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)/ 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)
NB: Causes NOT associated with thyroid disease
o Struma ovarii (ovarian teratoma with ectopic thyroid)
o Factitious thyrotoxicosis (exogenous thyroid intake)
How can struma ovarii cause thyroid disease?
Ovarian teratomas can secrete ectopic thyroxine
What autoimmune condition can cause hypothyroidism?
Hashimoto’s
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
What are the main symptoms of Hashimoto’s?
Clinically hypothyroid
Painless goitre
Recall differentials for the cause of hypothyroidism
- Postablative
- Iodine deficiency
- Congenital biosynthetic defect
- Autoimmune (Hashimoto’s)
Secondary Causes
o Pituitary or hypothalamic failure (MOST COMMON)
What is a thyroid adenoma?
Benign neoplasm of follicular thyroid epithelium
How are thyroid adenomas diagnosed?
FNA and cytology
What is the most common type of thyroid carcinoma?
Papillary (75-85%)
Follicular (10-20%)
Medullary (5%)
Anaplastic (< 5%)
What are the key histological features of papillary thyroid cancer?
Optically clear nuclei Psammoma bodies (little folliculi of calcification)
Which type of thyroid carcinoma is associated with Multiple Endocrine Neoplasia?
Medullary
Neuroendocrine neoplasm derived from parafollicular C cells (which secrete calcitonin)
- 80% are sporadic in adults (present at 50-60 years)
- 20% are familial (associated with MEN) which are seen in younger patients*
Which type of thyroid carcnoma is most aggressive?
Anaplastic
- Occurs in elderly patients
- It is very aggressive
What are the 4 subtypes of thyroid carcinoma?
Follicular
Papillary
Medullary
Anaplastic
What is the most common cause of primary hyperparathyroidism?
Solitary adenoma (80-90%)
10-20% are due to hyperplasia of ALL four glands
o Sporadic
o Part of MEN1
- < 1% are due to a carcinoma
What is the most common symptom/finding in hyperparathyroidism?
Clinically silent hypercalcaemia (so not really a symptom)
stones
bones
abdominal moans - constipation, pancreatitis and gallstones
psychic groans - depression, lethargy, fits
What is secondary hyperparathyroidism almost always caused by?
Renal failure
(caused by any condition that causes chronically low calcium)
Recall 3 possible causes of hypoparathyroidism
Surgical ablation - most common
Congenital absence
Auto-immune
Recall 4 possible symptoms of hypoparathyroidism
Those of hypocalcaemia:
Muscle spasms/ tetany
Cardiac arrhythmias
Fits
Cataracts
Mnemonic: CATS go numb (convulsions, arrhythmia, tetany, spasms,
numbness)
Recall the synthetic function of each zone of the adrenals
- *Medulla**: Noradrenaline and adrenaline
- *Reticularis**: androgens + glucocorticoids
- *Fasciculata**: cotrtisol (glucocorticoids)
- *Glomerulosa**: aldosterone (mineralocorticoids)
What is Waterhouse-Friedrichson syndrome?
Adrenal insufficiency with sepsis and DIC
What are anterior and posterior pituitary made of?
The anterior pituitary is made up of epithelial cells (from developing oral cavity)
The posterior pituitary cells is made up of nerve cells (from supraoptic and paraventricular nucleus)
Hyopthalmic factor for each pituitary hormone?
TRH + TSH
PIF (dopamine) - PRL
CRH + ACTH
GHRH + GH
Somatostatin - GH
GnRH + FSH/LH
Clinical effects of prolactinoma
Amenorrhoea, galactorrhoea, loss of libido, infertility
Usually diagnosed quicker in females of reproductive age
Most common pituitary adenoma
Clinical effects of Growth hormone adenoma
Prepubertal children - gigantism
Adults - acromegaly
o Diabetes, muscle weakness, hypertension, congestive cardiac failure
Clinical Features of Anterior Pituitary Hypopituitarism
Children- growth failure (pituitary dwarfism)
- Gonadotrophin deficiency (usually the first manifestation seen in adults)
o Amenorrhoea and infertility in women
o Decreased libido and impotence in men
- TSH and ACTH deficiency (seen later in adulthood)
o Hypothyroidism
o Hypoadrenalism
- Prolactin deficiency- failure of postpartum lactation
What hormones does the posterior pituitary produce?
ADH and Oxytocin
Clinical Features of Posterior Pituitary syndromes
Diabetes insipidus - Produces large amounts of dilute urine
o Inappropriately high ADH (SIADH)
Can occur after head injury, brain tumours, serious illness
Typically presents with profound hyponatraemia (due to dilutional
effects)
What do parafollicular cells in the thyroid do?
synthesise calcitonin- this promotes absorption of calcium by the skeletal system
Cushings causes?
Endogenous causes:
- pituitary adenoma - most common
- hyperplasia of ACTH-secreting cells in the pituitary rather than a discrete adenoma
- ectopic ACTH by non-endocrine tumours (most commonly small cell lung cancer)
- In these cases, the adrenals will show bilateral hyperplasia as they are driven by ACTH
Clinical features of cushings?
Hypertension and weight gain
Truncal obesity
‘Moon’ facies
‘Buffalo hump’
Cutaneous striae
Hyperaldosteronism causes
35% are due to an adenoma (Conn’s syndrome) – this is primary hyperaldosteronism
- 60% bilateral adrenal hyperplasia
Hyperaldosteronism clinical features
Hypertension
Hypokalaemia
Congenital Adrenal Hyperplasia causes
Group of autosomal recessive disorders
Caused by hereditary defects in enzymes involved in cortisol biosynthesis
Reduced cortisol production results in increased ACTH, adrenal stimulation and increased androgen production
More commonly presents in childhood (less commonly in adults)
Causes of primary adrenal insufficiency?
ACUTE
Sudden withdrawal of corticosteroid therapy
Haemorrhage (into the adrenals) – seen in neonates
Sepsis with DIC (Waterhouse-Friderichson syndrome)
CHRONIC (Addison’s Disease)
Autoimmune (75-90%)
TB
HIV
Metastatic tumour (lung and breast particularly)
Rarely amyloid, fungal infections, haemochromatosis, sarcoidosis
Secondary to reduced ACTH
o Non-functioning pituitary adenomas (compressing the rest of the pituitary)
o Other lesions of pituitary or hypothalamus including infarction
Phaeochromocytoma rule of 10s?
10% arise in association with a familial syndrome, including:
MEN 2A and 2B
Von Hippel Lindau disease
Sturge-Weber syndrome
o 10% are bilateral
o 10% are malignant
o 10% of catecholamine-secreting tumours arise OUTSIDE of the adrenal
(paragangliomas)
Tend to occur along the sympathetic chain, along either side of the spine or neck
Multiple Endocrine Neoplasia (MEN) Syndromes causes
- These are a group of inherited diseases resulting in proliferative lesions
(hyperplasias, adenomas and carcinomas) of multiple endocrine organs - Tumours can occur at a younger age than sporadic tumours
- Arise in ≥ 1 endocrine organ OR may be multi-focal within one endocrine organ
- Tumours are often preceded by hyperplasia
- Tumours are often more aggressive than sporadic tumours and therefore are harder
to treat
Multiple Endocrine Neoplasia (MEN) types
MEN 1
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumours
MEN 2A
Medullary thyroid carcinoma
Parathyroid hyperplasia
Phaeochromocytoma
MEN 2B
Same as 2A
Marfanoid body habitus
Mucosal neoplasms
