Migraines Suggest Possibility of Endocrine and Metabolic Disorders

Considering the increased likelihood that patients with migraine may also have hypothyroidism, diabetes, metabolic syndrome, and obesity, elevates the prospect of better overall medical management and improved quality of life.

With Gloria Simms, MD, and B. Lee Peterlin, DO

Migraine, a chronic neurovascular disease marked by recurrent, debilitating head pain, is a leading cause of disability, loss of productivity, and extensive utilization of healthcare resources.1

Reporting in Current Pain and Headache Reports,1 the researchers ask: Is Migraine Primarily a Metaboloendocrine Disorder?

Migraine occurs in patients with hypothyroidism, insulin sensitivity, and type 1 diabetes.

Unraveling the potential relationship of migraine with numerous comorbidities may pave the way to better overall patient management and even better headache reduction and relief,1 said Italian researchers who reviewed the literature on coexisting metabolic and endocrine disorders and migraine headaches.

Migraine Could Lead to Endocrine-Related Conditions

In reviewing the meta-analysis, Gloria Simms, MD, a neurologist and headache specialist at Valley Baptist Medical Center and an attending physician at the University of Texas at Rio Grande Valley, reviewed the data and is not yet convinced about the connection between neuroendocrine disorders and headaches.

"However, I do believe it is important to keep in mind how important it will be to address metabolic disease as a means to reduce the burden of disability migraines cause patients," she told EndocrineWeb.

Researchers from the University of Torinoin Italy, combed the literature for published studies about migraine's potential association with different metabolic and endocrine disorders.1

"All the clinical studies that used the oral glucose tolerance test to examine insulin sensitivity found that, after glucose load, migraine patients experience a significant increase of both plasmatic insulin and glucose concentrations in comparison with controls," according to the authors. 

Once type 2 diabetes (T2D) develops, however, no association between glucose levels and migraine was found. Interestingly, type 1 diabetes (T1D) seems to have protective effects on migraine.1

Both obesity and hypertension appear likely risk factors for episodic and chronic migraine, and metabolic syndrome is linked to migraine with aura and raises the risk for medication overuse headache. A two-way association was found between migraine and hypothyroidism.1

Looking for Comorbid Neuroendocrine Disorders

Under the label of metaboloendocrine disorders, the authors focused on trials that targeted neuroendocrine conditions such as diabetes, body weight, thyroid disease, blood pressure, and metabolic syndrome.1

A closer look at the findings teased out by individual condition:

Insulin resistance: Insulin resistance has been strongly associated with both episodic and chronic migraine.2-4

One study found that hyperinsulinemia, in the highest quartile is associated with a 5.7-fold higher risk of migraine, compared with those with levels in the lowest quartile.5

While not all the studies concurred,1 when looked at collectively the authors found that the onset of migraine is characterized by alterations in the insulin response.

The authors said, the interrelationship makes sense since insulin receptors are distributed abundantly throughout the brain.

Another study found that giving alphalipoic acid (400 mg twice daily for six months) to migraine sufferers who were insulin resistant achieved a reduction in headache episodes and treatment days.6

Diabetes:  While insulin resistance increased the risk of migraine, having T2D did not maintain the same rigor in effect.7-9  However, type 1 diabetes has been linked with fewer migraine events.10  The experts readily acknowledge no rationale for these inconsistent findings.1

Body Weight: An association between obesity and migraine has been confirmed in many studies, including a recent meta-analysis of 12 trials found that the risk of migraine increased by 27% in people with obesity as compared to similar patients without obesity (OR 1.27; 95% CI. 1.16-1.37, P < 0.001). 11

Results of a population-based trial indicated that migraine headache frequency, severity, and clinical features increased incrementally with rise in body weight.12

Equally compelling, people who fell below the healthy weight range for body mass index had a 13% increased risk for migraine when compared to subjects in the healthy weight range (OR 1.13, 95% CI 1.02, 1.24, P < 0/001).11

Can weight loss help? Rena R. Wing, PhD, professor of psychiatry and human behavior at the Alpert Medical School at Brown University and director of the Weight Control & Diabetes Research Center at Miriam Hospital in Providence, Rhode Island, and her team reported that behavior weight loss intervention was effective but so was migraine education in women of reproductive age who were followed for 16 weeks.13 Also, migraine headaches were reduced more so in individuals who underwent bariatric surgery as compared to monthly behavioral weight loss intervention.13

Hypertension: Any association between elevated blood pressure and increased incidence of migraine headaches remains unclear,1 according to Rainero et al. However, the investigators speculate that if confirmed, possible mechanisms to be considered include environmental factors, shared biological factors, or a common genetic vulnerability.

