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Thyroiditis Dr Gabriela Brenta

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Thyroiditis Dr Gabriela Brenta Thyroiditis Dr Gabriela Brenta Department of Endocrinology Milstein Hospital, Buenos Aires, Argentina THYROIDITIS Thyroiditis - definition Thyroiditis is characterized by the presence of inflammation in the thyroid Can be painful or indolent Thyroid dysfunction and goiter may or may not be present THYROIDITIS Types of thyroiditis Classification according to clinical presentation PAINFUL • Acute • Subacute • Radiation • Trauma PAINLESS • Hashimoto • Post-partum • Silent • Drug-induced • Riedel THYROIDITIS Types of thyroiditis Classification according to clinical course acute subacute chronic INFECTIOUS SUPPURATIVE: GRANULOMATOUS Suppurative • Infectious unspecific (or De Quervain) Non suppurative • Infectious specific (TBC, syphillis, NON INFECTIOUS actinomicosis) Traumatic LYMPHOCYTIC OR PAINLESS NON SUPPURATIVE: Actinic (sporadic or post- • Fibrous (or Riedel) Chemical: induced by partum) • Lymphocytic (or drugs Hashimoto’s) THYROIDITIS Chronic thyroiditis Suppurative: • Infectious unspecific • Infectious specific (TBC, syphillis, actinomicosis) • Non suppurative: • Fibrous (or Riedel) •Lymphocytic (or Hashimoto) THYROIDITIS Dr Hakaru Hashimoto described thyroiditis in 1912, hence it’s name THYROIDITIS Lymphocytic or Hashimoto’s thyroiditis Part of the spectrum of autoimmune thyroid diseases (AITDs) Characterized by the destruction of thyroid cells by various cell- and antibody-mediated immune processes More frequent in women (estrogen + X chromosome, fetal microchimerism) from age 30 onwards Most frequent cause of primary hypothyroidism THYROIDITIS Lymphocytic or Hashimoto’s thyroiditis Background factors: increased iodine intake, selenium deficit, stress, toxins, drugs, infection smoking (decreases incidence) Incidence in US: 3.5 per 1000/year in women and 0.8 per 1000/year in men Prevalence of detectable TGAb and TPOAb levels were 10 and 12% of the healthy population1 Associated with development of B cell lymphoma 1Vanderpump F. British Medical Bulletin 2011 Sept1;99(1):39-51. THYROIDITIS Clinical manifestations of Hashimoto’s thyroiditis Asymptomatic (euthyroid or subclinical hypothyroidism) Clinical hypothyroidism: 10-20% (5% annual risk) Hyperthyroidism: 5% (Hashi-Graves). Alternating hypo- and hyperthyroidism Diffuse goiter. In 1/3 of cases uni- or multinodular. Painless, firm consistency, irregular surface or lobulated and of variable size Atrophic thyroiditis: late evolution, TPOAb positive, no goiter and with hypothyroidism THYROIDITIS Pathophysiology of Hashimoto’s thyroiditis Peripheral tolerance is guaranteed by regulatory B and T cells Autoimmunity (loss of tolerance) could be due to an imbalance between effector and regulatory cells in favour of a pro-inflammatory response Bliddal S, et al. 1000Research 2017;6(F1000 Faculty Rev):1776. THYROIDITIS Potential mechanisms of thyroid autoimmunity Infiltration of Thyroid hematopoietic expression Molecular mononuclear cells of HLA mimicry class II (mainly lymphocytes), into the interstitium among the thyroid follicles occurs, Bystander leading to thyroid cell activation lysis THYROIDITIS Hashimoto’s thyroiditis disease mechanism Hashimoto’s thyroiditis results when the effects of cumulative weaknesses line up to allow autoimmune destruction to occur Weetman AP. Eur Thyroid J 2013 Jan;1(4):243-50. THYROIDITIS Diagnosis Thyroid Thyroid antibodies ultrasonography THYROIDITIS Antibodies in Hashimoto’s thyroiditis Thyroid peroxidase antibody (TPOab) positive in 90-100% of cases 50-60% TPOab positive patients are thyroglobulin antibody (TGab) negative TGab positive: 80-90% Relatives of patients with Hashimoto’s: 30-50% are TPOab positive THYROIDITIS Ultrasonography (US) in Hashimoto’s thyroiditis • 20% of individuals with higher •• TheThe presencepresence ofof Hashimoto’sHashimoto’s TSH values and lymphocytic thyroiditisthyroiditis onon USUS increasesincreases thethe riskrisk infiltration of the gland have ofof thethe diseasedisease movingmoving fromfrom hypoechogenicity without subclinicalsubclinical toto clinicalclinical detectable thyroid antibodies hypothyroidismhypothyroidism Pedersen OM, et al. Thyroid 2000 Mar;10(3): 251-9. RosárioRosário PW, PW, et et al. al. Thyroid Thyroid 2009 2009 Jan;19(1):9-12. Jan;19(1):9-12. THYROIDITIS Ultrasonography in Hashimoto’s thyroiditis Ultrasound image of a patient with Hashimoto’s thyroiditis, showing a heterogeneous pattern to the gland and hypervascularization THYROIDITIS Clinico-pathological spectrum of Hashimoto’s thyroiditis Hashimoto’s thyroiditis variants: Primary forms Painless Fibrous IgG4-related thyroiditis Classic form Juvenile form Hashitoxicosis variant variant (sporadic or post-partum) Caturegli P, et al. Autoimmun Rev 2014 Apr-May;13(4-5):391-7. THYROIDITIS