Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated. RESULTS: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients). CONCLUSION: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Recovery using "float" from high intensity stress on growth hormone-like molecules in resistance trained men.

OBJECTIVE: The purpose of this study was to examine the influence of a novel "floatation-restricted environmental stimulation therapy" (floatation-REST) on growth hormone responses to an intense resistance exercise stress. DESIGN: Nine resistance trained men (age: 23.4 ±â€¯2.5 yrs.; height: 175.3 ±â€¯5.4 cm; body mass: 85.3 ±â€¯7.9 kg) completed a balanced, crossover-controlled study design with two identical exercise trials, differing only in post-exercise recovery intervention (i.e., control or floatation-REST). A two-week washout period was used between experimental conditions. Plasma lactate was measured pre-exercise, immediately post-exercise and after the 1 h. recovery interventions. Plasma iGH was measured pre-exercise, immediately-post exercise, and after the recovery intervention, as well as 24 h and 48 h after the exercise test. The bGH-L was measured only at pre-exercise and following each recovery intervention. RESULTS: For both experimental conditions, a significant (P ≤ 0.05) increase in lactate concentrations were observed immediately post-exercise (~14 mmol • L-1) and remained slightly elevated after the recovery condition. The same pattern of responses was observed for iGH with no differences from resting values at 24 and 48 h of recovery. The bGH-L showed no exercise-induced changes following recovery with either treatment condition, however concentration values were dramatically lower than ever reported. CONCLUSION: The use of floatation-REST therapy immediately following intense resistance exercise does not appear to influence anterior pituitary function in highly resistance trained men. However, the lower values of bGH suggest dramatically different molecular processing mechanisms at work in this highly trained population.

Acute Oral Ingestion of a Multi-ingredient Preworkout Supplement Increases Exercise Performance and Alters Postexercise Hormone Responses: A Randomized Crossover, Double-Blinded, Placebo-Controlled Trial.

Multi-ingredient preworkout supplements (MIPS) are marketed as a means to increase exercise performance. The purpose of this study was to determine the effect of a single serving of Bang Pre-Workout Master Blaster (BMB) on upper- and lower-body power output and local muscular endurance. Ten resistance-trained males participated in two exercise testing sessions consisting of the vertical jump (VJ), seated medicine ball throw (SMBT), and local muscular endurance tests for the bench press (BP) and leg extension (LE) exercises at 70% of one-repetition maximum. Participants consumed placebo (PLA) or BMB 30 minutes prior to each exercise session. No difference between trials was observed for SMBT distance or BP repetitions. Vertical jump (p = .006) and LE repetitions (p = .014) were greater for the BMB trial compared with placebo. A significant interaction between trial and time was observed for insulin-like growth factor-1 (IGF-1; p = .044). Serum IGF-1 was significantly increased at both 30 PS (p = .004) and 30PX (p = .038) compared with BL for the BMB trial only. In conclusion, acute ingestion of BMB increased lower-body power and endurance as measured by the VJ and LE repetition tests, respectively, without altering hemodynamics. Furthermore, serum IGF-1 increased in response to acute exercise with BMB supplementation, but not with PLA. No differences in human growth hormone (HGH) or serum cortisol responses were observed between trials.

Bioactive growth hormone in humans: Controversies, complexities and concepts.

OBJECTIVE: To revisit a finding, first described in 1978, which documented existence of a pituitary growth factor that escaped detection by immunoassay, but which was active in the established rat tibia GH bioassay. METHODS: We present a narrative review of the evolution of growth hormone complexity, and its bio-detectability, from a historical perspective. RESULTS: In humans under the age of 60, physical training (i.e. aerobic endurance and resistance training) are stressors which preferentially stimulate release of bioactive GH (bGH) into the blood. Neuroanatomical studies indicate a) that nerve fibers directly innervate the human anterior pituitary and b) that hind limb muscle afferents, in both humans and rats, also modulate plasma bGH. In the pituitary gland itself, molecular variants of GH, somatotroph heterogeneity and cell plasticity all appear to play a role in regulation of this growth factor. CONCLUSION: This review considers more recent findings on this often forgotten/neglected subject. Comparison testing of a) human plasma samples, b) sub-populations of separated rat pituitary somatotrophs or c) purified human pituitary peptides by GH bioassay vs immunoassay consistently yield conflicting results.

Acute Neuromuscular and Hormonal Responses to Different Exercise Loadings Followed by a Sauna.

