Thyrotoxic Periodic Paralysis, Susceptibility to, 1

Alternative Names

  • TTPP1
  • Hashitoxic Periodic Paralysis
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Disorders of thyroid gland

OMIM Number

188580

Mode of Inheritance

Autosomal dominant

Gene Map Locus

1q32.1

Description

Thyrotoxic Periodic Paralysis (TPP) is a condition characterized by intermittent episodes of muscle weakness or paralysis occurring in people with hyperthyroidism. Muscles of the arms and legs are most commonly affected. Other affected muscles include muscles of the eye, muscles involved in breathing and swallowing, and cardiac muscles, which may sometimes lead to vision changes, difficulty in breathing, swallowing, and speaking. The attacks are characterized by low levels of serum potassium levels. The paralytic episodes are usually triggered by hyperinsulinemia, carbohydrate overload, high salt intake, and/or vigorous exercise, and usually last from a few hours to several days. It is presumed that the thyroid hormone stimulates the Na+-K+ ATPase dependent K+ channel, resulting in the pathophysiology of the disease. TPP is the most common secondary hypokalemic periodic form of paralysis, and is more common in Asian and Hispanic individuals. Among Chinese, the prevalence of TPP is estimated to be 13-14%. The disease is not so common among Caucasians. In addition, TPP affects predominantly males.

A diagnosis of TPP is confirmed if intermittent paralytic episodes are supported by abnormally low levels of serum thyroid stimulating hormone, and high levels of thyroid hormone. During the attacks, ECG may show abnormalities, although the EMG will be normal, and the serum potassium level will be low. Treatment during an attack will involve immediate administration of potassium, and ensure rapid reduction in thyroid levels. Occasionally, patients may not respond to potassium administration, in which case intravenous propranolol is administered. Beta blockers are also indicated to reduce the severity of the attacks.

A recent study has described a mutation in the KCNE3 gene to be responsible for the TPP phenotype. The mutant was shown to decrease the outward potassium flux, resulting in a more positive membrane potential. HLA subtype differences with relation to TPP amongst different races have also been studied, among Japanese (DRw8), Singapore Chinese (A2BW22, AW19B17), and Hong Kong Chinese (B5, BW46). Apart from the KCNE3 gene, other polymorphisms have also been reported in CACNA1S, SCN4A, KCNE1, KCNE2, KCNE1L, KCNJ2, KCNJ8, and KCNJ11 genes.

Epidemiology in the Arab World

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Other Reports

Bahrain

Siddiqui (1998) reported on a 33 year old Bahraini male patient who presented with weakness in his legs, accompanied with nausea and vomiting. He had a similar attack two hours earlier, which resolved spontaneously. Also, a similar attack had occurred a year previously, which lasted for about two hours; during which he was diagnosed with having low serum potassium. He had no family history of such a condition. Upon examination, he was found to have a history of weight loss since one year. His thyroid was diffusely enlarged, but with no signs of thyrotoxicosis. Muscle tone was low in the limbs. Serum potassium was 1.8 mmol/L. The ECG showed U waves in most of the leads, which disappeared after the patient was given KCl in dextrose water. After 24 hours, his serum potassium level was 5.4 mmol/L and he was discharged. Results of his thyroid tests showed hyperthyroidism. On his follow-up visit, he was started on Carbimazole and Propranolol. However, his thyrotoxicosis was difficult to control. He was then treated with radioactive iodine, while reducing the doses of the other two drugs. The treatment was finally stopped a year later, when his thyroid level normalized.

[Siddiqui D. Thyrotoxicosis presenting as hypokalemic periodic paralysis. Bahrain Med Bull. 1998; 20(2):58-60.]

