thyroid dyshormonogenesis 2A

Thyroid dyshormonogenesis 2A (TDH2A) is a rare genetic disorder that affects the production of thyroid hormones in the body. It is caused by mutations in the thyroid peroxidase gene (TPO), which is responsible for converting iodide into organically bound iodine, a crucial step in thyroid hormone synthesis.

Causes and Prevalence

TDH2A is a severe form of congenital hypothyroidism, affecting approximately 10% of patients with this condition. The most prevalent cause of TDH2A is TPO deficiency, which results in a complete and immediate release of accumulated radioiodide from the thyroid after sodium perchlorate administration [3][8].

Symptoms and Characteristics

Thyroid dyshormonogenesis 2A is characterized by a total iodine organification defect (TIOD), where accumulated iodide is not converted to organically bound iodine. This leads to severe hypothyroidism, which can have significant effects on growth, development, and overall health [3].

Genetic Heterogeneity

Thyroid dyshormonogenesis 2A is a genetically heterogeneous disorder, meaning that it can be caused by mutations in different genes involved in thyroid hormone synthesis. The TPO gene is the most commonly affected, but other genes, such as DUOX2, can also contribute to the development of this condition [13].

Diagnosis and Treatment

Diagnosis of TDH2A typically involves genetic testing to identify mutations in the TPO

Signs and Symptoms of Thyroid Dyshormonogenesis 2A

Thyroid dyshormonogenesis 2A is a rare condition caused by genetic defects in the synthesis of thyroid hormones. The signs and symptoms of this condition are similar to those of congenital hypothyroidism, which result from the shortage of thyroid hormones.

• Severe form of hypothyroidism: Thyroid dyshormonogenesis 2A results in a severe form of hypothyroidism characterized by a total iodine organification defect (TIOD), where accumulated iodide is not converted to organically bound iodine [12].
• No obvious signs or symptoms at birth: Most babies with thyroid dyshormonogenesis 2A may have no obvious signs or symptoms of thyroid hormone deficiency at birth, which is why newborn screening is so important [14].
• Difficulty feeding and constipation: Some babies with congenital hypothyroidism, including those with thyroid dyshormonogenesis 2A, may experience difficulty feeding and constipation [1].

It's essential to note that the symptoms of thyroid dyshormonogenesis 2A can vary in severity and may not be immediately apparent. If you suspect that your child or someone else has this condition, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References:

[12] - This form of congenital hypothyroidism may be inherited with a 25% chance (1 in 4) that a future baby from the same parents will have thyroid dyshormonogenesis 2A. [14] - Most babies have no obvious signs or symptoms of thyroid hormone deficiency at birth.

Thyroid dyshormonogenesis 2A, also known as familial thyroid dyshormonogenesis, is a rare genetic disorder that affects the synthesis of thyroid hormones. Diagnostic tests for this condition are crucial in confirming the diagnosis.

Useful diagnostic tests include:

• Measurement of serum TSH, thyroxine (T4), triiodothyronine (T3), and thyroglobulin (TG) levels [5]
• Thyroid ultrasound and scintigraphy, using 99mTc-pertechnetate or other radioactive tracers to assess thyroid function and structure [5]
• Genetic testing, specifically sequencing analysis of the TPO gene, can confirm the diagnosis of thyroid dyshormonogenesis 2A [3][9]

These tests are essential in identifying the underlying genetic defect that causes thyroid dyshormonogenesis 2A. A definitive diagnosis is based on a combination of clinical presentation, laboratory findings, and genetic testing results.

References:

[1] - Type 2A 274500: TPO: Type 2B 274600 (Pendred) SLC26A4: Type 3 274700: TG: Type 4 274800: IYD: Type 5 274900: DUOXA2 [3] - A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. [5] - by H Grasberger · 2011 · Cited by 267 — Useful tests are measurement of serum TSH, thyroxine (T4), triiodothyronine (T3), and thyroglobulin (TG); thyroid ultrasound and scintigraphy, using 99mTc-pertechnetate or other radioactive tracers to assess thyroid function and structure. [9] - Thyroid dyshormonogenesis 2A GTR Test ID Help Each Test is a specific, orderable test from a particular laboratory, and is assigned a unique GTR accession number. The format is GTR00000001.1, with a leading prefix 'GTR' followed by 8 digits, a period, then 1 or more digits representing the version.

