Pathology of Endocrine Diseases Flashcards
what is 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
where are hormones synthesised and stored?
glands
how are endocrine glands described?
packets of cells with secretory granules
vascular
ductless
how is balance of the endocrine system maintained?
negative feedback
what makes up the classical endocrine system?
Pineal gland
Hypothalamus
Pituitary gland
Thyroid gland
Parathyroid gland
Adrenal glands
Pancreas
but several organs eg ovary, testes, kidneys, produce hormones also endocrine type cells scattered throughout body lung, GI tract, paraganglia (under neuropeptide control)
what can dysregulated hormone release lead to?
HYPERFUNCTION
HYPOFUNCTION
effect of a mass lesion
what disease processes affects endocrine organs?
HYPERPLASIA
increased number and secretory activity of cells
ATROPHY
diminution of cells due to lack of stimulation
TISSUE DAMAGE
inflammation, autoimmune disease, compression, trauma, infarction
NEOPLASIA
Adenoma – functioning or non functioning
Carcinoma – 1ry or metastatic
CONGENITAL ABNORMALITY
what is a benign neoplasm?
Often circumscribed, localised, cannot invade, don’t usually transform
what is malignant neoplasm?
Synonymous with cancer, invades, metastasises, if untreated, will often prove fatal
what does the thyroid gland synthesise store and release?
thyroxine (T4), triiodothyronine (T3)
Regulates basal metabolic rate
calcitonin
Regulates calcium homeostasis
what is the role of thyroxine (T4), triiodothyronine (T3)?
Regulates basal metabolic rate
what is the role of calcitonin?
Regulates calcium homeostasis
what physiological effects do thyroxine (T4), triiodothyronine (T3) have?
Increases BMR; Accelerates protein synthesis in children; Enhances sympathetic tone (sympathomimetic effect on heart, brown fat) carbohydrate and lipid metabolism
stimulates protein synthesis
what are manifestations of thyroid diseases?
Hyperthyroidism
Thyrotoxicosis*
Hypothyroidism
Myxoedema, Cretinism
Subclinical
Thyroid enlargement
Goitre
Isolated nodule/mass
what are primary and secondary causes of thyroid diseases?
Thyroiditis
Autoimmune
Others
Gland destruction
Multinodular goitre
Tumours
Benign
Malignant
what are causes of hyperthyroidism?
Diffuse toxic hyperplasia (Graves disease) – 70%
Toxic multinodular goitre – 20%
Toxic adenoma
what is graves disease?
F>M, peak 20-40 yrs, genetic predisposition
Autoimmune production of anti- TSH receptor antibodies
stimulate activity, growth, inhibit TSH binding
ophthalmopathy immune mediated – ocular fibroblasts have TSH receptor
what affect does graves disease have on the thyroid?
diffuse hyperplasia and hyperfunction
how does graves disease affect the thyroid gland?
enlarged gland (meaty)
what are causes of hypothyroidism?
Hashimoto’s thyroiditis
(auto-immune destruction)
Iatrogenic – surgery, drugs
Iodine deficiency
Congenital hypothyroidism
what is hashimotos thyroiditis?
F>M , 45-65yrs
Autoimune destruction of thyroid epithelial cells
Cytotoxic T cells, cytokine and antibody mediated destruction
Circulating autoantibodies to
thyroglobulin ,
thyroid peroxidase
what effect does hashimotos thyroiditis have on the thyroid?
Diffuse enlargement gradual failure
describe the manifestation of a multinodular goitre?
Iodine deficiency, goitrogens
↓
Impaired synthesis of T3,T4
↓
↑TSH
↓
Hypertrophy and hyperplasia of thyroid epithelium
Simple → → multinodular
what are causes of multinodular goitre?
