Category Archives: Thyroid

Myxedema

Myxedema

- hypothroidism in older child, adult
- slowing of activity and mentation
- listless, cold intolerance, overweight, dry skin and hair

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Cretinism

Cretinism

- secondary to hypothryoidism in utero
- seen in infants
- severe mental retardation, impairment of skeletal and central nervous system

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Causes of Hypothyroidism

Causes of Hypothyroidism

- ↓ thyroid parenchyma (thyroid tissue)
- radioablation
- surgical ablation
- Hashimoto’s thyroiditis

- Riedel’s thryoiditis
- interference with hormone synthesis
- idiopathic primary hypothyroidism
- dyshormonogenetic goitre
- drugs
- iodine deficiency
- suprathyroidal
- pituitary lesions (↓TSH)
- hypothalamic lesions (↓TRH)

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Thyrotoxicosis

Thyrotoxicosis

Thyrotoxicosis causes:

•    Graves disease with diffuse hyperplasia
•    Hashimoto’s thyroiditis (early)
•    Hyperfunctioning adenoma
•    Hyperfunctioning goitre
•    Exogenous thyroid hormone

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Thyroid Hormones

Thyroid Hormones

- thyroid releasing hormone (TRH) released by hypothalamus
- thyroid releasing hormone stimulates pituitary to release thyroid stimulating hormone (TSH)

Thyroid stimulating hormone stimulates the:
- conversion of thryoglobulin to T4 and T3
- release of T4 and T3

T4 and T3 are:
- bound to throxine binding globulin (TBG)
- provide feeback inhibition on thyroid

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Thyroiditis

Thyroiditis

Classification

·    Infectious thyroiditis

·    Hashimoto thyroiditis

·    Subacute granulomatous (DeQuervain) thyroiditis

·    Subacute lymphocytic (painless) thyroiditis

·    Riedel thyroiditis

·    Palpation thyroiditis

Evidence for autoimmune etiology of Hashimotos thyroiditis

·    Sensitization of CD4+ T-cells to thyroid antigens seems to be the inciting factor in this autoimmune disease

·    Effector mechanisms for thyrocyte death are:

o    CD8+ cytotoxic T-cell mediated cell death

-    CD8+ cytotoxic T-cells may cause thyrocyte destruction by one of two pathways:

·    Exocytosis of perforin/granzyme granules

·    Engagement of death receptors (CD95/Fas) on the target cell

o    Cytokine-mediated cell death:

-    T-cells produce cytokines such as IFN-γ in the vicinity of thyrocytes which recruits and activates macrophages resulting in damage to the follicles

o    Binding of antithyroid antibodies (anti-thyroglobulin antibody, anti-TSH receptor antibody, and anti-thyroid peroxidase antibody) followed by antibody-dependent cell-mediated cytotoxicity

Cytologic features of Hashimotos thyroiditis on FNAC

·    Polymorphous lymphocytic population (variably-sized lymphocytes)

·    Tingible-body macrophages

·    Hurthle cells

·    Clusters and sheets of follicular epithelial cells (macrofollicular, honeycomb arrangement)

Prognosis of Hashimotos thyroiditis

·    Benign condition

·    Causes hypothyroidism, although may be preceded by a period of hyperthyroidism (“hashitoxicosis”) with elevated T3 and T4, diminished TSH, and increased uptake of radioactive iodine

·    Increased risk of developing other autoimmune diseases

o    Endocrine (Type 1 diabetes, autoimmune adrenalitis)

o    Non-endocrine (Sjogren syndrome, SLE, myasthenia gravis)

·    Increased risk of developing B-cell non-Hodgkin lymphomas

·    No established risk of developing thyroid epithelial neoplasms

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Papillary Thyroid Carcinoma

Papillary Thyroid Carcinoma

Papillary thyroid carcinoma gene rearrangement

•    RET/PTC which occurs due to paracentric inversion of chromosome 10 or reciprocal translocation between chromosome 10 and 17 which places the RET gene under transcriptional control of constitutively active genes on these chromosomes

•    RET is part of a family of receptor tyrosine kinases that transduce extracellular signals for cellular growth and differentiation

- through signalling of the MAP kinase pathway

•    The receptor is not present on normal thyroid follicular cells

- the fusion protein produced due to the genetic rearrangement is found in approximately 20% of papillary thyroid cancers

Cytologic features in fine-needle aspirates

•    Sheets of follicular cells exhibiting a a syncytial arrangement, overlapping of cells, nuclei

•    Nuclei of follicular cells exhibit grooves, powdery chromatin, nuclear crowding and molding

•    Chromatin clearing within follicular cell nuclei (“Orphan Annie eye”) due to nuclear pseudoinclusions

•    Irregular nuclear outlines, prominent nucleoli

•    Rarely, papillary architecture with follicular epithelial cells surrounding fibrovascular core

