RESUMO
CONTEXT: The GH/IGF-I axis is important for bone growth, but its effects on joint function are not completely understood. Adult-onset GH-deficient individuals have often reduced bone mineral density (BMD). However, there are limited data on BMD in adult patients with untreated congenital isolated GH-deficient (IGHD). We have shown that adult IGHD individuals from the Itabaianinha, homozygous for the c.57+1G>A GHRHR mutation, have reduced bone stiffness, but BMD and joint status in this cohort are unknown. OBJECTIVE: The goal is to study BMD, joint function, and osteoarthritis score in previously untreated IGHD adults harboring the c.57+1G>A GHRHR mutation. DESIGN: This is a cross-sectional study. METHODS: Areal BMD by dual-energy X-ray absorptiometry was measured in 25 IGHD and 23 controls (CO). Volumetric BMD (vBMD) was calculated at the lumbar spine and total hip. Joint function was assessed by goniometry of elbow, hips, and knees. X-rays were used to measure the anatomic axis of knee and the severity of osteoarthritis, using a classification for osteophytes (OP) and joint space narrowing (JSN). RESULTS: Genu valgum was more prevalent in IGHD than CO. The osteoarthritis knees OP score was similar in both groups, and knees JSN score showed a trend to be higher in IGHD. The hips OP score and JSN score were higher in IGHD. Areal BMD was lower in IGHD than CO, but vBMD was similar in the two groups. Range of motion was similar in elbow, knee, and hip in IGHD and CO. CONCLUSIONS: Untreated congenital IGHD due to a GHRHR mutation causes hip joint problems and genu valgum, without apparent clinical significance, reduces bone size, but does not reduce vBMD of the lumbar spine and hip.
Assuntos
Nanismo Hipofisário/genética , Geno Valgo/genética , Osteoartrite do Quadril/genética , Osteoartrite do Joelho/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Absorciometria de Fóton , Adulto , Densidade Óssea , Estudos Transversais , Nanismo Hipofisário/diagnóstico por imagem , Nanismo Hipofisário/epidemiologia , Feminino , Geno Valgo/diagnóstico por imagem , Geno Valgo/epidemiologia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Homozigoto , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Mutação Puntual , Prevalência , Adulto JovemRESUMO
OBJECTIVE: To assess the sizes of intra-abdominal organs of adult subjects with untreated severe congenital isolated GH deficiency (IGHD) due to lack of functional GHRH receptor (GHRH-R), and to verify whether there is proportionality between size of organ and adult stature and body surface area (BSA). SUBJECTS AND METHODS: By using ultrasound, we studied the sizes (absolute and corrected by height, weight and BSA) of the intra-abdominal organs of 18 adult subjects with IGHD (eight females, IGHD group) who have never received GH replacement therapy. They were all homozygous for the same null mutation (IVS1 + 1G --> A) in the GHRH receptor gene (GHRH-R). They were compared with normal controls from the same region. RESULTS: After correction for BSA, subjects lacking a functional GHRH-R have normal prostate and ovaries size, small spleen and uterus, and large liver, pancreas and kidney. CONCLUSIONS: Size of individual abdominal organs is influenced in different ways by severe and congenital lack of GH due to a GHRH-R mutation.