This communication describes the concept of endocrine fluidity, defining it as the phenomenon of changing endocrine and metabolic function, in health and/or in disease, over time. Awareness of physiological endocrine fluidity helps avoid overdiagnosis and unnecessary investigations. Knowledge of endocrine fluidity in pathological conditions allows the astute physician to keep a high index of clinical suspicion for relevant diseases. The concept of endocrine fluidity can be used to anticipate, and address changes in the clinical course of a disease, and to allow for possible deviations from the expected natural trajectory.

The word fluidity is a noun, which describes the physical property of a substance that enables it to flow. Fluidity has been used to describe not only physical substances like liquids, but also intelligence, cognition, movements and business transactions.¹ In medicine, fluidity is used in the context of anatomy (membrane fluidity) as well as physiology (gender fluidity). We use this word to create a construct, endocrine fluidity, which encompasses both physiological and pathological aspects of hormonal action.

Physiological Fluidity

Circadian rhythms, or physical, mental, behavioral and hormonal changes that follow a 24-hour cycle, are well known to science. Most circadian rhythms are controlled from the suprachiasmatic nucleus of the hypothalamus, which operates various feedback mechanisms. The Nobel Prize 2017 was awarded to Hall, Rosbash and Young for isolating the gene which controls the biological clock.²

Other rhythms have also been described, including ultradian (less than 24-hour cycle), circasemidian (12-hour cycle) and infradian (longer than 24-hour cycle).³ These can be considered a form of endocrine fluidity. Table 1 lists some physiological examples of endocrine fluidity. The changes in the hypothalamic-pituitary-gonadal axis that govern the monthly rhythm of ovarian physiology in menstruating women may also be viewed as a form of endocrine fluidity.

Another example of fluidity is gender fluidity.⁴ Though not related directly to hormonal levels, gender fluidity or change in perceived gender, can be considered a physiological form of life.

Pathological Fluidity

Endocrine fluidity can be noticed in endocrine pathology as well. Cyclic Cushing’s syndrome, pulsatile prolactin secretion from pituitary adenomas and cyclic pheo­chromocytoma are examples of this. Hashitoxicosis represents another form of endocrine fluidity, albeit over a longer time frame.

Type 1.5 diabetes, both LADA (late-onset autoimmune diabetes of adult) and Flatbush diabetes (ketosis prone type 2 diabetes) represent forms of metabolic fluidity. Changes in insulin requirement in persons with diabetes, which are so familiar to endocrinologists are the clinical presentations of this fluidity. Another manifestation is the change in diagnostic label that is not so uncommon in endocrine clinics. Diabetes, metabolic bone disease and gonadal disease often change their presentation, and this fluidity reflects as a change in diagnosis.

Physician-Centered Fluidity

Yet another form of endocrine fluidity is created by endocrinologists themselves. Therapeutic targets, therapeutic strategies and pharmacological tools change with advances in research.5 This leads to frequent changes in the information and advice that physicians share with their patients. From a patient perspective, this can be construed as a form of medical fluidity, and specifically as endocrine fluidity. While part of this fluidity can be explained by advances in science, some are due to changes phases of life. The targets for glucose, blood pressure, lipid and thyroid health, for example, vary according to age group, natal status and comorbidities.

Summary

Endocrine fluidity is an easily observed phenomenon, both in physiology and disease. Awareness about the condition will help physicians offer counseling and reassurance to those with physiological variants of fluidity, and prescribe appropriate diagnostic and therapeutic interventions for those who need them.

 Authors: Dr Sanjay Kalra, Dept. of Endocrinology, Bharti Hospital, Karnal, Haryana, India;

Dr Nitin Kapoor, Dept. of Endocrinology, Diabetes and Metabolism, CMS, Vellore, Tamil Nadu, India

Dr Atul Dhingra, Dept. of Endocrinology, Gangaram Bansal Hospital, Sri Ganganagar, Rajasthan, India

References

1. Fluidity. Available at:  https://www.merriam-webster.com/dictionary/fluidity. Last accessed November 29, 2022.
2. The Nobel Prize in Physiology or Medicine 2017. Available at: https://www.nobelprize.org/prizes/medicine/2017/summary/. Last accessed November 29, 2022.
3. Ruan W, Yuan X, Eltzschig HK. Circadian rhythm as a therapeutic target. Nat Rev Drug Discov. 2021;20(4):287-307.
4. Catalpa JM, McGuire JK, Fish JN, Nic Rider G, Bradford N, Berg D. Predictive validity of the Genderqueer Identity Scale (GQI): differences between genderqueer, transgender and cisgender sexual minority individuals. Int J Transgend. 2019;20(2-3):305-14.
5. Kalra S, Baruah MP, Sahay R, Kishor K. Pentads and hexads in diabetes care: numbers as targets; numbers as tools. Indian J Endocrinol Metab. 2017;21(6):794-6.