Hypercalcemia in disseminated coccidioidomycosis: expression of parathyroid hormone-related peptide is characteristic of granulomatous inflammation.
BACKGROUND
Hypercalcemia is an uncommon complication of disseminated granulomatous infections. The pathogenesis of hypercalcemia associated with infection is not clear.


METHODS
We investigated a case of disseminated coccidioidomycosis with hypercalcemia. We used a sensitive radioimmunoassay to measure serum parathyroid hormone-related peptide (PTHrP) and a mouse monoclonal antibody to PTHrP to immunostain biopsies.


RESULTS
We found elevated serum levels of PTHrP while the patient was hypercalcemic that became undetectable when serum calcium normalized. We also found that the inflammatory cells and some surrounding tissues in skin biopsies expressed PTHrP. PTHrP was expressed by all biopsied lesions of patients with coccidioidomycosis that we examined, whether localized to the lung or disseminated, but no other cases were hypercalcemic. PTHrP was also expressed by the 3 mycobacterial granulomas we examined, and in a lymph node from a patient with sarcoidosis.


CONCLUSIONS
The expression of PTHrP is a property of infectious granulomas regardless of etiology or the tissue involved, suggesting that PTHrP expression is part of the normal granulomatous immune response. Hypercalcemia may result if there is disseminated infection and multiple granulomas. We propose that excess production of PTHrP is the cause of hypercalcemia in granulomatous infections.
VA San Diego Healthcare System, University of California, San Diego School of Medicine, USA. jfierer@ucsd.edu
Joshua
J
Fierer
Douglas W
DW
Burton
Parviz
P
Haghighi
Leonard J
LJ
Deftos
D003047:Coccidioidomycosis / Q000150:complications*; D006099:Granuloma / Q000473:pathology; D006801:Humans; D006934:Hypercalcemia / Q000175:diagnosis*; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood / Q000378:metabolism*; D044967:Serum / Q000737:chemistry
D044162:Parathyroid Hormone-Related Protein