Clinical Case # 1: Weakness

Clinical Case #1: Muscular System - Medicine

Case: Weakness

Introduction

Thyrotoxic periodic paralysis is a well-established phenomenon. When the symptoms of thyrotoxicosis are separated from the clinical picture, many features of this disease are identical to those of familial hypokalemic (Decrease in Potassium) periodic paralysis. Patients with thyrotoxic periodic paralysis have recurrent muscular weakness of the four extremities, affecting mainly the lower extremities. The onset of paralytic attacks usually coincides with the onset of hyperthyroidism, though overt findings of thyrotoxicosis are rarely present with the initial paralytic attack (as exemplified in our case 1 patient). In some cases, the periodic paralysis is the sole manifestation of the hyperthyroidism. A clinically distinguishing characteristic of thyrotoxic periodic paralysis includes predominance in men, with a male-to-female ratio of 11:1.2 This is in contrast to hyperthyroidism alone in the general population, in which women are predominantly affected. The age of onset is usually in the third to fifth decades of life.





The condition has been linked with genetic mutations in genes that code for certain ion channels that transport electrolytes (Na and k ) across cell membranes . The main ones are the L- Type calcium channel alpha1- subunit potassium inward rectifier, it is therefore classified as a channelopathy. The abnormality in the channel is thought to lead to shifts of potassium into cells, under conditions of high Thyroxine (thyroid hormone) levels, usually with an additional precipitant.

Treatment of the hypokalemia, followed by correction of the hyperthyroidism, leads to complete resolution of the attacks. It occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent. TPP is one of several conditions that can cause periodic paralysis

Symptoms:

> Cramps / Pain
> Aching
> Stiffness
> Weakness/paralysis

• Comes and goes
• Lasts for up to several days
• More common in legs than arms
• Most common in shoulders and hips
• Triggered by heavy, high-carbohydrate, high-salt meals
• Triggered by rest after exercise

Paralysis occurs only when the patient is at rest, and usually in bed at night. The rest commonly follows a period of unusually great physical activity and consumption of a high-carbohydrate meal. Observant patients, realizing that paralysis did not occur while they were active, rapidly learn to "work off" an impending attack on the appearance of premonitory symptoms. The attacks of paralysis vary widely in severity and range from weakness of the muscles of the pelvic girdle, lasting several hours, to a total paralysis of all the muscles from the neck downward, lasting up to 48 hours. Proximal muscles are affected more severely than distal muscles. The paralysis can be asymmetrical in distribution, severely affecting the proximal muscles and the muscle groups that underwent the most strenuous physical exertion before the attack.Rare presentations include findings of upper motor neuron disorder, suggesting a possible spinal cord lesion or impairment of ventilatory function. In our patient in case 1, respiratory acidosis was found in arterial blood gas, which could signify a weakness of the respiratory muscles. Other reported cases have had respiratory and bulbar paralysis and paralysis of the pharyngolaryngeal junction. Mental function and sensation are not affected, and deep tendon reflexes are either absent or reduced. Recession of the paralysis is usually in the reverse order of its appearance. The muscles are commonly tender during and for a short time after recovery.




Biochemical Abnormalities:


> The hypokalemia probably does not reflect a depletion of the body's potassium stores.

> Study of arteriovenous serum potassium and sodium changes during an induced attack of thyrotoxic periodic paralysis suggested that the mechanism of serum potassium reduction is the result of influx of extracellular potassium to the intracellular space. In some cases, the serum potassium remains at a normal level.

> The neuromuscular symptoms usually improve as the potassium moves back from the intracellular space into the extracellular space. In some instances, hypophosphatemia has been reported in association with thyrotoxic periodic paralysis and hypokalemia, as occurred in our two patients. The correction of hypophosphatemia without phosphate administration supports the possibility of intracellular shift of phosphate in our two patients and the cases reported by Norris and Guthrie .

Mechanism/Pathophysiology:



The muscle weakness and increased risk of irregular heart beat in TPP result from markedly reduced levels of potassium in the bloodstream. Potassium is not in fact lost from the body, but increased Na+/K+ Atpase activity (the enzyme that moves potassium into cells and keeps sodium in the blood) leads to shift of potassium into tissues, and depletes the circulation. In other types of potassium derangement, the acid-base balance is usually disturbed, with metabolic alkalosis and metabolic acidosis often being present. In TPP, these disturbances are generally absent. Hypokalemia leads to hyperpolarization of muscle, making the neuromuscular junction less responsive to normal nerve impulses and leading to decreased contractility of the muscles.

It is not clear how the described genetic defects increase the Na+/K+-ATPase activity, but it is suspected that the enzyme becomes more active due to increased thyroid hormone levels. Hyperthyroidism increases the levels of  catecholamines (such as adrenaline) in the blood, increasing Na+/K+-ATPase activity. The enzyme activity is then increased further by the precipitating causes. For instance, increased carbohydrate intake leads to increased insulin levels; this is known to activate Na+/K+-ATPase. Once the precipitant is removed, the enzyme activity returns to normal levels. It has been postulated that male hormones increase Na+/K+-ATPase activity, and that this explains why males are at a higher risk of TPP despite thyroid disease being more common in females.

TPP is regarded as a model for related conditions, known as "channelopathies", which have been linked with mutations in ion channels; the majority of these conditions occurs episodically.

Patients with thyrotoxic periodic paralysis have attacks only when they are thyrotoxic. Graves' disease appears to be the most common cause of thyrotoxic periodic paralysis, since this disorder represents the majority of patients with hyperthyroidism. However, it appears that the specific cause of the thyrotoxic state is not a critical factor for the expression of the paralytic attacks because cases have been documented in association with jodbasedow, TSH-secreting pituitary tumor, abuse of thyroid hormone, and solitary toxic thyroid adenoma. These associations of paralysis with the different causes of thyrotoxicosis indicate that the attacks are induced in susceptible persons by a mechanism that is not autoimmune in origin. Paralytic attacks can be induced by insulin and carbohydrate administration in hyperthyroid patients with a history of thyrotoxic periodic paralysis but not in patients with a history of thyrotoxic periodic paralysis who have become euthyroid. Restoring the euthyroid state in patients with a history of thyrotoxic periodic paralysis usually prevents the recurrence of paralytic attacks. However, paralytic attacks recur if thyrotoxicosis recurs. In comparing thyrotoxic patients with recurrent paralytic attacks and those without such episodes, it was noted that the occurrence of paralysis was not related to the duration and severity of the thyrotoxicosis.

Grave's Disease- Graves' disease is one of the most common of all thyroid problems. It is also the leading cause of hyperthyroidism, a condition in which the thyroid gland produces excessive hormones.


Electronic References:


http://www.medscape.com/viewarticle/410649_3
http://en.wikipedia.org/wiki/Thyrotoxic_periodic_paralysis
http://www.webmd.com/a-to-z-guides/understanding-graves-disease-basics

Y.O.L.O