Edition 66 - 2017, December / Images

Images in Pediatric Endocrinology: Infrequent cause of hypercalcemia – Ed. 66

Cintia Anahí Morales, Florencia Soto, Gisela Lorena Viterbo

Servicio de Endocrinología. Hospital de Pediatría Juan. P Garrahan, Buenos Aires, Argentina



A.Thorax X-ray: Osteolytic rounded and circumscribed lesion at the proximal right humerus (arrow).

B. Renal ultrasound. Increased renal echogenicity secondary to calcium deposits compatible with nephrocalcinosis (arrow head).


A 9 months old boy diagnosed with disseminated BCGítis was referred to this Hospital for second opinion.
He is the second child of healthy non-consanguineous parents, product of a controlled pregnancy, born by vaginal delivery, full-term and with adequate weight for gestational age. He has a healthy 6-year-old brother.
At 5 months old right axillary adenitis was diagnosed, and he received intravenous antibiotic treatment for 10 days. Mycobacterium bovis was rescued in drained collection culture, so he started on Isoniacid and Rifampicin treatment. Approximately one month later, he presented with another lesion in the right submaxillary region, abscessed, that drained spontaneously, so Etambutol was added.

Because the lesions present insufficient clinical response to treatment and the baby developed failure to thrive his parents asked for a second opinion.

On physical examination at 9 months old, he was in relatively good general condition, afebrile, and normohydrated. His parents referred polydipsia and polyuria that started several months before. He had abscessed lesions at the submaxillary and right axillary regions. He was clinically euthyroid with normal male genitalia. Weight: 7.930 kg (-1 SDS), Length: 70.7 cm (-0.76 SDS), Head circumference: 45.5 cm (PC 75).

The diagnosis was of disseminated infection by mycobacterium BCG (Bacillus Calmette-Guérin) and the patient was admitted to the hospital for further immunological studies, and treatment.

Complementary studies:
-Thorax X-ray without pulmonary involvement. Osteolytic rounded and circumscribed lesion in the proximal right humeral bone.
– Abdominal ultrasound: Multiple hypoechoic and irregular lesions in the spleen and nephrocalcinosis.
– Biochemical studies that showed hypercalcemia and hypercalciuria (TABLE 1)

With these results, he was referred to the Endocrinology Service. The baby presented with a symptomatic severe PTH independent hypercalcemia (polydipsia, polyuria, slight drop in glomerular filtration rate, nephrocalcinosis). Excessive calcitriol production due to disseminated granulomatous lesions was suspected as the most probable mechanism.Vitamin D intake was suspended. Hyper-hydration and treatment with PHP at 150ml / kg / d (3000ml / m2 / day) and furosemide (0.5mg / kg / dose BID) were started. After 48 hours of hospitalization, bisphosphonates were added with a good response; as the general measures were suspended, a new increase in calcemia was observed, so the patient received another infusion of pamidronate.

Table 1. Laboratory tests and treatment


Due to the disseminated infection, the Infectology Service added levofloxacin to the antibiotic scheme.
With concerns regarding the Immunological aspect, diseases such as HIV, Chronic Granulomatous Disease and Severe Combined Immunodeficiency were ruled out. Studies were conducted to assess IL-12 / IFN-gamma pathway deficiencies that were suggestive of Mendelian Susceptibility to Mycobacteria, the specific molecular study is ongoing.

Clinical multidisciplinary control will continue on an outpatient basis.

Several diseases and infections that cause granulomas and secondary hypercalcemia have been described, such as Tuberculosis and other mycobacteria, Leprosy, HIV, Cat scratch disease, fungi infections (histoplasmosis, coccidioidomycosis), CMV, Sarcoidosis, Crohn’s disease, Subcutaneous fat necrosis of the newborn (1) and in recent years, secondary to granulomas of injections of methylmethacrylate, silicone, cosmetic oils.

The underlying pathophysiological mechanism is based on the fact that macrophages represent an extrarenal site of 1α-hydroxylase activity and the sequestration of these cells in granulomas and inflammatory tissues can cause a dysregulated production of 1,25 (OH) vitamina D independent of PTH, calcemia, phosphatemia and other regulators. Classically, the increase in calcemia and the production of calcitriol inhibit PTH with the consequent increase of calciuria.
Over time, hypercalcemia and hypercalciuria can produce nephrocalcinosis and renal failure (1).
Hypercalcemia secondary to BCG-induced granulomas (vaccine prepared from attenuated extract of Mycobacterium bovis) has been previously described in older adults when it was used as an immunotherapeutic agent in bladder cancer (3,4). We have found two reported cases of infants with hypercalcemia secondary to BCGitis followed to BCG vaccine applied at birth (5,6).

The therapy in these cases consists of suppressing calcium and vitamin D supplements, hyperhydration in conjunction with diuretics such as furosemide and the treatment of the underlying disease. Subcutaneous calcitonin is an effective antiresorptive agent for symptomatic hypercalcemia but its effects have a short half-life and produce tachyphylaxis (1). Corticosteroids are also used, since they reduce the production of 1,25-OH2 vitD and decrease the intestinal absorption of calcium, but this effect is not constant, it is limited in time and it has important adverse effects in this age group. Bisphosphonates are another possible option for their more constant and constant effect, of them pamidronate (0.5-1.0 mg / kg) is the most commonly used in children (6).



  1. Stokes V. Hypercalcemic Disorders in Children. Journal of Bone and Mineral Research. 2017.
  2. Lietman, Levine etal.Hypercalcaemia in children and adolescents. CurrOpin Pediat2010 22 (4) 508-515
  3. Ami Schattner, AviGilad, Joel Cohen. Systemic granulomatosis and hypercalcaemia following intravesical bacillus Calmette-Guerin immunotherapy. Journal of Internal Medicine.2002 ;251: 272-277.
  4. Navar N, Briscoe K. Systematic Bacillus Calmette-Guerin sepsis manifesting as hyperclcaemia and thrombocytopenia as a complication of intravesicalCalmette-Guerin therapy. Intern Med J.2015 Oct;45(10):1091-2.
  5. GauthamPai, Satish Kumar, Shah, Ankita Pal, HariPrasadDhimal, Sushil Kumar Kabra. Disseminated BCG disease with unusual manifestation. Pediatric Infectious disease. Volme8, Issue 3. July- September 2016
  6. Kojmane W, Chaouki S, Souilmi FZ, Atmani S, Idrissi M, Bouharrou A, Hida M. Hypercalcemia complicating BCG lymphadenitis. Arch Pediatr.2015 Mar;22(3):276-8.

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