positively with age and indices of adiposity, and inversely with VO2‐max. TC, LDL‐C, and triglycerides also correlated significantly and negatively with arginine‐stimulated GH secretion (peak GH) (TC vs. peak GH (r = − 0.395, P = 0.01); LDL‐C vs. peak GH (r = − 0.365, P = 0.017); triglycerides vs. peak GH (r = − 0.386, P = 0.01)). Multiple linear regression analysis showed GH status to be an independent predictor of both TC, LDL‐C, and triglycerides.

CONCLUSION

We hypothesize that GH may exert direct effects on lipid metabolism.
Association of molecular variants of luteinizing hormone with menstrual disorders
Authors: Ramanujam L. N. , Liao W. X. , Roy A. C. , Loganath A. , Goh H. H. , Ng S. C.
Published: March 2003

OBJECTIVE

Luteinizing hormone (LH) promotes ovulation and luteinization of the ovarian follicle, and stimulates steroidogenesis in the ovaries. It is known to be present in different molecular forms, and secretion of abnormal LH has been implicated in menstrual disorders and infertility. The purpose of this study was to determine any association of two recently described LH variants with menstrual disorders in Singapore Chinese women. One of these variants had Trp8 to Arg8 and Ile15 to Thr15 replacements in the LH β‐subunit, while the second variant possessed Ser102 substitution for Gly102.

PATIENTS

One hundred and seventy six patients with menstrual disorders and two hundred normal ovulatory women were recruited and screened for the presence of these two LH variants.

METHODS

The polymerase chain reaction (PCR) products of patients were analysed by restriction fragment length polymorphism (RFLP) and the results were compared with those of normal ovulatory women and confirmed by DNA sequencing.

RESULTS

Twenty one (11.9%) patients with menstrual disorders and twenty (10%) normal ovulatory women were found to carry the first variant, but its occurrence did not show any significant statistical difference between the patient and control groups (P = 0.679). However, the second variant was only detected in seven (4%) patients with menstrual disorders, and none of the normal ovulatory subjects (P = 0.005).

CONCLUSIONS

the study showed that the first variant was not associated with menstrual disorders, whereas the second variant might be implicated in menstrual disorders in some Singapore Chinese women.
Enhancement of the GH responsiveness to GH releasing stimuli by lysine vasopressin in type 1 diabetic subjects
Authors: Coiro  , Volpi  , Capretti  , Speroni  , Caffarri  , Marchesi  , Chiodera
Published: March 2003

OBJECTIVE

We tested the possibility that lysine vasopressin (LVP) changes the GH responsiveness to exogenously administered GH‐RH (at its minimal and maximal doses), clonidine (which is thought to stimulate endogenous GH‐RH release) and arginine (which is thought to inhibit somatostatin) in patients with type 1 diabetes mellitus and normal subjects.

DESIGN AND PATIENTS

Normal male subjects (NC) and age‐ and weight‐matched insulin‐dependent diabetic men (DM) with good metabolic control were studied. An iv bolus of LVP at a dose (15 μg/kg body weight (BW)) lower than the minimal GH releasing effective dose was injected just before the I.V. injection of the minimal effective dose of GH‐RH (0.035 μg/kg BW) in 10 NC and 10 DM, the I.V. injection of the maximal effective dose of GH‐RH (100 μg) in 7 NC and 7 DM, the I.V. infusion of arginine (30 g over 30 min) in 7 NC and 8 DM or the oral administration of clonidine (150 μg) in 7 NC and 8 DM. On different occasions, GH stimuli, LVP or normal saline were given alone to the same normal and diabetic subjects.

MEASUREMENTS

GH responses in the presence and absence of LVP were measured and compared within each group and between normal and diabetic groups.

RESULTS

LVP or normal saline administration did not modify the basal concentrations of GH in any subject. The administration of GH‐RH (at the minimal dose), arginine or clonidine alone induced significantly higher GH responses in the diabetic subjects than in the normal controls. At the maximal dose GH‐RH induced similar GH responses in normal and diabetic subjects. The simultaneous administration of LVP did not change the GH response to any challenging stimulation in the normal controls; in contrast, GH‐RH‐ (at both minimal and maximal dose), arginine‐ and clonidine‐induced GH increments were significantly enhanced by LVP in the diabetic subjects.

