Hyperaldosteronism (inc Conn's) Flashcards
Primary Hyperaldosteronism
Primary hyperaldosteronism was previously thought to be most commonly caused by an adrenal adenoma, termed Conn’s syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases. Differentiating between the two is important as this determines treatment. Adrenal carcinoma is an extremely rare cause of primary hyperaldosteronism
Primary Hyperaldosteronism - Features
Features
- hypertension
- hypokalaemia (e.g. muscle weakness)
- alkalosis
- polyuria and polydipsia can result from the kidneys inability to concentrate urine.
Primary Hyperaldosteronism - Ix
Investigations
- high serum aldosterone
- low serum renin
- high-resolution CT abdomen
- adrenal vein sampling
Primary Hyperaldosteronism - Mx
Management
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
NB: Treatment of adrenal adenoma involves removal of the aldosterone secreting tumour. However, those pursuing adrenalectomy must undergo adrenal vein sampling first. CT imaging alone is not diagnostic of the symptomatic side responsible for aldosterone secretion.
Conn’s syndrome - Diagnosis: Example Question
A 28-year-old woman is referred by her GP with refractory hypertension. Despite combination therapy with ramipril, amlodipine, bendroflumethiazide and atenolol, her blood pressure in clinic today is 181/105 mmHg. Some of her bloods are shown below. On direct questioning she also admits passing urine more than 10 times per day. What is the most likely diagnosis?
Na+ 145 mmol/l
K+ 3.0 mmol/l
Urea 6.0 mmol/l
Creatinine 71 µmol/l
What is the most likely diagnosis?
Phaeochromocytoma Coarctation of the aorta Renal artery stenosis 21-hydroxylase deficiency Conn's syndrome
All of the answers above are causes of secondary hypertension, except for 21-hydroxylase deficiency which accounts for over 90% of congenital adrenal hyperplasia.
The high sodium and low potassium in the bloods reflects the increased levels of aldosterone produced in Conn’s syndrome. Aldosterone stimulates the Na+/K+-ATPase membrane transporter in the distal convoluted tubule resulting in increased sodium reabsorption and potassium excretion. Polyuria and polydipsia can result from the kidneys inability to concentrate urine.
The diagnosis is usually confirmed using plasma aldosterone:renin ratio
Primary Hyperaldosteronism: Mx - Example Question
45 year old female presents with a 2 year history of headache and visual blurring. When initially presenting to her GP 2 years ago, her blood pressure was found to be 235/160mmHg. Subsequently, despite maximal doses of four anti-hypertensives, including 50mg spironolactone, her blood pressure remains poorly controlled. Her latest blood tests demonstrate the following:
Na+ 140 mmol/l K+ 2.9 mmol/l Urea 5.8 mmol/l Creatinine 78 µmol/l CRP 2 mg/l
Serum ambulatory renin activity 0.34 pmol/L @ 3-4 hours (normal range 0.8-3.5 pmol/ml/hr)
Serum ambulatory aldosterone 2052 pmol/L@ 3-4 hours (normal range 100-800)
A CT adrenal reveal a right adrenal mass of 2.5cm diameter. The patient is keen to take away the underlying problem. What is the most appropriate next management step?
Add amiloride Add eplenerone Increase spirnolactone to 100mg OD > Adrenal vein sampling Right adrenalectomy
The patient presents with poorly controlled hypertension, is hypokalaemic, hypertensive, metabolically alkalotic, has increased aldosterone and reduced renin. The underlying diagnosis is Conns disease. The treatment involves removal of the aldosterone secreting tumour. However, those pursuing adrenalectomy must undergo adrenal vein sampling first, CT imaging alone is not diagnostic of the symptomatic side responsible for aldosterone secretion.
Hypertension - Secondary Causes
Hypertension: secondary causes
It is thought that between 5-10% of patients diagnosed with hypertension have primary hyperaldosteronism, including Conn’s syndrome. This makes it the single most common cause of secondary hypertension.
