The potential effects of anabolic-androgenic steroids and growth hormone as commonly used sport supplements on the kidney: a systematic review.

BACKGROUND: Anabolic-androgenic steroids and growth hormone are among the most commonly used supplements by sportsmen and sportswomen. The aim of this systematic review is to collect and report available data about renal safety of anabolic-androgenic steroids and growth hormone (GH). METHODS: The search strategy was in accordance with the PRISMA guideline. Seven databases such as Scopus, Medline, Embase, and ISI Web of Knowledge were searched using keywords, such as "growth hormone", "anabolic-androgenic steroids", and "kidney injury". Articles published from 1950 to December 2017 were considered. Randomized clinical trials, prospective or retrospective human studies, case series as well as case reports, and experimental (in vivo) studies were included. Twenty one clinical and experimental articles were selected (12 for anabolic-androgenic steroids and 9 for GH). RESULTS: Anabolic-androgenic steroids can affect the kidney in different aspects. They can induce or aggravate acute kidney injury, chronic kidney disease, and glomerular toxicity. These adverse effects are mediated through pathways such as stimulating renin-angiotensin-aldosterone system, enhancing the production of endothelin, producing reactive oxygen species, over-expression of pro-fibrotic and pro-apoptotic mediators (e.g., TGF-ß1), as well as inflammatory cytokines (e.g., TNF-α, IL-1b, and IL-6). Although GH may affect the kidney in different aspects, such as size, glomerular filtration rate, and tubule functions, either directly or indirectly, there is no conclusive clinical evidence about its detrimental effects on the kidney in athletes and body builders. CONCLUSION: Evidence regarding effects of anabolic-androgenic steroids exists; However, GH's exact effect on the kidney at doses used by athletes and body builders has not yet been clarified. Cohort clinical studies with long-term follow-up are warranted in this regard.

Guía de recomendaciones para el diagnóstico clínico, bioquímico y por imágenes de la acromegalia. Federación Argentina de Sociedades de Endocrinología (FASEN) - 2017 / Guidelines for the clinical, biochemical and imaging diagnosis of acromegaly. Federación Argentina de Sociedades de Endocrinología (FASEN) - 2017

RESUMEN Objetivo El objetivo de esta guía es formular pautas para el diagnóstico de acromegalia adecuadas a los parámetros internacionales y a los recursos disponibles en Argentina. Participantes El grupo de trabajo propuesto por la Federación Argentina de Sociedades de Endocrinología (FASEN) incluyó un equipo multidisciplinario compuesto por 5 médicos endocrinólogos (4 especialistas y una profesional joven), un neurocirujano y una bioquímica, expertos en el tema. Evidencia Esta guía basada en la evidencia se desarrolló utilizando la metodología AGREE para describir tanto las recomendaciones como la calidad de las pruebas. Los borradores de esta guía fueron revisados por un grupo multidisciplinario de especialistas reconocidos en acromegalia. Conclusiones Utilizando un enfoque basado en la evidencia, esta guía aborda la evaluación diagnóstica de la acromegalia en Argentina.

ABSTRACT Objective The aim is to formulate guidelines for the clinical, biochemical and imaging diagnosis of acromegaly in accordance with international criteria and resources available in Argentina. Participants The task force selected by FASEN included a multidisciplinary team of 5 endocrinologists (4 senior and 1 junior), a neurosurgeon and a biochemist, experts in the field. Evidence This evidence-based guidelines were developed using the AGREE methodology to describe both the recommendations and the quality of evidence. The draft of these guidelines was reviewed by endocrinologists, biochemists and neurosurgeons experts in the field. Conclusions Using an approach based on evidence, these guidelines address the diagnosis of acromegaly in Argentina.

Epifisiolisis y hormona de crecimiento recombinante / Epiphysiolysis and recombinant growth hormone

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Impact of the growth hormone replacement on bone status in growth hormone deficient adults.