Rissanen, JA, Häkkinen, A, Laukkanen, J, Kraemer, WJ, and Häkkinen, K. Acute neuromuscular and hormonal responses to different exercise loadings followed by a sauna. J Strength Cond Res 34(2): 313-322, 2020-The purpose of this study was to investigate acute responses of endurance (E + SA), strength (S + SA), and combined endurance and strength exercise (C + SA) followed by a traditional sauna bath (70° C, 18% relative humidity) on neuromuscular performance and serum hormone concentrations. Twenty-seven recreationally physically active men who were experienced with taking a sauna participated in the study. All the subjects performed a sauna bath only (SA) first as a control measurement followed by S + SA and E + SA (paired matched randomization) and C + SA. Subjects were measured PRE (before exercise), MID (immediately after exercise and before sauna), POST (after sauna), POST30min (30 minutes after sauna), and POST24h (24 hours after PRE). Maximal isometric leg press (ILPFmax) and bench press (IBPFmax) forces, maximal rate of force development (RFD) and countermovement vertical jump (CMVJ), serum testosterone (TES), cortisol (COR), and 22-kD growth hormone (GH22kD) concentrations were measured. All exercise loadings followed by a sauna decreased ILPFmax (-9 to -15%) and RFD (-20 to -26%) in POST. ILPFmax, RFD, and CMVJ remained at significantly (p ≤ 0.05) lowered levels after S + SA in POST24h. IBPFmax decreased in POST in S + SA and C + SA and remained lowered in POST24h. SA decreased ILPFmax and IBPFmax in POST and POST30min and remained lowered in ILPFmax (-4.1%) at POST24h. GH22kD, TES, and COR elevated significantly in all loadings measured in the afternoon in MID. SA only led to an elevation (15%) in TES in POST. The strength exercise followed by a sauna was the most fatiguing protocol for the neuromuscular performance. Traditional sauna bathing itself seems to be strenuous loading, and it may not be recommended 24 hours before the next training session. A sauna bath after the loadings did not further change the hormonal responses recorded after the exercise loadings.

Efficacy of L-leucine Supplementation Coupled With Resistance Training in Untrained Midlife Women.

Objective: This study investigated the effects of leucine supplementation with resistance training (RT) in untrained peri- and postmenopausal women on fat free mass, strength, and select anabolic-related hormones.Method: This was a randomized, double-blind, placebo-controlled trial, in which 36 untrained women were randomly assigned to either a leucine or placebo supplement group coupled with 10 weeks of RT, performed thrice weekly, while ingesting either 5 g of placebo or leucine. Before and after RT, body composition and muscle strength were assessed and venous blood samples obtained to determine the levels of estradiol, testosterone, insulin-like growth factor-1, growth hormone, and cortisol. Data were analyzed by utilizing separate 2 × 2 [group × time (pretest and posttest)] factorial analyses of variance with repeated measures (p ≤ .05).Results: There were no significant changes or differences between groups in fat free mass or with any of the serum hormones assessed in response to supplementation. However, there were significant increases in strength in both groups in response to RT, but not supplementation.Conclusions: Peri- and postmenopausal women had significant increases in strength following 10 weeks of RT, with no additional effects from supplementing with leucine. There were no significant changes in either group regarding fat free mass or serum hormones.

The Effects of 12 Weeks of a Combined Exercise Program on Physical Function and Hormonal Status in Elderly Korean Women.

Aging causes a decline in physical function and hormonal balance. Exercise can improve these parameters. However, the beneficial effects of a combined exercise program (Korean dance and yoga) on physical function and hormonal status in elderly women remain unknown. This study aims to investigate the effects of a 12-week combined exercise program on balance, flexibility, muscle strength, and hormonal status in elderly Korean women. Twenty-five healthy elderly women were recruited and randomly divided into the control (CON) and exercise (EXE) groups. The EXE group underwent the combined exercise program (60 min/day and 3 times/week) for 12 weeks. The two groups did not differ in body weight, lean body mass, fat mass, body fat percentage, or body mass index at baseline or in the changes following the experimental conditions. A significant time × group interaction was detected for anterior and posterior dynamic balance, static balance, and growth hormone (GH). After the combined exercise program, anterior dynamic balance, posterior dynamic balance, static balance, flexibility, muscle strength, GH, dehydroepiandrosterone-sulfate, and estrogen significantly increased in the EXE group compared to the CON group. In conclusion, the combined exercise program contributed to improvements in overall health, including physical function and hormonal status, in elderly Korean women.

