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ORIGINAL ARTICLE
Year : 2020  |  Volume : 151  |  Issue : 1  |  Page : 42-46

Thyrotoxic periodic paralysis: A retrospective, observational study from India


1 Department of Endocrinology, Command Hospital, Lucknow, Uttar Pradesh, India
2 Department of Endocrinology, Command Hospital, Kolkata, West Bengal &, India
3 Department of Endocrinology, Army Hospital (R & R), New Delhi, India

Date of Submission15-Feb-2018
Date of Web Publication24-Feb-2020

Correspondence Address:
Dr Yogesh Kumar
Department of Endocrinology, Command Hospital, Kolkata 700 027, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmr.IJMR_335_18

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   Abstract 

Background & objectives: Thyrotoxic periodic paralysis (TPP) is an endocrine emergency presenting with acute-onset flaccid paralysis in a patient having thyrotoxicosis accompanied by hypokalaemia. This study was conducted to evaluate the clinical profile of patients with TPP presenting to three centres in India.
Methods: This retrospective, observational study was conducted at three tertiary care Armed Forces medical centres, located at Lucknow, Kolkata and Delhi. The history, clinical features, treatment details and outcomes were evaluated.
Results: Of the 244 patients with thyrotoxicosis, 15 were diagnosed with TPP and included in the study. These 15 patients (14 male and 1 female) had 32 episodes of TPP which were analyzed. The mean age was 30.2±6.2 yr (range: 21-39), and overt thyrotoxicosis was seen in all patients except one who had subclinical hyperthyroidism. Graves' disease was the most common cause of thyrotoxicosis (13/15) and the remaining two patients had subacute thyroiditis and gestational thyrotoxicosis. Hypokalaemia (serum potassium <3.5 mmol/l) was seen in 12 patients, and the mean serum potassium was 3.2±0.9 mmol/l (range: 2.1-4.9). All patients had flaccid weakness, predominantly involving the lower limb with no bulbar, respiratory or cranial nerve involvement. The average duration of paralysis was 10.6±5.7 h (range: 3-28 h).
Interpretation & conclusions: Our study demonstrated an early age of presentation and presence of clinical and biochemical thyrotoxicosis in majority of patients with TPP. Hypokalaemia may not always be evident in patients with TPP.

Keywords: Channelopathies - hypokalaemia - paralysis - periodic palsy - thyroid hormones - thyrotoxicosis - TPP


How to cite this article:
Verma V, Kumar Y, Kotwal N, Upreti V, Hari Kumar K, Singh Y, Menon AS. Thyrotoxic periodic paralysis: A retrospective, observational study from India. Indian J Med Res 2020;151:42-6

How to cite this URL:
Verma V, Kumar Y, Kotwal N, Upreti V, Hari Kumar K, Singh Y, Menon AS. Thyrotoxic periodic paralysis: A retrospective, observational study from India. Indian J Med Res [serial online] 2020 [cited 2020 Aug 13];151:42-6. Available from: http://www.ijmr.org.in/text.asp?2020/151/1/42/279141

Thyrotoxic periodic paralysis (TPP) is an endocrine emergency presenting with acute-onset flaccid paralysis in a patient with thyrotoxicosis. This is often accompanied by hypokalaemia, and the attacks resolve on the treatment of thyrotoxicosis. TPP is the most common form of acquired periodic paralysis, and the disease is more common in the Asian ethnicity[1],[2]. Early diagnosis and prompt treatment of TPP prevent life-threatening complications of this curable disorder[1],[3]. The disease has an atypical presentation and requires a high index of clinical suspicion for the diagnosis. TPP is a subcategory of patients presenting with hypokalaemic periodic paralysis (HPP)[4],[5] and the diagnosis is difficult in patients without overt thyrotoxicosis and a fraction of patients are normokalemic[6].

Previous studies[7] have suggested that these patients are often misdiagnosed as idiopathic HPP (IHPP) or familial periodic paralysis (FPP). FPP is an autosomal dominant disorder due to a mutation in the gene coding for calcium channel on chromosome 1. Although hyperthyroidism is common in females, TPP has shown male preponderance in previous studies[3]. Kalita et al[8] have published a series of 52 patients with HPP, of whom TPP was seen in only nine patients. This study was conducted to review the clinical profile of patients with TPP presenting to three centres of the Armed Forces hospitals and identify the differences in these patients.


