Reduced Growth Hormone Levels Research Articles

Circulating follicle stimulating hormone levels influence body growth in pre-menarcheal girls in a latitude-dependent manner

IntroductionAge at menarche is an essential determinant of reproductive life of a woman. Latitude is an important driver of age at menarche, however the contributions of circulating follicle stimulating hormone (FSH) and socio-economic status (SES) to age at menarche in a latitude-dependent manner is not known. MethodsThis population-based cross-sectional study is a component of our major cohort of 10,050 schoolgirls aged 8–16 years from 35 schools across 10 districts. The selected districts were categorised into high and low latitudes by applying a cut-off point at latitude 31.5⁰N. We evaluated the physical parameters, SES, circulating FSH, and growth hormone (GH) levels in pre-menarche girls (N = 252) at different latitudes. ResultsSelf-reported age at menarche of girls residing at different latitudes in Pakistan showed that higher latitude is associated with delayed age at menarche. Higher latitude was associated with reduced circulating FSH levels, as well as lower parameters of physical growth including body mass index (BMI), waist-hip ratio and, waist-height ratio (all p < 0.05) in the pre-menarcheal girls. However, circulating GH levels were not affected by latitude. On the other hand, lower SES was associated with reduced GH levels and lower BMI, which are considered as probably the primary determinants of physical growth. ConclusionsTaken together, we show that higher latitude may delay the sexual maturation, while poor SES may delay the physical growth in girls.

Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice

ObjectiveThe increasing prevalence of obesity makes it important to increase the understanding of the maturation and function of the neuronal integrators and regulators of metabolic function. MethodsBehavioral, molecular, and physiological analyses of transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using the Synapsincreallele. ResultsConditional deletion of the homeodomain transcription factor Six3 in mature neurons causes dwarfism and weakens circadian wheel-running activity rhythms but increases general activity at night, and improves metabolic function, without impacting pubertal onset or fertility in males. The reduced growth in 6-week-old Six3fl/fl:Synapsincre (Six3syn) males correlates with increased somatostatin (SS) expression in the hypothalamus and reduced growth hormone (GH) in the pituitary. In contrast, 12-week-old Six3syn males have increased GH release, despite an increased number of the inhibitory SS neurons in the periventricular nucleus. GH is important in glucose metabolism, muscle function, and bone health. Interestingly, Six3syn males have improved glucose tolerance at 7, 12, and 18 weeks of age, which, in adulthood, is associated with increased % lean mass and increased metabolic rates. Further, 12-week-old Six3syn males have reduced bone mineralization and a lower bone mineral density, indicating that reduced GH levels during early life cause a long-term reduction in bone mineralization. ConclusionOur study points to the novel role of Six3 in post-proliferative neurons to regulate metabolic function through SS neuron control of GH release.

The Role of Growth Hormone in Depression: A Human Model.

BackgroundAlthough the relationship between acromegaly and depression has been ascribed to the effects of chronic disease, the role of growth hormone (GH), and insulin like growth factor-1 (IGF-1) is not clear.ObjectiveTo determine whether related hormones levels in acromegalics are correlated with depressive symptoms and whether these symptoms are ameliorated following surgery.Materials and MethodsA prospective cohort study was conducted on patients diagnosed with acromegaly (n = 15) or non-functioning pituitary adenomas (NFPA; n = 20, as controls) and undergoing first-time surgery, who completed the Center for Epidemiological Studies Depression (CES-D) questionnaire both pre-surgery and post-surgery. The primary outcome was the patient’s severity of depression symptomatology using the CES-D score; GH, IGF-1 levels, and tumor characteristics were also measured.ResultsHormone levels (GH and IGF-1) and depression scores in acromegaly patients showed significant reductions following surgery (p < 0.05). The average change in CES-D score was 5.73 ± 2.58 (mean ± SE). A moderate correlation was found between GH levels and CES-D scores (r = 0.52, p < 0.01). The depressed affect subscale accounted for the most improvement in CES-D scores postoperatively and correlated most highly with GH levels. We did not find similar declines in the matched cohort of NFPA patients.Conclusion and RelevanceSurgical resection of the pituitary tumor in acromegaly patients leads to reduction in GH levels that is correlated with reduction in CES-D scores. The results suggest a role for GH in depression and provide a stronger foundation on which to build the hypothesis that GH impacts affect. The study also suggests that hormones should be factored into the matrix that entails the neuro-biological underpinnings of depressive disorders. Future work could explore the mechanisms involved, further brain and neuropeptide interactions, and, novel potential therapeutic targets in depressive and other mental health disorders.

Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation.

Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRG). However, specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. Growth hormone modulates homeostasis and tissue repair after injury, but how GH affects nociception in neonates is not known. To determine whether GH played a role in modulating sensory neuron function and hyperresponsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-DRG-spinal cord preparation. Results show that inflammation of the hairy hind paw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated through an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that after GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced pain-like behaviors, possibly by suppressing the upregulation of IGFr1 within DRG.

Impact of gsp mutations in somatotroph pituitary adenomas on growth hormone response to somatostatin analogs: a meta-analysis.

Somatic mutations in the GNAS1 gene, which encodes the alpha-subunit of G stimulatory proteins (gsp), are frequently detected in somatotroph pituitary tumors and have been associated to specific clinical and histopathological characteristics. However, the question whether the presence of a somatic gsp mutation affects the response to somatostatin analog treatment remains unresolved. Following a literature search, we performed a meta-analysis, including 8 eligible studies, in order to estimate the effect of gsp mutation on the percent reduction of growth hormone (GH) levels during an acute octreotide suppression test (OST). A total of 310 patients with acromegaly [126 gsp (+) and 184 gsp (-)] were included in the analysis. The presence of the gsp mutation was related with a greater reduction in GH levels on OST [Weighted Mean Difference (WMD): 9.08% (95% CI, 2.73, 15.42); p=0.005; random effects model]. There was significant heterogeneity for this effect estimate (I(2)=58%, p value for heterogeneity=0.02). A sensitivity analysis after exclusion of a study with different methodology of OST provided similar estimates [WMD: 6.93% (95% CI, 1.40, 12.46); p=0.01], albeit with no significant heterogeneity (I(2)=35%, p value for heterogeneity=0.16). The present meta-analysis suggests a role for gsp mutation as a prognostic factor of treatment response to somatostatin analogs.

Higher estimated net endogenous Acid production may be associated with increased prevalence of nonalcoholic Fatty liver disease in chinese adults in Hong Kong.

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to ascertain the link between diet-induced acid load and NAFLD and to investigate the underlying mechanisms.

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy forde novopatients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Percent reduction of growth hormone levels correlates closely with percent resected tumor volume in acromegaly

Correlation between tumor volume and hormone levels in individual patients would permit calculation of the fraction of tumor removed by surgery, by measuring postoperative hormone levels. The goals of this study were to examine the relationship between tumor volume, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) levels, and to assess the correlation between percent tumor removal and the reduction in plasma GH and IGF-1 in patients with acromegaly. The 3D region of interest-based volumetric method was used to measure tumor volume via MRI before and after surgery in 11 patients with GH-secreting adenomas. The volume of residual tumor as a fraction of preoperative tumor volume was correlated with GH levels before and after surgery. Examination of this potential correlation required selection of patients with acromegaly who 1) had incomplete tumor removal, 2) had precise measurements of initial and residual tumor, and 3) were not on medical therapy. Densely granulated tumors produced more peripheral GH per mass of tumor than sparsely granulated tumors (p = 0.04). There was a correlation between GH and IGF-1 levels (p = 0.001). Although there was no close correlation between tumor size and peripheral GH levels, after normalizing each tumor to its own plasma GH level and tumor volume, a comparison of percent tumor resection with percent drop in plasma GH yielded a high correlation coefficient (p = 0.006). Densely granulated somatotropinomas produce more GH per mass of tumor than do sparsely granulated tumors. Each GH-secreting tumor has its own intrinsic level of GH production per mass of tumor, which is homogeneous over the tumor mass, and which varies greatly between tumors. In most patients the fraction of a GH-secreting tumor removed by surgery can be accurately estimated by simply comparing plasma GH levels after surgery to those before surgery.