Iodine deficiency commonest cause – also goitrogens like cabbage brussels sprouts and cassava which contains thiocyanate
Endemic/Sporadic Endemic >10% population
Physiological
Puberty
Pregnancy
Autoimmune
Graves’ disease
Hashimoto’s disease
Thyroiditis
Acute (de Quervain’s )
Chronic fibrotic (Reidel’s)
Iodine deficiency (endemic goitre)
Dyshormogenesis
Goitrogens
what can a thyroid nodule be?
Dominant nodule in multinodular goitre
Cyst
Follicular adenoma
Carcinoma (5% of nodules)
Differentiated thyroid carcinoma
Papillary carcinoma 75-85%
Follicular carcinoma 10-20%
Anaplastic carcinoma <5%
Medullary carcinoma 5%
(lymphoma)
how should a thyroid nodule be investigated?
TFTs
Ultrasound
FNA - cytology
how are thyroid carcinomas often found?
inicdentally
what are risk factores for thyroid carcinoma?
Family Hx
Chronic inflammatory conditions
Radiation exposure
Obesity
what is follicular adenoma?
Most non-functioning
Circumscribed, encapsulated tumour
Histology often small microfollicles
how would you describe follicular carcinoma?
Rare, usually solitary
Malignant cells breach capsule
Metastases – blood, bones
invasion through thyroid capsule
how would you describe a papillary carcinoma?
Usually <50yrs
BRAF mutation or RET/PTC gene rearrangement
Associated with exposure to ionizing radiation
Spreads via lymphatics… but
Excellent prognosis - 85% survival 10 yrs (esp <55yrs)
how would you describe a thyroid medullary carcinoma?
Malignant tumour of C – cells
produces calcitonin (+/- other polypeptides)
70% sporadic
30% MEN 2A, 2B, familial FMTC – mutations in RET proto-oncogene – prophylactic thyroidectomy
how are thyroid carcinomas treated?
Surgery
Radioactive iodine
External radiotherapy
Chemotherapy
what are parathyroid glands?
4 small glands – 120mg
Produce PTH – regulates plasma Ca2+
what is Primary hyperparathyroidism?
often asymptomatic hypercalcaemia
Sporadic or familial (MEN-1)
Adenoma (85-95%)
Hyperplasia (5-10%)
Carcinoma (rare)
what is Secondary hyperparathyroidism?
Physiological response to ↓ Ca2+ renal failure
describe the pitiutary gland?
Small gland, located in sella turcica
Connected to hypothalamus by pituitary stalk
Critical role in regulating other endocrine glands
what are the two distinct components of the pituiatary gland?
anterior pituitary
posterior pituitary
describe the function of anterior pituitary?
adenohypophysis 80%
secretes ACTH, TSH, GH, PROLACTIN, FSH/LH
blood supply from hypothalamus
controlled by release factors from hypothalamus
describe the function of the posterior pituitary?
neurohypophysis
downgrowth of hypothalamus
Secretes ADH, OXYTOCIN
what is the most common cause of pituitary hyperfunction?
pituitary adenoma
(pituitary carcinomas v rare and some hypothalamic disorders)
what is the aetiology of pituitary adenoma?
usually adults, 35 to 60 yrs
most sporadic; 5% inherited eg MEN1
how does a pituitary adenoma appear macroscopically?
soft, well-circumscribed lesion
small microadenomas may be incidental
eg at post mortem
what are the effects of pituitary adenoma?
If functioning - hormone excess
Prolactinoma - 20-30%
galactorrhoea, menstrual disorders
GH secreting
acromegaly, gigantism
ACTH secreting
Cushing’s disease
Non-functioning - 25-30% of detected tumours
immunohistochemical demonstration (mostly prolactin)
describe clinically some effects of a pituitary adenoma?
if the pituitary tumour is large what affect might this have?
