bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of body composition on hexarelin‐induced growth hormone release in normal elderly subjects
Authors: Rahim  , O'Neill  , Shalet
Published: March 2003

OBJECTIVE

Growth hormone (GH) release is influenced by several factors including age, gender, physical exercise, nutritional status, sex steroids and body composition. The relationship with body composition is complex. Obesity is accompanied by suppression of spontaneous and stimulated GH release. As increasing body fat reduces stimulated GH secretion following a standard provocative test, the potential clinical uses of GH‐releasing peptides (GHRPs), therapeutically or diagnostically, may be dependent on the relationship between body fat and GHRP‐stimulated GH release. We have therefore assessed the effect of body composition and gender on the GH releasing capacity of hexarelin.

DESIGN

A single bolus of subcutaneous hexarelin at a dose of 1.5 μg per kg of body weight was administered at time 0. Blood samples were taken at − 10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min.

SUBJECTS

Twenty‐one (eight male) healthy elderly subjects with a median (range) age of 68 (60–81) years and BMI of 26 (19–30) kg/m2 were studied.

METHODS

Dual‐energy X‐ray absorptiometry (DEXA) was used to assess body composition.

RESULTS

Peak GH response correlated negatively with fat mass, BMI, percentage body fat, and weight [r = − 0.72, P = 0.0001; r = − 0.56, P = 0.009; r = − 0.63, P = 0.002 and r = − 0.48, P = 0.029, respectively,]. AUC GH correlated negatively with fat mass, BMI and percentage fat mass [r = − 0.58, P = 0.006; r = − 0.51, P = 0.019 and r = − 0.66, P = 0.001 respectively]. Using multiple linear regression, fat mass was the most useful predictor for both peak GH response [R2 = 0.61, P < 0.0001] and AUC GH [R2 = 0.38, P = 0.003]. Gender was not a significant variable.

CONCLUSIONS

Increasing total fat mass results in a blunted GH response following subcutaneous hexarelin. Total fat mass appears to be a useful predictor of peak GH response even in normal individuals as none of the subjects in the present study was morbidly obese. This indicates that there is a continuum of effect of fat mass on hexarelin‐stimulated GH release. Any impact of gender on the GH response to hexarelin is almost certainly indirect and mediated via differences in body composition.This observation will have an impact on the potential diagnostic and therapeutic uses of hexarelin and related GH secretagogues.
Bone mineral density, bone metabolism and body composition of children with chronic renal failure, with and without growth hormone treatment
Authors: Boot Annemieke M. , Nauta Jeroen , De Jong Maria C. J. W , Groothoff Jaap W. , Lilien Marc R. , Van Wijk J. Ans E. , Kist‐van Holthe Joana E. , S. Hokken‐Koelega Anita C. , Pols Huibert A. P. , De Muinck Keizer‐Schrama Sabine M. P. F.
Published: March 2003

OBJECTIVE

Osteopenia has been reported in adult patients with chronic renal failure (CRF). Only a few studies have been performed in children. The objective of this study was to evaluate bone mineral density (BMD), bone turnover, body composition in children with CRF and to study the effect of GH on these variables.

DESIGN

Two groups were identified: patients with growth retardation who received GH (GH‐group) and patients most of whom were not growth retarded who did not receive GH (no‐GH‐group). After an observation period of 6 months, the patients in the GH‐group started GH treatment. Patients were studied every 6 months during 18 months.

PATIENTS

Thirty‐six prepubertal patients (27 boys and 9 girls), mean age 7.9 years, with CRF participated in the study. The GH‐group consisted of 17 patients of whom 14 completed one year treatment. The no‐GH‐group consisted of 19 patients, of whom 16 were followed for 6 months, 14 for 12 months and 13 for 18 months.

MEASUREMENTS

Lumbar spine BMD, total body BMD and body composition were assessed by dual energy X‐ray absorptiometry, compared to age‐and sex‐matched reference values of the same population and expressed as standard deviation scores (SDS). BMD of appendicular bone was measured by quantitative microdensitometry (QMD). Blood samples were obtained to assess bone metabolism and growth factors.

RESULTS

Baseline mean lumbar spine and total body BMD SDS of all patients were not significantly different from normal. Mean lumbar spine and total body BMD SDS did not change significantly in the GH‐group during GH treatment. The change of QMD at the midshaft during the first 6 months of GH treatment was significantly smaller than during the observation period (P < 0.01). Height SDS and biochemical markers of both bone formation and bone resorption increased significantly during GH treatment; 1,25‐dihydroxyvitamin D remained stable. Lean tissue mass increased (P < 0.001) and percentage body fat decreased (P < 0.01) during GH treatment. BMD, the biochemical markers of bone turnover which are independent of renal function, and body composition remained stable in the no‐GH‐group.

