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      Thyrotoxic periodic paralysis associated with Graves’ disease: a case series

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          Abstract

          Summary

          Thyrotoxic periodic paralysis (TPP) is a rare condition characterised by acute onset hypokalaemia and paralysis which most commonly affects men of Asian descent between the ages of 20 and 40 years ( 1, 2). It has been reported in approximately 2% of patients with thyrotoxicosis in China and Japan ( 1, 2, 3). Hypokalaemia in TPP results from a massive intracellular shift of potassium induced by the thyroid hormone sensitisation of Na +/K +-ATPase ( 4). Treatment of TPP includes prevention of this shift by using beta-blockade, rapid potassium replacement and treatment of the underlying hyperthyroidism. We present two cases of TPP with differing outcomes. In the first case, a 33-year-old Filipino gentleman presented to our emergency department (ED) with a 3-month history of recurrent proximal lower limb weakness. Serum potassium was 2.2 mmol/L (3.3–5.1) and he was given i.v. potassium replacement. Thyroid function tests (TFTs) and thyroid antibodies were consistent with Graves thyrotoxicosis. He was discharged home on carbimazole and remains well controlled on long-term medical therapy. In the second case, a 22-year-old Malaysian gentleman presented to our ED with new-onset bilateral lower limb painless paralysis. Serum potassium was 1.9 mmol/L with TFTs demonstrating Graves thyrotoxicosis. He was treated with i.v. potassium replacement and discharged home on carbimazole and propranolol. He represented to the hospital on two further occasions with TPP and was advised to consider total thyroidectomy given his refractory Graves’ disease. These cases highlight the importance of prompt recognition of this rare life-threatening complication of Graves’ disease, especially in patients of Asian descent.

          Learning points
          • Thyrotoxic periodic paralysis is a rare condition characterised by hypokalaemia and acute painless muscle weakness in the presence of thyrotoxicosis.

          • The signs and symptoms of thyrotoxicosis can be subtle in these patients.

          • It is most commonly seen in Asian males between the ages of 20 and 40 and is most frequently caused by Graves’ disease.

          • Prompt recognition is essential as it is a life-threatening condition.

          • Urgent i.v. potassium replacement and beta-blockade with a non-selective beta-blocker are the mainstays of treatment.

          • i.v. potassium replacement should not be given in dextrose as this can potentiate hypokalaemia.

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          Most cited references13

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          2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

          Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.
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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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              Mechanism of thyrotoxic periodic paralysis.

              The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na(+)-K(+) ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. This mechanism alone, however, cannot adequately explain how hypokalemia occurs during acute attacks or the associated paradoxical depolarization of the resting membrane potential. Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K(+) (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K(+) efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na(+) channels and causes muscle unexcitability and paralysis.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                17 January 2022
                2022
                : 2022
                : 21-0178
                Affiliations
                [1 ]Department of Diabetes and Endocrinology , Ryde Hospital, Eastwood, N ew South Wales , Australia
                [2 ]Department of Medicine , Macquarie University, Sydney, Australia
                [3 ]Department of Medicine , University of Western Sydney, Sydney, Australia
                Author notes
                Correspondence should be addressed to S Ludgate; Email: ludgates@ 123456tcd.ie
                Author information
                http://orcid.org/0000-0002-9597-9471
                Article
                EDM210178
                10.1530/EDM-21-0178
                8859961
                3bfbc654-d0ed-4b28-a4d8-5bf8d39a0214
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 29 December 2021
                : 17 January 2022
                Categories
                Adult
                Male
                Asian - Filipino
                Asian - other
                Australia
                Thyroid
                Thyroid
                Cardiology
                Insight into Disease Pathogenesis or Mechanism of Therapy
                Insight into Disease Pathogenesis or Mechanism of Therapy

                adult,male,asian - filipino,asian - other,australia,thyroid,cardiology,insight into disease pathogenesis or mechanism of therapy,february,2022

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