Etiology | Conditions, drugs or environmental agents affecting this step in iodide transport | Manifestations |
---|---|---|
Deficient nutritional iodine intake | Iodine deficiency disorders | All ages: |
• Goiter | ||
Mother/fetus: | ||
• Abortion | ||
• Stillbirth | ||
• Congenital anomalies | ||
• Perinatal mortality | ||
Newborn: | ||
• Infant mortality | ||
• Cretinism with neurological deficits and mental retardation | ||
Child and adolescent: | ||
• Growth retardation and delayed puberty | ||
Child, adolescent and adult: | ||
• Impaired mental function | ||
• Hypothyroidism | ||
• Increased risk to develop iodide induced-hyperthyroidism and toxic nodular goiter after exposure to iodine | ||
Abnormal basal iodide uptake | NIS mutations (autosomal recessive) | Congenital hypothyroidism, typically with goiter. Iodide-trapping defect with little or no uptake of radioactive iodide both at the thyroid and salivary gland level |
Perchlorate, thiocyanate and nitrates | Increased risk of goiter development and hypothyroidism, specially in iodine deficient populations | |
Goitrogens (soy and other flavonoids, glucosinolates and cyanogenic glucosides) | Increased risk of goiter development and hypothyroidism in iodine deficient populations | |
Apical iodide efflux | Pendred syndrome. Mutations in the SLC26A4 gene (autosomal recessive) | Sensorineural hearing loss, variable phenotype of goiter and hypothyroidism and partial organification defect |
Congenital hypothyroidism with atrophic thyroid gland associated with SLC26A4 mutations (autosomal recessive) | Congenital hypothyroidism | |
Organification and coupling | Tg gene mutations (autosomal recessive) | Congenital hypothyroidism and/or variable degrees of goiter and hypothyroidism with low Tg levels |
TPO gene mutations (autosomal recessive) | Congenital hypothyroidism and/or variable degrees of goiter and hypothyroidism with partial or total organification defects | |
Mutations in DUOX2 or DUOXA2 (autosomal recessive or dominant) | Transient or permanent congenital hypothyroidism | |
Anti-thyroid medications (i.e. PTU, methimazole, carbimazole) | Medication-induced hypothyroidism | |
Recycling of iodide | Mutations in DEHAL1 (autosomal recessive) | Congenital hypothyroidism, goiter, increased MIT and DIT serum levels and severe urinary loss of MIT and DIT |
Thyroid hormone degradation exceeds thyroid synthetic capacity | Overexpression of D3 in hemangiomas and gastrointestinal stromal tumors | Consumptive hypothyroidism with elevated rT3 and resistance to treatment with physiological doses of levothyroxine |
Increased stimulation or constitutive activity of the TSHR or downstream pathways | TSHR stimulating immunoglobulins | Graves’ disease |
Transient congenital hyperthyroidism | Â | |
TSHR activating mutations | Sporadic congenital or autosomal dominant familial non-autoimmune hyperthyroidism (germline mutations) | |
Toxic adenomas (somatic mutations) | Â | |
Pregnancy | hCG-induced gestational hyperthyroidism | |
Somatic, activating mutations of Gsα | Toxic nodular hyperthyroidism and hyperthyroidism in McCune Albright syndrome | |
Decreased stimulation or inactivation of the TSHR or downstream pathways | Presence of TSHR blocking immunoglobulins | Hypothyroidism |
Inactivating mutations of the TSHR (autosomal recessive) | Resistance to TSH with overt or compensated hypothyroidism | |
Inactivating Gsα mutations | Hypothyroidism in the context of pseudohypoparathyroidism type Ia | |
Iodide mediated alterations in thyroid function | Iodine containing solutions | Transient hypothyroidism (Wolff-Chaikoff effect) |
 | In iodine deficiency: Hyperthyroidism (Jod-Basedow) | |
Iodine containing contrast agents (iodine containing IV contrasts) | Transient hypothyroidism (Wolff-Chaikoff effect) | |
In iodine deficiency: Hyperthyroidism (Jod-Basedow) | ||
Amiodarone | Amiodarone induced thyrotoxicosis (AIT): type 1: iodine inducedthyrotoxicosis, Jod-Basedow type 2: thyroiditis | |
 | Amiodarone induced hypothyroidism (AMH); often associated with underlying autoimmune thyroid disease | |
Other defects in thyroid hormone release | Lithium | Hypothyroidism due to decrease release of T4 |