The LDIFLARE and CCM Methods Demonstrate Early Nerve Fiber Abnormalities in Untreated Hypothyroidism: A Prospective Study.

Context: Recent studies using skin biopsy suggest presence of small-fiber neuropathy in subclinical hypothyroidism. This study uses two noninvasive methods-the laser Doppler imager flare technique (LDIFLARE) and corneal confocal microscopy (CCM)-to assess small-fiber function (SFF) and small-fiber structure (SFS), respectively, in newly diagnosed hypothyroidism (HT) before and after adequate treatment. Design and Setting: Single-center, prospective, intervention-based cohort study. Patients and Participants: Twenty patients with newly diagnosed HT (15 with primary HT and 5 with post-radioiodine HT) along with 20 age-matched healthy controls (HCs). Interventions: Patients with HT and HCs were assessed neurologically at diagnosis and baseline, respectively. The HT group was reassessed after optimal replacement (defined as TSH level of 0.27 to 4.20 mIU/L) with levothyroxine (LT4) and HCs were reviewed after 1 year. Main Outcome Measures: Neurologic assessment for small fibers was performed by using LDIFLARE for SFF and CCM for SFS; large fibers were studied by sural nerve conduction velocity (SNCV) and sural nerve amplitude (SNAP). Results: At baseline, both LDIFLARE (mean ± SD) (6.74 ± 1.20 vs 8.90 ± 1.75 cm2; P = 0.0002) and CCM nerve fiber density (CNFD) (expressed as number of fibers per mm2: 50.77 ± 6.54 vs 58.32 ± 6.54; P = 0.002) were significantly reduced in the HT group compared with HCs whereas neither SNCV nor SNAP was different (P ≥ 0.05). After optimal LT4 treatment, both LDIFLARE (7.72 ± 1.12 vs 6.74 ± 1.20 cm2; P ≤ 0.0001) and CNFD (54.43 ± 5.70 vs 50.77 ± 6.54 no./mm2; P = 0.02) improved significantly but remained significantly reduced compared to HCs (P = 0.008 and P = 0.01, respectively) despite normalization of TSH. Conclusions: This study demonstrates that dysfunction of small fibers precedes large neural fiber abnormalities in early HT. This can be reversed by replacement therapy to achieve a biochemically euthyroid state, but small-fiber neural outcomes continued to remain low compared with values in HCs.

Nutritional Supplementation for Diabetic Foot Ulcers: The Big Challenge.

Diabetic foot ulcers remain difficult to heal and nutritional supplementation may be an important complementary therapeutic measure. However, we need to clarify many issues before such supplementation is more widely used. Indeed, improvements are needed in the following areas: evaluation of nutritional inadequacy, completion of randomized controlled trials, understanding of patient and ulcer characteristics that favor response to nutritional supplementation, optimal duration of supplementation therapy, and evaluation of patient adherence. The challenge is now to acquire more knowledge in the aforementioned areas.