   Material & Methods Top


This retrospective study was conducted at three tertiary care endocrine centres of Armed Forces located at Lucknow, Kolkata and New Delhi, India. All patients with a diagnosis of TPP presented to any of the three centres between January 2012 and June 2017 were included. Patient data were obtained by computerized hospital records, clinical notes and interview of patients attending the outpatient departments or admitted to the hospitals. A total of 244 (112 from New Delhi, 81 from Lucknow and 51 from Kolkata centres) thyrotoxicosis patients were evaluated, of whom only 15 (9 from New Delhi, 4 from Lucknow and 2 from Kolkata centres) patients had TPP, as shown in the [Figure 1]. Patients with incomplete clinical data and those using amiodarone or any other drugs that could affect the thyroid function, were excluded. The patients were divided into two groups, group 1 (TPP) and group 2 (thyrotoxicosis without TPP). The study protocol was approved by the Ethics Committee of the three centres.
Figure 1: Flow diagram of the study. TPP, thyrotoxic periodic paralysis.

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Study measures: Details of history including any precipitating factors were noted from the available data and medical records. Clinical and systemic findings at the time of presentation were recorded. Thyroid function and biochemical parameters at the time of presentation were reviewed. The final diagnosis, treatment history and end outcome were also noted. All patients with clinical and biochemical thyrotoxicosis were managed as per the guidelines laid down by the American Thyroid Association/American Association of Clinical Endocrinologists[9],[10].

Study definitions: TPP was defined based on the presentation with acute flaccid paralysis, intermittent nature of the paralysis as manifested by spontaneous recovery or recovery with intervention, presence of thyrotoxicosis as per the biochemical criteria with elevated thyroid hormones and suppressed thyroid-stimulating hormone (TSH) and absence of other known causes of acute quadriparesis including myasthenia, Guillain-Barre syndrome, myelopathy, snakebite and botulism[3]. Graves' disease was diagnosed in the presence of clinical (hypermetabolic symptoms and eye signs), biochemical (elevated T3, T4 and suppressed TSH) and Technetium-99m pertechnetate scan (increased uptake) findings. Subacute thyroiditis (SAT) was diagnosed with similar clinical and biochemical findings of thyrotoxicosis along with reduced uptake in the Technetium-99m pertechnetate scan.

Statistical analysis: The continuous variables are presented as mean±SD and range and categorical variables using the frequency and percentages. The comparison between the two groups was done using the unpaired t test and Chi-square test. Data were analyzed using the Excel 2010 program (Microsoft®, Redmond, Washington, USA).


   Results Top


The comparison of features between the patients with thyrotoxicosis with and without TPP is given in [Table 1]. Briefly, patients without TPP (group 2) were older, had higher T4 (thyroxine) level and the most common cause remained Graves' disease. The clinical and demographic data of the patients with TPP (group 1) are given in [Table 2]. Briefly, precipitating factors could be identified in 24 (75%) of the 32 episodes, and majority had clinically overt thyrotoxicosis features and had Graves' disease as the aetiology for thyrotoxicosis. Overall, 32 attacks of TPP were observed with an average of 2.1±1.2 (range: 1-5) attacks per patient. The muscular weakness was variable, and none of the patients had bulbar, facial or ocular weakness. Myalgia preceded the attack of TPP in 14 (44%) of the 32 attacks. Myalgia was common in patients with exercise and carbohydrate meal (10 vs. 4) as precipitating factors, respectively.
Table 1: Clinical comparison between the patients with and without thyrotoxic periodic paralysis

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Table 2: Characteristics of the patients with thyrotoxic periodic paralysis (TPP)

