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Congenital Hypothyroidism

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Description: Congenital hypothyroidism is a condition present at birth characterized by an underactive thyroid gland, leading to insufficient production of thyroid hormones critical for growth and development.
Type: Congenital hypothyroidism can be caused by genetic and non-genetic factors. When it has a genetic basis, it is typically inherited in an autosomal recessive manner.
Signs And Symptoms: Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often go unrecognized as a problem: excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, significant jaundice, and low body temperature. If the fetal thyroid hormone deficiency is severe because of complete absence (athyreosis) of the gland, physical features may include a larger anterior fontanel, persistence of a posterior fontanel, an umbilical hernia, and a large tongue (macroglossia).In the era before newborn screening, less than half of cases of severe hypothyroidism were recognized in the first month of life. As the months proceeded, these babies would grow poorly and be delayed in their development. By several years of age, they would display the recognizable facial and body features of cretinism. Persistence of severe, untreated hypothyroidism resulted in severe mental impairment, with an IQ below 80 in the majority. Most of these children eventually ended up in institutional care.
Prognosis: Most children born with congenital hypothyroidism and correctly treated with thyroxine grow and develop normally in all respects. Even most of those with athyreosis and undetectable T4 levels at birth develop with normal intelligence, although as a population academic performance tends to be below that of siblings and mild learning problems occur in some.Congenital hypothyroidism is the most common preventable cause of intellectual disability. Few treatments in the practice of medicine provide as large a benefit for as small an effort. The developmental quotient (DQ, as per Gesell Developmental Schedules) of children with hypothyroidism at age 24 months that have received treatment within the first 3 weeks of birth is summarised below:
Onset: Congenital hypothyroidism typically has an onset at birth or shortly thereafter. It occurs when the thyroid gland is absent, underdeveloped, or dysfunctional. Early diagnosis and treatment are crucial for normal growth and development.
Prevalence: Congenital hypothyroidism occurs in approximately 1 in 2,000 to 1 in 4,000 newborns.
Epidemiology: Congenital hypothyroidism (CH) occurs in 1:1300 to 1:4000 births worldwide. The differences in CH-incidence are more likely due to iodine deficiency thyroid disorders or to the type of screening method than to ethnic affiliation. CH is caused by an absent or defective thyroid gland classified into agenesis (22-42%), ectopy (35-42%) and gland in place defects (24-36%). It is also found to be of increased association with female sex and gestational age >40 weeks.
Intractability: Congenital hypothyroidism is not considered intractable. With early diagnosis and proper treatment, typically through thyroid hormone replacement therapy, affected individuals can lead healthy and normal lives. Regular monitoring and adjustment of medication ensure that the condition is well-managed.
Disease Severity: The severity of congenital hypothyroidism varies depending on the early diagnosis and treatment. If detected and treated early, affected infants can lead normal lives with proper thyroid hormone replacement. Without treatment, the condition can lead to severe intellectual disability and growth failure. Prompt screening and lifelong treatment are crucial for managing the disease and preventing serious complications.
Healthcare Professionals: Disease Ontology ID - DOID:0050328
Pathophysiology: Congenital hypothyroidism is a condition present at birth where the thyroid gland is underactive or absent, leading to a deficiency in thyroid hormone production. Pathophysiologically, this can result from various causes, such as:

1. **Thyroid Dysgenesis:** The most common cause, where the thyroid gland is missing (agenesis), abnormally small (hypoplasia), or located in an abnormal position (ectopia).
2. **Thyroid Dyshormonogenesis:** Genetic defects affecting the enzymes responsible for thyroid hormone synthesis.
3. **Central Hypothyroidism:** Due to hypothalamic or pituitary dysfunction, which leads to insufficient stimulation of the thyroid gland by thyroid-stimulating hormone (TSH).

Thyroid hormone is crucial for growth and brain development, so a deficiency can lead to intellectual disability, growth retardation, and other developmental issues if not treated promptly. Newborn screening and early treatment are essential to prevent these severe outcomes.
Carrier Status: Congenital hypothyroidism is not typically associated with a carrier status because it often results from genetic mutations that lead to the thyroid gland's underdevelopment or dysfunction. However, certain genetic forms of congenital hypothyroidism can be inherited in an autosomal recessive manner, where a carrier would have one mutated copy of the gene but usually not show symptoms. In those cases, both parents would be carriers, having one mutated copy each, to have an affected child.
Mechanism: Congenital hypothyroidism is a condition present at birth that results in insufficient production of thyroid hormones. The mechanisms and molecular mechanisms underlying this condition can vary:

### Mechanism:
1. **Thyroid Dysgenesis:** This refers to the improper development of the thyroid gland. It is the most common cause and includes agenesis (absence of the gland), hypoplasia (underdeveloped gland), or ectopy (misplaced gland).
2. **Thyroid Hormone Synthesis Defects:** These include various inherited defects that affect the biochemical steps involved in the synthesis of thyroid hormones, such as iodide trapping, organification, and coupling processes.
3. **End-organ Resistance:** In rare cases, the thyroid gland is normal, but the tissues are resistant to thyroid hormones.

