Healthy Thyroid Follicular Architecture
Normal follicles store colloid and secrete thyroid hormone steadily.
- ~3M: Thyroid follicles (adult) (microscopic hormone units)
- 100%: Functional tissue (full secretory capacity)
- <35: Anti-TPO titer (IU/mL, normal range)
- 0.4–4.0: TSH level (mIU/L, euthyroid range)
Follicle structure
Cuboidal cells ring a colloid core storing thyroglobulin.
Hormone synthesis
TPO oxidizes iodide, iodinating thyroglobulin to build T4/T3.
Immune tolerance
Self-antigens are normally shielded from autoreactive lymphocytes.
Anti-TPO and Anti-Thyroglobulin Autoantibodies
Genetic and environmental triggers break self-tolerance to thyroid antigens.
- ↑3×: HLA-DR3 risk allele (genetic susceptibility factor)
- ~90%: Anti-TPO positivity (of Hashimoto patients)
- 7:1: Female:male ratio (strong sex skew)
- Yes: Iodine excess link (known environmental trigger)
Break in tolerance
Genetic risk plus environmental triggers activate autoreactive clones.
Antibody targets
Anti-TPO and anti-Tg bind key hormone-synthesis proteins.
Early detection
Antibody titers rise years before symptoms appear.
Lymphocytic Infiltration of Thyroid Tissue
T and B cells infiltrate the gland and attack follicular cells directly.
- T+B: Infiltrate composition (lymphocytic + plasma cells)
- Common: Germinal centers (ectopic lymphoid follicles)
- Fas/FasL: Cytotoxic mechanism (apoptosis induction pathway)
- Firm: Gland texture change (diffuse goiter forms)
Infiltration pattern
Lymphocytes cluster diffusely between follicles across the gland.
Cytotoxic killing
CD8+ T cells trigger apoptosis in follicular epithelium.
Cytokine damage
IFN-γ and TNF-α amplify local inflammatory injury.
Progressive Follicle Destruction Over Time
Functional tissue mass falls steadily across months to years.
- Yrs: Progression timeframe (months to years typical)
- ↑: Fibrous replacement (scar tissue accumulates)
- Common: Hürthle cell change (oxyphilic metaplasia)
- Gradual: Reserve capacity loss (compensated until threshold)
Tissue attrition
Follicles shrink and are replaced by fibrous stroma.
Compensation phase
TSH rises to drive remaining follicles harder.
Titer correlation
Higher antibody titers track faster tissue loss.
Overt Hypothyroidism and Hormone Replacement
Sufficient tissue loss raises TSH and lowers T4 below normal.
- >10: TSH (overt) (mIU/L, elevated)
- Low: Free T4 (below reference range)
- Levothyroxine: Treatment (daily oral replacement)
- ~5%: Prevalence (women) (lifetime risk estimate)
Hormonal failure
Remaining follicles cannot meet peripheral hormone demand.
Feedback response
Pituitary TSH climbs sharply as T4 output falls.
Lifelong management
Levothyroxine restores euthyroid state with regular monitoring.
Progression markers at a glance