Adrenal Cortex Flashcards
What is the endocrine fucntion of the adrenal cortex?
The adrenal cortex produces hormones that controls sex (androgens, estrogens), salt balance in the blood (aldosterone), and sugar balance (cortisol)
Where does the glucocorticoid production take place and what does it produce?
Aldosterone, which is produced in the zona glomerulosa, via a aldosterone synthase.
Function of aldosterone
maintain BP, promote renal sodium reabsorption and promote potassium excretion by acting via mineralocorticoid receptors
What can stimulate aldosterone production?
Low BP, ACTH effects, posture
What is the main glucocorticoid produced?
Cortisol in the zonae fasiculata and reticularis
How is cortisol secreted?
Interplay with hypothalamus and pituitary, using CRH and ACTH respectively. Occurs in response to stress
How is cortisol production regulated?
Negative feedback loop: Cortisol on hypothalamus and pituitary gland
What are glucocorticoids actions?
Bone
- inhibit bone formation
- increase resorption
- induce negative calcium balance
Skin
- inhibit fibroblast activity causing bruising and poor wound healing
Glucose
- increase blood glucose by decreasing tissue glucose uptake
- increase hepatic gluconeogenesis
Cortisol action on water balance
Are inhibited by 11beta hydroxysteroid dehydrogenase. Important because cortisol and aldosterone are structurally similar, meaning both activate mineralocorticoid receptors. The protecting enzyme converts cortisol to cortisone - so circadian rhythm of cortisol cant affect water balance/status.
What androgens are produced in the adrenal cortex?
Precursors of testosterone and oestrogen.
- androstenedione, DHEA, DHEA-S
What is the difference between primary and secondary/tertiary adrenal insufficiency?
Primary is caused due to a problem in the adrenal, whilst secondary/tertiary is problems in the pituitary or hypothalamus.
What is primary AI caused by?
Decreased cortisol production due to:
- autoimmune disease (70%),
- infection (AIDS)
- congenital (enzyme deficiency )
- drugs (ketoconazole)
- haemorrhage (heparin treatment),
- metastatic tumour,
- amyloid,
- haemochromatosis or sarcoidosis.
What is secondary AI caused by?
Decreased ACTH production.
- Pituitary tumours
- autoimmune disease.
- pituitary tumors or infection.
- bleeding in the pituitary.
- genetic diseases that affect the way the pituitary gland develops or functions.
- surgical removal of the pituitary to treat other conditions.
- traumatic brain injury link.
What are symptoms of adrenal insufficiency?
fatigue, weight loss, postural dizziness, anorexia, abdominal discomfort
What are the biochemical features of AI?
Hyponatraemia, hyperkalaemia, hypo/hyperglycaemia (uncommon)
What is adrenal crisis?
Acute adrenal crisis is a medical emergency caused by a lack of cortisol. Can occur in patients with AI
Symptoms and biochemical features of adrenal crisis?
severe weakness (hyponatraemia), syncope (hyperkalaemia), abdominal pain (hypoglycaemia), nausea, vomiting, back pain (hypercalcaemia) and confusion.
Explain the hyperpigmentation in primary AI?
Hyperpigmentation occurs as a byproduct of ACTH overmaturation. POMC is the ACTH precursor, which contains a Melanocyte stimulating hormone.
- The MSH increases melanocytes present result in hyperpigmentation
Biochemical features of primary AI?
Hyponatraemia Hyperkalaemia Acidosis Mildly elevated urea Low/normal cortisol Hypoglycaemia
What can cause adrenal crisis and what are some clinical features?
Precipitated by major stress
- Shock
- hypotension
- abdomen pain
- unexplained feve
How is the adrenal crisis treated?
The main treatment is rehydration and replacement
How is adrenal insufficiency investigated?
Using a short synacthen test
- Administer IV tetracostratin (250ug) and take cortisol+ ACTH at 30 and 60 min
- Abnormal response <500nmol/L
- Flat response in primary AI
- Impaired response for secondary
How can you elucidate the cause of adrenal insufficiency (primary or secondary)?
If there is an impaired cortisol response to the short synacthen test then ACTH >300ng/L is primary adrenal failure or <10ng/L is secondary adrenal failure (pituitary test follows).
What further investigations can be done in primary adrenal insufficiency?
Elucidating the cause by measurign 17-OH progesteron (CAH, idiopathic PAI), 21-OH antibody (congenital and autoimmune)
Examine how the rest of the adrenal hormones are affected, e.g. renin/aldosterone and androgens
How do you treat adrenal insufficiency?