### Molecular Mechanisms:
1. **Genetic Mutations:** Specific gene mutations are often implicated in congenital hypothyroidism. These include mutations in:
- **TSHR (Thyroid-Stimulating Hormone Receptor) Gene:** Affects the receptor responsible for stimulating thyroid hormone production.
- **NKX2-1 and PAX8 Genes:** Involved in thyroid gland development and differentiation.
- **DUOX2, SLC5A5, and TPO Genes:** Affect thyroid hormone synthesis pathways.
2. **Transcription Factors:** Abnormalities in transcription factors that regulate the expression of genes critical for thyroid development and function, such as FOXE1 and HHEX.

Congenital hypothyroidism, if untreated, can lead to severe growth delays and intellectual disability, but early diagnosis and treatment with thyroid hormone replacement can mitigate most adverse effects.
Treatment: The goal of newborn screening programs is to detect and start treatment within the first 1–2 weeks of life. Treatment consists of a daily dose of thyroxine, available as a small tablet. The generic name is levothyroxine, and several brands are available. The tablet is crushed and given to the baby with a small amount of water or milk. The most commonly recommended dose range is 10-15 μg/kg daily, typically 12.5 to 37.5 or 44 μg.
Within a few weeks, the T4 and TSH levels are rechecked to confirm that they are being normalized by treatment. As the child grows up, these levels are checked regularly to maintain the right dose. The dose increases as the child grow.
Compassionate Use Treatment: Compassionate use treatment refers to the use of investigational drugs outside of clinical trials for patients with serious or life-threatening conditions who have no other treatment options. For congenital hypothyroidism, the primary treatment is typically hormone replacement with levothyroxine.

Regarding off-label or experimental treatments, there are no widely recognized off-label or experimental drugs specifically for congenital hypothyroidism. The standard of care remains hormone replacement to ensure normal growth and development. Off-label treatments aren't generally needed as levothyroxine is highly effective when used properly. Experimental treatments would be more commonly explored if conventional therapy was inadequately effective or unavailable, but this is rare for congenital hypothyroidism.
Lifestyle Recommendations: For congenital hypothyroidism, lifestyle recommendations focus on ensuring proper growth and development through early and consistent treatment.

1. **Medication Compliance**: Administer thyroid hormone replacement therapy (levothyroxine) daily as prescribed.
2. **Regular Monitoring**: Frequent blood tests to monitor thyroid hormone levels and adjust medication dosage accordingly.
3. **Healthy Diet**: Ensure a balanced diet rich in iodine, crucial for thyroid function, unless contraindicated by a healthcare provider.
4. **Developmental Milestones**: Close monitoring of developmental milestones, and seeking early intervention if delays are noticed.
5. **Routine Checkups**: Regular visits to a pediatric endocrinologist for ongoing management.
Medication: For congenital hypothyroidism, the standard medication is levothyroxine. This synthetic thyroid hormone is used to replace the missing thyroxine (T4) in the body, thereby normalizing metabolic processes. It is typically administered orally and requires regular monitoring of thyroid hormone levels to adjust dosage as the child grows.
Repurposable Drugs: Repurposable drugs for congenital hypothyroidism have not been widely studied or established. The standard treatment for congenital hypothyroidism is levothyroxine, a synthetic form of the thyroid hormone. This treatment is critical for normal growth and development in infants and children with congenital hypothyroidism. If you are looking for innovative or alternative treatments, consulting a healthcare provider or endocrinologist for the most current research and therapy options is recommended.
Metabolites: Congenital hypothyroidism is characterized by low levels of thyroid hormones (thyroxine, T4, and triiodothyronine, T3) and elevated levels of thyroid-stimulating hormone (TSH). Metabolites typically measured in the context of this condition include:

- **Thyroxine (T4)**
- **Triiodothyronine (T3)**
- **Thyroid-Stimulating Hormone (TSH)**

Elevated TSH levels and low T4 levels in newborn screening tests often indicate congenital hypothyroidism.
Nutraceuticals: For congenital hypothyroidism, nutraceuticals are not a standard treatment. The condition is primarily managed through thyroid hormone replacement therapy, specifically with levothyroxine. This medication is used to normalize thyroid hormone levels and support normal growth and development in affected individuals. Nutraceuticals or dietary supplements may not provide adequate control of hormone levels and should not be relied upon as a primary treatment option. Always consult a healthcare provider for appropriate diagnosis and treatment options.
Peptides: Congenital hypothyroidism (CH) is a condition present at birth resulting from an underactive thyroid gland. Peptides are short chains of amino acids, and in the context of CH, they may be involved in thyroid hormone synthesis and regulation. However, the primary treatment for CH typically involves thyroid hormone replacement, not peptides.

"Nan" is not directly relevant to congenital hypothyroidism. If you meant "nanomedicine," which involves the use of nanotechnology for medical purposes, it is an emerging field but not yet a standard approach for treating CH.