Category: Calcium/Bone Disorders

Monitor: 17

17 - CALCITRIOL MEDIATED HYPERCALCEMIA DUE TO METHOTREXATE ASSOCIATED PNEUMONITIS

Friday, Apr 26
11:30 AM – 12:00 PM

Objective : To describe a case of 1,25-dihydroxyvitamin D mediated hypercalcemia secondary to methotrexate (MTX) pneumonitis.


Methods : N/A


Results :

A 68-year-old woman with a history of psoriasis, malignant melanoma, and tobacco use was admitted to the hospital for respiratory failure and hypercalcemia. She reported a several week history of fatigue, constipation, cough, dyspnea, chills and slowed mentation. On exam she appeared fatigued with clear lungs to auscultation and no respiratory distress.  Labs showed a serum Calcium: 11.5 (8.5 – 10.6 mg/dL), PTH: 7.3 (10 - 65 pg/mL), 1,25-dihydroxyvitamin D: > 200 (19.9 – 79.3 pg/mL), and angiotensin converting enzyme: 60 (8-53 U/L). A polymerase chain reaction type respiratory viral panel was negative for 16 common upper respiratory viruses. Screening for Herpes simplex virus, Cytomegalovirus, Histoplasma, Cryptococcus, Pneumocystis, acid fast organisms, Mycoplasma and Chlamydophila were negative.  A hypersensitivity pneumonitis screen revealed elevated immunoglobulin G to Aspergillus fumigatus 58.3 ( < 46.0 mcg/mL) and Penicillium notatum 50.5 (< 22.0 mcg/mL). CT of the chest revealed diffuse bilateral ground glass opacities consistent with pneumonitis or atypical infection. A whole body positron emission tomography scan was negative for adenopathy or malignancy. The ground glass opacities did demonstrate some fludeoxyglucose uptake, suggestive of pneumonitis.  Pathology from two bronchoscopies was negative for malignancy, granuloma and infection. Her hypercalcemia was attributed to MTX pneumonitis and improved after discontinuation of MTX and treatment with a bisphosphonate and high dose glucocorticoid. A follow up CT showed interval improvement in the bilateral ground glass opacities. Approximately 6 weeks after discontinuing MTX, her calcitriol had decreased to 8.3 (19.9 – 79.3 pg/mL).


Discussion : MTX pneumonitis occurs in approximately 0.3 - 7.5% of treated patients, usually within the first year of therapy. Activated macrophages within granulomas are responsible for the conversion of 25-hydroxyvitamin D to calcitriol. The diagnosis should only be considered after all other etiologies including infectious, neoplastic and autoimmune have been excluded. Particular attention should be directed to excluding sarcoidosis as it is responsible for 50% of the cases of calcitriol mediated hypercalcemia. Hypersensitivity pneumonitis due to aspergillus seemed less likely as it is quite rare, particularly in a non-occupational setting, and is implicated in less than 2% of cases.


Conclusion : MTX induced pneumonitis is a rare cause of calcitriol mediated hypercalcemia. Discontinuation of MTX and glucocorticoids can be an effective treatment.

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Michael D. Holyoak

Endocrine Fellow
University of Kansas Medical Center
Merriam, Kansas

Michael Holyoak attended Idaho State University in his home town of Pocatello where he graduated with a Bachelors of Science in zoology. He completed his medical degree at Des Moines University and attended Internal Medicine residency at the University of Kansas Medical Center, where he is currently an endocrine fellow. Current research projects involve bone health and pulmonary function in patients with cystic fibrosis related diabetes. Michael enjoys treating diabetes and thyroid disorders.

Michael D. Holyoak

Endocrine Fellow
University of Kansas Medical Center
Merriam, Kansas

Michael Holyoak attended Idaho State University in his home town of Pocatello where he graduated with a Bachelors of Science in zoology. He completed his medical degree at Des Moines University and attended Internal Medicine residency at the University of Kansas Medical Center, where he is currently an endocrine fellow. Current research projects involve bone health and pulmonary function in patients with cystic fibrosis related diabetes. Michael enjoys treating diabetes and thyroid disorders.