Introduction: Hypothyroidism (HypoT)-related polyneuropathy is reported to range between 42 to 72%. However, there is paucity of information regarding the prevalence and clinical course of small fibre neuropathy in HypoT. This prospective study examines small fibre function (SFF) using the Laser doppler imager flare (LDIFLARE) technique and structure (SFS) using in-vitro corneal confocal microscopy (IVCCM) in a cohort of HypoT subjects before and after Levothyroxine(LT4) treatment and compares the outcomes with a cohort of age-matched healthy controls (HC).
Material and methods: Twenty patients with HypoT (TSH ≧35 μ/l) 15 primary and 5 post-radioiodine along with 20 HC were assessed at baseline for SFF and SFS whilst large fibre neuropathy was assessed by determining sural nerve conduction velocity (SNCV) and amplitude (SNAP). After optimal replacement of HypoT patients with LT4 (target TSH 1.54 μ/l) for at least 6 months, all subjects including HCs were re-evaluated to determine change in both small and large fibre modalities.
Results: At baseline, compared to HC, both LDIFLARE (±SD) (6.74±1.20 vs 8.90±1.75 cm2; P=0.0002) and IVCCM (50.77±6.54 vs 58.32±6.54 no/mm2; P=0.002) were significantly reduced in HypoT. Neither SNCV nor SNAP were different compared with HC (P=0.10 and P=0.05 respectively). Following LT4 treatment, both LDIFLARE (7.72±1.12vs.6.74±1.20 cm2; P=<0.0001) and IVCCM (54.43±5.70 vs 50.77±6.54 no/mm2; P=0.02) improved significantly whilst both SNCV and SNAP showed no significant change. Interestingly, both SFF and SFS despite improving in HypoT remained significantly reduced compared to HC (P=0.008 and P=0.01 respectively) at the end of the study period.
Conclusions: Our study shows that compared to HC, both SFF and SFS are significantly reduced in untreated HypoT. Following optimal LT4 replacement, both modalities improved significantly but compared to HC remained low. The latter perhaps suggests that using TSH as the sole biomarker to monitor replacement strategies may not be adequate to improve small fibre dysfunction. Further studies are required to explore this hypothesis.