Resistance to thyroid stimulating hormone

Resistance to Thyroid Stimulating Hormone (RTH), also known as Thyroid Hormone Resistance or Thyroid Stimulating Hormone Resistance, is a rare condition characterized by the failure of thyroid gland cells to respond to Thyroid Stimulating Hormone (TSH), which is produced by the pituitary gland. This condition can lead to various clinical manifestations, including hypothyroidism or, paradoxically, symptoms of hyperthyroidism, depending on the level of thyroid hormone resistance and the presence of other thyroid disorders.

Etiology

Resistance to Thyroid Stimulating Hormone is most commonly caused by mutations in the thyroid hormone receptor beta (THRB) gene, which leads to a decreased sensitivity of the thyroid hormone receptors to TSH. This genetic mutation is usually inherited in an autosomal dominant manner, meaning that only one copy of the altered gene in each cell is sufficient to cause the disorder.

Clinical Presentation

Patients with RTH may present a wide range of symptoms that can vary significantly from one individual to another. Some may remain asymptomatic, while others may exhibit signs and symptoms of hypothyroidism, such as fatigue, weight gain, cold intolerance, and constipation. Conversely, symptoms of hyperthyroidism, including weight loss, palpitations, increased sweating, and heat intolerance, can also occur due to elevated levels of circulating thyroid hormones.

Diagnosis

The diagnosis of Resistance to Thyroid Stimulating Hormone is primarily based on laboratory tests showing elevated levels of circulating thyroid hormones (free T4 and T3) with non-suppressed or inappropriately normal TSH levels. Genetic testing for mutations in the THRB gene can confirm the diagnosis and help in the differentiation from other thyroid disorders.

Treatment

Management of RTH is challenging and should be tailored to the individual's symptoms and thyroid hormone levels. In cases where hypothyroid symptoms predominate, thyroid hormone replacement therapy may be considered. However, careful monitoring is required to avoid overtreatment, which can exacerbate symptoms of hyperthyroidism. In contrast, symptomatic treatment may be sufficient for individuals with mild or no symptoms.

Prognosis

The prognosis for individuals with Resistance to Thyroid Stimulating Hormone varies depending on the severity of the condition and the presence of other comorbidities. With appropriate management, most individuals can lead a normal life, although they may require lifelong monitoring of their thyroid function.