Vasculometabolic effects in patients with congenital growth hormone deficiency with and without GH replacement therapy during adulthood.

PURPOSE: To evaluated the metabolic profiles and vascular properties in congenital growth hormone (GH) deficiency (GHD) and its replacement in adults. PATIENTS AND METHODS: Cross-sectional study conducted in a single tertiary center for pituitary diseases. Eighty-one adult subjects were divided into three groups: (1) 29 GHD patients with daily subcutaneous GH replacement therapy (GHRT) during adulthood; (2) 20 GHD patients without GHRT during adulthood and (3) 32 controls. Only patients with adequate adherence to others pituitary hormone deficiencies were included. Anthropometric parameters, body composition by dual-energy X-ray absorptiometry, metabolic profiles and vascular properties (carotid intima media thickness, pulse wave velocity and flow-mediated dilation) were compared among the groups. RESULTS: Waist-to-height ratio (WHR), body fat percentages and fat mass index (FMI) were lower in patients with GHRT than patients without GHRT during adulthood (0.49 ± 0.06 vs. 0.53 ± 0.06 p = 0.026, 30 ± 10 vs. 40 ± 11 p = 0.003 and 7.3 ± 4 vs. 10 ± 3.5 p = 0.041, respectively). In addition, association between longer GHRT and lower body fat percentage was observed (r = - 0.326, p = 0.04). We found higher triglyceride (113.5 ± 62 vs. 78 ± 36, p = 0.025) and lower HDL cholesterol (51 ± 17 vs. 66 ± 23, p = 0.029) levels in patients without GHRT during adulthood in comparison to controls. No statistical differences were observed for vascular properties among the groups. CONCLUSIONS: No differences in vascular properties were observed in congenital GHD adult patients with or without GHRT despite patients without GHRT had an unfavorable body composition. GHRT currently remains an individualized decision in adults with GHD and these findings bring new insight into the treatment and follow-up of these patients.

Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations.

BACKGROUND: Mutations in PROP1, HESX1 and LHX3 are associated with combined pituitary hormone deficiency (CPHD) and orthotopic posterior pituitary lobe (OPP). OBJECTIVE: To identify mutations in PROP1, HESX1 and LHX3 in a large cohort of patients with CPHD and OPP (35 Brazilian, two Argentinian). DESIGN AND METHODS: We studied 23 index patients with CPHD and OPP (six familial and 17 sporadic) as well as 14 relatives. PROP1 was sequenced by the Sanger method in all except one sporadic case studied using a candidate gene panel. Multiplex ligation-dependent probe amplification (MLPA) was applied to one familial case in whom PROP1 failed to amplify by PCR. In the 13 patients without PROP1 mutations, HESX1 and LHX3 were sequenced by the Sanger method. RESULTS: We identified PROP1 mutations in 10 index cases. Three mutations were novel: one affecting the initiation codon (c.1A>G) and two affecting splicing sites, c.109+1G>A and c.342+1G>C. The known mutations, c.150delA (p.Arg53Aspfs*112), c.218G>A (p.Arg73His), c.263T>C (p.Phe88Ser) and c.301_302delAG (p.Leu102Cysfs*8), were also detected. MLPA confirmed complete PROP1 deletion in one family. We did not identify HESX1 and LHX3 mutations by Sanger. CONCLUSION: PROP1 mutations are a prevalent cause of congenital CPHD with OPP, and therefore, PROP1 sequencing must be the first step of molecular investigation in patients with CPHD and OPP, especially in populations with a high frequency of PROP1 mutations. In the absence of mutations, massively parallel sequencing is a promising approach. The high prevalence and diversity of PROP1 mutations is associated with the ethnic background of this cohort.