Clinical features

The clinical features of hypothyroidism include:

Causes

Over 90% of cases of hypothyroidism occur as a consequence of:

Rarer causes include:

Diagnosis

Hypothyroidism is caused by a deficiency of thyroid hormones. Primary hypothyroidism is failure of the thyroid gland itself and is one of the most commonly encountered endocrine problems. The demonstration of an elevated TSH concentration is usually diagnostic. Secondary hypothyroidism, failure of the pituitary to secrete TSH, is much less common. Isolated pituitary deficiency of TSH is rare, but impairment of the hypothalamic–pituitary–thyroid axis may happen as a result of any pituitary disease or damage.

Clinical features other than those of hypothyroidism may indicate the need for investigation of pituitary function (see pp. 84–85), and the TRH test will be included in such a protocol.

A strategy for the biochemical investigation of clinically suspected hypothyroidism is shown in Figure 45.1.

Treatment

Replacement therapy with T₄ is the treatment of choice since the hormone is readily available in a pure stable form, and is inexpensive. Monitoring TSH concentrations can be helpful in assessing the adequacy of treatment. Once the dosage is established, the patient will be required to continue treatment for life (Fig 45.2).

Figure 45.3 shows the need for careful monitoring of treatment. This graph shows the changes in thyroid hormone results as a hyperthyroid woman patient became hypothyroid after radioiodine treatment, and it subsequently proved difficult to stabilize her on a replacement dose of thyroxine.

Screening for neonatal hypothyroidism

Congenital hypothyroid disorders occur with a frequency of one in every 4000 live births (pp. 156–157). If they are diagnosed at an early age, replacement thyroid hormone can be given and normal development can occur. Delays in treatment result in cretinism (see p. 156). Elevated TSH, measured in blood spots, is diagnostic of disorders of the thyroid itself, i.e. primary neonatal hypothyroidism. The TSH screening test does not pick up pituitary dysfunction in the newborn.

Non-thyroidal illness

In health the major factor that regulates the serum concentration of TSH is the feedback of thyroid hormone activity on the pituitary and, to a lesser extent, on the hypothalamus. Other factors also play a role. There is a diurnal rhythm with the serum TSH reaching a peak between 2 and 4 am and a nadir in the afternoon. In systemic illness the normal regulation of TSH, T₄ and T₃ secretion, and the subsequent metabolism of the thyroid hormones, is disturbed. Increased amounts of T₄ are converted to the biologically inactive reverse T₃, rather than to T₃. The resultant reduction in thyroid hormone activity does not result in an increased serum TSH concentration. TSH secretion is suppressed (hypothesized to be due to increased circulating levels of endogenous steroids, dopamine and prostaglandins); T₄ and T₃ concentrations are usually decreased.

The concentrations of the transport proteins also decrease. A low serum albumin and transthyretin (pre-albumin) are classic features of the metabolic response to illness, and increased free fatty acid concentrations compete with T₄ and T₃ for their binding sites.

These changes result in sick patients having low serum T₄, T₃ and TSH, and if thyroid function tests are requested the results may well be misinterpreted. A typical non-thyroidal illness pattern might be:

These results were obtained in a man with acute pancreatitis. In developing hypothyroidism the T₃ would be maintained within the reference range. In decreased TBG states the T₄ and T₃ would fall in parallel. A low T₃ is almost invariably due to the presence of non-thyroidal illness.

Equally, for reasons that are not yet fully understood, the TSH is increased in acute illness and the serum T4 and FT₄ may be increased or decreased though the T₃ is decreased. These disturbances in the normal regulation of the hypothalamic-pituitary-thyroid axis in systemic illness is usually referred to as the “sick euthyroid syndrome” As this term implies the patients are euthyroid and there is no evidence to support treating them with either T₄ or T₃. Studies have shown that in 90% of acutely ill patients in whom the TSH is <0.04 or >20.0 mU/L, i.e. clearly outside the reference interval, are not found to have thyroid dysfunction when they recover. In clinical practice, one should postpone measuring thyroid function tests until the patient has recovered from their acute illness unless there is good clinical evidence that hypo- or hyperthyroidism is a primary cause of their acute condition.