CONCLUSIONS

Mean lumbar spine and total body BMD of children with chronic renal failure did not differ from healthy controls. The lack of a GH‐induced increase in 1,25‐dihydroxyvitamin D levels, probably due to treatment with alpha‐calcidol, might be linked to the absence of a response in BMD during GH treatment in children with chronic renal failure.
Endothelial dysfunction in hypopituitary adults with growth hormone deficiency
Authors: M Evans  , Davies  , Goodfellow  , Rees  , Scanlon
Published: March 2003

OBJECTIVES

Adult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age‐and sex‐matched controls.

PATIENTS

Seventeen hypopituitary adults with GHD (13 male, 4 female) aged 26–54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age‐ and sex‐matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction.

MEASUREMENTS

Using an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium‐dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium‐independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF‐1, and studied the relationship of these parameters to endothelial function.

RESULTS

Flow mediated endothelium‐dependent dilatation (FMD), expressed as a percentage change from resting base‐line diameter, was significantly impaired in the GHD group (3.70 ± 2.36% vs. 7.30 ± 2.42%, P < 0.001). In contrast, GTN‐mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 ± 18.1 vs. 15.89 ± 6.65 mU/l, P < 0.05) and glycated haemoglobin (HbA1c) levels (5.29 ± 0.43 vs. 4.91 ± 0.43%, P < 0.05) were significantly higher in the GHD group. FMD in both groups showed an inverse relationship with total cholesterol (r = − 0.58, P < 0.05, GHD and r = − 0.55, P < 0.05 controls). However, in the GHD subjects, there was a strong inverse relationship between FMD and LDL‐cholesterol (r = − 0.81, P < 0.0001). No other relationships were noted between FMD and any other metabolic parameters, or characteristics of GHD.

CONCLUSIONS

Endothelial dysfunction is present in GH deficient adults prior to the onset of overt atherosclerotic disease. The similar glucose yet elevated fasting insulin levels imply a state of relative insulin insensitivity. The strong inverse correlation between endothelial dysfunction and LDL‐cholesterol suggests a possible aetiological role for LDL‐cholesterol in the pathogenesis of any excess cardiovascular risk associated with adult hypopituitarism.
Relationships between dehydroepiandrosterone‐sulphate and anthropometric, metabolic and hormonal variables in a large cohort of obese women
Authors: Maccario Mauro , Mazza Enrico , Ramunni Josefina , Oleandri Salvatore E. , Savio Paola , Grottoli Silvia , Rossetto Ruth , Procopio Massimo , Gauna Carlotta , Ghigo Ezio
Published: March 2003

OBJECTIVE

The aim of the present study was to measure dehydroepiandrosterone‐sulphate (DHEA‐S) levels in obesity and assess the relationships between DHEA‐S and anthropometric, metabolic and hormonal variables.

SUBJECTS AND METHODS

We evaluated the serum DHEA‐S levels in 217 obese but otherwise normal female subjects (age (mean ± SEM): 39.4 ± 0.9, range 18–67 years, body mass index (BMI) = 36.1 ± 0.4, range 27.1–57.1 kg/m2).

RESULTS

DHEA‐S levels showed an age‐dependent fall similar to that observed in normal women (n = 156, age 46.2 ± 1.2, range 22–69 years, BMI < 25 kg/m2). Adjusting for age, obese women had mean DHEA‐S levels higher than the control group (P < 0.02). In obese patients, DHEA‐S levels were directly associated with serum testosterone, androstendione, IGF‐I, fT3 levels and 24 h‐urinary cortisol. On the other hand, DHEA‐S levels were negatively associated with age, total cholesterol, triglycerides levels and systolic blood pressure. No correlation was found with BMI, waist:hip ratio, basal and post‐OGTT insulin and glucose, free fatty acids, GH, PRL, fT4, TSH, SHBG levels or diastolic blood pressure. Multiple regression analysis indicated that in obese women, DHEA‐S levels were associated negatively to age and positively to testosterone, androstendione and IGF‐I levels and daily urinary cortisol. In a subgroup of 20 obese women, DHEA‐S levels significantly (P < 0.001) fell after OGTT without any correlation with the insulin response.

CONCLUSIONS

The present results show that dehydroepiandrosterone‐sulphate levels are not reduced in obesity, being slightly increased, particularly in young adulthood. Dehydroepiandrosterone‐sulphate levels are positively and independently associated with androgen, 24‐h urinary cortisol and IGF‐I levels but do not seem associated with insulin levels or cardiovascular risk indices.
The continuous 7‐hour intravenous dexamethasone suppression test in the differential diagnosis of ACTH‐dependent Cushing's syndrome
Authors: Van Den Bogaert Debby P. M. , De Herder Wouter W. , De Jong Frank H. , Biemond Piet , Van Der Lely Aart‐Jan , Lamberts Steven W. J.
Published: March 2003

OBJECTIVE

A recent report showing disappointingly low sensitivity and specificity for the oral high dose dexamethasone test in the differential diagnosis of Cushing's syndrome prompted us to re‐evaluate the results obtained in our centre using the continuous 7‐hour intravenous dexamethasone suppression test for this purpose.

