http://informahealthcare.com/rnf ISSN: 0886-022X (print), 1525-6049 (electronic) Ren Fail, 2014; 36(3): 461–463 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/0886022X.2013.868296

CASE REPORT

Iodine-induced thyrotoxic hypokalemic paralysis after ingestion of Salicornia herbace Seong Eun Yun1, Yeojin Kang1, Eun Jin Bae1, Kyungo Hwang1, Ha Nee Jang1, Hyun Seop Cho1, Se-Ho Chang1,2, and Dong Jun Park1,2 1

Department of Internal Medicine, College of Medicine, Gyeongsang National University Hospital, Jinju, South Korea and 2Institute of Health Science, Gyeongsang National University Hospital, Jinju, South Korea Abstract

Keywords

A 56-year-old Korean man visited to emergency room due to paroxysmal flaccid paralysis in his lower extremities. There was no family or personal history of periodic paralysis. His initial potassium levels were 1.8 mmol/L. The patient had been taking Salicornia herbacea for the treatment of diabetes and hypertension. Results of a thyroid function test were as follows: T3 ¼ 130.40 ng/dL, TSH ¼ 0.06 mIU/L, and free T4 ¼ 1.73 ng/dL. A thyroid scan exhibited a decreased uptake (0.6%). His symptoms clearly improved and serum potassium levels increased to 4.4 mmol/L by intravenous infusion of only 40 mmol of potassium chloride. Eight months after the discontinuation of only Salicornia herbacea, the patient’s thyroid function tests were normalized. Large amounts of iodine can induce hypokalemic thyrotoxic paralysis and it may be necessary to inquire about the ingestion of iatrogenic iodine compounds, such as Salicornia herbacea.

Hypokalemia, hyperthyroidism, iodine, nutraceuticals, paralysis

Salicornia herbacea is a halophytic perennial dicot which grows in various zones of intertidal salt marshes. Salicornia species are native to North America, Europe, South Africa, and South Asia. In Korea, this plant is known as ‘‘Tungtungmadi’’ and is mainly distributed amongst the tidelands along the western coast.1,2 Salicornia herbacea contains a variety of minerals in addition to calcium, potassium, fiber, and iodine and has been used in Korea as an alternative medicine for the prevention of diabetes mellitus, the amelioration of constipation, treating obesity, and to remedy poor blood circulation. Recently, S. herbacea has also been consumed as a food. To date, there have been no reports of side effects or complications following the ingestion of S. herbacea. Hypokalemic thyrotoxic periodic paralysis (TPP) is a rare, acute complication of thyrotoxicosis that is relatively common in Oriental men. This disease presents with hypokalemia and proximal muscle weakness, which are thought to result from an abrupt transcellular potassium shift that is indicative of hyperthyroidism. Large amounts of iodine, which may be present in synthetic thyroid hormone and some dietary supplements, drugs, and nutraceuticals used for

Address correspondence to Dong Jun Park, MD, Department of Internal Medicine, College of Medicine, Gyeongsang National University Hospital, 816 Beongil 15 Jinju-daero, Jinju, Gyeongnam, South Korea. Tel: +55 750 8739; Fax: +55 758 9122; E-mail: [email protected]

Received 3 September 2013 Revised 14 November 2013 Accepted 16 November 2013 Published online 17 December 2013

weight reduction, may induce transient hyperthyroidism.3–6 However, although some reports have identified the use of drugs such as amiodarone and weight-reducing agents containing tiratricol, triiodothyronine, or iodine contrast with hypokalemic TPP,7–11 cases of hypokalemic paralysis associated with the intake of dietary supplements or nutraceuticals are extremely rare.12 This is a unique report describing hypokalemic TPP associated with the ingestion of S. herbacea, a common nutraceutical in South Korea.

Case report

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Introduction

History

A 56-year-old Korean male presented to the emergency room with paroxysmal paralysis of the lower extremities, which had begun 2 h prior. He had felt mild weakness on his lower extremities 2 days ago, but had been able to walk about. However, he could not walk or lift himself off the bed upon admission to the hospital. There was no family or personal history of periodic paralysis. He had been diagnosed with diabetes mellitus and hypertension 5 years before his admission and had taken medications of glimepiride 4 mg, amlodipine besylate 5 mg, and atenolol 25 mg without changes. Four days before admission, he got a cold and took medicines such as ambroxol (30 mg bid), acetaminophen (600 mg bid), and cetirizine (10 mg bid) that are not known to induce hypokalemia. In addition, the patient did not have a history of trauma, had not ingested known toxins, did not suffer from polyuria or polydipsia and did not suffer from diarrhea and vomiting.

