How low (K⁺)an you go: a case report of thyrotoxic periodic paralysis and concomitant renal tubular acidosis in a young patient successfully treated with electrolyte replacements and antithyroid medications

Introduction

Thyrotoxic periodic paralysis (TPP) is a rare, potentially fatal complication of thyrotoxicosis (1). The condition is part of the periodic paralysis (PP) family of myotonic syndromes (including hypokalemic, hyperkalemic, Anderson syndrome, and thyrotoxic). This family of syndromes is defined by episodes of muscle weakness in the setting of an inherited or acquired muscle channelopathy (2). TPP has been posited to be caused by underlying defects in the sarcolemma Na/K-ATPase and the inward-rectifying potassium channel (K_ir) that are unmasked in thyrotoxicosis, thus making it an acquired form of PP (2,3). TPP presents with intermittent episodes of conscious, flaccid paralysis of the proximal muscles, most commonly of the lower extremities (1). Episodic triggers include carbohydrate-rich food, strenuous exercise, a high-salt diet, stress, and drugs such as diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and laxatives (1). Clinical features of hyperthyroidism can precede the onset of PP by months or years, but have also been noted to occur at the same time or following paralytic symptoms (4,5). Severe hypokalemia can lead to fatal complications such as respiratory muscle paralysis and cardiac arrhythmias.

TPP has been well-documented in Asian populations with an incidence rate of approximately 2% in thyrotoxic patients (6). Its incidence in other parts of the world is unknown but likely lower, with an estimated incidence of 0.1–0.2% in thyrotoxic patients worldwide (1). In Western countries, TPP may be misdiagnosed as familial hypokalemic PP, and there is limited research on its incidence outside of Asian populations (6). Renal tubular acidosis (RTA), a disorder of renal acid-base handling, is an uncommon coexisting condition in TPP. The coexistence of TPP with RTA is exceptionally rare and presents a complex diagnostic and therapeutic challenge. Recognizing and understanding this overlap is crucial for prompt diagnosis, targeted therapy, and prevention of recurrence. This is a case of a Ghanaian patient diagnosed in the Bronx, NY, with TPP along with RTA. We present this case in accordance with the CARE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-152/rc).

Case presentation

A 37-year-old man with no significant past medical history presented to the emergency department with the inability to walk in the setting of acute-on-chronic weakness and multiple falls for the past year. He reported that these episodes of weakness started after a motor vehicle accident one year ago. During this period, the patient reported four episodes of sudden muscle weakness and cramping that self-resolved after 6 hours without any dizziness, lightheadedness, or loss of consciousness. He also reported weight loss, heat intolerance, and diplopia over the past year. His medical, family, and surgical history were noncontributory. The patient’s social history was significant for working at a parking garage, and he did not report any smoking, alcohol, or drug use.

Vitals were notable for a heart rate of 130 beats/minute and a blood pressure of 168/81 mmHg. Physical examination was notable for 1/5 strength in the bilateral hips and knees, 3/5 strength in the bilateral ankles, and 4/5 in the right shoulder, with full strength in the left upper extremity. The Medical Research Council Scale was utilized to evaluate the muscle strength. Tremor was noted upon extension of hands without any dysmetria or pronator drift. The patient had intact sensations in all extremities, as examined by light touch. Thyromegaly was present without palpable nodules, and a bruit was audible on auscultation.

Laboratory investigation revealed a hypokalemic (<2 mEq/L), hyperchloremic non-anion gap metabolic acidosis with hypomagnesemia and hypophosphatemia. hemoglobin A1c (HbA1c) was 5.8%. Urine studies revealed a urine potential of hydrogen (pH) >5.5 and an elevated random spot urine potassium of 41 mmol/L. Thyroid studies were as noted in Table 1.

Laboratory findings were suggestive of Graves’ hyperthyroidism. Due to the presence of non-anion gap metabolic acidosis, hypokalemia, and high urine pH, type 1 distal RTA is suspected. Electrocardiogram (ECG) on presentation showed sinus tachycardia with a corrected QT interval (QTc) of 539 (Figure 1). Additional ECGs showed an accelerated junctional tachycardia with intermittent junctional bradycardia. Computed tomography of the cervical to lumbar spine did not show any spinal cord pathology.

Figure 1 ECG of the patient on presentation showed sinus tachycardia with a QTc of 539. ECG, electrocardiogram; QTc, corrected QT interval.