PATIENTS

105 patients with ACTH–dependent Cushing's syndrome were included in this study; 78 with Cushing's disease, 8 with ectopic ACTH‐secreting tumours and 19 were classified as ‘of unknown aetiology’.

RESULTS

In 74/78 (94.9%) of patients with Cushing's disease and in 3/8 (37.5%) patients with the ectopic ACTH syndrome, a plasma cortisol decrease > 190 nmol/l at 7 h as compared to baseline values was achieved in the continuous 7‐hour intravenous dexamethasone suppression test. Using a plasma cortisol decrease > 190 nmol/l at 7 h as compared to baseline values as the cut‐off value, the sensitivity and specificity of the continuous 7‐hour intravenous dexamethasone suppression test for the diagnosis of Cushing's disease in patients with ACTH–dependent Cushing's syndrome were 94.9% and 62.5%, respectively.

CONCLUSIONS

In patients with ACTH–dependent Cushing's syndrome with a plasma cortisol decrease > 190 nmol/l at 7 h in the continuous 7‐hour intravenous dexamethasone suppression test, additional localizing investigations such as bilateral simultaneous inferior petrosal sinus sampling and/or pentetreotide scintigraphy should be performed when no clearly discernible pituitary adenoma is observed on MRI studies. Patients with ACTH–dependent Cushing's syndrome with a plasma cortisol decrease < 190 nmol/l at 7 h in the continuous 7‐hour intravenous dexamethasone suppression test should also undergo bilateral simultaneous inferior petrosal sinus sampling and/or pentetreotide scintigraphy to demonstrate the presence of a nonpituitary source of ACTH overproduction.
The relationship among circulating insulin‐like growth factor components, biochemical markers of bone turnover and bone mineral density in postmenopausal women under the age of 60
Authors: Kim  , Shin  , Choi  , Moon  , Kim  , Lee
Published: March 2003

OBJECTIVES

The changes in circulating IGF components after the menopause and the potential role of new markers of bone turnover and circulating IGF components in predicting bone mass in postmenopausal women are still controversial and the relationship between these two systems has not been investigated. The aims of this study were to investigate the changes in circulating IGF components after the menopause, to evaluate whether new markers of bone turnover and circulating IGF components reflect bone mass in postmenopausal women under the age of 60 and to study the relationship between these two systems.

DESIGN, PATIENTS AND MEASUREMENTS

Serum IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2, IGFBP‐3, osteocalcin (OST), bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPYD) and N‐telopeptide of type I collagen (NTX) were measured in 31 premenopausal women aged 31–43 and 65 postmenopausal women aged 47–60: this latter group comprised 30 normal healthy women and 35 osteoporotic women.

RESULTS

Compared with premenopausal women or normal postmenopausal women, serum IGF‐1 and IGFBP‐3 levels were significantly lower in osteoporotic postmenopausal women while no significant differences in serum levels of IGF‐II, IGFBP‐1 and IGFBP‐2 were observed. The correlations between bone turnover markers and circulating IGF components (except between serum BAP and IGF‐II), and between bone turnover markers and bone mineral density (BMD) in postmenopausal women were not significant. However, serum IGF‐I and IGFBP‐3 correlated positively with BMD of the lumbar spine and/or Ward's triangle even if age, BMI and menopause duration were taken into account in a multiple regression analysis model.

CONCLUSIONS

Circulating IGF‐I and IGFBP‐3 may be involved in the mechanism of bone loss in postmenopausal women under the age of 60. They may also provide indirect information on the current bone microenvironment different from that provided by new markers of bone turnover.
Splanchnic exchange of insulin‐like growth factor binding protein‐1 (IGFBP‐1), IGF‐I and acid‐labile subunit (ALS) during normo‐ and hyper‐insulinaemia in healthy subjects
Authors: Fernqvist‐Forbes Eva , Ekberg Karin , Lindgren Björn F. , Brismar Kerstin
Published: March 2003

OBJECTIVE

The main source of circulating IGF‐I, insulin like growth factor binding protein‐1 (IGFBP‐1) and acid‐labile subunit (ALS) is considered to be the liver, but their production rates have not been determined in healthy individuals. Thus, the splanchnic exchange of IGFBP‐1, IGF‐I, ALS and glucose were studied.

STUDY DESIGN

In five overnight fasting healthy, normal weight men (mean age 29 ± 1 years) blood samples were taken from a hepatic vein, a brachial artery and a peripheral vein in the basal state and during 3 h i.v. infusion of insulin (1.0 mU/kg/min). Normoglycaemia was maintained with a variable glucose infusion and splanchnic blood flow was determined using a constant rate indicator infusion technique.