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Clinically, overt thyrotoxicosis was present in 14 patients and one had subclinical hyperthyroidism. Five patients were already diagnosed with thyrotoxicosis (Graves' disease) for a mean period of 8.4 months (range: 4-14 months) at the time of TPP. T4 was raised in 14 (93%) patients with a mean of 20.5±4.5 μg/dl (range: 11.1-30.2 μg/dl). Of the 32 episodes of paralysis, serum potassium reports were available for 17 (53%) episodes. The mean potassium levels were 3.2±0.9 mmol/l (range: 2.1-4.9 mmol/l. In three patients, hypokalaemia was not documented. Phosphorus levels were reduced in three patients. Of the 32 episodes, data for urine calcium/phosphorus ratio (UCPR) were available for only four episodes and the mean UCPR was 2.6±0.6 (range: 1.9-3.2). Alkaline phosphatase was raised in 13 (87%) patients with a mean of 222.7±66 IU/ml (range: 114-316 IU/ml). Two patients revealed a myopathic pattern during the attack on electromyography, which was resolved on correction of thyrotoxicosis.

The diagnosis of Graves' disease was confirmed in 13 (87%) patients and these were treated with antithyroid drugs and 11 amongst them were radio-ablated. The patient with SAT was managed with analgesics and the patient with gestational transient thyrotoxicosis was treated with oral propranolol. The average time to resolution of the periodic paralysis was 10.6±5.7 h (range: 3-28 h). It was also noted that spontaneous recovery took more time as compared to recovery with intervention (13.2 vs. 7.8 h; P=0.015). One patient with Graves' disease and post-ablative hypothyroidism had a relapse of TPP due to the overdosing of thyroxine replacement. None of the patients had a recurrent attack of TPP after the resolution of thyrotoxicosis during the mean follow up period of 15.4 (range: 2-48) months.


   Discussion Top


The incidence of TPP in individuals of Asian descent is two per cent as compared to 0.8 per cent in non-Asian patients[11],[12]. Our retrospective data showed 6.7 per cent patients with TPP in a group of patients collected at three centres. This could be due to the referral bias associated with the tertiary care centres, where only complicated cases of thyrotoxicosis are referred. TPP was shown to be predominantly affecting males in their second and third decades of life in all the case series[13]. The male-to-female ratio of TPP varies amongst the countries with a reported ratio of 20:1 in Japan, 48:1 in the USA and 4 to 76:1 in China[12],[14],[15]. The predominance of males over females in our study could be explained by the natural profile of the disease being more common in the former[3] and the sample being derived from the armed forces population, where males outnumberd the females.

TPP is usually associated with proximal quadriparesis, and occasionally, patients are reported to have bulbar weakness and respiratory failure[8],[13],[16],[17],[18]. The weakness may be preceded by a prodrome of myalgias in less than half of the patients[19]. The attacks of HPP may be precipitated by high-carbohydrate meal, physical exertion, preceding febrile illness and often on getting up from sleep[20]. In our patients, heavy meal and strenuous exercise were the predominant risk factors. The daily routine in Armed Forces involves a high level of physical activity, which could be the precipitating factor. Chang et al[21] recorded precipitating factors in 34 per cent of their 135 patients. Our study documented a higher percentage (75%) of patients due to the targeted history taking and small sample. A quarter of patients with TPP may not have overt features of hyperthyroidism[11],[22]. The occurrence of TPP does not depend on the severity of coexisting thyrotoxicosis, and thyroid hormone overdosage is rarely known to precipitate an attack of TPP in genetically predisposed individuals[3],[4],[23].

Hypokalaemia is a cardinal feature of TPP and is because of the inward movement of potassium ion across the cell membrane[11],[24]. However, normal or increased potassium is not an uncommon finding in TPP[6],[25]. Normalization of serum potassium precedes the recovery of muscle weakness[26]. Provocative tests to induce hypokalaemia with either insulin or carbohydrate challenge are often dangerous and unreliable and hence not recommended[3],[27]. Serum phosphorus can be low and serum alkaline phosphatase (ALP) is raised in half of the patients with TPP, which may be utilized to differentiate TPP from IHPP. Electromyography (EMG) may show a myopathic pattern during an attack of TPP. EMG studies, muscle biopsy and CSF studies are occasionally required to either refute or corroborate the diagnosis of TPP[3]. TPP is often associated with hypercalciuria and hypophosphaturia. Therefore, spot UCPR (more than 1.7) has emerged as a tool for diagnosing TPP and to differentiate it from IHPP with a 100 per cent sensitivity and a 96 per cent specificity[1],[2].