INTRODUCTION: Growth hormone deficiency (GHD) is associated with reduced bone mineral density (BMD). GH replacement has positive effect on BMD but the magnitude of this effect and its mechanism are debated. OBJECTIVES: The objectives of this study was first, to assess the effect of GH replacement on BMD, and second, to evaluate the effect of GH treatment on bone turnover and microarchitecture and to assess the factors influencing the effect of the therapy on BMD. PATIENTS AND METHODS: Adult GHD (AO-GHD) and childhood onset GHD (CO-GHD) patients treated with GH using IGF-I normalization GH replacement regimen were prospectively followed during 2 years. Lumbar spine (L1-L4) and total femur BMD by Hologic discovery, in the subset of patients also bone turnover markers; osteocalcin and carboxy-terminal collagen crosslinks (CTx) were assessed at baseline and at months 3, 6, 12 and 24, respectively. The trabecular bone score (TBS) derived from lumbar spine DXA by the iNsight® software was assessed in a subset of study population at baseline and months 12 and 24. RESULTS: In total, 147 GHD patients (age 35.1 years, 84 males/63 females, 43 of childhood onset GHD/104 AO-GHD) were included. BMD of lumbar spine and femur increased significantly during the treatment (14% and 7% increase at 2 years, respectively; p<0.0001). Bone markers increased during the first 12 months of treatment with subsequent decrease of CTx. At month 24, significant increase in TBS was observed (4%, p=0.02). BMD increase was significantly higher in males (15% increase in males vs. 10% in females, p=0.037) and childhood onset GHD (CO-GHD) patients (13% increase in CO-GHD, p=0.004). CONCLUSION: GH supplementation leads to an increase of BMD with corresponding changes in bone turnover markers and changes in microarchitecture as assessed by trabecular bone score. Positive effect of GH on bone status is more pronounced in males and CO-GHD adults.

Cardiometabolic risks during anabolic hormone supplementation in older men.

OBJECTIVE: To determine the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging. DESIGN AND METHODS: A double-masked, partially placebo controlled study in 112 men 65-90 years-old was conducted. Transdermal testosterone (5 g vs. 10 g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0 vs. 3 vs. 5 µg/kg/day) were administered for 16-weeks. Measurements included testosterone and IGF-1 levels, body composition by DEXA, and cardiometabolic risk factors (upper body fat, blood pressure, insulin sensitivity, fasting triglycerides, HDL-cholesterol, and serum adiponectin) at baseline and after 16 weeks of treatment. RESULTS: Some cardiometabolic factors improved (total and trunk fat, triglycerides, HDL-cholesterol) and others worsened (systolic blood pressure, insulin sensitivity index [QUICKI], adiponectin). Cardiometabolic risk composite scores (CRCSs) improved (-0.69 ± 1.55, P < 0.001). In multivariate analyses, QUICKI, triglycerides, and HDL-cholesterol contributed 33%, 16%, and 14% of the variance in CRCS, respectively. Pathway analyses indicated that changes in fat and lean mass were related to individual cardiometabolic variables and CRCS in a complex manner. Changes in BMI, reflecting composite effects of changes in fat and lean mass, were more robustly associated with cardiometabolic risks than changes in fat mass or LBM individually. CONCLUSIONS: Testosterone and rhGH administration was associated with diverse changes in individual cardiometabolic risk factors, but in aggregate appeared not to worsen cardiometabolic risk in healthy older men after 4-months. The long-term effects of these and similar anabolic therapies on cardiovascular events should be investigated in populations with greater functional limitations along with important health disabilities including upper body obesity and other cardiometabolic risks.

Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone.

BACKGROUND: There are limited long-term randomized controlled trials of growth hormone (GH) supplementation to adult height and few published reports of the health-related quality of life (HRQOL) following treatment. The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome (TS) yielded data to examine whether GH supplementation resulted in a higher HRQOL (either due to taller stature or from the knowledge that active treatment and not placebo had been received) or alternatively a lower HRQOL (due to medicalization from years of injections). METHODS: The original trial randomized 154 Canadian girls with TS aged 7-13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections; estrogen prescription for induction of puberty was standardized. Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up. The instrument used to study HRQOL was the SF-36, summarized into physical and mental component scales (PCS and MCS); higher scores indicate better HRQOL. RESULTS: Thirty-four of the 48 eligible participants (71%) consented to participate; data were missing for one patient. Both groups (GH and no treatment) had normal HRQOL at this post-treatment assessment. The GH group had a (mean ± SD) PCS score of 56 ± 5; the untreated group 58 ± 4; mean score for 16-24 year old females in the general population 53.5 ± 6.9. The GH group had a mean MCS score of 52 ± 6; the untreated group 49 ± 13; mean score for 16-24 year old females in the general population 49.6 ± 9.8. Secondary analyses showed no relationship between HRQOL and height. CONCLUSIONS: We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term randomized controlled trial, confirming larger observational studies. We suggest that it remains ethically acceptable as well as necessary to maintain a long-term untreated control group to estimate the effects of pharmacological agents to manipulate adult height. Young adult women with TS have normal HRQOL suggesting that they adjust well to their challenges in life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00191113.

