Contribution of Asian Haplotype of KCNJ18 to Susceptibility to and Ethnic Differences in Thyrotoxic Periodic Paralysis

Abstract Context and Objectives Thyrotoxic periodic paralysis (TPP) is an acute complication of thyrotoxicosis that can be lethal. TPP is rare in Caucasians but often affects young men in East Asian populations. This study aimed to clarify the contribution of KCNJ18 to susceptibility to TPP in East Asian populations. Participants and Methods The study comprised 635 participants including 13 Japanese patients with TPP, 208 Japanese patients with Graves disease without TPP, and 414 healthy control subjects from the Japanese (n = 208), Korean (n = 111), and Caucasian populations (n = 95). DNA samples from 29 participants (13 with TPP, 8 with Graves disease, and 8 controls) were sequenced for KCNJ18, and all participants (n = 635) were genotyped for six variants of KCNJ18 and a polymorphism of KCNJ2 (rs312691). Results Six single-nucleotide variants (SNVs) with amino acid substitutions were identified by direct sequencing of KCNJ18. Among these, four SNVs comprised three haplotypes under strong linkage disequilibrium. Haplotype 1 (AAAG) of KCNJ18 was significantly associated with susceptibility to TPP in the Japanese population (OR = 19.6; 95% CI, 1.5 to 256.9; P = 0.013). Haplotype frequencies in the general East Asian (Japanese and Korean) and Caucasian populations differed significantly (haplotype 1: 80.8% vs 48.4%, P = 1.1×10−27). Conclusion A major haplotype of KCNJ18 in East Asian populations is significantly associated with susceptibility to TPP. The haplotype is much more common in East Asian than Caucasian populations, suggesting its contribution to the high prevalence of TPP in East Asian populations.

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A Case of Nonfatal Ventricular Arrhythmia Due to Thyrotoxic Periodic Paralysis in a Saudi Patient as an Initial Presentation of Graves’ Disease

Clinical Medicine Insights Case Reports ◽

10.4137/ccrep.s34560 ◽

2016 ◽

Vol 9 ◽

pp. CCRep.S34560 ◽

Cited By ~ 1

Author(s):

Osamah Hakami ◽

Maswood M. Ahmad ◽

Naji Al Johani

Keyword(s):

Muscle Weakness ◽

Early Recognition ◽

Periodic Paralysis ◽

Graves Disease ◽

Thyrotoxic Periodic Paralysis ◽

Asian Populations ◽

Definitive Therapy ◽

Life Threatening ◽

Acute Paraparesis ◽

Saudi Male

Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism characterized by recurrent muscle weakness and hypokalemia. It has been commonly reported in non-Asian populations. Four cases were reported in Saudis so far, and one had a life-threatening arrhythmia. We describe an additional case of a 28-year-old apparently healthy Saudi male patient, who presented with acute paraparesis associated with hypokalemia (K: 2.0 mmol/L), complicated by ventricular tachycardia and cardiac arrest. He was successfully resuscitated and his hypokalemia was corrected. A diagnosis of Graves’ disease associated with TPP was made. He was initially treated with carbimazole and β-blockers and then given a definitive therapy with radioactive iodine, which showed a good response. This case highlights the importance of early recognition and prompt treatment of TPP as a differential diagnosis for muscle weakness. A brief review of TPP and associated arrhythmia is included.

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Thyrotoxic Periodic Paralysis due to Graves' disease: a mandatory differential diagnosis in Asian patients presenting with paralysis and hypokalemia

Endocrine Abstracts ◽

10.1530/endoabs.49.gp237 ◽

2017 ◽

Author(s):

David Barbosa ◽

Carolina Faria ◽

Ana Sofia Osorio ◽

Ema Nobre ◽

Ana Paula Vilas ◽

...

Keyword(s):

Differential Diagnosis ◽

Periodic Paralysis ◽

Graves Disease ◽

Thyrotoxic Periodic Paralysis ◽

Asian Patients

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Thyrotoxic Periodic Paralysis Causing Back Pain and Leg Weakness: An Unusual Presentation of Hyperthyroidism

Case Reports in Endocrinology ◽

10.1155/2021/6622658 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

Henrik Elenius ◽

Marie Cesa ◽

Corina C. Nava Suarez ◽

Abhishek Nimkar ◽

Prasanta Basak ◽

...