CONCLUSIONS

These data show that in diabetic, but not in normal subjects LVP enhances the GH responsiveness to secretagogues, such as GH‐RH, clonidine and arginine, which act through three different mechanisms. These findings suggest that in diabetes mellitus, vasopressin functions as a primer for various GH responses.
Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent
Authors: Toogood  , Taylor  , Shalet  , Monson
Published: March 2003

OBJECTIVE

The net interconversion of inactive cortisone to active cortisol by 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11βHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post‐menopausal, oestrogen‐deficient women and elderly men.

PATIENTS

Fifteen healthy men, aged 60.8–82.0 years, and 7 healthy women, aged 62.4–87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post‐menopausal and none was receiving sex steroid replacement therapy.

MEASUREMENTS

24‐h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X‐ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF‐I and IGFBP1 levels.

RESULTS

The ratio of 11‐hydroxy cortisol metabolites to 11‐oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55–1.86) vs. 0.67 (0.46–0.98) (P < 0.02), as was the ratio of allo‐tetrahydrocortisol (5α‐THF) + tetrahydrocortisol (THF)/tetrahydrocortisone (THE), 0.74 (0.37–2.08) vs. 0.40 (0.22–1.10) (P < 0.047). In the group as a whole there was a negative correlation between Fm/Em and percent body fat, r = − 0.43 (P < 0.05), and the negative relationship between cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = − 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = − 0.48, and Fm/Em and trunk fat mass, r = − 0.48 which approached significance (both P = 0.07). Serum IGFBP‐1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP‐1 and Fm/Em in the men, r = 0.84 (P < 0.0001) which persisted when total body fat mass, r = 0.85 (P < 0.0001) and trunk fat mass, r = 0.83 (P < 0.0001), were controlled for. This relationship was not evident among the women.

CONCLUSION

This study demonstrates that the previously described sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11β‐HSD1 gene expression during the pre‐menopausal period cannot be excluded. The findings confirm the primary importance of body fat as a determinant of cortisol–cortisone conversion.
Parathyroidectomy for primary hyperparathyroidism induces positive uncoupling and increases bone mineral density in cancellous bones
Authors: Abe  , Ejima  , Fujiyama  , Kiriyama  , Ide  , Sera  , Tominaga  , Ashizawa  , Yokoyama  , Eguchi
Published: March 2003

OBJECTIVE

Osteopenia is an important feature of primary hyperparathyroidism (PHP). However, little is known about the change of bone mineral density (BMD) in PHP after surgery. The aim was to investigate the mechanisms of increased BMD after parathyroidectomy in patients with PHP.

DESIGN

Prospective observational study.

PATIENTS

Ten patients with PHP (7 women, 3 men; mean age 53.2±9.1 years). All patients underwent parathyroidectomy for excision of parathyroid adenoma.

MEASUREMENTS

BMDs of two cancellous bone‐rich sites (L2‐L4 lumbar spine and ultra‐distal end of the radius, RUD) and one cortical bone‐rich site (distal third of the radius, R33%) were measured using dual energy X‐ray absorptiometry, before, and 3, 6 and 12 months after surgery. Serum intact PTH, intact osteocalcin, bone type alkaline phosphatase (b‐ALP), alkaline phosphatase, calcium, and urinary deoxypyridinoline (Dpd) were measured before, and 1 and 3 days, and 1, 2, 3, 4, 6, 8, 12, and 24 weeks after surgery.

RESULTS

Parathyroidectomy resulted in a significant increase in BMDs of L2‐L4 and RUD at 3 months postoperatively. Urinary Dpd levels decreased within a few days after surgery, while b‐ALP and osteocalcin decreased more slowly throughout the first few months after surgery. The ratio of osteocalcin/Dpd at 1 week after surgery correlated significantly with the percentage change in BMD of L2‐L4 at 3 and 6 months after surgery. The ratio of osteocalcin/Dpd at 2 weeks correlated significantly with the percentage change in BMD of L2‐L4 at 3, 6 and 12 months after surgery. The preoperative values of osteocalcin, b‐ALP, PTH and calcium were positively correlated with the change in BMD of RUD at 3 months and L2‐L4 at 12 months, RUD at 6 months, RUD at 3 months and L2‐L4 at 12 months, respectively.

