Archives of Academic Emergency Medicine. 2021; 9(1): e19 https://doi.org/10.22037/aaem.v9i1.1083 CA S E RE P O RT Thyrotoxic Periodic Paralysis with Thyroid Storm as the First Presentation of Graves’ disease; a Case Report Tejaswee Banavathu1, Swapnil Tripathi1, Pankaj Sukhadiya1, Kamlesh Ahari1, Durga Shankar Meena1∗ Mahendra Kumar Garg1 1. Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur, India. Received: January 2021; Accepted: January 2021; Published online: 17 February 2021 Abstract: Thyrotoxic periodic paralysis is a rare endocrine emergency that manifests as acute onset muscle weakness and hypokalaemia secondary to thyrotoxicosis. It mainly occurs due to rapid and dramatic intracellular shift of potassium resulting in hypokalaemia and acute flaccid paralysis. This condition predominantly affects males of Asian descent, and presentation can range from mild generalized weakness to complete quadriplegia, as seen in our case. We herein report a case of a 40-year-old female, who presented to us with acute onset flaccid quadriple- gia and thyroid storm, which is the first ever manifestation of previously undiagnosed Grave’s disease. Liver abscess was found to be the underlying trigger for thyrotoxic paralysis and thyroid storm. Keywords: Hypokalemic Periodic Paralysis; Thyrotoxicosis; Graves disease; Quadriplegia; Thyroid Crisis Cite this article as: Banavathu T, Tripathi S, Sukhadiya P, Ahari K, Shankar Meena D, Kumar Garg M. Thyrotoxic Periodic Paralysis with Thy- roid Storm as the First Presentation of Graves’ disease; a Case Report. Arch Acad Emerg Med. 2021; 9(1): e19. 1. Introduction Periodic paralysis and thyroid storm are two different man- ifestations of thyrotoxicosis-related medical emergencies, which are life-threatening without prompt diagnosis and treatment (1, 2). Thyrotoxic periodic paralysis (TPP) is the acquired form of hypokalaemic paralysis, which usually oc- curs after the second or third decade of life. The incidence of TPP among the Western and Asian population is around 0.1% and 1.8%, respectively (3). Hypokalaemic paralysis with thyrotoxic crisis, as an initial presenting feature of hyperthy- roidism, is rarely reported in the literature (4). Our case had both of these features on the first hospital visit along with an occult liver abscess, which was the probable trigger for TPP. Diagnosis of TPP is often overlooked, which may have fatal consequences in the form of cardiac arrhythmias and res- piratory paralysis (5). Emergency physicians should have a high index of suspicion of TPP while treating a case of hy- pokalaemic paralysis. ∗Corresponding Author: Durga Shankar Meena; Room no- 134, Medicine OPD Block, Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India, 342005. Email: dsmims14@gmail.com, Tel: +91 9772200453, ORCID: 0000-0001-9524-5278 2. Case presentation A 40-year-old Asian female presented to the emergency de- partment with complaints of high-grade fever associated with palpitation for 7 days, loose stools for 2 days and altered sensorium for the last 1 day. She had a history of episodic right upper quadrant pain and weight loss for the last 1 month. No history of blood in the stool, cough, chest pain, headache, or vomiting could be elicited. She had not had similar episodes in the past. On presentation, she was drowsy with a Glasgow Coma Score (GCS) of E3V3M4, febrile (tem- perature: 100.8◦F), blood pressure of 98/68 mmHg, pulse rate of 160/minutes, and respiratory rate of 24/minutes. General physical examination revealed a thin-built female with pal- lor and acral hypopigmentation (present since birth). Neuro- logical examination showed flaccid paralysis of all limbs with power of 1/5 and diminished reflexes. No signs of meningeal irritation were present. No sensory or cranial nerve deficit was detected. Systolic flow murmur was heard on cardiac auscultation suggestive of hyperdynamic circulation. Rest of the systemic examination was unremarkable. Based on the clinical findings, acute transverse myelitis, Guillain-Barre syndrome (GBS) and periodic paralysis were considered as differential diagnoses of acute flaccid paralysis. Magnetic resonance imaging (MRI) of spine and nerve conduction studies were normal, which ruled out acute transverse myeli- tis and GBS. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem T. Banavathu et al. 2 Arterial blood gas analysis revealed serum potassium of 2.23 mmol/L with normal acid-base status. Other blood investi- gations are tabulated in table 1. Electrocardiogram showed sinus tachycardia with ST segment depression in V3-V6. The initial diagnosis of hypokalaemic paralysis was made, and she was given intravenous potassium supplementation along with intravenous fluids, but her altered sensorium was still unexplained. In addition, computed tomography (CT) of brain and cerebrospinal fluid (CSF) analysis were done, both were found to be normal. On further evaluation, her thyroid function test showed thyroid stimulating hormone (TSH) = 0.0056 mIU/L, T3 = 28.26 pg/ml, T4 = 66.66 ng/ml, TSH Re- ceptor antibody level of 30.27 IU/L, and Anti Thyroperoxi- dase (TPO) of 1433 IU/L (Table 1). Thyroid scan also showed an increased radioactive iodine uptake. The final diagno- sis of Graves’ disease with thyroid storm and thyrotoxic hy- pokalaemia paralysis was made on the basis of clinical fea- tures and blood investigations. Patient was immediately put on propylthiouracil (600 mg loading dose followed by 200 mg, 6 hourly), propranolol (80 mg, 8 hourly), and hydrocortisone (100 mg intravenous, 8 hourly) along with supportive care, which included cold water sponging and antipyretics. On in- vestigating the precipitant of thyroid storm, she was found to have an abscess about 90 ml in segment VI of liver. She underwent needle aspiration of the abscess and received in- travenous antibiotics (metronidazole). Abscess culture was sterile. In addition, blood and urine culture were also per- formed to rule out other potential sources of infection, which were sterile. The patient regained full consciousness on day 3 and a re- peat neurological examination revealed quadriparesis with predominant proximal muscle involvement. On day 3, her potassium level was 3.12 mmol/L which increased to 5.4 mmol/L on day 5 without further potassium supplementa- tion suggesting rebound hyperkalaemia. At day 6 of hospi- talization, her power of bilateral lower limb and upper limb improved and the patient was able to stand with support and feed herself. Hydrocortisone was stopped on day 6 due to the improvement in thyroid storm. Patient was continued on antibiotics in view of liver abscess for 14 days along with antithyroid drugs. On day 14 the patient was discharged in fully oriented state, with improved power of 4/5 in all limbs. The dose of propylthiouracil was further reduced (100 mg, 8 hourly), which was scheduled for tapering based on further clinical improvement. On day 30 of follow-up, repeat thyroid function showed further improvement (Table 1). 3. Discussion Neurological involvement in hyperthyroidism is not uncom- mon and may present with diverse clinical features. Symp- toms may vary from mild features like tremors, chorea, headache, peripheral neuropathy, and hyperthyroid myopa- thy to life-endangering seizures, thyroid storm and thyro- toxic periodic paralysis (6). TPP as the first presenting feature of hyperthyroidism is a rare entity. Another highlight of our report was thyroid storm, which was precipitated by liver ab- scess along with TPP. Thyrotoxic periodic paralysis is a medical emergency, man- ifesting as paraparesis or quadriparesis mainly in the Asian population suffering from hyperthyroidism. It is more com- monly present in young males compared to females with a ratio of approximately 20:1 (7). Clinical features of thyro- toxic periodic paralysis include recurrent attacks of muscle weakness with predominant proximal muscle involvement (8). Episodes may range from prodromes (mild weakness, cramps, stiffness) to complete quadriparesis and respiratory muscle involvement (9). Guillain-Barre syndrome, myas- thenia gravis, transverse myelitis, snake envenomation and hysterical disorder are among the common differential diag- noses of thyrotoxic hypokalaemic paralysis. Unlike GBS, res- piratory involvement is rare in TPP (10). In our patient, the absence of toxin exposure, lack of diurnal variation of weak- ness, and normal neuroimaging and CSF findings ruled out the other possibilities. Proposed pathogenesis behind TPP is related to ion channel defect. Hypokalaemia is due to transcellular shift of potas- sium ion, which is controlled by Na+K+ ATPase pump. The activity of Na+K+ ATPase is mainly influenced by insulin and beta-adrenergic