Local mass effects: may be confined to the sella turcica but as adenoma expands, may lead to
radiographic abnormalities of the sella turcica, including sellar expansion, bony erosion of sella turcica and anterior clinoid processes, and disruption of the diaphragma sella
visual field abnormalities, classically in the form of defects in the lateral (temporal) visual fields, so-called bitemporal hemianopsia. – as tumour extend superiorly through the diaphragm sella into the suprasellar region, where they often compress the optic chiasm
elevated intracranial pressure, including headache, nausea, and vomiting
compression damage – hypopituitarism esp non functioning which present later
describe pituitary hypofunction?
75% needs to be lost
Compression by tumours – craniopharyngioma. metastatic
what can be caused by pituitary hypofunction?
Trauma
Infection (rare)
TB
Sarcoidosis
what syndrome is characterised by post partum ischaemic necrosis?
Sheehan’s syndrome
what is produced by the adrenal cortex?
Steroid hormones
what is produced by the adrenal medulla?
Neuroendocrine (chromaffin) cells
Adrenaline/ noradrenaline
response to stress maintain BP
Extra adrenal paraganglia similar
what is the adrenal cortex made up of?
what are different adrenal pathologies?
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 three syndromes are characterised by adrenal cortical hyperfunction?
Hypercortisolism– CUSHING’S SYNDROME
Hyperaldosteronism (Conn’s syndrome)
Adrenogenital syndormes
what are different causes of cushings syndrome (hypercortisolism)
Exogenous -Iatrogenic steroids
Endogenous
ACTH dependent
pituitary adenoma Cushings disease – 70%
ectopic ACTH
ACTH independent
functioning adrenal adenoma 10%
what is ACTH independent hypercortisolism?
what is ACTH dependent hypercortisolism?
what is hyperaldosteronism (conns syndrome)?
Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
(2ry hyperaldosteronism – physiological due to ↓renal perfusion ↑renin-angiotensin)
Increases sodium retention in the nephron
what is adrenogenital syndrome?
Functioning adrenal tumour
Pituitary tumour Cushings disease
Congenital adrenal hyperplasia – steroid enzyme deficiency
what is acute adrenal insufficiency caused by?
destruction of the glands through:
meningococcal septicaemia
Waterhouse Friderichsen
what is chronic adrenal insufficiency caused by?
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
[causing destruction of the glands]
what affect do functioning adrenocortical tumours have?
hyperadrenal syndromes, atrophy of adjacent cortex
how are non functioning adrenocortical tumours found?
often incidental – imaging/autopsy
what are the appearance of adrenocortical tumours?
Yellow-brown circumscribed
Most 2-3cm <30g
what are primary adrenocortical carcinomas?
rare, any age
More likely functional – virilising
Most large >20cm , haemorrhage and necrosis, cystic
Metastasises by lymphatics and blood – invades adrenal vein
what are metastatic carcinomas?
More common
lung, breast
what is a type of adrenal medullary tumour?
PHAEOCHROMOCYTOMA
describe PHAEOCHROMOCYTOMA?
Adrenal medulla neuroendocrine cells
secrete catecholamines → hypertension
Usually benign behaviour, can be bilateral
Up to 30% inherited – eg MEN 2, SDH
10% extra adrenal (paraganglioma)
what is multiple endocrine neoplasia?
Inherited disorders with underlying genetic mutation
Hyperplasia/ neoplasms of endocrine organs –
younger age, multifocal
Several distinct syndromes
what distinct syndromes does multiple endocrine neoplasia have?
MEN 1 (Wermer syndrome)
MEN 2
describe MEN 1 (wermers syndrome)
MEN 1 tumour suppressor gene mutation -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 is MEN 2?
RET proto-ongogene mutations
Medullary carcinoma of thyroid
Phaeochromocytoma
what is MEN 2A?
MEN 2A (Sipple syndrome)
+ Parathyroid hyperplasia
Extracellular domain auto dimerisation of RET receptor
what is MEN 2B?
+ Neuromas of skin &mucous membrane, skeletal abnormalities
+ Younger patients, aggressive
Autoactivation of tyrosine kinase pathway
