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      A 10-year analysis of thyrotoxic periodic paralysis in 135 patients: focus on symptomatology and precipitants

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          Abstract

          Background

          A comprehensive analysis has not been performed on patients with thyrotoxic periodic paralysis (TPP) characterized by acute hypokalemia and paralysis in the setting of thyrotoxicosis.

          Purpose

          The aim of this study was to analyze the detailed symptomatology of thyrotoxicosis and precipitating factors for the attack in a large cohort of TPP patients.

          Patients and methods

          A prospective observational study enrolled patients with TPP consecutively over 10 years at an academic medical center. Clinical features, including signs/symptoms of thyrotoxicosis and precipitating factors, were analyzed. The Wayne's index was used to assess the severity of thyrotoxicosis at presentation. Patients who agreed to receive an oral glucose-loading test after recovery were evaluated.

          Results

          Among the 135 TPP patients (male:female, 130:5), 70% of paralytic attacks occurred in the morning, especially during the seasons of summer and fall. Two-thirds of patients did not have a known family or personal history of hyperthyroidism. Only 17% of TPP patients manifested overt signs/symptoms of thyrotoxicosis (Wayne's index >19). A clear precipitating factor, such as high carbohydrate load, acute upper respiratory tract infection, strenuous exercise, high-salt diet, or the use of steroids or bronchodilators, was identified in only 34% of TPP patients. A glucose load to stimulate insulin secretion induced acute hypokalemia (K +2.47±0.6 mmol/l) with reparalysis in only 18% (10/55) of TPP patients.

          Conclusions

          Most TPP patients have only subtle clinical signs/symptoms of thyrotoxicosis and only a small fraction has clear precipitating factors. In addition to the effects of hyperinsulinemia, other insulin-independent mechanisms may participate in the pathogenesis of TPP.

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          Most cited references47

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          Strength and cross-sectional area of human skeletal muscle.

          The maximum voluntary force (strength) which could be produced by the knee-extensor muscles, with the knee held at a right angle, was measured in a group of healthy young subjects comprising twenty-five males and twenty-five females. Both legs were tested: data from the stronger leg only for each subject were used in the present study. Computed tomography was used to obtain a cross-sectional image of the subjects' legs at mid-thigh level, measured as the mid-point between the greater trochanter and upper border of the patella. The cross-sectional area of the knee-extensor muscles was determined from the image obtained by computer-based planimetry. The subjects' height and weight were measured. An estimate of body fat content was obtained from measurements of skinfold thicknesses and used to calculate lean body mass. Male subjects were taller (P less than 0.001), heavier (P less than 0.001), leaner (P less than 0.001) and stronger (P less than 0.001) than the female subjects. No significant correlation was found to exist between strength of the knee-extensor muscles and body weight in the male or in the female subjects. In the male subjects, but not in the female group, there was a positive correlation (r = 0.50; P less than 0.01) between strength and lean body mass. Muscle cross-sectional area of the male subjects was greater than that of the female subjects (P less than 0.001). The ratio of strength to cross-sectional area for the male was 9.49 +/- 1.34 (mean +/- S.D.). This is greater but not significantly so, than that for females (8.92 +/- 1.11). In both male and female groups, there was a significant (P less than 0.01) positive correlation between muscle strength and cross-sectional area. A wide variation in the ratio of strength to muscle cross-sectional area was observed. This variability may be a result of anatomical differences between subjects or may result from differences in the proportions of different fibre types in the muscles. The variation between subjects is such that strength is not a useful predictive index of muscle cross-sectional area.
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            Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge.

            The aim of this article was to review the clinical presentation, pathogenesis, and management of thyrotoxic periodic paralysis (TPP). A MEDLINE search was conducted for articles published during the last 40 yr based on the key words thyrotoxic periodic paralysis and hypokalemic periodic paralysis. A total of 281 primary articles and 168 references of the retrieved articles were also reviewed. TPP is a common complication of hyperthyroidism in Asian men but is increasingly seen in Western countries. Hypokalemia and muscle paralysis results from a sudden intracellular shift of potassium and is not due to potassium deficiency. Clinical features of hyperthyroidism in patients with TPP may be subtle. Immediate potassium supplementation prevents serious cardiopulmonary complications and may hasten the recovery of muscle weakness. Nonselective beta-adrenergic blockers can ameliorate and prevent recurrence of the paralytic attacks. This episodic paralysis will remit with definitive control of hyperthyroidism. Increased sodium-potassium ATPase pump activity and enhanced insulin response in patients with TPP is postulated to contribute to the hypokalemia. The genetic predisposition for TPP is not entirely clear. Association of polymorphisms of the calcium channel alpha1-subunit gene with TPP has been noted. Due to population mobility, TPP is increasingly common in Western countries. Early diagnosis and prompt treatment prevent life-threatening complications associated with hypokalemia and muscle weakness. Assaying of thyroid function in patients with hypokalemic paralysis distinguishes TPP from other forms of hypokalemic periodic paralysis.
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              Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis.

              Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis.

                Author and article information

                Journal
                Eur J Endocrinol
                Eur. J. Endocrinol
                EJE
                European Journal of Endocrinology
                BioScientifica (Bristol )
                0804-4643
                1479-683X
                November 2013
                29 July 2013
                : 169
                : 5
                : 529-536
                Affiliations
                [1]Division of Nephrology, Department of Medicine Tri-Service General Hospital National Defense Medical Center No 325, Section 2, Cheng-Kung Road, Neihu 114, TaipeiTaiwan
                [2]Division of Clinical Pathology, Department of Pathology Tri-Service General Hospital National Defense Medical Center No 325, Section 2, Cheng-Kung Road, Neihu 114, TaipeiTaiwan
                [3]Division of Endocrinology and Metabolism, Department of Medicine Tri-Service General Hospital National Defense Medical Center No 325, Section 2, Cheng-Kung Road, Neihu 114, TaipeiTaiwan
                [4]Department of Medicine Providence St Vincent Medical Center Portland, OregonUSA
                Author notes
                (Correspondence should be addressed to S-H Lin; Email: l521116@ 123456ndmctsgh.edu.tw )
                Article
                EJE130381
                10.1530/EJE-13-0381
                3789562
                23939916
                ec272bab-bb7c-4af5-b3ca-64f899a220af
                © 2013 European Society of Endocrinology

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 6 May 2013
                : 7 August 2013
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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