Hyperthyroidism in thyroid autonomyE05.2; E05.1; E05.0

Thyroid autonomy is defined as the uncontrolled (autonomous) production of thyroid hormones - in parenchymal areas of the thyroid gland that grow independently of the thyrotropic regulatory circuit (hypothalamus - pituitary - thyroid) and are endocrine active (Wieler H et al. 1992). According to the scintigraphic image, thyroid autonomy is divided into:

• Unifocal thyroid autonomy (autonomous adenoma, toxic autonomous adenoma)
• Multifocal thyroid autonomy (multinodular, often euthyroid nodular goiter, with several autonomous regions)
• Disseminated (diffuse) thyroid autonomy: increased uptake of the whole organ

Besides immunogenic hyperthyroidism (Graves' disease), functional thyroid autonomy is the most common cause of hyperthyroidism.

The most frequent cause of thyroid autonomy is an iodine deficiency goiter. The iodine-deficient goiter shows an increasing tendency to develop TSH-independent (autonomous) functional parenchymal areas (hot nodules) with increasing duration of the goiter, as well as depending on goiter size and nodular transformation of the organ. Here, iodine deficiency leads to a focal hypertrophy of thyroocytes which are activated due to a somatic point mutation in the gene of the TSH receptor (80%) or (more rarely) in the alpha subunit of the G protein of the TSH receptor gene via the activation of growth factors (EGF, IGF-1). These somatic heterozygous mutations each lead to a constitutive activation of the cAMP cascade in the mutated thyroid cell. The increased cAMP production in turn causes a stimulation of growth and hormone production of the thyroid epithelial cells (Paschke R et al 2000).

Toxic nodular goiter is a multinodular goiter with several autonomous regions (multifocal autonomy) leading to hyperthyroidism.

In this autonomous functionality with decoupling from the control loop, for example, a random exogenous iodine supply (e.g. administration of iodine-containing contrast media and drugs such as amiodarone) leads to acute onset of hyperthyroidism.

Patients mostly >40 years.

Thyroid autonomy develops slowly over several years and usually becomes symptomatic only at an advanced age due to the initial euthyroid metabolic state. Elderly patients with large nodular goiter show functional autonomy in >50% of cases. The oligosymptomatic adenomas can become manifest as a random finding when cardiac arrhythmias are clarified.

Clinically, a palpable or sonographically detectable thyroid node is usually found. Hyperthyroidism in autonomy can be triggered by exogenous iodine supply, e.g. by X-ray contrast medium or by amiodarone (clinical signs: tachycardia, weight loss, heat intolerance, psychomotor agitation, subtle tremor, diarrhoea, in women cycle disorders)

Sonography: Detection of adenoma nodes in the thyroid parenchyma. Determination of strumagrade according to WHO classification (grade 1 - grade 3).

Scintigraphy: The thyroid scintigraphy allows the localization of the autonomous tissue. Tc99m-pertechnetate or iodine-131 are used as tracers, which accumulate under TSH-suppression only in autonomous areas (with complete suppression of the remaining thyroid tissue) (shown as "hot iodavid node" in the scintigraphy).

Determination of TSH basal, fT3 and fT4 for the assessment of thyroid function (euthyroid, latent hyperthyroid, manifest hyperthyroid). Thyroid autoantibodies (TSH receptor autoantibodies, thyroid peroxidase antibodies) are usually negative.

There are 4 options for the therapy of uni- and multifocal thyroid autonomy: thyroid resection, radioiodine therapy (Meller J, et al. 2002), sclerotherapy by alcohol injection, drug therapy (thyrostatics). Since long-term treatment with thyrostatic drugs does not eliminate the cause of the disease, it is only indicated for the therapy of acute hyperthyroidism and preparation for curative procedures (Paschke R et al 2000). In surgical therapy, a function and morphology adapted and in cases of doubt rather generous resection strategy is aimed for.

Radioiodine therapy is a well established alternative to surgical procedures with few side effects. The ablative method of sclerotherapy is a possible alternative to surgery and radioiodine therapy, especially for autonomous volumes <30 ml and for patients with increased risk of surgery or dialysis patients.

The combination of immunohyperthyroidism of the Graves' disease type and thyroid autonomy is known as Marine-Lenhart syndrome. This constellation occurs in about 10% of Graves' cases.

1. Gotthardt M et al (2006) Decrease of (99m)Tc-uptake in autonomous thyroid tissue in Germany since the 1970s. Clinical implications for radioiodine therapy. Nuclear Medicine 45:122-125
2. Meller J, et al (2002) Radioiodine Treatment (RIT) of thyroidal functional autonomy. Nucl Med Rev Cent East Eur 5:1-10.
3. Paschke R et al (2000) Therapy of uni- or multifocal thyroid autonomy. Dtsch Arztebl 97: A-1463 / B-1245 / C-1168
4. Wieler H et al (1992) Diagnosis of functional thyroid autonomy. Vienna Med Weekly 142:213-216.