Magnus R.Dias da Silva
GENETIC AND CLINICAL ASPECTS OF THYROTOXIC PERIODIC PARALYSIS (TPP).
Silva MRD, Cerutti JM, Tengan CH, Gabbai AA, Maciel RMB. Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine and department of Neurology, Escola Paulista de medicina, Universidade Federal de Sao Paulo.
TPP is a subtype of Hypokalemic Priodic Paralysis (HoPP) characterized by attacks of intermittent muscle weakness during hypokalemia and thyrotoxicosis; the symptoms of paralysis are very similar in both forms. TPP, however, appears always in the sporadic form, shows complete remission after the treatment of thyrotoxicosis and 90% of patients have oriental ancestry (albeit cases from other ethnic groups were also described). Its pathogenesis is unknown; however, the almost identical clinical features of TPP and HoPP may indicate that both diseases share the same molecular defect.
Recently, in families with HoPP, two kinds of mutations have been located in the calcium channel of the skeletal muscle membrane: Arg528His and Arg 1239His. Among 29 patients with HoPP in our clinic, TTP was confirmed in 15 patients, being 13 in the sporadic form and, for the first time in the literature, in 2 family members(father and son). All patients are male, have had attacks of weakness accompanied by thyrotoxicosis and hypokalemia, 5 have relativies with thyroid disease and 2 oriental ancestry. Resting after hard exercise as the precipitaing factor was reportd by 4 patients and none after large carbohydrate load. In on patient we found a positive family history of TPP, his father affected being 30 years before. All patients had signs or symptoms of thyrotoxicosis such as weigth loss, tremor and tachycardia; 10 had midly increased thyroid gland; although the patients had clinical signs of thyrotoxicosis, this diagnosis, however, was made only after the attacks of weakness. Thyroxicosis was due to Graves' disease, confirmed through autoantibodies and radiodine uptake. After euthyroidism, reached with treatment with anti-thyroid drugs or radioiodine, all patients recovered completely from the attacks of paralysis. The search for those 2 mutations described in HoPP families by restriction fragment length polymorphism (RFLP analysis) we negative in all 15 patients.
In conclusion, our study shows that TPP is a frequent form of periodic paralysis (52% in our series), affects also non-oriental patients and shows discrete forms of thyrotoxicosis; in addtion, we describe for the first time a familial case of TPP. Furthermore, despite a complete clinical similarity with the familial HoPP it is not linked to the same genetic defect.