High-dose intravenous hydrocortisone for the treatment of hyperthyroidism: a rare precipitant of thyrotoxicosis periodic paralysis

Background

Thyrotoxic periodic paralysis (TPP) is a rare but severe complication of hyperthyroidism characterized by episodes of flaccid muscle paralysis most affecting the proximal muscles. With supporting clinical presentation, the diagnostic laboratory finding is hypokalemia which is proportional to the severity of the muscle paralysis (1).

TPP episodes are hypothesized to be caused by increased activity of Na+/K+ ATPase in the skeletal muscles, stimulated by thyroid hormone, hyperadrenergic activity, and/or hyperinsulinemia. Androgens are associated with increased Na+/K+ ATPase activity because of their effects on hypertrophy of myoblasts, which could help explain the large male predominance of TPP, found to be 130:5 in a 10-year prospective observational study, even though hyperthyroidism is significantly more prevalent in females (2).

Associated triggers of potassium movement into the intracellular space by the Na+/K+ ATPase include a large carbohydrate meal invoking an increased insulin response, strenuous activity, acute upper respiratory infection, a high-salt diet, alcohol ingestion, and cold exposure. Drugs can rarely trigger TPP, including insulin and diuretics as well as the focus of our case report, steroids (3). Steroids, particularly high-dose hydrocortisone used in severe thyrotoxicosis, increase mineralocorticoid activity, promoting hypokalemia. In addition, glucocorticoids facilitate hyperglycemia and hyperinsulinemia, which further facilitates intracellular potassium uptake, stimulating a TPP episode (1). We believe that the high-dose corticosteroids used to treat acute thyrotoxicosis uniquely triggered TPP in this case.

Case presentation

A 34-year-old African American man presented to the emergency department (ED) with complaints of 2 days of uncontrollable diaphoresis. This was accompanied by heat intolerance, lethargy, agitation, confusion, lightheadedness, chest pain, nausea, vomiting, decreased appetite, and dyspnea for the last week. These symptoms started while working at his job at a plastics recycling facility. He denied any previous such symptoms. He had no previous medical conditions and did not take any medications on a regular basis, including over-the-counter medications. He had a family history of autoimmunity with his twin sister having systemic lupus.

On arrival at the ED, he was afebrile with a pulse of 123, respiratory rate of 20, blood pressure of 132/77, and oxygen saturation of 99% on room air. His exam revealed a non-tender, diffusely enlarged thyroid gland, brisk deep tendon reflexes, and a fine tremor in outstretched hands. The rest of the systems exams were unremarkable, and no exophthalmos was noted. Labs were pertinent for undetectable TSH, free thyroxine (T4) of 7.21 ng/dL (0.89–1.76) and total triiodothyronine (T3) of >800 ng/dL (Table 1). Sinus tachycardia was observed on his ECG, and thyroid ultrasound showed a diffusely enlarged and hypervascular thyroid gland most consistent with Graves’ disease.

The Endocrinology team was consulted for the evaluation and management of primary hyperthyroidism and appropriate autoantibody testing was ordered. Given his Burch–Wartofsky score of 25 which suggested impending thyroid storm and the degree of his thyrotoxicosis, he was started on propranolol 40 mg oral every 8 h, methimazole 30 mg oral twice daily, and i.v. hydrocortisone 100 mg every 8 h. The aim of the hydrocortisone was to decrease T4 to T3 conversion given the severely elevated T3 levels. Patient responded well to therapy initially.

However, on day 2 of admission, right after he ate his lunch on the low carbohydrate diet (less than 45 g per meal), he developed sudden onset bilateral lower extremity weakness with an inability to bear weight. The stroke team was called and while there were no other focal symptoms, his deep tendon patellar reflexes were also diminished bilaterally.

Investigation

Given the concern for acute stroke, a non-contrasted head CT and basic labs including complete blood cell counts and electrolytes were ordered. This workup revealed severe hypokalemia with a potassium of 2.0 mEq/L (3.5–5.5) having been normal a few hours ago when checked in the morning. His glucose at that time was 231 mg/dL (Table 1). The rest of the neurologic workup including the head CT was normal.

Treatment

The patient was diagnosed with TPP likely precipitated by the high-dose corticosteroids and hyperglycemia. The patient had no ECG changes associated with hypokalemia. He was promptly transferred to the progressive care unit to be monitored with a bedside cardiac monitor.

