Thyroid hormones and energy metabolism in amyotrophic lateral sclerosis

Weight loss, partially caused by hypermetabolism, represents a well-documented and therapeutically relevant feature of the amyotrophic lateral sclerosis phenotype world-wide. In this study, we retrospectively analyzed the association between thyroid function and clinical, prognostic and metabolic parameters in a cohort of patients with amyotrophic lateral sclerosis in an experienced center in Germany (n = 1,754). Specifically, we examined the relationship between thyroid stimulating hormone levels, age, glucose and body mass index, and – in subgroups – phosphorylated neurofilament heavy chain levels in CSF. There was no association between thyroid stimulating hormone levels and body mass index in patients with amyotrophic lateral sclerosis (n = 954). In contrast with other cohorts, thyroid stimulating hormone levels decreased with age in patients with amyotrophic lateral sclerosis indicating hypothalamic deficiency in the aging patients. There was no association between thyroid stimulating hormone and phosphorylated neurofilament heavy chain (prognostic marker) in CSF of a subcohort (n = 646). Thyroid stimulating hormone levels correlated with glucose levels, an effect more pronounced in male patients. In conclusion, our results suggest that thyroid metabolism does not significantly contribute to amyotrophic lateral sclerosis-related weight loss or disease prognosis as estimated by phosphorylated neurofilament heavy chain; thyroid dysfunction is unlikely to be a primary driver of the metabolic dysregulation observed in amyotrophic lateral sclerosis. Most interestingly, thyroid stimulating hormone levels show an unexpected negative relation to age in patients with amyotrophic lateral sclerosis.