Calcium and Bone Disorders — Written Clinical Reasoning

SAQ 1 — Primary Hyperparathyroidism with Osteoporosis, CKD, and Nephrolithiasis (20 marks, 30 minutes)

Prompt: Outline your integrated assessment, the investigations you would order, your immediate and definitive management plan addressing each problem, and the shared decision-making framework. Justify each decision with reference to evidence. [1]

Model Answer

Problem list (4 marks): [1]

1. Primary hyperparathyroidism — hypercalcaemia with inappropriately elevated PTH, hypophosphataemia, elevated ALP, meeting multiple Fifth International Workshop criteria for parathyroidectomy.
2. Osteoporosis with prior fragility fracture — T-scores below -2.5 at all three DEXA sites, plus a distal radial fracture 18 months ago; severe (established) osteoporosis.
3. CKD stage 3b — eGFR 42 mL/min, which independently meets the surgical criterion and constrains bisphosphonate dosing.
4. Nephrolithiasis — 5 mm right renal stone on ultrasound; another surgical criterion.
5. Vitamin D deficiency — 25-hydroxyvitamin D 32 nmol/L; common in PHPT and worsens the disease.
6. Symptomatic hypercalcaemia — fatigue, polyuria, and bone pain attributable to the elevated calcium. [1]

Step 1 — Confirm the diagnosis and complete the workup (3 marks): [1]

The biochemical pattern is diagnostic of primary hyperparathyroidism — corrected calcium 2.85 mmol/L with an inappropriately high PTH of 8.5 pmol/L, hypophosphataemia (PTH-mediated phosphaturia), and elevated ALP (high bone turnover). I would first exclude familial hypocalciuric hypercalcaemia (FHH) by calculating the calcium-to-creatinine clearance ratio — the 24-hour urinary calcium of 310 mg and a clearance ratio above 0.02 confirm calciuria consistent with PHPT and exclude FHH (which has a ratio below 0.01) [1]. I would check a serum and urine protein electrophoresis to exclude coexisting myeloma (a cause of bone pain and fractures in this age group) and screen for MEN1 if there is any family history of endocrine tumours. I would arrange a parathyroid sestamibi (MIBI) scan with SPECT-CT and a high-resolution neck ultrasound to localise the adenoma pre-operatively (both together have a localisation rate of 85 to 90% in single-gland disease). I would repeat the DEXA formally to confirm the measurements and perform a lateral thoracolumbar spine X-ray to look for unrecognised vertebral fractures.

Step 2 — Assess the surgical indication (3 marks): [1]

This patient meets four of the Fifth International Workshop (2022) criteria for parathyroidectomy [1]:

• Serum calcium 0.3 mmol/L above the upper limit of normal (criterion is above 0.25).
• T-score below -2.5 at all sites plus a prior fragility fracture.
• eGFR below 60 (criterion is below 60).
• 24-hour urinary calcium above 300 mg (criterion is above 300 mg in men or above 250 mg in women) and nephrolithiasis on imaging.

She is a clear surgical candidate. I would refer to an experienced endocrine surgeon (minimum caseload is associated with cure rates above 95% for single adenoma). [1]

Step 3 — Pre-operative optimisation (2 marks): [1]

Before surgery, I would replete the vitamin D deficiency cautiously — colecalciferol 1000 to 2000 IU daily (not high-dose loading, as this can transiently raise calcium in PHPT). I would ensure the patient is well hydrated. I would check vocal cord function pre-operatively (baseline for recurrent laryngeal nerve assessment). I would manage the hypertension perip­eratively. [1]

Step 4 — Post-operative management and hypocalcaemia prevention (3 marks): [1]

Post-parathyroidectomy, I would anticipate hungry bone syndrome — the sudden drop in PTH causes rapid osteoblast-mediated bone uptake of calcium and phosphate, producing hypocalcaemia that can be profound and prolonged. I would check calcium within 6 hours post-op, then every 6 to 12 hours for the first 48 hours. I would start oral calcium carbonate 1 to 2 g three times daily and calcitriol 0.5 to 1 microgram daily as soon as the patient can tolerate oral intake, and use IV calcium gluconate for symptomatic or severe hypocalcaemia (corrected calcium below 1.9 mmol/L or symptoms). I would check PTH intra-operatively (if available) to confirm cure (a drop of more than 50% at 10 minutes post-excision predicts cure). [1]

Step 5 — Osteoporosis management (3 marks): [1]

Her osteoporosis is severe (T-score below -2.5 with a prior fracture). The primary treatment is cure of the PHPT, which improves bone density over 1 to 3 years. However, given her very high risk (prior fracture, multiple-site T-scores below -2.5), I would also initiate antiresorptive therapy after parathyroidectomy once the calcium has stabilised — the 2020 AACE/ACE guidelines recommend pharmacotherapy for all patients with T-score below -2.5 or a prior fragility fracture [5]. Given her CKD (eGFR 42), IV zoledronic acid needs dose reduction (3.5 mg if CrCl 35 to 60). Oral alendronate is an alternative if renal function is acceptable and she can tolerate oral therapy. She should also receive calcium 1000 to 1200 mg elemental daily and vitamin D to maintain 25-hydroxyvitamin D above 50 nmol/L [6].

