Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

Thyrotoxic Periodic Paralysis As The Initial Presentation For Graves’ Disease In A Hispanic Male Rachel Hemsath OMS-III, Shawn Votruba OMS-III, Nadim Salman M.D. Edward Via College of Osteopathic Medicine- Carolinas Campus, Spartanburg, SC.

Abstract

Case

Discussion/Conclusions

The Na+-K+ ATPase pump in skeletal muscle is activated by the elevated thyroid hormones which pumps potassium into cells, creating a hypokalemic extracellular environment [3]. The change in potassium gradient results in an inability for depolarization to occur causing flaccid paralysis, as displayed in Figure 2 . Hyperinsulinemia can also be involved in this condition and contribute to the intracellular shift of potassium [3].

Thyrotoxic Periodic Paralysis (TPP) is a condition most often seen in Asian males ages 30-50 that present with sudden onset of muscle weakness, typically lower extremities. It can involve general symptoms of hyperthyroidism such as tremor, diaphoresis, tachycardia, palpitations, and arrhythmias. Labs will generally show hypokalemia and hyperthyroidism, as well as possible hypomagnesemia and hypophosphatemia. Patients with these episodes commonly have a medical history of a hyperthyroid disorder, most commonly Graves’ Disease. The diagnosis of TPP typically should be considered when a patient presents with sudden muscle weakness, hypokalemia, and hyperthyroid labs, particularly if the patient is of Asian origin and has a medical history of hyperthyroid disease. We present a unique case of TPP in a Hispanic male with no diagnosed history of thyroid disease. We aim to highlight the importance of considering TPP as a diagnosis in other ethnicities as well as in patients without a history of a hyperthyroid condition as this could be an initial presentation.

A 26 year old Hispanic male presented to the Emergency Department with a complaint of “bilateral lower extremity muscle weakness.” He reported having muscle twitches in both of his thighs the previous day. Early the morning of his presentation he stated he went to the bathroom and both of his legs ``gave out.”. After this, he continued to experience lower extremity weakness bilaterally, leaving him unable to ambulate. On evaluation, the patient was tachycardic and reported having palpitations. The patient reported some mild back pain but denied any recent illness, fevers, chills, congestion, headache, vision changes, chest pain, shortness of breath, nausea, vomiting, or diarrhea. He did report one prior episode 5-6 months ago of mild leg weakness after over-exerting himself while playing soccer, but said this episode resolved spontaneously. Physical exam revealed the patient had leg strength of 2 out of 5 in his lower extremities. Evaluation in the Emergency Department included laboratory studies and imaging. X-ray and MRI of the lumbar spine showed no acute pathology. Laboratory studies are shown Table 1.

Managing this condition involves rapid correction of hypokalemia with IV or oral potassium while watching for overcorrection and rebound hyperkalemia [1,5]. Definitive treatment is treating the underlying cause of hyperthyroidism [6] Given a patient with hypokalemic paralysis of an unknown cause thyroid studies should be considered to differentiate TPP from familial hypokalemic periodic paralysis. Thyroid studies

will differentiate TPP from familial hypokalemic periodic paralysis and hypokalemia will differentiate TPP from Guillain-Barré syndrome or myasthenic syndromes [7].

Introduction

Study

Patient Value Reference Range 2.2 mg/dL 3.5-5.2 mg/dL 1.4 mg/dL 1.7-2.2mg/dL <0.010 mlU/L 0.5-5.0 mlU/L

Figure 2. Mechanism of hypokalemia due to hyperthyroidism

Potassium Magnesium

Thyrotoxic Periodic Paralysis (TPP) is a condition that typically affects Asian males, with just under 2% affected by this condition. Patients present most commonly with sudden bilateral lower extremity weakness and hypokalemia [1]. TPP is progressive and if the potassium is not corrected patients may go on to have full quadriplegia which may also include respiratory musculature [1]. Patients affected by this condition generally have had similar episodes in the past and have been previously diagnosed with a hyperthyroid disorder, commonly Graves’ Disease [2]. Other etiologies are shown in Figure 1 . The pathophysiology of the extremity weakness involves elevated thyroid hormone levels contributing to the intracellular shift of potassium,

The patient being a Hispanic male is a unique divergence from the most likely population who present with TPP, which is typically Asian males. This patient had not been previously diagnosed with any thyroid disorder, but had positive thyroid receptor antibody tests and ultrasound, which confirm a diagnosis of Graves’ disease and therefore TPP being the first presentation of this illness. We aim to make three important conclusions: ● To emphasize considering TPP in patients of non-Asian origin who present with episodes of lower extremity paralysis. More broadly it should be understood that although a disease may have a characteristic population differential diagnosis of that disease should not be confined to that population. ● To consider a presentation of extremity weakness and hypokalemia as an indication to order further studies to determine if the patient has Graves’ Disease or another hyperthyroid disorder. ● To highlight the importance of accurately diagnosing the underlying cause of TPP so that definitive treatment can be initiated, thus avoiding further episodes or complications.

Thyroid Stimulating Hormone

Thyroxine (T4)

3.61 ng/dL

0.7-1.53 ng/dL

Thyroid receptor antibody (TrAB) Thyroid stimulating immunoglobulin (TSI)

Positive Positive

Negative Negative

Table 1. Laboratory results for patient presenting with bilateral lower extremity weakness.

Treatment of hypokalemia was initiated, and the patient was given 80 milliequivalents of potassium and 2 grams of magnesium. For symptomatic HR control, 20 milligrams of propranolol with instructions to take twice a day was initiated. With electrolyte repletion the patient’s symptoms of lower extremity weakness eventually resolved. Antithyroid medications were considered as part of the treatment pending thyroid antibody results. He was admitted for further workup and treatment of hyperthyroidism, as well as observation to avoid overcorrection of potassium. Ultrasound showed a diffusely enlarged, heterogeneous thyroid echotexture with parenchymal hyperemia, consistent with findings of thyroiditis. Serology was eventually found to be positive for Thyroid receptor antibodies (TRAb) and Thyroid Stimulating immunoglobulin (TSI) confirming the diagnosis of Thyrotoxic periodic paralysis with hypokalemia as a result of underlying Graves’ disease. Patient was advised to follow up with their primary care physician and endocrinology for management of Graves’ disease.

while the total body potassium levels remain constant [1,3]. This condition requires immediate correction of electrolytes to resolve the muscle weakness as well as further studies to evaluate the cause of thyrotoxicosis, including thyroid autoantibody tests and thyroid ultrasound [4]. The following case is unique in that it presents in a Hispanic male with the typical presentation of TPP who has never been diagnosed with any thyroid disorder.

References

Figure 1. Common etiologies of TPP

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2024 Research Recognition Day