Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis

Abstract

Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.

Keywords: Autoimmune thyroiditis; Autonomic neuropathy; Heart rate variability; Hypothyroidism; Quantitative sensory testing; Somatosensory function.

Figure 1

Frequencies of abnormal QST findings (A) and mean sensory profiles (B) in patients with treated AIT. (A) Each column gives the percentage of patients with abnormal findings for a particular quantitative sensory testing (QST) parameter (outside the 95% confidence interval [CI] of healthy controls). Positive values indicate positive sensory signs (hyperalgesia); negative values indicate negative sensory signs (hypoesthesia, hypoalgesia). Dashed lines show expected value for healthy controls (± 2.5%). ^#p < 0.05 compared to the expected value of a healthy population. (B) Sensory profiles of all AIT patients presented as mean z scores + 95% CI. Positive z scores indicate positive sensory signs (hyperalgesia); negative z values indicate negative sensory signs (hypoaesthesia, hypoalgesia). Dashed lines show 95% CI for healthy controls (− 1.96 < z < 1.96). ^#QST z-values were abnormal compared to the expected values of an ideal healthy population with a mean z-value = 0 and a standard deviation = 1. Data are presented in Mean + SEM. CDT = cold detection threshold; CPT = cold pain threshold; HPT = heat pain threshold; MDT = mechanical detection threshold; MPS = mechanical pain sensitivity; MPT = mechanical pain threshold; PPT = pressure pain threshold; TSL = thermal sensory limen; VDT = vibration detection threshold; WDT = warm detection threshold; WUR = wind-up ratio.

Figure 2

Correlation of respiratory arrhythmia to anxiety (A, B) and depression (C, D).