thyroid dyshormonogenesis 1

Thyroid dyshormonogenesis, also known as congenital hypothyroidism due to dyshormonogenesis, is a rare condition that affects the production of thyroid hormones in the body.

Causes and Genetics

This condition is caused by genetic defects in the synthesis of thyroid hormones. It can be due to either deficiency of thyroid enzymes, inability to concentrate, or ineffective binding. The genetic causes of thyroid dyshormonogenesis are complex and involve mutations in several genes involved in thyroid hormone production and recycling.

• Sodium-iodide symporter (NIS) gene: Mutations in the NIS gene can cause Thyroid dyshormonogenesis-1 (TDH1), a form of congenital hypothyroidism due to dyshormonogenesis. [5]
• Thyroid peroxidase gene (TPO): Mutations in the TPO gene can also cause thyroid dyshormonogenesis, specifically Thyroid dyshormonogenesis-2A (TDH2A). [9]

Symptoms and Characteristics

Patients with thyroid dyshormonogenesis develop hypothyroidism, which is characterized by a goiter (enlargement of the thyroid gland), fatigue, physical or mental slowness, and difficulties in initiating or performing simple tasks. [3] The condition can be transient or permanent, depending on the severity of the genetic defect.

• Goiter: A goiter is a common symptom of thyroid dyshormonogenesis, resulting from the accumulation of iodide in the thyroid gland due to defective conversion. [7]
• Hypothyroidism: Patients with thyroid dyshormonogenesis develop hypothyroidism, which can lead to fatigue, physical or mental slowness, and difficulties in initiating or performing simple tasks. [3]

Inheritance Pattern

The mode of inheritance for all forms of thyroid dyshormonogenesis is autosomal recessive, except for DUOX2 mutations, which may be autos

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 signs and symptoms of this condition are crucial for early diagnosis and treatment.

• Hypothyroidism: Patients develop hypothyroidism, characterized by a shortage of thyroid hormones.
• Goiter: A goiter, an enlarged thyroid gland, may be present.
• Difficulty Feeding: Infants with congenital hypothyroidism due to thyroid dyshormonogenesis may experience difficulty feeding and weight gain issues.
• Constipation: Constipation is another common symptom in infants and children with this condition.

Long-term Consequences

If left untreated, congenital hypothyroidism can lead to:

• Intellectual Disability: Untreated congenital hypothyroidism can result in intellectual disability and slow growth.
• Growth Failure: Growth failure and delayed puberty are also potential long-term consequences of untreated thyroid dyshormonogenesis.

References

[4] Thyroid dyshormonogenesis is a rare condition due to genetic defects in the synthesis of thyroid hormones. [1] [2] [6] They may have difficulty feeding and experience constipation. [3] Familial thyroid dyshormonogenesis is a type of primary congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.

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

• Thyroid imaging: Thyroid ultrasonography, thyroid scintigraphy, or perchlorate discharge test can be used for etiological diagnosis. In thyroid dyshormonogenesis, thyroid ultrasonography shows eutopic thyroid and depending on the severity of hypothyroidism, the thyroid size may be normal or large [11].
• Thyroid radionuclide uptake and scan: This test can help pinpoint the underlying etiology, although treatment may be started without these tests. It is usually found in thyroid dyshormonogenesis where there is a defect in thyroid hormone production [12].
• Serum thyroglobulin determination: This test can also help determine the underlying cause of congenital hypothyroidism.
• Genetic testing: Genetic testing can help with making the diagnosis and can guide genetic counseling. 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 [6].
• Thyroid function tests (TFTs): TFTs, including TSH and T4, can be used to monitor the effectiveness of treatment.

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) [15].

Treatment of Congenital Hypothyroidism

The treatment for congenital hypothyroidism, also known as thyroid dyshormonogenesis, involves the administration of synthetic thyroid hormone, specifically levothyroxine (T4).

• The recommended starting dose of levothyroxine is 10-15 mcg/kg/day [1][2].
• The immediate goal of treatment is to raise the serum T4 above 130 nmol/L (10 ug/dL) as rapidly as possible [1].
• Treatment with levothyroxine should be started without delay, and the dose is carefully calculated based on factors such as age, weight, and severity of hypothyroidism [4].

Treatment Goals

The primary goal of treatment in congenital hypothyroidism is to prevent the development of irreversible complications, such as growth retardation, developmental delays, and cognitive impairment.

• Treatment aims to detect the disease early and replace the thyroid hormone to prevent these complications [8].
• The administration of levothyroxine into the amniotic fluid or umbilical vein may be considered in cases where fetal goiter is present [10].

Importance of Early Detection

Early detection and treatment of congenital hypothyroidism are crucial for preventing long-term consequences.

• In children with CH, early identification and treatment with high-dose levothyroxine has been shown to improve growth and developmental outcomes [5].
• The most common form of thyroid hormone used in treatment is synthetic T4, which is identical to the T4 produced by the thyroid gland [2].

References:

[1] Context 1 [2] Context 2 [4] Context 4 [5] Context 5 [8] Context 8 [10] Context 10

Differential Diagnoses for Thyroid Dyshormonogenesis

Thyroid dyshormonogenesis, a type of primary hypothyroidism, has several differential diagnoses that need to be considered. These include:

• Aplastic or Hypoplastic Thyroid: This condition refers to the underdevelopment or absence of the thyroid gland, leading to congenital hypothyroidism [2][7].
• Autoimmune Thyroiditis: In this case, the immune system attacks the thyroid gland, leading to inflammation and dysfunction [2][7].
• TSH Insensitivity: A rare condition where the body's cells are resistant to the effects of Thyroid-Stimulating Hormone (TSH), leading to hypothyroidism [6].

These differential diagnoses need to be considered when diagnosing thyroid dyshormonogenesis, as they can present with similar symptoms and laboratory findings.

References: [1] Not relevant [2] Context 7: "Clinically the differential diagnosis for congenital hypothyroidism includes aplastic or hypoplastic thyroid and autoimmune thyroiditis." [3] Not relevant [4] Not relevant [5] Not relevant [6] Context 5: "Thyroid enlargement due to various inherited defects in thyroid hormone synthesis; Lack of circulating thyroid hormone activates TSH..." [7] Context 2: "Clinically the differential diagnosis for congenital hypothyroidism includes aplastic or hypoplastic thyroid and autoimmune thyroiditis." [8] Not relevant [9] Not relevant [10] Not relevant