Thyroid hormone autoantibodies in primary Sjögren syndrome and rheumatoid arthritis are more prevalent than in autoimmune thyroid disease, becoming progressively more frequent in these diseases.

To verify the greater prevalence of circulating thyroid hormone autoantibodies (THAb) in primary Sjogren syndrome (SS) vs Hashimoto's thyroiditis (HT) and Graves' disease (GD), we measured THAb in the serum of patients with these 3 diseases who were sampled from 1998-1999 (no.=20, 88, 25) and 1990-1992 (no.=13, 75, 31). Patients with rheumatoid arthritis (RA) (no.=23 and 16) and other collagenoses (no.=20 and 16) were also studied. A third series of patients with these 5 diseases was studied from 1975-1982, and data have been taken into account. THAb were detected using a specific radioimmunoprecipitation method, and their presence was correlated with the presence of TG antibodies (TGAb). We found that IgG antibodies against T3, T4 or both were present with these prevalences in the 1975-1982, 1990-1992 and 1998-1999 series: HT=1, 4, 20%; GD=2, 6, 32%; SS=20, 31, 50%; RA=0, 12, 26%; other collagenoses=0, 0, 0%. The majority of the Sjogren or arthritis cases positive for THAb were negative for TGAb, while the opposite was true for the 2 autoimmune thyroid diseases. We conclude that prevalence of THAb in the 2 non-thyroid autoimmune diseases is greater than in the 2 thyroid autoimmune diseases. In addition, prevalence of THAb is increasing over time regardless of disease. Molecular similarity between extra-thyroid connective proteins (specifically associated to primary SS and RA) and iodinated regions of TG, and an increased preponderance of environmental factors as triggers of autoimmune diseases might account for our findings.

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.

Onset of hypothyroidism with polymyositis-like clinical features in elderly patients.

Impaired muscle function may be a predominant aspect of hypothyroidism and is virtually present in all patients with overt thyroid failure. Less common is the onset of hypothyroidism with clinical features mimicking a polymyositis. We have observed 3 patients, whose age ranged 63-68 years, presenting with muscle aches, cramps, proximal weakness and stiffness. Two patients had dysphagia. Serum creatine kinase (CK) and electromyography (EMC) were altered in two patients. Muscle biopsy showed type II atrophy, sporadic type I and type II grouping, "core-like" areas, and some myopathic changes such as central nuclei and muscle necrosis. No inflammatory changes were present. Immunohistochemistry of several muscle cytoskeletal proteins revealed increased desmin in "corelike" areas. Detection of serum thyroid hormone levels revealed very low triiodo-L-thyronine (T3) and thyroxine (T4), whereas thyroid-stimulating hormone (TSH) was greatly increased as well as serum anti-thyroglobulin, anti-peroxidase and anti-microsome antibodies. The patients were diagnosed having a hypothyroid myopathy due to Hashimoto thyroiditis. L-thyroxine treatment normalized clinical and hormone levels, but serum antibodies remained elevated. Muscle biopsy was fundamental to establish the correct diagnosis in our patients. Presence of over-expression of desmin in cores, as described in target lesions in neurogenic diseases, may suggest a nerve-mediated pathogenesis of hypothyroid myopathy.

Late-onset mitochondrial neuromyopathy: an age-related phenomenon?

Peripheral neuropathy has been described in a number of cases of mitochondrial diseases. In these patients the onset of neuropathy varies from childhood to adulthood, whereas late onset is quite rare. We report here three males, ranging from 71 to 75 years with onset of peripheral neuropathy between 64 and 74 years of age. They complain of ataxic gait, muscle aches, weakness and mild muscle atrophy, sensory impairment with predominant glove and stocking distribution, reduced or absent deep tendon reflexes. Neurophysiological examinations and sural nerve biopsy studies showed a sensorimotor neuropathy with axonal degeneration in two cases and demyelination in one. Peroneus brevis muscle biopsy revealed, apart from frank neurogenic changes, presence of ragged-red fibers and cytochrome c oxidase negative fibers. Electron microscopy confirmed an abnormally increased presence of subsarcolemmal and intermyofibrillar mitochondria in muscle samples. These morphological features suggested a mitochondrial disease that was confirmed by biochemical investigations on muscle homogenate showing that the mitochondrial respiratory chain (MRC) enzyme activities were all reduced when compared to citrate synthase activity. In addition the presence of a partially inactive cytochrome c oxidase protein by ELISA was demonstrated in two cases. According to a recent "mitochondrial theory of aging", we think that a progressive decline of MRC function has affected either skeletal muscle or peripheral nerves in our patients. Being energy-requiring processes, muscle metabolism as well as active axonal transport may become progressively defective with age resulting in a late-onset neuropathy.

Hypokalemic myopathy in pseudohyperaldosteronism induced by fluoroprednisolone-containing nasal spray.

A man who was using 9-alpha-fluoroprednisolone-containing nasal spray preparation for allergic rhinitis developed a pseudohyperaldosteronism and an acute hypokalemic myopathy. Muscle biopsy changes included variation in fiber size with preserved type 2a fibers, necrosis, phagocytosis and regeneration. This factitious mineralocorticoid excess syndrome, induced by uncontrolled use of intranasally administered steroid, should be considered among the various causes of hypokalemic myopathy.