Brazilian adult individuals with untreated isolated GH deficiency do not have accelerated subclinical atherosclerosis

Abstract

GH and its principal mediator IGF1 have important effects on metabolic and cardiovascular (CV) status. While acquired GH deficiency (GHD) is often associated with increased CV risk, the consequences of congenital GHD are not known. We have described a large group of patients with isolated GHD (IGHD) due to a homozygous mutation (c.57C1GOA) in the GH releasing hormone receptor gene, and shown that adult GH-naïve individuals have no evidence of clinically evident premature atherosclerosis. To test whether subclinical atherosclerosis is anticipated in untreated IGHD, we performed a cross-sectional study of 25 IGHD and 27 adult controls matched for age and gender. A comprehensive clinical and biochemical panel and coronary artery calcium scores were evaluated by multi-detector tomography. Height, weight, IGF1, homeostasis model assessment of insulin resistance, creatinine and creatininekinase were lower in the IGHD group. Median and interquartile range of calcium scores distribution was similar in the two groups: IGHD 0(0) and control 0(4.9). The vast majority of the calcium scores (20 of 25 IGHD (80%) and 18 of 27 controls (66.6%)) were equal to zero (difference not significant). There was no difference in the calcium scores classification. None of IGHD subjects had minimal calcification, which were present in four controls. Three IGHD and four controls had mild calcification. There were two IGHD individuals with moderate calcification and one control with severe calcification. Our study provides evidence that subjects with congenital isolated lifetime and untreated severe IGHD do not have accelerated subclinical coronary atherosclerosis.

Walking and postural balance in adults with severe short stature due to isolated GH deficiency

“…One study with 8300 women aged 65–89 years with a wide variation in physical function and lifestyles from four large metropolitan areas in the United States concluded that lifestyle factors (not smoking, going outdoors frequently, walking at a fast usual-paced walking speed and high physical activity) and shorter body height may reduce the fall risk (48). Our IGHD subjects rarely smoke (49) and have all the other protective factors against the fall risk. The satisfactory walking and postural balance contribute to the good quality of life, overall health and no evidence of falls in this IGHD cohort.…”

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

“…Similarly, these individuals do not exhibit increase in carotid intima medial thickness (IMT), or evidence of coronary atherosclerosis when assessed by stress echocardiograms (48). In addition, they have similar coronary (49) and aortic abdominal calcium scores as controls (50). Not surprisingly, they do not show any evidence of increased mortality (51).…”

“…These features have been published in 42 different publications (2,19,22,25,27,29,30,31,32,33,36,37,38,40,41,44,45,46,47,48,49,50,51,52,53,54,56,57,61,62,63,64,66,67,68,74,75,76,77,78,79,80). We have used this experiment of nature to discover 'usual laws of nature' as suggested by William Harvey, and to understand some aspects of more common conditions such as short stature, insulin resistance, diabetes, atherosclerosis, osteoporosis, cancer and ultimately longevity.…”

GH and ageing: Pitfalls and new insights

“…This is in spite of the fact that the bulk of information gathered from studies in various animal species (including humans) is in general agreement. To reiterate some of the key findings discussed earlier in this article: In laboratory mice, GH-deficiency or resistance is associated with extension of healthspan, delayed onset and reduced incidence of age-related disease and a remarkable extension of longevity [20, 21, 43, 44];In humans, the same endocrine syndromes are associated with protection from some of the age-related diseases [44, 145], and from insulin resistance [146];In endocrinologically normal humans, genetic polymorphisms in genes related to the somatotropic axis and its downstream target FOXO3, and variation in the level of IGF-1 are associated with differences in the “risk” of achieving exceptional longevity [119, 121–123];Adult body size, a GH/IGF-1 dependent trait, is associated with extended longevity in laboratory rodents (including both normal and genetically altered animals) [44, 105–108], in various domestic animals (carnivores and ungulates) [114–117], and also, albeit less consistently, in the human [118, 119]. …”

“…In humans, the same endocrine syndromes are associated with protection from some of the age-related diseases [44, 145], and from insulin resistance [146];…”