Durability of the effects of testosterone and growth hormone supplementation in older community-dwelling men: the HORMA Trial.

OBJECTIVES: To determine the durability of anabolic effects and adverse events (AEs) after stopping testosterone and growth hormone supplementation in older men. DESIGN: Secondary analysis of a double-masked, randomized controlled trial of testosterone gel (5 or 10 g/daily) plus rhGH (0, 3 or 5 µg/kg/day) with follow-up of outcomes 3 months later. PARTICIPANTS: A total of 108 community-dwelling 65- to 90-year-old men. MEASUREMENTS: Testosterone and IGF-1 levels, body composition (DEXA), 1-repetition maximum (1-RM) strength, stair-climbing power, quality-of-life (QOL) and activity questionnaires, AEs. RESULTS: Despite improvements in body composition during treatment, residual benefits 3 months later (week 28) were variable. For participants with improvements exceeding their week-17 median changes, benefits were sustained at week 28 for lean body mass (1·45 ± 1·63 kg, 45% of week-17 values, P < 0·0001 vs baseline), appendicular skeletal muscle mass (ASMM, 0·71 ± 1·01 kg, 42%, P < 0·0001), total fat (-1·06 ± 2·18 kg, 40%, P < 0·0001) and trunk fat (-0·89 ± 1·42 kg, 50%, P < 0·0001); retention of ASMM was associated with greater week-16 protein intake (P = 0·01). For 1-RM strength, 39%-43% of week-17 improvements (P ≤ 0·05) were retained and associated with better week-17 strength (P < 0·0001), change in testosterone from week 17-to 28 (P = 0·004) and baseline PASE (P = 0·04). Framingham 10-year cardiovascular risks were low (~14%), did not worsen and improved by week 28 (P = 0·0002). The hypothalamic-pituitary-gonadal axis recovered completely. CONCLUSIONS: Durable improvements in muscle mass, strength and fat mass were retained 3 months after discontinuing hormone supplementation in participants with greater than median body composition changes during treatment, but not in others with smaller gains. AEs largely resolved after intervention discontinuation. Additional strategies may be needed to sustain or augment muscle mass and strength gains achieved during short-term hormone therapy.

Sequential rupture of triceps and quadriceps tendons in a dialysis patient using hormone supplements.

Spontaneous rupture of tendons is rare, and typically occurs in large weight bearing tendons such as the quadriceps, Achilles and patellar tendon, in the context of various chronic diseases including end-stage renal disease. In general, tendon rupture in dialysis patients is associated with hyperparathyroidism, long duration of dialysis, steroid and quinolone use. We present a case of a young man on chronic dialysis who presented with sequential rupture of triceps and quadriceps tendons requiring surgical repair, several months after initiating use of multiple hormone supplements including human growth hormone and androgens. The supplements were obtained over the internet with the aim of improving his kidney function. Although this patient did have hyperparathyroidism, it is likely his PTH elevation was exacerbated by use of human growth hormone, and tendon rupture risk increased by concurrent use of an androgen supplement. This case highlights the fact that dialysis patients do utilize alternative remedies and that there may be unexpected, dialysis-specific complications associated with their use.

Treatment with growth hormone, somatostatin, and insulin in combination with hypocaloric parenteral nutrition in gastrointestinal cancer patients after surgery.

OBJECTIVE: The metabolic response to gastrointestinal cancer in patients undergoing surgery is associated with hypermetabolism and insulin resistance. The potential use of synergetic anabolic hormones in conjunction with hypocaloric parenteral nutrition (HPN) has become a significant area of investigation. The presented study was performed to determine the clinical efficiency and safety of hormone therapy combined with HPN in patients with gastrointestinal cancer. METHODS: One hundred patients with a Nutrition Risk Screening score of 3 or 4 undergoing surgery for gastrointestinal cancer were randomized into two groups. The patients in the control group received standard total parenteral nutrition and systemic insulin. The patients in the study group received HPN and systemic insulin in addition to pretreatment with recombinant human growth hormone and octreotide. Clinical efficiency and safety were evaluated by the measurement of hormones and protein metabolites, immune function, clinical outcome, and adverse events. Follow-ups were performed to determine the influence on prognosis. RESULTS: Treatment with recombinant human growth hormone, octreotide, and insulin in combination with HPN significantly increased protein synthesis, immune function, and metabolic tolerance, decreased infectious complications, and shortened postoperative hospital stays, but did not increase the risk of tumor development and recurrence in the study group compared with the control group. CONCLUSION: The proper short-term perioperative administration of growth hormone, somatostatin, and insulin in combination with HPN can overcome the postoperative stress response through the increase of protein synthesis to improve immune function in patients with gastrointestinal cancer after surgery.

