Our case today was a nice presentation of RTA induced by Iburpofen

The patient, a 52 year old man and a smoker went to his PCP for complaints of right shoulder pain that has been going on for the past three months, he has been consuming Ibuprofen without significant improvement. He was found to have severe hypokalemia (K of 1.9) and subsequently sent to the hospital. His shoulder pain was not associated with muscular weakness, however he did complain of some numbness and tingling in the right arm.

His work up included 1-Hypokalemia and 2-Shoulder pain. The fact that he was a smoker for the past twenty years, and the absence of a significant trauma or overuse history to explain the shoulder pain lead to the idea of having a common culprit that would explain his hypokalemia and shoulder pain putting together all the pieces of his history, the though process was to rule out a lung cancer that can cause hypokalemia via paraneoplastic syndrome and shoulder pain via tumor invasion of the surrounding structures.

A chest X-Ray showed a left upper lobe mass, and a subsequent CT chest showed a 7 cm left upper lobe mass, a 2 cm right upper lobe mass and a 7 cm paraspinal mass extending into the thoracic spinal canal prompting neurosugery to start him on dexamethasone and eventually he received laminectomy and resection of part of the paraspinal mass. The biopsy eventually showed poorly differentiated carcinoma with clear cell features.

Now going back to the hypokalemia, and starting workup to see whether this could be caused by this patient tumor, a basic metabolic panel was ordered and it showed a potassium level of 2.3, a normal sodium level (140) as well as metabolic acidosis with HCO3 of 17 and hyperchloremia (111)

Back to the tumor, usually small cell lung cancer can produce ectopic ACTH. SCLC usually shows densly packed small tumor cells with scant cytoplasm (picture on the right). Our patient had clear cells on pathology which points towards other types (SCC, AC, NSCLC).

The fact that the patient had metabolic acidosis with hypokalemia rather than alkalosis which would be expected in an ACTH secreting tumor prompted further search: A urine anion gap was calculated and was found to be negative (-16) and urine pH was 7. This translates into a possibility of a type 2 RTA versus a GI cause of NAGMA (which is less likely as the patient denied any diarrhea)

Further workup for underlying causes of type 2 RTA in this patient included SPEP to evaluate for light chains, which didn’t show spikes, and exclusion of other medications that can cause this disorder (Ifosfamide, Tenofovir, tacrolimus, cyclosporine) as well as vitamin D deficiency and further auto-immune syndromes.

So who could the culprit be? Some digging up in the literature yielded some case reports by Ng et al. and Dang et al. describing cases of type 2 RTA associated with Ibuprofen excessive ingestion, keep in mind that Ibuprofen usually gives a picture of type 1 RTA (hypokalemia and positive UAG) or type 4 RTA (hyperkalemia) .

Fun facts we learned today: GOLD MARK is the new MUD PILES for anion gap metabolic acidosis. GOLD MARK stands for Glycols (ethylene and propylene), Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis. 



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