Endocrine - Hyperaldosteronism and SIADH

Question 1

In the afferent arteriole in the kidney there are special cells that sense blood pressure, what are they called? What do they release in response to low blood pressure?

Answer 1

Juxtaglomerular cells

Renin

Question 2

How does renin result in the release of aldosterone?

Answer 2

The liver secretes a protein called angiotensinogen. Renin acts to convert angiotensinogen to angiotensin I. Angiotensin I converts to angiotensin II in the lungswith the help of angiotensin converting enzyme (ACE). Angiotensin II stimulates the release of aldosterone from the adrenal glands.

Question 3

Aldosterone is a mineralocorticoid steroid hormone. It acts on the kidney to:

Answer 3

• Increase sodium reabsorption from the distal tubule
• Increase potassium secretion from the distal tubule
• Increase hydrogen secretion from the collecting ducts

Question 4

What is primary hyperaldosteronism and what are its causes?

Answer 4

Primary hyperaldosteronism is when the adrenal glands are directly responsible for producing too much aldosterone. Serum renin will be low as it is suppressed by the high blood pressure.

There are several possible reasons for this:

• An adrenal adenoma secreting aldosterone (most common)
• Bilateral adrenal hyperplasia
• Familial hyperaldosteronism type 1 and type 2 (rare)
• Adrenal carcinoma (rare)

Question 5

What is secondary hyperaldosteonism?

Answer 5

Secondary hyperaldosteronism is where excessive renin stimulates the adrenal glands to produce more aldosterone. Serum renin will be high.

Question 6

What are the causes of high renin levels in secondary hyperaldosteronism?

Answer 6

There are several causes of high renin levels and they occur when the blood pressure in the kidneys is disproportionately lower than the blood pressure in the rest of the body:

• Renal artery stenosis
• Renal artery obstruction
• Heart failure

Question 7

What is renal artery stenosis and how would you confirm that it is present?

Answer 7

Renal artery stenosis is a narrowing of the artery supplying the kidney. This is usually found in patients with atherosclerosis. This can be confirmed with a doppler ultrasound, CT angiogram or magnetic resonance angiography (MRA).

Question 8

Investigations if you suspect someone has hyperaldosteronism

Answer 8

• Check the renin and aldosterone levels and calculate a renin / aldosterone ratio:
  
  • High aldosterone and low renin indicates primary hyperaldosteronism
  • High aldosterone and high renin indicates secondary hyperaldosteronism
• Other investigations relating to the effects of aldosterone:
  
  • Blood pressure (hypertension)
  • Serum electrolytes (hypokalaemia)
  • Blood gas analysis (alkalosis)
• If a high aldosterone level is found then 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

Question 9

Management of hyperaldosteronism

Answer 9

• Aldosterone antagonists
  
  • Eplerenone
  • Spironolactone
• Treat the underlying cause
  
  • Surgical removal of adenoma
  • Percutaneous renal artery angioplasty via the femoral artery to treat in renal artery stenosis

Question 10

Where is anti-diuretic hormone produced and what other name is it known by?

Answer 10

Anti-diurectic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland. It is also known as “vasopressin”.

Question 11

What is the function of ADH?

Answer 11

The main action of ADH in the kidney is to regulate the volume and osmolarity of the urine. ADH stimulates water reabsorption from the distal convoluted tubule and collecting ducts.

Question 12

Pathophysiology of syndrome of inappropriate anti-diuretic hormone (SIADH)

Answer 12

The excessive ADH results in excessive water reabsorption in the collecting ducts. This water dilutes the sodium in the blood so you end up with a low sodium concentration (hyponatraemia).

The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”. The urine becomes more concentrated as less water is excreted by the kidneys therefore patients with SIADH have a “high urine osmolality” and “high urine sodium”.

Question 13

Symptoms of SIADH

Answer 13

• Headache
• Fatigue
• Muscle aches and cramps
• Confusion
• Severe hyponatraemia can cause seizures and reduced consciousness

Question 14

Name some causes of SIADH

Answer 14

• Post-operative from major surgery
• Infection, particularly atypical pneumonia and lung abscesses
• Head injury
• Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,)
• Malignancy, particularly small cell lung cancer
• Meningitis

Question 15

How is SIADH diagnosed?

Answer 15

• Clinical examination will show euvolaemia
• U+Es will show a hyponatraemia
• Urine sodium and osmolality will be high.
• Other causes of hyponatraemia need to be excluded

Question 16

For a SIADH diagnosis what are the other causes that need to be excluded?

Answer 16

• Negative short synacthen test to exclude adrenal insufficiency
• No history of diuretic use
• No diarrhoea, vomiting, burns, fistula or excessive sweating
• No excessive water intake
• No chronic kidney disease or acute kidney injury

Question 17

How would you establish the cause of SIADH?

Answer 17

• Sometimes the cause will be obvious for example a chest infection or a recent major surgery - treat the underlying cause and assess whether the hyponatraemia resolves
• Perform a chest xray as a first line investigation for pneumonia, lung abscess and lung cancer
• We have to suspect malignancy in someone with persistent hyponatraemia with no clear cause
  
  • CT thorax/abodmen/pelvis and MRI brain to find the malignancy

Question 18

Why is it essential to correct sodium slowly? What rate of change should you aim for?

Answer 18

It is essential correct the sodium slowly to prevent central pontine myelinolysis.

Aim for a change in sodium of less than 10 mmol/l per 24 hours.

Question 19

How would you manage SIADH?

Answer 19

• Establish and treat the cause
• Fluid restriction involves restricting their fluid intake to 500mls – 1litre. This may be enough to correct the hyponatraemia without the need for medications
• Tolvaptan. “Vaptans” are ADH receptor blockers. They are very powerful and can cause a rapid increase in sodium. Therefore they are usually initiated by a specialist endocrinologist and require close monitoring, for example 6 hourly sodium levels.