Subjects with isolated GH deficiency due to a null GHRHR mutation eat proportionally more, but healthier than controls.

The GH/IGF-I axis has important interactions with the alimentary system and with the balance between energy intake (EI) and energy requirement (ER). Reduced EI has been described in adult-onset acquired GH deficiency (GHD). Individuals from the Brazilian Itabaianinha cohort, with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G→A) in the GHRH receptor gene, are an ideal model to study the consequences of lifetime GHD. The purpose of this study is to evaluate EI and ER in this untreated IGHD cohort. Cross-sectional study of 24 adult IGHD patients and 23 controls from the same region, matched for age and gender. Estimated EI (EEI) was evaluated by dietary recall, and estimated ER (EER) by the equation of the Dietary Reference Intakes. Fat mass was assessed by DXA. Both EEI and EER were lower in IGHD than controls. However, when corrected by body weight, EEI was higher in IGHD (p = 0.005). IGHD individuals consume in percentage more proteins (p < 0.0001), less carbohydrates (p = 0.013), and equal amount of lipids in comparison to controls. The higher EEI per body weight suggests a possible increase of orexigenic mechanisms in untreated IGHD individuals, ensuring greater caloric intake, which would have adaptive advantages for small-sized individuals in environments with limited access to food. IGHD individuals seem to have a healthier dietary pattern than CO.

Liver status in congenital, untreated, isolated GH deficiency.

Nonalcoholic fatty liver disease (NAFLD) is known to be associated with insulin resistance, atherosclerosis, and low serum IGF1 levels. We have described a large cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G→A mutation in the GHRH receptor gene. These subjects have increased insulin sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized that, despite visceral obesity, NAFLD would be absent or mild due to the increased IS. To assess the prevalence and severity of NAFLD in adult subjects with lifetime, congenital, untreated IGHD, we studied 22 IGHD adults and 25 controls (COs) matched for age and sex. NAFLD was assessed by a comprehensive liver function panel, and ultrasonographic pattern (hyperechogenic pattern, HP) coded as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. Compared with COs, IGHD individual had lower serum IGF1 (P<0.0001), higher total cholesterol (P=0.027), lower prothrombin time (P=0.017), and similar activated partial thromboplastin time and fibrinogen values. Alanine transaminase (ALT) values were similar in the two groups, but aspartate transaminase was higher in IGHD (P=0.013). However, more IGHD subjects (7/22) than COs (3/23) had ALT above the upper limit of normal (P=0.044). The prevalence of NAFLD was higher in IGHD than COs (61 vs 29%, P=0.032), and the HP score was higher in IGHD than COs (P=0.041), but severe NAFLD was not observed in any IGHD (or CO) individual. Liver HP score is increased in lifetime, untreated, congenital IGHD, but the increase in transaminases is mild, suggesting a lack of advanced forms of NAFLD.

Increased visceral adiposity and cortisol to cortisone ratio in adults with congenital lifetime isolated GH deficiency.

CONTEXT: Adult-onset GH deficiency (GHD) increases visceral adiposity and the activity of the enzyme 11ß-hydroxysteroid dehydrogenase, which converts cortisone (E) to cortisol (F), both linked to insulin resistance and increased cardiovascular risk. Conversely, we reported that adults with congenital isolated GHD (IGHD) have increased insulin sensitivity. OBJECTIVE: To assess the type of fat distribution and the amount of visceral and sc fat and to correlate them to the F/E ratio in adults with untreated IGHD due to a mutation in the GHRH receptor gene. METHODS: Body composition was assessed by dual-energy x-ray absorptiometry, thickness of sc and visceral fat was measured by sonography, and serum F and E were measured in 23 IGHD subjects and 21 age-matched controls. RESULTS: Waist/hip ratio (WHR), trunk fat, and trunk/extremity fat (TR/EXT) ratio were higher in IGHD subjects. Visceral fat index (VFI) (but not sc fat index [SFI]) was higher in IGHD. F and F/E ratio were also higher in IGHD. In all 44 individuals, WHR correlated with TR/EXT ratio, thickness of visceral fat, VFI/SFI ratio, F, and F/E ratio. TR/EXT ratio correlated with visceral fat thickness, VFI/SFI ratio, and F. Age had a significant effect on VFI and on F/E ratio. Body mass index SD score and WHR have a similar significant effect on TR/EXT ratio and on F/E ratio. CONCLUSIONS: Lifetime congenital untreated IGHD causes increased visceral adiposity with a high F/E ratio. However, the increased insulin sensitivity suggests that visceral adiposity needs a minimal GH secretion to translate into increased insulin resistance.