64 - Thyroid Pathology

Question 1

Features of inactive thyroid

Answer 1

Low cuboidal cells

Follicle filled with colloid

Question 2

Features of active thyroid

Answer 2

Tall cuboidal to columnar cells.

‘Scalloping’ of colloid (cells are eating into colloid)

Question 3

Thyrotoxicosis

Answer 3

An elevated circulating fT3 and fT4 state.

Question 4

Effects of thyrotoxicosis

Answer 4

Hypermetabolic state
-Heat intolerance; warm flushed skin; fatigue
–Weight loss (despite increased appetite); osteoporosis
•Other symptoms (autonomic effects)
–Palpitations, arrhythmias, cardiomyopathy
–Tremor, anxiety, insomnia, emotional lability
–GI (diarrhoea), MSK, ocular (lid lag), other…
•
TSH decrease, fT4 increase (generally)

Question 5

Cellular process associated with Graves’ disease

Answer 5

Hyperplasia of follicular cells

Question 6

Goitre

Answer 6

A non-specific term for any enlargement of the thyroid gland

Question 7

Diffuse nontoxic goitre (simple)

Answer 7

• Reflects impaired synthesis of thyroid hormone
• Low thyroid hormone causes elevation of TSH
• A compensatory response
• Usually euthyroid (normally functioning thyroid)
– TSH normal to slightly elevated, fT4 normal (generally)
• Will “involute” if TSH and thyroid hormone levels return to normal

Question 8

Endemic vs sporadic goitre

Answer 8

Endemic if over 10% of population have goitre (from lack of iodine in the diet, EG in Himalayas, areas far from the sea).

Question 9

Histology of nontoxic (simple) goitre
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2
3
4
5

Answer 9

Cells have responded to increased TSH:

• Hyperplastic follicles
• Follicles lined by crowded cells
• Some follicles larger than others, may have large colloid-filled cysts
• With resolution, follicles involute, low cuboidal epithelium, abundant colloid
• With chronic high TSH, some follicles rupture or haemorrhage

Question 10

Multinodular goitres
1
2

Answer 10

• Over time, with cycles of hyperplasia and involution, some follicles become large nodules, while others rupture and fibrose
• May see haemosiderin, calcification and cholesterol clefts

Question 11

What can arise from a multinodular goitre?

Answer 11

Autonomous nodule can arise.

Leads to toxic multinodular goitre (suppresses TSH levels, as synthesising so much TH)

Question 12

Management of simple goitre

Answer 12

• Iodine or thyroid hormone replacement therapy
– Diffuse goitre: regression over 3-6months
– Multinodular goitre: fewer than a third regress
• Surgery to relieve compressive symptoms (and for cosmetic effect)
• Autonomous nodule?
–

Question 13

What leads to simple goitre?

Answer 13

Iodine deficiency.

High TSH leads to hyperplasia of thyroid.

Question 14

Histological appearance of Hashimoto’s disease
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2
3

Answer 14

• Mononuclear inflammatory infiltrate
– Lymphocytes (equal proportions of T and B cells)
– Plasma cells
– Germinal centres
• Thyroid cells show changes
– With “abundant, eosinophilic, granular cytoplasm” (‘Hürthle cells’)
• Increased interstitial connective tissue
– Fibrosis/scarring: chronic inflammation

Question 15

Gross pathology of Hashimoto’s thyroid
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3

Answer 15

– Enlarged at first, eventually atrophic gland;
– Cut surface: firm, tan-yellow (similar to lymph nodes) pale (fibrotic), somewhat nodular
– Incision like “cutting through an unripe pear”

Question 16

Epidemiology of Hashimoto's 
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2
3
4

Answer 16

– Prevalence: ~5%, up to 10% of women with  age
– Female predominance of 10:1 to 20:1
– Most common cause of hypothyroidism (where iodine levels are sufficient)
– Most prevalent from 45 to 65 years of age

Question 17

What does Hashimoto’s come with an increased risk of?

Answer 17

Non-Hodgkin’s B cell lymphoma

Question 18

Clinical signs of Hashimoto's disease 
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4

Answer 18

– Gradual onset of hypothyroidism and/or goitre
– Antibodies against thyroglobulin (anti-TG) and especially thyroid peroxidase (anti-TPO)
– TSH elevated, fT4 decreased, Thyroglobulin ABs increased, Anti TPO ABs increased
– FNA (if performed) should show Hürthle cells with mixed population of lymphocytes

Question 19

Management of Hashimoto’s disaese

Answer 19

1) Thyroxine replacement

2) Monitor very closely if patient is elderly or pregnant (can tip elderly people into thyrotoxicity).

Question 20

Clinical findings of Graves’ disease
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2
3

Answer 20

1. Hyperthyroidism due to diffuse, hyperfunctional enlargement of the thyroid
2. Infiltrative ophthalmopathy with resultant exophthalmos
3. Localised infiltrative dermopathy (“pretibial myxoedema”) in a minority of patients

Question 21

Histology of Graves’ disease
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3

Answer 21

• Follicular cells are tall and more crowded: diffuse hypertrophy and hyperplasia
– May form papillae in follicle lumen
• Widespread scalloping of colloid
– Colloid is often paler-staining
• Lymphocytic infiltrates

Question 22

Gross pathology of Graves’ disease
1
2

Answer 22

• Diffuse symmetrical enlargement
(cf: multinodular goitre)
• Cut surface is “soft, meaty”

Question 23

Hashitoxicosis

Answer 23

Transient presentation of Hashimoto’s disease with hyperthyroidism

Question 24

Antibodies causing Graves’ disease
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2
3

Answer 24

– Thyroid stimulating immunoglobulins (“TSI”)
• Bind and stimulate TSH receptor

– Thyroid growth-stimulating immunoglobulins
• Bind and stimulate TSH receptor

– TSH-binding inhibitor immunoglobulins
• Stimulate or inhibit TSH receptor

– Can develop or even present with hypothyroidism

Question 25

Epidemiology of Graves' disease
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3
4

Answer 25

– Prevalence: 0.5-2%
– Female preponderance of 5:1 to 8:1
– Most prevalent from 20 to 50 years of age
– Strong genetic component (some genes in common with Hashimoto disease), association with smoking
• Most common cause of hyperthyroidism

Question 26

Clinical signs of Graves’

Answer 26

– Symptoms of thyrotoxicosis, possibly a goitre
– Associated non-thyroid changes
• Ophthalmopathy (30-50%), pretibial myxoedema (~5%)
– TSH decreased, fT4 increased, Anti TPO ABs increased, TSI increased (diagnostic)

Question 27

Cause of Graves’ ophthalmopathy

Answer 27

Fibroblasts behind eyes have epitopes that anti-thyroid hormone receptor antibodies can bind to.
Overstimulated fibroblasts release mucopolysaccharides.

Question 28

Type of hypersensitivity leading to Hashimoto’s

Answer 28

Type IV

Question 29

Type of hypersensitivity leading to Graves’

Answer 29

Type II