Diffuse Thyroiditis

"Diffuse thyroiditis" describes forms of thyroid inflammation where the entire gland is diffusely involved, as opposed to focal or nodular disease. The term most commonly points to Hashimoto thyroiditis (the prototype of diffuse autoimmune thyroiditis), but the full spectrum includes several clinically distinct entities. Below is a systematic overview.

Classification of Thyroiditis

Harrison's (22e) classifies thyroiditis by onset/duration and by presence or absence of pain:

Category	Type	Key Feature
Acute	Suppurative (bacterial/fungal)	Rare; painful; fever
Subacute	Granulomatous (de Quervain's)	Painful; post-viral
	Painless (lymphocytic/postpartum)	Autoimmune; transient
	Drug-induced (amiodarone, IFN, checkpoint inhibitors)	Variable
Chronic	Hashimoto's (chronic lymphocytic)	Most common; autoimmune
	Riedel's thyroiditis	Dense fibrosis; rare
	Atrophic thyroiditis	Autoimmune; no goiter

Harrison's Principles of Internal Medicine 22E, p. 3081

1. Hashimoto Thyroiditis (Chronic Autoimmune / Chronic Lymphocytic Thyroiditis)

The most important and common form of diffuse thyroiditis, and the leading cause of hypothyroidism in iodine-sufficient regions.

Epidemiology

Peak prevalence: 45-65 years
Female:male ratio = 10:1 to 20:1
Also a major cause of non-endemic goiter in children

Pathogenesis

Caused by breakdown of self-tolerance to thyroid autoantigens. Key immune mechanisms:

Fig. Pathogenesis of Hashimoto thyroiditis (Robbins & Kumar Pathologic Basis of Disease)

CD8+ cytotoxic T cells directly kill thyroid follicular cells via MHC-restricted recognition
Cytokine-mediated injury: CD4+ Th1 cells release IFN-γ, activating macrophages and damaging follicles
Autoantibodies: anti-thyroglobulin and anti-thyroid peroxidase (TPO) antibodies cause antibody-dependent cytotoxicity and complement-mediated follicular damage

Genetic risk loci include CTLA4, PTPN22, and IL2RA polymorphisms - all regulators of T-cell responses.

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 998

Morphology

Thyroid is diffusely enlarged, well-demarcated, pale yellow-tan, firm, and somewhat nodular
Extensive lymphoplasmacytic infiltration with germinal centers
Atrophic follicles lined by oncocytes (Hürthle cells) - metaplastic eosinophilic cells
Interstitial fibrosis (not extending beyond the capsule - distinguishes it from Riedel's)

Hashimoto thyroiditis histology - dense lymphocytic infiltrate with germinal centers and residual follicles lined by pink oncocytic cells

Fig. Hashimoto thyroiditis - lymphocytic infiltrate with germinal centers; residual follicles lined by oncocytic (Hürthle) cells. (Robbins, Cotran & Kumar Pathologic Basis of Disease)

FNA biopsy findings: oncocytes + heterogeneous lymphocytes = characteristic Hashimoto pattern.

Clinical Features

Painless symmetric diffuse goiter
Gradual onset of hypothyroidism (low T4/T3, elevated TSH)
Transient early thyrotoxicosis ("hashitoxicosis") due to follicle disruption and hormone release
Associated autoimmune diseases: type 1 diabetes, autoimmune adrenalitis, SLE, myasthenia gravis, Sjögren syndrome
Increased risk of extranodal marginal zone B-cell lymphoma of the thyroid (rare)
Controversial association with papillary thyroid carcinoma
Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 999

2. Subacute Granulomatous Thyroiditis (de Quervain's Thyroiditis)

Also called: viral thyroiditis, painful thyroiditis, giant-cell thyroiditis
Etiology: Post-viral (mumps, coxsackie, influenza, adenovirus, echovirus; also reported with SARS-CoV-2 and COVID vaccination)
Female:male = 5:1; age 20-60

