Pathology of the Endocrine System 1 Flashcards
what is the function of the endocrine system?
Integrated network of GLANDS - secrete chemical messengers – hormones - directly into bloodstream
HORMONES act on target cells distant from site of synthesis - bind to receptors – change cell activity
REGULATION of metabolism, growth and development, tissue function
maintain functional balance
what are the kind of hormones synthesised and stored in glands?
packets of cells with secretory granules
vascular
ductless
what are the contents of the classical endocrine system?
pineal gland hypothalamus pituitary gland thyroid gland parathyroid gland adrenal gland pancreas
what is hyperplasia?
increased number and secretory activity of cells
what is atrophy
diminution of cells due to lack of stimulation
what is tissue damage?
inflammation, autoimmune disease, compression, trauma, infarction
what are the two types of neoplasia?
adenoma
carcinoma
whats the difference between adenoma and carcinoma
adenoma- functioning or non functioning
carcinoma- 1ry or metastatoc
how would you determine the cause of congenital abnormality?
morphologic findings
biochemical measurements of hormone levels, regulators and metabolites.
what is the function of synthesis, storage, release of thyroxine T4 and triiodothyronine T3?
regulated basal metabolic rate
whats the function of calcitonin?
regulates calcium homeostasis
what is the histology of thyroid gland?
Follicles
Colloid-contains thyroglobulin
Epithelial cells – TG synthesis, iodination, resorption & release of T4 and T3
C-cells – secrete calcitonin (not visible)
what is the manifestation of thyroid diseases?
Hyperthyroidism
Thyrotoxicosis*
Hypothyroidism
Myxoedema, Cretinism
Subclinical
Thyroid enlargement
Goitre
Isolated nodule/mass
what are the causes of thyroid diseases?
Thyroiditis
Autoimmune
Others
Gland destruction
Multinodular goitre
Tumours
Benign
Malignant
what are the causes of hyperthyroidism?
Diffuse toxic hyperplasia (Graves disease) – 70%
Toxic multinodular goitre – 20%
Toxic adenoma
whos more likely to get graves disease?
females
peak- 20-40 years
genetic predisposition
what happens to the histology in graves disease?
cell activity increases and cell numbers increase
what are the causes of hypothyroidism?
Hashimoto’s thyroiditis
(auto-immune destruction)
Iatrogenic – surgery drugs
Iodine deficiency
Congenital hypothyroidism
whos more likely to get hashimotos thyroiditis?
females
45-65 yrs
what is graves disease?
Autoimmune production of anti- TSH receptor antibodies
stimulate activity, growth, inhibit TSH binding
ophthalmopathy immune mediated – ocular fibroblasts have TSH receptor
what is hashimotos thyroiditis?
Autoimune destruction of thyroid epithelial cells
Cytotoxic T cells, cytokine and antibody mediated destruction
Circulating autoantibodies to
thyroglobulin ,
thyroid peroxidase
what happens to the thyroid in hashimotos thyroiditis?
Diffuse enlargement gradual failure
what is the histology of hashimotos thyroiditis?
hurthle cell change
intense infiltrate of plasma cells
lymphocytes
crowded follicles
distended colloid filled follicles
haemorrhage, fibrosis, cycstic change
what is goitre?
enlarged thyroid
what is the pathway to multinodular goitre?
iodine deficiency, goitrogens –> impaired synthesis of T3 and T4 –> increase of TSH –> hypertrophy and hyperplasia of epithelium
goes from simple to multi nodular
what is a thyroid nodule?
dominant nodule in multinodular goitre
cysts
follicular adenoma
carcinoma
how would you investigate a thyroid nodule?
TFTs, ultrasound, FNA
name some thyroid tumours
Follicular adenoma
Carcinoma (5% of nodules)
Differentiated thyroid carcinoma (DTC)
Papillary carcinoma 75-85%
Follicular carcinoma 10-20%
Anaplastic carcinoma 5%
Medullary carcinoma 5%
(lymphoma)
what is the most non functioning thyroid neoplasm?
follicular adenoma
give some characteristics about follicular adenomas?
Most non-functioning
Circumscribed, encapsulated tumour
Histology often small microfollicles
how common are follicular carcinomas?
rare, usually solitary
where are follicular carcinomas most likely to metastasise?
blood, bones
what is the type of mutation in papillary carcinomas?
BRAF mutation or RET/PTC gene rearrangement
what is papillary carcinoma associated with?
exposure to ionizing radiation
where is papillary carcinoma most likely to spread?
lymphatics
what is the histology of papillary carcinoma?
Papillary projections
Empty nuclei
Psammoma bodies
May be cystic
what are some characteristics of thyroid medullary carcinomas?
Malignant tumour of C – cells
produces calcitonin (+/- other polypeptides)
70% sporadic
what are the type of genes in thyroid medullary carcinomas?
30% MEN 2A, 2B, familial FMTC – mutations in RET proto-oncogene – prophylactic thyroidectomy
how many glands are in the parathyroid gland?
4 small glands - 120mg
what do parathyroid glands produce?
PTH- regulates plasma Ca
what are the causes for parathyroid hyper function?
