ORCID Profile
0000-0002-2508-9588
Current Organisation
Garvan Institute of Medical Research
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Publisher: Archives of Endocrinology and Metabolism
Date: 2019
DOI: 10.20945/2359-3997000000187
Abstract: Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports. Athletic performance depends on muscle strength and the energy required to power muscle function. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that in muscle GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. In recreational athletes, GH improves anaerobic capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH appears likely to selectively benefit sprint events and not physical performance that depends on strength and endurance. Arch Endocrinol Metab. 2019 (6):576-81.
Publisher: The Endocrine Society
Date: 19-06-2021
Abstract: Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs −0.7 (−1.5 to 0.2) nmol/L P & 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ −0.4 (−0.9 to −0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (−0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g P & 0.02] and lean mass [∆ 0.8 (−0.1 to 1.7) kg P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.
Publisher: Wiley
Date: 14-10-2018
DOI: 10.1111/DOM.13539
Abstract: To investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans. In a randomized double-blind, cross-over designed trial, 10 healthy adults (two men, eight women) underwent 2 weeks of spironolactone (100 mg/d) treatment and placebo, with an intervening 2-week wash-out period. BAT function was assessed in response to cooling and to a mixed meal. Metabolic activity was measured by fluoro-deoxyglucose (FDG) uptake (maximal standardized uptake value, SUV During cooling, BAT metabolic activity (SUV 6.30 ± 2.16 vs 3.98 ± 1.34 P < 0.05) and volume (54.9 ± 22.8 vs 21.6 ± 11.8 cm MC antagonism enhanced human BAT function in response to cooling and to a meal during which lipid synthesis was suppressed. As postprandial EPR comprises energy dissipated as heat and energy required to store nutrients, the reduction in lipid synthesis during MC antagonism is a probable consequence of concurrent stimulation of BAT thermogenesis. The shift in energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity.
Publisher: Springer Science and Business Media LLC
Date: 30-09-2019
Publisher: The Endocrine Society
Date: 06-05-2020
Publisher: Springer Science and Business Media LLC
Date: 05-09-2023
Publisher: Springer Science and Business Media LLC
Date: 17-08-2023
Publisher: Wiley
Date: 21-07-2017
DOI: 10.1111/CEN.13402
Abstract: Factors determining recurrence of nonfunctioning pituitary adenomas (NFAs) that require further therapy are unclear as are postoperative follow-up imaging guidelines. We aimed to identify predictors for secondary therapy after surgical resection of NFAs and use this knowledge to inform postoperative management. A single-centre retrospective study of surgically resected NFAs in 108 patients followed for up to 15 years. Serial tumour images were analysed for size, location and growth rate (GR) and tissue analysed for hormone cell type and proliferation indices with secondary treatment as outcome measure. Twenty-four of 66 (36%) patients harbouring a postoperative remnant required secondary treatment, all occurring within 10 years. No secondary treatment was required in any of 42 patients with complete tumour resection. Age, gender, remnant volume and tumour histology were not different between patients requiring and not requiring secondary therapy. Remnant GRs in those requiring secondary therapy were more than 10-fold higher (P<.01). Tumours with a GR ≥80 mm In surgically resected NFAs further treatment is dependent on the presence of residual tumour, growth rate and location but not tumour histology. Postoperative growth rate of NFAs in the first 3 years of imaging can be used to tailor long-term follow-up to optimize use of health resources.
Publisher: Wiley
Date: 06-12-2017
DOI: 10.1111/DOM.13157
Abstract: To investigate the effect of glucocorticoids on brown adipose tissue (BAT) function in humans. In a randomized double-blind cross-over design, 13 healthy adults underwent 1 week of oral prednisolone treatment (15 mg/d) and placebo with an intervening 2-week wash-out period. BAT function was assessed in response to cooling (19°C) and to a standardized meal, by measuring fluoro-deoxyglucose (FDG) uptake using positron emission tomography-computed tomography and skin temperatures overlying the supraclavicular (SCL) BAT depots using infrared thermography. Postprandial energy and substrate metabolism was assessed by indirect calorimetry. During cooling, prednisolone significantly reduced BAT FDG uptake (standardized uptake value, SUV Prolonged exposure to glucocorticoid suppresses the function of human BAT. The enhancement of energy production and lipogenesis in the face of reduced dissipation of energy as heat suggests that glucocorticoids channel energy towards fat storage after nutrient intake. This is a novel mechanism of glucocorticoid-induced obesity.
Publisher: The Endocrine Society
Date: 06-03-2023
Abstract: Growth hormone (GH) regulates metabolic and physical health in the adult human. Because the GH system is regulated by estrogens, therapeutic estrogen compounds are likely to affect metabolic health. Estrogens are available for oral and parenteral use in natural, prodrug, and synthetic formulations including selective estrogen receptor modulators (SERMs). This review covers the pharmacology of estrogen and the effects on GH action to inform judicious use in the pituitary patient. The effects on the GH system are route dependent due to first-pass hepatic metabolism. Oral but not parenteral estrogen compounds inhibit GH action, reducing hepatic insulin-like growth factor-1 (IGF-1) production, protein anabolism, and fat utilization. In patients with GH deficiency, oral estrogen therapy exacerbates the degree of hyposomatotrophism and attenuates the beneficial effects of GH replacement therapy, effects that are greater with contraceptive than replacement doses. Surveys report that less than one-fifth of hypopituitary women are appropriately replaced by a transdermal route and up to half on oral therapy are inappropriately treated with contraceptive steroids. In acromegaly, however, estrogens, especially synthetic formulations of greater potency, reduce IGF-1, improving disease control, an effect also observed in men treated with SERMs. The route-dependent effects and potency of estrogen formulations are important considerations for optimizing the management of hypogonadal patients with pituitary disease, in particular GH deficiency and acromegaly. For hypopituitary women, estrogens should be replaced by a nonoral route. For acromegaly, oral estrogen formulations can be considered as simple adjuvant therapy for disease control.
