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G Binder, BH Nagel, MB Ranke, and PE Mullis

OBJECTIVE: To determine the specific morphology of the pituitary gland in children with severe isolated GH deficiency due to GH-1 gene mutations (IGHD type II). DESIGN: The pituitary gland morphology in magnetic resonance imaging (MRI) of children with IGHD type II was analyzed and compared with the findings in a group of children with comparably severe IGHD of unknown origin. In addition, the birth histories of both groups were studied. SUBJECTS: Thirteen children with IGHD type II were diagnosed in seven European children's hospitals and they carried a corresponding GH-1 gene mutation. For comparison, we selected from a group of 66 MRI-studied GH-insufficient subjects diagnosed in our clinic, all children with severe IGHD (all GH peaks <4 microg/l) who had no GH-1 gene mutation, no first-grade relative with IGHD and no septo-optic dysplasia. METHODS: Sagittal and coronal images of the brain were analyzed for the presence of any malformation of the pituitary gland and the intracranium. The height of each adenohypophysis was measured in a strict midline sagittal image for quantification of the gland's size. In addition, patients' files were reviewed for birth trauma or breech delivery. RESULTS: Normal MRI morphology of the pituitary gland was observed in all patients of the familial IGHD type II group (P<0.003) in which, however, five of thirteen patients (38%) exhibited a mild hypoplasia of their gland (mean sagittal adenohypophysial height -1.0+/-0.03 SD score (SDS)). In contrast, the pituitary gland in the idiopathic group showed a definitive malformation with hypoplasia of pituitary stalk and adenohypophysis in all cases, while ectopia of the neurohypophysis was present in nine of the ten cases. The adenohypophysis was significantly smaller in the idiopathic group (mean sagittal adenohypophysial height -3.2+/-0.3 SDS) (P<0.0001). All thirteen birth histories in the familial group (IGHD type II) were unremarkable while, in the idiopathic group, three of eight available birth histories recorded a breech delivery or traumatic birth (37.5%) (P<0.05). CONCLUSIONS: This study shows for the first time that MRI pituitary morphology may correlate with the etiology of severe IGHD: normal morphology suggests the presence of GH-1 gene mutations, while severe hypoplasia with malformation have other causes which might include so far unknown genetic defects as well as traumatic insults.

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Natia Kajaia, Helge Binder, Ralf Dittrich, Patricia G Oppelt, Bianca Flor, Susanne Cupisti, Matthias W Beckmann, and Andreas Mueller

Background: The aim of the present study is to assess insulin resistance (IR) in women with hyperandrogenic syndrome, which was suggested to replace the term polycystic ovary syndrome by the Androgen Excess Society, and to evaluate whether sex hormone-binding globulin (SHBG) can be used as a predictive marker of IR in hyperandrogenic women.

Methods: Clinical, metabolic, and endocrine parameters were measured, and an oral glucose tolerance test was carried out. The women were classified as IR group or non-IR group, in accordance with defined cutoff points for the homeostatic model assessment of IR (HOMA-IR) at ≥2.5, the quantitative insulin sensitivity check index at ≤ 0.33, and the Matsuda insulin sensitivity index (ISI) at ≤ 5.

Results: The women classified as having IR had a significantly higher body mass index (BMI) and free androgen index (FAI) and showed significantly lower SHBG and high-density lipoprotein (HDL) levels, regardless of the indices used. However, with the Matsuda ISI, generally more women were diagnosed as having IR, and this group had significantly higher total testosterone and triglyceride values, as well as a higher incidence of hirsutism.

Conclusions: Women who were classified as being insulin resistant using insulin sensitivity indices showed significantly higher BMI and FAI values and lower SHBG and HDL levels. However, the Matsuda ISI may be more favorable for identifying IR in hyperandrogenic women. SHBG may serve as a predictive marker of IR in these women, particularly in those who are obese.