1ry hyperparathyroidism
often assymptomatic
hypercalcaemia
Sporadic or familial (MEN-1)
Adenoma (85-95%
Hyperplasia (5-10%)
Carcinoma (rare)
2ry hyperparathyroidism
Physiological response to ↓ Ca2+ renal failure
what are the functions of the hypothalamus?
maintains homeostasis
governs emotional behaviour
links nervous system to endocrine system via the pituitary gland
what is the function of pituitary gland?
small gland, located in sella turcica
connected to hypothalamus by pituitary stalk
critical role in regulating other endocrine glands
what is the adenohypophysis
the anterior part of the pituitary gland that is derived from the embryonic pharynx and is primarily glandular in nature
where is the blood that supplies the anterior pituitary from?
hypothalamus
what does the anterior pituitary secrete?
ACTH, TSH, GH, PROLACTIN, FSH/LH
how is the anterior pituitary controlled?
release factors from hypothalamus
what is neurohypophysis?
that posterior part of the pituitary gland
what does the posterior pituitary secrete?
ADH, OXYTOCIN
what are the 3 major cell types of pituitary glands?
pink ACIDOPHILS secrete GH and PRL
dark purple BASOPHILS secrete ACTH, TSH, FSH, LH
pale CHROMOPHOBES
what is the most common cause of pituitary hyper function?
pituitary adenoma
what is the histology of pituitary adenoma?
cells of same appearance as normal gland
classified by hormone(s) produced by the neoplastic cells - detected by immunohistochemical stains
whos most likely to get pituitary adenomas?
usually adults, 35 to 60 yrs
most sporadic;
what are the effects of pituitary adenomas?
if functioning- hormone excess
what effect does prolactiinoma have on pituitary adenomas?
galactorrhoea, menstrual disorders
what effect does GH secreting have on pituitary adenoma?
acromegaly, gigantism
what effect does ACTH secreting have on pituitary adeomas?
Cushing’s disease
what effect does non-functioningn pituitary have on pituitary adenomas
immunohistochemical demonstration (mostly prolactin)
what is the result of a large pituitary adenoma?
radiographic abnormalities
visual field abnormalities
elevated intracranial pressure
compression damage – hypopituitarism
what are the causes of pituitary hypofunction?
Compression by tumours – craniopharyngioma. metastatic
Trauma
Infection (rare)
TB
Sarcoidosis
Post partum ischaemic necrosis Sheehan’s syndrome
what is the pathology of adrenal?
Hyperfunction
clinical syndromes depend on which adrenal hormones stimulated
Hypofunction
Mass lesion - effect late
Effect on adrenal gland –hyperplasia (diffuse or nodular), atrophy, mass lesion
what are the three syndromes of adrenal cortical hyper function?
Hypercortisolism– CUSHING’S SYNDROME
Hyperaldosteronism (Conn’s syndrome)
Adrenoginital syndormes
what are characteristics of hypercorticolism?
Exogenous -Iatrogenic steroids
Endogenous
ACTH dependent
pituitary adenoma Cushings disease – 70%
ectopic ACTH
ACTH independent
functioning adrenal adenoma 10%
what are some characteristics of hyperaldosteronism?
Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
(2ry hyperaldosteronism – physiological due to ↓renal perfusion ↑renin-angiotensin)
what are characteristics of adrenogenital syndromes?
Functioning adrenal tumour
Pituitary tumour Cushings disease
Congenital adrenal hyperplasia – steroid enzyme deficiency
what are the acute causes of adrenal insufficiency destruction of glands?
meningococcal septicaemia
waterhouse friderichsen
what are the chronic causes of adrenal insufficiency destruction of glands?
1ry - Addison’s disease
Autoimmune : autoimmune polyendocrine syndromes – spare medulla
Infections: TB, fungus HIV-related infections
Replacement: metastatic carcinoma amyloidosis,
Atrophy: prolonged steroid therapy
Congenital hypoplasia
2ry - Pituitary failure
what are the characteristics of adrenocortical tumours?
Functioning – hyperadrenal syndromes, atrophy of adjacent cortex
Non functioning – often incidental – imaging/autopsy
Yellow-brown circumscribed
Most 2-3cm <30g
what are the characteristics of primary adrenocortical carcinoma?
rare, any age
More likely functional – virilising
Most large >20cm , haemorrhage and necrosis, cystic
Metastasises by lymphatics and blood – invades adrenal vein
what are the characteristics of adrenal medullary tumour (phaeochromocytoma)
Adrenal medulla neuroendocrine cells secrete catecholamines → hypertension Usually benign behaviour, can be bilateral Up to 25% inherited – eg MEN 2 10% extra adrenal
what is the histology of adrenal medullary tumour?
Nests “Zellballen” of polygonal cells in vascular network
Granular cytoplasm containing catecholamines
what syndrome does MEN 1 cause?
wermer syndrome
what does the MEN 1 tumour supressor gene mutation cause?
defect in menin protein involved in regulating cell growth
Parathyroid hyperplasia and adenomas
Pancreatic and duodenal endocrine tumours (hypoglycaemia and ulcers)
Pituitary adenoma (prolactinoma)
what does MEN 2 cause?
Medullary carcinoma of thyroid
Phaeochromocytoma
what does MEN2A cause?
sipple syndrome
parathyroid hyperplasia
what does MEN 2B cause?
Neuromas of skin &mucous membrane, skeletal abnormalities
+ Younger patients, aggressive