The treatment of HPP during an attack remains a careful potassium replacement (100-200 mEq) depending on the severity of weakness[13],[28],[29]. Potassium replacement decreases the time to recovery, and rebound hyperkalaemia is seen in about half of the treated attacks[30],[31]. Regular potassium supplementation does not work as a prophylactic for the prevention of the TPP attack. Non-selective beta-blockers may be used to terminate an attack or for prophylaxis of recurrent attacks[13],[28].

Our study was limited by the retrospective design and lack of complete data for all the TPP attacks. The data being derived from the Armed Forces hospitals may not be applicable for the general population.

To conclude, our study showed an early age of presentation of TPP precipitated by a heavy meal or strenuous exercise predominantly in males. The diagnosis is based on the demonstration of thyrotoxicosis and hypokalaemia during an attack of intermittent flaccid paresis. Hypokalaemia may not be mandatory in TPP, and further clinical studies involving a large sample size from India will delineate the role of new diagnostic aids such as spot UCPR.

Financial support & sponsorship: None.

Conflicts of Interest: None.



 
   References Top

1.
Lin SH, Chu P, Cheng CJ, Chu SJ, Hung YJ, Lin YF. Early diagnosis of thyrotoxic periodic paralysis: Spot urine calcium to phosphate ratio. Crit Care Med 2006; 34 : 2984-9.  Back to cited text no. 1
    
2.
Falhammar H, Thorén M, Calissendorff J. Thyrotoxic periodic paralysis: Clinical and molecular aspects. Endocrine 2013; 43 : 274-84.  Back to cited text no. 2
    
3.
Maciel RM, Lindsey SC, Dias da Silva MR. Novel etiopathophysiological aspects of thyrotoxic periodic paralysis. Nat Rev Endocrinol 2011; 7 : 657-67.  Back to cited text no. 3
    
4.
Fialho D, Griggs RC, Matthews E. Periodic paralysis. Handb Clin Neurol 2018; 148 : 505-20.  Back to cited text no. 4
    
5.
Salih M, van Kinschot CMJ, Peeters RP, de Herder WW, Duschek EJJ, van der Linden J, et al. Thyrotoxic periodic paralysis: An unusual presentation of hyperthyroidism. Neth J Med 2017; 75 : 315-20.  Back to cited text no. 5
    
6.
Wang PH, Liu KT, Wu YH, Yeh IJ. Periodic paralysis with normokalemia in a patient with hyperthyroidism: A case report. Medicine (Baltimore) 2018; 97 : e13256.  Back to cited text no. 6
    
7.
Vijayakumar A, Ashwath G, Thimmappa D. Thyrotoxic periodic paralysis: clinical challenges. J Thyroid Res 2014; 2014 : 649502.  Back to cited text no. 7
    
8.
Kalita J, Goyal G, Bhoi SK, Chandra S, Misra UK. Comparative study of thyrotoxic periodic paralysis from idiopathic hypokalemic periodic paralysis: An experience from India. Ann Indian Acad Neurol 2012; 15 : 186-90.  Back to cited text no. 8
    
9.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21 : 593-646.  Back to cited text no. 9
    
10.
Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016; 26 : 1343-421.  Back to cited text no. 10
    
11.
Kelley DE, Gharib H, Kennedy FP, Duda RJ Jr., McManis PG. Thyrotoxic periodic paralysis. Report of 10 cases and review of electromyographic findings. Arch Intern Med 1989; 149 : 2597-600.  Back to cited text no. 11
    
12.
Ober KP. Thyrotoxic periodic paralysis in the United States. Report of 7 cases and review of the literature. Medicine (Baltimore) 1992; 71 : 109-20.  Back to cited text no. 12
    
13.
Chaudhry MA, Wayangankar S. Thyrotoxic periodic paralysis: A concise review of the literature. Curr Rheumatol Rev 2016; 12 : 190-4.  Back to cited text no. 13
    
14.
Okinaka S, Shizume K, Iino S, Watanabe A, Irie M, Noguchi A, et al. The Association of periodic paralysis and hyperthyroidism in Japan. J Clin Endocrinol Metab 1957; 17 : 1454-9.  Back to cited text no. 14
    
15.
McFadzean AJ, Yeung R. Periodic paralysis complicating thyrotoxicosis in Chinese. Br Med J 1967; 1 : 451-5.  Back to cited text no. 15
    
