64 - Thyroid Pathology Flashcards
Features of inactive thyroid
Low cuboidal cells
Follicle filled with colloid
Features of active thyroid
Tall cuboidal to columnar cells.
‘Scalloping’ of colloid (cells are eating into colloid)
Thyrotoxicosis
An elevated circulating fT3 and fT4 state.
Effects of thyrotoxicosis
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)
Cellular process associated with Graves’ disease
Hyperplasia of follicular cells
Goitre
A non-specific term for any enlargement of the thyroid gland
Diffuse nontoxic goitre (simple)
• 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
Endemic vs sporadic goitre
Endemic if over 10% of population have goitre (from lack of iodine in the diet, EG in Himalayas, areas far from the sea).
Histology of nontoxic (simple) goitre 1 2 3 4 5
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
Multinodular goitres
1
2
- 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
What can arise from a multinodular goitre?
Autonomous nodule can arise.
Leads to toxic multinodular goitre (suppresses TSH levels, as synthesising so much TH)
Management of simple goitre
• 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?
–
What leads to simple goitre?
Iodine deficiency.
High TSH leads to hyperplasia of thyroid.
Histological appearance of Hashimoto’s disease
1
2
3
• 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
Gross pathology of Hashimoto’s thyroid
1
2
3
– 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”
Epidemiology of Hashimoto's 1 2 3 4
– 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
What does Hashimoto’s come with an increased risk of?
Non-Hodgkin’s B cell lymphoma
Clinical signs of Hashimoto's disease 1 2 3 4
– 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
Management of Hashimoto’s disaese
1) Thyroxine replacement
2) Monitor very closely if patient is elderly or pregnant (can tip elderly people into thyrotoxicity).
Clinical findings of Graves’ disease
1
2
3
- Hyperthyroidism due to diffuse, hyperfunctional enlargement of the thyroid
- Infiltrative ophthalmopathy with resultant exophthalmos
- Localised infiltrative dermopathy (“pretibial myxoedema”) in a minority of patients
Histology of Graves’ disease
1
2
3
• 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
Gross pathology of Graves’ disease
1
2
• Diffuse symmetrical enlargement
(cf: multinodular goitre)
• Cut surface is “soft, meaty”
Hashitoxicosis
Transient presentation of Hashimoto’s disease with hyperthyroidism
Antibodies causing Graves’ disease
1
2
3
– 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
Epidemiology of Graves' disease 1 2 3 4
– 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
Clinical signs of Graves’
– 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)
Cause of Graves’ ophthalmopathy
Fibroblasts behind eyes have epitopes that anti-thyroid hormone receptor antibodies can bind to.
Overstimulated fibroblasts release mucopolysaccharides.
Type of hypersensitivity leading to Hashimoto’s
Type IV
Type of hypersensitivity leading to Graves’
Type II
