E-Poster Presentation ESA-SRB-ANZBMS 2021

Refractory hypokalaemia - An unusual case of a metastatic neuroendocrine tumour (#410)

James McNeil 1 , Gabrielle Cehic 2 3 , Liesl Altus 2 , Peak Mann Mah 1 4
  1. Endocrinology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
  2. Nuclear Medicine, Queen Elizabeth Hospital, Adelaide, South Australia, Australia
  3. University of South Australia, Adelaide, South Australia, Australia
  4. University of Adelaide, Adelaide, South Australia, Australia

A 67-year-old man presented with asymptomatic unexplained hypokalaemia on a background of metastatic ileal neuroendocrine tumour (mNET). It was diagnosed in 2004 and treated with long-acting somatostatin analogue (SSA) and surgical resection. Structural imaging in 2014, performed for increased flushing, found enlargement of hepatic metastatic lesions. Given disease progression, peptide receptor radionucleotide therapy (PRRT) with 177Lutetium Octreotate (LuTate) was commenced with disease control for 6 years.

Routine biochemistry showed unexplained hypokalaemia with metabolic alkalosis. Investigation results were consistent with Ectopic ACTH Cushing’s syndrome (Table 1). Pituitary magnetic imaging did not show an adenoma. Biopsy of omental metastasis remained as. a well-differentiated grade 1 NET with immunohistochemistry negative for ACTH. He was urgently treated with Lutate, Metrypone and ketoconazole.

611f720cb2562-Table+1.png

Despite improvement in 24hr Urinary-Free-Cortisol with steroidogenesis inhibitors, he had rapid clinical deterioration. Bilateral adrenalectomy was considered high risk, but deemed urgent and occurred within 2 weeks without immediate complication. Histology showed hyperplasia of the zona glomerulosa consistent with chronic hyperstimulation with ACTH.

Cushing’s syndrome is a state of mineralocorticoid excess due to substrate saturation of the 11 beta-hydroxysteroid dehydrogenase leading to more bioactive available cortisol binding to mineralocorticoid receptors and resulting in hypokalaemia [1].

In a series of 166 patients with Cushing’s syndrome, 3.6% had a carcinoid tumour causing ectopic ACTH production [2]. Interestingly in the case presented, the metastatic small bowel NET was diagnosed over 15 years before the rapid development of the Cushing's syndrome. Most cases of ectopic ACTH production are synchronous with NET diagnosis (within three months [3]).

Ectopic ACTH syndrome has high mortality. In cases of inoperable disease, that do not respond to medical therapy, bilateral adrenalectomy can definitively cure the Cushing’s syndrome. Despite systemic reviews showing high mortality post bilateral adrenalectomy (1 year mortality rate 46% [4]) it is often required to manage refractory disease.

  1. [1] Steward P, Walker B. 11 beta-hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1995 Dec;80(12):3617-20
  2. [2] Lindholm J, Juul S. Incidence and late prognosis of Cushing's syndrome: a population-based study. J Clin Endocrinol Metab 2001 Jan;86(1):117-23
  3. [3] Kamp K, Alwani R. Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors. European Journal of Endocrinology 2016;174(3):271–280
  4. [4] Ritzel K, Beuschlin F. Outcome of Bilateral Adrenalectomy in Cushing’s Syndrome: A Systematic review. J Clin Endocrinol Metab. 2013 Oct; 98 (10):3939-3948