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Diagnosis of Growth Hormone Deficiency is Affected by Calibrators Used in GH Immunoassays

Growth hormone (GH) values vary among immunoassays depending on different factors, such as the assay method used, specificity of antibodies, matrix difference between standards and samples, and interference with endogenous GH binding proteins (GHBPs). We evaluated whether the use of different calibrators for GH measurement may affect GH values and, consequently, the formulation of GH deficiency (GHD) diagnosis in children. Twenty-three short children (5 F, 18 M; age 11.4±3.1 years), with the clinical characteristics of GHD (height: -2.3±0.5 SDS; height velocity -2.3±1.5 SDS; IGF-I -1.2±0.9 SDS), underwent GH stimulation tests to confirm the clinical diagnosis of GHD. Serum GH values were measured with Immulite 2000, using 2 different calibrators, IS 98/574, a recombinant 22 kDa molecule of more than 95% purity, and IS 80/505, of pituitary origin and resembling a variety of GH isoforms. We found blunted GH secretion in 20 subjects with the Immulite assay using the IS 98/574 GH as a calibrator, confirming the diagnosis of GHD. Subsequently, using IS 80/505 GH as a calibrator, in the same samples only 14 children showed reduced GH levels. The total cost for the first year of GH therapy of patients diagnosed with IS 98/574 as a calibrator was higher than that for patients diagnosed with IS 80/505 as a calibrator. These data confirm that GH values may depend on different calibrators used in the GH assay, affecting the formulation of GHD diagnosis and the consequent decision to start GH treatment.

Desensitization treatment for hypersensitivity reaction to octreotide in an acromegalic patient

Octreotide is widely used as medical therapy for acromegaly. It is known to markedly reduce growth hormone levels, improve symptoms and reduce tumor size. Common side effects include gastrointestinal symptoms, hepatobiliary disorders, dizziness, headaches, bradycardia, hyperglycemia or hypoglycemia and thyroid dysfunction. Although urticaria, allergy/hypersensitivity reactions and anaphylaxis have been noted as possible adverse reactions, there is a lack of data showing a causal relationship between octreotide and hypersensitivity reactions and there is no information on management when continued use of this medication is essential. We now report a case of a 60 year old male with acromegaly who had presented with a cutaneous hypersensitivity reaction to octreotide. In addition he failed treatment with surgery, radiation, and dopamine agonist and could no longer afford to continue treatment with pegvisomant. The patient underwent desensitization treatment for his octreotide allergy and was able to resume treatment without any further side effects. We believe this case represents the first report of successful desensitization treatment for octreotide allergy in an acromegalic patient.

Long-Term Dietary Potential Renal Acid Load During Adolescence Is Prospectively Associated with Indices of Nonalcoholic Fatty Liver Disease in Young Women 3

Nonalcoholic fatty liver disease (NAFLD), frequently already present in young subjects, has been linked to reduced growth hormone levels and signaling. Similar hormonal changes occur during metabolic acidosis (MA), which may thus contribute to an increased NAFLD risk. Because subclinical MA can be diet induced, we aimed to examine whether a higher diet-dependent acid load during adolescence is prospectively associated with several currently used NAFLD surrogates in young adulthood. Dietary acidity during adolescence (boys:10–15 y, girls: 9–14 y) was calculated as potential renal acid load (PRAL) from at least three 3-d weighed dietary records according to a published algorithm considering dietary protein and minerals in 145 healthy participants. Routine measurements derived from blood analysis and anthropometric data in participants’ young adulthood (18–25 y) were used to determine the NAFLD surrogates alanine-aminotransferase (ALT), hepatic steatosis index (HSI), and fatty liver index (FLI). Sex-stratified linear regression models, adjusted for dietary fiber, saturated fat, protein, and adolescent BMI SD scores, were run with PRAL as the independent variable. Dietary PRAL during puberty was positively associated with ALT (P= 0.02), HSI (P= 0.002), and FLI (P= 0.005) in adult females but not males. Females with an adolescent dietary acid load in the highest tertile had 3.5, 4.4, and 4.5 higher values of ALT, HSI, and FLI as adults, respectively, compared to females with the lowest PRAL. The present findings suggest that higher dietary acidity in adolescence may be prospectively associated with hepatic lipid accumulation in females. Whether this relationship is due to the higher proton load or rather represents an unhealthy dietary pattern requires further investigation.