Replace glucocorticoids and mineralocorticoids
- hydrocortisone and fludrocortisone - monitor efficacy using cortisol and renin curves
What is hypoaldosteronims?
Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone
What causes hypoaldosteronism?
- Impaired renin production (hyporeninaemic hypoaldosteronism, diabetic neuropathy)
- Inherited defects in aldosterone biosynthesis
- Acquired forms (heparin therapy).
- Pseudohypoaldosteronism: inherited resistance to actions of aldosterone
What are some metabolic changes to hypoaldosteronism?
- hyponatraemia
- hyperkalaemia,
- acidosis,
- mildly elevated urea
- hypotension.
What biochemical test can be used to diagnose hypoaldosteronims
- U&E panel: hyponatraemia, hyperkalaemia, urea
- Acidosis: blood gas analyse/anion gap
- Most accurate is renin/aldosterone measurement
Describe patterns in diagnosing hypoaldosteronism
Primary HA
- renin high, aldosterone low
Secondary HA
- low renin, low aldosterone
What is cushing syndrome?
Syndrome characterised by elevated glucocorticoids - glucose
What are some causes
80% ACTH dependent - secondary
- pituitary adenoma
- ectopic ACTH
20% adrenal origin
- adrenal adenoma
- adrenal carcinoma, nodular hyperplasia
Clinical features of cushings syndrome
weight gain, central obesity, proximal wasting, muscle weakness/malaise, buffalo hump, moon face, acne, osteoporosis, hirsutism, purple striae, skin thinning, bruising, depression, decreased libido, psychosis, oligo-, amenorrhoea, hypertension, susceptibility to infections
What are some non-cushings hypercortisolism?
non-cushings conditions causing elevated cortisol.
Seen in obesity, alcohol, depression, PCOS, serious illness/cancer.
What test is used to diagnose cushings?
DST test
- overnight, give 1mg DST at midnight and measure cortiol at 9am
48hr
- 2mg DST given when there is a physiological cause for high cortisol (non-cushing)
- 0.5mg DST given at 0900, 1500, 2100, 0300 and cortisol measured at 09 on second day
When is DST test inappropriate?
For cyclical cuhsings
How can you elucidate cause of cushings?
Potassium levels
- In patient with high ACTH 10% pituitary dependent and 100% ectopic have K<3.2 mmol/L (with alkalosis).
CRH test
- 95% pituitary dependent and <1% ectopic have exaggerated cortisol response in CRH test
DST (high dose)
-90% pituitary dependent and 10%ectopic will suppress cortisol >50% basal.
Imaging to see presence of tumours can be done
How does petrosal sinus sampling work?
Acts to measure ACTH from veins that drain pituitary gland
- Measured before and after IV CRH.
- The ratio of central to peripheral allow for diagnosis
How does the ratio of central to peripheral allow for diagnosis?
central: peripheral ratio >2 suggests cushings disease (A ratio of >3 is more sensitive (90-95%)).
How is cushings syndrome treated?
Most common is to remove the tumour via a trans-sphenodial surgery.
- non operable patients will receive radiotherapy
- Limited medical treatment, but can be used whilst waiting for surgery/radiotherapy, e.g. metyrapone, ketoconazole, mitotane.
- adrenalectomy if its an adrenal cause
When can Nelsons syndrome occur?
Patients that had bilateral adrenalectomy as treatment for cushing disease.
- manifest as hyperpigmentation,
- ACTH increase
- Enlarged pituitary tumours
Incidence- 50% within 10 years
What is hyperaldosteronims?
Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal glands, which is non-suppressible with sodium loading
Causes of hyperaldosteronism
- idiopathic adrenal hyperplasia
- Conns syndrome: aldosterone-producing adrenal hyperplasia
- Adrenocorticoid carcinoma
Who are susceptible to developing hyperaldosteronism?
- hypertensives
- with hypokalaemia
- with adrenal incidentaloma
How do you screen for hyperaldosteronism?
Screening of PA can be done using the aldosterone renin ratio
Describe patient preperations ahead of renin aldosterone measurement
- Unrestricted dietary salt intake day before
- Out of bed for at least 2h
- Discontinue meds: antihypertensives
Why is direct plasma renin activity more accurate than direct renin concentration?
PRA is more effective measurement as DRC will be interfered by oestrogens
Patients on either spironolactone, eplerenone, amiloride and triamterene need to what before renin:aldosterone measurement?
need to be discontinued 4 weeks prior to the measurement of PRR to limit interference
Why cant AAR samples not be placed on ice?
because as the pro-renin becomes renin causing a skewed analysis
TRUE OR FALSE.