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His initial vital signs were as follows: blood pressure ¼ 140/85 mmHg, heart rate ¼ 90 beats/min, respiratory rate ¼ 18 breaths/min, and body temperature ¼ 37.2  C. A neurological examination revealed symmetrical flaccid paralysis in his lower extremities but the patient was alert and the sensory system was intact. Examination of the neck did not reveal an enlarged thyroid and there was no exophthalmos. We could not hear thyroid bruit. There were no other signs or symptoms of hyperthyroidism including palpitation, fever, tremor, heat intolerance, or myalgias, except for paralysis. We could not find any features of Cushing’s disease such as moon face, buffalo hump, truncal obesity, and thinning of the skin. We also could not detect diastolic bruit on abdomen examination. Initial laboratory tests were as follows: sodium ¼ 138 mmol/L (135–145 mmol/L), potassium ¼ 1.8 mmol/L (3.3– 5.1 mmol/L), chloride ¼ 99.4 mmol/L (98–110 mmol/L), blood urea nitrogen (BUN) ¼ 8.2 mg/dL (6–20 mg/dL), creatinine ¼ 0.97 mg/dL (0.6–1.2 mg/dL), glucose ¼ 178 mg/dL (70–110 mg/dL), calcium ¼ 9.6 mg/dL (8.6– 10.2 mg/dL), phosphate ¼ 1.2 mg/dL (2.7–4.5 mg/dL), creatine phosphokinase (CPK) ¼ 160 U/L (0–190 U/L), magnesium ¼ 2.5 mmol/L (1.5–2.5 mmol/L), white blood cells (WBCs) ¼ 11,650/mL (4000–10,000/mL), hemoglobin ¼ 15.1 g/dL (13.3–17.0 mg/dL), hematocrit ¼ 42% (39–52%), and platelet count ¼ 151,000/mL (130,000– 400,000/mL). An arterial blood gas analysis revealed a pH of 7.42 (7.35–7.45), pCO2 ¼ 42 mmHg (32–46 mmHg), and HCO3 ¼ 27 mmol/L (23–29 mmol/L). The calculated transtubular potassium gradient (TTKG) was 1.66, serum osmolality was 299 mOsm/kg (276–300 mOsm/kg), urine osmolality was 424 mOsm/kg, urine sodium was 50 mmol/L, and urine potassium was 4.5 mmol/L. An electrocardiogram (ECG) revealed a normal QT interval but prominent U waves. A thyroid function test showed that serum thyroid stimulation hormone (TSH) was 0.06 mIU/L (0.27–4.2 mIU/L), T3 was 130.40 ng/dL (80–200 ng/dL), and free T4 was 1.73 ng/dL (0.93–1.70 ng/dL). Anti-thyroid antibodies including anti-thyroid peroxidase antibodies, thyrotropin receptor antibodies, and thyroglobulin antibodies were all negative and thyroid uptake was decreased in a thyroid scan (0.6%; Figure 1). The patient received intravenous replacement of 40 mmol potassium chloride during the initial 12 h of treatment after which his paralysis clearly improved and his serum potassium level increased to 4.4 mmol/L. A detailed history revealed that he had been taking S. herbacea for the treatment of diabetes and hypertension for the previous 6 months. Eight months after the discontinuation of S. herbacea without other treatments, the patient’s thyroid function tests were normalized: T3 ¼ 120.69 ng/dL, TSH ¼ 1.90 mIU/L, and free T4 ¼ 1.28 ng/dL. In addition, his serum potassium level was 3.5 mmol/L.

