Pathology of the Endocrine System Flashcards
What is hyperplasia?
An increased number and secretory activity of cells
What is atrophy?
Wasting of cells due to lack of stimulation
Causes of endocrine tissue damage?
Inflammation Autoimmune Disease Compression Trauma Infarction
What is a neoplasia?
The presence or formation of new, abnormal growth of tissue.
Types of neoplasia affecting endocrine glands?
Adenoma
Carcinoma
An adenoma can be…
Functioning or non-functioning
A carcinoma can be…
Primary or metastatic
What else can cause an endocrine disease?
A congenital abnormality?
How do we determine the cause of the pathology?
Morphological findings
Measinging hormone levels, hormone regulators and metabolites in blood
What are some general considerations when should remember in endocrine disease?
Disease in 1 gland may effect other glands, or have multi-organ effects
Feedback loops may be effected causing changes in glands
Endocrine organs have a high reserve capacity
What does the thyroid gland do?
Synthesizes, stores and releases triiodo-thyronine, thyroxine and calcitonin
Describe the histology of a thyroid gland?
Has circular follicles
Inside of circle called colloid and it contains thyroglobulin
C cells are not visable but secrete calcitonin
Describe the hypothalamus-pituitary-thyroid axis.
TRH from H to P
TSH from P to Thyroid
T3 and T4 released
Describe the feedback loops of the thyroid.
T3 and T4 have a short (acting on pit gland inhibiting TSH) and a long (inhibiting TRH at hypothalamus)
Causes of 1y thyroid disease?
Thyroiditis
Gland destruction
Multinodular goitre
Tumours
Causes of hyperthyroidism from most to least common?
Diffuse toxic hyperplasia - 70%
Toxic multinodular goitre - 20%
Toxic adenoma
Pathology behind graves?
Autoimmune production of anti-TSH receptor antibodies
These stimulate activity, growth and inhibit TSH binding
What is Graves opthalmopathy? Why does it happen?
Inflammation and other immune system events affect muscles and other tissues around your eyes
This is because ocular fibroblasts have TSH receptors
Why happens to the thyroid in graves?
Undergoes diffuse hyperplasia and hyperfunction
Causes of hypothyroidism?
Hashimoto’s
Iatrogenic - surgery or drugs
Iodine deficiency
Congenital hypothyroidism
What type of patients does hashimoto’s affect more?
45-65 yrs
Females over males
What type of patients does graves affect more?
20-40s
Female over male
Has a genetic predisposition
What is hashimotos?
Autoimmune destruction of thyroid epithelial cells by cytotoxic T cells, cytokines and antibody mediated destruction
What happens to the thyroid gland in hashimotos?
Diffuse enlargement with gradual failure
Causes of multinodular goitre?
Iodine deficiency
Goitrogens
Pathology of how a multinodular goitre affects the thyroid?
Impairs synthesis of T3 and T4
Leads to increases of TSH which causes hypertrophy and hyperplasia of the epithelium
What is the “thyroid nodule”
Can be: The dominant nodule in a multi-nodular goitre A cyst A follicular adenoma A cacrinoma
Most common type of thyroid carcinoma? And types of this ?
Differentiated thyroid carcinoma - Papillary and follicular carcinomas
How to investigate a thyroid nodule?
TFTs
Ultrasounds
FNAs
Features of a follicular adenoma?
Is the most non-functioning neoplasm
Is a circumscribed, encapsulated tumour
Histology often shows small microfollicles
Features of the DTC - papillary carcinoma?
Usually <50yrs
Causes by a BRAF mutation or RET/PTC gene rearrangement
Associated with exposure to ionizing radiation - spread via lymphatics but has excellent prognosis
There is papillary projections with empty nuclei and psammonma bodies
May be cyctic
Features of the DTC - Follicular carcinoma ?
Rare and usually solitary
Malignant cells breach the follicular capsules
Mets to blood and bones
What mutation causes a follicular carcinoma?
RAS mutation
PAX8/PPARG translocation
What is a thyroid medullary carcinoma? Effects?
A malignant tumour of the C-cells
Makes calctionin +/- other polypeptides
How do thyroid medullary carcinomas arise?
70% are sporadic
30% - Genetic - can be treated with a prophylactic thyroidectomy
What do parathyroid glands make?
PTH which regulates plasma calcium
How does 1y hyperparathyroidism present?
Assymptomatic hypercalcaemia
Causes of hyperparathyroidism?
Sporadic or familial Adenomas (85-95%), Hyperplasia’s or carcinomas (rare)
What is 2y hyperparathyroidism in response to?
