Pathology of the Endocrine System 1 & 2 Flashcards
the endocrine system:
uIntegrated network of ______ - secrete chemical messengers – hormones - directly into bloodstream
___________ act on target cells distant from site of synthesis - bind to receptors – change cell activity
___________ of metabolism, growth and development, tissue function
maintain functional balance __________
glands
hormones - by binding to receptors which change cell activity, differentiation, mitosis. It is instrumental in regulating metabolism, growth, development and puberty and tissue/organ function
regulation
homeostasis
Hormones synthesised and stored in glands, what are the features of a gland?
packets of cells with secretory granules
vascular
ductless
balance of hormones is maintained by
feedback inhibition
what makes up the endocrine system?
Pineal gland - produces melatonin - regulates circadian rhythm
Hypothalamus
Pituitary gland
Thyroid gland
Parathyroid gland
Adrenal glands
Pancreas
other organs (ovary, testes, kidney)
diffuse endocrine cells (lung, GIT)
Often two - in - one (endocrine organ often does more than one thing)
example of major system pathways:
TRH – TSH – T3/T4
GnRH – LH/FSH – sex hormones
CRH – ACTH – cortisol
Renin – angiotensin – aldosterone
what is endocrine disease?
Disease processes lead to changes in function and/or structure
Dysregulated hormone release -HYPERFUNCTION and HYPOFUNCTION
Effect of a MASS lesion (tumour – may secrete a hormone or have an effect of being a mass and compressing things nearby)
Disease Processes in Endocrine Organs:
what is hyperplasia?
increased number and secretory activity of cells
Disease Processes in Endocrine Organs:
what is atrophy?
shrinking of an organ
diminution of cells due to lack of stimulation
Disease Processes in Endocrine Organs:
what can cause tissue damage?
inflammation, autoimmune disease, compression, trauma, infarction
Disease Processes in Endocrine Organs:
what are examples of neoplasia (unregulated growth)
Adenoma – functioning or non functioning
Carcinoma – 1ry or metastatic
Disease Processes in Endocrine Organs:
what is it called when something is wrong form birth
congenital abnormality
what are the properies of benign neoplasia in endocrine organs?
Often circumscribed, localised, cannot invade, don’t usually transform
what are the properies of malignant neoplasia in endocrine organs?
Synonymous with cancer, invades, metastasises, if untreated, will often prove fatal
Disease in one endocrine gland may have __________ clinical effects
__________ effects may cause endocrine gland changes
Endocrine organs have high _______ capacity
multiorgan
feedback
reserve
what does thyroid gland secrete and what are its functions?
Synthesis, storage, release of thyroxine (T4), triiodothyronine (T3) - Regulates basal metabolic rate
calcitonin - Regulates calcium homeostasis
describe the histology of the thyroid gland
Thyroid epithelial cells are arranged in follicles filled with colloid –thyroglobulin.
Synthesis in colloid of thyroglobulin
Roles of iodine and tyrosine in T3/T4 synthesis
Involved in synthesise thyroglobulin – this requires iodine tyrosine
Cells reabsorb thyroglobulin and convert it to T3 and T4
Follicles
Colloid-contains thyroglobulin
Epithelial cells – TG synthesis, iodination, resorption & release of T4 and T3
C-cells – secrete calcitonin (not visible)
decsribe the hypothalamus - pituitary- thyroid axis
what is a manifestation of hyperthyroidism and what causes hyperthyroidism?
Thyrotoxicosis
Thyroiditis, Autoimmune, Others
what are manifestations of hypothyroidism and what are the causes hypothyroidism?
Myxoedema, Cretinism (a condition characterized by physical deformity and learning difficulties that is caused by congenital thyroid deficiency), Subclinical
Gland destruction
what are the manifestations of thyroid enlargement and what causes thyroid enlargement?
Goitre, Isolated nodule/mass
Multinodular goitre
Tumours - Benign or Malignant
what are the causes of hyperthyroidism?
Diffuse toxic hyperplasia (Graves disease) – 70%
Toxic multinodular goitre – 20%
Toxic adenoma
who is graves disease common in?
F>M
peak 20-40 yrs
genetic predisposition
what happens in graves disease?
Autoimmune production of anti- TSH receptor antibodies:
stimulate activity, growth, inhibit TSH binding
ophthalmopathy immune mediated - ocular fibroblasts have TSH receptor
Thyroid - diffuse hyperplasia and hyperfunction
what does the histology of a thyroid gland look like in graves disease?
increased cell activity
increased cell numbers
what are causes of hypothyroidism?