The patient received an inpatient ultrasound of his thyroid gland, which showed the right thyroid lobe measuring 8.2 cm × 3.0 cm × 2.2 cm (Figure 2A) and the left thyroid lobe measuring 6.2 cm × 3.1 cm × 2.5 cm (Figure 2B), and the isthmus measuring 1.5 cm in anteroposterior (AP) dimension. The texture of the thyroid is generally heterogeneous, largely replaced by nodular/lobular regions, none of which are conclusively identified on submitted images as representing discrete nodules in orthogonal planes. However, the thyroid was also found to be hypervascular, as shown in Figure 2C,2D.

Figure 2 Ultrasound of the thyroid glands. (A) Ultrasound of the right thyroid. (B) Ultrasound of the left thyroid. (C) Color Doppler of the right thyroid. (D) Color Doppler of the left thyroid.

The patient was started on oral propranolol 20 mg every 6 hours and oral methimazole 10 mg daily for rapid, simultaneous symptomatic and disease control. In the emergency department, a central line was placed, and potassium, magnesium, and phosphate were aggressively repleted. Around 240 mEq of potassium chloride replacement was given over 12 hours (Table 2). The patient was admitted to the medical intensive care unit, where he continued to have tachycardia, undetectable thyroid-stimulating hormone (TSH), and high free thyroxine (FT4). Propranolol was changed to atenolol 50 mg twice a day for ease of dosing, and methimazole was increased to 20 mg twice a day. The patient was also started on sodium bicarbonate for suspected type 1 RTA. He experienced no adverse events from medications during his hospital course. On hospital day 3, the patient was hemodynamically stable [hazard ratio (HR) 84, blood pressure (BP) 125/76], his thyroid hormone levels were down-trending (TSH <0.05 µIU/mL, free T4 2.7 ng/dL), and his weakness had improved.

The patient was discharged with plans for an outpatient endocrinology follow-up. He had resolution of his symptoms, and he is currently weighing the risks and benefits of definitive treatment with radioactive iodine versus thyroidectomy.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Our institution does not require ethical approval for reporting individual cases or case series. Verbal informed consent was obtained from the patient for their anonymized information to be published in this journal.

Discussion

Pathophysiology

TPP is thought to be caused by the derangement of the Na⁺/K⁺-ATPase and the K_ir (7). As a metabolic regulator, thyroid hormone acts on the Na⁺/K⁺-ATPase directly, indirectly, and genomically (7). Directly, thyroid increases the intrinsic activity of the Na⁺/K⁺-ATPase while promoting its insertion into the cell membrane (7). Indirectly, thyroid hormone amplifies the activity of β₂-agonists, which further promotes Na⁺/K⁺-ATPase channel activity (7). Similarly, thyroid hormone promotes transcription of the gene encoding the Na⁺/K⁺-ATPase (7). By increasing the pump’s number, availability, and activity, thyroid hormone drives potassium into muscle cells, leading to sarcolemmal hyperpolarization, intracellular hyperkalemia, and relative serum hypokalemia (7).

Patients without TPP can correct these electrochemical changes physiologically. Cations (Na⁺, H⁺) can enter cells to quench the negative charge through a cation leak current. Another intramembrane channel, K_ir, has been suggested to play a role in the correction of potassium equilibrium; at low serum potassium levels, K_ir has been shown to favor the outward current of potassium, thus helping to restore the potassium electrochemical gradient to its physiologic concentrations (3). In TPP, however, it has been suggested that a specific K_ir channel (K_ir2.6) is mutated and cannot excrete potassium out of cells, leading to the intracellular sequestration of potassium (Figure 3) (3,8). As cells are still hyperpolarized, cation leak will continue to occur, and with potassium unable to exit via K_ir2.6, the resting potential is reset to the point at which delayed rectifier potassium channels open to allow the efflux of potassium. This is at a much more depolarized voltage, at which sodium channels are voltage-gated, leading to paralysis (3).

Figure 3 Effect of potassium movement out of cells with K_ir mutation (8). K_ir, inward-rectifying potassium channel; TPP, thyrotoxic periodic paralysis; SUR, sulfonylurea receptor.

Triggers for these paralysis episodes in TPP include carbohydrate-rich foods, strenuous exercise, and stress (1). High-carbohydrate-rich foods promote the production of insulin, which is one of the most potent activators of the Na⁺/K⁺-ATPase (9). Our patient with pre-diabetes is at risk for elevated baseline levels of insulin, which could further increase the risk of episodes of paralysis due to increased Na⁺/K⁺-ATPase activity. Both stress and exercise can increase the production of catecholamines, which increase the activity of the Na⁺/K⁺-ATPase (10,11). Furthermore, both insulin and catecholamines have been found to inhibit K_ir channels (8). Finally, studies have found that testosterone additionally enhances the activity of Na⁺/K⁺-ATPase, and it is theorized that this could be contributing to the majority of cases of TPP affecting men (1,12).