Publisher: Springer Science and Business Media LLC
Date: 15-11-2022
DOI: 10.1007/S11102-022-01283-3
Abstract: The long-term effects of long-acting growth hormone (LAGH) analogues on glucose metabolism in adult growth hormone deficiency (AGHD) are not known. We investigated the impact of LAGH somapacitan, administered once-weekly, on glucose metabolism in patients with AGHD. In post hoc-defined analyses, we compared the effects of somapacitan with daily growth hormone (GH) and placebo on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) in patients with AGHD across a unique data set from three phase 3 randomized controlled trials (REAL 1, REAL 2 and REAL Japan). No new cases of diabetes mellitus were reported with somapacitan. Among GH-naïve patients (n = 120 somapacitan, n = 119 daily GH), higher changes from baseline in FPG, HOMA-IR and fasting insulin levels were observed with daily GH versus somapacitan at 34 weeks, but not at 86 weeks. HbA1c and HOMA-β did not differ between groups at either timepoint. Among treatment-naïve patients, sex, age, fasting insulin, glucose tolerance status and body mass index did not influence changes in glucose metabolism. In previously treated patients (REAL 1 extension: n = 51 somapacitan, n = 52 daily GH REAL 2: n = 61 and n = 31, respectively REAL Japan: n = 46 and n = 16, respectively), the difference in changes from baseline were not statistically significant between somapacitan and daily GH for any glucose metabolism parameters. Somapacitan, compared with daily GH, did not adversely affect glucose metabolism up to 86 weeks in a large cohort of treatment-naïve or previously treated patients with AGHD. Trial registrations (date of registration): NCT02229851 (2 September 2014), NCT02382939 (3 March 2015), NCT03075644 (7 March 2017).
Publisher: Wiley
Date: 17-11-2018
DOI: 10.1111/CEN.13499
Abstract: Insulin-like growth factor 1 (IGF1) has anabolic and growth-promoting effects, raising concerns regarding its potential to promote tumour growth. Circulating IGF1 is bound to binding proteins, which modulate bioavailability of IGF1. This study assessed the associations of IGF1 and its binding proteins 1 (IGFBP1) and 3 (IGFBP3) with cancer risk. A prospective cohort study of 4042 men aged ≥70 years. Plasma total IGF1, IGFBP1 and IGFBP3 were measured between 2001 and 2004. Cancer-related outcomes were assessed until 20 June 2013 using data linkage. Analyses were performed using proportional hazards models with death as a competing risk, and adjustments were made for potential confounders. Results are expressed as subhazard ratios (SHR). There were 907 men who were diagnosed with cancer during a median of 9-year follow-up. Of these, there were 359, 139 and 125 prostate, colorectal and lung cancers, respectively. After adjustments, total IGF1 was not associated with the incidence of any cancer, prostate, lung or colorectal cancer. In the fully-adjusted model, higher IGFBP3 was associated with increased incidence of colorectal cancer (SHR = 1.20, 95% CI 1.01-1.43 P = .041 for every 1 standard deviation increase in IGFBP3) but not other cancers. This effect was not attenuated by inclusion of total IGF1 into the multivariate model (SHR = 1.28, 95% CI 1.03-1.58 P = .025). Neither total IGF1, IGFBP1 nor IGFBP3 were associated with cancer-related deaths. Higher IGFBP3 predicted increased incidence of colorectal cancer in older men independent of conventional risk factors and total IGF1. Further studies are warranted to explore potential underlying mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 17-10-2023
Publisher: Springer Science and Business Media LLC
Date: 07-01-2020
Publisher: Bioscientifica
Date: 05-2023
DOI: 10.1530/JOE-22-0197
Abstract: 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.
Publisher: The Endocrine Society
Date: 10-06-2019
Abstract: GH is banned by the World Anti-Doping Agency as a performance-enhancing anabolic agent. Doping with GH likely began in the early 1980s and became more prevalent with the advent of recombinant technology well before any scientific evidence of benefit. The expectation that GH improves physical function stems from its anabolic and lipolytic properties. Athletic performance depends on muscle strength and the energy required to power muscle function. In recreational athletes, GH selectively improves anaerobic sprint capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH is secreted as a family of isoform peptides in a pulsatile manner reflecting intermittent secretion and rapid clearance. Its anabolic actions are largely mediated by IGF-I, which stimulates whole-body protein synthesis, including skeletal muscle and collagen proteins. Two methods have been validated for detecting GH abuse in athletes. The first (the isoform method) is based on distinguishing pure recombinant 22-kDa GH from the heterogeneous isoforms secreted from the pituitary. The second (the marker method) is based on measuring blood levels of GH-responsive proteins, specifically IGF-I and the N-terminal propeptide of type III collagen (P-III-NP). Only a handful of athletes have been caught since the implementation of GH doping tests in 2004. The low rate likely reflects the limitation of in-competition testing using current methods. Improved detection rates may be achieved by more out-of-competition testing, introducing athletes’ biological passports, and the development of novel methods. Governance, operational, technical, and political factors influence the effectiveness of an anti-doping program.
Publisher: The Endocrine Society
Date: 09-02-2021
Abstract: The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
Publisher: Oxford University Press (OUP)
Date: 06-2022
DOI: 10.1530/EJE-21-1186
Abstract: Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful in idual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.
No related grants have been discovered for Ken Ho.