Metabolic Syndrome (MetS). A positive association was demonstrated in individuals with MetS and migraine with aura who had a higher risk of headaches (OR 3.45, 95% CI, 1.63-7.29) as when compared to individuals without metabolic disease.14

Another study reported a greater rate of chronic migraines in women who also had metabolic syndrome (OR 5.342, P = 0.032), but in those patients with comorbid disease who were found to suffer from migraine medication overuse headaches, the risk was even higher (OR=12.68, P = 0.007).15  The authors suggest that excessive analgesia use appears to related to greater likelihood of these patients developing MetS.

Thyroid Disease:  Research evaluating an association between hypothyroidism and migraine date back to 1998 but researchers have a renewed interest in delving deeper into this possible relationship.15,16 For example, findings from more recent studies suggest a bidirectional association.

In one study, migraine patients had a 41% increased risk of developing hypothyroidism,16 and in a study of patients with existing hypothyroidism, investigators found that 60% of these individuals met the criteria for a migraine disorder.17

Role of Migraine and Neurometabolic Link: Jury Remains Out  

While numerous studies show the link between migraine and various metabolic and endocrine disorders, any causation and an understanding of the possible mechanisms of action to explain an interrelationship between migraine headaches and endocrine and metabolic conditions require further elucidation,1 the researchers concluded.

Yet, the research is strongly suggestive that insulin may modulate several brain functions such as metabolism and motivational behaviors.1

Meanwhile, based on the cumulative results of this meta-analysis, the authors suggest that clinicians may want to discuss the possibility that patients consider increasing their physical activity, achieving at least modest weight loss as appropriate, and managing cardiovascular risk factors so as to prevent and improve migraine management.1

The number of associations with migraine and comorbidities does not surprise Dr. Simms. "Migraine is multifactorial," Dr. Simms told EndocrineWeb. "We don't fully understand it," so the thoroughness of the review definitely adds further confirmation pertaining to insulin resistance as a relevant factor related to sensitivity to migraines.1

"This study summarizes the evidence in support of keeping the whole metabolic approach [in mind] when dealing with patients who have any of these endocrine-related conditions as some of these factors will impact the outcomes of patients with migraine."

Check Patients with Migraines for Insulin Resistance

These findings offer a heads up for healthcare practitioners ''to be more aggressive in diagnosing and treating insulin resistance," said Dr. Simms, "not only as a 'prediabetes condition' but as a pathology that is already impacting the quality of life of our patients."

Perhaps the review will begin to lessen the stigma of migraine, which Dr. Simms said, remains a lingering issue. Because of this, patients avoid seeking treatment for recurring headaches, even migraines, chocking these episodes up to a “live with it” kind of problem.

"Having migraine is not normal, many factors, as this review and other studies suggest, including genetic components. "While we may not be able to cure patients’ migraines, we can certainly make their lives much better."  

Appreciating the metabolic-endocrine interrelationships of these conditions and migraines makes good sense, said B. Lee Peterlin, DO, director of the Headache Clinic at Penn Medicine Lancaster General Health. Impaired insulin sensitivity has long been linked with migraine, she told EndocrineWeb, ''and we know a big trigger for migraine is fasting."

Overall, Dr. Peterlin said, the findings from this review of the literature suggests that those with a migraine condition ''do not do well with big changes in how their bodies function." This may include swings in blood sugar, for instance, and fluctuations in body weight

In short, Dr. Peterlin said, migraine ''is not an isolated disorder. There is impact from the other endocrine and metabolic disease mechanisms." As such, the value of this reviewis that the evidence has been pulled together concisely, including the areas cited as in need of more information.

Neither Dr. Simms nor Dr. Peterlin have any relevant financial disclosures.

Continue Reading:
Emerging Treatments in Pituitary, Adrenal, and Neuroendocrine Disorders
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