Diseases of Endocrine System Flashcards
Endocrine system
What is an endocrine organ?
Secretes products directly into blood stream to reach a distant target e.g. Islets of Langerhan cells secrete hormones into blood vessels
What is an exocrine organ?
Secretes products into ducts that lead to target e.g. acinar cells secrete pancreatic enzymes into pancreatic duct
What are the 4 types of hormones?
- Neurocrine
- Endocrine
- Paracrine
- Autocrine
What are neurocrine hormones?
Secretion of hormones into the bloodstream by neurons
What are endocrine hormones?
Secretion of hormones into the bloodstream by endocrine glands
What are paracrine hormones?
Hormone molecule secreted by one cell affects adjacent cells
What are autocrine hormones?
Hormone molecule secreted by a cell affects the secreting cell
Pituitary gland
Where is the pituitary gland located?
In sella turcica; saddle shaped depression) in body of sphenoid bone of skull just beneath hypothalamus
What does the pituitary gland consist of?
2 lobes; anterior and posterior
What is the ‘adenohypophysos’?
Another name for anterior lobe of pituitary gland
What is the ‘neurohypophysis’?
Another name for posterior lobe of pituitary
What is the anterior pituitary lobe under control of?
Hypothalamus
Function of hypothalamus?
Produces and secretes the majority of pituitary hormones:
- TSH
- FSH & LH
- ACTH
- GH
- Prolactin
- Endorphins
Function of the hormones secreted by the anterior pituitary?
- TSH –> stimulates thyroid to produce T3 and T4
- GH –> skeletal muscle growth and function
- Prolactin –> acts on mammary glands (lactation)
- FSH and LH –> sex hormones
- ACTH –> stimulates adrenal cortex to release cortisol
- Endorphins –> acts on pain receptors in brain
Function of posterior pituitary lobe?
Stores hormones that are initially produced by hypothalamus:
- ADH
- Oxytocin
Function of hormones stored by posterior pituitary?
- Oxytocin; stimulation of mamillary glands (provokes milk ejection) and uterine muscles (childbirth)
- ADH (vasopressin); increases water reabsorption
Pituitary lobe hormones overview
What is an ‘adenoma’?
a type of non-cancerous tumor or benign that may affect various organs
Are pituitary tumours normally benign or malignant?
Almost always benign - ‘adenoma’
If a pituitary adenoma is ‘functional’, what does this mean?
- Adenoma is producing hormones - the hormone produced depends on the cell type that is proliferating e.g. prolactinoma, GH secreting, ACTH secreting
- If functional, the clinical effects of the tumour reflect the effects of excess hormone production
What are local effects of pituitary tumours?
- Pressure on the optic chiasm anteriorly (bitemporal hemianopia)
- Pressure on adjacent pituitary cells (hypofunction of other cells)
- Stretching of meningeal cover of brain due to tumour –> pain
What is a prolactinoma? What does it result from?
- A noncancerous tumor of the pituitary gland that causes the pituitary to make too much prolactin.
- Result from mutation in lactotroph cells of anterior pituitary which are responsible for producing prolactin –> results in uncontrollable division of lactotrophs
Prolactinomas cause an increase in prolactin. What are the symptoms of this?
- Infertility
- Amenorrhea
- Gynecomastia
- Galactorrhea
What measurements define a:
- microprolactinoma?
- macroprolactinoma?
- microprolactinoma <10mm
- macroprolactinoma >10mm
What is bitemporal hemianopia?
‘Tunnel vision’ –> impaired peripheral vision in outer temporal halves of visual field of each eye (i.e. partial blindness affecting lateral halves of vision due to compression/lesions of optic chiasm)
What does bilateral hemianopia result from?
Prolactinoma compresses optic nerve/chiasm
What is a growth hormone–secreting pituitary adenoma? What does it result from?