catecholamines. Increased adrenergic state in thyrotoxicosis leads to increased activity of Na+K+ AT- Pase, which causes transcellular shift of potassium resulting in the various manifestations of hypokalaemia (3). Hyper- insulinemic state, stress, infections, high carbohydrate diet, beta-2 adrenergic bronchodilators and strenuous physical activity may also act as TPP precipitants. However, precip- itating factors could not be identified in nearly 34% of the cases (11). Genetic mutations have been found to increase susceptibility to TPP, the most commonly noted mutation is the one affecting the gene that encodes Kir2.6, an inwardly rectifying potassium channel, which is regulated by thyroid hormone (12). Diagnosis involves hypokalaemia with nor- mal acid base balance associated with suppressed TSH and raised T3 and T4 levels. The potassium levels have shown to be correlated with severity of muscle weakness; however, no correlation is seen with T3 and T4 levels (2). Management of TPP includes initial supplementation of potassium along with beta-blockers and achievement of eu- thyroid state using anti-thyroid drugs. Potassium supple- mentation should be gradual and under continuous potas- sium monitoring as total body potassium remains the same, which can cause life-threatening rebound hyperkalaemia af- ter the achievement of euthyroid state. Rebound hyper- kalaemia is reported in around 50% of the cases with TPP This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2021; 9(1): e19 (13). Beta blockers (propranolol) have 2 mechanisms in TPP, the first one is to antagonise the adrenergic stimulation of Na+K+ ATPase and the second one is to decrease the periph- eral conversion of T4 to T3, which is the active form. Another important facet of TPP management is to mitigate the risk of paradoxical hypokalaemia, which can be seen in 25% of the patients, particularly those with late administration of anti- thyroid drugs and beta blockers (13). Our patient also had simultaneous thyroid storm with thyrotoxic periodic paraly- sis. Corticosteroids are useful for thyroid storm management but at the same time could precipitate TPP, which makes it even more difficult to treat. Furthermore, our patient also had a liver abscess, which is an unusual trigger for thyrotoxic crisis and periodic paralysis. Further large-scale studies will be needed to understand the effect of corticosteroids on the course of periodic paralysis. 4. Conclusion Prompt diagnosis and treatment of thyrotoxic periodic paral- ysis is vital to prevent fatal complications like cardiac ar- rhythmias. Thyroid function test should be sought in ev- ery patient presenting to emergency department with hy- pokalaemic paralysis. 5. Declarations 5.1. Source of Funding None. 5.2. Conflict of interest The authors declare that they have no conflict of interest 5.3. Authors’ contributions All the authors meet the standard criteria of authorship based on recommendations of the international committee of med- ical journal editors. 5.4. 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Banavathu et al. 4 Table 1: Laboratory findings of the presented case Laboratory Parameters Patient values Normal Hemoglobin (g/dl) 11.1 12-15 White blood cell count (/µL) 14×103 (4-11) ×103 Serum sodium (mEq/L) 137 135-145 Creatine kinase-MB (U/L) 25 0-24 TSH Receptor Antibody (IU/ml) 30.27 <1.22 Anti TPO antibody (IU/ml) 1433 < 60 Serum calcium (mg/dl) 9.1 8.8-10.6 Serum phosphorus (mg/dl) 3.38 2.5-4.5 Serum magnesium (mg/dl) 1.9 1.5-2.5 Serum anion gap (mmol/L) 8 8-12 Arterial blood gas analysis pH 7.40 7.35-7.45 pCO2 (mmHg) 23 35-45 HCO3 (mmol/L) 19.6 22-28 Natrium (mmol/L) 140 - Potassium (mmol/L) 2.25 - Chloride (mmol/L) 106 - Urinalysis pH 7.5 Urinary Na (mmol/L) 157.1 40-220 Urinary K (mmol/L) 14.47 <20 Urinary Chloride (mmol/L) 121.7 - Pus cells Nil - Red blood cell Nil - Albumin Nil - Serum potassium (mEq/L) On admission 2.23 3.5-5.1 Day 5 5.14 Day 7 4.2 TSH (mIU/L) On admission 0.005 0.3 - 4.0 After 2 weeks 0.016 At 4 weeks 0.1 Free T3 (pg/ml) On admission 28.26 2.2-4.2 After 2 weeks 3.2 At 4 weeks 3.82 Free T4 (ng/dl) On admission 66.66 0.80-1.70 After 2 weeks 3.69 At 4 weeks 1.20 TSH: thyroid stimulating hormone; TPO: Thyroperoxidase; Na: natrium; K: potassium. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Case presentation Discussion Conclusion Declarations References