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: Pneumocystis jiroveci pneumonia (PJP) is a severe complication in immunocompromised hosts including transplant recipients. Hypercalcemia (HCa) is not a classic symptom of the disease. However, HCa (mean [SD; range], 2.90 [0.20; 2.71-3.17] mmol/L) was detected in 5 patients with PJP at diagnosis. The HCa was associated with decreased concentrations of circulating parathormone (PTH), from 294 (292) ng/L 3 to 6 months previously to 20 (23.5; 7-53) ng/L. Concentrations of 1,25-(OH)2 vitamin D, measured in 3 patients, were in the high normal range (54.66 [7.23; 225-66] microg/L), whereas 25-(OH) vitamin D concentrations were low (13.9 [2.17; 20-60] microg/L). After treatment with trimethoprim-sulfamethoxazole for 21 days, 4 patients recovered and 1 died. Calcium and PTH concentrations rapidly returned to normal (2.36 [0.05] mmol/L and 89 [29.7] ng/L, respectively) at 2 months after the acute phase of the disease. Although fewer than 10 cases of PJP-associated HCa have been reported to date, it is possible that this association is more frequent than previously thought because our cases were detected during 2 years. As in other granulomatous disease-induced HCa, including fungal infections, it is likely that endogenous extrarenal production of 1-alpha-hydroxylase by activated macrophages and by interferon-gamma involved in granuloma formation results in increased conversion from 25-(OH) vitamin D to 1,25-(OH)2 vitamin D and, consequently, in transient HCa and suppression of PTH secretion. Fortuitous detection of HCa in transplant recipients with pulmonary symptoms must raise suspicion of PJP or fungal infection.Transplantation Proceedings 10/2009; 41(8):3320-2. · 0.95 Impact Factor
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ABSTRACT: Hypocalcaemia, defined by serum calcium level less than 8.5 mg/dl, could be caused by human immunodeficiency virus (HIV) and diarrheal diseases. In Ethiopia, while morbidities from diarrheal diseases and HIV are serious health problems, studies assessing the interactions amongst of the three do not exist. Therefore, the present study was undertaken to investigate the level of calcium among diarrheic patients with and without HIV co-infection.BMC Public Health 07/2014; 14(1):679. · 2.08 Impact Factor
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ABSTRACT: 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.Clinical Infectious Diseases 06/2012; 55(7):e61-6. · 9.37 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 - email@example.com; Loureno Cezana - firstname.lastname@example.org; Daniela Miti
Lemos Tsukumo - email@example.com; Marco Antônio de Carvalho-Filho - firstname.lastname@example.org; Mário José
Abdalla Saad* - email@example.com
* 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, 2:262 http://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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