ENDOCRINOLOGY AND ADOLESCENCE: Dealing with transition in young patients with pituitary disorders.

INTRODUCTION: The transition age is the period between childhood to adulthood; it refers to a broad set of physical, cognitive and sociocultural modifications, arbitrarily defined as starting in late puberty and ending with full adult maturation. Pituitary disorders in adolescence represent a challenge that requires careful management during the transition to adult care. METHODS: Given the complexity of care of pituitary disorders in the transition age, we have reviewed the relevant medical literature focusing on aetiology, clinical manifestations, treatment strategies of GH deficiency (GHD), hypogonadotrophic hypogonadism (HH) in male and female adolescents, central hypothyroidism (CH), central adrenal insufficiency (CAI) and cranial diabetes insipidus (CDI) at this time. The objective of the present review is to provide an up-to-date evaluation of the transition period to evaluate the specific needs of adolescents with chronic pituitary disease in order to optimise their management. RESULTS: We provide an overview of current clinical management of GHD, HH, CH, CAI and CDI in the transition age. CONCLUSIONS: Specific changes occur in pituitary function during the transition period. A holistic approach including discussion of patients' concerns and emotional support should constitute a key component of managing pituitary disorders in adolescence. Special transition clinics where paediatric and adult endocrinologists work together, should be increasingly created and strengthened to bridge care, to promote continuity and adherence to treatment and to limit potential negative development, metabolic, skeletal and cardiovascular sequelae of discontinuity of care among adolescents with pituitary disorders.

Surgical-pharmacological interactions in the treatment of acromegaly.

INTRODUCTION: Acromegaly requires a multimodal treatment approach that includes surgery by an expert pituitary neurosurgeon, pharmacological treatment with one or more of the available drugs and radiation therapy. These treatment alternatives are not mutually exclusive but rather complement each other when properly indicated in the individual patient. In this review, we summarize and analyze the available data concerning the choice of the surgical approach (microscopy vs. endoscopy) and the interactions between medical treatment with somatostatin analogs and pituitary surgery. AREAS COVERED: Technical aspects, complications and outcome of transsphenoidal surgery (TSS); Advantages and disadvantages of the microscopic and endoscopic approaches; Safety and efficacy of somatostatin analogs (SSA); Primary pharmacological therapy versus primary TSS; Benefits of the preoperative treatment with SSA; and the effect of surgical tumor debulking in the therapeutic response to SSA. EXPERT COMMENTARY: Continuing efforts at improving surgical techniques and at generating more efficacious pharmacological therapies for acromegaly are likely to improve the outcome of these patients. However, an integral approach of the patient aimed not only at achieving biochemical criteria of cure but also at treating the individual comorbidities is mandatory to improve the quality of life of these patients and to reduce their mortality rate.

Leucine Metabolites Do Not Enhance Training-induced Performance or Muscle Thickness.

Leucine metabolites, α-hydroxyisocaproic acid (α-HICA) and ß-hydroxy-ß-methylbutyrate (calcium, HMB-Ca and free acid, HMB-FA), have been proposed to augment resistance training-induced changes in body composition and performance. PURPOSE: We aimed to conduct a double-blind randomized controlled pragmatic trial to evaluate the effects of off-the-shelf leucine metabolite supplements of α-HICA, HMB-FA, and HMB-Ca on resistance training-induced changes in muscle thickness and performance. METHODS: Forty men were randomly assigned to receive α-HICA (n = 10, fat-free mass [FFM] = 62.0 ± 7.1 kg), HMB-FA (n = 11, FFM = 62.7 ± 10.5 kg), HMB-Ca (n = 9, FFM = 65.6 ± 10.1 kg), or placebo (PLA; n = 10, FFM = 64.2 ± 5.7 kg). The training program consisted of whole body thrice weekly resistance training for 8 wk (seven exercises per session, three to four sets per session, at 70%-80% one repetition maximum). Skeletal muscle thickness by ultrasound, performance measures, and blood measures (creatine kinase, insulin-like growth factor 1, growth hormone, cortisol, and total testosterone) were evaluated at baseline and at the end of weeks 4 and 8. RESULTS: Time-dependent changes were observed for muscle thickness (P < 0.001), one repetition maximum bench press and squat (P < 0.001), Wingate peak power (P = 0.02), countermovement jump height (P = 0.03), power (P = 0.006), creatine kinase, insulin-like growth factor-1, growth hormone, and cortisol (all P < 0.001). No significant between-group or time-group interactions were observed. CONCLUSIONS: No leucine metabolite resulted in any ergogenic effects on any outcome variable. Supplementation with leucine metabolites-α-HICA, HMB-FA, or HMB-Ca-is not a supplementation strategy that improves muscle growth and strength development in young adult men.