Kuwait

Al-Khaledy et al. (2000) reported the case of a 46-year old Kuwaiti man who presented with severe weakness of the lower limbs since waking up in the morning. He had had a similar, although milder, condition a week prior to presentation, which had resolved by itself. Physical examination showed normal findings for pulse, respiratory rate, blood pressure, and body temperature. In addition, no sensory deficit was detected, and chest, heart and abdomen examinations were also normal. Power in the upper and lower limbs was found to be reduced. The patient had no family history of thyroid disease or periodic paralysis. ECG showed first degree heart block, right bundle branch block, and the presence of U waves. Electrolyte levels were found to be abnormal with sodium at 133.8 mmol/L, potassium at 1.76 mmol/L, magnesium at 0.82 mmol/L, calcium at 2.4 mmol/L, and glucose at 6.3 mmol/L. The patient was put on 80 mmol intravenous KCL, and 8-hours later, showed a marked improvement in the muscle power. Serum potassium was also found to increase to 4.8 mmol/L. ECG at this stage showed a normalized interval, with disappearance of the U waves. Serum thyroxin was found to be increased (49.13 Pmol/L), while TSH level was decreased (0.03). The patient refused radioactive iodine treatment, and was treated with another drug for hyperthyroidism. Two months later, the patient had shown no recurrence at follow-up. Al-Khaledy et al. (2000) cautioned physicians against considering patients who present with unexpected generalized paralysis, but are otherwise healthy and have an intact sensorium, as hysterical. Neglecting such patients could lead to serious complications.

[Al-Khaledy EH, Ashour N, Al-Mutairi S. Thyrotoxic hypokalemic periodic paralysis. Qatar Med J. 2000; 9(2):70-2.]

Oman

Redha et al. (1998) reported hypokalemic periodic paralysis in a 41-year old Omani male who presented with acute weakness of his lower limbs with mild weakness of upper limbs for one hour and a half. He had similar history two days prior to this presentation which spontaneously resolved after four hours. Clinically, the patient had grade 2/5 flaccid paraparesis, hypoactive reflexes, 2/5 symmetric proximal muscle weakness of upper limbs and mild bilateral distal weakness. Apart from significant tachycardia (122/min), his vitals were stable, and there was no goiter, bruit, or opthalopathy. Investigations revealed hypokalemia (1.9 mmol/L) with ECG changes (sinus tachycardia, and non-specific ST and T wave changes). The patient was immediately managed by parentral potassium chloride (40 mmol) followed by oral replacement (64 mmol) over a period of six hours. After eight hours, the potassium level was 4.1 mmol/L and the weakness had improved. After the patient was stabilized, further investigations revealed elevated free thyroxine (49.9 pmol/L) and low TSH (less than 0.03 mlU/L), with positive thyroid microsomal antibodies at 1:400 dilution and positive TSH-receptor antibody (3 units). Technetium scan revealed increased activity, just over the maximum upper limit. The patient was discharged on medications. [Redha SA, Walia HK, Al Lamki M, Ketheri S. Thyrotoxic periodic paralysis. Oman Med J. 1998; 14(4):35-6.]

Bhattacharya and Varghese (2000) reported low platelet counts in a 35-week pregnant Omani female (23 years old, Gradiva 5, para 1) who was a known case of idiopathic thrombocytopenic purpura (ITP). She had had a history of three miscarriages at eight weeks, after which she was diagnosed with ITP for which splenectomy was done. During this pregnancy, she was doing well until 26 weeks of gestation when she was admitted for low platelet count of 59,000/ml, for which she was transfused a unit of fresh platelet-rich plasma. At 35-weeks, her platelet count again dropped to 40,000/ml, and then to 31,000/ml, with no evidence of bleeding diathesis. The fetus was in cephalic presentation and 34 weeks on abdominal examination, which was confirmed by ultrasound. She was managed by intravenous immunoglobulin infusion (500 mg/kg/day for five days) with twice daily fetal monitoring with non stress test, which showed isolated deceleration on the fifth day. But the patient refused the termination of pregnancy by emergency LSCS. The platelet count improved to 197,000/ml, but again dropped to 96,000/ml by the tenth day. The baby was delivered at this time by LSCS with good Apgar scores and the mother was intraoperatively transfused with 1 pint of whole blood (for 700 ml blood loss and low platelets), which was followed by another pint the next day along with two units of platelet-rich plasma. The mother and the baby remained well and were discharged on the sixth day. [Bhattacharya P, Varghese P. Platelet dysfunction in pregnancy. Oman Med J. 2000; 17(2):21-5.]

Saudi Arabia

Johnson and Hoque (1992) reported an adult male from Saudi Arabia with thyrotoxic periodic paralysis. However, no further details could be obtained at the time this record was edited.

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