1. | Primary hypothyroidism |
---|---|
 | Thyroid dysgenesis: hypothyroidism due to a developmental anomaly |
 |    (Thyroid ectopia, athyreosis, hypoplasia, hemiagenesis) |
 |    Associated mutations: (these account for only 2% of thyroid dysgenesis cases; 98% unknown) |
 | TTF-2, |
 | NKX2.1, |
 | NKX2.5 |
 | PAX-9 |
 | Thyroid dyshormonogenesis: hypothyroidism due to impaired hormone production |
 |    Associated mutations: |
 | Sodium-iodide symporter defect |
 | Thyroid peroxidase defects |
 | Hydrogen peroxide generation defects (DUOX2, DUOXA2 gene mutations) |
 | Pendrin defect (Pendred syndrome) |
 | Thyroglobulin defect |
 | Iodotyrosine deiododinase defect (DEHAL1, SECISBP2 gene mutations) |
 | Resistance to TSH binding or signaling |
 |    Associated mutations: |
 | TSH receptor defect |
 | G-protein mutation: pseudohypoparathyroidism type 1a |
2. | Central hypothyroidism (syn: Secondary hypothyroidism) |
 | Isolated TSH deficiency (TSH β subunit gene mutation) |
 | Thyrotropin-releasing hormone deficiency |
 |    Isolated, pituitary stalk interruption syndrome (PSIS), hypothalamic lesion, e.g. hamartoma |
 | Thyrotropin-releasing hormone resistance |
 |    TRH receptor gene mutation |
 | Hypothyroidism due to deficient transcription factors involved in pituitary development or function |
 |    HESX1, LHX3, LHX4, PIT1, PROP1 gene mutations |
3. | Peripheral hypothyroidism |
 | Resistance to thyroid hormone |
 |    Thyroid receptor β mutation |
 | Abnormalities of thyroid hormone transport |
 |    Allan-Herndon-Dudley syndrome (monocarboxylase transporter 8 [MCT8] gene mutation) |
4. | Syndromic hypothyroidism |
 | Pendred syndrome - (hypothyroidism- deafness - goiter) Pendrin mutation |
 | Bamforth-Lazarus syndrome - (hypothyroidism - cleft palate - spiky hair) TTF-2 mutation |
 | Ectodermal dysplasia - (hypohidrotic - hypothyroidism - ciliary dyskinesia) |
 | Hypothyroidism - (dysmorphism - postaxial polydactyly - intellectual deficit) |
 | Kocher - Deber - Semilange syndrome - (muscular pseudohypertrophy- hypothyroidism) |
 | Benign chorea - hypothyroidism |
 | Choreoathetosis - (hypothyroidism - neonatal respiratory distress) NKX2.1 /TTF-1 mutation |
 | Obesity - colitis - (hypothyroidism - cardiac hypertrophy - developmental delay) |
5. | Transient congenital hypothyroidism |
 | Maternal intake of antithyroid drugs |
 | Transplacental passage of maternal TSH receptor blocking antibodies |
 | Maternal and neonatal iodine deficiency or excess |
 | Heterozygous mutations of THOX2 or DUOXA2 |
 | Congenital hepatic hemangioma/hemangioendothelioma |