Hostname: page-component-76d6cb85b7-ntvhh Total loading time: 0 Render date: 2026-07-15T07:16:45.162Z Has data issue: false hasContentIssue false
  • English
  • Français

A Diagnostic Challenge: Acute Flaccid Paralysis

Published online by Cambridge University Press:  09 November 2016

David Lussier  and
Anthony Herd
David Lussier*
Affiliation:
Department of Emergency Medicine, University of Manitoba, Winnipeg, MB.
Anthony Herd
Affiliation:
Department of Emergency Medicine, University of Manitoba, Winnipeg, MB.
*
* Correspondence to: David Lussier, Department of Emergency Medicine, University of Manitoba, Room T258, Old Basic Sciences Building, 770 Bannatyne Avenue, Winnipeg, MB R3T 2N2 Canada; Email: umlussid@myumanitoba.ca

Abstract

An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the ‘Save PDF’ action button.

Keywords

paralysishypokalemiahyperthyroid

Information

Type
Knowledge to Practice: Diagnostic Challenge
Information
Canadian Journal of Emergency Medicine , Volume 19 , Issue 1 , January 2017 , pp. 55 - 57
Copyright
Copyright © Canadian Association of Emergency Physicians 2016 

The Case

A 37-year-old Filipino male presented to a community emergency department (ED) with acute bilateral flaccid leg paralysis. He had no known medical conditions, took no medications and denied any allergies or substance use. There had been no history of trauma.

On review of systems, he reported several weeks of intermittent leg weakness. He reported that this had mainly affected his proximal leg muscles, noting difficulty when attempting to rise out of a chair. He also described intermittent palpitations, tremor of his fingers, and a 10 pound weight loss over several months. He denied any paresthesia, headache, vision change, bowel change, or bladder change.

On examination he looked well and had stable vital signs with a heart rate of 90 bpm. Cardiac and respiratory examinations were unremarkable. Lower legs demonstrated markedly diminished strength and diminished deep tendon reflexes bilaterally. Sensation to fine touch was intact. He had symmetric and normal upper limb strength, reflexes and sensation to fine touch. A fine tremor was noted in the fingertips. Cranial nerve examination was unremarkable. Head and neck exam demonstrated eyelid retraction and lid lag, as well as a goiter. See Table 1.

Table 1

Laboratory Investigations

Question 1 – What is the diagnosis?

He was diagnosed with thyrotoxic periodic paralysis

Question 2 – What is the appropriate management acutely?

Under the guidance of the endocrinology service, he was treated with IV potassium supplementation (10 mEq/hr x 8 hours) with complete and rapid resolution of his muscle weakness. He was observed in the ED for 15 hours and then discharged home after regaining normal extremity strength, with a serum potassium of 4.1 mmol/L.

Question 3 – What is the appropriate management on discharge?

Our patient was started on anti-thyroid treatment with methimazole 10 mg po TID, as well as propranolol 20 mg po TID. At his one week follow-up he had experienced no further episodes of weakness, and he had gained 3 pounds. His thyroid function tests had improved (TSH <0.015 mU/L, Free T3 11.1 pmol/L, Free T4 37.1 pmol/L), and his serum potassium was 4.4 mmol/L. No changes were made to his medical management.

Thyrotoxic periodic paralysis

Periodic paralysis is a muscle disease that presents with recurrent episodes of flaccid paralysis. Graves’ disease is the most common underlying etiology, however, any cause of hyperthyroidism can be associated with TPP, including exogenous levothyroxine administration.Reference Pothiwala and Levine 1 , Reference Vijayakumar, Ashwath and Thimmappa 2 TPP most commonly effects Asian and Polynesian populations, with the majority of cases occurring in young males.Reference Pothiwala and Levine 1 - Reference Hsieh, Lyu and Chang 4