Diagnosis and Management of Acromegaly in 2012

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy, including somatostatin analogs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with somatostatin analogs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Diagnosis and Management of Acromegaly in 2012

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumour growth, and to limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy, including somatostatin analogues, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with somatostatin analogues. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.

Effect of Ghrelin and Thyrotropin-releasing Hormone on Prolactin Secretion in Normal Women

It is known that ghrelin stimulates the secretion of prolactin in women. The aim of this study was to examine the effect of exogenous thyrotropin-releasing hormone (TRH) on ghrelin-induced prolactin release. Ten healthy normally cycling women were studied in four menstrual cycles. The women were injected intravenously in late follicular phase (follicle size 16-17 mm) with a single dose of normal saline (cycle 1), ghrelin (1 microg/kg) (cycle 2), thyrotropin-releasing hormone (200 microg) (cycle 3), and ghrelin plus thyrotropin-releasing hormone (cycle 4). Blood samples in relation to saline or drugs injection (time 0) were taken at -15, 0, 15, 30, 45, 60, 75, 90, and 120 min. The prolactin and growth hormone responses were assessed. After ghrelin administration (cycles 2 and 4), plasma ghrelin, serum prolactin, and growth hormone levels increased rapidly, peaking at 15-30 min (p<0.001). The injection of thyrotropin-releasing hormone (cycle 3) stimulated prolactin secretion markedly (p<0.001), but reduced growth hormone levels significantly (p<0.05). Ghrelin induced a smaller prolactin increase than thyrotropin-releasing hormone (p<0.05). The combination of ghrelin and thyrotropin-releasing hormone induced a similar increase in prolactin levels as with thyrotropin-releasing hormone alone. No changes in growth hormone and prolactin levels were seen after saline injection. These results demonstrate that the stimulating effect of ghrelin on prolactin secretion is not additive with that of thyrotropin-releasing hormone.

Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel® therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension

The study was designed to evaluate the long-term efficacy and safety of the 28-day prolonged-release Autogel formulation of the somatostatin analogue lanreotide (Lan-Autogel) in unselected patients with acromegaly. The study comprised four phases: washout; a double-blind comparison with placebo, at a single randomized dose (60, 90 or 120 mg) of Lan-Autogel; a single-blind, fixed-dose phase for four injections (placebo group was re-allocated to active treatment); and eight injections with doses tailored according to biochemical response. Serum samples were assessed for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, at weeks 4, 13, 14, 15, 16, 32 and 52. 108 patients were enrolled and 99 completed 52 weeks’ treatment. Four weeks after the first injection, serum GH levels decreased by >50% from baseline in 63% of patients receiving Lan-Autogel compared with 0% receiving placebo (P < 0.001). After four injections, 72% of patients had a >50% reduction in GH levels; 49% patients achieved GH levels ≤ 2.5 ng/ml; 54% had normalized IGF-1; and 38% achieved the combined criterion of GH level ≤ 2.5 ng/ml and normalized IGF-1. The corresponding proportions by week 52 were 82, 54, 59 and 43%, respectively. In patients not requiring dose escalation to 120 mg, 85% achieved biochemical control (combined criterion). Treatment was well tolerated by all patients. In conclusion, Lan-Autogel was effective in controlling GH and IGF-1 hypersecretion in patients with acromegaly and showed a rapid onset of action.

