Migraine and thyroid dysfunction: Co‐occurrence, shared genes and biological mechanisms

Migraine and thyroid dysfunction, particularly hypothyroidism, are common medical conditions and are known to have high heritability. Thyroid function measures, thyroid stimulating hormone (TSH) and free thyroxine (fT4), are also known to be genetically influenced. Although observational epidemiological studies report an increased co-occurrence of migraine and thyroid dysfunction, a clear and combined interpretation of the findings is currently lacking. A narrative review is provided of the epidemiological and genetic association evidence linking migraine, hypothyroidism, hyperthyroidism and thyroid hormones TSH and fT4.An extensive literature search was conducted in the PubMed database for epidemiological, candidate gene and genome-wide association studies using the terms migraine, headache, thyroid hormones, TSH, fT4, thyroid function, hypothyroidism and hyperthyroidism.Epidemiological studies suggest a bidirectional relationship between migraine and thyroid dysfunction. However, the nature of the relationship remains unclear, with some studies suggesting migraine increases the risk for thyroid dysfunction whilst other studies suggest the reverse. Early candidate gene studies have provided nominal evidence for MTHFR and APOE, whilst more recently genome-wide association studies have provided robust evidence for THADA and ITPK1 being associated with both migraine and thyroid dysfunction.These genetic associations improve our understanding of the genetic relationship between migraine and thyroid dysfunction, provide an opportunity to develop biomarkers to identify migraine patients most likely to benefit from thyroid hormone therapy, and indicate that further cross-trait genetic studies have excellent potential to provide biological insight into their relationship and inform clinical interventions.