What are the other Names for this Condition? (Also known as/Synonyms)

• PRTH (Peripheral Resistance to Thyroid Hormones)

What is Peripheral Resistance to Thyroid Hormones? (Definition/Background Information)

• Peripheral Resistance to Thyroid Hormones (PRTH) may be a cause of permanent congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth
• The majority of cases are asymptomatic, but some may have features of hypothyroidism including decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia

(Source: Peripheral Resistance to Thyroid Hormones; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Peripheral Resistance to Thyroid Hormones? (Age and Sex Distribution)

• Peripheral Resistance to Thyroid Hormones is a congenital disorder involving the thyroid gland, which occurs at an estimated prevalence of 1:40,000
• The onset of symptoms may occur at birth or in infancy
• Both males and females may be affected by this disorder
• Worldwide, individuals of all races and ethnicities may be affected

What are the Risk Factors for Peripheral Resistance to Thyroid Hormones? (Predisposing Factors)

• A positive family history may be an important risk factor, since Peripheral Resistance to Thyroid Hormones can be inherited
• Currently, no other risk factors have been clearly identified for this congenital disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Peripheral Resistance to Thyroid Hormones? (Etiology)

• In majority of cases, Peripheral Resistance to Thyroid Hormones is caused by mutation(s) in the THRB gene. This gene codes for the thyroid hormone receptor beta
• The condition is inherited in an autosomal dominant manner

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Peripheral Resistance to Thyroid Hormones?

The signs and symptoms of Peripheral Resistance to Thyroid Hormones may vary among affected individuals in type and severity. Whereas some of those affected may be asymptomatic, others may have the following signs and symptoms:

• Abdominal distention
• Coarse facial features
• Constipation
• Feeding difficulties
• Hypothyroidism
• Jaundice
• Large fontanelles
• Macroglossia
• Muscular hypotonia
• Sleep disturbance
• Umbilical hernia

(Source: Peripheral Resistance to Thyroid Hormones; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Peripheral Resistance to Thyroid Hormones Diagnosed?

Peripheral Resistance to Thyroid Hormones is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative THRB gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Peripheral Resistance to Thyroid Hormones?

The complications of Peripheral Resistance to Thyroid Hormones may include:

• Development of permanent congenital hypothyroidism
• Poor feeding

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Peripheral Resistance to Thyroid Hormones Treated?

There is no cure for Peripheral Resistance to Thyroid Hormones, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Peripheral Resistance to Thyroid Hormones be Prevented?

Peripheral Resistance to Thyroid Hormones may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Peripheral Resistance to Thyroid Hormones? (Outcomes/Resolutions)

• The prognosis of Peripheral Resistance to Thyroid Hormones is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Peripheral Resistance to Thyroid Hormones:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/