Equivalent Hypertrophy and Strength Gains in ß-Hydroxy-ß-Methylbutyrate- or Leucine-supplemented Men.

Ingestion of proteins with high leucine content during resistance training (RT) can augment hypertrophy. Some data suggest that a leucine metabolite, ß-hydroxy, ß-methylbutyrate (HMB), is substantially more anabolically efficacious than leucine. PURPOSE: We aimed to test whether supplementation with HMB versus leucine, added to whey protein, would result in differential muscle hypertrophy and strength gains in young men performing RT. METHODS: Twenty-six resistance-trained men (23 ± 2 yr) performed 12 wk of RT with three phases. Phase 1: 8 wk of periodized RT (three training sessions per week). Phase 2: 2 wk overreaching period (five sessions per week). Phase 3: 2 wk taper (three sessions per week). Participants were randomly assigned to twice daily ingestion of: whey protein (25 g) plus HMB (1.5 g) (whey+HMB; n = 13) or whey protein (25 g) plus leucine (1.5 g) (whey+leu; n = 13). Skeletal muscle biopsies were performed before and after RT. Measures of fat- and bone-free mass, vastus lateralis (VL) muscle thickness and muscle cross-sectional area (CSA) (both by ultrasound), muscle fiber CSA, and 1-repetition maximum (1-RM) strength tests were determined. RESULTS: We observed increases in fat- and bone-free mass, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM strength with no differences between groups at any phase. We observed no differences between groups or time-group interactions in hormone concentrations at any phase of the RT program. CONCLUSIONS: ß-Hydroxy-ß-methylbutyrate added to whey did not result in greater increases in any measure of muscle mass, strength, or hormonal concentration compared to leucine added to whey. Our results show that HMB is no more effective in stimulating RT-induced hypertrophy and strength gains than leucine.

The cause-effect relationship between bone loss and Alzheimer's disease using statistical modeling.

BACKGROUND: Animal studies provide strong evidence that the CNS directly regulates bone remodeling through the actions of the hypothalamus via two distinct pathways, the neural (mediated by leptin) arm and neurohumoral (mediated by neurohormones and growth factors) arm. The impact of AD on central regulatory mechanisms of bone mass is not known. OBJECTIVES: To test a model that assesses the relationship between hypothalamic atrophy and bone loss in Alzheimer's disease (AD) and potential mediation through neural (leptin) and neurohumoral (insulin-like growth factor -1, IGF-1) mechanisms. HYPOTHESES: AD-related hypothalamic structural change alters neural and neurohumoral regulatory systems of bone remodeling and contributes to bone loss in early AD. DESIGN: A secondary data analysis of data obtained in a two-year longitudinal study with path analysis and longitudinal mediation modeling. PARTICIPANTS: The data were collected as a part of the University of Kansas Brain Aging Project, a two-year observational study of 71 older adults with early stage AD and 69 non-demented controls. MEASUREMENTS: Demographic characteristics and measures of bone density, body composition, and hypothalamic volume, serum levels of leptin, growth hormone, and IGF-1 were collected. RESULTS: Hypothalamic atrophy and bone loss were observed in AD group and were associated. Data modeling suggests that bone loss may precede measurable changes in the brain. Leptin increased over two years in AD and the increase in leptin was associated with hypothalamic atrophy. However, changes in leptin or IGF-1 levels did not mediate the relationship between hypothalamic atrophy and bone loss. CONCLUSIONS: This study extends previous findings by suggesting that bone loss in AD may be related to neurodegenerative changes (atrophy) in the hypothalamus. Further studies are needed to explore the role of brain atrophy and mediating mechanisms in bone loss. Further exploring temporal relationship between bone loss and AD may have an important diagnostic value.

Aromatized Estrogens Amplify Nocturnal Growth Hormone Secretion in Testosterone-Replaced Older Hypogonadal Men.

