50: Nondiabetic Endocrine Disease

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Chapter 50 Nondiabetic Endocrine Disease

Joel E. Wilson, MD

1 Describe four steps involved in thyroid hormone synthesis

1. Uptake of iodide: Iodide from the bloodstream is concentrated in thyroid cells by an active transport mechanism.
2. Iodination of thyroglobulin: Thyroglobulin, a large glycoprotein rich in tyrosine, is enzymatically iodinated and stored in the thyroid follicles.
3. Coupling reactions: The monoiodotyrosine and di-iodotyrosine moieties within the thyroglobulin molecule are coupled to one another to form tri-iodothyronine (T3) and thyroxine (T4).
4. Release of hormones: T3 and T4 are enzymatically cleaved from thyroglobulin within the follicular cell and released into the bloodstream.

2 How much tri-iodothyronine and thyroxine are produced? What regulates their production?

Approximately 8 mcg of T3 and 90 mcg of T4 are produced daily. Additional T3 is formed from the peripheral conversion of T4 to T3. T3 is approximately four times more potent than T4 but has a much shorter half-life; therefore the contribution of each to total thyroid activity is approximately equal. Thyroid-stimulating hormone (TSH) (produced by the anterior pituitary gland) acts on thyroid tissue to increase the rates of all steps involved in thyroid hormone synthesis and release. Thyrotropin-releasing hormone (TRH) (produced by the hypothalamus) in turn regulates the amount of TSH produced by the pituitary. T3 and T4 inhibit release of TSH and to a much smaller degree the release of TRH, thus establishing a negative feedback control mechanism.

3 List the common thyroid function tests and their use in assessment of thyroid disorders

Thyroid function tests include total T4 level, total T3 level, TSH level, and resin T3 uptake (T3RU). The T3RU is useful in conditions that alter levels of thyroid-binding globulin, which would alter total T4 results (Table 50-1).

Table 50-1 Usefulness of Thyroid Function Tests in the Diagnosis of Hypothyroid or Hyperthyroid States

image

4 List common signs, symptoms, and causes of hypothyroidism

Symptoms Signs
Fatigue Bradycardia
Cold intolerance Hypothermia
Constipation Deep tendon reflex relaxation phase prolongation
Dry skin Hoarseness
Hair loss Periorbital edema
Weight gain  

The most common cause of hypothyroidism is surgical or radioiodine ablation of thyroid tissue in the treatment of hyperthyroidism, most commonly Graves’ disease. Other causes of hypothyroidism include chronic thyroiditis (Hashimoto’s thyroiditis), drug effects, iodine deficiency, and pituitary or hypothalamic dysfunction.

The signs and symptoms observed in patients with mild hypothyroidism are nonspecific, and clinical detection is extremely difficult. Patients with severe long-term untreated hypothyroidism may progress to myxedema coma, which is frequently fatal. Factors that may lead to myxedema coma in hypothyroid patients include cold exposure, infection, trauma, and administration of central nervous system depressants. Myxedema coma is characterized by hypoventilation, hypothermia, hypotension, hyponatremia, hypoglycemia, obtundation, and adrenal insufficiency.

5 Of the numerous manifestations of hypothyroidism, which are most important in relation to anesthesia?

Hypothyroidism causes depression of myocardial function caused by protein and mucopolysaccharide deposition within the myocardium and depression of intracellular myocardial metabolism. Cardiac output declines as a result of decreased heart rate and stroke volume. Decreased blood volume, baroreceptor reflex dysfunction, and pericardial effusion may also accompany hypothyroidism. All of these effects make the hypothyroid patient sensitive to the hypotensive effects of anesthetics.

Hypoventilation may be a feature of hypothyroidism. The ventilatory responses to both hypoxia and hypercarbia are significantly impaired, making the hypothyroid patient sensitive to drugs that cause respiratory depression. Hypothyroidism also decreases the hepatic and renal clearance of drugs. In addition, patients are prone to hypothermia because of lowered metabolic rate and consequent lowered heat production.

6 How does hypothyroidism affect minimum alveolar concentration of anesthetic agents?

Animal studies show that minimum alveolar concentration (MAC) is not affected by hypothyroidism. Clinically it has been noted that hypothyroid patients have increased sensitivity to anesthetic agents. This is caused not by a decrease in MAC per se but by the patient’s metabolically depressed condition.

7 How is hypothyroidism treated?

Treatment consists of supplementation with exogenous thyroid hormones, most frequently levothyroxine (T4), because its long half-life, 6 to 7 days, results in a more constant serum level. Levothyroxine is available for intravenous use with the intravenous dose being one half the oral dose. The principal risk with treatment is in patients with coronary artery disease (CAD). An increase in the basal metabolic rate may result in myocardial ischemia. A suggested thyroid supplementation protocol for hypothyroid patients is summarized below:

image Patients without CAD: T4 50 mcg/day increasing monthly by 50-mcg/day increments until a euthyroid state is reached.
image Patients with CAD: T4 25 mcg/day increasing monthly by 25-mcg/day increments until a euthyroid state is achieved.
image In urgent situations thyroid supplementation may be given with caution intravenously. The recommended dose is T4 300 mcg/m2 by slow infusion. Hypothyroid patients receiving intravenous supplementation must be monitored closely for signs and symptoms of cardiac ischemia and adrenal insufficiency.
image When treating severe hypothyroidism, glucocorticoids should also be administered.

8 Under what circumstances should elective surgery be delayed for a hypothyroid patient?

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