RESULTS

The basal net splanchnic glucose output amounted 0.96 ± 0.09 mmol/min and the splanchnic production of IGFBP‐1 was 7 ± 2 μg/min. There was a net splanchnic uptake of IGF‐I (7 ± 2 μg/min) in the basal state, while no significant splanchnic exchange of ALS was found. During the insulin infusion, insulin concentration increased from 78 ± 12 to 660 ± 30 pmol/l, resulting in a complete inhibition of splanchnic glucose production after 40 min of infusion. Splanchnic IGFBP‐1 production rose initially to 13 ± 4 μg/min (P < 0.05) and then gradually decreased and was completely inhibited at 180 min (P < 0.05). Insulin infusion influenced neither ALS nor IGF‐I splanchnic exchange.

CONCLUSION

Splanchnic production of IGFBP‐1 in the basal state was demonstrated and it is completely inhibited after 180 min of hyperinsulinaemia. In contrast to what is generally held, there was no net splanchnic production of IGF‐I in the basal state or during insulin stimulation.
The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome
Authors: Ünlühizarci Kürşad , Keleştimur Fahrettin , Bayram Fahri , Şahin Yilmaz , Tutuş Ahmet
Published: March 2003

OBJECTIVE

Polycystic ovary syndrome (PCOS) is a form of functional ovarian hyperandrogenism and affects approximately 5‐10% of women of reproductive age. Insulin resistance and hyperinsulinaemia appear to be almost universal feature of the polycystic ovary syndrome. Abnormal regulation of cytochrome P450c17α causes the exaggerated secretion of ovarian androgens in PCOS. The aim of the present study was to determine whether reduction of insulin levels by metformin would attenuate FSH, LH, 17‐Hydroxyprogesterone (17‐OHP) and androstenedione hyperresponsiveness to buserelin testing in PCOS women.

DESIGN

The presence of hyperinsulinaemia in 16 women with PCOS was demonstrated by an oral glucose tolerance test (OGTT) and results were compared with 13 healthy women. PCOS women were also evaluated with insulin tolerance test (ITT) for the assessment of insulin sensitivity. FSH, LH, 17‐OHP and androstenedione responses to buserelin testing were measured in all the women with PCOS. PCOS patients were given metformin (500 mg, orally, two times daily) for 12 weeks and re‐evaluated at the end of the treatment period.

RESULTS

Women with PCOS were hyperinsulinaemic (basal insulin 92.1±14.3 vs. 44.0±4.0 pmol/l ; AUCinsulin 68087.4±8862.3 vs. 13075.5±1327.6 pmol/l×120 min) compared with healthy women. Metformin therapy improved menstrual disturbances in 25% of the women with PCOS and also resulted in some improvement in insulin sensitivity and reduced basal and post glucose load insulin levels. However, FSH, LH, 17‐OHP and androstenedione responses to buserelin testing were unaltered in response to metformin.

CONCLUSION

It is clear that PCOS is often associated with profound insulin resistance and hyperinsulinaemia. These abnormalities explain the increased prevalence of glucose intolerance in women with PCOS and metformin has beneficial effects on insulin sensitivity in women with PCOS. Amelioration of hyperinsulinaemia has no significant effect on ovarian cytochrome P450c17α enzyme activity. However, it can be used in obese women with PCOS as an adjuvant therapy and long term studies should be performed to evaluate the endocrine effects of metformin in women with PCOS.
A comparison of lanreotide and octreotide LAR for treatment of acromegaly
Authors: Turner  , Vadivale  , Keenan  , Wass
Published: March 2003

BACKGROUND AND OBJECTIVE

Two long‐acting depot somatostatin analogues have recently been licensed for the treatment of acromegaly. We wished to assess the effectiveness of both these drugs in suppressing mean GH to a target of < 5 mU/l in patients with acromegaly unselected for responsiveness to octreotide, and also to compare the effects of both drugs

METHODS

We prospectively studied 10 unselected patients with acromegaly who were treated first with lanreotide (LAN) and then octreotide LAR (LAR) following a washout period. The target for therapy was to achieve mean GH less than 5 mU/l.

RESULTS

Five (50%) patients achieved mean GH < 5 mU/l on lanreotide 30 mg every 10 days, and 7 out of 9 (77.8%) achieved this level when the dose frequency was increased to every 7 days. On 20 mg octreotide LAR, 6 (60%) patients achieved the target mean GH and a further 2 (80%) when the dose was increased to 30 mg. Normalization of IGF‐1 occurred in 5/9 (55.6%) patients who received lanreotide and 7/10 (70%) of those who received octreotide LAR. There was a significant difference in mean GH attained on the 2 drugs. The patients' mean GH was significantly lower when treated with octreotide LAR 20 mg every 4 weeks compared with lanreotide 30 mg every 10 days (P = 0.037). Maximal suppression of mean GH with 30 mg octreotide LAR or 7 day dosing of lanreotide was significantly greater on octreotide LAR (P < 0.02).

