Case details
A 76-year-old man was referred to Endocrinology Clinic with a 25-year history of treatment-refractory hypertension and suspected primary aldosteronism. Notably, he had a history of thiazide diuretic induced hypokalaemia and suboptimal blood pressure control despite four anti-hypertensive medications including olmesartan, atenolol, prazosin and moxonidine. To investigate for primary aldosteronism, these medications were switched to prazosin, verapamil and moxonidine to reduce interference with aldosterone and renin measurements. A seated saline suppression test confirmed the diagnosis of primary aldosteronism, with a baseline plasma aldosterone concentration of 533 pmol/L (100-950 pmol/L erect), direct renin concentration of 1.1 mU/L (3.3 – 4.1 mU/L erect) and aldosterone renin ratio of 490 (<70), and plasma aldosterone concentration of 290 pmol/L 4 hours following the administration of 2L 0.9% sodium chloride solution (normal response <170 pmol/L). A dedicated adrenal CT scan demonstrated a left adrenal adenoma measuring 12 x 7 mm with absolute contrast washout of 83.6% while the right adrenal gland was normal in size, shape and enhancement characteristics with no discrete lesion. However, adrenal vein sampling demonstrated right sided lateralisation (bilateral simultaneous adrenal vein sampling, pre-ACTH infusion: right adrenal vein aldosterone cortisol ratio to left adrenal vein aldosterone cortisol ratio 47.9; both adrenal veins were successfully cannulated with left and right adrenal vein to peripheral cortisol ratio >2). Laparoscopic right adrenalectomy was performed 8 weeks later with histology consistent with a benign adrenocortical adenoma. A mineralocorticoid receptor antagonist was not introduced prior to surgery. On day 1 post-adrenalectomy, the patient’s serum sodium was 133 mmol/L (135 - 145 mmol/L), serum potassium 3.8 mmol/L (3.5 – 5.5 mmol/L) and blood pressure up to 170/90 mmHg. All anti-hypertensive medications were ceased with a plan to reintroduce if required.
The Endocrine Surgery team reviewed the patient 1 week post-operatively, noting ambulatory systolic blood pressure measurements up to 150 mmHg on moxonidine, which was changed to verapamil but no electrolyte monitoring was performed. The Endocrinology team reviewed the patient 12 weeks post-operatively, with a recorded blood pressure of 136/76 mmHg on verapamil modified release 240mg daily. Assessment of serum electrolytes at this time revealed severe hyponatraemia (Na 124 mmol/L) and mild hyperkalaemia (5.7 mmol/L). Due to initial concern of glucocorticoid and mineralocorticoid deficiency, hydrocortisone 10mg twice daily and fludrocortisone 50microg daily were commenced whilst other investigations were arranged. Subsequent investigation was consistent with isolated mineralocorticoid deficiency with low plasma aldosterone (74 pmol/L), minimally stimulated renin (27 mU/L) and a normal cortisol response to ACTH (peak cortisol 667 nmol/L at 60 minutes following administration of ACTH). Hydrocortisone was ceased and fludrocortisone 50 microg daily was continued with subsequent normalisation of serum sodium (139 mmol/L) and .
