Occurrence of total thyroid agenesis
Executive summary
Total thyroid agenesis — the congenital complete absence of the thyroid gland — is an uncommon cause of congenital hypothyroidism with published occurrence estimates that vary by study and definition, commonly cited near 1 in 28,000 births for agenesis/hypoplasia spectra while congenital hypothyroidism overall affects roughly 1 in 2,000–4,000 newborns and thyroid dysgenesis (which includes agenesis, ectopy and hypoplasia) accounts for about 80% of those cases [1] [2] [3] [4].
1. What “occurrence” means in the literature and why numbers vary
Reports of “occurrence” conflate several related metrics — prevalence of congenital hypothyroidism (CH), proportion of CH due to thyroid dysgenesis, and within dysgenesis the fraction that represents complete agenesis — and those different denominators produce varying headline numbers in the literature [3] [5] [4].
2. Commonly cited population-level estimates
Several authoritative sources place thyroid agenesis or severe hypoplasia in the ballpark of one case per ~28,000 births when grouped with related hypoplastic forms (Orphanet and Springer summaries cite ~1/28,000) while broader congenital hypothyroidism is reported at about 1:2,000–1:4,000 newborns worldwide, reflecting that only a subset of CH is due to agenesis [1] [6] [2] [5].
3. How often agenesis is the specific cause inside congenital hypothyroidism cohorts
Within cohorts of infants identified with CH, the share attributable to true agenesis varies by series: some reports list agenesis as roughly 22–42% of CH etiologies, others a lower proportion (for example one clinical series reported 14.9% of developmental thyroid defects as agenesis), reflecting differences in imaging, screening sensitivity, and local population factors [5] [7].
4. Anatomical variants and more frequent, distinct entities
Complete absence of the whole gland is rarer than other developmental variants such as hemiagenesis (absence of one lobe) and isthmus agenesis; hemiagenesis prevalence estimates range from roughly 0.05% to 0.5% in screening studies, while isthmus absence appears common in anatomical and CT series (reported between about 0.05–5–10% depending on method), underscoring that many thyroid developmental anomalies are more frequent than total agenesis [8] [9] [10].
5. Demographic, genetic and methodological modifiers of reported rates
Population, ethnic and familial patterns modify occurrence estimates: some series show higher dysgenesis prevalence in Hispanic and Caucasian infants and lower in Black infants, familial cases are uncommon (about 2–3% linked to homeobox gene mutations) and newborn-screening strategies, imaging modality and regional environmental factors influence measured rates [11] [3] [12].
6. Clinical and reporting implications — what the numbers mean for practice and surveillance
Because early detection and replacement therapy prevent irreversible neurodevelopmental injury, newborn screening identifies CH broadly but determining whether CH reflects agenesis, ectopy or dyshormonogenesis requires imaging and biochemical follow‑up; therefore epidemiologic figures for “total agenesis” are best viewed as approximate, context-dependent estimates rather than a single fixed frequency [3] [2] [13].
7. Limits of available reporting and open questions
The literature presents heterogeneity in case definitions, diagnostic imaging sensitivity and population screening intensity, so precise global incidence of isolated total thyroid agenesis cannot be nailed to one number from the sources provided; the cited ranges and proportions above reflect the best-supported estimates in the available reporting but are not a comprehensive meta-analysis [1] [5] [7].