The patient’s hydrocortisone was discontinued, and potassium was checked every 2 h. He was given a total of 60 mEq of potassium chloride, and 3 h later, his potassium reached its nadir at 1.6 mEq/L (see Fig. 1). He got another 40 mEq at that time which resulted in potassium to get normalized 8 h after the paralysis attack. His glucose was also monitored closely which stayed normal off the hydrocortisone. He had received a total of four doses of 100 mg i.v. hydrocortisone. The patient showed symptomatic improvement within 6 h of potassium repletion, and no electrical cardiac changes were seen at any time on continuous cardiac monitoring. His potassium continued to be monitored closely to watch for rebound hyperkalemia, which he did not experience. He was observed for 48 h after the episode with no recurrence of hypokalemia or paralysis thereafter. By the time of discharge, his thyroid-stimulating immunoglobulin came back elevated at 18.8 IU/L (<0.54) confirming the presumptive diagnosis of Graves’ disease and he was advised to follow up in the Endocrinology clinic for further management.

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Potassium levels over the course of the hospitalization before and after the development of TPP.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 1; 10.1530/EDM-22-0358

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Outcome and follow-up

The patient was doing clinically well on propranolol and methimazole with no subsequent TPP episodes. He was being followed by the outpatient endocrinology service but has been lost to follow-up. The plan was to have total thyroidectomy for definitive management of Graves’ disease per patient preference, but this has not happened yet due to the patient being lost to follow-up.

Discussion

The differential diagnosis for acute-onset proximal lower extremity muscle weakness includes other autoimmune conditions besides those related to thyrotoxicosis, including myasthenia gravis and Guillain–Barre syndrome, inflammation from transverse myelitis, neurotoxins from ticks or Clostridium botulinum, myelopathic viral infection associated with thyroid dysfunction, genetic predisposition with calcium channel α1-subunit polymorphisms, and inherited familial periodic paralysis syndromes. Among the causes of hypokalemic periodic paralysis, familial hypokalemic periodic paralysis is the most common cause in Western countries, while TPP is the most common cause in Asian countries (4). Given the acute thyrotoxicosis in this case, the development of a thromboembolic event secondary to atrial fibrillation could lead to spinal cord infarction or cerebrovascular accident.

High-dose steroids are commonly used to treat severe thyrotoxicosis and thyroid storm in conjunction with anti-adrenergic non-selective beta-blocker medications like propranolol and thioamides like methimazole. Steroids have been shown to be effective in controlling hyperthyroidism by inhibiting the conversion of T4 to T3 peripherally and also by blocking the release of T4 from the thyroid gland.

In this case, high-dose steroids precipitated TPP likely from the effects of hyperglycemia and hyperinsulinemia, which intracellularly moves potassium via Na+/K+ ATPase activity in the skeletal muscle. While the moderate carbohydrate ingestion with the meal may have contributed to the attack, the elevated blood glucose was likely primarily associated with steroid use, resulting in increased endogenous insulin production (1).

There are no case reports where the use of high-dose steroids in the context of treatment of thyrotoxicosis resulted in TPP. There are two case reports of patients with known primary hyperthyroidism (3, 5). There is literature on TPP secondary to steroids used for other settings, including i.m. treatment for streptococcal throat infection (6) and uvulitis (3), epidural treatment for traumatic low back pain (7), and i.v. treatment for anaphylaxis where i.m. epinephrine was unavailable locally (8). In medical literature, different types of steroids have been implicated in precipitating TPP. These include prednisone (9), methylprednisolone (5), and hydrocortisone as in this case. There has been only one other case report on TPP that was associated with hydrocortisone usage (8).

Another key finding from our case is the understanding that in TPP, the patient is typically not total-body potassium depleted, as trans-cellular shifts primarily drive the hypokalemia. Hence, clinicians need to be cautious about over-replacing and the potential for rebound hyperkalemia. In our case, even though the patient's potassium was as low as 1.6 mEq/L, it took a total of 100 mEq of potassium chloride to completely normalize the potassium over time.

Lastly, while TPP is most commonly seen in Asian men and is more prevalent in Caucasian than African or African American patients, this condition should not be overlooked in races and ethnicities where it may be rare (10).

In conclusion, this case highlights the scenario where the treatment of hyperthyroidism with high-dose corticosteroids to reduce the conversion of T4 to T3 inadvertently resulted in TPP. Clinicians should be aware of this potentially rare but serious consequence of using steroids to manage hyperthyroidism.

Declaration of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding statement

This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Patient consent

Verbal consent had been obtained from the patient for publication of their clinical details. However, since then, patient has been lost to follow-up. Every effort was made to contact patient and next of kin but was unsuccessful. The authors attest that full anonymity has been maintained in this case report and no patient identifiable information has been shared.

Author contribution statement

M Scheive helped conceptualize the case report by constructing the early drafts and responding to author feedback. N Patel and Z Saaed helped conceptualize and provide feedback on the manuscript from their varied clinical expertise and backgrounds.