Hashimoto’s thyroiditis (auto-immune destruction)
Iatrogenic – surgery, drugs
Iodine deficiency
Congenital hypothyroidism
who is at risk of hashimotos thyroiditis
F>M , 45-65yrs
how does hashimotos thyroiditis occur?
Autoimune destruction of thyroid epithelial cells
Cytotoxic T cells, cytokine and antibody mediated destruction
Circulating autoantibodies to thyroglobulin, thyroid peroxidase
Thyroid - Diffuse enlargement gradual failure
what is the histology of hashimotos thyroiditis?
goite is
an enlarged thyroid
what are the causes of multinodular goitre?
Physiological - Puberty, Pregnancy
Autoimmune - Graves’ disease, Hashimoto’s disease
Thyroiditis - Acute (de Quervain’s ), Chronic fibrotic (Reidel’s)
Iodine deficiency (endemic goitre)
Dyshormogenesis
Goitrogens
describe the process of multinodular goitre
Iodine deficiency, goitrogens
↓
Impaired synthesis of T3,T4
↓
↑TSH
↓
Hypertrophy and hyperplasia of thyroid epithelium
Simple → → multinodular
describe the histology of multinodular goite
Distended colloid filled follicles
Haemorrhage, fibrosis, cystic change
Nodular appearance
what is the cause of a dominant nodule in multinodular goitre?
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 do you investigate a thyroid nodule?
TFTs
Ultrasound
FNA - cytology
how is thyroid carcinoma normally detected?
Often incidentally detected
what are the risk factors of a thyroid carcinoma?
Family Hx
Chronic inflammatory conditions
Radiation exposure
Obesity
what is a Follicular adenoma?
a benign encapsulated tumor of the thyroid gland
Most non-functioning
Circumscribed, encapsulated tumour
Histology often small microfollicles
desribe the featurrs of a follicular carcinoma
Rare, usually solitary
Malignant cells breach capsule
uMetastases – blood, bones
what are the features of a papilllary carcinoma?
Papillary carcinoma (PTC) is the most common form of well-differentiated thyroid cancer, and the most common form of thyroid cancer to result from exposure to radiation. Papillary carcinoma appears as an irregular solid or cystic mass or nodule in a normal thyroid parenchyma
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)
describe the histology of a papillary carcinoma
Papillary projections
Empty nuclei
Psammoma bodies
May be cystic
what are the featrues of 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
what is the treatment of thyroid carcinoma?
Surgery (no surgical option in anaplastic)
Radioactive iodine - gets rid of any bits that are left
External radiotherapy
Chemotherapy
what are the parathyroid glands and their function?
4 small glands -120mg
Produce PTH - regulates plasma Ca2+
thyroid Calcitonin opposes PTH (Calcitonin promotes bony absorption of calcium and prevents bone resorption)
if someone has got a parathyroid adenoma they will often present __________
hypercalcaemic
Primary hyperparathyroidism often asymptomatic _____________
hypercalcaemia
what are the causes of primary hyperparathyroidism?
Sporadic or familial (MEN-1)
- Adenoma (85-95%)
- Hyperplasia (5-10%)
- Carcinoma (rare)
What is secondary hyperparathyroidism due to?
Physiological response to ↓Ca2+ renal failure
where and what is the role of the hypothalamus and the pituitary gland?
Small gland, located in sella turcica
Connected to hypothalamus by pituitary stalk
Critical role in regulating other endocrine glands
what does the the anterior pituitary secrete, what is its blood supply and what is it controlled by?
(adenohypophysis 80%)
secretes - ACTH, TSH, GH, PROLACTIN, FSH/LH
blood supply from hypothalamus
controlled by release factors from hypothalamus
where is the posterior pituitary and what does it secrete?
(neurohypophysis)
downgrowth of hypothalamus
Secretes ADH, OXYTOCIN
what is the most common cause of pituitary hyperfunction?
pituitary adenoma (not all secrete so may just cause a mass effect)
(pituitary carcinomas v rare and some hypothalamic disorders)
what people are pituitary adenomas common in?
uusually adults, 35 to 60 yrs
most sporadic; 5% inherited eg MEN1
pituitary adenomas are macroscopic, what do they look like?
soft, well-circumscribed lesion
small microadenomas may be incidental eg at post mortem
what are the effects of a 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)
what is the difference between cushings syndrome and cushings disease?
Cushing’s syndrome refers to the condition caused by excess cortisol in the body, regardless of the cause
When Cushing’s syndrome is caused by a pituitary tumor, it is called Cushing’s disease
what happens if a pituitary adenoma is large, what are some mass pressure effects?
radiographic abnormalities
visual field abnormalities
elevated intracranial pressure
compression damage – hypopituitarism
how much function needs to be lost for someone to have pituitary hypofunction?