CONCLUSIONS

In primary hyperparathyroidism patients, the major increase in bone mineral density following parathyroidectomy occurs within 3 months. Parathyroidectomy resulted in a marked increase in bone mineral density of cancellous bones compared to that of cortical bones. The early increase in bone mineral density was due to a preferential activation of bone formation over bone resorption as evidenced by changes in bone metabolic markers. Our results also showed that the preoperative levels of bone metabolic markers may predict the gain in bone mineral density after parathyroidectomy.
A longitudinal study on bone mineral density until adulthood in girls with Turner's syndrome participating in a growth hormone injection frequency‐response trial
Authors: Sas Theo C. , De Muinck Keizer‐Schrama Sabine M. , Stijnen Theo , Asarfi Anjalie , Van Leeuwen Wibeke J. , Van Teunenbroek Arne , Van Rijn Rick R. , Drop Stenvert L. ,   the Dutch Advisory group on Growth Hormone
Published: March 2003

OBJECTIVE

The aim of this study was to assess the volumetric bone mineral density (BMD) in girls with Turner's syndrome (TS) before and during growth hormone (GH) treatment in combination with low dose oestrogens as well as three years after discontinuation of GH treatment.

DESIGN

In a prospective, randomized injection frequency‐response study, the effect of GH treatment in combination with low dose ethinyl oestradiol (starting with 0.05 μg/kg/day), on BMD was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 IU/m2/day until adult height was reached. After discontinuation of GH treatment, the dosage of oestrogens was further increased to adult supplementation levels.

PATIENTS

Nineteen untreated girls with TS, mean (SD) baseline pretreatment age 13.3 (1.7) (range 11.0–17.6) year.

MEASUREMENTS

Before and during GH treatment, measurements of volumetric BMD were performed using phalangeal radiographic absorptiometry. In addition, the BMD measurements were repeated three years after discontinuation of GH treatment. BMD results were adjusted for bone age and sex, and expressed as SD‐scores (SDS) using reference values of healthy Dutch girls.

RESULTS

At baseline, most individual BMD values of cortical bone as well as those of trabecular bone were within the normal range of healthy girls. However, the mean BMD SDS of the trabecular bone was significantly lower than zero. During treatment, the BMD SDS showed a significant increment to values equal or higher than zero after mean (SD) GH treatment period of 36.6 (7.5) months. The increase in BMD of the cortical bone was significantly higher in the OD group than in the BID group. The BMD SDS in the last year of GH treatment was not significant different between the two injection frequency groups. Three years after discontinuation of GH treatment, the BMD values had increased further similar as in healthy girls, resulting in BMD values all within normal range or even higher.

CONCLUSIONS

Most untreated girls with Turner syndrome, age ≥ 11 years, have a normal volumetric BMD of the cortical, as well as of the trabecular bone compared to healthy girls. During GH treatment with 6 IU/m2/day in combination with low dose oestrogens, the BMD SDS increases significantly. After discontinuation of GH treatment and the use of oestrogens in an adult dosage, the BMD was as high as in young healthy women.
Assessment of disease activity in Graves' ophthalmopathy by orbital ultrasonography and clinical parameters
Authors: Gerding Martin N. , Prummel Mark F. , Wiersinga Wilmar M.
Published: March 2003

OBJECTIVE

To study if A‐mode ultrasonography (US) in combination with the Clinical Activity Score (CAS) and duration of Graves' ophthalmopathy (GO) could predict the response to immunosuppression in Graves' ophthalmopathy.

DESIGN

A prospective clinical study.

PATIENTS AND METHODS

Fifty‐six consecutive patients with moderately severe GO were treated with retrobulbar irradiation (10 fractions of 2 Gy). Before treatment the internal reflectivity in the extraocular eye muscles, the CAS, and the duration of Graves' ophthalmopathy were assessed and related to the therapeutic outcome 26 weeks after irradiation.

