A Dimorphic Diagnosis of a Pleomorphic Disease: An Unusual Cause of Hypercalcemia

Am J Med. 2020 Nov;133(11):e659-e662. doi: 10.1016/j.amjmed.2020.03.035. Epub 2020 Apr 19.

Abstract

Background: Histoplasmosis is a rare cause of 1, 25-dihydroxy vitamin-D-mediated hypercalcemia. In this study, we report 2 cases of hypercalcemia secondary to histoplasmosis seen at Mayo Clinic, Rochester and a review of cases reported in the literature.

Methods: We conducted a PubMed search using the keywords "hypercalcemia" and "histoplasmosis." Fourteen cases of hypercalcemia secondary to histoplasmosis were reported between 1977 and 2020. We identified an additional 2 patients from our institution.

Results: We reviewed a total of 16 cases. The median age at presentation was 58.5 years (interquartile range, 41.5-68.75 years), and 13 of 16 patients (81.2%) were men. Serum parathyroid hormone level was available in 13 of 16 (81.25%) patients, of whom 11 patients (84.6%) had a low level, 1 patient (7.6%) had a normal level, and 1 patient (7.6%) had an elevated level. 1, 25-dihydroxy vitamin D level was reported in 9 of 16 (56.25%) patients. Of these, 5 patients (55.5%) had levels within normal limits, and 4 patients (44.4%) had levels above normal. Serum angiotensin-converting enzyme level was evaluated in 4 of 16 patients (25%), and it was elevated in all 4 (100%) cases. Four patients received corticosteroids before a diagnosis of histoplasmosis was made, which resulted in rapidly progressive disease and death in 2 patients.

Conclusions: In patients with granulomatous disorder and hypercalcemia, it is crucial to rule out infectious etiologies before initiating steroids. Histoplasmosis can cause nonparathyroid hormone-mediated hypercalcemia and, if not suspected, may have catastrophic implications.

Keywords: 1, 25-dihydroxy vitamin D-/calcitriol-mediated hypercalcemia; Histoplasmosis; Nonparathyroid hormone-mediated hypercalcemia; Serum angiotensin-converting enzyme; Steroids.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / therapeutic use
  • Bone Density Conservation Agents / therapeutic use
  • Calcitonin / therapeutic use
  • Calcitriol / blood
  • Diphosphonates / therapeutic use
  • Female
  • Fluid Therapy
  • Histoplasmosis / blood
  • Histoplasmosis / complications*
  • Histoplasmosis / drug therapy
  • Humans
  • Hypercalcemia / blood
  • Hypercalcemia / etiology*
  • Hypercalcemia / therapy
  • Infant
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Parathyroid Hormone-Related Protein / blood
  • Peptidyl-Dipeptidase A / blood
  • Phosphorus / blood
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Young Adult

Substances

  • Antifungal Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Vitamin D
  • Phosphorus
  • 1,25-dihydroxyvitamin D
  • Calcitonin
  • 25-hydroxyvitamin D
  • Peptidyl-Dipeptidase A
  • Calcitriol