Chasing Hormones You Never Knew You Had

Not many of us know what hormones do, where they come from and why we need them. Even fewer could name the recognised glands that secrete hormones.

“A Physician’s Journey” describes a remarkable story of how collaborations between clinicians and scientists put the science of clinical endocrinology on the map in Christchurch – leading to the discovery many tissues outside those recognised as hormone secreting glands also secrete hormones vital to our health.

Hormones are chemicals (mostly small proteins, also called peptides) or steroids secreted into the blood stream by specialised tissues such as the pituitary gland, adrenal, thyroid, gonads (ovary or testis), pancreatic islets (secreting insulin) and parathyroid glands (regulating calcium balance).

All except the latter two are regulated by a discrete area of brain tissues (the hypothalamus) just above the pituitary gland which is situated in a small cavity within the skull, at the base of the brain.

A distinguishing feature of a hormone has been the ability of the secreted product (the hormone) to activate the function of other tissues at a distant site – which means each hormone should, in theory, be detectable and measurable if blood samples are analysed appropriately.

For example, by secreting a protein known as ACTH (adrenocorticotrophin) the pituitary controls and regulates the output of steroid hormones made by the adrenal gland (located just above each kidney). These secreted steroid hormones serve to control such diverse functions as blood pressure, salt balance, glucose and fat metabolism, immune and brain function.

An excess or deficiency of adrenal hormones may profoundly impact health and be lethal in their absence.

The science underpinning this complex system of communicating is encapsulated by “endocrinology” – the purview of the clinical endocrinologist – a specialist specialising in the management of subjects with disorders of hormone function.

This physician’s journey begins in 1960 when the author (Eric Espiner) as a recently qualified doctor was deputed to work as a medical registrar at the recently commissioned Princess Margaret Hospital at the foot of the Cashmere hills in Christchurch.

This post would be supervised by Donald Beaven (later knighted for his work in diabetes), who was heading a new Medical Unit funded by the University of Otago to train final-year students and initiate research. Don Beaven set about recruiting scientists to aid clinicians in detecting abnormal hormone function — but doing so required reliable hormone measurement. At that time, there were no such methods.

Their diagnosis would be based on the patient’s history and perhaps appearance but never proven objectively.

Don Beaven’s passion for finding the factors responsible for the putative endocrine disorder — using scientific methods of hormone measurement — was to be the catalyst of an explosive increase in knowledge that placed the discipline of endocrinology firmly on the map in Christchurch. From such small beginnings an amazing flowering of the science pertaining to stress or organ failure ensued in the next decade.

The key ingredients of this success were Don Beaven’s passion for clinical research, the recruitment of curious like-minded clinicians working with committed scientists across disciplines, and the coincidental breakthrough in methods that used immunoassay techniques. For the first time, these methods enabled accurate and precise measurement of very small concentrations of the relevant hormone.

As a result, as described in the Memoir, the Unit soon became the hub of a National Hormone Assay Service. Discovery of how stress hormones were regulated – for example by examining the changes in pituitary ACTH and adrenal hormones during surgical operations, or discovery of the role of hormones secreted by the kidney and adrenal combining together to affect a failing heart’s performance – were critical to improving patient care.

Later, to find and show that in humans the heart itself is an endocrine gland – secreting a unique class of hormones into the blood stream with every heart beat – was an outstanding achievement made possible by bringing science into clinical practice. The Christchurch group were well positioned to take these findings from experimental animals and show the concentration of heart hormones in the blood stream could distinguish the cause of severe breathlessness at rest in patients admitted to the emergency room. Values were much higher if heart failure was the cause when compared to values in other patients where the disorder was caused by lung diseases such as emphysema or pneumonia. Some 30 years later, this test is still the recommended initial approach world-wide to diagnosis in patients presenting with symptoms consistent with heart failure. The findings have changed the approach to prediction of heart disease, diagnosis and monitoring of cardiovascular health, and have been further successfully pursued by the Christchurch Heart Institute, now funded privately to expand related research internationally.

The discovery of heart hormones expanded the landscape whereby endocrinology hitherto was seen as a discipline focusing on disorders of the discrete endocrine glands but there was much more to come. Once again it was the Christchurch group leading the charge. One of the three heart hormones discovered was also identified as a leading player in promoting growth of the skeleton. By some clever detective work, the Christchurch team of scientists identified an “inactive” portion of this tissue-based hormone that could be measured in the blood stream – in contrast to the “active” form that functioned to increase bone growth in tissues but was not detected in the blood stream. They then showed in both growing lambs, and in neonates and children, the concentration of this form of the heart hormone closely paralleled the rate of long bone growth – levels in the blood were much higher in rapidly growing subjects than in later months or years when the growth rate had slowed. These findings have been used successfully to aide diagnosis in several disorders of bone growth including genetic mutations causing congenital disorders affecting bone quality and orderly growth. Other revelations followed rapidly; evidence the heart hormone participates in maintaining fetal maternal health; the same hormone has neuroprotective actions in the brain tissues including those with Parkinson’s disease and participates in learning and memory give some idea of the wide- ranging impact of these new hormones – not so surprising in light of their ancestral lineage dating back more than 200 million years

This narrative is much more than a factual account of new hormones and what they do. The ups and downs due to chance, good luck and fluctuating support from big pharma pepper the narrative, closing off some ventures and opening others. Fighting the liquorice wars and assisting the crown’s prosecution of a poisonous professor were fascinating diversions. Shining through is the sustained commitment of clinicians working in collaboration with scientists across disciplines, linking validated hormone measurements with specific disorders of organ function —a recipe for improved health outcomes.

A Physician’s Journey: Chasing Hormones You Never Knew You Had and Why You Need Them by Eric Espiner, Quentin Wilson Publishing, RRP $45.00