Clinico-pathological spectrum of Hashimoto’s thyroiditis Hashimoto’s thyroiditis can be part of the “Polyglandular autoimmune syndromes” (PAS) PAS Type 1: Juvenile, also PAS Types 2-4 known as autoimmune Adults, polyendocrinopathy-candidiasis- ectodermal dystrophy (APECED) Polygenetic inheritance or Whitaker syndrome AITD 70-75% Monogenic T1D 50-60% Mucocutaneous candidiasis is Autoimmune Addison disease associated with glandular failure 40-50% Kahaly GJ, et al. J Endocrinol Invest 2018 Jan;41(1):91-98. THYROIDITIS Classic form of Hashimoto’s thyroiditis • Few thyroid follicles • Interstitial infiltration of hematopoietic mononuclear cells, mainly composed of lymphocytes • Lymphoid follicles • Fibrosis • Hürthle cells Caturegli P, et al. Autoimmun Rev 2014 Apr-May;13(4-5):391-7. THYROIDITIS Fibrous variant of Hashimoto’s thyroiditis • Enlarged, hard gland • Thyroid capsule contains the fibrosis • Pseudonodular • Represents 10% of Hashimoto variants • In the elderly, it may explain idiopathic myxedema with a small gland Caturegli P, et al. Autoimmun Rev 2014 Apr-May;13(4-5):391-7. THYROIDITIS IgG4-related variant of Hashimoto’s thyroiditis • First described by Li et al. in Japan in 2009.* • Pronounced lympho-plasmacytic infiltrate • Plasmatic cells produce IgG4 • Fibrosis *Li Y, et al. Pathol Int 2009;59:636-41. Caturegli P, et al. Autoimmun Rev 2014 Apr-May;13(4-5):391-7; Watanabe T. Scand J Rheumatol 2013;42(4):325-30. THYROIDITIS Differences among the Hashimoto forms Classic Fibrous IgG4-related Juvenile Hashi-toxicosis Post-partum Peak age 40-60 60-70 40-50 10-18 40-60 20-40 (years) at onset F:M ratio 12:1 10:1 3:1 6:1 5:1 N/A Thyroid Normal in Hypo- Hypothyroidism Normal/ Hyper-thyroidism Hyper-or function at most patients thyroidism subclinical hypothyroidism presentation hypothyroidism Sonographic Hypoecho- Hypoecho- Pronounced Hypo- Hypo- Hypo- findings genicity genicity with hypo- echogenicity echogenicity echogenicity nodularity echogenicity 24h RAI Variable Decreased Unknown Variable Increased Decreased uptake Fibrosis Yes Severe Yes No No No Caturegli P, et al. Autoimmun Rev 2014 Apr-May;13(4-5):391-7. THYROIDITIS Post-partum thyroiditis occurs in 5-10% of pregnancies Risk is higher in those with: • Autoimmune disease: DM1 (25%) • TPOab+ (50%) • Personal or family history of thyroid autoimmune disease • Previous post-partum thyroiditis (70%) Stagnaro-Green A. J Clin Endocrinol Metab, 2012 Feb;97(2):334-42. THYROIDITIS Chronic thyroiditis Suppurative: Bilateral • Infectious unspecific compromise of the thyroid • Infectious specific (TBC, gland syphillis, actinomicosis) Mildly painful, • Non suppurative: slow progression • Fibrous (or Riedel) • Lymphocytic (or May be Hashimoto’s) euthyroid THYROIDITIS Chronic thyroiditis Suppurative: • Infectious unspecific • Infectious specific (TBC, syphillis, actinomicosis) • Non suppurative: • Fibrous (or Riedel) • Lymphocytic (or Hashimoto’s) THYROIDITIS Fibrous or Riedel thyroiditis Very infrequent, incidence 1.06/100,000 prevalence 0.05% of thyroidectomies (Mayo Clinic data) Occurs in women 30-50 years 5-10x more often than in males Fibrosis is widely invasive Most cases are isolated (70%), can be systemic Associated with other autoimmnune disorders Has been related to IgG4 Kottahachchi D, Topliss DJ. Eur Thyroid J 2016;5:231-9; Fatourechi MM, et al. Thyroid 2011;7:765-72. THYROIDITIS Subacute thyroiditis GRANULOMATOUS (or De Quervain) LYMPHOCYTIC OR PAINLESS (sporadic or post-partum) THYROIDITIS Classical evolution of thyroiditis Hypo- Hyper- Euthy- Recovery: thyroid roid thyroid Euthyroidism phase phase phase THYROIDITIS Granulomatous (or De Quervain) thyroiditis Frequency 5‒6% Female gender (7:1) 30–60 years Limited to 1‒3 Summer/early Associated with months Autumn HLA B35 (ad integrum restitution) Viral: enterovirus, VEB, influenza, coxackie, adenovirus, Malaria, Q fever echovirus, CMV. Post- vaccine VHB. Kramer AB, et al. Thyroid 2004;14:544-7; Ohsako N, et al. J Clin Endocrinol Metab 1995;80:3653-6. THYROIDITIS Granulomatous (or De Quervain) Clinical presentation: Subacute pain in the front of the neck Preceded by upper respiratory tract infection 2-8 weeks prior Fever (30%), astenia, myalgia arthralgias, anorexia • Thyroid gland enlargement: uni- or bilateral (64%) or migratory • Symptomatic thyrotoxicosis (60%) THYROIDITIS Granulomatous (or De Quervain) Laboratory test findings: Erythrocyte sedimentation (>50 mm/h)/ high PCR Leucocytosis TPOab and TG ab negative Thyroid function: • Hyperthyroid phase: Elevation of thyroglobulin, T3 and T4. TSH suppressed • Hypothyroid phase: Low free T4 and high TSH Images: US: Thyroid volume increased, focally or diffusely hypoechoic. Not hypervascularized Radioiodine (RAI) uptake and scintigraphy: reduced uptake THYROIDITIS Granulomatous (or De Quervain) Treatment
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