Context: Testosterone (T) increases GH secretion in older men with a relative lack of T, in hypogonadal men of all ages, and in patients undergoing sex reassignment. The role of estradiol (E2) in men is less well defined. Objective: To assess the contribution of aromatization of T to spontaneous nocturnal and stimulated GH secretion. Participants: Four groups of healthy older men (N = 74, age range 57 to 77 years) were studied. The gonadotropic axis was clamped with the gonadotropin-releasing hormone antagonist degarelix. Three groups received T and one group placebo addback. Two T-replaced groups were treated with anastrozole (an aromatase inhibitor) and either placebo or E2 addback. Main Outcome Measures: Ten-minute GH concentration profiles were quantified by deconvolution analysis, after overnight (2200 to 0800 hours) sampling, and after combined IV injection of GHRH (0.3 µg/kg) and GHRH-2 (0.3 µg/kg) and withdrawal of a 2-hour somatostatin infusion (1 µg/kg/h). Results: E2 addback during aromatase inhibition increased basal (P = 0.046), pulsatile (P = 0.020), and total (P = 0.018) GH secretion by 60% to 70%. E2 did not potentiate GH secretory stimuli. Logarithmically transformed pulsatile GH secretion correlated strongly and positively with concurrent E2 concentrations overall (P = 0.028) and under anastrozole treatment (P = 0.005). Conclusion: E2 administration in older men transdermally stimulates overnight pulsatile GH secretion. The exact site of E2 action cannot be ascertained from these experiments but may include hypothalamic loci involved in GH regulation, especially because GH secretagogue effects on somatotrope pituitary cells were not affected.

Auditory closed-loop stimulation of EEG slow oscillations strengthens sleep and signs of its immune-supportive function.

Sleep is essential for health. Slow wave sleep (SWS), the deepest sleep stage hallmarked by electroencephalographic slow oscillations (SOs), appears of particular relevance here. SWS is associated with a unique endocrine milieu comprising minimum cortisol and high aldosterone, growth hormone (GH), and prolactin levels, thereby presumably fostering efficient adaptive immune responses. Yet, whether SWS causes these changes is unclear. Here we enhance SOs in men by auditory closed-loop stimulation, i.e., by delivering tones in synchrony with endogenous SOs. Stimulation intensifies the hormonal milieu characterizing SWS (mainly by further reducing cortisol and increasing aldosterone levels) and reduces T and B cell counts, likely reflecting a redistribution of these cells to lymphoid tissues. GH remains unchanged. In conclusion, closed-loop stimulation of SOs is an easy-to-use tool for probing SWS functions, and might also bear the potential to ameliorate conditions like depression and aging, where disturbed sleep coalesces with specific hormonal and immunological dysregulations.

Do anabolic nutritional supplements stimulate human growth hormone secretion in elderly women with heart failure?

Growth hormone treatment has gained attention over the past decade as a treatment for heart failure. Human growth hormone (HGH) must be administered by injections (usually daily), so there is considerable advantage to stimulation of endogenous secretion by amino acid-based nutritional supplementation. However, studies investigating the effect of amino acid (AA) supplementation show conflicting results. Therefore, in this study we aimed to investigate the effect of nutritional supplementation on HGH production in elderly women with heart failure. Eight elderly women with heart failure participated in this randomized cross-over study. Plasma HGH concentration was measured before and for 4 h following ingestion of a mixture of protein, carbohydrate, and fat or an AA beverage. HGH concentration was determined with ELISA kits and AA concentrations were analyzed by Liquid Chromatography-Mass Spectrometry (LCMS). Linear mixed models was performed to analyze the effect of time, treatment, and interaction. Plasma arginine and lysine concentrations were significantly higher after consumption of the AA drink compared to the mixture of protein, carbohydrate, and fat. Nonetheless, only ingestion of the protein, carbohydrate, and fat mixture (meal replacement) increased HGH concentration. HGH concentration was increased in elderly women with heart failure following consumption of a meal replacement containing protein, carbohydrate, and fat. Consumption of a mixture of amino acids failed to increase HGH concentration despite significantly greater elevations in plasma amino acid concentrations, including arginine and lysine. The stimulatory effect of the protein/carbohydrate/fat mixture was presumably mediated by factors other than increases in free amino acid concentrations.

Growth and Growth hormone - Insulin Like Growth Factor -I (GH-IGF-I) Axis in Chronic Anemias.

Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) was considered to be among the most important contributing factors to the global burden of disease. Prolonged and/or chronic anemia has a negative effect on linear growth especially during the rapid phases (infancy and puberty). Additionally infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. In view of the significant impact of chronic anemias on growth, pediatricians endocrinologists and hematologists should advocate primary prevention and screening for growth disturbance in these forms of anemias. The extent of the negative effect of different forms of chronic anemias on linear growth and its possible reversibilty is addressed in this review. The possible mechanisms that may impair growth in the different forms of anemias are addressed with special attention to their effect on the growth hormone (GH) - insulin like growth factor -I (IGF-I).

Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

PURPOSE: High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. DESIGN: Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. RESULTS: Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. CONCLUSION: High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

Multi-modal exercise training and protein-pacing enhances physical performance adaptations independent of growth hormone and BDNF but may be dependent on IGF-1 in exercise-trained men.

OBJECTIVE: Protein-pacing (P; 5-6meals/day @ 2.0g/kgBW/day) and multi-mode exercise (RISE; resistance, interval, stretching, endurance) training (PRISE) improves muscular endurance, strength, power and arterial health in exercise-trained women. The current study extends these findings by examining PRISE on fitness, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and brain-derived neurotrophic factor (BDNF) response, cardiometabolic health, and body composition in exercise-trained men. DESIGN: Twenty active males (>4daysexercise/week) completed either: PRISE (n=11) or RISE (5-6meals/day @ 1.0g/kgBW/day; n=9) for 12weeks. Muscular strength (1-repetition maximum bench and leg press, 1-RM BP, and 1-RM LP), endurance (sit-ups, SU; push-ups, PU), power (squat jump, SJ, and bench throw, BT), flexibility (sit-and-reach, SR), aerobic performance (5km cycling time-trial, TT), GH, IGF-1, BDNF, augmentation index, (AIx), and body composition, were assessed at weeks 0 (pre) and 13 (post). RESULTS: At baseline, no differences existed between groups except for GH (RISE, 230±13 vs. PRISE, 382±59pg/ml, p<0.05). The exercise intervention improved 1-RM, SJ, BT, PU, SU, SR, 5km-TT, GH, AIx, BP, and body composition in both groups (time, p<0.05). However, PRISE elicited greater improvements in 1-RM BP (21 vs. 10∆lbs), SJ (171 vs. 13∆W), 5km-TT (-37 vs. -11∆s), and sit-and-reach (5.3 vs. 1.2∆cm) over RISE alone (p<0.05) including increased IGF-1 (12%, p<0.05). CONCLUSIONS: Exercise-trained men consuming a P diet combined with multi-component exercise training (PRISE) enhance muscular power, strength, aerobic performance, and flexibility which are not likely related to GH or BDNF but possibly to IGF-1 response.

The effects of physical therapeutic agents on serum levels of stress hormones in patients with osteoarthritis.

To investigate the effects of physical agents on the levels of stress hormones in patients with osteoarthritis (OA).Transcutaneous electrical nerve stimulation, hot packs, and therapeutic ultrasound were applied to the lumbar region and knees of patients with OA. Blood samples were taken for the measurement of the serum levels of glucose, insulin (INS), growth hormone (GH), prolactin (PRL), cortisol (COR), and plasma adrenocorticotropic hormone (ACTH) immediately before and after the 1st session, to investigate the acute effects of those physical agents on the endocrine system. The hormone levels were also measured every 5 sessions in a total of 10 sessions. The treatment response was also evaluated by using the visual analogue scale (VAS), Roland Morris Disability Questionnaire (RMDQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) throughout the therapy period.After the 1st session, there was a decrease in INS levels and a mild decrease in PRL levels (P = 0.001 and P < 0.05, respectively). Throughout the 10-session therapy period, the INS levels increased, whereas the ACTH and COR levels decreased (P < 0.05 for all). The VAS-spine, RMDQ, VAS-knee, and WOMAC scores decreased (P = 0.001 for VAS-spine and P < 0.001 for all others). A positive correlation was detected between the changes in serum COR and WOMAC-pain score (P < 0.05).Although the combination therapy caused changes in INS level accompanied with steady glucose levels, the application of physical agents did not adversely affect the hormone levels. The decrease in ACTH and COR levels may be attributed to the analgesic effect of agents and may be an indicator of patient comfort through a central action.

Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors.

OPINION STATEMENT: Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT <50 Gy, the primary site of radiation damage is the hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.