Metabolism - Pituitary And Adrenal Glands Flashcards
What hormones are released from the posterior pituitary?
ADH
Oxytocin
What are the 5 cell types and hormones they produce in the anterior pituitary?
Gonadotrophs - LH/FSH Lactotrophs - Prolactin Corticotrophs - ACTH Thyrotrophs - TSH Somatotrophs - GH
How is GH released?
Pulsation fashion through day but peaks at night.
How does GH cause an effect?
Stimulates the production of IGF-1 by the liver
Acts on cell surface receptors to activate secondary messenger cAMP.
What mediates GH?
Mediated by IGF–1
What are the functions of GH?
Skeletal growth
Increased muscle strength
Quality of life
Metabolism
What will the effects of a deficiency in GH be?
Short stature if in children
Metabolic problems
Depression
Muscle wasting
What will be the effect of excess GH?
Gigantism in children Acromegaly in adults --> coarse features --> headaches --> hypertension --> sweating
What stimulates ACTH?
CRH and stress
How are CRH and ACTH released?
In a pulsatile fashion with 9am being peak
What is the function of ACTH?
It controls cortisol levels which increase glucose production and use.
What controls TSH release?
Negative feedback from T3/4 and TRH
What is the function of TSH?
Activates follicular cells to produce T3/4
What occurs in primary gland failure of TSH?
The thyroid fails
= little T3/4 and lots of TSH
OR
= lots T3/4 and little TSH
What occurs in secondary gland failure of TSH?
The pituitary gland fails
= little TSH, little T3/4, normal TRH
OR
= lots of TSH, lots of T3/4
What stimulates prolactin?
Oestrogen and a little TRH.
What inhibits and controls prolactin release?
Dopamine under tonic inhibitory control (NOT UNDER PITUITARY CONTROL)
What do high levels of prolactin cause and how does this occur?
Causes menstrual disturbance and lactation
Result of:
- Pharmalogical
- Polycystic ovaries
- Pregnancy
- Pituitary problem
- Physiological
What is the function of ADH and how does it achieve this?
It acts on the kidneys to recycle water when the body is becoming dehydrated.
Osmoreceptors in the pituitary gland control release of ADH
- if blood is more concentrated, secrete ADH = more water retained.
- a lower blood concentration or alcohol intake inhibit release of ADH
How is prolactin released?
Pulsatile fashion but greater amounts at night.
What is the anatomy of the pituitary gland?
Held by the pituitary stalk below the optic chiasma and in the middle of cranial nerves.
Where does the pituitary gland develop from?
Posterior = down growth of neural tissue
Anterior = up growth of primitive gut tissue
What is the hypothalamo-pituitary axis?
The link between the body’s endocrine and nervous systems.
What are the 2 types of tumour that can affect the pituitary hormones?
1) . Pituitary tumour
2) . Endocrine hypersecretion
What effect would a pituitary tumour have and what are its symptoms?
Symptoms may include lack of peripheral/blurred vision (press on optic chiasma) or cranial nerve palsied (cavernous sinus invasion).
It will decrease the secretion of all the hormones except prolactin, as this is not under pituitary control = hypopituitarism.
What are endocrine hypersecretion tumour and how will they affect the pituitary hormones?
Where a tumour elsewhere in the body secretes that hormone.
TSHoma
- high TSH = high T3/4
Prolactinoma
- can also be lost by loss of dopamine secretion
- shrink using dopamine
- galactorrhea
- infertility (inhibits LH/FSH)
GH secreting tumour
- acromegaly (coarse features, headaches, high BP, sweating)
Gonadotropinoma
- high sex steroids
- high LH/FSH
ACTH secreting
- cushings
How is LH/FSH released?
Pulsatile fashion
What stimulates LH/FSH release?
GnRH
How does LH/FSH affect men and women?
MEN LH - testosterone production FSH - sperm production Works by simple negative feedback Slight circadian rhythm
WOMEN
LH - oestrogen and progesterone release
FSH - follicle development
Works on simple positive feedback
How can hormone affecting tumours be managed?
1) . Hormone replacement
2) . Removal of tumour (often transphenoidally if on pituitary)
3) . Irradiating the tumour
4) . Medical solutions
- -> somatostatins inhibit GH
- -> dopamine inhibits prolactin
- -> GH receptor blockers to stabilise IGF-1 levels
What are the two types of tests for tumours causing hormone problems?
1) . Basal - if hormone is released stably, simply take a measurement.
e. g. Testosterone
2) . Dynamic - if hormone is released in a pulsatile way
e. g. GH, ACTH
- -> if deficiency in ACTH is suspected, make hypoglycaemic = see if ACTH rises
- -> if excess of ACTH is suspected, make hyperglycaemic = see if ACTH falls
What are the 5 layers of the adrenal gland?
Capsule Zona glomerulosa Zona fasciculata Zona reticularis Medulla
What is the function of mineralocorticoids and what happens if they are deficient or in excess?
