Hashimoto's Thyroiditis Phenotypes
Hashimoto's thyroiditis manifests in several distinct clinical and pathological phenotypes, including the classic lymphocytic form, fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or postpartum). 1
Classic Lymphocytic Form
The most common presentation involves pronounced lymphoid goiter with characteristic pathological features:
- Lymphoplasmacytic infiltration with lymphoid follicle formation and germinal centers throughout the thyroid interstitium 1, 2
- Thyroid follicular cell changes including atrophy and transformation into Hürthle cells (oxyphilic cells rich in mitochondria) 1, 2
- Predominantly affects women with a 7-10:1 female-to-male ratio 3
- Presents with diffuse or nodular goiter, which may cause compression of surrounding cervical structures in advanced cases 1, 4
Fibrous Variant
This phenotype demonstrates extensive fibrosis replacing normal thyroid architecture:
- Characterized by marked fibrotic changes beyond typical lymphocytic infiltration 1
- May present with firmer goiter on palpation requiring differentiation from malignancy 1
IgG4-Related Variant
A distinct immunological subtype with specific pathological features:
- Demonstrates IgG4-positive plasma cell infiltration 1
- Represents a subset of the broader IgG4-related disease spectrum 1
Juvenile Form
Presents in childhood or adolescence with specific characteristics:
- Occurs in younger patients with similar pathological features to adult disease 1
- May have more rapid progression to hypothyroidism 1
Hashitoxicosis (Thyrotoxic Phase)
This phenotype presents with hyperthyroidism due to release of stored thyroid hormones from destroyed follicles:
- Occurs when lymphocytic destruction releases preformed thyroid hormones into circulation 3
- Management focuses on symptom control with beta-blockers rather than antithyroid drugs, as this is not true hyperthyroidism 3
- Typically transitions to euthyroidism or hypothyroidism as stored hormones are depleted 3
- Patients may be hyperthyroid at presentation despite underlying autoimmune destruction 1
Painless Thyroiditis
This phenotype includes two temporal variants:
Sporadic Painless Thyroiditis
- Occurs without temporal relationship to pregnancy 1
- Follows similar course of transient thyrotoxicosis followed by hypothyroidism 1
Postpartum Thyroiditis
- Develops within one year after delivery 1
- Particularly important as positive TPO antibodies increase risk of recurrent miscarriages and preterm birth by 2-4 fold 3
- Requires careful monitoring as untreated maternal hypothyroidism increases risk of preeclampsia and low birth weight 5
Clinical Progression Spectrum
All phenotypes can present across three functional states:
Thyrotoxic State (Hashitoxicosis)
- Stored hormones released from destroyed follicles 3
- Requires beta-blocker therapy for symptom management 3
Euthyroid State
- Preserved thyroid tissue compensates for destroyed thyrocytes 3
- Requires periodic TSH monitoring to detect progression 5, 3
- Positive TPO antibodies confer 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative individuals 5
Hypothyroid State
- Insufficient thyroid hormone production from damaged gland 3
- Requires levothyroxine replacement at 1.4-1.8 mcg/kg/day based on lean body mass and residual thyroid function 3
- Treatment indicated when TSH >10 mIU/L (5% annual progression risk) or TSH 4.5-10 mIU/L with symptoms or positive TPO antibodies 5
Associated Thyroid Eye Disease Phenotype
When Hashimoto's thyroiditis occurs with normal-functioning or under-functioning thyroid (distinct from Graves' disease):
- Presents bilaterally but often asymmetrically 6
- Can manifest with edema and erythema of periorbital tissues, upper eyelid retraction, and exposure keratopathy 6, 7
- Risk factors include family history of thyroid disorders, cigarette smoking, and low selenium levels 6, 7
Malignant Transformation Risk
Hashimoto's thyroiditis carries increased malignancy risk: