The physiology of growth hormone (GH) in adults: translational journey to GH replacement therapy.

The fact that growth hormone (GH) plays an important role in health after the cessation of growth requiring replacement therapy in adult life has only been recognised in the last three decades. This has only been made possible by recombinant technology providing GH supplies required to undertake investigations in the physiology of GH action and the benefits of replacement therapy in patients identified by rigorously validated diagnostic tests for GH deficiency (GHD). Human studies have revealed important regulatory roles in substrate metabolism, sodium homeostasis, body composition, and physical function. GH-induced anabolism is achieved by stimulating amino acid incorporation into protein while reducing oxidative loss simultaneously enhancing lipid utilisation by stimulating fatty acid oxidation and reducing lipid storage. Sodium and fluid retention are enhanced by activating the renin-angiotensin system and distal renal tubular reabsorption. GH stimulates the aerobic and anaerobic energy systems that underpin muscle and cardiovascular function. These pleiotropic actions explain the clinical picture of increased adiposity, reduced lean mass, and impaired physical and psychological function in the GHD adult, all of which are reversed when GH is replaced. Women require a greater replacement dose of GH than men. This is because androgens enhance while oestrogens attenuate GH action. The oestrogen effect is route-dependent, occurring with oral delivery blunting the liver-mediated actions of GH by directly inhibiting GH receptor signalling, global experience spanning over 30 years has attested to the safety, efficacy, and benefits of replacement therapy for adults with GHD.

A case of pituitary apoplexy in pregnancy.

UNLABELLED: Pituitary apoplexy is a rare event in pregnancy. A 41-year-old woman with a known pituitary microadenoma presented with visual disturbance and headache during the second trimester of pregnancy. Magnetic resonance imaging (MRI) demonstrated pituitary apoplexy with chiasmal compression. After treatment with corticosteroid therapy, she underwent transsphenoidal excision of the pituitary adenoma. Visual abnormalities were completely restored and pituitary function preserved. There was no evidence of impact on the foetus. The literature on the subject is reviewed with emphasis on the management of the apoplectic patient with mild and stable neuro-ophthalmological signs. LEARNING POINTS: There are no clear guidelines on the management of pituitary apoplexy in pregnancy. A multidisciplinary approach can minimise morbidity and mortality.Pituitary apoplexy has an unpredictable clinical course and determining which clinical situations warrant early surgery needs to take into consideration the presence and severity of neurological signs and their stability.The management of conscious apoplectic patients with absent or mild and stable neuro-ophthalmological signs is controversial.

Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training.

BACKGROUND: Reductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass. METHODS: Participants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance. RESULTS: Twelve months of PRT tended to reduce CRP compared to sham exercise (ß = -0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively). CONCLUSIONS: We have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations.

Psychiatric symptoms as a clinical presentation of Cushing's syndrome.

Cushing's syndrome can present with a spectrum of symptoms; however, it is less recognised that psychiatric symptoms can form part of the clinical presenting features. In the investigations for an organic cause for a psychiatric illness, Cushing's syndrome needs to be considered, especially if there are other features such as hirsutism or hypertension. In this article, the two cases reported demonstrate that a prompt diagnosis is not only important for psychiatric management but also crucial for timely institution of the necessary treatment of life-threatening causes of hypercortisolaemia such as metastatic adrenal carcinoma.

Acupuncture for polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea (infrequent or very light menstruation), infertility (failure to conceive), and hirsutism (excessive hair growth). Whilst Aleem 1987 revealed the presence of beta-endorphin in the follicular fluid of both normal and polycystic ovaries, Petraglia 1987 demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture has an impact on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction and fertility. OBJECTIVES: To assess the efficacy and safety of acupuncture treatment for women with polycystic ovarian syndrome (PCOS). SEARCH STRATEGY: Relevant studies were identified from the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE® In-Process and other non-indexed citations, Ovid MEDLINE® Daily and Ovid MEDLINE(R), EMBASE, PsycINFO, AMED, Chinese National Knowledge Infrastructure (CNKI) (including the Chinese journal full-text database (CJFD)), Chinese BioMedical Literature Database (CBM), VIP database for Chinese Technical Periodicals, China's important Conference Papers Database, and the China dissertation database. SELECTION CRITERIA: Truly randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for infertility in women with PCOS. We excluded quasi- or pseudo-RCTs. DATA COLLECTION AND ANALYSIS: We aimed to extract data independently by three authors using a piloted data extraction form. Data on study characteristics including methods, participants, interventions, and outcomes would be extracted. Crossover trials were not included unless there were first-phase data provided. Non-randomised controlled studies have been excluded. MAIN RESULTS: No truly randomised controlled trials of acupuncture for PCOS were found . AUTHORS' CONCLUSIONS: The current conventional medical treatments for women with PCOS are prescription medications, surgery, and lifestyle changes. Associated problems with current western therapies are the cost, risk of multiple pregnancies, undesirable side effects, and inconsistent effectiveness. Non-randomised acupuncture studies in PCOS have suggested a low associated adverse events rate, no increased risk of multiple pregnancies, and that it is inexpensive. However, there no RCTs have been performed in this area thus far. Therefore, properly designed RCTs are required before a conclusive statement can be drawn to support the use of acupuncture in the management of PCOS.

