Adrenal Glands, Disorders Flashcards
What are the 3 regions of an Adrenal Gland
- Capsule (CT, contains blood vessels)
- Cortex
- Medulla (Contains Chromaffin cells)
What are the 3 regions of the Adrenal Cortex?
What hormones are made in each
Zona Glomerulosa;
- Mineralocorticoids
Zona Fasciculata;
- Glucocorticoids
Zona Reticularis;
- Glucorticoids + small amounts of Androgens
Name 3 glucocorticoids made in Zona fasciculata
Name 1 Mineralocorticoid made in Zona glomerulosa
- Cortisol (One of main 2)
- Corticosterone (One of main 2)
- Cortisone
Aldosterone (Most abundant)
What are steroid hormones made from? Where?
What TYPE of hormones are secreted from the Adrenal Cortex?
Made from cholesterol in adrenal glands and gonads
Corticosteroids
Androgens/ Mineralocorticoids/ Glucocorticoids
How do Corticosteroids exert their actions on cells, by regulating gene transcription?
In 4 steps
- Diffuse across plasma membrane
- Bind to cytoplasmic receptors, causing dissociation of chaperone proteins
- Hormone/ receptor complex enters nucleus
- Receptors bind to GREs (Glucocorticoid response elements) or other Transcription factors on DNA
How is Aldosterone transported in the blood?
On a carrier protein Mainly Albumin (to a lesser extent, Transcortin)
What 3 things does Aldosterone regulate?
How does it do this in the kidney?
Plasma Na+, K+ and Arterial Blood Pressure
- Promotes expression of Na-K pump in Distal Tubules and Collecting Ducts (of nephrons)
- Leads to increased Reabsorption of H20/Na+ and Excretion of K+ (affecting water retention, blood volume and blood pressure)
Other than the kidney Na-K pumps, what else does Aldosterone up regulate the expression of?
What is the effect?
Upregulates expression of ENaCs in collecting duct and colon
Increased Na+ absorption
What is Hyperaldosteronism?
Compare the 2 types of HA?
How do you distinguish between them?
A physiological state/ condition caused by excess Aldosterone production
Primary Hyperaldosteronism;
- Defect in Adrenal Cortex
- Low renin levels
Secondary Hyperaldosteronism;
- Overactive RAAS
- High renin levels
What are 5 signs of Hyperaldosteronism
What are 2 treatments
- Hypertension
- Hypernatraemia
- Hypokalaemia
- Stroke
- LV Hypertrophy
- Aldosterone producing adenomas are removed by surgery
- Spironolactone (Mineralocorticoid receptor antagonist)
What is the most abdunant corticosteroid, and primary glucocorticoid?
Describe the secretion pattern of the main factor controlling cortisol release
Cortisol
ACTH/ Corticotropin is secreted with a circadian rhym in a pulsatile fashion
What are 2 important precautions when sampling blood for cortisol measurement?
Why?
- Time should be noted when taking blood
- Repeated measurements should be taken at same time of day
Blood cortisol varies throughout the day (Peak at 7am, trough at 7pm)
How is Cortisol transported in blood
(Bound to plasma proteins)
Mainly Transcortin/ CBG (90%)
Rest is by Albumin (10%)
Give 2 occasions when most cortisol is released
Starvation
Stress
How does cortisol affect;
- Amino acid uptake
- Protein synthesis
- Proteolysis (Not in liver)
- Gluconeogenesis and glycogenolysis
- Peripheral glucose uptake
- Lipolysis (in adipose)
- Lipogenesis (in adipose, when in high levels)
- Decreased
- Decreased
- Increased
- Increased (both)
- Decreased (Glucose sparing effect)
- Increased
- Increased
What are 3 net effects of glucocorticoids
- Protein breakdown
- Increased glucose production
- Re distribution of fat
What are 3 non metabolic effects of cortisol
- Resistance to stress ( More glucose, higher BP by making vessels more sensitive to vasoconstriction)
- Anti inflammatory effects (Inhibits macrophages, Causes mast cell degranulation so can be used as allergy medication)
- Depression of immune response (So used for organ transplant patients)
Describe the HPA Axis in 4 steps
- Stress (Pain, Low glucose, Low BP)-> Hypothalamus releases CRH
- CRH acts at Ant. Pit. Gland-> ACTH secreted
- ACTH acts at adrenal cortex-> Cortisol secreted
- Cortisol acts at target tissues
Which 2 hormones’ secretion can be inhibited by Cortisol by negative feedback in the HPA Axis
How does ACTH increase Cholesterol availability for cortisol production? In 2 steps
CRH and ACTH
- Acts on cell surface receptors in Zona fasciculate and reticularis.
