Hypothyroidism is caused by a deficiency in the production of thyroid hormone and may be either primary or secondary. Primary hypothyroidism occurs when the thyroid gland does not make sufficient amounts of thyroid hormone. It is usually characterized by high levels of thyroid-stimulating hormone (TSH) and low levels of the thyroid hormones triiodothryronine (T3) and tetraiodothryonine (T4).

Secondary (or central) hypothyroidism is caused by disorders of the pituitary gland or hypothalamus. Generally, secondary hypothyroidism is associated with low TSH and low T3 and T4. However, TSH levels may also be normal or even slightly elevated. For this reason, TSH is often an unreliable measure of secondary hypothyroidism and should not be used to assess the adequacy of thyroid replacement in these patients.


Thyroid hormone deficiency causes mental retardation in infants, growth delay in children, and myxedema in adults. Symptoms of thyroid hormone insufficiency include cold intolerance, weight gain, memory loss, dry skin, hair loss, brittle nails, constipation, increased sleep demand, and fatigue. Severe hypothyroidism left untreated can lead to coma and even death.

Hypothyroidism from TSH or TRH deficiency can result from hypothalamic or pituitary destruction (neoplastic, inflammatory, granulomatous, vascular, traumatic, autoimmune, and radiation necrosis). Typically, loss of TSH secretion is associated with other hormonal abnormalities because there is a step-wise loss of pituitary function starting with growth hormone, gonadotropins, and then thyrotropin (lastly ACTH) in the presence of an expanding pituitary tumor.


Treatment of most types of hypothyroidism is successful with replacement therapy with thyroxine, which is adjusted until normal serum hormone levels are achieved. Our preferred approach for treating secondary hypothyroidism is to base the initial dose on the patient’s estimated lean body mass. We find that a starting dose of about 0.8 micrograms of T4 per pound of estimated lean body mass suffices for most patients.

Much lower doses are used initially in the elderly and in patients with cardiovascular disorders. We take into account other factors that may affect the dose such as other concomitant medical conditions, drugs, etc. Patients in need of cortisol replacement are treated with glucocorticoids for a few days before the institution of thyroid hormone.

We recommend treatment for 6 to 8 weeks and then a history and examination along with measurement of the free T4 level to assess the adequacy of the dose. We aim to resolve any symptoms and signs of thyroid hormone deficiency while at the same time avoiding symptoms and signs of thyroid hormone excess. This is usually accomplished by increasing the thyroid hormone dose by 12.5 to 25 micrograms every 6 to 8 weeks until the free T4 level is in the middle or even the upper one-half of the normal range. Once a stable dose is reached, we re-evaluate every 6 to 12 months and adjust the dose as necessary.