Thyroid dyshormonogenesis
| Thyroid dyshormonogenesis | |
|---|---|
| Other names | Dyshormogenetic goiter |
| Thyroid dyshormonogenesis is inherited in an autosomal recessive manner | |
| Specialty | Endocrinology |
Thyroid dyshormonogenesis is a rare condition due to genetic defects in the synthesis of thyroid hormones.[1][2]
It is due to either deficiency of thyroid enzymes, inability to concentrate, or ineffective binding.[3]
Signs and symptoms
The symtptoms of this disease are:[4]
Very Frequent
- Decreased circulating thyroxine level
- Elevated circulating TSH concentration
Frequent
- Abnormality of epiphysis
- Congenital hypothyroidism
- Constipation
- Delayed closure of the cranial suture.
- Delay of proximal femoral epiphyseal ossification
- Feeding difficulties
- Goitre
- Big posterior fontanelle
- Neurodevelopmental problems
- Neonatal jaundice
- Umbilical hernia
Occasional
- Abnormality of circulating thyroglobulin concentration
- Slow heart rate
- Saddle nose deformity
- Edema of face
- Decreased reflexes
- Hypotonia
- Hypothermia
- Increase of radioactive iodine uptake
- Mental handicap
- Large tongue
- Neonatal hyperbilirubinemia
Very Rare
- Sensorineural hearing loss
Cause
This is due to inability to produce thyroid hormones due to congenital absence of peroxidase or dehalogenase enzymes[3]
Types
One particular familial form is associated with sensorineural deafness (Pendred's syndrome).[5]
OMIM includes the following:
| Type | OMIM | Gene |
|---|---|---|
| Type 1 | 274400 | SLC5A5 |
| Type 2A | 274500 | TPO |
| Type 2B | 274600 (Pendred) | SLC26A4 |
| Type 3 | 274700 | TG |
| Type 4 | 274800 | IYD |
| Type 5 | 274900 | DUOXA2 |
| Type 6 | 607200 | DUOX2 |
Diagnosis
Diagnosis can be made by elevated serum TSH level and low T4 or free T4 level. Thyroid dyshormonogenesis diagnosis is based on high radioactive iodine (RAI) uptake of the thyroid gland followed by more than 90% release after sodium perchlorate administration. Thyroid dyshormonogenesis is diagnosed with a 50%-90% release after perchlorate administration, which can be confirmed by genetic testing.[6]
Treatment
Levothyroxine is the treatment of choice (starting dose 10-15 mcg/kg/day), with the immediate goal of raising the serum T4 level above 130 nmol/L (10 ug/dL) as quickly as possible; with these doses, serum TSH usually normalizes within 2–4 weeks. Frequent laboratory monitoring in infancy is essential to make sure of optimal neurocognitive outcome. Serum TSH and T4 should be measured every 1–2 months in the first 6 months of life, every 3 months between 6 months and 3 years of age, and 4 weeks after any dose change.[6]
References
- ^ Avbelj M, Tahirovic H, Debeljak M, et al. (May 2007). "High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis". Eur. J. Endocrinol. 156 (5): 511–9. doi:10.1530/EJE-07-0037. PMID 17468186.
- ^ Kumar PG, Anand SS, Sood V, Kotwal N (December 2005). "Thyroid dyshormonogenesis" (PDF). Indian Pediatr. 42 (12): 1233–5. PMID 16424561.
- ^ a b Grasberger, Helmut; Refetoff, Samuel (August 2011). "Genetic causes of congenital hypothyroidism due to dyshormonogenesis". Current Opinion in Pediatrics. 23 (4): 421. doi:10.1097/MOP.0b013e32834726a4. ISSN 1040-8703. PMC 3263319.
- ^ "Orphanet: Clinical signs and symptoms". www.orpha.net. Retrieved 2025-02-26.
- ^ Sheffield, Val C.; Kraiem, Zaki; Beck, John C.; Nishimura, Darryl; Stone, Edwin M.; Salameh, Muhamad; Sadeh, Orit; Glaser, Benjamin (April 1996). "Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification". Nature Genetics. 12 (4): 424–426. doi:10.1038/ng0496-424. ISSN 1546-1718.
- ^ a b "Orphanet: Familial thyroid dyshormonogenesis". www.orpha.net. Retrieved 2025-02-26.