- Activation of Cholesterol Esterase (Cholesterol esters-> Free cholesterol)
What are 2 causes of Primary Hyperaldosteronism
What are 2 causes of Secondary Hyperaldosteronism
Primary;
- Bilateral idiopathic adrenal hyperplasia (Most common)
- Aldosterone secreting adrenal adenoma (Conn’s Syndrome)
Secondary;
- Renin producing tumour (Rare)
- Renal artery stenosis
What is Cushing’s Syndrome
What are 2 types of causes
A clinical condition caused by chronic excessive cortisol production
Exogenous Endogenous (Rare)
What is the most common Exogenous cause of Cushing’s Syndrome
Chronic use of prescribed glucocorticoids (Especially Prednisone and Hydrocortisone)
Describe 3 Endogenous causes of Cushing’s Syndrome
- Cushing’s disease;
- Benign ACTH secreting pituitary adenoma - Adrenal Cushing’s;
- Excess cortisol made by adrenal tumour - Small cell lung cancer (very rare);
- Non pituitary adrenal tumours, producing ACTH and/or CRH
Name 7 symptoms/ signs of Cushing’s Syndrome
- Moon shaped face (Fat redistribution)
- Buffalo hump (Fat redistribution)
- Abdominal obesity
- Acute weight gain
- Hypeglycaemia
- Hypertension
- Purple striae
Name 2 steroid drugs
What are 2 uses
What are the side effects
Prednisolone, Dexamethasone
- Suppress immune reaction to organ transplants
- Treat inflammatory disorders
Side effects: Same as with excess cortisol+ possible mineralocorticoid effects
What is an important point to consider when taking a patient off of steroid drug?
Steroid dosage should be reduced gradually, not suddenly (Can lead to Addison’s disease)
What is Addison’s disease
Are women or men affected more?
Identify 4 causes, which is most common?
Clinical condition due to chronic adrenal insufficiency
- Destructive atrophy from autoimmune response (Most common)
- Fungal infection
- Adrenal cancer
- Adrenal haemorrhage (Trauma)
Identify 6 signs/ symptoms of Addison’s disease
- Postural hypotension
- Lethargy
- Weight loss
- Anorexia
- Hypoglycaemia
- Hyperpigmentation (Of skin)
Describe the relationship between POMC, ACTH and Alpha-MSH
Why does high ACTH have some MSH-like activity
POMC is a large protein that undergoes post translational processing to produce ACTH and MSH
POMC contains ACTH, which contains MSH
Explain 2 wayshow Addison’s disease causes hyperpigmentation
- Low cortisol-> less Negative feedback on Ant Pit gland
- More POMC used to make ACTH, so more MSH released as well
- MSH causes melanin synthesis
- ACTH can activate Melanocortin receptors (MC2) on melanocytes (the receptors use cAMP)
What is an Addisonian Crisis?
What are 5 symptoms?
How is it treated?
A life threatening emergency due to adrenal insufficiency
- Nausea
- Vomiting
- Pyrexia
- Hypotension
- Vascular collapse
Immediate fluid replacement and cortisol
What are 7 possible causes of an Adisonian Crisis
- Severe stress
- Salt depravation
- Infection
- Trauma
- Cold exposure
- Overexertion
- Abrupt steroid drug withdrawal
Name 2 Androgens made in Zona reticularis
What is Androgen secretion regulated by?
