Summary about Disease
Thyroxine-binding globulin (TBG) deficiency is a genetic condition characterized by reduced levels or absence of TBG, a protein in the blood that carries thyroid hormones (thyroxine, or T4, and triiodothyronine, or T3). Because TBG binds to most of the thyroid hormones in the bloodstream, a deficiency impacts the levels of thyroid hormones circulating in the body. In many cases, individuals with TBG deficiency are asymptomatic and have normal thyroid function.
Symptoms
Many individuals with TBG deficiency are asymptomatic. When symptoms do occur, they are usually mild signs of hypothyroidism (underactive thyroid). These can include:
Fatigue
Weight gain
Constipation
Dry skin
Sensitivity to cold
Goiter (enlarged thyroid gland - rare)
In children, possible developmental delays (rare and usually associated with severe TBG deficiency and/or concurrent thyroid issues).
Causes
TBG deficiency is almost always caused by genetic mutations in the TBG gene (SERPINA7) located on the X chromosome. It is inherited in an X-linked pattern. Males, having only one X chromosome, will express the condition if they inherit the mutated gene. Females, having two X chromosomes, can be carriers (having one normal and one mutated gene) or can express the condition if they inherit two mutated genes. Some acquired causes are elevated androgens, nephrotic syndrome, and severe illness.
Medicine Used
4. Medicine used Treatment is typically not necessary for individuals with TBG deficiency who have normal thyroid function and are asymptomatic. If thyroid hormone levels are low or symptoms of hypothyroidism are present, thyroid hormone replacement therapy (levothyroxine) may be prescribed to normalize thyroid hormone levels. The dosage is individualized based on the patient's needs and thyroid hormone levels.
Is Communicable
No. TBG deficiency is a genetic condition and is not communicable (cannot be spread from person to person through infection).
Precautions
Individuals diagnosed with TBG deficiency, especially those with reduced thyroid hormone levels, should adhere to their prescribed medication regimen.
Regular monitoring of thyroid hormone levels is important to ensure adequate thyroid hormone replacement (if applicable).
Genetic counseling is recommended for families with a history of TBG deficiency to understand the inheritance pattern and risks of having affected children.
How long does an outbreak last?
As TBG deficiency is a genetic condition, the concept of an "outbreak" does not apply. It is a chronic condition, present from birth, though it may be diagnosed at any age. Symptoms, if present, are ongoing unless treated.
How is it diagnosed?
TBG deficiency is typically diagnosed through blood tests that measure:
Total T4 (thyroxine)
Total T3 (triiodothyronine)
Free T4 (unbound thyroxine)
TBG levels
TSH (thyroid-stimulating hormone) The combination of low total T4 and T3 levels with low TBG levels, and normal TSH, strongly suggests TBG deficiency. Genetic testing can confirm the diagnosis by identifying mutations in the TBG gene.
Timeline of Symptoms
9. Timeline of symptoms TBG deficiency is present from birth due to its genetic origin. Symptom onset can vary widely:
Infancy/Childhood: Severe cases may present with developmental delays. However, most children are asymptomatic.
Adulthood: Symptoms, if present, are usually mild hypothyroid symptoms and can appear at any time in adulthood. Many individuals remain asymptomatic throughout their lives.
Important Considerations
It is crucial to interpret thyroid function tests in the context of TBG levels. Lower total T4 levels in someone with TBG deficiency do not automatically indicate hypothyroidism. Free T4 and TSH levels are more reliable indicators of thyroid function in these individuals.
During pregnancy, TBG levels naturally increase. This can mask the presence of TBG deficiency in pregnant women. Thyroid hormone levels should be carefully monitored during pregnancy in women with known or suspected TBG deficiency.
Drug interactions can impact TBG levels. Medications like androgens, glucocorticoids, and certain antiepileptic drugs can decrease TBG levels.
It is important to inform healthcare providers about the diagnosis of TBG deficiency to ensure proper interpretation of thyroid function tests during routine checkups or if thyroid-related symptoms arise.