Thyrotoxic periodic paralysis - Symptoms and Treatment

Thyrotoxic periodic paralysis is a type of secondary periodic paralysis that leads to recurrent muscle weakness and is associated with hyperthyroidism and hypokalemia is usually present during attacks.

It is most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis.

The presentation is similar to familial hypokalemic periodic paralysis and often cause for confusion.

It is important to distinguish thyrotoxic periodic paralysis from familial hypokalemic periodic paralysis. Following are the differentiating features

Absence of a family history of paralysis
Male sex
Presentation in the second to fourth decades of life
Signs of thyrotoxicosis

Thyrotoxic periodic paralysis is most common in Asian populations, with an incidence of approximately 2% in patients with thyrotoxicosis of any cause.

The typical age of onset is 20–40 years.

It is not unknown why males are predominantly affected despite hyperthyroidism being much more common in women.

the paralysis is not related to the etiology, severity, and duration of thyrotoxicosis and is most commonly seen in Grave’s disease.

Family history of periodic paralysis is usually absent

Genetic mutations in the L-type calcium channel α1-subunit (Ca_v1.1) have been described in some population

Thyroid disease associated with Thyrotoxic Periodic Paralysis

Graves’ disease
Thyroiditis
Toxic nodular goiter
Toxic adenoma
TSH-producing pituitary adenoma
Excessive ingestion of thyroxine or iodine
Amiodarone-induced hyperthyroidism.

Pathophysiology

The muscle weakness result from markedly reduced levels of potassium in the bloodstream. There is no actual loss of potassium in the body.

There is increased Na⁺/K⁺-ATPase activity that leads to shift of potassium into tissues, and depletes potassium from the circulation. Hypokalemia leads to hyperpolarization of muscle cells, making the neuromuscular junction less responsive to normal nerve impulses.

It is not clear but suspected that the enzyme becomes more active due to increased thyroid hormone levels.

Hyperthyroidism may result in a hyperadrenergic state, which may lead to the activation of the Na+/K+–ATPase pump and result in cellular uptake of potassium.

Thyroid hormones may also directly stimulate Na+/K+– ATPase activity and increase the number and sensitivity of beta receptors. Hyperinsulinemia has been found during the during episodes of paralysis. That may explain the attacks after high-carbohydrate meals but exact mechanism is not known.

Various trigger factors that can precipitate the paralysis are

Trauma
Exposure to cold
Emotional stress
Infection
Alcohol ingestion
Menses
Drug
- Diuretics
- Insulin
- Steroids

Clinical manifestations

There is acute onset of weakness of proximal musculature of lower-extremity which mat be ascending in nature.Rarely does the paralysis affect ocular, bulbar, or respiratory muscles. There have been some reports of ventialtion being affected.

The weakness usually occurs int during the early morning hours or while resting after strenuous exertion and a high-carbohydrate meal.

Acute episodes may be preceded by muscle aches, cramps, and muscle stiffness.

A history should be sought for triggers.

On examination, the deep tendon reflexes are decreased or absent.

Sensation and level of consciousness are usually spared.

There might be subtle finding suggesting thyrotoxicosis

Warm and moist skin
Fever
Tachycardia
Exophthalmoses
Goiter

The paralysis can last 3 to 96 hours, and it resolves in the reverse order from which it occurred.

Lab Studies

Following findings could be present

Hypokalemia
Hypophosphatemia
mild hypomagnesemia
Normal acid-base balance
Low potassium excretion rate
- (low urinary potassium—creatinine ratio <2 and low TTKG <3)
- If high shows urinary potassium loss
Hypercalciuria – incresed loss of calcium in urine
hypophosphaturia – Decrease in urine phosphate
Abnormal thyroid function tests
- Low TSH
- Elevated free and total T3 and T4

ECG abnormalities

Sinus tachycardia [Unlike hypokalemia from other causes]
Hypokalemic changes
- Prominent U wave
- Prolonged PR interval
- Increased P-wave amplitude
- Widened QRS complexes
First-degree atrioventricular block
Atrial and ventricular arrhythmias

Differential Diagnosis

Here is a list of differential diagnoses of paralyses associated with hypokalemia [other than thyrotoxiv periodic paralysis]

Type of potassium imbalance due to Transcellular shift

Familial periodic paralysis
Barium poisoning
Drugs
- Diuretics
- Tocolytics
- Theophylline toxicity
- Chloroquine toxicity
- Insulin overdose
Primary hyperaldosteronism
Pseudohyperaldosteronism: licorice ingestion

Renal loss of potassium

Bartter’s syndrome
Gitelman’s syndrome
Renal tubular acidosis
Nephrotic syndrome
Aacute tubular necrosis
Diabetic ketoacidosis
Ureterosigmoidostomy
Celiac disease
Tropical sprue

Gastrointestinal loss of potassium

Infectious diarrhea
- Salmonella enteritis
- Strongyloides enteritis
- Yersinia enterocolitis
Short bowel syndrome

Thyroid function tests on the blood are used to differentiate thyroid periodic paralysis. These are normal in the other forms.

Treatment of Thyrotoxic Periodic Paralysis

Acute Therapy

Correction of Hypokalemia

Intravenous or oral potassium
- Hasten muscle recovery
- Prevent cardiopulmonary complications
Risk of rebound hyperkalemia
- Release of potassium and phosphate from the cells on recovery
  - Occurrs in approximately 40% of patients
  - Greater risk if they received >90 mEq of potassium chloride within the first 24 hours (
  - Those who receive a total dose of ≤50 mEq of potassium chloride rarely develop rebound hyperkalemia.

Propanolol

A nonselective beta-blocker
Prevents the intracellular shift of potassium and phosphate by blunting the hyperadrenergic stimulation of Na+/ K+–ATPase
Given alone either orally (3 mg/kg) or intravenously
Normalizes serum potassium levels on an average of 120 minutes
Can be given as initial therapy

The combination of nonselective beta-blockers and low-dose potassium appears to be the treatment of choice for facilitating recovery and reducing rebound hyperkalemia.