They pump Na+ and therefore water into the kidney and K+ out via a pump.
Deficient - dehydration, low BP
Excess - high BP
What is the function of glucocorticoids and what happens if they’re in excess/deficit?
They increase glucose and protein breakdown and redistribute fats.
Excess = high BP, cushingoid, increased appetite Deficiency = lethargic, underweight, low BP
What are mineralo/glucocorticoids formed from and what will occur in an enzyme deficiency?
All are steroids that form from cholesterol, so if an enzyme is missing in the pathway, no mineralo/glucocorticoids may be made but an increase in androgens will occur.
What is primary adrenal failure and what usually causes it?
Failure of cortisol production due to an issue with the adrenal gland.
Often due to autoimmune destruction of the adrenal cortex.
What is the most common form of primary adrenal failure and its common features?
Addison’s disease
Female preponderance
Often occurs alongside other autoimmune diseases - type I diabetes, vitiligo
What are the clinical features of Addison’s disease?
Pigmentation - no cortisol = high ACTH = stimulates ACTH mediated melanocytes
Postural hypotension - due to fluid depletion as mineralocorticoids production will also suffer
Weight loss
Amenorrhea
Fever
Weakness
What are the biochemical features of Addison’s disease and why?
Low Na+ and high K+ due to lack of aldosterone too.
What tests can be performed to diagnose Addison’s disease?
Synthacthen test - give ACTH and see if cortisol is produced
9am cortisol level check - see if its in reference range
ACTH level check - see if its above reference range
Adrenal antibody check - elevated due to autoimmune destruction
How do you treat Addison’s disease both long term, and in an emergency?
Emergency -
Give fluids
IV glucose drip
IV cortisol
Long term -
Hydrocortisone to replace glucocorticoids
Fluorocorticoid to replace mineralocorticoids
What effect does long term steroid have on bone?
It decreases bone mass/formation
What is secondary adrenal failure and its main causes?
Where the pituitary gland fails to make enough ACTH = cortisol levels are low.
Caused by long term steroid use (as these block CRH after 3 weeks) or by a pituitary tumour.
What are the symptoms of adrenal failure?
Hypotension (due to low Na+ and high K+)
Weight loss
Dehydration
Mass lesion and other hormone effects of pituitary tumour.
How is secondary adrenal failure treated?
Fluids
IV glucose
IV insulin dextrose
What is congenital adrenal hyperplasia?
A deficiency in the enzyme that allows formation of mineralo/glucocorticoids = androgens formed instead.
What are the clinical features of congenital adrenal hyperplasia?
Virilisation of females due to exposure of high testosterone in utero. Dehydration Loss of Na+ Hypotension Hypoglycaemia
How and when can congenital adrenal hyperplasia be diagnosed and how is it treated?
Diagnosed by high ACTH and androgen levels and low Na+.
Needs confirming before gender assignment is made.
Treated by providing steroids.
What is cushings?
A condition arising from an excess of cortisol secretion, which may or may not be due to excess ACTH
What are the symptoms of cushings?
Straie - breakdown of proteins
Thin arms/legs - breakdown of proteins
Cushingoid - high cortisol = fat deposition
Hypertension - cortisol in high amounts can stimulate mineralocorticoid receptors = increased Na+ intake
Hyperglycaemia - increased protein breakdown/gluconeogenesis
Osteoporosis - Ca2+ catabolism
Bruising - thinning of skin
Pigmentation if cushings is caused by high ACTH
In what 2 ways can excess cortisol occur and what are these usually due to?
1) . Autonomous cortisol secretion = ACTH independent
- -> adrenal tumour
2) . Autonomous ACTH secretion = ACTH dependant
- -> pituitary tumour
What are the tests for cushings?
Midnight cortisol test
Monitoring 24h cortisol levels
Dextramethasone test
What is a dextramethasone test?
Test for diagnosing cushing’s and differentiating between cushing’s disease and cushing’s syndrome.
DMS acts as cortisol
1) . Give low dose of DMS
- -> if ACTH decreases, no cushings.
- -> if ACTH stays high, cushings.
2). Give high dose of DMS
–> if ACTH finally falls, its a pituitary problem (cushings DISEASE)
= autonomous ACTH secretion = ACTH dependant
–> if ACTH doesn’t change, its an ectopic or adrenal problem (cushings SYNDROME)
= autonomous ACTH secretion from ectopic or autonomous cortisol secretion from adrenal gland
How can cushings be treated?
Removal of the pituitary tumour transphenoidally
Removal of the adrenal glands (bilateral adrenalectomy)
Pituitary irradiation
Cortisol lowering tablets
What can a bilateral adrenalectomy cause and how?
Cause nelsons syndrome; due to lack of negative feedback from cortisol, ACTH levels rocket
= uncontrolled pituitary growth
= pigmentation
How does excess ACTH increase pigmentation?
It is produced at same time as alpha MSH (both from POMC). Alpha MSH binds to melanocortin receptors = forms melanin.