Improvement in growth after 1 year of growth hormone therapy in well-nourished infants with growth retardation secondary to chronic renal failure: results of a multicenter, controlled, randomized, open clinical trial.

BACKGROUND AND OBJECTIVES: Our aim was to evaluate the growth-promoting effect of growth hormone (GH) treatment in infants with chronic renal failure (CRF) and persistent growth retardation despite adequate nutritional and metabolic management. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study design included randomized, parallel groups in an open, multicenter trial comparing GH (0.33 mg/kg per wk) with nontreatment with GH during 12 months. Sixteen infants who had growth retardation, were aged 12+/-3 months, had CRF (GFR

Recurrent exacerbations of protein-losing enteropathy after initiation of growth hormone therapy in a Fontan patient controlled with spironolactone.

Protein-losing enteropathy (PLE) is a rare, but serious complication in single ventricle patients after Fontan palliation, and is associated with a 5-year mortality of 46%. We describe a patient with PLE after Fontan palliation who achieved remission with high-dose spironolactone (an aldosterone antagonist), but had three exacerbations each temporally correlated with the use of growth hormone (an aldosterone agonist). Because of the opposing mechanisms of action of these two medications, caution might be indicated when using growth hormone for patients with PLE who are successfully treated with spironolactone.

[Growth hormone revisited]. / Hormona de crecimiento: acciones y aplicaciones preventivas y terapéuticas.

Growth hormone (GH) is a pleiotropic hormone, expressed at pituitary and peripheral level, which plays a number of different roles far beyond of those classically described. Among these effects it is remarkable the neurotropic role of GH: the hormone increases the proliferation and survival of neural precursors in response to neurological injuries. At the cardiovascular level, GH improves the lipidic profile and decreases the factors of cardiac risk; the hormone recovers the endothelial function, improves the cardiac function and potentiates revascularisation in ischemic territories. Differently to that occurring with autocrine GH, exogenous GH administration does not seem to be related to oncogenesis. According to its effects, there are multiple potential clinical applications of GH: acute treatment of brain injury, due to its antiapoptotic effect; central or peripheral neural regeneration; acute treatment of perinatal anoxia, prevention cerebral palsy; revascularisation of ischemic areas; decrease of the time of bone consolidation after a bone fracture; and torpid ulcer healing.

[Growth hormone treatment inTurner syndrome: data and reflections]. / O hormônio de crescimento na síndrome de Turner: dados e reflexões.

Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsufficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.

O hormônio de crescimento na síndrome de Turner: dados e reflexões: [revisão] / Growth hormone treatment inTurner syndrome: data and reflections: [review]

A baixa estatura é a principal característica na síndrome de Turner (ST). O agravo estatural na ST é precoce e torna-se mais evidente na puberdade. A haploinsuficiência do gene SHOX tem sido implicada como principal fator na definição da estatura de mulheres, no entanto, ainda que a maioria das pacientes não tenha deficiência do hormônio de crescimento, a terapia com GHr melhora a altura final. Recentemente, tem-se chamado a atenção para a associação entre GH e câncer. O risco de câncer nessas pacientes está associado à presença de fragmentos do cromossomo Y que pode levar ao desenvolvimento de gonadoblastoma. Dessa forma, a administração de GHr na ST deve ser feita com cautela. A investigação de seqüências do cromossomo Y deve ser realizada, bem como a gonadectomia profilática nos casos positivos, conferindo maior segurança ao tratamento.

Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsuficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.

[Prevention and anti-aging in endocrinology]. / Prävention und "Anti-aging" mit Hormonen Ersetzen, was im Alter fehlt?

