Disruption of the GHRH receptor and its impact on children and adults: The Itabaianinha syndrome

Aguiar‐Oliveira, Manuel H.; Salvatori, Roberto

doi:10.1007/s11154-020-09591-4

Cited by 31 publications

(33 citation statements)

References 63 publications

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“…This observation can be supported by the findings described in Itabaianinha County, in the Brazilian state of Sergipe, where 105 study subjects have severe isolated GH deficiency due to a homozygous inactivating mutation in the GH releasing hormone (GHRH) receptor (GHRHR) gene [14]. The authors hypothesized an IGF-I dual action, either promoting (by increasing proliferation of vascular smooth muscle cells), or preventing (by increasing nitric oxide formation, vascular compliance, and insulin sensitivity) atherogenesis.…”

Section: Introductionsupporting

confidence: 58%

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

Rosa

Soares

Rodrigues

et al. 2021

Clin Diabetes Endocrinol

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Background Hypopituitarism in the elderly population is an underdiagnosed condition and may increase comorbidities related to glucose metabolism, dyslipidemia, and cardiovascular risk factors. Optimization of hormone replacement that considers alterations in clearance rates of hormones, interaction with other medications, and evaluation of the risk-benefit ratio of treatment is a big challenge for clinical practice. Objectives This study aimed to evaluate classic cardiovascular risk factors in hypopituitary septuagenarians and octagenarians by diagnosis and after long-term hormone replacement. Methods This is a retrospective observational study, with patients recruited and selected from a registry in a tertiary medical center. We included patients aged 70–99 years with hypopituitarism, evaluated hormonal and biochemical parameters, and cardiovascular risk scores were calculated by diagnosis and compared after long-term follow-up. All patients gave informed consent. Patient data were compared to a sex and age-matched control group, with long-term geriatric follow-up, without endocrine diseases. Results Thirty-five patients were included, 16 patients aged 70–75 years (72.61), 12 patients 76–80 years (72.28), 7 patients 81–99 years (89.28). Pituitary macroadenomas were the main cause of hypopituitarism, mean maximal diameter 3.4 cm (2.9–4.3), and invasive craniopharyngiomas. At the moment of diagnosis, most patients were overweight, and abdominal adiposity was observed in 76.9% of women and 36.4% of men, primarily in octagenarians and nonagenarians. Comorbidities were frequent; 85.7% presented hypertension, 37.1% diabetes, 53.1% low HDL, 51.5% hypertriglyceridemia. Most patients presented more than two combined pituitary deficiencies; hypogonadism in 88.6%, central hypothyroidism in 82.9%, GH deficiency in 65.7%, and adrenal insufficiency in 25.7%. Analysis of cardiovascular risk prediction in the total cohort showed that 57.1% of patients presented a reduction in the General Cardiovascular Disease (CVD) Risk Prediction Score and 45.7% in atherosclerotic CVD risk estimated by ACC/AHA 2013 Pooled Cohort Equation, despite being submitted to conventional hormone replacement, during the mean follow-up of 14.5 years. This reduction was not observed in the control group. Discussion and conclusion In this study, aged hypopituitary patients presented a reduction in estimated general CVD risk during long-term follow-up, despite replacement with corticosteroids, levothyroxine, or gonadal steroids. Early diagnosis and treatment of hypopituitarism in the elderly remain challenging. Larger studies should be performed to assess the risk-benefit ratio of hormone replacement on the metabolic profile in septuagenarian and octogenarian patients.

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Section: Introductionsupporting

confidence: 58%

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

Rosa

Soares

Rodrigues

et al. 2021

Clin Diabetes Endocrinol

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“…Several interventions that successfully slow down aging target the mTOR pathway (Johnson et al, 2013). In the whole IGHD Itabaianinha cohort, during 25 years of medical care, our team did not diagnose any cases of breast, colon, or prostate cancers (Aguiar‐Oliveira & Salvatori, 2020), suggesting reduced risk of cancer, as shown in Ecuadorian GH‐resistant individuals (Guevara‐Aguirre et al, ,1993, 2011). On the other hand, these individuals exhibit a low, but not negligible, frequency of diabetes (15.6%, assessed by an oral glucose tolerance test) (Vicente et al, 2013), while there was no self‐reported diagnosis of diabetes in the Ecuadorian GH‐resistant cohort.…”

Section: Discussionmentioning

confidence: 79%

Circulating microRNA profile in humans and mice with congenital GH deficiency

et al. 2021

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“…In mice, GHRH treatment was found to reverse age-related changes, increasing the thickness of the epidermis and dermis, increasing moisture content, and improving the morphology of the skin tissue and collagen fibers [64]. GHRH deficiency in a Brazilian cohort showed delayed pigmentation, and reported to have youthful hair and no alopecia, even with profoundly decreased serum GH and IGF-1 levels [42]. This cohort aligns with GH acting as an inhibitor of hair growth previously seen ex vivo in female donors [23].…”

Section: Other Skin Phenotype Changes Associated With Signaling Abnor...mentioning

confidence: 99%

Growth Hormone and the Human Hair Follicle

Horesh

Chéret

Paus

2021

IJMS

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Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology. Acromegaly, or GH excess, is associated with hypertrichosis, excessive androgen-independent growth of body hair, and hirsutism in females, while dysfunctional GH receptor-mediated signaling (Laron syndrome) is associated with alopecia and prominent HF defects. The outer root sheath keratinocytes have recently been shown to express functional GH receptors. Furthermore, and contrary to its name, recombinant human GH is known to inhibit female human scalp HFs’ growth ex vivo, likely via stimulating the expression of the catagen-inducing growth factor, TGF-β2. These limited available data encourage one to systematically explore the largely uncharted role of GH in human HF biology to uncover nonclassical functions of this core neurohormone in human skin physiology.

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Disruption of the GHRH receptor and its impact on children and adults: The Itabaianinha syndrome

Cited by 31 publications

References 63 publications

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

Circulating microRNA profile in humans and mice with congenital GH deficiency

Growth Hormone and the Human Hair Follicle

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