Hypokalaemia can make interpretation hard as it decreases aldosterone and increases renin.
True
What is a definite indication of primary hyperaldosteronism?
ARR>2000
What follow up tests are useful for primary hyperaldosteronism?
Saline infusion test Oral sodium loading Captopril challenge test CT Adrenal vein sampling
How is primary hyperaldosteronims treated?
- Unilateral adrenalectomy where possible
- medical intervention include minaralocorticoid receptor antagonist, e.g.spironolactone, amiloride, eplerenone.
What is secondary hyperaldosteronism?
due to overactivity of the renin–angiotensin–aldosterone system (RAAS)
What causes secondary hyperaldosteronims?
Caused by nephrosis, cirrhosis, cardiac failure or associated with oedema and reduced oncotic pressure
- renin producing tumours as well
Overall- false sense of hypovolaemia and activates aldosterone secretion
What are the results for DRC and PRA in 2nd hyperaldosteronism?
High as the renin causes the hyperaldosteronims
What are familial hyperaldosteronism?
A group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone
What 3 types of familial hyperaldosteronism are there?
Type I - glucocorticoid remediable aldosteronism
Type II - 7p22 mutation
Type III - germline mutations in the K channel subunit KCNJ5
Familial hyperaldosteronims type I?
- inherited autosomal dominant disorder
- chimeric gene causes’
- This chimeric gene result in the expression of an aldosterone synthase gene in zonae fasiculata and glomerulus
- Expression controlled by ACTH
Treatment is using DST/prednisone
What is syndrome of apparent mineralocorticoid excess?
Congenital deficiency of 11-beta-HSD 2 enzyme causing cortisol to act on the mineralocorticoid receptor. Causes water imbalances.
- Symptoms: hypertension, suppressed renin/aldosterone, hypokalaemic alkalosis, increase cortisol:cortisone ration
What is syndrome of apparent mineralocorticoid excess caused by ?
Excess intake of glycyrrhetinic acid (liquorice, cough medicine, chewing tobacco)
Treatment of syndrome of apparent mineralocorticoid excess
carbonic anhydrase inhibitor known as acetazolamide.
What are congenital adrenal hyperplasias?
Group of autosomal recessive disorders where an enzyme deficiency leads to decreased cortisol
- Often associated with the overproduction of steroids.
- Severity is dependent on what enzyme is affected
Describe what happens in 21 hydroxylase deficiency?
This condition is associated with no cortisol and no aldosterone production. This results in high 17 hydroxyprogesterone and excess androgen production.
Symptoms of 21 hydroxylase deficiency?
Ambiguous genitalia in female neonates – clitoromegaly (looks like penis) or fusion of labia (scrotum)
Biochemical features of 21 hydroxylase deficiency?
Hypoglycaemia, dehydration, vomiting and pigmentation
- Can cause salt-crisis causing collapse during stress or illness
What are the milder forms of 21 hydroxylase deficiency associated with?
Cause rapid growth (still short stature) and precocious puberty (due to increased androgens)
Non-classical form has onset in adulthood, which presents in female as hirsuitism, virilism, amenorrhoea (diagnose with SST and 17-OH P)
11 hydroxylase deficiency
deficiency in the enzyme catalysing the last step in cortisol production and penultimate in aldosterone
- The aldosterone and cortisol production is blocked. It results in 11 deoxycortisol and 11 deoxycorticosterone
Biochemical features of 11 Hydroxylase
Low potassium, high BP, can cause virilisation in women
Mild forms: 17OHP moderately raised, but 11deoxycortisol is high
17 hydroxylase deficiency
block aldosterone intermediates becoming cortisol intermediates.
- Aldosterone is produced, but not cortisol or androgens
17 hydroxylase deficiency features
Males are born feminised, whilst females will have a delayed puberty.
- Hypotension
Cholesterol side chain cleavage
Complete adrenal steroid deficiency. Same for cortisol and aldosterone
How is congenital adrenal hyperplasia treated?
Hormones not produced need to be replaced.
- hydrocortisone (increase dose at times of stress/illness), fludrocortisone, testosterone/oestrogen
- If previous child has 21hydroxylase then prenatal diagnosis using free neonatal DNA can be used to diagnose - Treat with steroid cover during pregnancy
Investigating congenital adrenal hyperplasia
The first line tests include U&E, 9am cortisol, BP and physical examination. 2nd line tests include SST with 17OHP, renin & aldosterone, 11DOC, karyotyping, androgen profile, urine steroid profile.
