Medical Thyroid

Question 1

Ectopic thyroid tissue

Answer 1

• Lingual thyroid, back of tongue –> 90% of cases
• Often found within thyroglossal duct cysts –> 25-65%
• Neck midline organs (layrnx, trachea)
• Superior mediastinum
• Benign thyroid follicles occur in perithyroid soft tissue –> harmless

Question 2

Thyroglossal duct cyst

Answer 2

• The most common developmental anomaly of thyroid gland, and the most common congenital neck mass
• Midline neck developmental anomaly due to persistence and cystic dilation of thyroglossal duct
• Thyroglossal duct (TGD) is the embryonic tract characterized by the presence of epithelial lined remnants and heterotopic thyroid tissue
• May appear as blind tubular structure in mid neck or as sinus tract connected to foramen cecum or suprasternal notch skin
• Appears in midline neck anywhere along path of TGD, from foramen cecum in tongue base to suprasternal region
• Most TGD cysts are connected to hyoid bone, which is excised during TGD excision (Sistrunk procedure)
• If hyoid not removed –> recurrence rate 60%
• 75% thyrohyoid (between hyoid bone and thyroid cartilage)
• 25% suprahyoid, including submental
• 2% - 4% intralingual (base of tongue)

Question 3

Goitres

Answer 3

Simple (Diffuse) Goitre
Diffuse hyperplastic goitre
* Physiological
* Pubertal
* Pregnancy

Multinodular

Toxic Goitre
* Diffuse (Grave’s disease)
* Multinodular (Plummer’s disease)
* Toxic adenoma

Question 4

Diffuse Simple Goitre

Answer 4

• Diffuse
• Without nodules
• Most frequently endemic
• Due to iodine deficiency in specific areas of the world
• Most patients are euthyroid

Question 5

Multinodular Goitre

Answer 5

• Asymetrically enlarged gland
• Can grow to 2kg
• Distinct multinodular architecture
• Nodularity is due to uneven response of thyroid follicles to TSH stimulation
• Nodules may cause vascular compression
• Nodule rupture –> necrosis, scarring, haemosiderin, calcification, cyst formation
• Toxic or non-toxic
• Toxic MNG –> Plummer disease –> Hormonally MNG with hyperthyroidism

Question 6

Graves disease

Answer 6

• Commonly seen in middle aged women
• Autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies against thyrotropin (TSH receptor) that activates the receptor, leading to increased thyroid hormone synthesis and secretion and growth of the thyroid gland
• Associated with diffuse goiter, infiltrative ophthalmopathy and less commonly infiltrative dermopathy, including pretibial myxedema and thyroid acropachy (extremity swelling, clubbing of fingers and toes due to periosteal new bone formation)
• Presence of thyrotropin receptor antibody in the serum and orbitopathy on clinical examination distinguishes Graves disease from other causes of hyperthyroidism
• Maternal Graves disease may lead to neonatal thyroidism in 1 - 5% of children due to transplacental transfer of antibodies
• People with other autoimmune diseases such as type 1 diabetes and rheumatoid arthritis are more likely to be affected

Autoantibodies:
* Thyrotropin receptor antibody (TRAb)
* Thyroperoxidase (TPOAb) antibodies
* Thyroglobulin (TgAb) antibodies
* Anti-thyroid stimulating hormone receptor antibodies (TSHR-Ab)
* Anti-nuclear autoantibodies (ANAs)

• Anti-thyrotropin antibodies are specific for Graves disease

Molecular:
* HLA-DR3
* CTLA-4
* Tyrosine phosphatase PTPN22

Micro:
* Hyperplastic thyroid follicles with papillary infoldings
* Tall follicular cells with papillae usually lacking fibrovascular cores
* Nuclei are round, often basally located, rarely overlap
* Colloid is typically decreased, when present shows peripheral scalloping
* Colloid may increase after treatment
* Variable patchy lymphoid infiltrate in the stroma –> T-Cells with fewer B Cells and plasma cells, germinal centres common

Question 7

Hashimoto thyroiditis

Answer 7

• Most common cause of hypothyroidism in iodine sufficient areas
• Hyperthyroidism –> Hypothyroidism
• Infiltration of thyroid parenchyma by mononuclear cells, lymphoid follicles with germinal centers, oncocytic cells lining residual thyroid follicles, fibrosis
• CD8+ T cell mediated cytotoxicity, cytokine mediated cell death and antibody dependent cell mediated cytotoxicity
• Hashitoxicosis: transient thyrotoxicosis due to follicle destruction in Hashimoto thyroiditis
• Rarely progresses to lymphoma

Autoantibodies:

• Thyrotropin receptor antibody (TRAb)
• Thyroperoxidase (TPOAb) antibodies
• Thyroglobulin (TgAb) antibodies
• Anti-thyroid stimulating hormone receptor antibodies (TSHR-Ab)

Molecular:
* HLA-DR5 (goiterous form)
* HLA-DR3 (atrophic form)

Micro:
* Classic form: diffuse infiltration of thyroid parenchyma with lymphocytes and plasma cells; lymphoid follicle formation with germinal centers
* Polymorphic lymphocytic infiltrate, predominantly T cells
* Thyroid follicular destruction
* Atrophic thyroid follicles; many lined by oncocytic cells / oncocytes having abundant granular eosinophilic cytoplasm; rarely squamous metaplasia
* Later fibrosis and nodularity

Question 8

Subacute Granulomatous Thyroiditis

Answer 8

• Historical name: de Quervain thyroiditis
• Granulomatous inflammation of the thyroid gland with characteristic clinical and microscopic findings
• Most common cause of thyroid related neck pain and typically occurs a few weeks after a viral infection
• Associated with coxsackievirus, echovirus infections, mumps, measles, influenza and other viruses
• Fatigue, low grade fever, myalgias, along with neck pain and diffuse goiter
• Self limited in most of cases, usually resolves in 1 - 2 months
• Thyrotoxic phase: hyperthyroid (suppressed thyroid stimulating hormone [TSH] and elevated T4 and T3) due to follicle destruction and release of hormone
• After 4 - 8 weeks: TSH and free T4 levels may be low

Micro:
* Inflammatory infiltrate composed of multinucleated giant cells, foamy histiocytes, epithelioid histiocytes, neutrophils, lymphocytes, plasma cells
* Occasional microabscesses
* Variable background of fibrosis

Question 9

Riedel thyroiditis

Answer 9

• Densely fibrotic inflammatory process involving thyroid gland and adjacent neck tissue
• Associated with inflammatory fibrosclerosis / multifocal systemic fibrosclerosis (mediastinal or retroperitoneal fibrosis, sclerosing cholangitis, inflammatory pseudotumor of orbit)
• Part of the spectrum of IgG4-related disease
• 65% have antithyroid antibodies
• Clinically resembles carcinoma
• Extensive stony hard fibrosis involving a goitrous thyroid gland and infiltration into adjacent muscle and other structures, obliterating tissue planes at surgery
• Binds soft tissues of neck in an “iron collar,” may compress trachea

Micro:
* No normal lobular pattern
* Follicles are obliterated or compressed by extensive dense fibrous tissue, which also infiltrates adjacent skeletal muscle
* Patchy lymphocytes (B & T cells), plasma cells (IgA, lambda) and eosinophils, inflammation in walls of trapped veins
* 25% have adenoma centrally in fibrous mass