Renal disease accounts for a large percentage of the other cases of secondary hypertension. Conditions which may increase the blood pressure include: glomerulonephritis pyelonephritis adult polycystic kidney disease renal artery stenosis
Endocrine disorders (other than primary hyperaldosteronism) may also result in increased blood pressure:
phaeochromocytoma
Cushing’s syndrome
Liddle’s syndrome
congenital adrenal hyperplasia (11-beta hydroxylase deficiency)
acromegaly
Other causes include: NSAIDs pregnancy coarctation of the aorta the combined oral contraceptive pill steroids MAOI
Secondary Causes of HTN - Example Question
A 57-year-old man with a 2 year history of hypertension is referred for further evaluation due to his blood pressure being difficult to control. The following results were obtained prior to commencing medications:
Na+ 148 mmol/l K+ 3.2 mmol/l Creatinine 130 µmol/l Renin 102 (7-50 IU/mL ambulatory) Aldosterone 1105 (N: 80-800 ng/dL ambulatory) Renin:Aldosterone Ratio 10.8 (< 500) Plasma Metanephrines 0.35 (<0.50 nmol/L)
These results are most consistent with which of the following:
Congenital Adrenal Hyperplasia Phaeochromocytoma Cushing's disease > Renovascular disease Primary hyperaldosteronism
The key underlying diagnosis is renal artery stenosis. The key is that the renin-aldosterone ratio is normal. If it was Conn’s disease, or primary hyperaldosteronism the renin would be suppressed. The plasma metanephrines indicate that no pheochromocytoma is present as the sensitivity of plasma metanephrines for a pheochromocytoma approaches 100%
Liddle’s Syndrome - Example Question
A 16 year old male presents with 3 months of chronic headache and visual blurring. He has no past medical history and no known family history. On examination, his heart sounds are normal with no added sounds, respiratory examination is unremarkable. He has no focal neurological signs. Fundoscopy reveals papilloedema, hard exudates and flame haemorrhage. His blood pressure is 226/160mmHg. His blood tests and arterial blood gas are as follows:
Na+ 145 mmol/l
K+ 2.9 mmol/l
Urea 5.4 mmol/l
Creatinine 72 µmol/l
pH 7.49
PaO2 13kPa
PaCO2 3.4 kPa
Bicarbonate 34 mmol/L
Serum ambulatory renin activity 0.2 pmol/L @ 3-4 hours (normal range 0.8-3.5 pmol/ml/hr)
Serum ambulatory aldosterone 24 pmol/L@ 3-4 hours (normal range 100-800)
What is the optimal long-term treatment?
Amlodipine Ramipril Atenolol Doxazosin > Amiloride
The patient is young and presents with grade 4 hypertensive retinopathic changes associated with a systolic of over 200mmHg, associated with hypopkaelamia and a metabolic alkalosis. Importantly, both renin and aldosterone are decreased, ruling out primary hyperaldosteronism. The diagnosis is thus likely to be Liddles syndrome, a genetic disorder of ENaC channels in the collecting duct, leading to increased sodium reabsorption and increased potassium excretion. The treatment is with amiloride, a potassium sparing diuretic that directly blocks collecting tubule sodium channels and resolves hypertension.
Conn’s Syndrome - Example Question
A 38-year-old man is referred to the pharmacology clinic for review. He is currently managed for hypertension with three anti-hypertensive agents, (ramipril, amlodipine and indapamide). His GP is concerned as he has still not achieved blood pressure target. On examination his blood pressure is 155/95 mmHg, pulse is 78 beats per minute and regular. There are no heart murmurs or bruits. Abdomen is soft and non tender with no masses and his body mass index is 24 kg/m².
Investigations:
Na+ 142 mmol/l K+ 3.1 mmol/l HCO3- 30 mmol/l Urea 7.0 mmol/l Creatinine 90 µmol/l
Which of the following is the most likely diagnosis?
Bartter's syndrome > Conn's syndrome Cushing's syndrome Licorice overdose Renal artery stenosis
This patient has resistant hypertension in the presence of hypokalaemia and high bicarbonate, despite initiation of three different anti-hypertensive medications. Although the lack of symptoms or signs of cardiovascular disease doesn’t rule out renal artery stenosis completely, it makes it less likely versus Conn’s or licorice overdose as a cause of hypertension with hypokalaemia. Licorice overdose is made less likely by the fact that most licorice sold in shops in the UK now has glycyrrhizic acid removed, and this is the active agent which leads to hypokalaemia and hypertension. Conn’s is the single most common cause of secondary hypertension, making up between 5 and 10% of cases of hypertension overall.
Bartter’s syndrome leads to hypokalaemia with hypotension and is therefore not an appropriate answer here.