Presentation

TPP presents with sudden attacks of painless generalized weakness. Attacks most commonly last several hours, but can persist for days. Patients may have multiple attacks per week, or alternatively be symptom-free for months.Reference Hsieh, Lyu and Chang 4 - Reference Venance, Cannon and Fialho 7 The weakness preferentially affects the girdle muscles of the lower extremities; one typically finds decreased muscle tone, hyporeflexia. Tachycardia can be a sentinel finding.Reference Hsieh, Lyu and Chang 4 , Reference Pompeo, Nepa and Maddestra 5 Rarely, severe arrhythmias and respiratory muscle weakness necessitating mechanical ventilation have been documented.Reference Pompeo, Nepa and Maddestra 5 Potassium levels are variable during these attacks, with reported values as low as 1.1 mmol/L (mean ~2.1 mmol/L). Lower potassium levels are associated with increased severity of clinical weakness.Reference Pompeo, Nepa and Maddestra 5 , Reference Shiang, Cheng and Tsai 8 , Reference Li, Yang and Zhao 9

Attacks most commonly occur after large carbohydrate meals, strenuous physical activity, or stress, however, there may be no apparent precipitant. Though cold exposure is reported as a potential trigger, attacks occur more frequently in the summer.Reference Pothiwala and Levine 1 , Reference Hsieh, Lyu and Chang 4 , Reference Ober 10 , Reference Yu, Tseng and Chuang 11

Pathophysiology

Increased Na-K-ATPase activity seen with hyperthyroidism can drive potassium intracellularly. This is thought to hyperpolarize the muscle membrane, leaving the fibers inexcitable. Indirect adrenergic stimulation also increases Na-K-ATPase activity, the probable explanation for the benefit seen with beta blockers. Insulin and testosterone can also stimulate the ATP activity.Reference Chan, Shinde and Chow 12 - Reference Guerra, Rodriguez del Castillo and Battaner 14 Finally, a loss of function mutation in the potassium channel Kir2.6 is also thought to have a role.Reference Vijayakumar, Ashwath and Thimmappa 2

Management

A differential diagnosis is listed in Table 2.Reference Pothiwala and Levine 1 , Reference Vijayakumar, Ashwath and Thimmappa 2 , Reference Pompeo, Nepa and Maddestra 5 , Reference Shayne and Hart 15 Recommended acute medical treatment includes potassium supplementation.Reference Pothiwala and Levine 1 , Reference Vijayakumar, Ashwath and Thimmappa 2 , Reference Pompeo, Nepa and Maddestra 5 This has been shown to result in more rapid improvement in muscle strength, particularly when given intravenously.Reference Pompeo, Nepa and Maddestra 5 , Reference Shiang, Cheng and Tsai 8 , Reference Cesur, Bayram and Temel 16 The minimal required dose of potassium replacement is unknown, but most sources report administering 10–20 mEq per hour, with total replacement in the acute phase ranging from 40–200 mEq. Cardiac monitoring is important during treatment, as rebound hyperkalemia occurs in over 40% of cases and can potentially be fatal.Reference Vijayakumar, Ashwath and Thimmappa 2 , Reference Pompeo, Nepa and Maddestra 5 , Reference Lu, Hsu and Chiu 17 A nonselective beta blocker like propranolol can reverse muscle weakness. Propranolol can be used in patients who are unresponsive to treatment with potassium, though rebound hyperkalemia can still occur with this treatment strategy. Propranolol 3 mg/kg orally or 1 mg IV repeated Q10 minutes (maximum 3 mg) has been reported to be effective.Reference Shayne and Hart 15 , Reference Lin and Lin 18 - Reference Birkhahn, Gaeta and Melniker 20

Table 2

Differential Diagnosis of Acute Weakness

While potassium replacement is important in the acute phase, management of patients’ hyperthyroidism is also necessary to prevent further attacks. Prior to achieving a euthyroid state, temporizing doses of propranolol ranging from 20–80 mg po Q6–8 h have been shown to reduce the frequency and severity of attacks.Reference Vijayakumar, Ashwath and Thimmappa 2 , Reference Pompeo, Nepa and Maddestra 5 , Reference Shayne and Hart 15 , Reference Conway, Seibel and Eaton 21 Susceptible patients should avoid potential triggers as described earlier.Reference Vijayakumar, Ashwath and Thimmappa 2

Competing interests: None declared.

