KM Bhargav1, V Sai Krishna Mohan2, N Mounika1, M Haneesha1, P Seelabanu1, Alladi Mohan1
1 Department of Medicine, Tirupati, Andhra Pradesh, India
2 Department of Nuclear Medicine, Tirupati, Andhra Pradesh, India
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|Date of Submission||30-Oct-2020|
|Date of Acceptance||25-May-2021|
|Date of Web Publication||13-Jan-2022|
A 39 -year-old male, with primary hyperthyroidism for the last-3 years, for which he was not receiving any treatment, presented with complaints of sudden onset weakness in all four limbs for one day. Weakness was more in the lower limbs; and was not associated with sweating or related to a carbohydrate-rich diet. Family history, drug- history was unremarkable. On physical examination, he was anxious; exophthalmos was evident. Resting pulse rate was 112/min; rest of the general physical examination was normal. Systemic examination revealed complete absence of movement in lower limbs power 0/5 [Medical research Council (MRC) grading], but he was able to move his upper limbs against gravity 3/5 (MRC grading). Deep tendon reflexes were absent. Rest of the neurological and other systems examination were unremarkable. Laboratory testing showed hypokalemia (serum potassium 2.6 mEq/L ); thyroid profile revealed TSH 0.01 mIU/L, T3 2.0ng/ml, free T4 3.3 ng/mL. A possible diagnosis of thyrotoxic periodic paralysis was considered; he was treated with intravenous correction of potassium and was started on carbimazole and propranolol . On the next 48 hours, power in all the limbs became normal and deep tendon reflexes were normally elicitable. He was asymptomatic by the third day and was discharged in a stable condition with advice to follow-up in Medicine out-patient department.Thyrotoxic paralysis is a benign condition if it is diagnosed early and treated promptly. Though it is a rare condition, it requires special mention because of its life-threatening complications. The diagnosis at initial presentation is often delayed because of the subtleness of clinical features of thyrotoxicosis.
Keywords: Hyperthyroidism, hypokalaemia, periodic paralysis
| Introduction|| |
Thyrotoxic periodic paralysis (TPP) is a curable cause of hypokalaemia periodic paralysis with rapid response to treatment and without any residual weakness. Although clinical features are specific and diagnosis can be made out on clinical features alone, subtleness of clinical features makes it easily overlooked. TPP is most common in Asian men with an incidence of 2% due to thyrotoxicosis of any cause. It is easily misdiagnosed as familial periodic paralysis which has similar neuromuscular presentation. Early diagnosis of this condition is not only essential in preventing respiratory paralysis but also in preventing rebound hyperkalaemia. Here, we report a case of TPP.
| Case Report|| |
A 39-year-old male diagnosed to have primary hyperthyroidism 3 years ago, for which he was not receiving any treatment, presented with acute onset ascending paralysis of all four limbs. On general examination, the patient was anxious; exophthalmos was evident and no goitre was seen. Resting pulse rate was 112/min, single breath count was 18 at that time; rest of the general physical examination was normal. Systemic examination revealed power of Grade 0/5 in both the lower limbs and Grade 3/5 in both the upper limbs. Deep tendon reflexes were diminished. Plantars were flexor bilaterally. The rest of the neurological and other systems examination were unremarkable. On further investigations, serum potassium: 2.6 mEq/L; thyroid profile revealed thyroid stimulating hormone 0.01 mIU/L, triiodothyronine (T3) 2.9 ng/mL and thyroxine (T4) 185 ng/mL, urine potassium per gram of creatinine was 11 mM/g. Transtubular potassium gradient suggested no urinary loss. Arterial blood gas analysis was within normal limits. Electrocardiogram showed ST depression and T wave flattening. Thyroid scan (99mTc pertechnetate) showing homogenously increased radiotracer uptake in enlarged thyroid gland suggestive of Graves' disease [Figure 1]. Serum phosphate and magnesium are within normal limits. The patient was started on antithyroid drugs oral carbimazole and beta blocker along with potassium supplementation. His power improved to normal within 48 h of admission and was discharged.
