Histopathology 4 - Endocrine disease Flashcards
What are the most common causes of hyper- and hypo-pituitarism?
Hyperpituitarism: functional adenoma
Hypopituitarism: nonsecretory adenomas/ ischaemic necrosis (Sheehan’s syndrome)/ surgery
What are the 3 symptoms of local mass effect of pituitary tumours?
Bitemporal hemianopia
Elevated ICP
Obstructive hydrocephalus
Recall 4 differentials for primary hyperthyroidism
- Grave’s
- Hyperfunctioning multinodular goitre
- Hyperfunctioning adenoma
- Thyroiditis
What is the cause of secondary hyperthyroidism?
TSH-secreting pituitary adenoma (rare)
How can struma ovarii cause thyroid disease?
Ovarian teratomas can secrete ectopic thyroxine
What autoimmune condition can cause hypothyroidism?
Hashimoto’s
most common cause of hypothyroidism in the UK
Differentiate the type of auto-antibodies involved in Grave’s vs Hashimoto’s
Grave’s: anti-TSH
Hashimoto’s: anti-TPO and anti-TG (thyroglobulin)
What is the histological appearance of a Hashimoto’s thyroid?
Lymphocyte aggregates and transformed follicular cells
Hurthle cells
What are the main symptoms of Hashimoto’s?
Clinically hypothyroid
Painless goitre
Recall 4 differentials for the cause of hypothyroidism
- Postablative
- Iodine deficiency - most common worldwide
- Congenital biosynthetic defect
- Autoimmune (Hashimoto’s) - most common in the UK
What is a thyroid adenoma?
Benign neoplasm of follicular thyroid epithelium
A small proportion causes thyrotoxicosis
How are thyroid adenomas diagnosed?
FNA and cytology
What are the 4 subtypes of thyroid carcinoma?
Papillary
Follicular
Medullary
Anaplastic
What is the most common type of thyroid carcinoma?
Papillary
What are the key histological features of papillary thyroid cancer?
Optically clear nuclei
Psammoma bodies
Orphan Annie eye: intranuclear inclusions
**this is the basis for diagnosis
NOT based on markers!
Which type of thyroid adenoma is associated with Multiple Endocrine Neoplasia?
Medullary
Which type of thyroid adenoma is most aggressive?
Aplastic
What is the most common cause of primary hyperparathyroidism?
Solitary adenoma
Followed by:
parathyroid hyperplasia
Carcinoma (very rare)
a before h; adenoma is more common than hyperplasia
What is the most common symptom of hyperparathyroidism?
Clinically silent hypercalcaemia (so not really a symptom)
If it is symptomatic:
bones- osteitis fibrosa cystica
stones - kidney stones
abdominal groans - constipation, nausea and ovmiting
psychic moans- depression
thrones - polyuria, polydipsia
What is secondary hyperparathyroidism almost always caused by?
Renal failure –> low calcium
Recall 3 possible causes of hypoparathyroidism
Surgical ablation
Congenital absence - di george syndrome
Auto-immune
Recall 4 possible symptoms of hypoparathyroidism
Those of hypocalcaemia:
Muscle spasms/ tetany
Cardiac arrhythmias
Fits
Cataracts
CATS go numb
convulsions
arrythmia
tetany
spasms
numbness
Recall the synthetic function of each zone of the adrenals
Medulla: Noradrenaline and adrenaline
Reticularis: androgens
Fasciculata: glucocorticoids
Glomerulosa: aldosterone
GFR - out to in
What is Waterhouse-Friedrichson syndrome?
Adrenal insufficiency with sepsis and DIC
Most common functional adenoma
Prolactinoma
Size of amicroadenoma
<1cm
Features of growth hormone excess
- Diabetes
- muscle weakness
- hypertension
- congestive cardiac failure
Which anterior pituitary hormone deficiency manifests earliest?
Gonadotrophin deficiency
- Amenorrhoea and infertility in women
- Decreased libido and impotence in men
Which type of cells make up anterior vs posterior pituitary?
Anterior: epithelial cells
Posterior: nerve cells
Cells of the thyroid gland
- Follicular cells - epitehlial cells lining the follicles
- these respond to TSH
- convert Thyroglobulin –> T3 and T4 - Stromal cells
- Parafollicular cells - aka C cells
- release calcitonin
Causes of non-toxic thyroid goitre
- iodine deficiency
- cabbage
- enzyme defects
- puberty especially in girls
What leads to multi-nodular goitre?
- With time, simple thyroid enlargement may → multi-nodular pattern
- This may reach a massive size which can → mechanical effects including:
- dysphagia
- and airway obstruction
- A hyperfunctioning autonomic nodule may develop within multi-nodular goitre:
- → hyperthyroidism
Marker for follicular carcinoma
Thyroglobulin
Causes of follicular carcinoma
80% are sporadic
20% are familial- associated with MEN- specifically in younger individuals
Histology of medullary thyroid carcinoma
- sheets of dark cells
- apple green birefringence under polarised light
- due to calcitonin being broken down into amyloid
Which thyroid carcinoma is associated with amyloid?
Medullary
- tumour of parafollicular C cells which produce calcitonin
calcitonin is broken down into amyloid
aMyloid- medullary
Which cells are affected in medullary thyroid carcinoma?
Parafollicular c cells
What type of nodule is more likely to be cancerous?
- solitary
- solid
- younger patient
- M>F
- cold nodules more likely to be neoplastic compared to hot nodules
Most common cause of cushing’s syndrome
exogenous steroids
- atrophic adrenals
Causes of endogenous cushing’s syndrome
Cushing’s disease (ACTH secreting tumour) –> solitary adrenal neoplasm (adenoma/carcinoma)–> bilateral adrenal hyperplasia (least common)
*contrast with adldosterone where bilateral adrenal hyperplasia is a more common cause than solitary adenoma/conn’s*
Most common causes of primary hyperadlosteronism
60% bilateral adrenal hyperplasia
35% aldosterone secreting adenoma - Conn’s syndrome
Causes of acute adrenal deficiency
–Sudden withdrawal of corticosteroid therapy
–Haemorrhage (neonates)
–Sepsis with DIC (Waterhouse-Friderichson syndrome)
Causes of chronic adrenal insufficiency (Addison’s)
–Autoimmune (75-90%)
–TB
–HIV
–Metastatic tumour (lung and breast particularly)
–Rarely amyloid, fungal infections, haemochromatosis, sarcoidosis
Rule of 10s for phaeochromocytoma
–10% arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome
–10% are bilateral
–10% are malignant
–In addition 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas)
Two tumours of adrenal medull
- Phaeochromocytoma
- neuroblastoma
Inheritance pattern of MEN syndromes
autosomal dominant
Features of MEN1
3Ps
pituitary adenoma
parathyroid adenoma
pancreatic tumour - insulinoma
Features of Men2A
3Cs
Calcium (parathyroid adenoma)
Calcitonin (medullary thyroid carcinoma)
Catecholamines (phaeochromocytoma)
Features of Men2B
Medullary thyroid carcinoma
Phaeochromocytoma
Marfanoid body habitus
Mucosal neoplasms/ ganlgioneuromas
Which MEN syndromes cause hyperparathyroidism?
Men1 and Men2A
