Increased Visceral Adiposity and Cortisol to Cortisone Ratio in Adults With Congenital Lifetime Isolated GH Deficiency

Gomes-Santos, Elenilde; Salvatori, Roberto; Ferrão, T. O.; Oliveira, Carla R. P.; Diniz, Rachel D C Araújo; Santana, João A. M.; Pereira, Fernanda Aparecida Castro; Barbosa, Rita A. A.; Souza, Anita H. O.; Melo, Enaldo Vieira de; Epitácio-Pereira, Carlos C.; Oliveira-Santos, Alécia A; Oliveira, Ingrid; Machado, Julianne Alves; Santana-Junior, Francisco Jose; Barreto‐Filho, José Augusto; Aguiar‐Oliveira, Manuel H.

doi:10.1210/jc.2014-2132

Cited by 31 publications

(20 citation statements)

References 30 publications

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“…In addition, lifetime congenital untreated isolated GHD in adults increases visceral adiposity and the activity of the enzyme 11β-hydroxysteroid dehydrogenase, which converts cortisone to cortisol, both linked to insulin resistance and increased cardiovascular risk [26]. Subjects with congenital untreated GHD due to a homozygous mutation in the GHRH receptor gene present reduced beta-cell function and higher frequency of impaired glucose tolerance [27], despite these subjects also have normal bone status and do not develop premature atherosclerosis [28].…”

Section: Discussionmentioning

confidence: 99%

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

2016

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The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51 ± 13 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensitivity check index, insulin sensitivity index Matsuda, insulin-like growth factor-I and visceral adiposity index. At baseline growth hormone deficiency patients showed higher waist circumference (p < 0.001), low-density lipoprotein cholesterol (p < 0.001) and visceral adiposity index (p = 0.003) with lower insulin sensitivity index (p = 0.007) and high-density lipoprotein cholesterol (p = 0.001) than controls. During growth hormone treatment we observed a significant increase in insulin-like growth factor-I (p < 0.001), high-density lipoprotein (p < 0.001) with a trend toward increase in insulin sensitivity index (p = 0.055) and a significant decrease in total cholesterol (p < 0.001) and visceral adiposity index (p < 0.001), while no significant changes were observed in other clinical and metabolic parameters. The visceral adiposity index was the only parameter that significantly correlated with growth hormone peak at diagnosis (p < 0.001) and with insulin-like growth factor-I and insulin sensitivity index both at diagnosis (p = 0.009 and p < 0.001) and after 12 (p = 0.026 and p = 0.001) and 24 months (p < 0.001 and p = 0.001) of treatment. The visceral adiposity index, which has shown to be associated with both insulin-like growth factor-I and insulin sensitivity, proved to be the most reliable index of metabolic perturbation, among the most common indexes of adiposity assessment and a marker of benefit during treatment in adult growth hormone deficiency patients.

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Section: Discussionmentioning

confidence: 99%

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

2016

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“…Affected IGHD subjects have higher basal cortisol levels than controls, likely reflecting increased activity of the enzyme 11 beta-hydroxysteroid dehydrogenase, which converts cortisone to cortisol (28). The high circulating cortisol levels together with the small amount of detectable circulating GH may contribute to the lack of neonatal symptomatic hypoglycemia episodes in GHRHR mutations (22), which typically occurs in severe IGHD due to GH1 gene defects causing complete absence of GH protein.…”

Section: Other Hormonal Findingsmentioning

confidence: 99%

“…It is noteworthy that the truncal obesity of the Itabaianinha IGHD subjects is indeed the expression of real visceral adiposity. The reduced IR despite this feature suggests that there is a threshold of GH secretion necessary for visceral adiposity to impair IS (28). Given the lack of increased IR, it is not surprising that these individuals exhibit normal longevity (51).…”

Section: Metabolic and Cardiovascular Consequencesmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The multiple facets of GHRH/GH/IGF-I axis: lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation

Aguiar‐Oliveira

Souza

Oliveira

et al. 2017

European Journal of Endocrinology

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Twenty years ago, we described kindred of 105 individuals with isolated GH deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a homozygous mutation in the GH-releasing hormone receptor gene. These subjects exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3 and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF-II. The most striking physical findings of these IGHD individuals are the proportionate short stature, doll facies, high-pitched voice and visceral obesity with reduced fat-free mass. There is neither microphallus, nor neonatal hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is preserved in both genders. The reduction in bone sizes is not even, with mean standard deviation scores for height of −7.2, total maxillary length of −6.5, total facial height of −4.3 and cephalic perimeter of −2.7. In addition, the non-osseous growth is not uniform, preserving some organs, like pancreas, liver, kidney, brain and eyes, and compromising others such as thyroid, heart, uterus and spleen. These subjects present higher prevalence of dizziness, mild high-tones sensorineural hearing loss, reduction of vascular retinal branching points, increase of optic disk, genu valgum and increased systolic blood pressure. Biochemically, they have high low density lipoprotein cholesterol and C-reactive protein levels, but maintain increased insulin sensitivity, and do not show premature atherosclerosis. Finally, they have normal immune function, and normal longevity. This review details the findings and summarizes 20 years of clinical research carried out in this unique population.

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“…The end effect of GH therapy on glucose metabolism is the result of two opposite effects: a favorable one (mediated by the body composition improvement) and a negative (directly caused by its counter-insular effect of GH). The importance of GH in causing insulin resistance is highlighted by the observation that subjects with severe, lifetime, untreated isolated GHD are insulin sensitive despite an increased visceral fat [11]. Nevertheless, most studies show that the net effect of GH replacement (both in GHD and obese subjects) is a positive effect on insulin sensitivity, at least in the short term [3].…”

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confidence: 99%

Growth hormone deficiency in patients with obesity

Salvatori

2015

Endocrine

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Increased Visceral Adiposity and Cortisol to Cortisone Ratio in Adults With Congenital Lifetime Isolated GH Deficiency

Abstract: 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.

Cited by 31 publications

References 30 publications

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

MECHANISMS IN ENDOCRINOLOGY: The multiple facets of GHRH/GH/IGF-I axis: lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation

Growth hormone deficiency in patients with obesity

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