This document presents the case of an 80-year-old woman with metastatic breast cancer and a history of parathyroid adenoma who presented with vomiting, diarrhea, fatigue and severe abdominal pain. Initial workup found hypercalcemia likely due to both bony metastases and primary hyperparathyroidism. She was aggressively rehydrated and further testing found suppressed PTH levels, supporting the diagnosis of hypercalcemia secondary to bony metastatic disease rather than parathyroid adenoma. Her calcium levels responded well to intravenous fluids and she was managed conservatively.

1. Intern Case Presentation Mrs EB

2. Overview Mrs B, 80yo woman, home alone, I with ADLs Presents with: 1/52 vomiting & diarrhoea, fatigue, malaise 5/7 constipation 3-4/7 severe generalised abdominal pain ~20kg weight loss since 4/08! Nil fevers/sweats; nil haematemesis/melaena/PR bleed PHx Metastatic breast ca  T3, ribs, femur, lungs on exemestane, monthly zolendronic acid (Zometa) Sick sinus sx (PPM inserted 4/4/08) Parathyroid adenoma Past DVT/PE on warfarin Rx: tamoxifen, warfarin, perindopril, vitamin D, pantoprazole, bisoprolol, GTN

3. Further PMHx Breast Ca: Dx 26 years ago: mastectomy, chemo, radiotherapy Recurrence 5 years ago; lung mets discovered and resected; commenced on aromatase inhibitor 4/08: bony mets  ribs 8 & 9, T3, femur Switched from aromatase inhibitor  tamoxifen Commenced on monthly zolendronic acid (bony mets)

4. Further PMHx Parathyroid adenoma: Episode of hypercalcaemia 4/08 PTH found to be high ?cause Sestamibi parathyroid scan: area of avid sestamibi uptake right lower neck corresponding to 2.0x1.0cm density on SPECT/CT ?parathyroid adenoma Surgery refused at this stage Sick sinus syndrome: Permanent pacemaker inserted 4/08

5. Examination Findings General findings Unwell thin looking elderly lady JVP low Dry mucous membranes BP 110/50, HR 100/regular, SaO2 95% RA, afebrile Abdominal exam Generalised tenderness w/o peritonism Bowel sounds present Chest Clear lung fields Dual heart sounds no added sounds

6. Investigations FBE: Hb 143/WCC 9.7/PLT 268 UEC: Na 129/K 3.3 Urea 13.4 Creat 92 eGFR 54 (baseline >60) Ca2+: 3.29 ; albumin 37; corr ca 3.35 ; Phos 0.75; Mg2+ 0.61 CRP 1.4, LFT normal AXR: multiple fluid-air levels suggestive of small bowel ileus. CXR: old right lower zone changes

7. Diagnosis Hypercalcaemia causing secondary ileus and marked volume depletion Dx Dilemma: cause = bony mets, parathyroid tumour or both?

8. Initial Management Rehydration: 1L N. Saline/2hrs (ED), 4L N. Saline/24hrs (and continued) Not for bisphosphanates as already on monthly zolendronic acid Ileus managed conservatively

9. Further Ix & Mx PTH 6/4/08 = 26.3 , Sestamibi- right lower neck PTH adenoma; sestamibi-avid metastatic disease right ribs, pleura, hilum ?PTHrP secreting mets Endocrinology: Dx likely due to combination of met breast ca and primary parathyroidism Recommended surgical referral for r/o adenoma However : PTH now = 0.1 (Suppressed by very high calcium?) Sestamibi scan for diagnosis of parathyroid lump, surgical opinion to follow Therefore diagnosis: Hypercalcaemia secondary to bony metastatic disease. Date 0145 24/6 0731 24/6 1900 24/6 0950 25/6 26/6 Calcium 3.29 2.84 2.92 2.81 2.57

10. Hypercalcaemia

11. The presentation of Hypercalcaemia can be as vague and confusing as this patient!

12. Calcium, Vit D, PTH metabolism

13. Calcium, Vit D, PTH metabolism

14. Calcium, Vit D, PTH metabolism

15. Causes :: Overview Parathyroid Adenomas Malignancy Renal failure Paget’s Disease Drugs – thiazides, calcium, lithium… Endocrine: Hyperthyroidism, addisonism Genetic – Hypervitaminosis D, Hypercalcaemic hypocalciuria Sarcoidosis, Granulomatosis (incl TB) Account for >90% of cases!

16. Causes :: When to suspect Past history of malignancy- esp bony mets, multiple myeloma Endocrine problems On calcium supplementation Renal patients Old people, delirium, confusion of unknown aetiology Specific drugs – calcium, lithium, thiazides, vitamin D etc Other indicators in HOPC/PHx

17. Causes :: Malignancy  (Poor prognostic factor)

18. Investigations Serial Ca, PO4 Correct Ca with albumin!! (40-Alb)*0.2 + serum Ca = corrected Ca UEC – renal function (ARF 2° dehydration/hypercalcaemia, CRF causing hypercalcaemia) PTH level, ALP, Vit D Consider multiple myeloma screen – ESR, serum electrophoresis, urine BJP etc. Consider ordering urine calcium – 24 hour urine calcium collection High PTH - Hyperparathyroidism: Sestamibi parathyroid scan Low PTH - Malignancy: CT chest, abdo, pelvis, bone scan

19. Management REHYDRATE aggressively with normal saline (aim for 200-300mL/hr initially then urine output 100-150mL/hr) Volume depletion most dangerous complication acutely Na+, H2O administration  renal Ca excretion Frusemide if overloaded – promotes renal ca excretion IV bisphosphanate eg pamidronate if Ca>3 Calcitonin if Ca resistant to intervention Steroids in granulomatous disease, multiple myeloma, others If Ca still doesn’t come down- consider haemodialysis

20. And of course… Treat the underlying cause. Renal failure: 2° hyperparathyroidism (high PTH) Calcimimetics – cinacalcet Vit D analogues (not increasing Ca) – paracalcitriol 3° hyperparathyroidism (autonomic PTH) Surgical intervention Parathyroid nodule/tumour: surgical intervention Granulomatous disease: steroids Drugs: cease offending drug Treat endocrine conditions