A previously well 67-year-old man was diagnosed with myelodysplastic syndrome in 2014 (refractory cytopaenia with multilineage dysplasia - RCMD). He was treated with chemotherapy (daunorubicin and cytarabine), which was complicated by a fungal chest infection. Antifungal therapy, initially intravenous ambisome and caspofungin, was given. Subsequently, he was started on prophylactic posaconazole 200 mg TDS. His serum potassium decreased at this point, but this was attributed to gastrointestinal losses from diarrhoea and was not further investigated. He was normotensive at this time with systolic blood pressure in the range of 120-130 mmHg.
During 2015, he had a second cycle of chemotherapy and a subsequent stem cell transplant, complicated by reactivation of TB (bone marrow and mediastinal glands), which was treated with quadruple anti-tuberculosis therapy. Posaconazole was briefly interrupted twice during this year: for intravenous antifungal treatment (ambisome/caspofungin) and during the stem cell transplant. Prophylactic posaconazole was stopped completely at the end of 2015, as he was in remission. Serum potassium normalised.
Over the following 12 months (2016), while not taking posaconazole, potassium remained within the normal range and the patient continued to be normotensive.
In January 2017, there was a relapse of myelodysplastic syndrome, treated with chemotherapy (Azacitidine), and posaconazole 300 mg OD was recommenced. Posaconazole was interrupted for an admission with neutropenic sepsis and decompensated heart failure but then restarted on discharge in February 2017. At this point, he was also taking ramipril and bisoprolol, commenced for heart failure.
Hypokalaemia (2.7-2.9 mmol/L) was noted shortly after this and his doses of antihypertensive medication were increased to control elevated blood pressure (systolic blood pressure 150-170 mmHg). There had been no previous history of hypertension. Hypokalaemia was managed with oral and intermittent intravenous potassium replacement, but despite these measures, he required admission for symptomatic hypokalaemia (2.4 mmol/L). No other sources of potassium loss were identified on clinical history; he was not on any medications causing potassium loss at this time, had no diarrhoea or vomiting and had a normal dietary intake of potassium.
He was at this point referred to the endocrine team. On clinical assessment, he was hypertensive but had no symptoms or clinical features of Cushing's or other endocrinopathy. Investigations were undertaken to assess for suspected mineralocorticoid hypertension and hypokalaemia.
Laboratory results confirmed persistent hypokalaemia (2.7-2.9 mmol/L) with an alkalosis (pH 7.52 bicarbonate 32 mmol/L). Other serum electrolytes were normal apart from mild hypomagnesaemia. Renal function was normal. Urinary potassium was very high (59 mmol/L).
Plasma renin levels (Diasorin Liaison XL immunoassay) were undetectable (<0.5 U/L) and serum aldosterone was also very low (32 pmol/L) (normal >140 pmol/L). Cortisol (Siemens Centaur XPi immunoassay) at 09:00 h was 269 nmol/L and a short synacthen test (250 microg) demonstrated inadequate cortisol response (baseline: 384 nmol/L, 30 min: 430 nmol/L, 60 min: 446 nmol/L). ACTH was 118 ng/L (normal: 10-50). An overnight 1 mg dexamethasone test showed full cortisol suppression (<30 nmol/L).
A serum steroid profile by LC-MS/MS showed (nmol/L, (normal range)) markedly elevated 11-deoxycorticosterone (DOC): 12.5 (<1.4) and 11-deoxycortisol: 63.1 (<2.7). The serum cortisol (227)-to-cortisone (14.8) ratio was raised at 15.3 (1.0-10.5). Androstenedione was slightly elevated at 9.1 nmol/L (<7.0).
A urinary steroid profile also demonstrated marked relative increases of metabolites of DOC and 11-deoxycortisol, with lesser increases of metabolites of 17-hydroxyprogesterone. 11-Hydroxylated androgen metabolites were at very low levels relative to cortisol metabolites. The ratio of cortisol/cortisone metabolites was normal. These findings mimic genetic 11beta-hydroxylase deficiency and also use of the specific 11beta-hydroxylase inhibitor, metyrapone.
Axial imaging to evaluate progression of his haematological malignancy noted bilateral hyperplastic adrenal glands. There were no radiological features of adrenal TB.