Normocalcemic Primary Hyperparathyroidism and Non-Uremic Calciphylaxis

Presentation Number: SAT 301
Date of Presentation: April 1st, 2017

Tanvi Parikh*1, Joseph G. Verbalis2, Fady Hannah-Shmouni3, Sharleen Sidhu4 and Shirisha Avadhanula5
1MedStar Georgetown University/MedStar Washington Hospital Center, Silver Spring, MD, 2Georgetown University Medical Center, Washington, DC, 3Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 4MedStar Georgetown University Hospital/MedStar Washington Hospital Center, Arlington, VA, 5Medstar Georgetown University/Washington Hospital Center, Washington, DC

Abstract

Introduction:

Calciphylaxis is a rare disorder of calcium (Ca) homeostasis associated with significant morbidity and mortality. Calciphylaxis due to end stage renal disease or medications (e.g., warfarin) has been previously described. We report a case of normocalcemic primary hyperparathyroidism (PHPT) with non-uremic calciphylaxis (NUC).

Case Description:

A 60-year-old African American female was evaluated for long standing (3 years), painful and non-healing right leg ulcers. Past medical history was significant for presumed normocalcemic PHPT, morbid obesity and pre-diabetes. She had failed previous wound debridement and grafting procedures. Medications included Vitamin D3 2,000 IU daily. She denied symptoms of hypercalcemia or history of fractures. Physical examination showed several indurated and darkened plaques, with non-healing, tender ulcers on the right lower leg. Biochemical evaluation revealed: corrected Ca=9.8 mg/dl (8.7-10.2), Phosphorus (P)=4.2 mg/dl (2.5-4.5), Ca X P product=41.6 mg/dl (goal < 55), PTH=92.1 pg/ml (12-65), 25-OHD=43 ng/ml (30-100), 1,25-OHD=62 pg/ml (21-65), Cr=0.9 mg/dl (0.5-1.04), GFR >60 ml/min, ALP=99 U/L (45-117), Ca/Cr=0.03, calcitonin=2 pg/ml (0-5). Right tibia/fibula X-ray showed extensive soft tissue calcifications and subchondral sclerosis. Sestamibi scan revealed mediastinal focus of early uptake with washout on delayed (6h) imaging, concerning for a parathyroid lesion. Excisional biopsy of the ulcer showed arteriolar thrombi and Ca deposits in the subcutaneous fat, confirming the diagnosis of calciphylaxis. She was treated with phosphate binders (PB, sevelamer 800 mg 3X daily), and received hyperbaric oxygen therapy and allografts to the leg ulcers. Parathyroid surgery was considered but deferred.

Discussion:

  1. The reported disorders associated with NUC include: PHPT, malignancies (lymphomas), autoimmune diseases (SLE, rheumatoid arthritis), alcoholic liver disease, DM, chemotherapy-induced Protein C and Protein S deficiency, obesity, warfarin and glucocorticoid exposure. (1,2)
  2. A high index of clinical suspicion for NUC should be maintained if a patient with any of the aforementioned diagnoses presents with unexplained skin lesions. 
  3. Data on the treatment of NUC is very limited; strategies such as local wound care and hyperbaric oxygen therapy are commonly employed; the roles of PB, cinacalcet or parathyroidectomy in PHPT-induced NUC remains unclear.
  4. In this case, we hypothesized that her Ca X P was normal due to rapid Ca deposition in soft tissues; we therefore chose to use PB, which lowered post-treatment (i.e., 4d) P=3.4 mg/dl, PTH=42 ng/dl and increased Ca=10.1 mg/dl.
  5. We postulate that PB might retard progression of calciphylaxis by further lowering the Ca X P product. If PB therapy is unsuccessful, we will consider parathyroid surgery, cinacalcet and genetic testing as possible next steps.

 

Disclosure: JGV: , Ferring Pharmaceuticals, , Otsuka. Nothing to Disclose: TP, FH, SS, SA