Hyperaldosteronism, CAH, Phaeochromocytoma Flashcards
a) where are juxtaglomerular cells found and what do these do?
b) where is angiotensinogen secreted from?
c) where is AT I converted into AT II?
a) afferent arteriole, sense low BP
b) the liver
c) the lungs
What type of hormone is aldosterone?
From where is it secreted
mineralocorticoid - secreted from the zona glomerulosa of the adrenal gland
List 3 actions of aldosterone
- ↑ Na+ reabsorption from DCT
- ↑ K+ secretion from DCT
- ↑ H+ secretion from CD
What is Primary Hyperaldosteronism?
When the adrenal glands are directly responsible for producing too much aldosterone
How does hyperaldosteronism present?
- Hypertension
- Hypokalaemia → muscle weakness
- Alkalosis
- Polyuria and polydipsia
List the two most common causes of Primary hyperaldosteronism
- Bilateral adrenal hyperplasia
- Adrenal adenoma → Conn’s syndrome
What classic triad should make you suspect possible Conns syndrome?
- Hypertension
- Hypokalaemia
- Alkalosis
What is Secondary Hyperaldosteronism?
Where excessive renin stimulating the adrenal glands to produce more aldosterone
List 3 causes of secondary hyperaldosteronism
Highlight the most common
- Renal artery stenosis
- Renal artery obstruction
- Heart failure
Compare levels of renin in primary vs secondary hyperaldosteronism
1o Serum renin is low as it is suppressed by the high BP
2o Serum renin is high
What is Renal artery stenosis
In which patients is it more commonly found and how it it diagnosed?
How does it lead to hyperaldosteronism?
Narrowing of the artery supplying the kidney
Usually found in patients with atherosclerosis, can be confirmed with a doppler ultrasound, CT angiogram or MRA
What is the first-line investigation in suspected primary hyperaldosteronism?
What would results indicate
Plasma aldosterone / renin ratio
- ↑ aldosterone, ↓ renin = primary hyperaldosteronism
- ↑ aldosterone, ↑ renin = secondary hyperaldosteronism
If high aldosterone is found on first line investigation what is the next step?
Investigate for the cause:
- CT / MRI to look for an adrenal tumour
- Renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis or obstruction
What is the gold standard for localising the cause of primary hyperaldosteronism?
Selective adrenal venous sampling
To distinguish between unilateral adenoma and bilateral hyperplasia
List 3 other investigations which may aid diagnosis of hyperaldosteronism
- Blood pressure (hypertension)
- Serum electrolytes (hypokalaemia)
- Blood gas analysis (alkalosis)
Management of Hyperaldosteronism
Bilateral adrenocortical hyperplasia → aldosterone antagonists ie. Spironolactone (nonselective), Eplerenone (selective)
Adrenal adenoma → surgical adrenalectomy
Renal artery stenosis → Percutaneous renal artery angioplasty via femoral artery
☆ Hyperaldosteronism is the most common cause of what?
Secondary Hypertension
If you have a patient with ↑BP that is not responding to treatment consider screening for hyperaldosteronism with a renin:aldosterone ratio
What is Congenital adrenal hyperplasia?
Autosomal recessive condition caused by a congenital deficiency in enzymes required for adrenal steroid biosynthesis
Causes underproduction of cortisol and aldosterone and overproduction of androgens from birth
Which enzymes may be affected in CAH?
Highlight the most common
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
17-hydroxylase deficiency (very rare)
Pathophysiology of Congenital Adrenal Hyperplasia?
21-hydroxylase converts progesterone to aldosterone and cortisol
Progesterone is also used to create testosterone, but this doesn’t rely on 21-hydroxylase
In CAH, the defect in the enzyme means there is extra progesterone that is not converted to aldosterone or cortisol, and instead is converted to testosterone
When and how does CAH present in non-classic (mild) form?
Incl both male and female
During childhood or after puberty. Sx related to ↑ androgens
Females:
- Tall for their age
- Deep voice
- Early puberty
- Facial hair
- Absent periods
Male patients:
- Tall for their age
- Deep voice
- Early puberty
- Large penis
- Small testicles
When and how does CAH present in classic (severe) form?
Females present at birth with: virilised genitalia “ambiguous genitalia” and an enlarged clitoris
Males present with little signs at birth except, salt-losing form presents at 7-14 days with:
- hyponatraemia, hyperkalaemia (arrhythmias), hypoglycaemia
- poor feeding, vomiting and dehydration
What other feature on appearance tends to occur in CAH
Skin hyperpigmentation
Anterior pituitary responds to ↓cortisol by ↑ACTH. Byproduct of ACTH is melanocyte simulating hormone which (+) melanin within skin cells
Management of CAH
Hydrocortisone → cortisol replacement
Fludrocortisone → aldosterone replacement
Female patients with “virilised” genitals may require corrective surgery
Which organ and specific cell type produce adrenaline
Adrenaline produced by the “chromaffin cells” in the adrenal medulla of the adrenal glands
What is a Phaeochromocytoma?
Tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline
What is adrenaline and what is its function
Adrenaline is a “catecholamine” hormone and NT that stimulates the SNS and is responsible for the “fight or flight” response
What gene may be assocuated with Phaeochromocytoma?
25% are familial - a/w multiple endocrine neoplasia type 2 (MEN 2)
What is the 10% rule ofP haeochromocytomas?
- 10% bilateral
- 10% cancerous
- 10% outside the adrenal gland
How is Phaeochromocytoma diagnosed?
- 24 hour urine catecholamines
- Plasma free metanephrines
Why do we not measure adrenaline for diagnosis of Phaeochromocytoma
Adrenaline has a short half life of only a few minutes in the blood
Metanephrines (breakdown product of adrenaline) have a longer half life
Hense metanephrines are less prone to dramatic fluctuations and a more reliable diagnostic tool
How does Phaeochromocytoma present?
Signs and symptoms fluctuate relating to periods when tumour is secreting adrenaline
- Anxiety
- Sweating
- Headache
- Hypertension
- Palpitations, tachycardia and paroxysmal atrial fibrillation
Management of Phaeochromocytoma?
- Alpha blockers (i.e. phenoxybenzamine)
- Beta blockers once established on alpha blockers
- Adrenalectomy to remove tumour is the definitive management