CONCLUSIONS

At current dose recommendations, lanreotide and octreotide LAR are both effective in lowering mean GH to 'safe’ (< 5 mU/l) levels in 80% patients but octreotide LAR treatment leads to significantly lower mean GH.
Analysis of the intracellular signalling domain of the human growth hormone receptor in children with idiopathic short stature
Authors: Johnston Linda B. , Pashankar Farzana , Camacho‐Hübner Cecilia , Savage Martin O. , Clark Adrian J.L.
Published: March 2003

OBJECTIVE To investigate the hypothesis that intracellular, dominant‐negative mutations of the growth hormone receptor (GHR) exist in children with idiopathic short stature (ISS) and partial growth hormone insensitivity (GHI).

SUBJECTS We studied 31 children aged 4.55–13.14 years with ISS (height ≤‐1.8 standard deviation scores, UK standards 1990). GH provocation tests (glucagon 15μg kg−1 i.m.) excluded GH deficiency In all subjects. Serum IGF‐I levels were below the 50th centile for age in all subjects and below the 10th centile in 64.5% of cases. GH binding protein levels were normal in the 24 subjects in whom It was measured (mean 25.2%; range 10–42.6%).

METHODS Exons 9 and 10 of the GHR were amplified by PCR from leucocyte‐derived DNA. Samples were directly sequenced on the ABI 377 DNA analyser using the −21 M13 dye primer cycle sequencing protocol for optimum heterozygote detection.

RESULTS No abnormalities were detected in exon 9 which encodes the proline‐rich box 1 motif. In exon 10 two sequence variants were found; a heterozygous, single base alteration (TCT to TCC) in codon 325 which does not change the amino acid sequence in one patient, and the L5261 variant in 24 subjects. L5261 is a conservative amino acid change and had an allele frequency of 0.53 in our patients, which is similar to that reported in a control population.

CONCLUSIONS The apparent partial growth hormone insensitivity in this group of idiopathic short‐stature subjects is not related to heterozygous, dominant‐negative variants of the intracellular signalling domain of the GHR. Hence it is likely that other genetic and environmental factors may be involved.
Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: analysis of 20 Japanese sporadic cases with MEN1
Authors: Hai Noritaka , Aoki Norihiko , Shlmatsu Akira , Mod Toru , Kosugi Shinjl
Published: March 2003

OBJECTIVE Multiple endocrine neoplasia type 1 (MEN1) is a familial tumour syndrome of endocrine tumours involving parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner with high penetrance. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned from chromosome 11q13.

PATIENTS To characterize sporadic MEN1 patients, we analysed the MEN1 gene by direct sequencing of the entire open reading frame from 20 individuals. RESULTS We identified heterozygous germline mutations of the MEN1 gene in 8 of 20 (40%) cases. Seven were novel MEN1 germline mutations. Three mutations were splicing abnormalities, and all were confirmed to be splicing defects by RT‐PCR. The clinical significance of detecting germline MEN1 mutations, not only in familial MEN1 but also in sporadic MEN1, was confirmed by the finding of asymptomatic mutant carriers among family members of the sporadic MEN1 patients. Seven of 8 cases with MEN1 mutations had enteropancreatic lesions in contrast to 4 of 12 (P<0.018) in those cases with no mutation. Ten of the 12 cases without MEN1 mutation were more than 50–year‐old. Six of these 10 cases had the same clinical features; primary hyperparathyroidism and a GH‐secreting pituitary tumour.

CONCLUSIONS It Is likely that the six cases without mutations were MEN1 phenocopies due to (i) two kinds of tumours with high natural incidence in older subjects developed by chance (ii) another familial tumour syndrome with low penetrance, e.g. familial acromegaly with primary hyperparathyroidism by mutation of another gene, or (iil) somatic mutation during early embryonic stages.
Growth hormone and prolactin are secreted more irregularly in patients with Cushing's disease
Authors: Veldman Ronald Groote , Frölich Marijke , Pincus Steve M. , Veldhuis Johannes D. , Roelfsema Ferdinand
Published: March 2003

OBJECTIVE

To investigate whether the spontaneous secretion of growth hormone and prolactin in adult patients with pituitary‐dependent Cushing's disease is decreased.

PATIENTS

Fourteen adult patients (9 women, 5 men; age: 34 ± 3.4 years, mean ± SEM) with pituitary‐dependent Cushing's disease and 14 controls matched for age, gender and body mass index were studied.

METHODS

Blood samples were withdrawn at 10 minutes intervals starting at 0900 h for 24 h. GH and PRL release were quantified with deconvolution methods. The regularity of GH and PRL release was measured with approximate entropy statistics.

