Hypercalcemia in a patient with disseminated paracoccidioidomycosis: a case report.
ABSTRACT Hypercalcemia is well described in various granulomatous disorders, such as sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of Paracoccidioides brasiliensis and hypercalcemia is rare: to the best of our knowledge, only two cases have previously been reported, and neither had a clear documentation of the etiology of the hypercalcemia.
We report the case of a 22-year-old man in whom disseminated infection with paracoccidioidomycosis was associated with hypercalcemia. The patient had a high normal serum level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication that the hypercalcemia was not mediated by parathyroid hormone and might be associated with 1,25-dihydroxyvitamin D.
The episode resolved readily with administration of corticosteroids, an outcome suggesting that this is an effective treatment of hypercalcemia of this origin. On follow-up, while receiving antifungal therapy for P. brasiliensis the patient's calcium values remained normal.
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ABSTRACT: Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71-year-old female woman with end-stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), was diagnosed. Her serum concentration of calcium and 1,25(OH)2D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)2D in this patient.Renal Failure 06/2004; 26(3):333-8. · 0.94 Impact Factor
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ABSTRACT: Hypercalcemia can occur in patients with granulomatous disorders such as sarcoidosis, and is commonly related to high serum 1,25-dihydroxyvitamin D (OHD) concentrations. We here report a 68-year-old man with a history of mild renal insufficiency who presented with hypercalcemia (serum calcium of 3.11 mmol) and normal 1,25-OHD levels (38 pg/ml, RIA/IDS, Boldon, UK, measuring both 1,25-OH D2 and D3). Imaging and laboratory investigations were suggestive of sarcoidosis. After hydration and prednisone therapy (40 mg/day) for 7 days, serum calcium dropped to 2.7 mmol and 1,25-OHD levels to 13.4 pg/ml. Six weeks after prednisone therapy, serum calcium was 2.41 mmol (normal) and 1,25-OHD 6.2 pg/ml (low). Computed tomography of the chest showed shrinkage of the right hilar mass. This case illustrates that hypercalcemia can occur in granuloma-forming disorders such as sarcoidosis in the setting of inappropriately normal (and not elevated) 1,25-OHD levels. Contributing factors may include dehydration, increased uptake of oral calcium and/or decreased calcium excretion, especially in mild renal insufficiency. Therapy of choice are hydration and glucocorticoid (prednisone) therapy. In this setting, prednisone may lead to a decline of activated mononuclear cells (in the lung and lymph nodes) that are able to produce extrarenal PTH-independent 1,25-OHD.Medical science monitor: international medical journal of experimental and clinical research 12/2007; 13(11):CS133-136. · 1.36 Impact Factor
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ABSTRACT: Metabolism of [3H]25-hydroxyvitamin D3(25-OH-D3) was studied in primary cultures of pulmonary alveolar macrophages (PAM) from seven patients with sarcoidosis and two patients with idiopathic pulmonary fibrosis. Production of a [3H]1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3)-like metabolite of [3H]25-OH-D3 was detected in lipid extracts of cells from five patients with sarcoidosis. Synthesis of this compound in vitro was limited to viable PAM and was greatest in cells derived from a patient with hypercalcemia and an elevated serum concentration of 1,25-dihydroxyvitamin D. The tritiated PAM metabolite coeluted with authentic 1,25-(OH)2-D3 in three different solvent systems on straight-phase high performance liquid chromatography (HPLC) and demonstrated binding to extracted receptor for 1,25-(OH)2-D3, which was identical to that of commercially available [3H]1,25-(OH)2-D3 of comparable specific activity. Incubation of PAM with high concentrations of 25-OH-D3 resulted in production of an unlabeled metabolite that co-chromatographed with the 3H-PAM metabolite on HPLC and that was bound with high affinity by both the specific receptor for 1,25-(OH)2-D3 and antiserum to 1,25-(OH)2-D3.Journal of Clinical Investigation 12/1983; 72(5):1856-60. · 12.81 Impact Factor
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Journal of Medical Case Reports
Hypercalcemia in a patient with disseminated
paracoccidioidomycosis: a case report
Rafael Moura Almeida, Loureno Cezana, Daniela Miti Lemos Tsukumo,
Marco Antônio de Carvalho-Filho and Mário José Abdalla Saad*
Address: Department of Internal Medicine, State University of Campinas, 13081-970 Campinas, SP, Brazil
Email: Rafael Moura Almeida - firstname.lastname@example.org; Loureno Cezana - email@example.com; Daniela Miti
Lemos Tsukumo - firstname.lastname@example.org; Marco Antônio de Carvalho-Filho - email@example.com; Mário José
Abdalla Saad* - firstname.lastname@example.org
* Corresponding author
Introduction: Hypercalcemia is well described in various granulomatous disorders, such as
sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of
Paracoccidioides brasiliensis and hypercalcemia is rare: to the best of our knowledge, only two cases
have previously been reported, and neither had a clear documentation of the etiology of the
Case presentation: We report the case of a 22-year-old man in whom disseminated infection
with paracoccidioidomycosis was associated with hypercalcemia. The patient had a high normal
serum level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication
that the hypercalcemia was not mediated by parathyroid hormone and might be associated with
Conclusion: The episode resolved readily with administration of corticosteroids, an outcome
suggesting that this is an effective treatment of hypercalcemia of this origin. On follow-up, while
receiving antifungal therapy for P. brasiliensis the patient's calcium values remained normal.
