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V Gasco, G Corneli, G Beccuti, F Prodam, S Rovere, J Bellone, S Grottoli, G Aimaretti and E Ghigo

GH deficiency (GHD) in adults has to be shown by a single provocative test, provided that it is validated. Insulin tolerance test (ITT) has been indicated as the test of choice; now also glucagon test is validated and represents an alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH secretagogue are equally reliable diagnostic tools, and are now considered as ‘golden’ standards as ITT. Childhood-onset (CO) GHD needs retesting in late adolescence or young adulthood; this is a major clinical challenge and raises questions about the most appropriate method and cut-off value. Appropriate re-evaluation of GH status is represented by simple measurement of IGF1 concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of persistent severe GHD in subjects with genetic GHD or panhypopituitarism. However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1 levels must undergo a provocative test. The appropriate GH cut-off limit is specific for each provocative test. As shown by the ROC curve analysis, in late adolescents and young adults, the lowest normal GH peak response to ITT is 6.1 μg/l while that to GHRH+ARG test is 19.0 μg/l. These cut-off limits, however, are just indicative as being variable as a function of the assay used. No other test is validated for retesting. As GHRH+ARG test mostly explores the GH-releasable pool, normal GH response would be verified by a second ITT in order to rule out subtle hypothalamic defect.

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H J Schneider, S Rovere, G Corneli, C G Croce, V Gasco, R Rudà, S Grottoli, G K Stalla, R Soffietti, E Ghigo and G Aimaretti

Objective: Hypopituitarism frequently follows pituitary neurosurgery (NS) and/or irradiation. However, the frequency of hypothalamic–pituitary dysfunction after NS of non-pituitary intracranial tumors is unclear. The aim of this study was to assess the presence of endocrine alterations in patients operated on for intracranial tumors.

Design: This is a retrospective study.

Methods: We studied 68 consecutive adult patients (28 female, 40 male, age 45.0 ± 1.8 years; body mass index (BMI): 26.5 ± 0.6) with intracranial tumors who underwent NS only (n = 17) or in combination with radiotherapy (RT) and/or chemotherapy (CT) (n = 51). In all subjects, basal endocrine parameters and the GH response to GHRH + arginine test (using BMI-dependent cut offs) were evaluated.

Results: In 20.6% of the patients, peripheral endocrinopathy related to CT and/or RT was present. Hypopituitarism was found in 38.2% of the patients. Total pituitary hormone, multiple pituitary hormone, and isolated pituitary hormone deficits were present in 16.2, 5.8, and 16.2% respectively. The most common pituitary deficits were, in decreasing order: LH/FSH 29.4%, GH 27.9%, ACTH 19.1%, TSH 17.7%, and diabetes insipidus 4.4%. Hyperprolactinemia was present in 13.2%. The prevalence of hypopituitarism was higher in patients who underwent NS only and with tumors located closely to the sella turcica, but a substantial proportion of patients with tumors not directly neighboring the sella also showed hypopituitarism.

Conclusions: Hypopituitarism frequently occurs after NS for intracranial tumors. Also, exposure of these patients to CT and/or RT is frequently associated with peripheral endocrinopathies. Thus, endocrine evaluation and follow-up of patients treated for intracranial tumors should be performed on a regular basis.

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Iris J G Ketel, Mariken N M Volman, Jacob C Seidell, Coen D A Stehouwer, Jos W Twisk and Cornelis B Lambalk

Objective: To determine which anthropometric measurement is the most reliable alternative for fat distribution as measured by dual-energy X-ray absorptiometry (DXA).

Design: Population-based survey carried out in Amsterdam, The Netherlands.

Subjects and methods: A total of 376 individuals (200 women) with a mean age of 36.5 years and mean body mass index (BMI) of 24.0 (±3.1) kg/m2 underwent various anthropometric and DXA measurements of central (CFM) and peripheral fat mass (PFM). Furthermore, for the assessment of apple-shaped body composition, CFM-to-PFM ratio was calculated. Anthropometric measurements were waist and hip circumference, waist-to-hip ratio (WHR), BMI, waist/length and the skinfold thickness of biceps, triceps, suprailiacal (SI), subscapular (SS) and upper leg. We determined whether equations of combined anthropometrics were even more reliable for the assessment of fat mass.

Results: In both women and men, reliable alternatives for CFM are central skinfolds and waist (Pearson’s correlation (r) ≥ 0.8). Peripheral skinfolds are the best predictors of PFM (r ≥ 0.8). In contrast, WHR correlated only marginally with any of the DXA measurements. Equations based on several anthropometric variables correlate with CFM even better (R 2 ≥ 0.8). CFM-to-PFM ratio has the highest correlation with the ratio (SS+SI)/BMI in women (r = 0.66) and waist/length in men (r = 0.71). Equations are reasonable alternatives of CFM-to-PFM ratio (R 2 ≥ 0.5).

Conclusion: Waist and skinfolds are reliable alternatives for the measurement of body fat mass in a cohort of Caucasian adults. WHR is not appropriate for the measurement of fat distribution.

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Mirte R Caanen, Esther A Kuijper, Peter G Hompes, Mark M Kushnir, Alan L Rockwood, Wayne A Meikle, Roy Homburg and Cornelis B Lambalk

Objective

Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls.

Design

Prospective case–control study.

Methods

Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E1), estradiol (E2), estriol (E3)) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.

Results

At 20 weeks of gestation: T (P=0.019) and ADION (P=0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E1, E2, and E3 were not different. Maternal concentration at birth: T (P=0.004) and ADION (P=0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E1, E2 and E3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E2, E3, and AMH between the PCOS mothers and the controls respectively. E1 was lower in girls from PCOS mothers (P=0.007).

Conclusions

Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

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Koen M A Dreijerink, André P van Beek, Eef G W M Lentjes, Jan G Post, Rob B van der Luijt, Marijke R Canninga-van Dijk and Cornelis J M Lips

Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome that is characterised by the occurrence of tumours in the parathyroid glands, the endocrine pancreas, the pituitary gland and the adrenal glands and by neuroendocrine carcinoid tumours, often at a young age. The penetrance of MEN1 among gene carriers is reported to be high; 82–99% at age 50. We present a patient with a history of parathyroid adenomas also showing signs of acromegaly. He turned out to be a carrier of a MEN1 germ-line mutation in intron 3 (IVS3-6C > G). This germ-line mutation was also found in nine of his family members. However, none of these relatives have developed any MEN1-related lesion yet, although several are older than 60 years. To our knowledge, a MEN1 family with as few clinical features as this family has not been reported to date. Because MEN1 patients have an increased risk of developing acromegaly, insulin-like growth factor (IGF-I) levels are monitored periodically. We investigated whether IGF-I levels might serve as a presymptomatic marker for acromegaly; 9% (3/33) of MEN1 patients showed temporary IGF-I elevations. One patient (1/3) later developed clinical signs of acromegaly. Possibly, acromegaly in MEN1 is preceded by a transient preacromegalic state.