Growth Hormone–Releaser Diet Attenuates β-Amyloid(1-42)–Induced Cognitive Impairment via Stimulation of the Insulin-Like Growth Factor (IGF)-1 Receptor in Mice

We previously demonstrated that the growth hormone (GH)-releaser diet ameliorated β-amyloid (Aβ) (1-42)–induced memory impairment, but the underlying mechanism remained to be characterized. We show here that the GH-releaser diet significantly attenuated Aβ(1-42)-induced impairment in context-dependent conditioned fear, with a reduction in GH levels and changes in hippocampal acetylcholine, acetylcholinesterase, choline acetyltransferase, insulin-like growth factor (IGF)-1, and IGF-1–receptor activity in mice. JB-1, an IGF-1–receptor antagonist, significantly blocked GH-releaser diet–mediated pharmacological actions. Our results suggest that the GH-releaser diet prevents Aβ(1-42)-induced cognitive deficits via stimulation of the hippocampal IGF-1 receptor.

Time course alterations of plasma obestatin and growth hormone levels in response to short-term anaerobic exercise training in college women

Obestatin is a 23-amino-acid peptide encoded by the same gene as ghrelin. Because there is a paucity of data concerning the effects of exercise on obestatin, this study investigated the effect of anaerobic exercise training-detraining on obestatin and growth hormone (GH) plasma levels. Ten young female volunteers participated. Blood was collected 24 h before, and 24 h, 48 h and 7 days after the training. The data indicate that anaerobic training caused a significant reduction in GH levels but had no effect on plasma obestatin concentrations.

Does acromegaly enhance mortality?

The increased mortality associated with acromegaly was first demonstrated in early epidemiological studies. Since the seminal paper by Wright et al. in 1970, nearly 20 studies have analyzed mortality rates in over 5,000 patients with acromegaly. Overall standardized mortality rates are approximately two times higher than in the general population, relating to an average reduction in life expectancy of around 10 years. The excess deaths are due predominantly to cardiovascular, cerebrovascular and respiratory disease. Malignancy deaths have been high in some studies but not others; in the largest series looking at cancer mortality in acromegaly, overall cancer deaths were not increased, but colon cancer mortality was higher than expected. In 1993, Bates et al. first demonstrated that outcome was related to the latest measurable growth hormone (GH), and treatment to reduce GH levels led to improved outcomes. Other factors predicting poor outcome include the presence of hypertension and diabetes. On the basis of current evidence, a latest GH of less than 2-2.5 mug/L is a better predictor of good outcome than a normal insulin-like growth factor-1 (IGF-1), possibly due to discrepancy between GH and IGF-1 at low GH levels. There is some evidence to suggest a more stringent GH cut-off (less than 1 mug/L) may yield additional benefit but further studies are required to investigate any added risk of increased mortality from hypopituitarism. Radiotherapy has been linked specifically to cerebrovascular mortality and its use in patients with acromegaly must involve a careful risk-benefit analysis in each case.

Pharmacologic Therapy in Growth Hormone Disorders and the Heart

Growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is not only involved in the regulation of somatic growth but also has important physiological functions in adults. Several studies have shown that GH deficiency in adults is associated with abnormalities in body composition, metabolic derangements, and suboptimal physical performance. Furthermore, GH/IGF-I axis plays an important role in the maintenance of heart structure and function. Until recently, GH therapy was only used to treat short stature children, with or without established GH deficiency, and it remains common practice to discontinue GH replacement therapy when final height is achieved. Acromegaly, entity characterized by GH hypersecretion, is associated with an increased risk of premature death. Cardiac complications are known to be major determinants of the shortened life expectancy. Treatment of acromegaly accounts for a substantial decrease in morbidity and mortality. Surgery, radiation therapy and bromocriptine have only been able to reduce GH levels to normal levels in 10-30% of patients. The synthesis of somatostatin analogs has provided a new approach to acromegaly treatment. These drugs reduce GH and IGF-I levels in 80% of cases and normalize them in 40-60% of cases. Finally, GH/IGF-I system improves left ventricular systolic function and has also indirect effects on the cardiovascular system, mainly as a consequence of the peripheral vasodilatation. These effects are important in the understanding of the potential role of GH on improving ventricular systolic dysfunction and point to the use of GH as a potential therapy for chronic heart failure. The aim of the present review is to provide an update overview describing the role of GH on acromegaly, adult GH deficiency and heart failure, as well as the influence of GH-based therapy on heart structure and function.