Clinical Course (Triphasic)

Thyrotoxic phase - follicle disruption releases preformed hormone; TSH suppressed
Hypothyroid phase - depleted hormone stores; transient hypothyroidism
Recovery - euthyroidism in most patients

Key Features

Painful, tender, firm thyroid - often referred to throat or ears
Elevated ESR (hallmark), low/absent anti-TPO antibodies
Low radioactive iodine uptake (RAIU)
Granulomatous inflammation on histology (giant cells engulfing colloid)
Self-limited; NSAIDs for pain; corticosteroids for severe cases

3. Subacute Lymphocytic (Painless) Thyroiditis

Includes postpartum thyroiditis and sporadic painless thyroiditis.

Autoimmune etiology (anti-TPO antibodies are high, unlike de Quervain's)
Painless diffuse/nodular goiter
Same triphasic course as de Quervain's but painless
ESR is normal
Histology: lymphocytic infiltration without granulomas
Postpartum variant: occurs within 1 year of delivery in ~5-10% of women; may recur with subsequent pregnancies

4. Acute (Suppurative) Thyroiditis

Rare bacterial/fungal infection of the thyroid
Common organisms: Staphylococcus, Streptococcus, Enterobacter; in immunocompromised: fungi, mycobacteria, Pneumocystis
In children: often due to a piriform sinus fistula (left-sided; remnant of 4th branchial pouch)
Features: acute painful thyroid, fever, dysphagia, erythema; leukocytosis + elevated ESR; thyroid function usually normal
Management: antibiotics guided by FNA culture; surgery if abscess forms (CT/US to localize)

5. Riedel's Thyroiditis (Fibrous Thyroiditis)

Rare; replaces thyroid parenchyma with dense, invasive fibrosis that extends beyond the capsule into surrounding neck structures (differentiating it from Hashimoto's)
"Woody, hard" thyroid on examination
Can cause tracheal/esophageal compression and hypoparathyroidism
Associated with IgG4-related disease in some cases
TPO antibodies may be present
Treatment: tamoxifen, corticosteroids; surgery for decompression

Comparative Summary (Scott-Brown's Classification)

Feature	Hashimoto's	Postpartum/Painless	de Quervain's	Suppurative	Riedel's
Sex ratio (F:M)	8-9:1	-	5:1	1:1	3-4:1
Pain	No	No	Yes	Yes	No
Cause	Autoimmune	Autoimmune	Unknown (viral)	Infectious	Unknown
TPO antibodies	High	High	Low	Absent	Present
ESR	Normal	Normal	High	High	Normal
Thyroid function	Hypothyroid	Mixed	Mixed	Euthyroid	Euthyroid
Gross pathology	Symmetrical diffuse enlargement, firm, pale	Firm, nodular	Firm, nodular	Abscess	Rock-hard, adherent

Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Table 58.4

Drug-Induced Thyroiditis

Several drugs can cause diffuse thyroid inflammation:

Amiodarone - type 1 (iodine-induced hyperthyroidism) or type 2 (destructive thyroiditis)
Lithium - inhibits thyroid hormone release
Interferon-alpha, interleukin-2 - trigger autoimmune thyroiditis
Tyrosine kinase inhibitors and immune checkpoint inhibitors - increasingly recognized causes

Diagnosis at a Glance

Test	Hashimoto's	de Quervain's	Painless	Suppurative
TSH	High (usually)	Variable	Variable	Normal
Anti-TPO	++++	+/-	+++	-
ESR	Normal	Very high	Normal	High
RAIU	Low	Very low	Low	Normal
FNA	Oncocytes + lymphocytes	Giant cells + granulomas	Lymphocytes	PMNs + organisms
Ultrasound	Diffuse heterogeneous, hypoechoic	Diffuse hypoechoic	Variable	Abscess

Almost all euthyroid diffuse goiters in the US are due to Hashimoto thyroiditis, confirmable by anti-TPO antibody measurement. - Washington Manual of Medical Therapeutics

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