7759 Undetectable PTHrP and Elevated Il-6 in a 517759 Year Old Male With Clear Cell Renal Carcinoma, Complicated by Paraneoplastic Hypercalcemia
Authors: Cedeno Evangelina , Patel Toral Aminbhai , Zacharia Christine 
Published: October 2024

Abstract
Disclosure: E. Cedeno: None. T. Patel: None. C. Zacharia: None.
Title Undetectable PTHrP and elevated IL-6 in a 51-year-old male with clear cell renal carcinoma, complicated by paraneoplastic hypercalcemia. Introduction: Malignant hypercalcemia as a paraneoplastic syndrome is very common in lung and kidney cancers. Traditionally, humoral hypercalcemia of malignancy (HHM) is linked to excess PTHrP production, but other possible contributors, such as interleukin-6 (IL-6), have been identified. We present a case of HHM with undetectable PTHrP and elevated levels of IL-6. Case A 51-year-old male with RCC presented with symptomatic hypercalcemia (polyuria and polydipsia), found during a pre-op visit. Initial tests were consistent with non parathyroid-mediated hypercalcemia: adjusted Ca 13.2 (9.1-11.2 mg/dL), iCal 1.69 (0.95-1.32 mmol/L), iPTH &lt;4.0 (8.0-85.0 pg/mL), 25-OH-Vit D 41(30-80 ng/mL), 1,25-OH D 64.7 (24.8- 81.5pg/mL), PTHrP undetectable (&lt;2.0 pmol/L), SPEP and UPEP without abnormalities. A CT showed a large 15x12x14 cm partially necrotic mass arising from the right kidney, consistent with malignancy. The patient was treated with isotonic IV fluids and underwent a right nephrectomy on day 6 of hospitalization with subsequent complete resolution of hypercalcemia 24 hours post-surgery. Adjusted Ca and iCal normalized. iPTH from initial 4 improved to 30.1 (8.0-85.0 pg/mL), and IL-6 was found to be high to 62.5 (0.0-13.0 pg/mL). Final pathology was consistent with clear cell RCC. The patient was discharged, with normal laboratory values on follow-up. Conclusion: Hypercalcemia is the most common paraneoplastic complication of RCC, and approximately 17% of all patients with RCC will develop hypercalcemia. Although usually mediated by PTHrP, evidence points towards other possible contributors. IL-6 has been hypothesized to be a possible mediator of malignant hypercalcemia in paraneoplastic syndromes¹. This is evidenced by our case, where our patient had undetectable levels of PTHrP in the setting of RCC, and was later found to have elevated IL-6, pointing to the latter as a possible culprit. In conclusion, our case supports IL-6 as a possible contributor to the pathogenesis of malignant hypercalcemia in RCC patients, literature is sparse on PTHrP-independent HHM and rare case reports demonstrated this phenomenon not just in RCC but also in other malignancies like ALL. There are some hypotheses implicating IL-6 influencing tumor growth as well as bone metastasis. Our case adds a valuable contribution to this limited database. Further studies are warranted to understand the role of IL-6 in HHM as well as anti-IL6 agents as a potential therapeutic option for treatment-resistant hypercalcemia. Reference: Max G. Weissglas, The Role of Interleukin-6 in the Induction of Hypercalcemia in RCC Transplanted into Nude Mice, Endocrinology, Volume 138, Issue 5, May 1997, Pages 1879-1885.
Presentation: 6/2/2024