Adrenal Hyperplasia - Example Question
You are seeing a 58-year-old man in clinic who has been referred by his GP with resistant hypertension despite treatment with ramipril, amlodipine, indapamide and bisoprolol. He looks comfortable at rest.
Observations are as follows: temperature 36.5ºC, blood pressure 182/125 mmHg, heart rate 88/min, respiratory rate 16/min, saturations 97% on air
Investigations are as follows:
Na+ 148 mmol/l
K+ 2.9 mmol/l
Urea 6.5 mmol/l
Creatinine 92 µmol/l
Renin Low
Aldosterone (supine) High
Aldosterone (prolonged standing) Increase from supine levels
Blood gases:
PaO2 11.2kPa PaCO2 5.2kPa pH 7.49 HC03- 32 mmol/l BE +4
What is the single most likely diagnosis?
> Adrenal hyperplasia Conn's adenoma Malignant hypertension Phaeochromocytoma Renal artery stenosis
All of the above diagnoses could cause hypertension. This patient has a hypokalaemic alkalosis and low renin. The differentials are therefore Conn’s adenoma and adrenal hyperplasia. To differentiate between the two look at the aldosterone on standing. In this case, the aldosterone increases on prolonged standing, therefore, the diagnosis is adrenal hyperplasia. In Conn’s adenoma, the aldosterone would stay the same or drop on standing.
In malignant hypertension and renal artery stenosis, the renin would be high.
AME - Apparent Mineralocorticoid Excess
= autosomal mutation of 11-hydroxysteroid dehydrogenase type 2 (usually autosomal recessive)
- Can result in findings similar to PRIMARY HYPERALDOSTERONISM:
- HTN
- Hypokalaemia
- Metabolic alkalosis
- Low plasma renin activity
However actually plasma aldosterone levels are LOW in these disorders, not elevated
- Excess liquorice ingestion can result in similar (chronic) findings due to inhibitor of 11-hydroxysteroid dehydrogenase type 2
Differentiating between Conn’s Adenoma and Adrenal Hyperplasia (without CT)
Conn’s adenoma vs adrenal hyperplasia.
To differentiate between the two look at the aldosterone on standing.
If aldosterone increases on prolonged standing the diagnosis is adrenal hyperplasia.
In Conn’s adenoma, the aldosterone would stay the same or drop on standing.
Hypokalaemia + HTN
For exams it is useful to be able to classify the causes of hypokalaemia in to those associated with hypertension, and those which are not
Hypokalaemia with hypertension
Cushing’s syndrome (Low Renin, High Aldosterone)
Conn’s syndrome (Low Renin, High Aldosterone)
Liddle’s syndrome (Low Renin, Low Aldosterone)
11-beta hydroxylase deficiency*
Renal artery stenosis (High Renin, High Aldosterone)
Ix to differentiate = Plasma Renin and Aldosterone
Carbenoxolone, an anti-ulcer drug, and liquorice excess can potentially cause hypokalaemia associated with hypertension
*21-hydroxylase deficiency, which accounts for 90% of congenital adrenal hyperplasia cases, is not associated with hypertension
Liddle’s Syndrome
Liddle’s syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.
Treatment is with either amiloride or triamterene
Example Question:
A 32 year-old man is referred by his GP after collapsing while at work. He does not remember the episode but witnesses say that there was no incontinence or fitting and the patient does not have a sore mouth or tongue. This is the first time this has happened and the patient does not have any other past medical history of note and takes no regular medication.
Examination reveals a blood pressure of 162/95 mmHg, a pulse of 74 beats per minute, a respiratory rate of 16 and a temperature of 37.4ºC. Heart sounds 1 and 2 are present with no added sounds, the lung fields are clear and his abdomen is soft and non-tender.
Blood tests performed and reveal:
Na+ 143 mmol/l K+ 3.0 mmol/l Urea 5.6 mmol/l Creatinine 76 µmol/l Bicarbonate 31 mmol/l Renin low Aldosterone low
Which of the following is the best treatment?
> Amiloride Bumetanide Spironolactone ACE inhibitor Angiotensin II receptor blocker
This man has Liddle’s syndrome, an autosomal dominant disorder characterised by hypertension associated with hypokalaemic metabolic alkalosis, low plasma renin activity, and suppressed aldosterone secretion. Amiloride is the best treatment for the hypertension and hypokalaemia as it acts on the sodium channels directly, as opposed to spironolactone, which acts on mineralocorticoid receptors