|Figure 1: 99mTechnetium pertechnetate scan. Initial flow images show increased vascular flow in both lobes of thyroid gland (a). Static images obtained 20 min later shows homogenously increased radiotracer concentration in both lobes of enlarged thyroid with faint uptake from medial aspect of left lobe suggestive of pyramidal lobe (b)|
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| Discussion|| |
Thyrotoxic hypokalaemic paralysis is one of the acquired causes of hypokalaemia. The majority of TPP is seen in hyperthyroidism due to Graves' disease, however, toxic adenoma, thyroiditis and toxic multinodular goitre have been associated with TPP., Rarely intake of nutraceuticals for weight loss containing T3 can result in TPP. In contrast to other thyroid diseases, which are common in women, this is common in Asian men. Our patient has Graves' disease which lead to TPP. Cold, stress and high carbohydrate meal may precipitate weakness and most of the attacks occur in early morning. Skeletal muscle is the largest pool of total body potassium (K+) stores and it plays an important role in extracellular K+ homeostasis. In the skeletal muscle, the sodium-potassium adenosine triphosphatase (Na+–K+ ATPase) and K+ channels, inward rectifying K+ (Kir) and delayed rectifying K+ channels provide the mainstay for inward and outward movement of K+ . Role of Na+–K+ ATPase in TPP is supported by increased activity in thyrotoxicosis. Thyroid hormone stimulates Na+–K+ ATPase in skeletal muscle by genomic mechanism. There is diurnal variation in potassium movement that is nocturnal potassium influx into skeletal muscle that explains the tendency for TPP to occur at night. Potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) gene has been reported to affect incidence of TPP. It also increases beta adrenergic activity that in turn increases pump activity by increasing cyclic adenosine monophosphate (AMP). Genetic mutations in Kir2.6 channel causes loss of function of Kir2.6 which results in increased activity of Na+–K+ ATPase triggering hypokalaemia. It leads to paradoxical depolarisation with consequent inactivation of Na+ channel and muscle paralysis. Hence, it is must to look for clinical symptoms and thyroid function in a case of weakness of limbs secondary to hypokalaemia, apart from renal and other endocrine abnormalities. In familial periodic paralysis, which is close differential to TPP, the intracellular shift of potassium is Na+-K+ ATPase independent and it improves with non-aldosterone mineralocorticoids. The presence of hypokalaemia and elevated levels of T3 and T4 in a setting of sudden onset non-painful quadriplegia without family history points towards TTP. Absent family history cannot rule out FPP. TPP and FPP must be differentiated, as treatment varies. Potassium supplementation will not help in TTP and acetazolamide may even worsen it. Management of TPP involves immediate K+ correction to reverse the paralysis followed by measures to prevent future attacks by creating a euthyroid state. It must be appreciated that patients with TPP do not have a total body deficiency of potassium. Hence, close attention must be given during potassium replacement to prevent cardiac arrhythmias and to reverse muscle weakness as overly aggressive treatment can result in hyperkalaemia. Risk of hyperkalaemia is less when the total administration of potassium chloride is <50 mMol. Reduction of sympathetic activity with high dose non-selective beta-blocker is highly effective., Hypomagnesaemia and hypocalcium are also frequently evident along with hypokalaemia. Urinary calcium levels are high due to increased filtration and decreased reabsorption, and urine phosphate excretion is decreased. Urine calcium/phosphate ratio of >1.4 detected TPP with a sensitivity of 100% and specificity of 96%. Our case highlights the importance of considering thyrotoxicosis in the differential diagnosis of patients presenting with acute onset quadriparesis.
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Conflicts of interest
Alladi Mohan is an Editor of Journal of Clinical and Scientific Research. The other authors are faculty members/residents of Sri Venkateswara Institute of Medical sciences, Tirupati, of which Journal of Clinical and Scientific Research is the official Publication. The article was subject to the journal's standard procedures, with peer review handled independently of these faculty and their research groups.
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Professor (Senior Grade and Head), Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, Andhra Pradesh
Source of Support: None, Conflict of Interest: None