•    Psammoma bodies, uncommonly

Papillary thyroid carcinoma histologic variants

•    Papillary microcarcinoma

•    Encapsulated variant

•    Follicular variant

•    Columnar variant

•    Tall cell variant

•    Diffuse sclerosing variant

•    Hyalinizing trabecular adenoma

•    Solid variant

Papillary Thyroid Carcinoma Prognosis

Encapsulated variant

o    Confined to thyroid gland, well encapsulated

o    Rarely presents with vascular or lymph node dissemination

o    Excellent prognosis

Follicular variant

o    Behavior and prognosis similar to that of classic papillary carcinoma

o    Exhibit lymphatic spread to adjacent lymph nodes

o    Excellent prognosis with 95% 10 year survival

o    5-20% local/regional recurrence

o    10-15% with distant metastases

Tall cell variant

o    Large tumors with prominent vascular invasion, extrathyroidal extension, and cervical and distant metastases

o    More aggressive than classical papillary thyroid cancer

Diffuse sclerosing variant

o    Present as bilateral goiter; demonstrates prominent papillary architecture with solid areas containing nests of squamous cells (squamous morules)

o    Extensive diffuse fibrosis associated with prominent lymphocytic infiltrate

o    Nodal metastases are present in all cases due to propensity to invade intrathyroidal lymphatic channels

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Hashimotos Thyroiditis

Hashimotos Thyroiditis

Pathogenesis

Hashimotos thyroiditis is an autoimmune disease due to sensitization of autoreactive CD4+ helper T-cells to thyroid antigens (the initiating event), followed by various effector mechanisms:

•    CD8+ cytotoxic T-cell mediated cell death (cause follicular cell death via exocytosis of granzyme/perforin, or engagement of death receptors such as CD95 or Fas)

•    Cytokine-mediated cell death (CD4+ cells release IFN-gamma recruiting macrophages which damage follicular cells)

•    Binding of antithyroid antibodies followed by antibody-dependent cell-mediated cytotoxicity (antibodies involved include anti-TSH receptor antibodies, antithyroglobulin, and antithyroid peroxidase antibodies)

Clinical features

1.    Enlarged thyroid (25-250 g)

2.    Hypothyroidism

3.    Can sometimes develop thyrotoxicosis

4.    Patients can also develop other autoimmune diseases (Sjogren’s syndrome, Type 1 diabetes, autoimmune adrenalitis, myasthenia gravis, SLE)

Histologic findings

1.    Small, atrophic thyroid follicles with dense/absent colloid

2.    Metaplastic thyroid follicular cells with oncocytic (Hurthle cell), clear cell or squamous metaplasia; nuclei of follicular cells show clearing, overlap and enlargement (can mimic papillary carcinoma)

3.    Lymphoplasmacytic infiltration of stroma and atrophic follicles with germinal centre formation

Associated neoplasms

1.    B-cell lymphoma (extranodal marginal zone lymphoma, DLBCL)

2.    Plasmacytoma

3.    Mucoepidermoid carcinoma

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Papillary Carcinoma

Papillary thyroid carcinoma

Fine needle aspiration findings

Sheets of follicular cells exhibiting a “drunken honeycomb”/microfollicular/syncytial arrangement (ie. overlapping of cells, nuclei)

Nuclei of follicular cells exhibit grooves, powdery chromatin, nuclear crowding and molding

Chromatin clearing within follicular cell nuclei (“Orphan Annie eye”)/nuclear pseudoinclusions

Irregular nuclear outlines, prominent nucleoli

Rarely, papillary architecture (ie. follicular epithelial cells surrounding fibrovascular core)

Psammoma bodies

Prognostic features

Age (>40 y.o.)

Lymph node metastases

Extrathyroidal extension

Size of tumour

Gender (male=worse prognosis)

Behaviour of Thyroid Papillary Carcinoma

- (route of metastases, prognosis)

Present as asymptomatic thyroid nodules (“cold” nodules on scintigraphy)

May present as asymptomatic cervical mass (papillary thyroid carcinoma metastatic to lymph node)

Hoarseness, dysphagia, cough, or dyspnea suggests advanced disease

Minority of patients present with hematogenous metastases (most commonly lung)

Typically papillary thyroid carcinoma spreads via lymphatics

Prognosis is good (>95% 10 year survival)

Local/regional recurrence (5-20% of patients)

Distant metastases in 10-15% of patients

Proto-oncogenes involved

RET/PTC or NTRK1

BRAF

RAS

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Hyperthyroidism Symptoms

Hyperthyroidism Symptoms

Clinical features of hyperthyroidism

1.    Exophthalmos, lid lag

2.    Tachycardia, palpitations

3.    Tremors

4.    Heat intolerance

5.    Myxedema

6.    Thyroid bruit

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