- Benign pituitary tumour that releases GH
- Mutation of somatotropic cells; responsible for releasing GH
Clinical presentation of growth hormone–secreting pituitary adenoma in:
a) adults
b) children
- Adults: acromegaly
- Excessive growth of the hands, feet, jaw, and internal organs
- MRI shows that a pituitary tumour in 90% of acromegalic patients
- Children: gigantism__
- Abnormally high linear growth due to the excessive action of growth hormone before the closure of the epiphyseal growth plates in childhood
Why does growth hormone–secreting pituitary adenoma present differently in adults and children?
Excessive action of growth hormone before the closure of the epiphyseal growth plates in childhood
Which test is used to diagnose a growth hormone–secreting pituitary adenoma?
Oral glucose suppression test;
- Normally glucose suppresses GH
- In acromegaly glucose does not suppress GH (due to tumour)
Thyroid gland anatomy
What 3 hormones does the thyroid gland produce?
- T3 (active); triiodothyronine
- T4; thyroxine
- Calcitonin
Describe stimulation from hypothalamus to thyroid gland
- Hypothalamus secretes TRH
- Stimulates thyrotrophs of pituitary gland to secrete TSH
- Stimulates thyroid gland to produce T3 and T4
This then is under a negative feedback loop.
Which cells of the pituitary gland secrete TSH?
Thyrotrophs
Which cells of the pituitary gland secrete GH?
Somatotropic cells
Which cells of the pituitary gland secrete prolactin?
Lactotrophs
What is thyroglobulin?
- protein produced by follicle cells and stored in thyroid gland
- is the main precursor to thyroid hormones; thyroglobulin’s tyrosine residues + iodine –> thyroid hormones
Regulation of thyroid hormones
What is hypothyroidism?
Overall insufficiency of circulating T3 and T4 hormones
How does hypothyroidism affect basal metabolic rate? How does this present?
Overall reduction in basal metabolic rate
What is myxedema? What does it indicate?
- Increased deposition of mucopolysaccharides in skin
- Due to severely advanced hypothyroidism
If hypothyroidism is congenital, what does this lead to?
Cretinism; Physical deformity and learning difficulties caused by congenital thyroid deficiency
What is the most common cause of hypothyroidism?
Hashimoto’s thyroiditis
What is Hashimoto’s thyroiditis?
- Autoimmune disorder
- Immune system attacks follicular cells of thyroid gland –> decreased T3 and T4
Signs and symptoms of hypothyroidism
What are other causes of hypothyroidism?
- iodine deficiency
- drugs
- post-radioiodine therapy
- post-surgery
- <1% by secondary (deficiency in TSH), tertiary (deficiency in TRH) and peripheral causes (extra-thyroidal causes).
Hashimoto’s disease increases risk of which 2 cancers?
- Thyroid lymphoma
- Papillary carcinoma
What is hyperthyroidism (thyrotoxicosis)?
due to excess T3 and T4
How does hyperthyroidism affect basal metabolic rate?
Increases basal metabolic rate
Commonest cause of hyperthyroidism?
Grave’s disease
What is Grave’s disease?
- Autoimmune disease
- Autoantibodies bind to receptors on follicular cells and stimulate them to produce thyroid hormone.
- These autoantibodies are often called long-acting thyroid stimulators (LATS) and functionally mimic the effects of TSH.
Clinical presentation of Grave’s disease?
- Diffuse goitre; entire thyroid gland swells and feels smooth to the touch
- Pretibial myxoedema
- hair loss
- wide-eyed stare / proptosis
- tachycardia
- hyperactive reflexes
Why does Grave’s disease lead to proptosis?
bulging of eyes due to immune system attacking muscles and fatty tissues around and behind eye –> swollen
Clinical presentation of hyperthyroidism?
- heat intolerance
- tremor
- palpitations
- anxiety
- weight loss despite a normal or increased appetite
- increased frequency of bowel movements
- shortness of breath
What are other causes of hyperthyroidism?
- Very rarely due to excess TSH
- functional adenoma
- toxic nodular goitre
How can a toxic nodular goitre cause hyperthyroidism?
