Familial Dysalbuminemic Hyperthyroxinemia - Causes, Symptoms, and Management

Introduction:

Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare genetic disorder affecting the body's thyroid hormone levels. It occurs due to a mutation in the gene that codes for the transthyretin (TTR) protein. TTR protein is responsible for carrying thyroid hormones in the blood. Mutation in TTR leads to the production of an abnormal form of the TTR protein. This abnormal protein cannot properly bind to thyroid hormones in the blood, leading to increased thyroid hormone levels and hyperthyroidism. FDH is a rare disorder and is misdiagnosed as other forms of hyperthyroidism; hence it is essential to be aware of this condition.

What Is the Cause of Familial Dysalbuminemic Hyperthyroxinemia?

There are several causes of FDH. These are sequence results in FDH. These are as follows -

• Mutation in the Transthyretin (TTR) Gene - The leading cause of FDH is a mutation in the TTR gene that leads to the production of an abnormal form of the TTR protein. The mutation in the TTR gene results in abnormal TTR protein, which cannot bind to thyroid hormones properly. As a result of the abnormal TTR protein, thyroid hormones remain free in the blood and cause an increase in their levels.

• Inheritance - FDH inherits as an autosomal dominant pattern, which means that if one parent has the disorder, there is a 50 % chance that their child will also have it.

• Amyloid Formation - Some mutations lead to the production of a transthyretin protein more prone to forming clumps called amyloids.

• Unstable TTR Protein - Some mutations lead to the production of a TTR protein that is more unstable and prone to breaking down.

• New Mutation - The disorder can also occur due to a new mutation in the TTR gene.

• Release of Free Thyroid Hormone - The protein breakdown can lead to the release of free thyroid hormone, which can cause hyperthyroidism.

What Are the Risk Factor Associated With Familial Dysalbuminemic Hyperthyroxinemia?

The presence of risk factors does not guarantee disease occurrence but increases the chance of having the disease in an individual. These include the following -

• Genetics and Family History - The main risk factor for FDH is a genetic predisposition caused by a mutation in the TTR gene.

• Age - FDH can develop at any age, but it is more common in older individuals.

• Gender - FDH affects both males and females equally.

• Ethnicity - FDH is a rare disorder, but it has been reported in individuals of different ethnicities.

• Amyloidosis - Individuals with FDH may be at an increased risk of developing amyloidosis, a condition in which amyloid protein builds up in organs and tissues.

What Are the Symptoms of Familial Dysalbuminemic Hyperthyroxinemia?

There are various symptoms of FDH. These include the following -

• Weight Loss - Individuals with familial dysalbuminemic hyperthyroxinemia (FDH) may experience weight loss as a symptom of hyperthyroidism.

• Palpitations - The disorder can cause palpitations or an increased heart rate due to the higher thyroid hormone levels in the blood.

• Nervousness - Hyperthyroidism caused by FDH may lead to feelings of nervousness or anxiety.

• Tremors - Individuals with FDH may experience tremors in their hands or other body parts due to hyperthyroidism.

• Fatigue - Hyperthyroidism can cause excessive fatigue and weakness in FDH patients.

• Insomnia - Some people with FDH may have trouble sleeping due to increased thyroid hormone levels.

• Heat Intolerance - Hyperthyroidism can cause increased sensitivity to heat in FDH patients.

• Goiter - An enlarged thyroid gland, or goiter, can also be a symptom of FDH.

• Irregular Menstrual Cycle - Women with FDH may experience irregular menstrual cycles or amenorrhea due to hyperthyroidism.

• Skin Changes - Hyperthyroidism can cause dry, thin, and itchy skin and hair loss in people with FDH.

How to Diagnose Familial Dysalbuminemic Hyperthyroxinemia?

A detailed diagnosis is essential as it is a rare disorder. These are the following steps in diagnosis -

• Blood Test - FDH can be diagnosed by measuring the levels of thyroid hormones and TTR protein in the blood.

• Genetic Testing - Genetic testing confirms the diagnosis of FDH by identifying the specific mutation in the TTR gene.

• Medical History - A healthcare professional will take a patient's medical history and perform a physical examination to identify symptoms of hyperthyroidism.

• Imaging Studies - Imaging studies such as ultrasound or CT (computed tomography) scans can evaluate the size and shape of the thyroid gland and detect any abnormalities.

• Thyroid Function Test - A thyroid function test checks the level of thyroid hormones in the blood to determine if the patient is hyperthyroid.

• TSH Test - A TSH (thyroid-stimulating hormone) test checks the level of TSH in the blood to determine if the patient is hyperthyroid.

• TTR Protein Measurement - TTR protein measurement identifies the abnormal TTR protein in FDH patients.

• Amyloidosis Diagnosis - If amyloidosis is suspected, a biopsy of the affected organ or a blood test confirms the diagnosis.

How to Treat Familial Dysalbuminemic Hyperthyroxinemia?

The treatment of dysalbuminemic hyperthyroxinemia includes the following -

• Medications - Treatment of familial dysalbuminemic hyperthyroxinemia (FDH) involves managing the symptoms of hyperthyroidism. Drugs such as Propylthiouracil or Methimazole can inhibit the production of thyroid hormones and manage the symptoms.

• Beta-Blockers- Beta-blockers control the symptoms of hyperthyroidism, such as palpitations and tremors.

• Liver Transplantation - In severe cases, liver transplantation may be considered a treatment option. A liver transplant can replace the affected liver with a healthy one, stopping the production of abnormal TTR protein.

• Management of Amyloidosis - If amyloidosis is present, it may treat with medications such as colchicine, which can help slow down the progression of the condition.

• Radioactive Iodine Therapy - This therapy uses a small amount of radioactive iodine to destroy some of the thyroid tissue, which helps to reduce the production of thyroid hormones.

• Surgery - Surgery sometimes removes all or part of the thyroid gland.

• Supportive Care - Supportive care, such as physical therapy and occupational therapy, can help individuals with FDH manage symptoms and maintain an optimal quality of life.

Conclusion:

It is essential to be aware of this rare disorder, which is often misdiagnosed as other forms of hyperthyroidism. Individuals experiencing symptoms of hyperthyroidism should consult a healthcare professional for evaluation and diagnosis. Diagnosis and treatment involve managing the symptoms of hyperthyroidism, and liver transplantation may be considered. Individuals with FDH can manage their symptoms and maintain an optimal quality of life.