Effect of resistance training during hemodialysis on circulating cytokines: a randomized controlled trial.

The purpose of this study was to evaluate the effect of a 12-week intradialytic progressive resistance training (PRT) regimen on circulating pro- and anti-inflammatory cytokines. Forty-nine patients (62.6 ± 14.2 years) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital, Sydney, Australia. Patients were randomized to: PRT + usual care (n = 24) or usual care control (n = 25). The PRT group performed two sets of 10 exercises at high intensity using free-weights, 3 times per week for 12 weeks during dialysis, while the control group did not exercise. Tumor necrosis factor-alpha, interleukin-1b, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10, and interleukin-12 were measured in serum before and after the intervention period. Muscle cross-sectional area (CSA), intramuscular lipid, intermuscular adipose tissue, and subcutaneous and total thigh fat, evaluated via computed tomography of the non-dominant mid-thigh, were also collected at both time points. All cytokines were significantly elevated in the total cohort at baseline compared with normative data. There were no cytokine changes over time or between groups (p > 0.05). In secondary analyses pooling the groups, changes in logIL-6 and IL-8 were inversely related to changes subcutaneous thigh fat (p < 0.05) while changes in logIL-6 were also inversely related to changes in thigh muscle CSA, and total thigh fat (p < 0.03). These data suggest that 12 weeks of intradialytic progressive resistance training does not improve circulating pro- and anti-inflammatory markers. Further research is required to elucidate the implications and mechanisms of the relationships between IL-6 and IL-8 and body composition in ESRD.

Adiponectin isoform distribution in women--relationship to female sex steroids and insulin sensitivity.

Little is known about the associations between adiponectin and its oligomeric isoforms with female sex steroids, and the relevance of these relationships to insulin sensitivity in women. In a cross-sectional study of 32 healthy women (12 premenopausal, 10 postmenopausal, and 10 early pregnant), we investigated the correlations of total adiponectin and the high-, medium-, and low-molecular weight oligomers (HMW, MMW, and LMW, respectively) with estrogen, progesterone, adiposity, and insulin resistance. Fat mass and serum concentrations of estradiol, progesterone, insulin, glucose, and total and isoform adiponectin were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum concentrations of total and HMW adiponectin were highest in postmenopausal women and lowest in pregnant women. Concentrations of the MMW and LMW isoforms were not significantly different between the 3 groups. Total adiponectin, HMW adiponectin, and MMW adiponectin were negatively associated with estradiol and progesterone; but no associations between the LMW isoform and female sex steroids were observed. Fat mass and HOMA-IR were highest in pregnant women and lowest in premenopausal women. The HOMA-IR was positively associated with fat mass, estradiol, and progesterone, and negatively associated with total, HMW, and MMW adiponectin. Multivariate stepwise regression analysis revealed that fat mass explained 34% of the variance in HOMA-IR and that total and isoform adiponectin contributed an additional 10% to 15%. In the multivariate linear regression analysis, there were significant interactions of estradiol and progesterone with adiponectin or fat mass in the associations with HOMA-IR. In conclusion, there are strong negative associations of serum adiponectin and some of its isoforms with estradiol and progesterone. Female sex steroids are likely to affect insulin sensitivity through modulation of adiponectin and body fat.

Short-term oral oestrogen therapy dissociates the growth hormone/insulin-like growth factor-I axis without altering energy metabolism in premenopausal women.

OBJECTIVE: Oral oestrogen has been shown to dissociate the growth hormone (GH)/insulin-like growth factor (IGF)-I axis and alter energy metabolism in postmenopausal women. This study was designed to determine whether these metabolic changes occur with short-term oral oestrogen in premenopausal women. STUDY DESIGN: A double-blind placebo controlled randomised-crossover design study was performed in 12 premenopausal women. Investigations were performed after either 5 days of oral 17beta-oestradiol valerate 2mg twice daily or placebo. Outcomes included body composition measured by bio-impedance, energy metabolism measured by indirect calorimetry and blood sampling. RESULTS: Oral oestrogen significantly suppressed IGF-I levels and increased fasting GH levels. No significant changes in energy metabolism or body composition were detected. CONCLUSIONS: Short-term oral oestrogen suppresses IGF-I and elevates GH levels in premenopausal women. No effects were seen on body composition and energy metabolism. Further research is required to determine whether metabolic effects of oral oestrogen may become apparent if longer courses of treatment were administered to premenopausal women.