We present a complex diagnostic and management case of a 60-year-old female who presented with severe hypercalcemia, refractory to conventional therapy, on a background of chronic stage IV diabetic nephropathy (Cr247 umol/L). Our patient presented with asymptomatic PTH-independent hypercalcemia (PTH 1.2pmol/L, CrCa 3.32mmol/L) with normal 25-hydroxy vitamin D (68nmol/L), mildly elevated 1,25-dihydroxyvitamin D (206 pmol/L), reduced ACE (<12U/L) and normal PTHrP. While undergoing further investigations to ascertain the cause, her calcium level remained persistently elevated above 3.0mmol/L for over five weeks despite intravenous fluids and multiple doses of pamidronate, denosumab and calcitonin.
The patient subsequently underwent a PET scan which revealed FDG avid lymphadenopathy and splenic uptake. A splenic biopsy was diagnostic of sarcoid-like well-formed, diffuse granulomas. Despite commencement of high-dose prednisolone therapy, her hypercalcaemia persisted. Moreover, judicious use of required intravenous fluid therapy was complicated by fluid overload on her background of chronic renal disease and had to be limited. Given her hypercalcemia was not responsive to steroid therapy, with a now normalised repeat 1,25-dihydroxyvitamin D (161pmol/L), the diagnosis of sarcoid-induced hypercalcemia was questioned. Ketoconazole was trialled as second-line with nil initial improvement in serum calcium levels until two weeks. After five weeks of ketoconazole and seven weeks of glucocorticoids calcium levels have normalised (2.20mmol/L).
This case illustrates the diagnostic and therapeutic challenges associated with asymptomatic hypercalcaemia attributed to systemic sarcoidosis on a background of chronic renal impairment. It demonstrates that hypercalcemia can occur in granuloma-forming disorders such as sarcoidosis and in the setting of only mildly elevated 1,25-dihydroxyvitamin levels. Contributing factors for refractory hypercalcaemia may include intravascular depletion and decreased calcium excretion, particularly in renal insufficiency. Therapy of choice includes hydration, glucocorticoids and second-line ketoconazole. It underscores the importance of considering systemic sarcoidosis as a potential aetiology in cases of acute PTH-independent hypercalcemia resistant to initial therapy.