Abstract
Thyrotoxic Periodic Paralysis (TPP) is an emergency associated with flaccid paralysis in which the paralysis is reversible with prompt potassium replacement and the attacks are terminated when hyperthyroidism is cured. Timely diagnosis and treatment are therefore prudent. While managing patients with flaccid paralysis, physicians should be aware of TPP as potential etiology and investigate history to identify the triggering factors and provide timely and cautious treatment with replacement of potassium, further addressing permanent approaches to treating thyrotoxicosis to prevent future recurrences of TPP. We report a clinical scenario of a patient who experienced TPP.22-year-old male, laying down at home at around 1:45pm developed sudden onset bilateral lower extremity weakness and was unable to stand up. His weakness was associated with thigh pain with exertion. He was eventually able to walk a few steps, but then fell onto his knees. He reported having a carbohydrate rich lunch at noon. Notably, patient underwent surgery under general anesthesia for a deviated nasal septum the day before. His neurological examination was remarkable for giveaway proximal lower extremity weakness involving only select muscle groups. Examination and CT/CTA of head and neck findings was not consistent with acute stroke. Myopathy secondary to electrolyte imbalance, drug/toxin, infection, or inflammatory disorders, myelopathy and myasthenia gravis were considered in the differential. Labs revealed suppressed TSH <0.01uIU/mL, elevated FT4 of 6ng/dL and low serum potassium of 2.6mmol/L. CT scan of the neck revealed enlarged thyroid gland and thymic enlargement. Patient was given intravenous bolus of potassium chloride 20 mEq and serum potassium normalized in 4 hours to 3.8mmol/L. His lower extremity weakness resolved within 3hours of potassium replacement. The next day his serum potassium was 5.2mmol/L. His thyroid stimulating immunoglobulin index was elevated at 1.4 (normal <1.3). He was started on propranolol, methimazole and advised to return to the endocrinology clinic to discuss permanent treatment options for hyperthyroidism to prevent TPP. Reviewing his prior medical history, he was diagnosed with Graves’ disease 5 months prior to the emergency room evaluation and was started on methimazole. He took methimazole for 2 months and did not return to follow up until the occurrence of TPP. He did not experience symptoms of hyperthyroidism in the interim. Discussion: TPP is a rare disorder with a prevalence of 0.1-0.2% in North America. TPP commonly affects Asian and Latin Americans males. The episodes of TPP are influenced by genetic, environmental, and ethnic factors. Common environmental triggers include carbohydrate rich meals, rest after intense physical exertion, fever, infection, trauma, emotional stress, and smoking. Thymic hyperplasia has also been reported to be associated with hypokalemic periodic paralysis. Clinical Presentation: The motor weakness tends to affect proximal lower extremities as noted in our patient’s presentation and is usually associated with hyporeflexia and is painless. Cardiac arrhythmias due to hypokalemia are rare, though ventricular fibrillation have been reported, and respiratory failure requiring mechanical ventilation is a possibility. Pathophysiology: TPP has been thought to be a channelopathy
associated with increased Na+–K+ ATPase activity and loss of function mutation of the Kir 2.6 potassium efflux channel resulting in intracellular pooling of potassium and transient hypokalemia. The attacks are stimulated by thyroid hormone excess and/or hyperadrenergic activity and hyperinsulinemia, most commonly due to carbohydrate load or intravenous fluids containing dextrose. Treatment should include:1.Potassium supplementation to reverse paralysis and prevent life threatening cardiac arrhythmias. Care must be taken to not over replace potassium, as it could result in hyperkalemia when potassium channels revert to functioning normally.2.Propranolol, a non-selective betablocker works by blocking the thyroid hormone mediated adrenergic overstimulation of the Na-K ATPase channel, there by limiting the intracellular pooling of potassium.3.Definitive treatment of thyrotoxicosis should be offered. Studies comparing various modalities of treatment of thyrotoxicosis in the setting of TPP indicate permanent treatment with either radioactive iodine or thyroidectomy are often successful in preventing recurrence of TPP, as relapse events are higher in treatment with antithyroid drugs. Caution should be taken to prevent surge of thyroid hormone release following radioactive iodine treatment, as this can trigger TPP. Higher doses of radioactive iodine might be required to render hypothyroidism and prevent TPP recurrences. There is one case report of hypokalemic periodic paralysis associated with thymic hyperplasia that was treated with thymectomy. Our patient had multiple triggers leading to periodic paralysis, including a prior untreated Graves’ disease due to non-adherence to treatment during COVID-19 pandemic, general anesthesia for nasal septal surgery the day before presenting with TPP, having a carbohydrate rich meal one hour before the episode, and thymic enlargement on neck CT scan. He responded well to potassium replacement, and propranolol. He was started on methimazole and offered permanent treatment options to address hyperthyroidism. References: 1.K Shizume1, Y Shishiba, K Kuma, S Noguchi, J Tajiri, K Ito, J Y Noh. Comparison of the incidence of association of periodic paralysis and hyperthyroidism in Japan in 1957 and 1991. Endocrinol Jpn1992 Jun;39(3):315-8, doi: 10.1507/endocrj1954.39.315 2. R C Griggs, J Resnick, W K Engel. Intravenous treatment of hypokalemic periodic paralysis. Arch Neurol 1983 Sep;40(9):539-40.3. Maciel, R., Lindsey, S. & Dias da Silva, M. Novel etiopathophysiological aspects of thyrotoxic periodic paralysis. Nat Rev Endocrinol7, 657–667 (2011). https://doi.org/10.1038/nrendo.2011.58 4. Chang RY, Lang BH, Chan AC, Wong KP. Evaluating the efficacy of primary treatment for graves’ disease complicated by thyrotoxic periodic paralysis. Int J Endocrinol. 2014; 2014:949068 doi:10.1155/2014/949068 5.Yang R, Jurkat-Rott K, Cao J, et al. Hypokalemic Periodic Paralysis Induced by Thymic Hyperplasia and Relieved by Thymectomy. JAMA Neurol. 2013;70(11):1436–1439. doi:10.1001/jamaneurol.2013.3918
Evaluating the Efficacy of Primary Treatment for Graves’ Disease Complicated by Thyrotoxic Periodic Paralysis