familial thyroid dyshormonogenesis

Familial thyroid dyshormonogenesis, also known as primary congenital hypothyroidism, is a rare condition characterized by a permanent deficiency of thyroid hormones present from birth. The signs and symptoms of this condition can vary in severity and may not be immediately apparent at birth.

Common Signs and Symptoms:

• Decreased activity and increased sleepiness
• Feeding difficulty and constipation
• Large fontanelles (soft spots on the skull)
• Macroglossia (enlarged tongue)
• Umbilical hernia
• Mottled, cool, and dry skin
• Coarse facial features
• Developmental delay

Clinical Features:

• Abnormality of head or neck, including macroglossia
• Abnormality of the digestive system, including constipation
• Abnormality of the endocrine system, including goiter (enlarged thyroid gland)

Age-Related Symptoms:

• Infants with familial thyroid dyshormonogenesis may show no features of the condition at birth, but as they grow and develop, symptoms such as decreased activity, feeding difficulty, and constipation may become apparent.
• Older children and adults with untreated congenital hypothyroidism may experience more severe symptoms, including developmental delay, coarse facial features, and mottled skin.

Incidence:

• Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns.
• The incidence of CH has increased over the past few decades due to improved detection methods.

It's essential to note that some babies with familial thyroid dyshormonogenesis may not show any obvious signs or symptoms at birth. Newborn screening is crucial for early detection and treatment of this condition. [1][2][3][4][5][6][7][8][9][10][11][12][13]

Familial thyroid dyshormonogenesis, a type of primary congenital hypothyroidism, can be diagnosed through various tests.

• Genetic testing: A definite molecular diagnosis of thyroid dyshormonogenesis allows genetic counseling and can guide the diagnosis. This test can detect high urinary MIT and DIT by tandem mass spectroscopy, which may become a useful diagnostic test [2].
• Thyroid scintigraphy: This is the most informative diagnostic procedure in patients with thyroid dysgenesis, providing etiologic diagnosis, as in alteration in the iodine transporter (NIS) [11]. It can help determine the underlying cause of congenital hypothyroidism.
• Perchlorate discharge test: Although relatively infrequently used, this test can differentiate the etiology of thyroid dyshormonogenesis. However, it is not necessary for treatment, as L-T4 replacement is always required for CH [13].
• Thyroid ultrasonography: This imaging technique can also be used to diagnose thyroid dyshormonogenesis.
• Gene panel testing: 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 [7].
• Hypothyroidism Panel: This panel includes sequence and deletion/duplication analysis of the listed genes, which can help diagnose familial thyroid dyshormonogenesis [8].

These diagnostic tests can help identify the underlying cause of familial thyroid dyshormonogenesis, allowing for proper treatment and management.

Treatment Options for Familial Thyroid Dyshormonogenesis

Familial thyroid dyshormonogenesis, a type of primary congenital hypothyroidism, can be effectively managed with drug treatment. The primary goal of treatment is to replace the deficient thyroid hormone and prevent irreversible neurological damage.

• Levothyroxine (T4): This synthetic thyroid hormone is the treatment of choice for familial thyroid dyshormonogenesis. The starting dose is typically 10-15mcg/kg/day, with the immediate goal of raising serum T4 above 130 nmol/L (10 ug/dL) as rapidly as possible [1]. With these doses, serum TSH usually normalizes in 2-4 weeks.
• Monitoring and Adjustment: Regular monitoring of thyroid hormone levels is essential to ensure that the treatment is effective. The dose may need to be adjusted based on individual patient needs.

Additional Treatment Considerations

While levothyroxine is the primary treatment, some patients may require additional medications or interventions. For example:

• Iodide Supplementation: In some cases, iodide supplementation may be recommended to address specific defects in thyroid hormone synthesis [5].
• Anti-thyroid Drugs: In rare instances, anti-thyroid drugs like MMZ may be used in conjunction with levothyroxine to manage the condition [7].

Importance of Early Detection and Treatment

Early detection and treatment are crucial in preventing irreversible neurological damage. Treatment should be initiated without delay, and the dose carefully calculated based on individual patient factors [6]. Regular follow-up and monitoring are essential to ensure that the treatment is effective and to make any necessary adjustments.

References:

[1] Knowledge on rare diseases and orphan drugs ... Familial thyroid dyshormonogenesis. [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 ... [6] Feb 1, 2022 — Treatment with levothyroxine (synthetic thyroid hormone, T4) should be started without delay. The dose is carefully calculated based on factors ... [7] by ASP van Trotsenburg · 2020 · Cited by 46 — Treatment consists of the anti-thyroid drug MMZ in a dose of approximately 0.5 (0.2–1.0) mg/kg/day, combined with levothyroxine.

Differential Diagnoses for Familial Thyroid Dyshormonogenesis

Familial thyroid dyshormonogenesis, a rare condition characterized by thyroid hormone deficiency present from birth, requires accurate differential diagnosis to rule out other forms of congenital hypothyroidism. The following conditions are considered in the differential diagnosis:

• Other forms of congenital hypothyroidism: These include defects in organogenesis of the thyroid gland (see [4] and [11]), which account for 85% of cases.
• Familial goiter: A history of congenital or familial goiter in a young individual may suggest thyroid dyshormonogenesis, although it can also be caused by other conditions (see [3]).
• Pendred syndrome: This rare genetic disorder can present with deafness and a palpable goiter, which may be confused with thyroid dyshormonogenesis (see [10]).
• Defects in thyroid hormone transport: A genetic defect affecting thyroid hormone transport can also lead to congenital hypothyroidism, although this is a rarer form of familial thyroid dysgenesis or dyshormonogenesis (see [10]).

Key Points

• Accurate differential diagnosis is crucial for identifying familial thyroid dyshormonogenesis.
• Other forms of congenital hypothyroidism, such as defects in organogenesis of the thyroid gland, are more common and should be ruled out first.
• A thorough medical history, including a family history of goiter or other thyroid disorders, can aid in differential diagnosis.

References

[3] History of congenital or familial goiter in a young individual (often diagnosed due to routine screening of newborns for congenital hypothyroidism) ... [10] This is usually found in thyroid dyshormonogenesis where there is a defect in thyroid hormone production. Pendred syndrome mentioned below can present with deafness and a palpable goiter. ... Differential diagnosis. [11] Abstract. Congenital hypothyroidism (CH) is the one of the most common preventable cause of mental retardation. In the majority of patients, CH is caused by an abnormal development of the thyroid gland (thyroid dysgenesis) that is a sporadic disorder and accounts for 85% of cases and the remaining 15% of cases are caused by dyshormonogenesis.