thyroid dyshormonogenesis 5

Thyroid dyshormonogenesis is a rare condition that affects the production of thyroid hormones in the body. It occurs due to genetic defects in the synthesis of these hormones, leading to a deficiency or malfunctioning of the enzymes responsible for their production.

Causes and Symptoms

The condition can be caused by various genetic mutations, including those affecting the sodium-iodide symporter (NIS) gene, which is essential for the uptake of iodine into the thyroid gland. This leads to a defect in the conversion of accumulated iodide to organically bound iodine, resulting in hypothyroidism.

The symptoms of thyroid dyshormonogenesis can be subtle and may include fatigue, physical or mental slowness, and difficulties in initiating or performing simple tasks. In some cases, goiter (enlargement of the thyroid gland) may also occur.

Types and Incidence

Thyroid dyshormonogenesis is a heterogeneous group of genetic diseases, with various forms caused by different genetic mutations. The condition can be inherited in an autosomal recessive manner, meaning that both parents must carry the mutated gene for their child to inherit it. In some cases, the mutation may be autosomal dominant.

The incidence of thyroid dyshormonogenesis varies depending on the population and the specific genetic mutation involved. However, it is generally considered a rare condition.

References

• [5] Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism.
• [6] Thyroid dyshormonogenesis-1 (TDH1) is caused by homozygous or compound heterozygous mutation in the sodium-iodide symporter (NIS) gene (SLC5A5; 601843).
• [7] A disorder due to defective conversion of accumulated iodide to organically bound iodine.
• [10] Defects in thyroid hormone synthesis (dyshormonogenesis) In about 15% of cases, CH is due to hormonogenesis defects caused by mutations in genes involved in thyroid hormone synthesis, secretion or recycling.

Signs and Symptoms of Thyroid Dyshormonogenesis

Thyroid dyshormonogenesis, a rare condition due to genetic defects in the synthesis of thyroid hormones, can manifest in various ways. The symptoms may vary depending on the severity of the condition and individual factors.

• Hypothyroidism: Patients develop hypothyroidism, characterized by a deficiency of thyroid hormones.
• Goiter: A goiter, an enlargement of the thyroid gland, may be present.
• Poor Feeding and Growth Failure: Infants with congenital hypothyroidism due to thyroid dyshormonogenesis may experience poor feeding and growth failure.
• Constipation: Constipation is another symptom that can occur in individuals with this condition.

If left untreated, congenital hypothyroidism can lead to more severe consequences, including:

• Intellectual Disability: Untreated congenital hypothyroidism can result in intellectual disability.
• Slow Growth: Slow growth and development are also potential outcomes if the condition is not addressed.

It's essential to note that these symptoms may be similar to those of other conditions, making accurate diagnosis crucial. A healthcare professional should be consulted for proper evaluation and treatment.

References:

• [4] Thyroid dyshormonogenesis is a rare condition due to genetic defects in the synthesis of thyroid hormones.
• [6] They may have difficulty feeding and experience constipation.
• [7] Aug 27, 2020 — Common signs of the condition include: large fontanelles;; myxoedema – with coarse features, a large head, and oedema of the genitalia and ...
• [8] May 2, 2023 — Signs and symptoms · Decreased activity · Large anterior fontanelle · Poor feeding and weight gain · Small stature or poor growth · Jaundice.

Thyroid dyshormonogenesis, also known as congenital hypothyroidism due to thyroid hormone biosynthesis defects, can be diagnosed through various diagnostic tests.

• Thyroid imaging: This includes ultrasonography, scintigraphy, or perchlorate discharge test. These tests can help identify the underlying cause of congenital hypothyroidism and differentiate between thyroid dysgenesis and dyshormonogenesis [6][11].
• Thyroid function tests (TFTs): TFTs, including TSH and T4 levels, are essential for diagnosing congenital hypothyroidism. Thyroxine hormone replacement with L-thyroxine is given once daily and titrated to TFTs [8].
• Genetic testing: Genetic testing can help identify the underlying genetic cause of thyroid dyshormonogenesis. A 22 gene panel that includes assessment of non-coding variants is ideal for patients with a clinical suspicion of congenital hypothyroidism or thyroid dyshormonogenesis [5].

Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may also be used to help pinpoint the underlying etiology. However, treatment may be started without these tests, especially in cases of thyroid dyshormonogenesis where there is a defect in thyroid hormone production [12].

It's worth noting that diagnostic testing may include measurement of thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, and thyroxine-binding globulin (TBG) to confirm the diagnosis of congenital hypothyroidism due to thyroid dyshormonogenesis [15].

Treatment Options for Thyroid Dyshormonogenesis

Thyroid dyshormonogenesis, a form of congenital hypothyroidism, can be treated with various medications to replace the missing or impaired thyroid hormones. According to medical research [6], treatment aims to detect the disease early and replace the thyroid hormone to prevent development of irreversible neurological disability.

Medications Used in Treatment

The most common medication used in the treatment of thyroid dyshormonogenesis is levothyroxine (synthetic thyroid hormone, T4) [4]. The dose is carefully calculated based on factors such as age, weight, and severity of the condition. Rapid genetic diagnosis has been suggested to allow for changes in management, as certain defects could possibly be treated with iodide supplementation rather than traditional T4 therapy [5].

Importance of Early Detection and Treatment

Early detection and treatment are crucial in preventing long-term complications associated with untreated congenital hypothyroidism. Studies have shown that T4 therapy is most effective in decreasing the size of small diffuse goiters in patients with a basal TSH within the normal range [9]. Compliance with thyroid hormone treatment was stressed, as non-compliance can lead to poor outcomes.

References

• [6] Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital).
• [4] Feb 1, 2022 — Treatment with levothyroxine (synthetic thyroid hormone, T4) should be started without delay. The dose is carefully calculated based on factors ...
• [5] by DP Sparling · 2016 · Cited by 11 — Rapid genetic diagnosis has been suggested to allow for changes in management, as certain defects could possibly be treated with iodide supplementation rather ...
• [9] Oct 5, 2021 — Studies have shown that T4 therapy is most effective in decreasing the size of small diffuse goiters in patients with a basal TSH within the ...

Differential Diagnosis of Thyroid Dyshormonogenesis

Thyroid dyshormonogenesis, a type of primary congenital hypothyroidism, can be challenging to diagnose due to its similarity with other conditions. The differential diagnosis for thyroid dyshormonogenesis includes:

• Aplastic or hypoplastic thyroid: This condition is characterized by the underdevelopment or absence of the thyroid gland, which can lead to congenital hypothyroidism.
• Autoimmune thyroiditis: In this condition, the immune system attacks the thyroid gland, leading to inflammation and potentially causing congenital hypothyroidism.
• Multinodular endemic goiter: This is a type of goiter that can be caused by iodine deficiency or other environmental factors. It can present with similar symptoms to thyroid dyshormonogenesis.

According to [8], dyshormonogenesis may be suspected in an infant detected with congenital hypothyroidism and a goiter, which can help narrow down the differential diagnosis.

In addition, [12] states that congenital hypothyroidism is caused by abnormal development of the thyroid gland (thyroid dysgenesis) in 85% of cases, while the remaining 15% are caused by dyshormonogenesis. This information can be useful in differentiating between these two conditions.

It's essential to note that a definitive diagnosis of thyroid dyshormonogenesis requires genetic testing and molecular analysis, as mentioned in [10].