Late diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia 2B with rapid clinical decline.

Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive of the MEN syndromes. It is characterised by medullary thyroid cancer (MTC), pheochromocytoma, marfanoid body habitus, mucosal neuromas and colonic dysfunction. Patients typically present with chronic constipation and MTC in early childhood. We discuss an atypical late presentation of MEN2B in a 19-year-old man with chronic constipation since childhood admitted with acute spinal cord compression. He underwent emergent neurosurgical intervention followed by postoperative radiotherapy. Bone biopsy revealed metastatic pheochromocytoma. Thyroid nodule biopsy showed MTC. MIBG scan confirmed pheochromocytoma as the dominant malignancy. Germline testing revealed a RET mutation (p.M918T). He received one cycle of cyclophosphamide, vincristine and dacarbazine and subsequently developed a pathological right femur fracture requiring repair. Postoperative course was complicated by hypoxic respiratory failure requiring intubation. Imaging showed lymphangitic spread of disease in the lungs. He unfortunately did not respond to a short trial of sunitinib and transitioned to comfort care.

Therapeutic Challenges in Chronic Myeloid Leukemia: A Case-Based Discussion.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by a reciprocal translocation between the long arms of chromosomes 9 and 22 that results in expression of the oncoprotein BCR-ABL1. An optimal response to tyrosine kinase inhibitors (TKIs) requires a BCR-ABL transcript level ≤ 10% at 3 months, ≤ 1% at 6 months, ≤ 0.1% at 1 year, and ≤ 0.01% onwards. Complex scenarios like P190BCR-ABL CML, unusual BCR-ABL transcripts, primary refractory CML, and detection of TKI-resistance mutations during treatment frequently pose a therapeutic challenge. In this article we present some of these clinical scenarios using a case-based approach.

Effective uric acid reduction with probenecid and febuxostat in a patient with chronic kidney disease.

A 33-year-old male with poorly controlled chronic tophaceous gout and chronic kidney disease (CKD) with estimated glomerular filtration rate (GFR) of 37 cc/min. His uric acid was 11 mg/dL despite maximal dosing of febuxostat. He had previously failed pegloticase infusions as well. This patient had a reduction in his uric acid level to less than 6 mg/dL following addition of probenecid to his febuxostat regimen. Most guidelines recommend against utilisation of probenecid therapy in patients with GFR <50, but there is no obvious contraindication to its use, provided renal calculi do not develop. Our case illustrates the synergistic effect probenecid can add to maximal xanthine oxidase inhibitor therapy for patients with refractory hyperuricaemia in a patient with CKD stage IIIb. With the approval of a new uricosuric medication, lesinurad, probenecid may remain a suitable alternative for patients with financial limitations to achieve target uric acid levels.