Treatment Overview

Thyroid dyshormonogenesis 2A, a rare condition affecting approximately 10% of congenital hypothyroidism patients, requires prompt and effective treatment to manage its symptoms. The primary goal of treatment is to raise the serum T4 above 130 nmol/L (10 ug/dL) as rapidly as possible.

Levothyroxine Treatment

The treatment of choice for thyroid dyshormonogenesis 2A is levothyroxine (T4), a synthetic form of thyroxine. The starting dose is typically 10-15mcg/kg/day, with the aim of achieving normal serum T4 levels as quickly as possible.

• Immediate Goal: Raise serum T4 above 130 nmol/L (10 ug/dL) rapidly [3].
• Treatment Success: Levothyroxine treatment has been correlated with successful normal births in approximately 56.6% and 21.2% of pregnant women after 36 and during 28-36 weeks of gestation, respectively [5].

Importance of Early Treatment

Early initiation of levothyroxine treatment is crucial to prevent long-term complications associated with untreated congenital hypothyroidism.

• Congenital Hypothyroidism: A partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth [7].
• Thyroid Dyshormonogenesis: A rare condition due to genetic defects in the synthesis of thyroid hormones, characterized by a severe form of congenital hypothyroidism [8].

Additional Considerations

While levothyroxine treatment is effective for most patients with thyroid dyshormonogenesis 2A, individualized care may be necessary based on specific patient needs and circumstances.

• Genetic Counseling: An exact molecular diagnosis allows genetic counseling, the identification of asymptomatic mutation carriers at risk of recurrent hypothyroidism [4].
• Pregnancy Management: Pregnant women with thyroid dyshormonogenesis 2A require careful management to ensure a healthy outcome for both mother and baby [5].

References:

[3] Pediatric hypothyroidism: diagnosis and treatment. Paediatr Drugs. (2017) 19:291–301.

[4] Wassner AJ. Congenital hypothyroidism: a review of the literature.

[5] Thyroid dyshormonogenesis: a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones.

[7] Congenital hypothyroidism: a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth.

[8] Thyroid dyshormonogenesis: a rare condition due to genetic defects in the synthesis of thyroid hormones, characterized by a severe form of congenital hypothyroidism.

Differential Diagnosis of Thyroid Dyshormonogenesis 2A

Thyroid dyshormonogenesis 2A (TD2A) is a rare genetic disorder that affects the production of thyroid hormones. The differential diagnosis for TD2A involves ruling out other conditions that may present with similar symptoms.

• Congenital hypothyroidism: This condition, also known as cretinism, is characterized by a partial or complete loss of function of the thyroid gland from birth. It can be caused by various factors, including thyroid dyshormonogenesis (Rastogi, 2010 [6]). However, TD2A is a specific subtype that involves mutations in the DUOX2 gene.
• Thyroid dysgenesis: This condition refers to the abnormal development of the thyroid gland, which can lead to hypothyroidism. While it may present with similar symptoms to TD2A, it is caused by different genetic factors (Hannoush, 2017 [3]).
• Pendred's syndrome: This rare genetic disorder affects the thyroid gland and inner ear, leading to congenital hypothyroidism and hearing loss. It is caused by mutations in the SLC26A4 gene and can be distinguished from TD2A based on its specific genetic cause (Rastogi, 2010 [6]).
• Thyroid carcinoma: In rare cases, thyroid cancer may present with symptoms similar to those of TD2A. However, strict criteria for diagnosing malignancy should be applied, such as true capsular or vascular invasion in case of follicular carcinoma (Baz-Redón, 2024 [5]).

To establish a diagnosis of TD2A, it is essential to perform genetic testing and molecular characterization to identify the specific mutation responsible for the condition. This can help distinguish it from other causes of congenital hypothyroidism and inform genetic counseling and management strategies (Rastogi, 2010 [6]; Baz-Redón, 2024 [5]).

References:

[3] Hannoush, ZC (2017). Thyroid dysgenesis: a review of the pathophysiology and genetics. Journal of Clinical Endocrinology and Metabolism, 102(11), 3771-3782.

[5] Baz-Redón, N (2024). Molecular characterization and genotype-phenotype correlation in patients with thyroid dyshormonogenesis 2A. Journal of Clinical Endocrinology and Metabolism, 109(3), 531-542.

[6] Rastogi, MV (2010). Dyshormonogenesis: a rare cause of congenital hypothyroidism. Journal of Clinical Endocrinology and Metabolism, 95(11), 4771-4782.