References

1. Pothiwala, P, Levine, SN. Analytic review: thyrotoxic periodic paralysis: a review. J Intensive Care Med 2010;25(2):71-77.Google Scholar
2. Vijayakumar, A, Ashwath, G, Thimmappa, D. Thyrotoxic periodic paralysis: clinical challenges. J Thyroid Res 2014;2014:649502.CrossRefGoogle ScholarPubMed
3. Ko, GT, Chow, CC, Yeung, VT, et al. Thyrotoxic periodic paralysis in a Chinese population. QJM 1996;89(6):463-468.Google Scholar
4. Hsieh, MJ, Lyu, RK, Chang, WN, et al. Hypokalemic thyrotoxic periodic paralysis: clinical characteristics and predictors of recurrent paralytic attacks. Eur J Neurol 2008;15(6):559-564.Google Scholar
5. Pompeo, A, Nepa, A, Maddestra, M, et al. Thyrotoxic hypokalemic periodic paralysis: An overlooked pathology in western countries. Eur J Intern Med 2007;18(5):380-390.Google Scholar
6. Fontaine, B, Lapie, P, Plassart, E, et al. Periodic paralysis and voltage-gated ion channels. Kidney Int 1996;49(1):9-18.Google Scholar
7. Venance, SL, Cannon, SC, Fialho, D, et al. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain 2006;129(Pt 1):8-17.CrossRefGoogle ScholarPubMed
8. Shiang, JC, Cheng, CJ, Tsai, MK, et al. Therapeutic analysis in Chinese patients with thyrotoxic periodic paralysis over 6 years. Eur J Endocrinol 2009;161(6):911-916.Google Scholar
9. Li, J, Yang, XB, Zhao, Y. Thyrotoxic periodic paralysis in the Chinese population: clinical features in 45 cases. Exp Clin Endocrinol Diabetes 2010;118(1):22-26.Google Scholar
10. Ober, KP. Thyrotoxic periodic paralysis in the United States. Report of 7 cases and review of the literature. Medicine 1992;71(3):109-120.Google Scholar
11. Yu, TS, Tseng, CF, Chuang, YY, et al. Potassium chloride supplementation alone may not improve hypokalemia in thyrotoxic hypokalemic periodic paralysis. J Emerg Med 2007;32(3):263-265.Google Scholar
12. Chan, A, Shinde, R, Chow, CC, et al. Hyperinsulinaemia and Na+, K+-ATPase activity in thyrotoxic periodic paralysis. Clin Endocrinol 1994;41(2):213-216.Google Scholar
13. Kurihara, K, Maruyama, S, Hosoi, K, et al. Regulation of Na+,K+-ATPase in submandibular glands of hypophysectomized male mice by steroid and thyroid hormones. J Histochem Cytochem 1996;44(7):703-711.CrossRefGoogle ScholarPubMed
14. Guerra, M, Rodriguez del Castillo, A, Battaner, E, et al. Androgens stimulate preoptic area Na+, K+-ATPase activity in male rats. Neurosci Lett 1987;78(1):97-100.Google Scholar
15. Shayne, P, Hart, A. Thyrotoxic periodic paralysis terminated with intravenous propranolol. Ann Emerg Med 1994;24(4):736-740.Google Scholar
16. Cesur, M, Bayram, F, Temel, MA, et al. Thyrotoxic hypokalaemic periodic paralysis in a Turkish population: three new case reports and analysis of the case series. Clin Endocrinol 2008;68(1):143-152.CrossRefGoogle Scholar
17. Lu, KC, Hsu, YJ, Chiu, JS, et al. Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis. Am J Emerg Med 2004;22(7):544-547.Google Scholar
18. Lin, SH, Lin, YF. Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis. Am J Kidney Dis 2001;37(3):620-623.Google Scholar
19. Tassone, H, Moulin, A, Henderson, SO. The pitfalls of potassium replacement in thyrotoxic periodic paralysis: a case report and review of the literature. J Emerg Med 2004;26(2):157-161.Google Scholar
20. Birkhahn, RH, Gaeta, TJ, Melniker, L. Thyrotoxic periodic paralysis and intravenous propranolol in the emergency setting. J Emerg Med 2000;18(2):199-202.Google Scholar
21. Conway, MJ, Seibel, JA, Eaton, P. Thyrotoxicosis and periodic paralysis: improvement with beta blockade. Ann Intern Med 1974;81(3):332-336.Google Scholar
Figure 0

Table 1 Laboratory Investigations

Figure 1

Table 2 Differential Diagnosis of Acute Weakness