RESULTS

Twenty‐eight (50%) of the patients responded favourably to radiotherapy (four patients became worse, and 24 did not change), and the eye muscle echogenecity indeed tended to be lower in the responders than in the non‐responders (P = 0.09). From a receiver operator characteristics curve, a cut‐off value of 30% yielded a good positive predictive value of 85%, but the negative predictive value was only 60%. The CAS (≥ 4/10) had a positive predictive value of 65%, and a negative predictive value of 56%. When combining the ultrasound with the CAS, the positive predictive value increased to 74% and the negative predictive value to 72%. Adding the duration of eye symptoms (cut‐off 18 months), the prediction of response further improved: positive predictive value 79%, and negative predictive value 89%.

CONCLUSIONS

A‐mode ultrasonography has a rather good positive predictive value, but its poor negative predictive value precludes its use as sole activity parameter. By adding the Clinical Activity Score and duration of Graves' ophthalmopathy, the negative predictive value increased considerably. By using this combination, inactive disease can be identified more precise, permitting rehabilitative surgery at an earlier stage in these patients.
Lack of relationship between 11β‐hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients*
Authors: Kerstens M. N. , Riemens S. C. , Sluiter W. J. , Pratt J. J. , Wolthers B. G. , Dullaart R. P. F.
Published: March 2003

OBJECTIVES To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11β‐hydroxysteroid dehydrogenase (11βHSD) mediated cortisol to cortisone Inter‐conversion towards cortisol, and to evaluate whether changes in insulin sensitivity induced by antecedent hyperinsulinaemia are related to changes in the 11βHSD setpoint.

PATIENTS AND MEASUREMENTS The urinary ratio of (tetrahydrocortisol + allo‐tetrahydrocortisol)/petrahydrocortisone ((THF + allo‐THF)/THE) and of free cortisol/ free cortisone (UFFNFE), as well as the plasma cortisol/ cortisone ratio were measured in 8 male type 2 diabetic patients and 8 healthy male subjects without and after 24 h of insulin infusion. Insulin was infused at a rate of 30 mU/kg/h with blood glucose being clamped at euglycaemic levels in healthy subjects and at isoglycaemic levels in diabetic patients. Insulin sensitivity was assessed by measurement of whole body glucose uptake (M‐value) during a 3–4h euglycaemic clamp, directly after the 24h insulin infusion and compared to the M‐value on a control day, at least 1 week apart from the 24 h insulin infusion.

RESULTS Despite impaired insulin sensitivity (M‐value, 11.6 ± 7.7 vs. 28.5 ± 11.6μmol/kg/minutes, in type 2 diabetic and healthy subjects, respectively, P<0.05), urinary (THF+ allo‐THF)/THE ratio and baseline plasma cortisol/cortisone ratio at 0800h were similar In type 2 diabetic patients (0.82 ±.0.07 and 3.77 ± 0.70, respectively) and healthy subjects (0.76±0.14 and 3.81±0.88, respectively, ns). Insulin sensitivity was not correlated with urinary (THF + allo‐THF)/VHE ratio nor with baseline plasma cortisol/ cortisone. In type 2 diabetic patients, insulin sensitivity was further Impaired by antecedent hyperinsulinaemia (P<0.05), but the urinary (THF+ allo‐THF)TTHE ratio (0.80±0.14, ns) and the plasma cortisol/cortisone at 0800h (3.66 ± 0.72, ns) did not change. In healthy subjects, insulin sensitivity did not change significantly (M‐value, 22.5 ± 9.7μmol/kg/minutes, ns), although the urinary (THF+ allo‐THF)/THE ratio (0.92±0.25, P<0.05) and the plasma cortisol/cortisone (4.59±0.63, P<0.05) increased. Insulin did not affect the UFF/UFE ratio in either group.

CONCLUSION The present study does not support the hypothesis that insulin resistance in type 2 diabetes mellitus Is associated with an overall change in the 11βHSD set point towards cortisol. In view of the stimulatory effects of insulin and cortisol on adipogenesis, long‐term stimulation of 11βHSD reductase activity by insulin could aggravate visceral obesity.