Reduced calcium due to renal failure
What does the anterior pit gland secrete?
ACTH TSH GH FSH/LH Prolactin
What does the posterior pit gland release?
Vasopressin/ADH
Oxytocin
Describe the histology of the pituitary gland?
3 major cells - acidophils, basophiles and chromophobes
Acidophils are pink and secrete GH and Prolactin
Basophils are dark purple and secerete ACTH, TSH, FSH and LH
Chormophobes are pale/white
Most common cause of pituitary hyperfunction? Rarer causes?
A pituitary ademona
A carcinoma is very rare, some can be caused by hypothalmic disorders
What age does a pituitary adenoma affect the most?
35-60 y/o
Causes of the adenoma?
Most are sporadic with 5% being inherited
Describe the lesion (in a pituitary adenoma)
Soft and well circumscribed macroscopic lesions
Effects of the pituitary adenoma?
If functioning causes hormone excess
If large has a mass pressure effect
What does excess Prolactin cause?
Galactorrhoea and menstrual disorders
What does xs GH cause?
Acromegaly/Gigantism
What does xs ACTH cause?
Cushings
How are non-functioning adenomas caught?
Via immunohistochemical demonstration (?)
Mass pressure effects of a adenoma in the pit gland is….
Radiographic abnormalities
Visual problems - bitemporal hemianopia
Elevated intracranial pressure
Compression damage leading to hypopituitarism
How much function of the pituitary must be lost to cause pituitary hypofunction?
75%
Causes of pituitary hypofunction?
Compression by tumours
Trauma
Infection by TB or sarcoid, which is rare
What does the cortex in the adrenal glands secrete?
Steroid hormones - cortisol, aldosterone and sex steroids
What does the medulla in the adrenal glands secrete?
Adrenaline/NA
What is the effect of adrenal pathology (hypo/hyper function and mass lesions) of the adrenal gland?
Hyperplasia - diffuse or nodular
Atrophy
Mass lesion’s
3 syndromes of adrenal hyperfunction?
Hypercortisolism - cushings
Hyperaldosteronism - conns
Adrenogenital syndromes
What is the difference between cushing’s syndrome and disease?
Syndrome is ACTH independent and only affects the adrenal gland (1y)
Disease involves ACTH and is when there is a pituitary adenoma or ectopic ACTH lesions making excess ACTH
Cause of exogenous cushings?
Iatrogenic steroids
What causes an ACTH independent cushings?
A functioning adrenal adenoma
Causes of 1y Conn’s syndrome?
Bilateral idiopathic hyperplasia
Functioning adrenal
Causes of 2y conns?
Reduced renal perfusion causing increased RAAS
What causes an adrenogenital syndrome?
Functioning adrenal tumour
Pit gland tumour - cushings disease
Congenital adrenal hyperplasia - steroid enzyme deficiency
Acute causes of adrenal gland destruction = insufficiency.
Meningococcal septicaemia
Chronic causes of 1y and 2y adrenal insufficiency.
1y - Addison’s disease
Autoimmune
Infection
Atrophy
Congenital hypoplasia
Replacements - metastatic carcinoma amyloidosis
2- Pit gland failure
What type of tumours affect the adrenal gland?
Adenoma
Carcinoma
Medullary
What does adenomas cause on adrenal gland?
Functioning = hyperadrenal syndromes and atrophy of cortex
Non- functioning = often found incidentally suggesting no effect?
Appearance of an adrenal adenoma?
Yellow-brown circumscribed
What does adenomas cause on adrenal gland?
Most likely functioning - causing “virilising” the abnormal development of male sexual characteristics in a female
Appearance of adrenal carcinomas?
Large - over 20cm, haemorrhage and necrosing and cystic
How does adrenal carcinoma metastasis and to where?
Via lymphatics and blood - invades the adrenal vein
Lung and breast
What does an adrenal medullary tumour cause?
Phaeochroocytoma - xc secretions of catecholamines (adrenaline etc) leading to hypertension
What is multiple endocrine neoplasia?
Inherited disorders due to mutations causing hyperplasia/ neoplasms
Aftects younger patients
Distinct syndromes of multiple endocrine neoplasia?
MEN 1 - Wermer’s
MEN 2 - Split into 2A and 2B
What causes MEN1 and waht is its effects
MEN 1 tumour suppressor gene mutated
Leads to parathyroid hyperplasia and adenomas
Pit. gland adenoma
Pancreatic and duodenal endocrine tumours
What does MEN 2 cause?
Medullary carcinoma of thyroid
Phaeochromocytoma
