Endocrine Abstracts

PTH-independent hypercalcaemia in infancy has a broad differential and poses a diagnostic challenge. Causes include vitamin D intoxication, idiopathic infantile hypercalcaemia (often due to CYP24A1 or SLC34A1 mutations), Williams-Beuren syndrome, subcutaneous fat necrosis, malignancy, and granulomatous diseases such as sarcoidosis or infections like tuberculosis. While Pneumocystis jirovecii pneumonia (PJP) is not classically associated with hypercalcaemia, case reports have described mild hypercalcaemia in immunosuppressed solid organ transplant recipients, particularly kidney and liver, leading to a diagnosis of PJP. We report an infant presenting with PTH-independent hypercalcaemia as the initial endocrine issue that led to a diagnosis of Pneumocystis jirovecii pneumonia secondary to an underlying primary immunodeficiency. A 5-month-old male presented with a two-week history of respiratory distress on a 2-month history of faltering growth. Investigations revealed persistent hypercalcaemia (adjusted calcium up to 3.33 mmol/l), suppressed PTH (0.3 pmol/l), and an inappropriately normal 1,25-dihydroxyvitamin D (209 pmol/l, reference range 77-471 pmol/l), suggesting a PTH-independent process. Vitamin D toxicity, genetic syndromes, and malignancy were excluded. Given an unsuppressed 1,25-vitamin D, granulomatous disease was considered, and PCR of bronchoalveolar lavage confirmed PJP. Immunological studies showed low IgG and IgA, elevated IgM, vaccine failure, and reduced CD40 ligand expression – consistent with X-linked hyper-IgM syndrome. Initial management of hypercalcaemia included intravenous fluid therapy and dietary calcium restriction. These measures were ineffective until targeted treatment for PJP, comprising intravenous co-trimoxazole and corticosteroids, was initiated. This led to clinical improvement and normalisation of serum calcium levels, permitting the reintroduction of standard feeding. The patient was commenced on regular immunoglobulin replacement therapy and is currently being assessed for haematopoietic stem cell transplantation.

Discussion: Our case is notable for unexplained hypercalcaemia as an initial feature of PJP. The proposed mechanism parallels other granulomatous diseases, where activated pulmonary macrophages and monocytes in inflammatory granulomas express extrarenal 1α-hydroxylase, driving increased 1,25-dihydroxyvitamin D production and PTH-independent hypercalcaemia.

Take-home message: Endocrinologists should consider opportunistic infections like Pneumocystis jirovecii in the differential diagnosis of PTH-independent hypercalcaemia, particularly in the context of known or suspected primary or secondary immunodeficiency.