Thyroid function disorders

Clinical information

Thyroid diseases are extremely common. In Germany, it is estimated that one in three adults suffers from thyroid disease at least once in their lifetime. The risk of disease increases with age. Generally, a distinction is made between hormonal dysfunctions, such as hyperthyroidism or hypothyroidism, and a change in the size and condition of the thyroid gland (e.g. strumae, nodules or tumours).

General symptoms of hyperthyroidism include weight loss, sweating, disturbed sleep and palpitations. In hypothyroidism, symptoms include fatigue, weight gain, sensitivity to the cold or depressive moods.

The hypothalamic-pituitary-thyroid axis regulates the concentration of thyroid hormones in the blood. Thyrotropin-releasing hormone (TRH), thyrotropin (thyroid-stimulating hormone, TSH) and the thyroid hormones triiodothyronine (T3) and thyroxine (T4) are closely related and regulate each other to maintain the delicate balance. The binding of TSH to the TSH receptors of the thyroid gland stimulates the synthesis and secretion of the hormones T3 and T4. Most of the circulating T3 and T4 is in bound form, so only free forms of thyroid hormones (fT3 and fT4) are considered biologically active. The biologically inactive metabolite reverse triiodothyronine (rT3) is produced due to the impaired conversion of T4 to T3. 

Calcitonin is a hormone produced in the parafollicular cells (C cells) of the thyroid gland and is involved in the regulation of calcium levels. 

Hyper- or hypothyroidism can be primary or secondary. While the origin of the primary disease lies in the thyroid gland itself, the cause of the secondary form can be found in the hypothalamus or the pituitary gland. 

In primary hyperthyroidism, the production of T3 and T4 is increased, which inhibits the pituitary gland’s release of TSH. Thus, the TSH concentration in the blood decreases and the fT4 or fT3 values are borderline or elevated. In secondary hyperthyroidism, the concentrations of fT3, fT4 as well as TSH are elevated. The pituitary gland is dysfunctional: Either it releases too much TSH, e.g. due to a TSH-producing tumour, which in turn causes the thyroid gland to produce more T3 and T4, or thyroid hormone resistance is present. The most common causes of hyperthyroidism are Graves’ disease (an autoimmune disease), multinodular strumae, thyroiditis or autonomous hyperfunctional nodules (so-called “hot” nodules). 

Primary hypothyroidism is characterised by increased TSH and decreased thyroid hormone concentrations. The most common cause is an autoimmune disease, most frequently, Hashimoto’s thyroiditis.  However, hypothyroidism with struma can also occur due to iodine deficiency, for example, as iodine reduces thyroid hormone production. This in turn causes an increase in TSH and an enlargement of the thyroid gland. Secondary hypothyroidism occurs when the hypothalamus produces insufficient amounts of TRH or the pituitary gland produces too little TSH. In addition to the TSH concentration, the concentration of thyroid hormones is also reduced. 

Hypothyroidism should be distinguished from low-T3 syndrome (euthyroid sick syndrome, non-thyroidal illness), which is characterised by a change in the homoeostasis of thyroid hormones: The inactive metabolite rT3 accumulates, TSH levels are normal to low, fT3 levels are low and fT4 levels are also reduced with long duration of disease. 

In addition to a disturbed thyroid hormone regulation, the symptoms of hyper- or hypothyroidism can also be caused by thyroiditis (inflammation of the thyroid gland).

Diagnostics

If hyperthyroidism or hypothyroidism is suspected, the results of a thyroid function test should be considered in addition to the clinical picture. Usually, this test includes the determination of the TSH level and the measurement of the free thyroid hormones (fT3 and fT4). The determination of antibodies against thyroid antigens can be useful in extended diagnostics, for example to determine a possible causative autoimmune disease. In patients with suspected low-T3 syndrome, the additional determination of rT3 can be useful to differentiate from central hypothyroidism. In the case of thyroid nodules, the calcitonin level should be determined, which can provide information on medullary thyroid carcinoma (C-cell carcinoma).