RESULTS

The number of GH secretory events per 24 h was higher in patients than in controls: 19 ± 1.3 vs. 14 ± 1.5 peaks per 24 h, respectively (P = 0.020). GH secretion rate was about one quarter lower in patients (ns), and the 24 h secretion of PRL was unchanged. Total GH production correlated negatively with the urinary excretion of free cortisol (R = 0.729, P = 0.005) and with the plasma cortisol production rate (R = 0.613; P = 0.026).

The orderliness of GH and PRL secretion was appraised with the approximate entropy statistic (ApEn). For GH secretion ApEn(1,20%) in patients was 0.952 ± 0.084 vs. 0.404 ± 0.047 in controls, P = 1.17 × 10−4, pointing to a markedly disordered secretion in patients. Similar results were obtained for PRL secretion: patients: 1.586 ± 0.063 vs. 1.003 ± 0.068 in controls, P = 3.67 × 10−5. No statistically significant differences in secretory dynamics were demonstrated between the 10 patients with a microadenoma and the four with a macroadenoma.

CONCLUSION

The amount of GH released spontaneously into the circulation in adult patients with pituitary‐dependent Cushing's disease is inversely related to the degree of cortisol hypersecretion. However, except for severe hypercortisolism, GH secretion is relatively preserved. In addition, secretion of GH and PRL is remarkably disordered in patients with Cushing's disease. Since we could not detect differences in GH and/or PRL secretory dynamics between patients with a microadenoma and those harboring a macroadenoma, we speculate that an intrapituitary paracrine mechanism and/or elevated cortisol feedback effects may be responsible for the evident disruption of GH and PRL secretion patterns.
The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism
Authors: Soule Steven , Van Zyl Smit Cathy , Parolis Gerry , Attenborough Shaun , Peter Debbie , Kinvig Sue , Kinvig Tanya , Coetzer Elizna
Published: March 2003

OBJECTIVE

The 1 μg ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic–pituitary–adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 μg ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease.

DESIGN

A prospective analysis of the performance of the 1 μg ACTH stimulation test in a group of patients with pituitary disease.

PATIENTS

The cortisol response to 1 μg ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11‐deoxycortisol response to overnight metyrapone: normal (11‐deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11‐deoxycortisol < 200 nmol/l).

MEASUREMENTS

In both controls and patients, blood was sampled for cortisol at − 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 μg synthetic ACTH (Synacthen®). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11‐deoxycortisol.

RESULTS

The 65 patients with pituitary disease were categorized according to the 11‐deoxycortisol response to metyrapone as follows: 53 normal (11‐deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 μg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut‐off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%.

CONCLUSIONS

The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 μg ACTH stimulation test, like the 250 μg‐test, lacks sensitivity for the diagnosis of ACTH deficiency.
Effects of successful parathyroidectomy on altered arterial reactivity in patients with hypercalcaemia: results of a 3‐year follow‐up study
Authors: Neunteufl Thomas , Heher Sandra , Prager Gerhard , Katzenschlager Reinhold , Abela Claudette , Niederle Bruno , Stefenelli Thomas
Published: March 2003

OBJECTIVE

Serum calcium was found to be an independent, prospective risk factor for myocardial infarction. We have previously shown that altered arterial reactivity in the course of primary hyperparathyroidism, a disease characterized by hypercalcaemia, may predominantly involve the arterial media and not the endothelium as observed in patients with various stages of atherosclerosis. The present study was performed to test whether successful parathyroidectomy can improve vascular reactivity in patients with primary hyperparathyroidism.

SUBJECTS AND DESIGN

Endothelium‐dependent, flow‐mediated and endothelium‐independent, nitroglycerin‐induced dilatation were assessed by brachial artery ultrasound (7 MHz) in 18 patients with primary hyperparathyroidism (mean ± SD; age, 55.1 ± 12.6) prior to and 3 years after successful parathyroidectomy.

RESULTS

Parathyroidectomy resulted in significant decreases of PTH (242 ± 186 vs. 34 ± 24 ng/l, P = 0.0001) and serum calcium levels (2.8 ± 0.3 vs. 2.4 ± 0.1 mm/l, P = 0.00001) and in an increase of serum phosphate levels (0.78 ± 0.23 vs. 1.17 ± 0.18 mm/l, P = 0.00001). However, normalization of hormone and electrolyte levels did not lead to an improvement of flow‐mediated dilatation (12.1 ± 3.1 vs. 11.0 ± 5.4&, P = 0.49) or nitroglycerin‐induced dilatation (12.5 ± 3.1 vs. 13.2 ± 6.8%, P = 0.68) within the follow‐up period. No changes were observed with respect to the risk factor profile, vessel size and blood flow.

CONCLUSION

These data suggest that restoration of normocalcaemia by parathyroidectomy cannot improve vascular reactivity in patients with primary hyperparathyroidism but may prevent further progression of vascular disease within this period of time.
No advantage of the new combined octreotide‐GHRH test over established GH‐stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults
Authors: Schütz Florian , Wüster Christian , Heilmann Peter , Ziegler Reinhard , Hadji Peyman
Published: March 2003

OBJECTIVE

To evaluate the sensitivity and specificity of a combined octreotide (SMS)‐GHRH test we compared it with established GH stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults.

