COMMENTARY Endocrinology

3 COMMENTARY Endocrinology: the next 60 years Ken K Y Ho Department of Endocrinology, St Vincent’s Hospital and Pituitary Research Unit, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia (Requests for offprints should be addressed to K K Y Ho; Email: [email protected]) Abstract Advances in clinical chemistry, molecular biology and paracrinology. The endocrine-related consequences of information technology have brought about major changes obesity and ageing will be major health problems, demand in the field of endocrinology. The future practice of for anti-obesity and anti-ageing treatments will escalate. endocrinology will be influenced by secular health trends, There will be increased blurring between endocrine disease consumer expectations and the globalisation of health. and non-disease. The future clinical endocrinologist must Pharmacotherapy will remain the backbone of endocrine continue to practice evidence-based medicine to improve the therapy led by developments in drug delivery technology, treatment of genuine endocrinopathies. pharmacogenomics, combinatorial chemistry and Journal of Endocrinology (2006) 190, 3–6 Introduction bioinformatics, advances that have catalysed the development of high-throughput technology, expanding the databases of The founding of the Society for Endocrinology 60 years catalogued knowledge for biomedical research. These ago marked the beginning of the specialty field of advances will have an unstoppable impact across all fields of hormones and chemical messengers. This was the period medicine. of steroid biochemistry and bioassays. The field has How will these advances impact on clinical endo- metamorphosed; major changes have occurred from crinology in the next 60 years? In this review, I will applications of advances in other fields. The development confine my crystal ball gazing to the pituitary and metabolic of immunological, receptor-binding and phosphorylation areas. The practice of endocrinology will be influenced by assays consolidated the principles of endocrinology, provid- secular health trends, demographics and consumer expec- ing the means of identifying and quantifying hormone tations. I will foreshadow major health issues confronting status and action. The tenets of hormone deficiency, excess the clinical endocrinologist, new treatments and changes in and resistance belong to this era. Endocrinology continues the landscape of endocrine practice. to be one of the most dynamic disciplines in biomedical science and among the most quantitative of the specialties in which the marriage of clinical and basic science is very The next 60 years strong (Wilson 2005). This period also began with the discovery of the genetic Secular trends code, heralding the dawn of molecular biology and The world is getting older. Life expectancy at 65 years culminating in the sequencing of the human genome 50 increased from 12 years by more than 50% over the 20th years later. The molecular revolution has led to the discovery century and this trend is continuing. According to the World of new receptors, signalling molecules and chemical Health Organization, the numbers over 60 years of age will messengers acting within complex networks. The new increase from 600 million in 2000 to 1.2 billion in 2025 and 2 insights gained from studying the molecular basis of hormone billion in 2050 with the greater increase occurring in the action and interactions have already changed, and will developing world (WHO 2006). In the US, the population continue to change, concepts of disease causation and older than 65 years increased from 12 million in 1950 to 26 treatment. The last few decades have also seen an evolution million in 2004 and there will be a further 50% increase by in information technology, knowledge engineering and 2050 (National Center for Health Statistics 2005). Journal of Endocrinology (2006) 190, 3–6 DOI: 10.1677/joe.1.06884 0022–0795/06/0190–001 q 2006 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.org Downloaded from Bioscientifica.com at 09/30/2021 05:04:20AM via free access 4 KKYHO $ Endocrinology: the next 60 years The world is also getting fatter. At present, obesity ranks normal and stress situations will be available. Thirty-day fourth as a major cause of morbidity and mortality by death- formulations of female hormones for HRT and higher dose and-disability adjusted life years (Powles & Day 2002). Many preparations for contraception will be the preferred alterna- leading journals have pointed out the pandemic in obesity, tives to the oral preparations of the 20th century. which is fuelling the alarming increase in the prevalence of Pharmacogenomics will come of age and will have a major metabolic syndrome and diabetes, both in