75%
what are the causes of pituitary hypofunction?
Compression by tumours (most common) – craniopharyngioma metastatic
Trauma
Infection (rare)
TB
Sarcoidosis
Post partum ischaemic necrosis - Sheehan’s syndrome - pituitary gland is damaged during childbirth. It’s caused by excess blood loss (hemorrhage) or extremely low blood pressure during or after labor. A lack of blood deprives the pituitary of the oxygen it needs to work properly
what is the weight of the adrenal glands
12g combined
what does the cortex and medulla of the adrenal gland do?
cortex - Steroid hormones
medulla:
Neuroendocrine (chromaffin) cells
Adrenaline/noradrenaline response to stress maintain BP
Extra adrenal paraganglia similar
what does each layer of the cortex of the adrenal gland secrete?
zona glomerulosa - mineralocorticoids - aldosterone
zona fasciculata glucocorticoids - cortisol
zona reticularis - sex steroids, oestrogen, androgens
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 are 3 syndromes caused by adrenal cortical hyperfunction?
Hypercortisolism (cushings syndrome)
Hyperaldosteronism (Conn’s syndrome)
Adrenogenital syndormes
what are the cuases of cushings syndrome?
Exogenous -Iatrogenic steroids
Endogenous:
ACTH dependent - pituitary adenoma Cushings disease – 70%, ectopic ACTH
ACTH independent - functioning adrenal adenoma 10%
how do you diagnose cushings syndrome?
measuring cortisol, ACTH and response to ACTH suppression
what are the causes of conns syndrome?
Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
(2ry hyperaldosteronism – physiological due to ↓renal perfusion ↑renin-angiotensin)
conns syndrome causes increased _____ retention in the nephron
sodium
To much aldosterone = hypertension
what are the causes of adrenogenital syndromes?
Functioning adrenal tumour
Pituitary tumour Cushings disease
Congenital adrenal hyperplasia – steroid enzyme deficiency
what are the symptoms of adrenogenital syndromes?
Symptoms are variable
Ambiguous genetalia, precocious puberty, failure of puberty, virilisation, infertility, undervirilisation
Adrenal Insufficiency - destruction of glands, can either by _____ or ______
acute
chronic
what is chronic adrenal insufficiency?
1 year - addisons
2 year - pituitary failure
what are the causes of addisons disease?
- Autoimmune: autoimmune polyendocrine syndromes – spare medulla
- Infections: TB, fungus HIV-related infections
- Replacement: metastatic carcinoma amyloidosis
- Atrophy: prolonged steroid therapy
- Congenital hypoplasia
what are the effects of adrencortical tumours?
Functioning – hyperadrenal syndromes, atrophy of adjacent cortex
Non functioning – often incidental - imaging/autopsy
Yellow-brown circumscribed
Most 2-3cm <30g
describe the histology of adrenocortical tumours
Cells similar to those of normal cortex
nuclei small
Some pleomorphism (“endocrine atypia”).
Cytoplasm eosinophilic to vacuolated, depends on lipid
Mitoses inconspicuous
What are the features 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
are metastatic adrenal carcinoma more common? and where do they come from?
More common
lung, breast
name an adrenal medullary tumour?
PHAEOCHROMOCYTOMA
Adrenal medulla neuroendocrine cells
what does a phaeochromocytoma secrete?
secrete catecholamines → hypertension
Is a phaeochromocytoma benign or malignant? and is it inherited?
Usually benign behaviour, can be bilateral
Up to 30% inherited – eg MEN 2, SDH
10% extra adrenal (paraganglioma)
describe the histology of a phaeochromocytoma?
Nests “Zellballen” of polygonal cells in vascular network
Granular cytoplasm containing catecholamines
What is multiple endocrine neoplasia?
Inherited disorders with underlying genetic mutation
Hyperplasia/neoplasms of endocrine organs -
younger age, multifocal
Several distinct syndromes
what is MEN 1 (Wermer 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 (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
Disease in one endocrine gland may have _________ clinical effects
Disease in one endocrine gland may lead to altered activity of another __________ _____
________ effects may cause changes in endocrine glands
Endocrine organs have high _______ capacity
nb - ectopic hormone production by other organs
Disease in one endocrine gland may have multiorgan clinical effects
Disease in one endocrine gland may lead to altered activity of another endocrine gland
Feedback effects may cause changes in endocrine glands
Endocrine organs have high reserve capacity
nb - ectopic hormone production by other organs
