Endocrine Causes of Hypokalaemia Flashcards
Bartter’s Syndrome
Bartter’s syndrome
Bartter’s syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn’s, Cushing’s and Liddle’s syndrome which are associated with hypertension).
Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide
Features usually presents in childhood, e.g. Failure to thrive polyuria, polydipsia hypokalaemia normotension weakness
Gitelman’s Syndrome
Gitelman’s syndrome
Gitelman’s syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
Features hypokalaemia hypomagnesaemia hypocalciuria metabolic alkalosis normotension
Gitelman’s syndrome is an autosomal recessive disorder resulting in a normotensive hypokalaemic metabolic alkalosis with hypocalciuria and is often accompanied with hypomagnesaemia. The defect is in the thiazide-sensitive sodium chloride symporter within the distal convoluted tubules, in contrast to Bartter’s syndrome which presents in the same way but with hypercalciuria owing to a defect within the ascending loop of Henle. Patients with both conditions are often asymptomatic or may complain of fatigue, cramps and weakness.
Bartter’s Syndrome - Example Question
A 15-year-old girl was seen in clinic with lethargy, weakness worsening over the past 4 weeks. She also complains of recurrent muscle cramps in her legs, causing her to have trouble sleeping. On further questioning she admits to urinary frequency, passing urine up to ten times a day, and feels dehydrated all the time. She has also previously been diagnosed with cyclical vomiting syndrome and vomits 2-3 times a week.
On examination, she is thin, with a body mass index of 17.5kg/m². Her heart rate is 89 bpm and blood pressure is 103/76 mmHg.
The results of the investigations at the clinic are as follow:
C Reactive protein 3 mg/l Haemoglobin 158 g/l White cell count 7.6 x 10^9/L Na+ 136 mmol/l K+ 2.9 mmol/l Urea 7.2 mmol/l Creatinine 108 µmol/l Corrected calcium 2.42 mmol/l Serum renin levels 8.6 ng/ml/hr Serum aldosterone levels 750 ng/l
Urine chloride levels 90 mmol/l
Urine sodium concentration 88 mmol/l
Urine potassium levels 49 mmol/l
Urine calcium:creatinine ratio 0.3 (high)
Venous blood gas result
pH 7.532
Bicarbonate 37 mmol/l
Which of the following diagnosis would be consistent with the above clinical picture?
Liddle's syndrome Conn's syndrome Familial idiopathic hypercalciuria > Bartter's syndrome Gitelman's syndrome
Patients with hypokalaemia, metabolic alkalosis and a normal - low blood pressure the following differentials should be considered - diuretic abuse, Bartter’s syndrome, Gitelman’s syndrome. Bartter’s syndrome is an autosomal recessive disorder where there is a genetic defect involving the sodium-potassium-chloride transporters in the thick ascending limb of the glomerulus, resulting in an inability to reabsorb chloride and sodium in the loop of Henle, and subsequent distal sodium delivery results in distal tubular sodium and bicarbonate reabsorption with potassium and chloride loss. Serum renin and aldosterone levels are high despite a low or normal blood pressure. Treatment includes NSAIDs, potassium-sparing diuretics, and electrolyte replacement.
The biochemistry profile of Bartter’s syndrome is often indistinguishable from diuretic abuse, and this patient should have a urine diuretic screen.
Gitelman’s syndrome is an autosomal recessive disorder with a genetic defect in the sodium-chloride transporter in the distal tubule and can present with a similar hypokalaemic, alkalotic profile to Bartter’s syndrome. However they are often clinically asymptomatic or have milder symptoms, and they have hypocalciuria and hypomagnesaemia.
Liddle’s syndrome is an autosomal dominant disorder which tends to present with hypertension, hypokalaemia and metabolic alkalosis. Conn’s syndrome or hyperaldosteronism presents with hypertension and hypokalaemia. Patients with familial idiopathic hypercalciuria tend to be asymptomatic
Conn’s Syndrome
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
Features
- hypertension
- hypokalaemia (e.g. muscle weakness)
- alkalosis
Investigations
- high serum aldosterone
- low serum renin
- high-resolution CT abdomen
- adrenal vein sampling
Management
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
Liddle’s Syndrome
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
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.
BARTTERS vs GITELMANS
BOTH = HYPOKALAEMIA + NORMOTENSION
BARTTER'S = HYPERCALCURIA GITELMAN'S = HYPOCALCURIA + HYPOMAGNESAEMIA
Differentials of Hypokalaemia, Metabolic Alkalosis and Normo-Hypotension
Patients with hypokalaemia, metabolic alkalosis and a normal - low blood pressure the following differentials should be considered:
- Diuretic abuse
- Bartter’s syndrome
- Gitelman’s syndrome.
Bartter’s syndrome is an autosomal recessive disorder where there is a genetic defect involving the sodium-potassium-chloride transporters in the thick ascending limb of the glomerulus, resulting in an inability to reabsorb chloride and sodium in the loop of Henle, and subsequent distal sodium delivery results in distal tubular sodium and bicarbonate reabsorption with potassium and chloride loss. Serum renin and aldosterone levels are high despite a low or normal blood pressure. Treatment includes NSAIDs, potassium-sparing diuretics, and electrolyte replacement.
The biochemistry profile of Bartter’s syndrome is often indistinguishable from diuretic abuse, and this patient should have a urine diuretic screen.