the developed and impact across all endocrine-based therapies. Genetic variations developing world (McLellan 2002, Hedley et al. 2004, that affect the responses to hormones and drugs and their Yanovski 2005). The East is also catching up. A recent survey disposition within the complexendocrine network of the body in China indicates that approximately 30% of the population will be characterised (Wilke et al. 2005). At the patient level, are overweight and that 9$8% of men and 17$8% of women this will bring rationalisation and individualisation of therapy, have metabolic syndrome (Gu et al. 2005), a problem that may achieving optimal response with minimal side effects. Women well get worse. can be identified for safe treatment with oestrogens, the These demographic trends have clear implications for the hypoadrenal patient prescribed accurate dosage of steroid with endocrinologist. First, there is a predictable escalation in the confidence and the susceptible diabetic patient identified for societal burden of diabetes and associated micro- and preventative treatment against renal disease. cardiovascular diseases and the associated challenge of Combinatorial chemistry will bring treatment selectivity, controlling these. Secondly,the endocrinological management versatility and convenience. It will exploit knowledge gained of ageing will be an even bigger area. There will be strong from understanding how closely related hormones act on demands in the traditional areas of hormone replacement and similar classes of receptors to exert a range of effects. osteoporosis, albeit with newer drug formulations and Somatostatin receptor subtypes have already been shown to approaches. However, endocrine care of the aged will be exert differential effects on secretion and cell proliferation in increasingly blurred by endocrine treatment for ageing. the pituitary (Shimon et al. 1997, Zatelli et al. 2004). In the hypothalamus, a family of YY peptides interact with different Y receptor subtypes with overlapping and distinct functions Consumer trends regulating appetite, energy homeostasis, behaviour and The rejuvenists are of course going back to the future, driven reproduction (Lin et al. 2004). Synthetic compounds selective by consumer demand for eternal vigour and youth. There will for particular receptor subtypes will be available to target be increasing exploitation of the psychology of dissatisfaction treatment of selected tissues for different effects. Small non- and the promise of hormones to fix the woes of an unhealthy peptide oral mimetics will begin to replace insulin, GH, lifestyle or an unfulfilled life (Lamberts et al. 2003). The present gonadotrophins and parathyroid hormone and revolutionise day net-wise consumers are expert patients (Tattersall 2002); the treatment of many endocrine diseases. their wireless descendants will be more expert. They know that This era will also see the maturation of paracrinology, the hormones control growth, metabolism, fat, muscle, weight, science of fine-tuning hormone requirements at the tissue mood and sexual function; when these are not right, they level brought about by drugs regulating prohormone expect endocrinology to provide the solutions. A quick surf of conversion to, or inactivation of, active hormone. Tissue the World Wide Web reveals over 2 million sites for growth specific regulators of deiodinase, aromatase, 11ß-hydroxyster- hormone (GH) and over 1.2 million sites for dehydroepian- oid dehydrogenase (HSD) and 5a-reductase activities will drosterone use for anti-ageing therapy. These are only a fraction emerge. Cardiac function in the severe hypothyroid patient of the field of ‘cosmetic endocrinology’, which promises to with coronary artery disease will be protected by cardiac- offer much more. specific 30-deiodinase inhibitors during thyroid hormone replacement. Tissue-specific 11ß-HSD inhibitors will be available to protect against the catabolic, adipogenic and Therapy of endocrine disease diabetogenic effects of chronic hydrocortisone and predniso- What about mainstream endocrinology? Following the lone treatment. sequencing of the human genome, the complex path from In the battle against obesity, several classes of centrally genotype to phenotype will have been largely paved acting drugs controlling hypothalamic function will have (Strohman 2002). The new era will bring novel solutions to been developed. The major appetite-regulating pathways and the present problems from drug-delivery technologies, those regulating basal energy expenditure will have been combinatorial chemistry, pharmacogenomics, gene elucidated, with ligands and receptors identified. Chimeric regulation and manipulation. compounds

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