Back to ENDOCRINOLOGYThe single most useful measurement is the serum TSH. It is increased in the thyreoprivic and goitrous varieties and is usually normal or undetectable in pituitary or hypothalamic hypothyroidism. In the hypothalamic or pituitary hypothyroidism the hyposecretion of TSH is usually accompanied by hyposecretion of other pituitary hormones. It is extremely important to evaluate the possibility of deficiency of other hormones, since thyroid replacement exacerbates mild ACTH insufficiency associated with hypothalamic or pituitary disease. If unrecognized, such patients may have an addisonian crisis provoked by thyroid hormone replacement. It is necessary to differentiate pituitary from hypothalamic disease, and for this the TRH test is most helpful. Absence of TSH response to TRH indicates pituitary deficiency.
The levels of free T4 and T4 are decreased in all forms of hypothyroidism. The combination of low serum FT4 and an elevated serum TSH is diagnostic of primary hypothyroidism. Serum T3 levels are variable and may be within the normal range.
In a patient whose symptoms are nonspecific or borderline and in whom an equivocally reduced free T4 index is obtained, the serum TSH may be significantly elevated. This condition is called has been called subclinical hypothyroidism.
The patient may be taking thyroid medication when first seen. A palpable or enlarged thyroid gland and a positive test for thyroid auto-antibodies would suggest underlying Hashimoto’s thyroiditis, in which case the medication should be continued.
Serum cholesterol and triglycerides, creatine phosphokinase (MM isoenzime), aldolase, lactic dehydrogenase, and SGOT may all be elevated in the patient with moderate to severe hypothyroidism. Hyponatremia with or without the inappropriate ADH syndrome is seen. There is often a modest anemia of chronic disease that may be macrocytic. Serum vitamin B12 should be measured in these patients because of the coexistence of pernicious anemia and Hashimoto’s thyroiditis.
It is very easy to recognize the classic picture of cretinism or juvenile and adult hypothyroidism . Occasionally, an infant with Down’s syndrome may be confused with a cretin. Chronic nephritis and nephrotic syndrome may simulate myxedema, particularly because of facial puffiness, pallor, anemia, hypercholesterolemia, and the serum T4 may be decreased if TBG is lost in urine.
A. Myxedema Coma
Myxedema coma is the end stage of untreated hypothyroidism. The condition is characterized by progressive weakness, stupor, hypothermia, hypoventilation, hypoglicemia, hyponatremia, water intoxication, shock and death. Since it occurs most frequently in older patients with underlying pulmonary and vascular disease, the mortality rate is extremely high.
The pathophysiology of myxedema coma involves:
1 - CO2 retention and hypoxia, due in a large part to a marked depression in the ventilatory responses to hypoxia and hypercapnia, though factors such as obesity, heart failure, ileus, immobilization, pneumonia, CNS depression may also contribute.
2 - fluid and electrolyte imbalance. The major one is water intoxication due to syndrome of inappropriate secretion of vasopressin (SIADH). This presents with hyponatremia and is managed by water restriction.
3 - hypothermia
Disorders that may precipitate myxedema coma include heart failure, pneumonia, pulmonary edema, pleural and peritoneal effusions, ileus, excessive fluid administration.
Myxedema and Heart Disease
Patients with myxedema and coronary artery disease can be treated surgically first, and more rapid thyroxin replacement therapy will then be tolerated.
Hypothyroidism and Neuropsychiatric Disease
There is often an association between hypothyroidism and depression, which may be quite severe.
Treatment of Hypothyroidism
Initiation of therapy in patients with severe hypothyroidism, older patients, and patients with cardiovascular disease may have an increased sensitivity to thyroid hormone and are at risk for acute cardiovascular and other complications if the hypothyroidism is corrected too quickly. Therefore, these patients should be given a very small dose initially (25mg of T4, which is increased to a full maintenance dose during a 6- to 12-week period. Younger patients and patients with less severe disease may be started on a slightly higher dose (50mg) and advanced to a full replacement more quickly.
Hypothyroidism is treated with levothyroxine(T4), which is available and inexpensive. T4 is converted to T3, so that both hormones become available even though only one is administered. The half-life of levothyroxine is about 7 days, so it need to be given only once daily. It is best to take the drug in the morning to avoid symptoms such as insomnia if the medication is taken at bedtime.
Dosage
Replacement doses in adults range from 0.05 to 0.2 mg/d. The dose varies with the patient’s age and body weight. In adults, the mean replacement dose is about 1.7mg/kg/d. In older adults, the replacement dose is lower, about 1.6 mg/kg/d. Levothyroxine has a sufficiently long half-life so that if the patient is unable to take medication by mouth for a few days, omitting T4 therapy will not be detrimental.
Treatment of Myxedema Coma
Myxedema coma is an acute medical emergency and should be treated in the intensive care unit. Blood gases must be monitored regularly, and the patient usually requires intubation and mechanical ventilation. Intravenous fluids should be administered with caution, and excessive free water intake must be avoided. The drugs must be given intravenously. The patients should receive an initial loading dose of levothyroxine intravenously (300-400mg) followed by 50 mg of levothyroxine intravenously daily. The clinical guides of improvement are a rise in body temperature and the return of normal cerebral and respiratory functions. Care must be taken to discard concomitant adrenal insufficiency.
Toxic Effects of Levothyroxine Therapy
There are no reported instances of allergy to pure levothyroxine, though it is possible that a patient may develop an allergy to the coloring dye or some component of the tablet. The major toxic reactions to levothyroxine overdosage are symptoms of hyperthyroidism - arrhythmia, insomnia, tremor and others.
The course of untreated myxedema is one of slow deterioration. However, with appropriate treatment, the long-term prognosis is excellent.
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