DESIGN

Because there is no universally agreed gold standard for the diagnosis of GHD in adults it is difficult to define the relative merits of different tests in patients with structural pituitary disease. We have addressed this by grouping patients according to the degree of concordance between three established tests (insulin (IHT), arginine (ARG) and GHRH stimulation test (GHRH)) and serum IGF‐I levels and have subsequently analysed the frequency destribution of test results across defined groups: group 1, with complete GHD in all tests, group 2, with differences between tests with regard to the diagnosis of GHD and group 3, with normal GH response in all tests. The patients also underwent a new combined SMS‐GHRH test, the results of which were compared with IHT, ARG and GHRH.

MEASUREMENTS

Five hours after an octreotide injection GHRH was given intravenously and GH measured.

RESULTS

ARG had the highest sensitivity (Se = 100%) and specificity (Sp = 100%) of the tests used. The IHT also diagnosed GHD with precision but showed false positive as well as false negative results (Se = 90%, Sp = 100%). Se and Sp of GHRH were lower than those of IHT and ARG (Se = 100%, Sp = 89%). The SMS‐GHRH worked well and was superior to GHRH but had less precision than IHT and ARG (Se = 88%, Sp = 100%).

CONCLUSION

We conclude that there is discordance between the three established tests and that the octreotide‐GHRH test does not have any advantages for diagnosing GHD in adults. IGF‐I levels can be used as a screening test only. The arginine test was the best conventional test in our study.
Panhypopituitarism associated with severe retroperitoneal fibrosis
Authors: Braun Jens , Schuldes Horst , Berkefeld Joachim , Zanella Friedhelm , Jonas Dietger , Usadel Klaus‐Henning , Badenhoop Klaus
Published: March 2003

A 43‐year‐old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started.

Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis.

Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis ‘idiopathic retroperitoneal fibrosis’ is confirmed, fibrotic manifestations and complications involving extra‐retroperitoneal tissues including the endocrine system, should be sought.
Relationships with serum parathyroid hormone in old institutionalized subjects
Authors: Stein M. S. , Flicker L. , Scherer S. C. , Paton L. M. , O'Brien M. L. , Walton S. C. , Chick P. , Di Carlantonio M. , Zajac J. D. , Wark J. D.
Published: March 2003

OBJECTIVE and BACKGROUND Old people in residential care are at the highest risk of any group for hip fracture. This may relate to their high prevalence of hyperparathyroidism. There are few data, however, on relationships with serum parathyroid hormone (PTH) in these individuals. This study therefore examined complex associations with serum PTH in nursing home and hostel residents.

DESIGN Cross‐sectional analysis.

PATIENTS One hundred and forty‐three nursing home and hostel residents of median age 84 years.

MEASUREMENTS Serum PTH, 25‐hydroxyvitamin D (25OHD), 1,25‐dihydroxyvitamin D (1,25‐(OH)2D), plasma creatinine, phosphate, calcium, albumin, Bsm‐1 vitamin D receptor genotype, age, weight and use of frusemide or thiazide.

RESULTS The statistical models determined accounted for half the interindividual variation in serum PTH. Heavier weight was associated with both the prevalence of secondary hyperparathyroidism and the serum concentration of PTH. Novel interactions with serum PTH were identified between: weight and 25OHD; 25OHD and phosphate; and phosphate and thiazide diuretic use. Plasma phosphate was associated with PTH independently of calcium and 1,25‐(OH)2D. There was no independent association between PTH and nuclear vitamin D receptor genotype.

CONCLUSIONS Heavier weight is associated with both the prevalence and severity of secondary hyperparathyroidism and consistent with animal models of secondary hyperparathyroidism, phos‐phate may relate to serum PTH independently of 1,25‐(OH)2D or calcium.
Extramedullary plasmacytoma in the adrenal incidentaloma
Authors: Kahara T. , Nagai Y. , Yamashita H. , Nohara E. , Kobayashi K. , Takamura T.
Published: March 2003

High‐resolution imaging has led to the increasingly frequent discovery of adrenal incidentalomas. Most are nonfunctioning tumours and adenomas, but it is difficult to distinguish benign from malignant tumours using only morphological and laboratory data, and the diagnosis often remains uncertain without histological examination. Here we report the case of a 52‐year‐old Japanese man who had a right adrenal incidentaloma 4 cm in diameter. The tumour was removed by laparoscopic adrenalectomy. The pathology specimen revealed the typical histology of plasmacytoma. Extramedullary plasmacytoma is a very rare type of plasma cell proliferative disorder. This is the first documented case of an extramedullary plasmacytoma in the adrenal gland.
In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A
Authors: Wessels H. T. , Hofland L. J. , Van Der Wal R. , Van Gastel L. , Van Koetsveld P. M. , De Herder W. W. , De Jong F. H.
Published: March 2003

OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas.

PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn‐omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)‐producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn‐omas.

RESULTS Gn‐omas were found to secrete significantly more activin A in their culture medium than PRL‐ and GH‐producing adenomas (P < 0·05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0·56, P < 0·005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0·73, P < 0·0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0·79, P < 0·0005).

CONCLUSIONS It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.
Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism
Authors: Karjalainen A. , Paassilta M. , Heikkinen J. , Bäckström A‐C. , Savolainen M. , Kesäniemi Y. A.
Published: March 2003

OBJECTIVE

Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA1c have been studied only among diabetics. The objective of this studywas to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration.

DESIGN

The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17β‐oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double‐blind, double‐dummy study for six months.

PATIENTS

Seventy‐nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group.

MEASUREMENTS

Oral glucose tolerance tests (OGTT) with blood glucose, serum C‐peptide and insulin determinations were performed. GHbA1c, IGF‐I and IGFBP‐1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT.

RESULTS

A small significant reduction in the GHbA1c concentration was observed during both peroral (P < 0·05) and transdermal oestrogen therapy (P < 0·05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C‐peptide decreased by 8% both in the peroral group (P < 0·05) and in the gel group (P < 0·01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF‐I and increased IGFBP‐1, but these findings were not associated with the changes in glucose metabolism.

CONCLUSIONS

Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.
Hypogonadism in patients with acromegaly: data from the multi‐centre acromegaly registry pilot study
Authors: Katznelson Laurence , Kleinberg David , Vance Mary Lee , Stravou Stavros , Pulaski Karen J. , Schoenfeld David A. , Hayden Douglas L. , Wright Margaret E. , Woodburn Carol J. , Klibanski Anne
Published: March 2003

OBJECTIVE

Because acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi‐centre acromegaly patient registry.

DESIGN AND MEASUREMENTS

Medical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website. Hypogonadism was defined as amenorrhoea in women and testosterone deficiency in men. Subanalysis was performed in patients with microadenomas and women less than 50 years of age, to include women of reproductive age.

RESULTS

Information was available on 363 patients, of whom 54% were women. The mean age at diagnosis was 41 ± 13 years. In subjects less than 50 years of age, hypogonadism was present in 59%. Hyperprolactinaemia was present in 45% and 21% of hypogonadal and eugonadal patients of reproductive age, respectively (P = 0·0003). GH levels were higher in patients with hypogonadism (P = 0·03). In patients < 50 years of age with microadenomas, hypogonadism was present in nine of the 22 (41%) patients, including 55% of the women and 27% of the men (P = ns). Hyperprolactinaemia was present in three of the 10 and four of the 14 of microadenoma patients with hypogonadism and eugonadism, respectively.

CONCLUSION

We developed a web‐based acromegaly patient registry and used it to show that hypogonadism is a frequent consequence of acromegaly, even in patients with microadenomas, who are not at risk from hypopituitarism due to local mass effects. We also demonstrated that prolactin and GH hypersecretion contribute to the pathogenesis of hypogonadism in acromegaly, and that hypogonadism may occur in microadenoma patients even in the absence of hyperprolactinaemia.
The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision
Authors: Stuckey Bronwyn G. A. , Kent G. Neil , Allen Janet R.
Published: March 2003

To follow the clinical and biochemical course of a cohort of women who had postpartum thyroid dysfunction (PPTD) at 6 months postpartum and to examine the treatment practices of general practitioners and endocrinologists in the setting of PPTD.

Prospective longitudinal study.

Metropolitan, Perth, Australia.

Eighty‐six Caucasian women who were identified to have PPTD at 6 months postpartum in a cross‐sectional study of 748 women.

Characteristics of the clinical and biochemical course of PPTD and documentation of the treatment practices and factors influencing treatment of PPTD by general practitioners and endocrinologists.

Sixteen of 86 women (19%) were receiving treatment at 9 months postpartum and by 30 months postpartum 27% of women had received treatment for PPTD. Fifty‐one percent of those not treated were biochemically euthyroid at 9 months, although, for those with hypothyroid biochemistry at 6 months, the median TSH at 18 months was at the upper limit of the reference range. Thyroid peroxidase antibody titre fell over the 2 years of follow‐up. There was no significant change in clinical parameters over the study. Forty‐nine percent of endocrinologists and 73% of general practitioners reported that they required clinical signs or symptoms before initiating treatment for hypothyroid PPTD.

In a cohort of women with postpartum thyroid dysfunction, a quarter received treatment. Elevated TSH in untreated women does not completely return to the normal median. The role of clinical assessment in treatment decision‐making differs between primary care physicians and endocrinologists. A case is made for the early Institution of permanent thyroxine replacement in women with postpartum thyroid dysfunction, elevated TSH and positive thyroid antibodies.