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: k.ho@garvan.org.au)
Abstract
Advances in clinical chemistry, molecular biology and
information technology have brought about major changes
in the field of endocrinology. The future practice of
endocrinology will be influenced by secular health trends,
consumer expectations and the globalisation of health.
Pharmacotherapy will remain the backbone of endocrine
therapy led by developments in drug delivery technology,
pharmacogenomics, combinatorial chemistry and
paracrinology. The endocrine-related consequences of
obesity and ageing will be major health problems, demand
for anti-obesity and anti-ageing treatments will escalate.
There will be increased blurring between endocrine disease
and non-disease. The future clinical endocrinologist must
continue to practice evidence-based medicine to improve the
treatment of genuine endocrinopathies.
Journal of Endocrinology (2006) 190, 3–6
Introduction
The founding of the Society for Endocrinology 60 years
ago marked the beginning of the specialty field of
hormones and chemical messengers. This was the period
of steroid biochemistry and bioassays. The field has
metamorphosed; major changes have occurred from
applications of advances in other fields. The development
of immunological, receptor-binding and phosphorylation
assays consolidated the principles of endocrinology, providing
the means of identifying and quantifying hormone
status and action. The tenets of hormone deficiency, excess
and resistance belong to this era. Endocrinology continues
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
strong (Wilson 2005).
This period also began with the discovery of the genetic
code, heralding the dawn of molecular biology and
culminating in the sequencing of the human genome 50
years later. The molecular revolution has led to the discovery
of new receptors, signalling molecules and chemical
messengers acting within complex networks. The new
insights gained from studying the molecular basis of hormone
action and interactions have already changed, and will
continue to change, concepts of disease causation and
treatment. The last few decades have also seen an evolution
in information technology, knowledge engineering and
bioinformatics, advances that have catalysed the development
of high-throughput technology, expanding the databases of
catalogued knowledge for biomedical research. These
advances will have an unstoppable impact across all fields of
medicine.
How will these advances impact on clinical endocrinology
in the next 60 years? In this review, I will
confine my crystal ball gazing to the pituitary and metabolic
areas. The practice of endocrinology will be influenced by
secular health trends, demographics and consumer expectations.
I will foreshadow major health issues confronting
the clinical endocrinologist, new treatments and changes in
the landscape of endocrine practice.
The next 60 years
Secular trends
The world is getting older. Life expectancy at 65 years
increased from 12 years by more than 50% over the 20th
century and this trend is continuing. According to the World
Health Organization, the numbers over 60 years of age will
increase from 600 million in 2000 to 1.2 billion in 2025 and 2
billion in 2050 with the greater increase occurring in the
developing world (WHO 2006). In the US, the population
older than 65 years increased from 12 million in 1950 to 26
million in 2004 and there will be a further 50% increase by
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
www.endocrinology-journals.org3
The world is also getting fatter. At present, obesity ranks
fourth as a major cause of morbidity and mortality by deathand-disability
adjusted life years (Powles & Day 2002). Many
leading journals have pointed out the pandemic in obesity,
which is fuelling the alarming increase in the prevalence of
metabolic syndrome and diabetes, both in the developed and
developing world (McLellan 2002, Hedley et al. 2004,
Yanovski 2005). The East is also catching up. A recent survey
in China indicates that approximately 30% of the population
are overweight and that 9$8% of men and 17$8% of women
have metabolic syndrome (Gu et al. 2005), a problem that may
well get worse.
These demographic trends have clear implications for the
endocrinologist. First, there is a predictable escalation in the
societal burden of diabetes and associated micro- and
cardiovascular diseases and the associated challenge of
controlling these. Secondly, the endocrinological management
of ageing will be an even bigger area. There will be strong
demands in the traditional areas of hormone replacement and
osteoporosis, albeit with newer drug formulations and
approaches. However, endocrine care of the aged will be
increasingly blurred by endocrine treatment for ageing.
Consumer trends
The rejuvenists are of course going back to the future, driven
by consumer demand for eternal vigour and youth. There will
be increasing exploitation of the psychology of dissatisfaction
and the promise of hormones to fix the woes of an unhealthy
lifestyle or an unfulfilled life (Lamberts et al. 2003). The present
day net-wise consumers are expert patients (Tattersall 2002);
their wireless descendants will be more expert. They know that
hormones control growth, metabolism, fat, muscle, weight,
mood and sexual function; when these are not right, they
expect endocrinology to provide the solutions. A quick surf of
the World Wide Web reveals over 2 million sites for growth
hormone (GH) and over 1.2 million sites for dehydroepiandrosterone
use for anti-ageing therapy. These are only a fraction
of the field of ‘cosmetic endocrinology’, which promises to
offer much more.
Therapy of endocrine disease
What about mainstream endocrinology? Following the
sequencing of the human genome, the complex path from
genotype to phenotype will have been largely paved
(Strohman 2002). The new era will bring novel solutions to
the present problems from drug-delivery technologies,
combinatorial chemistry, pharmacogenomics, gene
regulation and manipulation.
Pharmacotherapy will continue to be the backbone of
endocrine treatment. Time-regulated formulations of steroid
hormones will have replaced the clumsy regimens of the past
(Romijn et al. 2003), allowing the endocrinologist to practise
truly physiological hormone replacement therapy (HRT).
Twenty-four-hour formulations of hydrocortisone for
normal and stress situations will be available. Thirty-day
formulations of female hormones for HRT and higher dose
preparations for contraception will be the preferred alternatives
to the oral preparations of the 20th century.