Step 6 — Communication, shared decision-making, and follow-up (2 marks): [1]

I would frame the consultation around the fact that her PHPT meets clear surgical criteria, that parathyroidectomy is the only definitive cure, and that surgery will address the hypercalcaemia, slow the bone loss, and reduce her stone risk. I would present the surgical risk honestly — cure rate above 95% in experienced hands, risk of permanent hypoparathyroidism 1 to 5%, risk of recurrent laryngeal nerve injury 1 to 2%, and the certainty of transient hypocalcaemia requiring temporary calcium and calcitriol. I would document her decision, arrange the surgical referral, and plan a post-operative review at 2 to 4 weeks and then at 6 months with a DEXA. [1]

SAQ 2 — Emergency Management of Severe Hypercalcaemia of Malignancy (10 marks, 20 minutes)

Prompt: A 65-year-old man with metastatic squamous cell carcinoma of the lung is admitted from the oncology clinic with confusion, polyuria, and constipation. Corrected calcium is 3.9 mmol/L, phosphate 1.3 mmol/L, intact PTH 0.6 pmol/L, PTHrP elevated, creatinine 140 micromol/L (baseline 90). Outline the emergency management, the sequencing and rationale of each intervention, and the anticipated timeline of effect. [1]

Model Answer

Step 1 — Recognise the emergency and the mechanism (2 marks): [1]

This is severe symptomatic hypercalcaemia of malignancy — corrected calcium above 3.5 mmol/L with neurological symptoms (confusion), dehydration (polyuria from nephrogenic diabetes insipidus induced by hypercalcaemia), and AKI. The mechanism is humoral hypercalcaemia of malignancy (PTHrP-mediated), confirmed by the suppressed PTH and elevated PTHrP [7]. The AKI is pre-renal from volume depletion and nephrocalcinosis.

Step 2 — Aggressive volume expansion (2 marks): [1]

The immediate priority is IV normal saline 3 to 6 L over the first 24 hours (starting at 200 to 300 mL per hour, titrated to euvolaemia and urine output of 100 to 150 mL per hour). This is the single most important first step — it reverses the dehydration, restores glomerular filtration, and promotes calciuresis by suppressing proximal tubular sodium and calcium reabsorption. I would monitor fluid balance, JVP, oxygen saturation, and urine output carefully given his AKI. I would NOT give furosemide until he is volume-replete, and would not use it routinely even then [3].

Step 3 — Antiresorptive therapy (3 marks): [1]

Once saline is running, I would give IV zoledronic acid 4 mg over 15 minutes. His creatinine is 140 micromol/L (estimated CrCl approximately 50 mL/min), so I would dose-reduce to 3.5 mg per the product information for CrCl 35 to 60. Zoledronic acid inhibits osteoclast-mediated bone resorption; the calcium begins to fall over 2 to 4 days, with a nadir at 4 to 7 days and a duration of 1 to 4 weeks [2]. If his renal function were to deteriorate further (CrCl below 35), I would use subcutaneous denosumab 120 mg instead, as it is not renally excreted.

Step 4 — Calcitonin as a bridge (1 mark): [1]

For the first 48 hours while waiting for the zoledronic acid to take effect, I would give calcitonin 4 to 8 IU per kg subcutaneously every 12 hours. Calcitonin lowers calcium within hours by inhibiting osteoclasts and increasing renal calcium excretion. Tachyphylaxis develops after 48 hours, so it is a bridge only, not sustained therapy [2].

Step 5 — Monitor, treat the cancer, and involve palliative care (2 marks): [1]

I would monitor corrected calcium, renal function, electrolytes (potassium, magnesium, phosphate), and mental state every 6 to 12 hours. I would correct hypomagnesaemia and hypokalaemia. I would liaise with oncology regarding anticancer therapy, which is the only definitive way to control PTHrP production. I would involve palliative care early, as hypercalcaemia of malignancy in advanced disease carries a poor prognosis (median survival 30 to 60 days without effective anticancer therapy) and the goals of care need to be clarified — repeated bisphosphonate or denosumab cycles may be appropriate for symptom control, but the overall trajectory needs to be discussed with the patient and family [2].