Development of the thyroid gland: lessons from congenitally hypothyroid mice and men
Bibliographic record
Abstract
Congenital hypothyroidism is the most common congenital endocrine disorder (one newborn in 3000) and represents the most common cause of preventable mental retardation. In 10-20% of cases, it is due to autosomal recessive functional disorders leading to goiter formation (thyroid dyshormonogenesis). In the remainder, it is due to thyroid dysgenesis, which comprises usually isolated defects in: (1) migration of the median thyroid anlage, leading to a round cluster of ectopic cells (usually in a sublingual position) with no other thyroid tissue present; (2) differentiation or survival of the thyroid follicular cells leading to athyreosis; and (3) growth of a thyroid with the normal bilobed shape and in the normal cervical position (orthotopic hypoplasia). Mouse knock-outs have demonstrated that thyroid transcription factor-1 (TTF-1) and PAX8 are required for the survival and proliferation of thyroid follicular cell precursors, TTF-2 for their downward migration and the thyrotropin receptor (TSHR) for post-natal thyroid growth. In humans, thyroid dysgenesis is generally a sporadic malformation but an affected relative is found in 2% of cases, a figure 15-fold higher than by chance alone. Pedigree analysis is most compatible with dominant inheritance with variable penetrance. However, mutations in TTF-1, TTF-2, PAX8 and TSHR are found in <10% of patients with congenital hypothyroidism and these predominantly have orthotopic thyroid hypoplasia, often associated with other malformations. This low yield and the discordance of >90% of monozygotic twin pairs suggests that isolated thyroid ectopy or athyreosis most often results from early somatic mutations, epigenetic modifications or stochastic developmental events.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".