Toxic nodular goiter involves an enlarged thyroid gland that contains a small rounded mass or masses called nodules, which produce too much thyroid hormone.
What is a ‘hot nodule’?
- produces excess thyroid hormone
- shows up darker on scan because they take up more of the isotope (absorb iodine) than normal thyroid tissue does
- Almost always noncancerous.
What is a ‘cold nodule’?
- composed of cells that do not make thyroid hormone (so don’t absorb iodine)
- take up less of isotope
- Are cancerous.
What is a multinodular goitre?
- An enlarged thyroid gland is called a goitre
- A multinodular goitre is a goitre where there are many lumps (nodules) that appear within the gland.
- Nodules may be clearly visible or only discovered through examination or scans.
- This is probably the most common thyroid gland disorder.
- Enlargement of thyroid with varying degrees of nodularity
Symptoms of multinodular goitre?
- Most patients are euthyroid
- Tracheal compression/dysphagia may develop with large nodules
What is Plummer disease?
Toxic multi-nodular goiter; a hormonally active multi-nodular goiter with hyperthyroidism.
What is a thyroid follicular adenoma?
- Benign encapsulated tumour of the thyroid gland; solid mass that is surrounded by a thin fibrous capsule
- Common cause of a solitary thyroid nodule
- Sometimes functional, usually cold nodule on radio-isotope scanning
What is a thyroid follicular carcinoma?
- Well-differentiated malignant tumour with good prognosis
- Invades capsule and blood vessels
- 10-20% of all thyroid cancers
How do 90% of Thyroid Follicular Carcinoms present
- 90% present with solitary nodule in thyroid
- 10% present with distant metastasis
What is a papillary thyroid carcinoma? What does it invade?
-
Well differentiated carcinoma with excellent prognosis
- Invades lymphatics and spreads to local lymph nodes
- Seen more in younger (<45 years old) and mostly female patients
Where are the parathyroid glands located?
4 glands located behind the thyroid gland.
What are the parathyroid glands responsible for?
Responsible for PTH for calcium homeostasis in close association with vitamin D and calcitonin
Describe calcium homeostasis related to the parathyroid and thyroid glands
Decreased Ca levels:
- Increased PTH release from parathyroids
- Increased bone resorption; calcium released into blood
Increased Ca levels:
- Increased release of calcitonin from c cells of thyroid gland
- Reduces calcium uptake in kidneys
- Reduces calcium uptake in intestines
What can cause low Ca levels?
- Hypoparathyroidism
- Vitamin D insufficiency
- Renal failure or liver failure; unable to convert vit D into active form
- Vit D required for absorption of calcium in GI
Causes of hyperparathyroidism
What is Primary Hyperparathyroidism?
Increased PTH from parathyroid glands
Primary Hyperparathyroidism can lead to hypercalcaemia and hyperkalaemia. How? What are the symptoms?
Hypercalcaemia:
- Due to increased PTH causing bone resorption
- Symptoms; renal stones, brittle bones
Hyperkalaemia:
- Due to ?
- Symptoms; muscle weakness, tiredness, thirst and polyuria, anorexia and constipation
What are other causes of hypercalcaemia (except 1ary hyperparathyroidism)?
bone mets, Vit D intoxication, sarcoidosis, multiple myeloma and rarely PTH producing tumours
What does the adrenal gland consist of?
- Outer cortex
- Inner medulla
What does each area of the adrenal gland produce?
- Cortex has 3 zones (GFR) and each produces specific hormones:
- zona glomerulosa (outer) –> produces mineralocorticoids (i.e. aldosterone)
- zona fasciculata –> produces glucocorticoids (i.e. cortisol)
- zona reticularis (inner) –> androgens (i.e. DHEA)
- Medulla consists of chromaffin cells that produces catecholamines (stress hormones) –> dopamine, adrenaline, noradrenaline
Which part of the adrenal gland produces:
- aldosterone?