Pharmacogenomics will come of age and will have a major
impact across all endocrine-based therapies. Genetic variations
that affect the responses to hormones and drugs and their
disposition within the complex endocrine network of the body
will be characterised (Wilke et al. 2005). At the patient level,
this will bring rationalisation and individualisation of therapy,
achieving optimal response with minimal side effects. Women
can be identified for safe treatment with oestrogens, the
hypoadrenal patient prescribed accurate dosage of steroid with
confidence and the susceptible diabetic patient identified for
preventative treatment against renal disease.
Combinatorial chemistry will bring treatment selectivity,
versatility and convenience. It will exploit knowledge gained
from understanding how closely related hormones act on
similar classes of receptors to exert a range of effects.
Somatostatin receptor subtypes have already been shown to
exert differential effects on secretion and cell proliferation in
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
regulating appetite, energy homeostasis, behaviour and
reproduction (Lin et al. 2004). Synthetic compounds selective
for particular receptor subtypes will be available to target
treatment of selected tissues for different effects. Small nonpeptide
oral mimetics will begin to replace insulin, GH,
gonadotrophins and parathyroid hormone and revolutionise
the treatment of many endocrine diseases.
This era will also see the maturation of paracrinology, the
science of fine-tuning hormone requirements at the tissue
level brought about by drugs regulating prohormone
conversion to, or inactivation of, active hormone. Tissue
specific regulators of deiodinase, aromatase, 11ß-hydroxysteroid
dehydrogenase (HSD) and 5a-reductase activities will
emerge. Cardiac function in the severe hypothyroid patient
with coronary artery disease will be protected by cardiacspecific
30
-deiodinase inhibitors during thyroid hormone
replacement. Tissue-specific 11ß-HSD inhibitors will be
available to protect against the catabolic, adipogenic and
diabetogenic effects of chronic hydrocortisone and prednisolone
treatment.
In the battle against obesity, several classes of centrally
acting drugs controlling hypothalamic function will have
been developed. The major appetite-regulating pathways and
those regulating basal energy expenditure will have been
elucidated, with ligands and receptors identified. Chimeric
compounds harbouring multiple properties are under active
development.
The global health system and the endocrine patient
The next 60 years will bring about a ‘googlelisation’ of
health with establishment of a Global HealthNet, evolved
4 K K Y HO $ Endocrinology: the next 60 years
Journal of Endocrinology (2006) 190, 3–6
www.endocrinology-journals.orgfrom the rudimentary beginnings of eHealth (Wyatt &
Sullivan 2005). The traditional boundaries of personal
health information available only to the practitioner or
local institution will have long disappeared. A global
Cybernet repository of medical knowledge from drug and
patient trials will be available. There will be parallel
platform systems, public and private, holding vast
information on millions of people with enabling bioinformatics
technology to guide treatment based on the
patient’s health profile. Patients will be empowered and
carry health information on a chip. Access to these global
health information systems will be variable depending on
public or private health subscription. Personalised genome
screening will be realised but at a cost. Genome-system
screening will have been established to provide a profile
of risks for various body systems. Combined with
proteomics, these technologies will define a whole range
of risk and outcomes from which therapeutic decisions
will be made.
What does this mean for the patient with endocrine
disease? There will be individualisation of hormone
replacement needs, tailored approaches to the therapy of
functional endocrine tumours and endocrine cancers. The
appropriate dose of glucocorticoid will no longer be a
guestimate, HRT will be safely prescribed based on
personalised genomics.
In the area of endocrine-disease prevention, it is
envisaged that more effective management will emerge
from an approach combining risk identification, lifestyle
and therapeutic intervention. In the area of obesity, the
energy homeostatic regulating pathways will have been
elucidated, with ligands and receptors identified. A
polypharmacy approach will combine the use of antiorexigenic
(e.g. leptin analogues, neuropeptide Y antagonists)
(Lin et al. 2004) and anorectic (e.g. melanocortin
receptor agonists and cannabinoid receptor antagonists)
agents (Ellacott & Cone 2004, Despres et al. 2005) with
new classes of olfactory receptor modulators, which remove
pleasant taste from food. There will have been successful
development of safe agents that enhance basal energy
expenditure by activating brown fat development and
activity. Their introduction into the clinic will result in a
downturn in the prevalence of obesity and diabetes midway
through the 21st century, at least in the Western world.
Cosmetic endocrinology will flourish under the guise of
improving health. Unscrupulous health clinics will provide
gene profiling and gene modification therapies for longevity
and improved satisfaction with life. They will offer a slippery
cocktail of myth and fact, as has been occurring through the
history of medicine. There will be therapies to slow down the
genetic clock or to correct gene profiles destined for short
stature, flabbiness, hirsuitism, baldness or hyposexuality. The
realm of re-tuning one’s glands in search of an elusive health
will be a zillion dollar industry.
Summary
There are exciting times ahead in endocrinology, as are
occurring across all fields of medicine, with an increasing
blurring between disease and ‘non-disease’ (Smith 2002).
There are genuine challenges ahead to win the battle against
obesity and diabetes, and to manage the consequences of
frailty in a progressively aged society. To protect the charter of
endocrinology, we must not confuse our goal to improve the
treatment of genuine endocrinopathy with the medicalisation
of the problems of life and lifestyle. The practice of evidencebased
medicine must be followed regardless of the degree of
technological advancement. The future generation should
be reminded that HRT did not improve health-related quality
of life, contrary to the predictions several decades earlier
(Hays et al. 2003).
Acknowledgements
The author expresses sincere thanks to Drs Kin Leung, Anne
Nelson and Professor Donald Chisholm for helpful suggestions
during the preparation of this paper. The author declares
that there is no conflict of interest that would prejudice the
impartiality of this scientific work.
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Received 27 March 2006
Received in final form 1 April 2006
Accepted 7 April 2006
Made available online as an Accepted Preprint
