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
• Nonsteroidal anti-inflammatory drugs • Methylprednisone 151 to 40 mg/day for 2–4 weeks • A longer period of treatment2 is related to fewer relapses (40 vs 20 days) • Improvement is expected in 24–48hs. (if not, look for a differential diagnosis) • Propanolol 40 to 120 mg/day or atenolol 25 to 50 mg/day while thyrotoxic, levothyroxine while hypothyroid 1Sato J, et al. Endocrine 2017 Jan;55(1):209-214; 2Arao T, et al. J UOEH. 2015 Jun 1;37(2):103-10.
THYROIDITIS Acute thyroiditis
INFECTIOUS Bacterial~85% Suppurative • mycobacterium and Non suppurative syphilis NON INFECTIOUS Traumatic Actinic Chemical: induced by Others: drugs mycotic, parasitic~15%
THYROIDITIS Infectious thyroiditis
Fistulae from piriform sinus (in children) 90% in left thyroid lobe
Fistulae from 4th branchial arch sinus or from a thyroglossal persistent duct
Hematogenous: pharingitis, parotiditis, mastoiditis, otitis, endocarditis, retropharingeal abscess, airway infections, odontological, etc.
THYROIDITIS Infectious thyroiditis
Severe cervical pain of abrupt onset, unilateral High fever, In case of with maxilar Odinophagia, Thyroid recurrence The abcess auricular or chills disphagia, dysfunction suspect can drain (bacteremia) occipital adenopathies disphony exceptional piriform sinus spontaneously irradiation, fistulae aggravated with hyperextension
THYROIDITIS Infectious thyroiditis
Laboratory: Leucocitosis, high erythrocyte sedimentation rate
Discount HIV
FNAB of the abscess and bacterial culture
THYROIDITIS Infectious thyroiditis
Barium- CT/MRI neck and contrasted US confirms if mediastinum esophagus study Gallium there is one or may alert of air in or laringoscopy scintigraphy more abscess the neck (fístulase and diverticulum)
THYROIDITIS Infectious thyroiditis treatment
Aspirate abscess and prescribe antibiotics
May not require surgery
Avoid steroids
THYROIDITIS Acute thyroiditis
INFECTIOUS Suppurative Non suppurative NON INFECTIOUS Traumatic Actinic Chemical: induced by drugs
THYROIDITIS Immune-related drug-induced thyroiditis
Immune- Immune Tyrosine modulators checkpoint Lithium Amiodarone kinase inhibitors (INF alpha/ inhibitors beta, IL-2) (ICIs)
Ferrari S, et al. Rev Endocr Metab Disord. 2018 Sep 21:doi: 10.1007/s11154-018-9463-2; Iyer PC, et al. Thyroid 2018 Oct;28(10):1243-1251.
THYROIDITIS Conclusions
If thyroiditis is suspected, check for pain
If no history of trauma or radiation, discard subacute or acute thyroiditis depending upon clinical presentation A low iodine uptake might be useful for diagnosis
In the absence of pain, drugs or the patient being post- partum, check thyroid function, thyroid antibodies and iodine uptake to confirm etiology
THYROIDITIS Conclusions
Treatment includes:
Acute: ATB and eventually drainage
Subacute: NSAID, glucocorticoids and beta-blockers
Chronic: Levothyroxine, eventually beta-blockers, surgery and tamoxifen (Riedel)
THYROIDITIS