The Calcium Conundrum: An Unexpected Diagnosis — ASN Events
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The Calcium Conundrum: An Unexpected Diagnosis (#409)

Samuel B Cato 1 2 , Rosalyn Ly 1 3 , Keeran Shivakumar 1 3 , Thuy Vu 1 3 4
  1. Austin Health, Heidelberg, VIC, Australia
  2. Bendigo Health, Bendigo, VIC, Australia
  3. Northern Health, Epping, VIC, Australia
  4. University of Melbourne, Austin Health, Melbourne, VIC, Australia

A 35-year-old Pacific Islander woman was admitted under Endocrinology with a 4-month history of malaise, 12 kilograms unintentional weight loss, and impaired cognition. Her history included type 2 diabetes mellitus, hypercholesterolaemia, and obesity. She was taking cholecalciferol 25 mcg. Investigations demonstrated elevated corrected calcium 3.14 mmol/L (2.1-2.6), undetectable PTH concentration, vitamin D 52 nmol/L (>75) and serum creatinine 82 umol/L (45-90; eGFR 80). She was treated with intravenous fluids, calcitonin, and zoledronate. 

Computed tomography revealed intracranial enhancement at the tectal plate and pituitary stalk, enlarged lymph nodes above and below the diaphragm, and multiple splenic lesions suspicious for lymphoma. Further testing showed elevated 1,25-vitamin D (209 pmol/L, 50-190) and serum ACE level (67 U/L, 20-70). Pituitary function testing demonstrated evolving hypopituitarism with low IGF-1 of 7.67 nmol/L (10.53-36.14), suppressed gonadotrophins [LH <0.2 IU/L (0.56-89.08), FSH 0.88 IU/L (1.38-16.69)], and secondary hypothyroidism [free T4 6.78pmol/L (9.0-19.0), free T3 2.3 pmol/L (2.4-6.0), inappropriately normal TSH 1.3 mU/L (0.4-4.9)]. Morning cortisol and ACTH were within normal limits. Prolactin was 1127 mIU/L (109-557).

Lymph node biopsy showed non-necrotising granulomas. Cerebrospinal fluid analysis and microbiological investigations were negative for tuberculosis. Following multidisciplinary review involving Haematology, Infectious Diseases, and Rheumatology a diagnosis of systemic sarcoidosis with neurosarcoidosis was made. Glucocorticoid therapy resulted in clinical improvement.

Although malignancy is the predominant cause of PTH-independent hypercalcaemia in hospitalised patients, sarcoidosis is an uncommon but important differential resulting from excess production of 1,25-dihydroxyvitamin D by activated macrophages within granulomas.(1-3) Hypercalcaemia occurs in up to 10% of patients with sarcoidosis and may be a presenting feature.(4) Corticosteroids are the mainstay of treatment as they suppress macrophage-mediated calcitriol production.(5)

This case highlights the importance of a structured diagnostic approach to PTH-independent hypercalcemia. It demonstrates the value of multidisciplinary collaboration in establishing the diagnosis of multisystem sarcoidosis and initiating appropriate therapy.

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  2. 2. Bollerslev J, Pretorius M, Heck A. Parathyroid hormone independent hypercalcemia in adults. Best Pract. Res. Clin. Endocrinol. Metab. 2018;32(5):621-638. doi: 10.1016/j.beem.2018.06.005
  3. 3. Walker MD, Shane E. Hypercalcemia: A review. JAMA. 2022;328(16):1624-1636. doi: 10.1001/jama.2022.18331.
  4. 4. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers. 2019:5:45. doi: https://doi.org/10.1038/s41572-019-0096-x
  5. 5. Robinson D, Crumpler D, Zhai G, Barney J. Response to corticosteroids and alternative therapies in sarcoidosis-related hypercalcemia: A guideline-lacking retrospective analysis. Sarcoidosis Vasc Diffuse Lung Dis.2025;42(2)16239. doi: 10.36141/svdld.v42i2.16239