Subclinical Hypothyroidism

The term 'subclinical hypothyroidism' applies to patients who have mildly increased levels of serum thyrotropin hormone (TSH) and normal levels of thyroxine and liothyronine (triiodiothyronine). This very common condition, also called 'mild thyroid failure', accounts for 75% of patients who have increased serum TSH. For patients with sustained increases above 10 mIU/L, there is uniform agreement that thyroxine therapy is indicated. Therapy for milder forms of hypothyroidism is controversial. Some randomized clinical trials favor therapy for mild thyroid failure, but they are inconclusive because they lack stratification for the subgroup of patients with TSH levels below 10 mIU/L. For this subgroup, we recommend individualized management. The presence of goiter, positive thyroperoxidase (TPO) antibodies, manic-depressive disorder, fertility problems, or pregnancy or the anticipation of pregnancy favors the initiation of therapy. Positive TPO antibodies are a strong indication for therapy because of the high likelihood in these patients of progression to overt hypothyroidism; patients who are already receiving thyroxine should have adjustments of their dosage. Children and adolescents with mild thyroid failure should also be treated because of possible adverse effects on growth and development. It has been suggested that subclinical hypothyroidism is a cardiovascular risk factor, however further investigation is needed. The controversy surrounding therapy will not be resolved until more randomized studies are available for the subgroup of patients with TSH <10 mIU/L, and until the question of cardiovascular risk factors is further clarified.     

Graves' dermopathy and acropachy are markers of severe Graves' ophthalmopathy.

It is generally considered that thyroid dermopathy and acropachy almost always occur with Graves' ophthalmopathy and that these two extrathyroidal manifestations are indicators of severe autoimmune disease and hence of more severe ophthalmopathy. However, documentation of these anecdotal impressions is needed. We assessed the presence of optic neuropathy and frequency of orbital decompression in 2 referral cohorts: 40 patients with acropachy and dermopathy (acropachy group) and 138 patients with Graves' dermopathy and no acropachy (dermopathy group). We compared those cohorts with a cohort of 114 patients who had ophthalmopathy without dermopathy and acropachy (control group). We considered optic neuropathy and the need for orbital decompression to be indicators of severe Graves' ophthalmopathy. The frequency of orbital decompression was significantly higher in the dermopathy group than in the control group (odds ratio, 3.55) and even higher in the acropachy group (odds ratios: 20.68 for acropachy group compared with control group; 5.83 for acropachy group compared with dermopathy group). The same trend occurred with optic neuropathy but was not statistically significant (alpha = 0.05; p = 0.07). Five patients were exceptions: they had definite Graves' dermopathy without clinically obvious ophthalmopathy. In conclusion, dermopathy and acropachy appear to be markers of severe ophthalmopathy. Occasionally, however, Graves' dermopathy occurs without clinical ophthalmopathy.     

MELAS- and kearns-sayre-type with myopathy and autoimmune polyendocrinopahy

A 35-year-old woman with features of Kearns-Sayre syndrome consisting of progressive ptosis, ophthalmoparesis, mitochondrial myopathy, and pigmentary retinopathy also had autoimmune polyglandular syndrome type I1 (Addison's disease, autoimmune insulin-dependent diabetes meuitus, Hashimoto's thyroiditis, and primary ovarian failure). There was no history of similarly affected relatives. Analysis of muscle mitochondrial DNA (mtDNA) revealed a 2,532-bp deletion of the type seen in Kearns-Sayre syndrome as well as a heteroplasmic A3243G mutation in the tRNA-Leu(UUR) gene of the type seen in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The patient's blood and her mother's blood harbored the A3243G mutation but not the deletion, and the maternal grandmother's blood had neither mutation. In muscle, the species of mtDNA harboring the deletion was exclusively associated with the species harboring the A3243G mutation, suggesting that the point mutation predisposed to the large-scale deletion. The mtDNA species with both mutations accounted for 88% of total muscle mtDNA. Other and as yet unrecognized point mutations in mtDNA might also be associated with, and possible causally related to, largescale mtDNA deletions.