1. Pertinent Laboratory Data
Severe metabolic alkalosis and refractory hypokalemia in a patient with metastatic olfactory neuroblastoma
Saurabh Chandan, MD1; John Anderson, DO1; Meredith Ross, MD2; Andjela T. Drincic, MD2
1. Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.  2. Diabetes, Endocrinology & Metabolism, University of Nebraska Medical Center, Omaha, NE, United States.
The differential diagnosis of hypokalemia and metabolic alkalosis is broad. In a patient with ONB, it is important to consider EAS as a possible cause for these metabolic abnormalities in a patient with weight loss despite steroid therapy.
Hypokalemia is present in more than 95% of patients with ectopic ACTH syndrome, and less than 10% of patients with Cushing disease. (5)
Hypokalemia in EAS is caused a state of mineralocorticoid excess, caused by cortisol saturation of the 11-beta-hydroxysteroid dehydrogenase.(5)
Another key feature of this case is the diagnostic dilemma internists face in establishing diagnosis of EAS in patients already on high dose steroid therapy.
This patient was on Dexamethasone 4mg twice daily and had inappropriately elevated ACTH and Cortisol levels, raising suspicion for Cushing’s syndrome.
Therefore, an accelerated workup was performed on his follow up admission with a high dose dexamethasone suppression test.
It is recommended that steroids be discontinued prior to hypercortisolemia workup, this may not always be possible, based on individual patient care.
Therapeutically, Dexamethasone therapy had to be continued to prevent progression of cerebral edema in metastatic disease.
The internist must be flexible with dynamic testing in cases with confounding and limiting factors.
Pertinent Laboratory Data
Learning Objectives
Recognizing hypercortisolism from ectopic ACTH production as possible cause of patients presenting with severe metabolic alkalosis and refractory hypokalemia.
Establishing diagnosis of Ectopic ACTH Syndrome (EAS) and diagnostic dilemma in patients on high dose oral steroid therapy.
Table 1: Admission Laboratory Data
Table 2: Adrenal Studies
* Patient on 6mg Dexamethasone
** High Dose Dexamethasone Suppression test
Case Report
Figure 1
71 year old Caucasian male with past medical history significant for essential hypertension, hyperlipidemia and metastatic olfactory neuroblastoma (ONB) previously treated with resection and chemotherapy, presented to the emergency department complaining of worsening leg swelling.
Pertinent medication includes Dexamethasone 4 mg twice daily.
Review of systems revealed a 30lb weight loss.
On exam, vital signs were within normal limits including BP 138/68. Pertinent abnormality includes pitting bilateral lower extremity edema.  
He was diagnosed with lower extremity deep venous thrombosis. He was started on therapeutic Low Molecular Weight Heparin.
Despite aggressive oral and intravenous electrolyte replacement, his potassium and phosphate levels did not normalize, leading to further work up, which revealed elevated random and post-dexamethasone cortisol and ACTH (Table 2), consistent with EAS.
For medical treatment of Cushing’s syndrome, he was started on ketoconazole 200mg BID with dose titration, spironolactone 50mg daily, and Acetazolamide 500 mg BID.
High dose dexamethasone was continued for treatment of metastatic disease to the brain and associated cerebral edema. Due to declining health the patient was transitioned to comfort measures.
Figure 1: MRI of brain demonstrates bilateral frontal dural enhancing masses, T2 hyperintensity consistent with extensive vasogenic edema and gliosis, and small subdural hemorrhage.
ONB is an uncommon malignant neoplasm of the nasal vault, believed to develop from olfactory neuroepithelium. They represents 2-3% of all endonasal tumors.(1,2,3)
EAS has been reported in patients with ONB.(4)
To the best of our knowledge, this is the 19th reported case. Pacak et al described a case of florid Cushing’s syndrome due to an ACTH-producing ONB found to have marked hypokalemia and significant metabolic alkalosis, similar to our case. (5)
Discussion
References
1. Butt MI, Olczak SA. Cushing Syndrome Secondary to Ectopic Adrenocorticotropic Hormone Secretion From Recurrent Olfactory Neuroblastoma. The Endocrinologist. 2007; 17:
2. Arnesen MA, Scheithauer BW, Freeman, S. Cushing’s Syndrome Secondary to Olfactory Neuroblastoma. Ultrastructural Pathology. 1994; 18:61-68.
3. Plasencia YL, Cortes MB, et al. Esthesioneuroblastoma Recurrence Presenting as a Syndrome of Inappropriate Antidiurectic Hormone Secretion. Head and Neck-DOI. 2006; ;
4. Pacak K et al. Ectopic Cushing’s Syndrome Caused by an Esthesioneuroblastoma Endocrine Practice Vol 10 No. 2 March/April 2004
5. Melmed, Shlomo, et al. Williams textbook of endocrinology. Elsevier Health Sciences, 2015.