Discussion A case of hypokalemic TPP induced by the ingestion of S. herbacea, a common nutraceutical in South Korea, is described. This report is very meaningful because excessive iodine intake via diet or nutraceuticals that are commonly

Ren Fail, 2014; 36(3): 461–463

Figure 1. Tc-99 m pertechnetate (8 mCi) thyroid scan showing diffusely decreased uptake (0.6%).

used as alternative or ancillary agents could result in acute complications such as hypokalemic TPP. TPP is characterized by transient, recurrent episodes of muscle paralysis in which proximal muscles are more severely affected than distal muscles. The lower extremities are frequently involved while bulbar, ocular, and respiratory muscles are infrequently affected. TPP usually presents as a complication of Grave’s disease but manifestations of thyrotoxicosis can be subtle and precede or coincide with the onset of paralytic attacks. During paralytic attacks, hypokalemia is almost always present and the severity of muscle weakness correlates with the degree of hypokalemia.13 Paralysis improves with restoration of normal serum potassium levels. In spite of a higher incidence of thyrotoxicosis in women, TPP is more frequent in men. In the current patient, there were no symptoms or signs of hyperthyroidism except for muscle paralysis, which involved his lower extremities and clearly improved with potassium replacement. The pathophysiology of TPP remains unclear. Hypokalemia is not an absolute deficiency of total body potassium but rather a rapid and exaggerated intracellular shifting of potassium into muscles during attacks. Enhanced sympathetic activity has been associated with the pathogenesis of TPP and increases the number and sensitivity of beta receptors. Thyroid hormone can directly stimulate Naþ/Kþ adenosine triphosphatase (ATPase) activity, which results in the transcellular shift of potassium into the cells.14,15 Hyperinsulinemia may be another important factor that provokes attacks of TPP.16 The higher incidence of TPP in males may be explained by the fact that Naþ/Kþ ATPase activity is increased by androgens.17 Many predisposing factors of TPP have been reported including high carbohydrate load, strenuous exercise, trauma, cold exposure, use of steroids, infection, and emotional stress. All the above factors are associated with TPP pathophysiology. Upper respiratory

DOI: 10.3109/0886022X.2013.868296

infection might also have been a predisposing factor in the current patient. The majority of hyperthyroidism cases associated with hypokalemic TPP are due to Grave’s disease although other conditions such as thyroiditis, toxic nodular goiter, toxic adenoma, TSH-secreting pituitary tumor, and the ingestion of T4 may also play a role. In addition, the inadvertent ingestion of excessive iodine is also associated with hypokalemic TPP. The majority of such patients have only mildly elevated serum thyroid hormone levels. In one report, the mean serum T3 and free T4 levels in patients with hypokalemic TPP were 247.5 (80–200 ng/dL) and 3.12 (0.77–1.94 ng/dL), respectively.18 Only 10% of patients with TPP have mild thyrotoxic symptoms19 and hyperthyroidism may not be clinically present.20 These particularities of hyperthyroidism along with the rarity of a paralytic condition make TPP a difficult condition to diagnose at presentation. Average dietary iodine intake varies widely from one individual and one population to another. Intake of up to 600 mg/day in the European Union and 1100 mg/day in the United States are declared as tolerable for adults. The thyroidal response to excessive iodine, or euthyroid, hypothyroid, or hyperthyroid, differs according to the individual and/or the normal or pathological status of their thyroid gland.21 A number of cases of iodine-induced hyperthyroidism following the ingestion of food or dietary supplements have been described,3–6 however, only one case of hypokalemic TPP induced by diet has been reported.12 This patient ingested additional 250–500 mg iodine/day via kelp tablets. The patient reported taking S. herbacea (seven tablets daily) for his diabetes and hypertension over a period of 6 months. According to the product information, a single tablet of S. herbacea includes approximately 700 mg iodine. His dietary history, the results of his thyroid function test (TFT), a lower uptake on the iodine scan, the complete recovery from his symptoms, and a normalization of the TFT after discontinuation of S. herbacea is compatible with a diagnosis of hypokalemic TPP induced by the intake of large amounts of iodine. The current case illustrates the importance of a cautious and detailed investigation by the clinician that can lead to the discovery of unusual sources of iodine. A definite diagnosis often requires thorough questioning by the physician. It should also be noted that large amounts of iodine can induce hypokalemic TPP and, thus, patients with an unknown etiology of hypokalemia and paralysis should be questioned regarding their ingestion of iatrogenic iodine compounds such as Salicornia herbacea.

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Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

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