Headaches are one of the most prevalent disorders worldwide, typically affecting more women than men and when recurrent, can be disabling.1,2 While the presentation and underlying causes of headaches are diverse and poorly understood, the International Headache Society (IHS) broadly classifies headaches as either primary or secondary. Primary headaches include symptom-based headaches with examples including migraine, tension-type headache, trigeminal autonomic cephalalgias and cluster headache, whereas secondary headaches — or etiology-based headaches — are often related to a pre-existing condition, such as trauma or injury to the head and/or neck, cranial or cervical vascular disorder, substance use (eg, medication), infection, disrupted homeostasis, or psychiatric disorder.3

The recently updated, third edition (beta version) of the International Classification of Headache Disorders (ICHD-3 Beta) provides a comprehensive update of the different types of headache, the criteria that distinguish them, and key considerations for diagnosis.3 The goal here is to focus on secondary headaches with an underlying etiology related to disorders of homeostasis, particularly in light of recent studies that suggest that headaches associated with homeostasis may predict medical morbidity.

The current nomenclature of headaches attributed to disorder of homeostasis includes headaches that resolve or significantly improve following treatment or spontaneous re-establishment of homeostasis. According to the ICHD-3 Beta, headaches secondary to a disruption of homeostasis include those attributed to hypoxia and/or hypercapnia (ie, high altitude, diving, or sleep apnea), dialysis, arterial hypertension, hypothyroidism, fasting, cardiac cephalalgia, and other factors affecting homeostasis.

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Headaches caused by disorder of homeostasis have a significant female preponderance with an estimated lifetime prevalence of approximately 22% of the general population based on limited population-based studies.4,5

Although the underlying pathophysiology of homeostasis-related headaches is not yet clearly defined, the nervous and endocrine systems are thought to be involved through the maintenance of homeostasis. Therefore, dysfunction of the endocrine system may lead to various neurologic manifestations, including headaches.6 In fact, in individuals with prediabetes or established diabetes, one of the early signs of hyperglycemia or hypoglycemia is headache,7 and fewer headaches are associated with tightly controlled diabetes.8

It thus appears that early and effective treatment of endocrine or hormonal imbalance can relieve neurologic symptoms associated with headaches. This then raises the question: Can manifestation of headaches can be regarded as a warning sign for homeostatic imbalance or disorder, similar to acute or chronic pain serving as a warning for body injury? Can homeostasis-related headaches therefore confer a survival advantage? A recent review explored these questions.4

High altitude (or hypobaric hypoxia) headache affects approximately 80% of individuals who ascend to high altitude and is thought to be due to hypoxia-induced changes in cerebral blood flow.9-11 Hypoxia as a trigger for migraine attacks was demonstrated in a randomized, double-blind, sham-controlled study in which a state of hypoxia increased lactate in a specific region of the brain and cranial arteritis.12

This article originally appeared on Clinical Pain Advisor