Hypercalcemia is well described in various granuloma-
tous disorders, such as sarcoidosis, tuberculosis, beryllio-
sis, leprosy and fungal infections. Among the fungal
diseases, disseminated candidiasis, histoplasmosis, cryp-
tococcosis and coccidioidomycosis have rarely been
implicated as causes of hypercalcemia [1-5]. In this report
we describe a patient in whom hypercalcemia was associ-
ated with disseminated infection with Paracoccidioides bra-
siliensis and a high normal serum level of 1,25-
The patient, a 22-year-old male agriculturalist was admit-
ted to our hospital in November 2006 with asthenia,
weight loss, fever, diffuse enlargement of cervical lymph
nodes and enlarged liver and spleen. The patient's temper-
ature was 38.5°C and his blood pressure was 120/80
mmHg with a pulse of 96 beats per minute.
Initial laboratory studies included an erythrocyte sedi-
mentation rate of 89 mm/hour, serum hemoglobin of
11.4 g/dl, white blood cell count of 13,690/mm3 (27%
Published: 8 August 2008
Journal of Medical Case Reports 2008, 2:262doi:10.1186/1752-1947-2-262
Received: 16 January 2008
Accepted: 8 August 2008
This article is available from: http://www.jmedicalcasereports.com/content/2/1/262
© 2008 Almeida et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Journal of Medical Case Reports 2008, 2:262http://www.jmedicalcasereports.com/content/2/1/262
Page 2 of 3
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eosinophils), serum albumin of 2.4 g/dl, normal serum
urea, creatinine, sodium and potassium. On admission,
the patient had a total serum calcium level of 10.4 mg/dl
(normal range 8.4 to 9.7 mg/dl; ~12 mg/dl when cor-
rected for albumin), ionized calcium of 1.46 mmol/l
(normal range 1.15 to 1.29 mmol/l) and phosphorus of
4.9 mg/dl (normal range 2.7 to 4.5 mg/dl). An aspiration
of the cervical lymph node demonstrated P. brasiliensis.
Results of other laboratory tests performed to help assess
the cause of the hypercalcemia were as follows: thyroid
stimulating hormone 4.51 IU/ml (normal range 0.41 to
4.5 IU/ml); parathyroid hormone (PTH) 3.4 pg/ml (nor-
mal range 15 to 65 pg/ml); 1,25-dihydroxyvitamin D 49.4
pg/ml (normal range 15.9 to 55.6 pg/ml); and 24-hour
urinary calcium 856.55 mg (normal range 100 to 300 mg/
24 hours). Chest X-ray and bone scans were normal. A
computed tomography scan of the chest and abdomen
revealed no underlying malignancy. Other causes of
hypercalcemia such as vitamin A and D intoxication, sar-
coidosis, multiple myeloma, milk-alkali syndrome, adre-
nal insufficiency and immobilization were excluded on
the basis of laboratory and clinical data.
Despite the administration of hydration with normal
saline and furosemide therapy, the patient's calcium level
increased to 1.59 mmol/l. Specific treatment for paracoc-
cidioidomycosis was initiated with trimethoprim-sulfam-
ethoxazole. At that time, prednisone (20 mg/day) was
added to the regimen. On the 13th day of hospitalization,
the ionized calcium level had decreased to 1.34 mmol/l
and on the day of discharge from hospital this level was
1.26 mmol/l. The patient received follow-up examina-
tions until May 2007 and during this time has been
asymptomatic, with normal levels of serum calcium and
1,25-dihydroxyvitamin D (22.4 pg/ml).
We have reported the case of a patient presenting with
hypercalcemia complicating disseminated infection with
paracoccidioidomycosis. Hypercalcemia is well described
in various granulomatous disorders; however, the associ-
ation of P. brasiliensis and hypercalcemia is rare. To the
best of the authors' knowledge, only two cases have been
reported previously, neither of which offered a clear doc-
umentation of the etiology of the hypercalcemia [6,7].
The endogenous overproduction of 1,25-dihydroxyvita-
min D by activated macrophages seems to have a central
causative role in some granuloma-forming diseases, par-
ticularly sarcoidosis , although it is not uniformly
observed [5,8]. In our patient, the high normal levels of
1,25-dihydroxyvitamin D suggest that it may have had a
role in the hypercalcemia.
Our patient demonstrated total and ionized hypercal-
cemia, associated with low serum PTH, elevated serum
phosphorous and normal renal function. The elevation of
1,25-dihydroxyvitamin D (high normal limit) was unu-
sual for the suppressed PTH and elevated phosphorous
levels, suggesting an inappropriately elevated production
or decreased clearance of 1,25-dihydroxyvitamin D .
The hypercalcemia was initially treated with hydration
and furosemide, without improvement. Hypercalcemia
normalized when prednisone 20 mg was initiated.
Although antifungal therapy may have contributed to a
partial improvement of the hypercalcemia, a more likely
explanation is that the prompt response was due to treat-
ment with prednisone. Thus, 1,25-dihydroxyvitamin D
might have a role in the pathogenic mechanism of hyper-
calcemia in paracoccidioidomycosis.
We have described a patient in whom hypercalcemia was
associated with disseminated infection with P. brasiliensis
and a high normal serum level of 1,25-dihydroxyvitamin
PTH: Parathyroid hormone.
The authors declare that they have no competing interests.
RMA, LC and DMLT contributed to the care of the patient,
were involved in the preparation of the manuscript and
undertook the medical literature search. DMLT, MACF
and MJAS were responsible for patient's management.
MJAS was involved in the conception of the article and
revised it critically for important intellectual data before
final approval. All authors read and approved the final
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
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Page 3 of 3
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