Keyword(s):

Muscle Weakness ◽

Periodic Paralysis ◽

Close Monitoring ◽

Respiratory Compromise ◽

Thyrotoxic Periodic Paralysis ◽

Asian Populations ◽

Life Threatening ◽

Common Etiology ◽

Leg Weakness ◽

Hispanic Male

Thyrotoxic periodic paralysis (TPP) is a rare muscular disorder, characterized by muscle weakness and hypokalemia triggered by thyrotoxicosis. In Asian populations, 2% of patients with thyrotoxicosis are affected, compared to only 0.1–0.2% of non-Asians. The vast majority of patients are male. Muscle weakness ranges in severity from very mild to life-threatening, due to respiratory compromise. We present a case of a previously healthy 39-year-old Hispanic male who presented with sudden quadriparesis and quickly recovered after being treated for hypokalemia and thyrotoxicosis. TPP, although unusual, is important to recognize as it is a potentially fatal condition that requires close monitoring and is readily reversible with appropriate therapy. Any cause of thyroid hormone excess can cause TPP, with Graves’ disease being the most common etiology. Acute treatment includes potassium repletion, while long-term management focuses on determining and treating the cause of thyrotoxicosis, since maintaining a euthyroid state will prevent further episodes of TPP.

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Thyrotoxic periodic paralysis

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.3171 ◽

2011 ◽

pp. 452-454

Author(s):

Annie W.C. Kung

Keyword(s):

African American ◽

American Indian ◽

Ethnic Groups ◽

Japanese Population ◽

Chinese Population ◽

Periodic Paralysis ◽

Thyrotoxic Periodic Paralysis ◽

Female Ratio ◽

Asian Populations ◽

Male To Female

The association of thyrotoxicosis and periodic paralysis was first described in 1902 in a white patient. However, it soon became evident that thyrotoxic periodic paralysis (TPP) affects mainly Asian populations, in particular Chinese and Japanese, although isolated cases have also been reported in other ethnic groups such as white, Hispanic, African-American, and American Indian populations. The incidence of TPP in non-Asian thyrotoxic patients is around 0.1%, whereas in Chinese and Japanese thyrotoxic patients, TPP affects 1.8% and 1.9%, respectively (1–3). Despite a higher incidence of thyrotoxicosis in women, TPP affects mainly men, with a male to female ratio ranging from 17:1 to 70:1, according to different series. In the Chinese population, TPP affects 13% of male and 0.17% of female thyrotoxic patients. In the Japanese population, TPP was reported to occur in 8.2% of male and 0.4% of female thyrotoxic patients in the 1970s, but in 1991 the reported incidence had decreased to 4.3% and 0.04%, respectively (4).

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THYROTOXIC PERIODIC PARALYSIS IN A PATIENT WITH GRAVES DISEASE AND WOLF PARKINSON WHITE SYNDROME

CHEST Journal ◽

10.1016/j.chest.2020.08.250 ◽

2020 ◽

Vol 158 (4) ◽

pp. A245

Author(s):

Brenda Nyatanga ◽

Bryan Stringer ◽

Srinivas Nadadur

Keyword(s):

Periodic Paralysis ◽

Graves Disease ◽

Thyrotoxic Periodic Paralysis ◽

White Syndrome

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Rhabdomyolysis Induced by Nonstrenuous Exercise in a Patient with Graves’ Disease

Case Reports in Endocrinology ◽

10.1155/2014/286450 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Sarawut Summachiwakij ◽

Issac Sachmechi

Keyword(s):

Differential Diagnosis ◽

Periodic Paralysis ◽

Graves Disease ◽

Past Medical History ◽

Thyrotoxic Periodic Paralysis ◽

Radioiodine Uptake ◽

Thyroid Stimulating Immunoglobulins ◽

History Of ◽

Brown Urine ◽

Thyroid Ophthalmopathy

Hyperthyroidism can result in several musculoskeletal conditions such as thyrotoxic periodic paralysis, thyrotoxic myopathy, and thyroid ophthalmopathy. Rhabdomyolysis has been rarely reported to be associated with hyperthyroidism. We describe a 33-year-old man who presented with bilateral thigh pain and dark brown urine after regular squatting. He had a past medical history of hyperthyroidism but stopped taking it 2 months prior to admission. He was found to have rhabdomyolysis, myoglobinuria, and thyrotoxicosis. Presence of thyroid-stimulating immunoglobulins (TSI) and high radioiodine uptake confirmed a diagnosis of Graves' disease. He received aggressive fluid resuscitation and sodium bicarbonate intravenously along with monitoring fluid and electrolyte. Methimazole was also resumed. The patient responded to treatment and rhabdomyolysis gradually resolved. Therefore, nonstrenuous exercise can potentially induce rhabdomyolysis in patients with hyperthyroidism. Although hyperthyroidism is not widely recognized as a cause of rhabdomyolysis, it should be considered in the differential diagnosis of rhabdomyolysis.

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