The aging process is associated with a characteristic decline in the levels of certain hormones. In both sexes, growth hormones, melatonin, dehydroepiandrosterone (DHEA) and its sulfate compound DHEAS reach their maximum levels in the third decade of life, and then decline progressively. In addition, a constant decrease in the production of biologically active free testosterone of approximately 1% per year is observed in men. The abrupt cessation of sex hormone production seen in women is not observed in men. Irrespective of the hormone being supplemented, it should always be remembered that not merely the hormone-producing organ, but also the target tissue has aged, and may thus manifest a different reaction to the substituted hormone than youthful tissue.

[Prospective study of effect of recombinant human growth hormone on nutritional status and immune function in early postoperative stage of liver transplantation].

OBJECTIVE: To evaluate influence of recombinant human growth hormone (rhGH) on nutritional status and immune function in early postoperative stage of liver transplantation including hepatic function, acute rejection and infection rate, in order to assess its safety in clinical use. METHODS: Sixty patients with non-malignant diseases of the liver in terminal stages were randomly divided into two groups: treatment group (rhGH treatment n=30) and control group (n=30). All the patients received the same nutritional support and immunodepressant treatment regimes. The patients in treatment group received rhGH 10 U hypodermically daily for 10 days 24 hours after liver transplantation. The following parameters including siderophilin, prealbumin, albumin, urea nitrogen, CD4/CD8, immunoglobulin G (IgG), IgM, IgA, growth hormone (GH), insulin-like growth factor-1 (IGF-1), aspartate aminotransferase (AST), alanine aminotransferase (ALT), dosage of insulin to control blood sugar (8-10 mmol/L) were determined on 1st, 4th, 8th, 14th days after the operation, and acute rejection rate after 28 days of operation (confirmed by liver acupuncture biopsy), and infection rate were also assessed. RESULTS: Compared with control group, levels of siderophilin, prealbumin, CD4/CD8, GH, IGF-1 within 14 days in treatment group were increased significantly 14 days after the operation (all P<0.05), and level of urea nitrogen was decreased significantly (P<0.05). The level of albumin in treatment group was lower than that in control group 14 days after operation (P<0.05), while dosages of exogenous insulin were higher on 4th and 8th days after operation than that in control group (both P<0.05). There were no significant differences in levels of AST, ALT within 14 days, or acute rejection rate and infection rate within 28 days between two groups (all P>0.05). CONCLUSION: rhGH can accelerate recovery of nutritional status in the early liver transplantation period. It does not show superiority in improving immune function and influence on recovery of hepatic function, acute rejection or infection rate. The safety has been challenged by inducing high blood sugar as a side effect.

Growth hormone deficiency in the adult.

Growth hormone deficiency (GHD) in adults may be of either adult or childhood onset and may occur as isolated GHD or as multiple hormone deficiencies. Adult-onset GHD (AoGHD) usually results from damage to the pituitary gland or hypothalamus. GH is frequently undetectable in normal subjects and thus GHD cannot be distinguished from the normal state using a single random GH measurement. In general, a stimulation test is required to recognize GHD. Insulin tolerance test (ITT) has been considered the gold standard by the most important scientific societies, although alternative tests, in particular GHRH plus arginine have been proposed as valuable alternative to ITT. The clinical syndrome associated with AoGHD is characterized by a wide array of symptoms and important chronic complications, such as cardiovascular complications, which may be responsible for an increased mortality. The rationale for GH replacement in adults GHD patients is justified by the beneficial effects on some clinical end-points, such as quality of life (QoL) and cardiovascular risk factors, whereas the effects on mortality risk are still controversial. Over the recent years, guidelines on the use of rhGH as a substitution treatment in adult hypopituitarism have been issued by international (Growth hormone research society-GRS, Endocrine Society) and relevant national (National Institute of Clinical Excellence-UK, NICE) institutions. The aim of the paper is to review and discuss these guidelines.

Performance-enhancing drug use in young athletes.

This article explores the issue of performance-enhancing drug use in adolescent athletes. The article describes current substances that are being used by adolescent athletes, explains their positive and negative effects, examines factors contributing to their increased use in adolescent athletes, and discusses approaches to educating adolescents about alternate means of enhancing their athletic performance. It is hoped that this information will be useful toward encouraging young athletes to pursue, safe, healthy, and natural means of performance enhancement, such as practice and strength training, to improve sports performance in a safe, effective manner.