Table 2 Mechanisms and disorders associated with abnormal iodide transport

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

TSHR activating mutations

Sporadic congenital or autosomal dominant familial non-autoimmune hyperthyroidism (germline mutations)

Toxic adenomas (somatic mutations)

Pregnancy

hCG-induced gestational hyperthyroidism

Somatic, activating mutations of G_sα

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 G_sα 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