Headache Linked to Hypothyroidism

Pauline Anderson

October 07, 2016

Patients with a headache disorder have a 21% increased risk of developing hypothyroidism, and the risk is even higher — 41% — in those with possible migraine, a new study has found.

"Just like female sex and age are risk factors for hypothyroidism, one should also now consider headache disorder as a risk," said study author Vincent T. Martin, MD, professor, medicine, and co-director, Headache and Facial Pain Program, Gardner Neuroscience, University of Cincinnati, Ohio.

Doctors might think about periodically screening patients with a headache disorder for the development of hypothyroidism and, if they uncover it, they should treat it, said Dr Martin.

Coauthors Dr Andrew T. Martin (left) and Dr Vincent T. Martin (right)

The study was published online September 27 in Headache.

Large Study

The analysis included 8412 adult participants in the Fernald Medical Monitoring Program (FMMP), a medical surveillance program. To be eligible for the FMMP, participants must have lived or worked within 5 miles of the Fernald uranium processing plant near Cincinnati, Ohio, for at least 2 years from 1952 to 1984.

Participants had physical examinations every 2 to 3 years. They also completed written questionnaires every year documenting new illnesses and current medications and submitted these by mail.

The mean duration of participants in the FMMP was 12.6 years.

To assess headaches, researchers asked participants about the presence or absence of "frequent headaches" during the initial examination for the FMMP. A headache disorder was determined through a physician diagnosis of headache, self-report of frequent headaches, or use of headache-specific abortive medications.

They defined "possible migraine" as use of headache-specific medications or a diagnosis of migraine headaches by a treating physician.

Investigators tested thyroid function during all examinations, but the type of test varied depending on the time period. From 1988 to 1994, thyroxine and triiodothyronine resin uptake tests were done, and from 1994 to 2008, thyroid-stimulating hormone tests were used.

Researchers adjusted for age, sex, medications, smoking, body mass index, and hypothyroid-inducing medications, such as lithium and interferon.

Two Models

One model included headache disorders (yes/no), and a second model included possible migraine (yes/no).

In the first model, new-onset hypothyroidism developed in 8.2% of patients with headache disorders and in 6.2% of patients without these disorders. After adjustment for covariates, the hazard ratio (HR) for developing hypothyroidism was 1.210 (95% confidence interval [CI], 1.001 - 1.462) in patients with headache disorders.

In the second model, incident hypothyroidism developed in 10.8% of participants with possible migraine compared with 6.2% of those without migraine. The HR for incident hypothyroidism in those with possible migraine compared with those without was 1.411 (95% CI, 1.009 - 1.973).

In both models, age was a significant predictor of new-onset hypothyroidism, with a progressive increase in the HRs from the youngest to the oldest participants. Other covariates that were significant for an increase in hypothyroidism in both models included female sex and hypothyroid-inducing medications.

The investigators found that smoking was very protective against the development of hypothyroidism in all patients with headache, which, according to Dr Martin, is not a new finding.

"What's interesting is that smoking is preventative for hypothyroidism, but provocative for hyperthyroidism."

Uranium exposure was not significant in any of the analyses. This makes sense because the kind of radiation in the uranium dust released by the plant "does not concentrate in the thyroid gland to any degree," said Dr Martin.

But exposure led to other health issues, including breast and kidney cancer, according to Dr Martin. In the late 1970s, the plant released amounts of uranium dust into the environment that far exceeded allowable levels, he said.

There are probably three main theories connecting headaches to hypothyroidism, said Dr Martin.

Potential Mechanism

One possible mechanism is that repeated attacks of headaches upregulate the immune system and make it more likely to attack the thyroid gland.

"We know that migraine is associated with different immune abnormalities, or sometimes an exaggerated immune response occurs during a migraine attack," said Dr Martin.

He noted that the most common form of hypothyroidism is Hashimoto's thyroiditis, an inflammation of the thyroid.

Another possibility is that headache disorders, migraine in particular, have alterations of the autonomic nervous system, which is important in converting thyroid hormone to its more active form, said Dr Martin.

Yet another theory — and this came from studies appearing after the current paper was written — is that use of anticonvulsant medications increases risk for hypothyroidism.

"It could be that the preventative therapies that we use for migraine — and we don't use for tension-type headaches — might be associated with development of hypothyroidism," said Dr Martin.

The researchers didn't examine whether the relationship between headaches and hypothyroidism could begin with decreased thyroid function, said Dr Martin. "We didn't examine the opposite relationship, so we can't exclude the possibility that it's a bidirectional relationship."

However, he noted some small case series of patients with hypothyroidism who developed a headache disorder, "and treating it with thyroid hormone actually decreased the frequency of headaches."

Past studies of the relationship between headache and hypothyroidism were cross-sectional. "We used a longitudinal design where we identified patients with headache disorder and followed them forward in time to see if they developed hypothyroidism," said Dr Martin. "So methodologically, this is much stronger evidence that the association exists."

Is there a relationship between headache and hyperthyroidism? According to Dr Martin, there are "maybe five case reports," so "we don't know for sure what the relationship is with hyperthyroidism."

One More Reason to Assess Thyroid

Commenting on the findings for Medscape Medical News, Werner Becker, MD, professor emeritus, Department of Clinical Neurosciences, University of Calgary, Alberta, said, "It's an interesting study" that "took advantage of an opportunity" to study the association between headache and hypothyroidism in a large group of people who for many years had thyroid function tests. 

Dr Becker thought it noteworthy that 10.8% of those with "possible migraine" developed hypothyroidism compared to 6.2% of those without migraine. 

"Given the size of the study, these results seem quite reliable, although more research will be needed to confirm these data," said Dr Becker.

He agreed that possible mechanisms underlying the association between migraine and hypothyroidism could include shared mechanisms related to inflammation and immune factors, but he said genetic mechanisms could also be at play.

Although the study results "must be regarded as only an estimate" because most cases of migraine weren't specifically diagnosed by a physician, they're consistent with most of the medical literature on this subject, said Dr Becker. 

As the increase in the incidence of hypothyroidism in patients with migraine is "relatively small," the study won't have a major effect on medical practice, he said.

"But they do constitute one more reason to assess thyroid function in patients with headache disorders."

Dr Martin revealed the following disclosures: Depomed: speaker, Neuroscion: consultant, Allergan: speaker, Teva: speaker, Lilly: research, consultant, Avenir: speaker. Dr Becker has disclosed no relevant financial relationships.

Headache. Published online September 27, 2016. Abstract

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