Update on the Diagnosis & Management of Homeostasis-Related Headaches

brain vasculature
brain vasculature
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.

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, 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.

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

With this knowledge, it may be possible to minimize or prevent migraine attacks by better managing a state of hypoxia. Habitual morning headaches may be suggestive of sleep apnea and thus may prompt clinicians to screen for sleep apnea. Morning headaches, however, are associated with other sleep disorders including cervicogenic headache and analgesic-overdose headache.13,14

Headache is common among individuals undergoing hemodialysis. The variables that have been associated as triggers include osmotic encephalopathy, which is thought to be linked to dialysis disequilibrium syndrome; caffeine withdrawal; and electrolyte abnormalities.15,16 These variable can be associated with poor outcomes if not clinically managed. Consequently, dialysis headache may be used as a warning to closely monitor and better treat risk factors associated with hemodialysis, potentially leading to improved outcomes.

The prevalence of headache attributed to hypothyroidism has been shown to be comparable among patients with either subclinical or overt hypothyroidism and with comparable improvement in headache when treated with levothyroxine.17 An association between pain sensitivity, thyroid status, and alteration in serotonin level and regulation have been speculated as underlying pathologic mechanisms.18-20 

The latter was demonstrated in rats in which diminished serotonin levels were observed after thyroidectomy.20 Clearly, further research is needed to elucidate the precise role of serotonin in hypothyroidism. These observations and studies suggest, however, that headache may act as a clinical marker to screen for individuals with subclinical hypothyroidism.

The significance of the association of headache with fasting may be a warning for hypoglycemia, caffeine withdrawal or dehydration, since under these circumstances, the headache is resolved with consumption of glucose, caffeine, or water.21 In fact, severe hypoglycemia and dehydration can be fatal, particularly in the elderly or among individuals for whom fasting is integral to religious practices. Under these circumstances, headache can be a warning sign to break a fast to avert poor outcomes.

While evidence is emerging linking headache with disorders of homeostasis, this is complicated by observations and studies that show persistence of headache despite re-establishment of homeostasis. The obvious question that arises is whether an imbalance of homeostasis is one of several causes of the presenting headache. A study reported that despite treatment of hypothyroidism, 21% of patients continued to experience headache 12 months after treatment.17 Confounding conditions such as underlying chronic migraine, sleep apnea, or other conditions that may predispose to headaches may also be present. Clearly, robust research is needed before cause and effect can be concluded with certainty.

Summary and Clinical Applicability

While headaches associated with homeostasis are recognized as a diverse diagnostic category, research that might inform treatment of homeostasis-related headaches is emerging. An improved understanding of the link between headache and homeostasis might allow earlier diagnosis and better management or treatment of conditions that trigger imbalance in homeostasis, thereby circumventing the morbidity and mortality that can result from diagnostic and treatment delays.


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This article originally appeared on Clinical Pain Advisor