Benefits and risks of growth hormone in adults with growth hormone deficiency

[Resumen] La deficiencia de hormona del crecimiento («growth hormone», GH) en el adulto es un síndrome clínico plenamente reconocido que entraña consecuencias adversas para la salud. Muchas de ellas pueden ser mejoradas mediante el tratamiento con GH recombinante. Este tratamiento induce un aumento de la masa magra y una reducción de la masa adiposa. En estudios a largo plazo la densidad mineral ósea se incrementa y mejora la fuerza muscular. La calidad de vida relacionada con la salud suele incrementarse. El perfil lipídico y algunos marcadores de riesgo cardiovascular mejoran con el tratamiento. Este, sin embargo, no está exento de riesgos. La GH eleva la glucemia, el índice de masa corporal y la circunferencia de la cintura, y puede favorecer el desarrollo a largo plazo de diabetes y de síndrome metabólico, según algunos estudios. El riesgo de neoplasia no parece incrementado en adultos tratados con GH, pero existen algunos subgrupos de riesgo elevado. Las deficiencias metodológicas y las dificultades inherentes a los estudios a largo plazo impiden extraer conclusiones definitivas sobre la relación entre GH y supervivencia, por lo que la investigación en este campo debe permanecer activa.[Abstract] Adult growth hormone (GH) deficiency is a well-recognized clinical syndrome with adverse health consequences. Many of these may improve after replacement therapy with recombinant GH. This treatment induces an increase in lean body mass and a decrease in fat mass. In long-term studies, bone mineral density increases and muscle strength improves. Health-related quality of life tends to increase after treatment with GH. Lipid profile and markers of cardiovascular risk also improve with therapy. Nevertheless, GH replacement therapy is not without risk. According to some studies, GH increases blood glucose, body mass index and waist circumference and may promote long-term development of diabetes and metabolic syndrome. Risk of neoplasia does not appear to be increased in adults treated with GH, but there are some high-risk subgroups. Methodological shortcomings and difficulties inherent to long-term studies prevent definitive conclusions about the relationship between GH and survival. Therefore, research in this field should remain active

Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications

Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-) releasing activity through the activation of the growth hormone secretagogue receptor (GHSR). The first studies about role of ghrelin were focused on its orexigenic ability, but despite indisputable pharmacological data, the evidence for a physiological role for ghrelin in the control of appetite is much less clear. Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake. RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin. For this reason, at least theoretically, ghrelin and/or its signalling manipulation could be useful for the treatment or prevention of diseases of glucose homeostasis such as type 2 diabetes

Clinical Manifestations and Diagnosis of Acromegaly

Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Acromegaly is a disabling disease that is associated with increased morbidity and reduced life expectancy. The diagnosis is based primarily on clinical features and confirmed by measuring GH levels after oral glucose loading and the estimation of IGF-I. It has been suggested that the rate of mortality in patients with acromegaly is correlated with the degree of control of GH. Adequately treated, the relative mortality risk can be markedly reduced towards normal

Thyroid Function Alteration in Obesity and the Effect of Bariatric Surgery

Review[Abstract] The most common endocrine disease in obesity is hypothyroidism and secondary endocrine alterations, including abnormal thyroid function, are frequent in obesity. It is unclear whether impaired thyroid function is the cause or the consequence of increased adiposity; furthermore, there are no clear data regarding the best way to dose levothyroxine for patients with both hypothyroidism and obesity, and the effect of bariatric surgery (BS). The aim of the present article is to review some controversial aspects of the relation between obesity and the thyroid: (1) Thyroid function in obesity and the effect of BS (2) Thyroid hormone treatment (THT) in obese patients with hypothyroidism and the effect of BS. In summary: In morbidly obese patients, TSH is moderately increased. Morbid obesity has a mild central resistance to the thyroid hormone, reversible with weight loss. In morbidly obese hypothyroid patients, following weight loss, the levothyroxine dose/kg of ideal weight did not change, albeit there was an increment in the levothyroxine dose/kg of actual weight. From a clinical practice perspective, in morbid obesity, diagnosing mild hypothyroidism is difficult, BS improves the altered thyroid function and THT can be adapted better if it is based on ideal weight.The results of this work have been funded by the Project Nº PI16/00884 to F.C. and S.S.-A.; integrated in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016, Spain, and funded by the ISCIII (Instituto de Salud Carlos III)—General Subdirection of Assessment and Promotion of the Research—European Regional Development Fund (FEDER) “A way of making Europe

Obesity, adipose tissue, inflammation and update on obesity management

Review[Abstract] Obesity is a serious, common and growing problem. Obesity can be defined as an excess of body fat. Its clinical management is complex and frequently unsuccessful. It has only recently been regarded as a chronic disease, linked with diabetes, dyslipidaemia and cardiovascular disease. It is increasingly known that obesity is a multifactorial disease; involving genetic determinants that interacting with environmental factors results in obesity. The global epidemic of obesity imposes a major disease burden, particularly cardiovascular disease. There is a clear link between adipose tissue and inflammation, object of the present review. Adipose tissue is considered a dynamic organ with extremely sophisticated functions. Obesity is associated with low chronic inflammation through the secretion of adipokines. Inflammation mediates on the development of metabolic diseases associated with obesity, dyslipidaemia, hypertension and type 2 diabetes. The treatment of obesity has evolved, from short time and simple diet together with increase in physical activity to long-term approaches based on changes in eating behavior and physical habits

Ghrelin and growth hormone secretagogues, physiological and pharmacological aspect

[Abstract] The first “growth hormone secretagogues” (GHSs) were discovered by Bowers et al. in 1977. In 1996 the GHSs receptor (GHS-R 1a) was cloned. The endogenous ligand for this receptor, ghrelin, was not identified until 1999. Synthetic molecules termed GHSs are substances that stimulate growth hormone (GH) release, via a separate pathway distinct from GH releasing hormone (GHRH)/somatostatin. Ghrelin displays strong GH-releasing activity through the activation of the GHS-R 1a. Apart from stimulating GH secretion, ghrelin and many synthetic GHSs: 1) stimulate prolactin and ACTH secretion; 2) negatively influence the pituitary-gonadal axis; 3) stimulate appetite and positive energy balance; 4) modulate pancreatic endocrine function and affect glucose levels; 5) have cardiovascular actions. The control of ghrelin secretion is not well established at present, although nutrition is an important regulator. Investigators have exploited the ability of GHSs and ghrelin to release GH by mechanisms different from GHRH as a diagnostic tool, which is the present main clinical use of some GHSs. As an alternative to GH, GH deficient conditions could be treated with any substance which would release endogenous GH, such as synthetic GHSs. It is likely that GHSs, acting as either agonists or antagonists on different pathophysiological processes, might have some other clinical impact and therapeutic potential. At least theoretically ghrelin receptor antagonists could be anti-obesity drugs, as blockers of the orexigenic signal from the gastrointestinal tract to the brain. Inverse agonists of the ghrelin receptor, by blocking the constitutive receptor activity, might lower the set-point for hunger between meals.Instituto de Salud Carlos III; PI021479Instituto de Salud Carlos III; PI051024Instituto de Salud Carlos III; PI050983Instituto de Salud Carlos III; PI070413Xunta de Galicia; PGIDT05PXIC91605PNXunta de Galicia; PS07/1