- cortisol?
- adrenaline?
- androgens?
- 1ary mineralocorticoid –> zona glomerulosa
- 1ary glucocorticoid –> zona fasciculata
- medulla
- zona reticularis
What is Cushing’s syndrome? What is it due to?
Rare endocrine disorder due to excess cortisol coming from the zona glomerulosa
What is cortisol important for?
glucose metabolism and modulates response to stress
Endogenous causes of Cushing’s syndrome?
- ACTH secreting tumour of adrenal glands or of pituitary
- Adrenocortical hyperplasia
Cushing’s disease vs syndrome?
Cushing disease is a specific type of Cushing syndrome. It occurs specifically due to ACTH secreting pituitary tumour.
Cushing disease is the most common form of endogenous (from the body) Cushing syndrome, and makes up about 70% of Cushing syndrome cases.
Exogenous cause of Cushing’s syndrome?
Seen in patients on steroid therapy
Symptoms of Cushing’s syndrome?
weight gain, central obesity, a rounded face, thin purple streaks (purple striae) which occur on the skin, increased fat around the neck, and slender arms and legs.
RAAS system overview
Effect of angiotensin II on aldosterone?
Acts on adrenal gland to stimulate release of aldosterone
Effects of aldosterone?
Acts on the kidneys to stimulate reabsorption of salt and water
What is Conn’s syndrome?
Occurs when the adrenal glands produce too much aldosterone; hyperaldosteronism
Causes of Conn’s syndrome?
Too much aldosterone production caused by:
- adrenal cortical hyperplasia
- adenoma
- carcinoma
- familial hyperaldosteronism
2 major clinical presentations of Conn’s syndrome? Explain
- High BP –> too much aldosterone leads to renal retention of H20 and Na+
- Low potassium –> too much aldosterone causing you to lose K and retain Na
Signs and symptoms of Conn’s syndrome?
Headache, muscular weakness, low potassium; muscle spasms, excessive urination, cardiac arrythmias
What is Addison’s disease?
Primary adrenal cortical insufficiency; adrenal glands produce too little cortisol and often too little aldosterone
Which cells of the pituitary secrete ACTH?
Corticotrophs
Causes of Addison’s disease?
- Secondary due to failure of ACTH secretion (many causes e.g. tumour suppressing corticotrophs in pituitary gland)
- Autoimmune form common
Triad of symptoms for Addison’s disease?
- hyperpigmentation
- postural hypotension
- hyponatraemia.
How is Addison’s disease treated?
- Treatment with long term steroid replacement.
- If undiagnosed can prove fatal.
Addison’s disease vs acute adrenal crisis?
- Acute adrenal crisis is a medical emergency caused by a lack of cortisol.
-
Acute adrenal crisis can be triggered by infections or other stresses like surgery, trauma or dehydration
- Leads to profound fatigue, vomiting, fluid loss, electrolyte disturbances, renal shut down and circulatory collapse.
What is a Pheochromocytom?
Tumour of the adrenal medulla (or ANS) that produces catecholamines
Clinical presentation of Pheochromocytoma ?
- Racing heartbeat
- Headaches
- Pallor
- Sweating
- High BP
- Elevated urine catecholamines, adrenaline, noradrenaline.
What can the dominant nodule in a multinodular goitre be mistaken for?
Thyroid carcinoma
What is a toxic multinodular goitre also known as?
Plummer disease
What is the most common cause of a solitary thyroid nodule?
Thyroid follicular adenoma
What disease is it called when a patient has hyperaldosteronism?
Conns syndrome
A thyroid adenoma may be “cold” or “warm”/”hot” adenoma. What does this mean?
Cold; Thyroid adenoma is clinically silent (“cold” adenoma)
Hot/warm: A functional tumour producing excessive thyroid hormone (it may result in symptomatic hyperthyroidism, and may be referred to as a toxic thyroid adenoma)
Which vitamin is required for calcium absorption?
Vitamin D