Genetics

Given the epidemiologic data, research has been done to pinpoint a genetic explanation for TPP. A study in Hong Kong found that the Na⁺/K⁺-ATPase was more active in those with TPP than in patients with thyrotoxicosis without paralysis (13). Additionally, one-third of patients with TPP were found to have a mutation in the gene that encodes K_ir2.6, KCNJ18 (3). Both this elevated intrinsic activity of Na⁺/K⁺-ATPase and the higher incidence of mutations in the K_ir2.6 can genetically predispose some individuals with thyrotoxicosis to progress to TPP (3).

TPP and RTA

Distal (type 1) RTA is a rare presentation in patients with TPP or Graves’ disease. In the literature, there have been four previous cases of patients with TPP and distal RTA (14-17). There have also been a handful of distal RTAs in patients with Graves’ disease without TPP (18-21). The exact relationship between distal RTA and Graves’ disease is not currently known; however, several mechanisms have been proposed. Thyrotoxicosis causes an increase in bone turnover and causes hypercalcemia and hypercalciuria (21). This increase in calcium excretion in the urine can lead to nephrolithiasis, which can cause damage to the renal tubules, resulting in the distal RTA (21). Two previous case studies had patients present with TPP and distal RTA who had nephrocalcinosis, which was believed to be contributing to the distal RTA (14,15). Our patient had no signs or symptoms of nephrolithiasis, including not having hypercalcemia, hematuria, or an elevated urine calcium/creatinine ratio. He had a normal ratio of 0.146 (normal ratio <0.2) (22).

The other etiology of type 1 RTA in TPP is secondary to the autoimmunity of Graves’ disease, which creates autoantibodies against H⁺-ATPase. This enzyme’s compromise inhibits the function in the alpha intercalated cell, as seen in Sjögren’s syndrome and lupus (23). It has been theorized that Graves’ disease can cause a similar process of creating autoimmune antibodies to H⁺-ATPase, causing the distal RTA (14). However, other etiologies need to be ruled as in two of the previous case studies in TPP patients with distal RTA, they were also found to be positive for anti-Ro antibodies (16,17). Decreased function of H⁺-ATPase leads to decreased positive anions in the lumen of the collecting duct and causes an increase in K⁺ secretion from the renal outer medullary potassium (ROMK) channel in the principal cell, leading to an increase in urine potassium and a decrease in serum potassium, as seen in our patient (23). The decreased H⁺ secretion also leads to decreased bicarbonate production in the alpha-intercalated cell. It leads to decreased activity of the HCO₃⁻/Cl⁻ antiporter, which leads to the hyperchloremic non-anion gap metabolic acidosis with increased urine pH >5.5, which is also how our patient presented (23). Due to the loss of potassium in the urine, we believe our patient had both a relative serum hypokalemia due to the channelopathy, but also had a total body hypokalemia due to the loss of K⁺ in the urine (23).

The potassium replacements in TPP should be judicious since the hypokalemia is from shift of K intracellularly rather than depletion; however, with concomitant RTA, it can be more liberal as seen in our case due to whole body K depletion from renal losses.

This case highlights a rare and diagnostically challenging presentation of coexistent TPP and RTA, which has seldom been reported in the literature, especially in a non-Asian patient. The strength of this report lies in the timely recognition and effective treatment of dual electrolyte-shifting pathologies, emphasizing the need for comprehensive metabolic evaluation in patients with acute weakness and thyrotoxicosis. Additionally, the case underscores the importance of considering multiple concurrent causes of hypokalemia rather than attributing it solely to one etiology. However, this report has limitations. As a single-patient observation, it cannot establish causality or generalize management protocols. Genetic testing for known mutations linked to TPP (e.g., KCNJ18) was not performed, and long-term follow-up was limited. Future studies or case series are needed to clarify the interaction between thyroid dysfunction and renal tubular handling of electrolytes.

