Pathology of Endocrine System Flashcards
What is the definition of hyperplasia and atrophy?
Hyperplasia:
Increased number and secretory activity of cells
Atrophy:
Diminution of cells due to lack of stimulation
What are important general considerations to make about disease in an endocrine gland?
May have multiorgan effects
May lead to altered activity of another endocrine gland
Feedback effects may cause changes in endocrine gland
Endocrine glands have high reserve capacity
What hormones does the thyroid gland release?
Thyroxine (T4)
Triiodothyronine (T3)
Calcitonin
What is the role of epithelial cells in the thyroid gland?
Thyroglobulin synthesis
Iodination
Resorption
Release of T4 and T3
What is the histological findings of grave’s disease?
Increased cell activity
Increased cell numbers
What mediates the destruction of the thyroid in hashimotos thyroiditis?
Autoimune destruction of thyroid epithelial cells
- Cytotoxic T cells, cytokine and antibody mediated destruction
- Circulating autoantibodies to thyroglobulin, thyroid peroxidase
What are the histological findings of hashimotos hypothyroidism?
Hurthle cell change
Intense infiltrate of plasma cells
Lymphocytes
What causes a goitre to become multinodular?
Something results to cause impaired synthesis of T3/T4 - (iodine deficiency or goitrogens)
To compensate the thyroid produces more TSH, this results in hypertrophy and hyperplasia of epithelium
Single becomes multi-nodular
What are the features of multinodular goitre on histology?
Follicles are crowded and filled with colloid (distended)
Haemorrhage, fibrosis, cycstic change
Nodular appearance
What might a dominant nodule be?
Cyst
Follicular Adenoma
Carcinoma (papillary, follicular, anaplastic, medullary)
Lymphoma (may result from hashimoto’s)
What are the relevant investigations for thyroid nodule?
TFT’s
Ultrasound
FNA
What are the features of a thyroid follicular adenoma?
Most are non-functioning
Encapsulated tumour
Circumscribed
What are the features of follicular cell carcinoma?
Rare
Usually solitary
Malignant cells breach capsule
Mets - bone, blood (previous lecture also said lungs)
Give an example of the cause of follicular cell carcinoma
RAS mutation
PAX8/PPARG transolcation
What is the aetiology of papillary carcinoma?
BRAF mutation
RET/PTC gene rearrangement
Associated with exposure to ionizing radiation
How does papillary carcinoma spread?
Via lymphatics
What are the histological findings of papillary carcinoma?
Papillary projections
Empty nuclei
Psammoma bodies
May be cystic
What cells does a thyroid medullary carcinoma arise from?
C- cells
What does a medullary carcinoma produce?
Calcitonin and maybe other peptides
What is medullary carcinoma associated with?
MEN 2A, 2B
Familial FMTC
Mutations in RET proto-oncogene
What are the histological findings of medullary carcinoma?
Amyloid deposits
What are causes of primary hyperparathyroidism?
Sporadic or Familial (MEN - 1)
Adenoma (common)
Hyperplasia
Carcinoma (rare)
What are causes of secondary parathyroidism?
Physiological response to reduced calcium - renal failure?
What is the role of the hypothalamus and the pituitary?
Hypothalamus - homeostasis and emotional behaviour
Pituitary gland - regulated other endocrine glands
What are acidophils and what do they secrete?
Stain pink! Acidophils exist in the anterior pituitary
Secrete GH and PRL
What are basophils?
Found in the anterior pituitary
Secrete ACTH, LH, FSH, TSH
What is the third type of cell found in the anterior pituitary?
Chromophobes
What is the most common cause of pituitary hyperfunction?
Pituitary adenoma
Carcinomas are rare
What is the cause of pituitary adenoma?
5% are inherited (MEN1)
Usually sporadic
What are the effects of pituitary adenoma?
Adenomas of the pituitary are classified according to the hormone produced by the neoplastic cells
Prolactinoma (galactorrhoe and menstrual disorders)
GH secreting (acromegaly or gigantism)
ACTH secreting - cushing’s disease
Non-functioning - 25-30% of detected tumours
If large - pressure effect - (radiographic abnormalities, visual field abnormalities, elevated intracranial pressure, compression damage - hypopituitarism)
What causes pituitary hypofunction?
Compression by tumours
(craniopharyngioma - metastatic)
Trauma
Infection (rare) - TB sarcoidosis
Post - partum ischaemic necrosis (sheehan’s syndrome)
What do the following portions of the adrenal crotex secrete?
Zona glomerulosa: Mineralcorticoids aldosterone
Zona fasciculata: Glucocorticoids cortisol
Zona reticularis: sex steroids, oestrogen, androgens
What are the casues of conn’s?
Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
Secondary - Renovascular hypertension, diuretic use, renin-secreting tumour, malignant hypertension, coarctation of the aorta
What causes adrenogenital syndromes?
Functioning adrenal tumour
Pituitary tumour (cushings)
Congenital adrenal hyperplasia (steroid enzyme deficiency - 21-hydroxylase)
What causes acute adrenal insufficiency?
Meningococcal septicaemia
What are the causes of chronic adrenal insufficiency?
What is the result of a hyperadrenal syndrome (adenoma on cortex) on the adjacent cortex?
Causes atrophy
How does an adrenal adenoma compare to an adrenal carcinoma?
Adenoma - small (usually 2-3 cm), yellow-brown and circumscribed
Carcinoma - more likely to be functional, usually large (over 20cm) = haemorrhage, necrosis, cystic
Describe the metastasis of adrenal carcinoma
By lymphatics and blood
Invades adrenal vein
Metastatic carcinoma to lung and breast
What is multiple endocrine neoplasia?
Inherited disorder with underlying genetic mutation
Neoplasms or hyperplasia of endocrine organs
What causes MEN1?
Tumour suppressor gene mutation - defect in menin protein involved in regulating cell growth
What are the features of MEN1?
Parathyroid hyperplasia and adenomas
Pancreatic and duodenal endocrine tumours (hypoglycaemia and ulcers)
Pituitary adenoma (prolactinoma)
What causes MEN2?
RET proto-oncogene mutations
What are the features of MEN 2?
Medullary carcinoma of thyroid
Phaeochromocytoma
MEN 2A
- Parathyroid hyperplasia
MEN 2B
- Neuromas of skin and mucous membrane, skeletal abnormalities
- Younger patients, aggressive