16.
Bertola G, Ausenda C, Bocchia M, Grassi F, Ciani M, Sassi L. Bulbar paralysis and flaccid tetraparesis in thyrotoxicosis. Recenti Prog Med 2002; 93 : 169-71.  Back to cited text no. 16
    
17.
Liu YC, Tsai WS, Chau T, Lin SH. Acute hypercapnic respiratory failure due to thyrotoxic periodic paralysis. Am J Med Sci 2004; 327 : 264-7.  Back to cited text no. 17
    
18.
Mathew B, Devasia AJ, Ayyar V, Thyagaraj V, Francis GA. Thyrotoxicosis presenting as acute bulbar palsy. J Assoc Physicians India 2011; 59 : 386-7.  Back to cited text no. 18
    
19.
Hsieh MJ, Lyu RK, Chang WN, Chang KH, Chen CM, Chang HS, et al. Hypokalemic thyrotoxic periodic paralysis: Clinical characteristics and predictors of recurrent paralytic attacks. Eur J Neurol 2008; 15 :559-64.  Back to cited text no. 19
    
20.
Charness ME. Clinical conferences at The Johns Hopkins hospital. Hypokalemic periodic paralysis. Johns Hopkins Med J 1978; 143 : 148-53.  Back to cited text no. 20
    
21.
Chang CC, Cheng CJ, Sung CC, Chiueh TS, Lee CH, Chau T, et al. A 10-year analysis of thyrotoxic periodic paralysis in 135 patients: Focus on symptomatology and precipitants. Eur J Endocrinol 2013; 169 : 529-36.  Back to cited text no. 21
    
22.
Ko GT, Chow CC, Yeung VT, Chan HH, Li JK, Cockram CS. Thyrotoxic periodic paralysis in a Chinese population. QJM 1996; 89 : 463-8.  Back to cited text no. 22
    
23.
Cheema MA, Zain MA, Cheema K, Ullah W. Thyroxine-induced periodic paralysis: A rare complication of nutritional supplements. BMJ Case Rep 2018; 11. pii: e227946.  Back to cited text no. 23
    
24.
Shishiba Y, Shizume K, Sakuma M, Yamauchi H, Nakao K, Okinaka S. Studies on electrolyte metabolism in idiopathic and thyrotoxic periodic paralysis. 3. Intra- and extracellular concentrations of potassium and sodium in muscle and their changes during induced attacks of paralysis. Metabolism 1966; 15 : 153-62.  Back to cited text no. 24
    
25.
Manoukian MA, Foote JA, Crapo LM. Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes. Arch Intern Med 1999; 159 : 601-6.  Back to cited text no. 25
    
26.
Gaul C, Leonhardt G, Spens A, Schneyer U, Zierz S. Hypokalemic thyrotoxic periodic paralysis (HTPP). Rare differential diagnosis in case of acute tetraparesis in Europe. Med Klin (Munich) 2005; 100 : 583-6.  Back to cited text no. 26
    
27.
Levitt JO. Practical aspects in the management of hypokalemic periodic paralysis. J Transl Med 2008; 6 : 18.  Back to cited text no. 27
    
28.
Correia M, Darocki M, Hirashima ET. Changing Management Guidelines in Thyrotoxic Hypokalemic Periodic Paralysis. J Emerg Med 2018; 55 : 252-6.  Back to cited text no. 28
    
29.
Shiang JC, Cheng CJ, Tsai MK, Hung YJ, Hsu YJ, Yang SS, et al. Therapeutic analysis in Chinese patients with thyrotoxic periodic paralysis over 6 years. Eur J Endocrinol 2009; 161 : 911-6.  Back to cited text no. 29
    
30.
Lu KC, Hsu YJ, Chiu JS, Hsu YD, Lin SH. Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis. Am J Emerg Med 2004; 22 : 544-7.  Back to cited text no. 30
    
31.
Chandramohan G, Dineshkumar T, Arul R, Seenivasan M, Dhanapriya J, Sakthirajan R, et al. Spectrum of hypokalemic paralysis from a tertiary care center in India. Indian J Nephrol 2018; 28 : 365-9.  Back to cited text no. 31
    


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