Discussion
Primary aldosteronism refers to a spectrum of conditions characterised by inappropriately high aldosterone production and suppressed renin, and can result in clinically significant hypertension, hypokalaemia, renal impairment and an increased risk of atrial fibrillation, stroke and myocardial infarction. (1) While primary aldosteronism may affect over 10% the hypertensive population, only a minority of eligible patients are screened in the primary care setting contributing to underdiagnosis and undertreatment. (1)
The diagnostic algorithm for primary aldosteronism involves screening, confirmatory testing and localisation studies to distinguish unilateral pathology which may be amenable to adrenalectomy from bilateral adrenal hyperplasia. Current Endocrine Society guidelines recommend dedicated adrenal imaging for all cases of primary aldosteronism and adrenal vein sampling in most cases to assist with localisation prior to surgery. (1) This is due to the high prevalence of non-functioning adrenal adenomas and poor correlation between CT finding and adrenal vein sampling: a review of 950 patients who underwent CT/MRI and adrenal vein sampling showed that CT/MRI accurately predicted unilateral or bilateral disease in only 62.2% of cases. (2)
Post-operative hyperkalaemia is an uncommon and usually transient phenomenon following adrenalectomy for primary aldosteronism, attributed to suppression of renin and therefore reduced aldosterone production from the contralateral adrenal gland. (3) Previously identified risk factors include age >50 years, duration of hypertension >10 years, pre-existing renal impairment, adrenal adenoma size >2cm (3, 4) and a contralateral suppression index <0.47 (calculated by dividing the aldosterone cortisol ratio of the non-dominant vein by the external iliac vein). (5)
The use of pre-operative mineralocorticoid receptor antagonists to stimulate renin activity has been suggested to decrease the risk of hypoaldosteronism post-adrenalectomy. While some studies have not demonstrated a benefit using this approach, this may be due to failure to achieve non-suppressed renin in patients prior to surgery. (3, 4) Post-operative hypoaldosteronism is conventionally managed with fludrocortisone. In the presence of relative contraindications to mineralocorticoid replacement such as significant heart failure or hypertension, alternatives such as furosemide, sodium bicarbonate or potassium binders may be considered as part of individualised therapy to manage hyperkalaemia.
Our case provides a pertinent example of primary aldosteronism due to a unilateral aldosterone-producing adenoma with discordant CT and adrenal vein sampling findings in an elderly man. Adrenalectomy cured primary aldosteronism and significantly improved hypertension, but was complicated by the delayed recognition of significant hyponatraemia and hyperkalaemia due to suppressed aldosterone production from the contralateral gland, which required fludrocortisone supplementation. Clinicians should be aware of the risk of post-operative hypoaldosteronism and hyperkalaemia following adrenalectomy and routinely measure electrolytes within the first 1 – 2 weeks post-adrenalectomy. Pre-operative mineralocorticoid antagonist therapy can improve control of blood pressure and hypokalaemia and may reduce the risk of hypoaldosteronism post-adrenalectomy if stimulation of renin is adequately achieved.
Table 1: Summary of key pre- and post-operative investigations
|
Test |
3/10/19 |
15/10/19 |
11/3/20 |
4/6/20 |
9/6/20 |
18/6/20 |
Reference range |
|
Sodium Potassium Urea Creatinine eGFR |
3.8
|
140 4.3 6.9 75 85 |
133 3.8 8.0 76 85 |
124 5.7 9.1 90 71 |
135 5.4 10.3 106 59 |
139 4.9 7.3 80 83 |
135 – 145 mmol/L 3.5 – 5.5 mmol/L 3.5 – 9.5 mmol/L 60 – 115 µmol/L >60 mL/min/1.73m2 |
|
Aldosterone Renin ARR |
533 1.1 490 |
|
|
|
74 27 3 |
<50 5.0 <10 |
100 -950 pmol/L erect 3.3 – 4.1 mU/L erect <70 |
|
Comments: 3/10/19 11/3/20 4/6/20 9/6/20
16/6/20 23/6/20 |
Saline suppression test Day 1 post- right adrenalectomy Hyponatraemia and hyperkalaemia detected, 12 weeks post adrenalectomy Endocrine review: hydrocortisone 10mg twice daily and fludrocortisone 0.5mg daily commenced ACTH stimulation test demonstrated normal cortisol response (662 nmol/L at 60 minutes). Endocrine review: hydrocortisone ceased, fludrocortisone continued |
Key messages
1. Adrenal vein sampling is an important investigation for the lateralisation of aldosterone excess, as the findings of adrenal imaging may be discordant
2. Clinically significant hyperkalaemia due to hypoaldosteronism may occur post-adrenalectomy for primary aldosteronism. Routine electrolyte monitoring is recommended for at least 1-2 weeks. While typically transient, there are cases of persistent hypoaldosteronism requiring ongoing mineralocorticoid replacement.
3. Risk factors include age >50 years, duration of hypertension >10 years, pre-existing renal impairment and adrenal adenoma size >2cm
4. Pre-operative use of a mineralocorticoid receptor antagonist to achieve non-suppressed renin may reduce the risk of post-operative hypoaldosteronism
References