Diagnosis and Treatment > Signs and Symptoms
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Summary
We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by spironolactone. We also suggest that posaconazole may cause cortisol insufficiency. Patients taking posaconazole should therefore be monitored for hypokalaemia, hypertension and symptoms of hypocortisolaemia, at the onset of treatment and on a monthly basis. Treatment with mineralocorticoid antagonists (spironolactone or eplerenone), supplementation of glucocorticoids (e.g. hydrocortisone) or dose reduction or cessation of posaconazole should all be considered as management strategies.
Learning points:
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Combined hypertension and hypokalaemia are suggestive of mineralocorticoid excess; further investigation is appropriate.
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If serum aldosterone is suppressed, then further investigation to assess for an alternative mineralocorticoid is appropriate, potentially using urine steroid profiling and/or serum steroid panelling.
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Posaconazole can cause both hypokalaemia and hypertension, and we propose that this is due to two mechanisms – both 11β hydroxylase inhibition and 11β HSD2 inhibition.
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Posaconazole treatment may lead to cortisol insufficiency, which may require treatment; however, in this clinical case, the effect was mild.
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First-line treatment of this presentation would likely be use of a mineralocorticoid antagonist.
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Patients taking posaconazole should be monitored for hypertension and hypokalaemia on initiation and monthly thereafter.
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Summary
A 33-year-old male was diagnosed with a metastatic neuroendocrine carcinoma of uncertain primary. He defaulted from follow-up without therapy and some months later developed episodic severe hypoglycaemia, which was found to be associated with inappropriately elevated insulin and C-peptide levels. It was considered likely that the neuroendocrine tumour was the source of the insulin secretion. Diazoxide and somatostatin analogue were used to control hypoglycaemia. Much later in the course of the disease, he developed metabolic derangement, increased skin pigmentation and psychological disturbance, without frankly Cushingoid physical findings. Investigations revealed highly elevated cortisol levels (the levels having previously been normal) with markedly raised ACTH levels, consistent with the co-secretion of ACTH and insulin by the tumour. Treatment with metyrapone improved his psychological state and electrolyte imbalance. Unfortunately, despite several cycles of first-, second- and third-line chemotherapy from the start of the first hormonal presentation onwards, imaging revealed widespread progressive metastatic disease and the patient eventually passed away. This case highlights the importance of keeping in mind the biochemical heterogeneity of endocrine tumours during their treatment.
Learning points
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The clinical presentation of insulin-secreting tumours includes symptoms of neuroglycopaenia and sympathetic overstimulation.
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Tumour-associated hypoglycaemia can be due to pancreatic insulinomas, and although ectopic hormone production occurs in a number of tumours, ectopic secretion of insulin is rare.
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A possible switch in the type of hormone produced can occur during the growth and progression of neuroendocrine tumours and, when treating neuroendocrine tumours, it is important to keep in mind their biochemical heterogeneity.
