Pathology of The Endocrine System Flashcards
How is balance in the endocrine system maintained?
Feedback inhibition
What is included in the endocrine system?
Pineal gland, hypothalamus, hypothalamus, pituitary gland, thyroid gland, parathyroid gland, adrenal glands, pancreas
Also ovary, testes and kidneys
What are some disease processes in endocrine organs?
Hyperplasia
Atrophy
Tissue damage
Neoplasia
Congenital abnormality
What is the differences between benign and malignant neoplasia?
Benign - often circumscribed, localised, cant invade and don’t usually transform
Malignant - cancer, invades, metastasises, and can be fatal
What are some important aspects of endocrine diseases?
Endocrine organs have high reserve capacity
Feedback effects may cause endocrine changes
Can have multiorgan effects
Describe the anterior pituitary
Adenohypophysis
Secretes ACTH, TSH, GH, prolactin, FSH/LH
Blood supply from hypothalamus
Controlled by release factors from hypothalamus
Describe the posterior pituitary
Neurohypophysis
Downgrowth of hypothalamus
Secretes ADH and Oxytocin
What is the most common cause for pituitary hyperfunction?
Pituitary adenoma
Describe a pituitary adenoma
Usually adults - 35-60years
Most sporadic - 5% inherited
Macroscopic - soft, well circumscribed and mainly an incidental finding
What are the effects pituitary adenoma?
If functioning then hormone excess
Prolactinoma, GH secreting and ACTH secreting (Cushing’s)
Non functioning
What large pressure effects can an pituitary adenoma give?
Radiograhic abnormalities
Visual field abnormalities
Elevated intracranial pressure
Compression damage - hypopituitarism
What is pituitary hypofunction?
75% needs to be lost
Can be compression by tumours
Trauma, infection, TB or sarcoidosis
Sheehan’s syndrome - post partum ischaemic necrosis
Describe the histology of thyroid gland
Follicles
Colloids containing thyroglobulin
Epithelial cells - TG synthesis, iodination resorption and release of T3/4
C cells - secrete calcitonin
What are manifestation of thyroid disease?
Hyperthyroidism - thyrotoxicosis
Hypothyroidism - myxoedema, cretinism, subclinical
Enlargement - goitre and isolated mass/ nodule
What are the causes of hyperthyroidism?
Graves disease - diffuse toxic hyperplasia
Toxic multinodular goitre
Toxic adenoma
Describe Graves disease
Autoimmune production of anti-TSH receptor antibodies
Stimulate growth, activity and inhibit TSH binding
More females - peak 20-40yrs
Genetic predisposition
Hyperplasia and hyperfunction
What is the histology for Graves disease?
Increased cell activity and cell numbers
Scalloping of colloids
What are some causes of hypothyroidism?
Hashimoto’s thyroiditis
Iatrogenic - surgery and drugs
Iodine deficiency
Congenital hypothyroidism
Describe Hashimoto’s thyroiditis
Autoimmune destruction of thyroid epithelial cells
More females - 45-65 yrs
Cytotoxic T cells, cytokine and antibody mediated destruction
Circulating autoantibodies to thyroglobulin and thyroid peroxidase
What happens to the thyroid gland in Hashimoto’s thyroiditis?
Diffuse enlargement gradual failure
Describe the histology of Hashimoto’s thyroiditis
Hurthle cell change - ore pink and rounded (more cytoplasm)
Intense infiltration of lymphocytes and plasma cells
Describe the process of formation of multinodular goitre
Iodine deficiency and goitrogens - impaired synthesis of T3 and T4 - increased TSH - hypertrophy and hyperplasia of epithelium
Then simple to multinodular
Describe the histology of multinodular goitre
Crowded follicles
Distended colloid filled follicles
Haemorrhage, fibrosis and cystic change
Nodular appearance
What can a thyroid nodule be?
Dominant nodule in multinodular goitre
Cyst
Follicular adenoma
Carcinoma - differentiated - papillary, medullary, follicular and anaplastic
What are the investigations for thyroid nodules?
TFTs
US
FNA - cytology
What are the risk factors for thyroid carcinoma?
FH, chronic inflammatory disease, radiation exposure and obesity
Describe follicular adenoma
Mostly non-functioning
Circumscribes and encapsulated
Histology - small micro-follicles
Describe follicular carcinoma
Rare and usually solitary
Malignant cells breach capsule
Metastases - blood and bones
RAS mutation or PAX8/PPARG translocation
Describe papillary carcinoma
Usually over 50 yrs
BRAF mutation or RET/PTC gene rearrangement
Spreads via lymphatics but good prognosis
Associated with ionising radiation
What is the histology of papillary carcinoma?
Papillary projections, empty nuclei, psammoma bodies and may be cystic
Describe medullary carcinoma
Malignant tumour of c cells
Produces calcitonin
70% sporadic
Some MEN2a, b and familial FMTC - mutations in RET proto-oncogene
What is the histology of medullary carcinoma?
Tumour cells
Amyloids
What is the treatment for thyroid carcinoma?
Surgery, radio-active iodine, external radiotherapy and chemo
What is primary hyperparathyroidism?
Often asymptomatic hypercalcaemia
Sporadic or familial (MEN1)
Adenoma mainly, hyperplasia or carcinoma (rare)
What is secondary hyperparathyroidism?
Physiological response to decreased Ca renal failure
As feedback loop so increases PTH
What are multiple endocrine neoplasia (MEN)?
Inherited disorders with underlying genetic mutation
Hyperplasia/ neoplasms of endocrine organs - younger age and multifocal
Autosomal dominant
Describe MEN1
MEN1 tumour suppressor gene mutation - defect in menin protein involved in regulating cell growth
What is affected in MEN1?
Parathyroid hyperplasia and adenomas
Pancreatic (hypoglycaemia) and duodenal (ulcers) endocrine tumours
Pituitary adenoma
Describe MEN2
RET proto-oncogene mutation
Medullary carcinoma of thyroid
Pheochromocytoma
What is involved in MEN2A?
Sipple syndrome
Parathyroid hyperplasia
Extracellular domain auto-dimerization of RET receptor
What is involved in MEN2B?
Neuromas of skin and mucous membrane
Skeletal abnormalities
Younger patients and aggressive
Autoactivation of tyrosine kinase pathway
