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

Abstract

Background and purpose: 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.Methods: 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.Results: 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.Conclusions: 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.

Assessment of the Relationship Between Genetic Determinants of Migraine and Thyroid Dysfunction - Review

“…The other three SNPs showed nominal significance for TSH and fT4 but did not reach the significance threshold [44,45,46]. The lack of replication of CGAS results in GWAS is likely due to the small number of samples (low statistical power) in CGAS, which can lead to false positive results [1,43]. It may also be due to the specificity of the studies for a particular population.…”

“…In the last decade, studies have been conducted on the relationship between migraine and thyroid features, using observational and cross-sectional methods. Recent genome-wide association studies (GWAS) aimed to identify genetic factors associated with these traits, revealing increased co-occurrence of migraine and thyroid traits, as well as identifying SNPs (single nucleotide polymorphism) and genes associated with this phenomenon [1].…”

Approach to the Patient With Headache

“…Certain conditions are associated with primary or secondary headaches, including thyroid disease, systemic lupus erythematosus, polycystic ovarian syndrome, and joint hypermobility disorders. [58][59][60][61] SOCIAL HISTORY. A standard social history reveals information about smoking, alcohol consumption, drug use, employment type and status, physical activity, and the home environment.…”

“…Examples include triptans in patients with coronary artery disease, tricyclic antidepressants in patients who are prone to constipation, and topiramate in patients with a history of calcium phosphate kidney stones. Certain conditions are associated with primary or secondary headaches, including thyroid disease, systemic lupus erythematosus, polycystic ovarian syndrome, and joint hypermobility disorders 58-61 …”

Influence of metabolic state and body composition on the action of pharmacological treatment of migraine

“…Thyroid dysfunction may be due to varying levels of thyroid hormones, such as thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) [ 160 ]. Thyroid dysfunction is known to be one of the major endocrine disorders, with a prevalence 3%-21% worldwide [ 161 ]. Thyroid hormone plays a prominent role in metabolism and brain development in humans [ 162 ].…”