Category: Calcium/Bone Disorders

Monitor: 10


Saturday, Apr 27
11:30 AM – 12:00 PM

Objective : To present case of non-PTHrp-mediated humoral hypercalcemia of malignancy (HHM) in a patient with renal cell carcinoma (RCC).

Methods : n/a

Results : n/a

Discussion :

Case Presentation: A 65 year-old male with recently diagnosed RCC was admitted for open left nephrectomy. Endocrinology was consulted for pre-operative hypercalcemia. Prior to admission, he had worsening constipation and fatigue. He denied bone pain or mental status changes. CT chest abdomen and pelvis confirmed multiple solid lung nodules and an exophytic left renal mass measuring 11.1 x 9.3 x 10.7 cm. Admission labs showed a corrected calcium level of 13.28 mg/dL and his operation was delayed. The patient was not immobilized, and he was not on any medications that could cause hypercalcemia. Hypercalcemia work-up was subsequently ordered showing: PTH 6 pg/mL (15-65 pg/mL), 25(OH)D 38.7 ng/mL (30-150 ng/mL), 1,25(OH)2D 45.90 pg/mL (18-64 pg/mL), PTHrp 1.5 pmol/L (

Discussion: Hypercalcemia of malignancy can occur through PTH-independent and rarely PTH-dependent mechanisms. HHM is a PTH-independent cause of hypercalcemia usually mediated by PTHrp. HHM is most commonly seen in RCC, squamous cell carcinoma of the lung, breast, ovarian and bladder cancers. Our patient had metastatic RCC with appropriately suppressed PTH in the setting of hypercalcemia without elevated PTHrp levels (confirmed by Mayo Clinic laboratory). Non-PTHrp mediated HHM is rare and only a few cases have been reported in the literature. Animal models have pointed to other humoral mediators such as TGF-β, IL-1, IL-6, TNF-α which may act as local regulators of osteoblast/osteoclast activity leading to bone resorption and hypercalcemia. Our patient did have elevated IL-6 levels and detectable TGF-β levels pre-operatively. While these markers are non-specific and further research is needed to elucidate other humoral mediators involved in HHM, it is important to recognize the uncommon phenomenon of non-PTHrp mediated hypercalcemia. Treatment is geared towards treating the underlying malignancies and other standard therapies such as calcitonin, bisphosphonates, and denosumab can be utilized for acute treatment.

Conclusion :

HHM can be non-PTHrp mediated and is likely to be mediated by other cytokines and humoral mediators. 


Spandana Brown

Endocrinology Fellow
Houston Methodist Hospital

Dr. Brown is currently a fellow at Houston Methodist Hospital. She completed her undergraduate training at Vanderbilt University and medical school at Baylor College of Medicine. She received her internal medicine training at Houston Methodist Hospital. Her research interests include metabolic bone disorders, obesity and thyroid disease.

Ahmad Yehya

Endocrinology Fellow
Houston Methodist Hospital

A graduate of the American University of Beirut, Lebanon, Dr. Yehya completed his Internal Medicine Residency at the University of Kansas Medical Center. Dr. Yehya has a profound interest in metabolism and participated in various weight management programs and clinics throughout his Residency. Dr. Yehya will be working closely with the weight management program at Houston Methodist with special emphasis on weight loss medications, diet adjustment and exercise. Dr. Yehya is also particularly interested in the impact of lifestyle on diabetes. Dr. Yehya has specifically chosen to pursue his Endocrinology Fellowship at Houston Methodist as this will serve as a great template for launching a successful career in Endocrinology and he hopes to be able to develop weight management centers dedicated to focus on lifestyle changes for the community.

Jawairia Shakil

Assistant Professor of Medicine
Houston Methodist Hospital

Dr. Shakil did medical training and graduated from Dow medical college in Pakistan, then went on to complete internal medicine training at Texas Tech university and endocrinology fellowship at Houston Methodist Hospital. Currently serving as Assistant professor of medicine in the department of endocrinology, diabetes and metabolism. She is also the Associate Program director endocrine fellowship program at Houston Methodist hospital. Main area of clinical expertise is general endocrinology.

Laila Tabatabai

Assistant Professor of Clinical Medicine; Director, Houston Methodist Endocrinology Fellowship
Houston Methodist Hospital

Laila S. Tabatabai, M.D., is the Program Director of the Houston Methodist Endocrinology Fellowship Program. She is also the Director of the Houston Methodist Hospital Fracture Liaison Service (FLS) and Assistant Professor of Clinical Medicine in the Division of Endocrinology. She received her medical degree, with distinction in research, at Albany Medical College in Albany, New York. Her postdoctoral training included an internship and residency in internal medicine at the University of Maryland Medical Center in Baltimore and a fellowship in endocrinology at Johns Hopkins Hospital in Baltimore.