Myopathy as the persistently isolated symptomatology of primary autoimmune hypothyroidism

Although disorders of thyroid function may cause a wide range of muscle disturbances, an overt myopathy has been rarely reported as an isolated clinical presentation of hypothyroidism. We observed 10 patients (5 males and 5 females) who had been referred to the department of neurology because of muscular fatigability, myalgia, cramps, or proximal weakness. Laboratory investigation showed that all patients had hypothyroidism due to Hashimoto's thyroiditis (atrophic variant in 9/10). Classic symptoms/signs of hypothyroidism such as lethargy, constipation, cold intolerance, myxedematous facies, and/or bradycardia were absent, as assessed independently by the three coauthoring thyroidologists. Muscular complaints improved greatly and then disappeared after substitutive levothyroxine treatment. Muscle biopsy revealed nonspecific changes. Nicotinamide adenine dinucleotide reductase (NADH-TR)-hyporeactive cores were present in two patients (10% and 90% of type 1 fibers). On electron microscopy, the core areas showed disorganized myofibrils, Z-band streaming, rod formation, and paucity of mitochondria and glycogen granules. Desmin intermediate filaments were overexpressed only in some cores. The similarity of the pattern of desmin expression between hypothyroid cores and target lesions of denervated fibers supports the hypothesis that, at least in some of our patients, myopathy was the result of an impaired nerve-mediated action of thyroid hormones on skeletal muscle. Our observations suggest that an isolated myopathy as the sole manifestation of hypothyroidism is not a rare event. We postulate that our cases may constitute a peculiar subgroup of Hashimoto's thyroiditis patients: (1) the strikingly abnormal F/M ratio of 1:1; (2) the relatively younger age; (3) the rarity of the goitrous variant; (4) the unusual finding of antithyroglobulin (Tg-Ab) > antithyroid peroxidase (TPO-Ab). Thorough evaluation of thyroid function is appropriate in patients with myopathy of uncertain origin.