What is a common function of Androgens in both sexes?
Androstenedione
Dehydroepieandrosterone (DHEA)
Partially regulated by ACTH and CRH
Promote Axillary and pubic hair growth
In Males, which hormone is converted to Testosterone?
Why is this insignificant after puberty?
DHEA
After puberty, testes release far more testosterone themselves
In females, what do adrenal androgens do?
What are the sources of oestrogens after menopause?
Promote libido and are converted to Oestrogens (by other tissues)
After menopause, only oestrogen sources are androgens
Name 3 hormones/ neurotransmitters made in the adrenal medulla
Adrenaline
Noradrenaline
Dopamine
80% of Chromaffin cells in Adrenal Medulla secrete Adrenaline
The other 20% secrete Noradrenaline
Explain this
20% don’t have N-methyl transferase (needed to make Adrenaline from Noradrenaline)
What is a Phaechromocytoma?
Identify 7 symptoms
A rare catecholamine secreting Chromaffin cell tumour
- Severe (possibly life threatening) hypertension
- Palpitations
- Anxiety
- Weight loss
- Pallor
- Sweating
- Glucose intolerance
What are Catecholamines
What are they derived from
Hormones made in adrenal medulla
Derived from Tyrosine
Compare the effect on patients of a Bilateral Adrenalectomy (Removed adrenal glands)
(With reference to Corticosteroids and Catecholamines )
Corticosteroids;
- Patient must receive cortisol and aldosterone for life
Catecholamines;
- No apparent ill effects (NA released from Nervous system to compensate)
Where does cleavage of Angiotensin I into Angiotensin II mainly occur?
Within lung capillaries (by ACE-Angiotensin Converting Enzyme)
Explain how Cushing’s Syndrome causes Purple Striae
Central obesity from cortisol induced fat redistribution causes skin to stretch
Appear purple due to increased proteolysis(Skin is thin and weakened) because of cortisol
What does Dexametasone normally do when given orally?
Suppresses ACTH secretion, reducing cortisol production
How do you differentiate between Cushing’s disease and an Adrenal or ectopic tumour being the cause of Cushing’s Syndrome?
Give dexamethasone orally
- Cortisol production is suppressed if the cause is Cushing’s disease
- No cortisol suppression if the cause is an adrenal or ectopic tumour
What is the ACTH stimulation test? What does a normal response exclude
IM synacthen (A synthetic analogue of ACTH) is given, normally it increases plasma cortisol.
Excludes Addison’s disease
What is Congenital Adrenal Hyperplasia?
A rare group of inherited genetics defects in 1/ more enzymes needed to make corticosteroid hormones.
The pituitary gland secretes large amounts of ACTH (due to low cortisol) which causes the adrenal cortex to enlarge
What is the most common form of Congenital Adrenal Hyperplasia
What is the result of this?
Deficiency of 21-hydroxylase, leading to reduced glucocorticoid and mineralocorticoid production.
This results in these hormones’ precursor being diverted to more androgen synthesis. (Can result in genital ambiguity in females and high sodium excretion in urine)
In Conn’s syndrome, how does decreased renin affect aldosterone?
It doesn’t
Why can high cortisol levels cause androgen and mineralocorticoid-like effects?
At high levels, cortisol can bind to mineralocorticoid and androgen receptors with low affinity.
This is because;
- Glucocorticoid receptors are 64% similar to Mineralocorticoid receptors
- Glucocorticoid receptors are 62% similar to Androgen receptors
List 6 effects of excess androgen secretion in females
- Hirsutism (excessive body hair growth)
- Acne
- Menstrual problems
- Deeper voice
- Increased muscle bulk
- Virilisation (Masculinisation)