Conclusions

TPP is understudied in Western Countries and needs to be considered in the differential diagnosis of patients with acute quadriparesis or paraparesis, along with others such as cord compression, transverse myelitis, myasthenic crisis, Guillain-Barré syndrome, and tick paralysis. Providers should be aware of this, especially in the setting of RTA, given that it is treatable, but it can be life-threatening if undiagnosed. Treatment includes repletion of electrolytes and control of the patient’s hyperthyroidism.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-152/rc

Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-152/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-152/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Our institution does not require ethical approval for reporting individual cases or case series. Verbal informed consent was obtained from the patient for their anonymized information to be published in this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Siddamreddy S, Dandu VH. Thyrotoxic Periodic Paralysis (Archived). 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
2. Chao A, Akhondi H. Periodic Paralysis Syndromes: A T3 Thyrotoxicosis Case and Review of Literature. HCA Healthc J Med 2020;1:27-33.
3. Ryan DP, da Silva MR, Soong TW, et al. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell 2010;140:88-98. [Crossref] [PubMed]
4. Ko GT, Chow CC, Yeung VT, et al. Thyrotoxic periodic paralysis in a Chinese population. QJM 1996;89:463-8.
5. Patel M, Ladak K. Thyrotoxic Periodic Paralysis: A Case Report and Literature Review. Clin Med Res 2021;19:148-51.
6. Lam L, Nair RJ, Tingle L. Thyrotoxic periodic paralysis. Proc (Bayl Univ Med Cent) 2006;19:126-9. [Crossref] [PubMed]
7. Lin SH, Huang CL. Mechanism of thyrotoxic periodic paralysis. J Am Soc Nephrol 2012;23:985-8.
8. Rolim ALR, da Silva MRD. Thyrotoxic Periodic Paralysis–Clinical Diagnosis and Management. In: Thyroid Disorders-Focus on Hyperthyroidism. Rijeka: InTech; 2014.
9. Wen XP, Wan QQ. Regulatory effect of insulin on the structure, function and metabolism of Na+/K+-ATPase Exp Ther Med 2021;22:1243. (Review).
10. Messan F, Tito A, Gouthon P, et al. Comparison of Catecholamine Values Before and After Exercise-Induced Bronchospasm in Professional Cyclists. Tanaffos 2017;16:136-43.
11. Arkhipov A, Khuzakhmetova V, Petrov AM, et al. Catecholamine-dependent hyperpolarization of the junctional membrane via β2- adrenoreceptor/G(i)-protein/α2-Na-K-ATPase pathway. Brain Res 2022;1795:148072. [Crossref] [PubMed]
12. Guerra M, Rodriguez del Castillo A, Battaner E, et al. Androgens stimulate preoptic area Na+,K+-ATPase activity in male rats. Neurosci Lett 1987;78:97-100.
13. Chan A, Shinde R, Chow CC, et al. In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis. BMJ 1991;303:1096-9. [Crossref] [PubMed]
14. Mohakuda SS, Pakhetra R, Yadav N. Thyrotoxicosis leading to Renal Tubular Acidosis presenting as periodic paralysis–A case report. Int J Clin Endocrinol Metab 2019;5:024-5.
15. Bolaños F, Ponce de León S, García Ramos G, et al. Hyperthyroidism associated with renal tubular acidosis, nephrocalcinosis, nephrogenic diabetes insipidus and periodic paralysis. Report of a case. Rev Invest Clin 1981;33:195-8.
16. Szeto CC, Chow CC, Li KY, et al. Thyrotoxicosis and renal tubular acidosis presenting as hypokalaemic paralysis. Br J Rheumatol 1996;35:289-91. [Crossref] [PubMed]
17. Im EJ, Lee JM, Kim JH, et al. Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular acidosis and nephrogenic diabetes insipidus. Endocr J 2010;57:347-50. [Crossref] [PubMed]
18. Jackson I, Addasi Y, Ahmed M, et al. Hypokalemic Periodic Paralysis Precipitated by Thyrotoxicosis and Renal Tubular Acidosis. Case Rep Endocrinol 2021;2021:4529009. [Crossref] [PubMed]
19. Dundar I, Akıncı A, Çamtosun E, et al. Distal Renal Tubular Acidosis can be the Cause of Hypokalemia in Graves’ Disease: A Rare Association. Medical Records 2023;5:423-5.
20. Sim EH, Shin YS, Park MG, et al. A Case of Renal Tubular Acidosis Associated With Graves' Disease. J Korean Geriatr Soc 2013;17:147-51.
21. Aljaberi AK, Shamsi SA. SUN-512 Graves’ Disease Induced Renal Tubular Acidosis. J Endocr Soc 2020;4:SUN-512.
22. Leslie SW, Sajjad H. Hypercalciuria. 2024. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
23. Ungureanu O, Ismail G. Distal Renal Tubular Acidosis in Patients with Autoimmune Diseases-An Update on Pathogenesis, Clinical Presentation and Therapeutic Strategies. Biomedicines 2022;10:2131. [Crossref] [PubMed]