Can a 21‑year‑old female with a giant‑cell tumor of the left distal femur, uncontrolled hyperthyroidism, mild leukocytosis, slightly elevated INR, and low‑normal serum calcium be cleared for wide resection and intramedullary nailing?

Surgical Clearance for Giant Cell Tumor Resection with Uncontrolled Hyperthyroidism

This patient should NOT be cleared for elective wide resection and intramedullary nailing until her hyperthyroidism is controlled, as her current thyroid function tests show overt hyperthyroidism (TSH 0.02, FT4 7.27) which significantly increases perioperative cardiac and metabolic risks.

Primary Contraindication: Uncontrolled Hyperthyroidism

Current Thyroid Status

• TSH is severely suppressed at 0.02 (reference 0.4-4.0) and FT4 is markedly elevated at 7.27 (reference 2.77-5.27), indicating overt, uncontrolled hyperthyroidism 1
• The patient discontinued methimazole after achieving euthyroid status but was lost to follow-up, resulting in disease recurrence 1

Perioperative Risks of Uncontrolled Hyperthyroidism

• Thyroid storm risk: Major surgery in uncontrolled hyperthyroidism can precipitate life-threatening thyroid storm with mortality rates of 20-30% 1
• Cardiac complications: Tachyarrhythmias, atrial fibrillation, high-output cardiac failure, and myocardial ischemia are significantly increased 1
• Metabolic derangements: Severe hyperthermia, dehydration, and electrolyte disturbances complicate anesthetic management 1

Secondary Concerns

Mild Coagulopathy

• INR is mildly elevated at 1.25 (normal <1.1), which poses bleeding risk during extensive bone resection 2
• This should be corrected with vitamin K (already prescribed) and rechecked before surgery 2

Leukocytosis

• WBC 13.5 with neutrophilia (71%) requires investigation to exclude active infection before proceeding with implant surgery 2
• Rule out occult infection at the tumor site or systemic infection 2

Low-Normal Calcium

• Serum calcium 2.24 mmol/L is at the lower end of normal, which is critical given the patient has received 6 weeks of denosumab 1, 3
• Denosumab suppresses osteoclast activity and can cause hypocalcemia, particularly problematic during the perioperative period 1, 3
• Brown tumor of hyperparathyroidism must be definitively excluded with parathyroid hormone levels, as this is a critical differential diagnosis for giant cell tumor 1, 4

Required Pre-Operative Optimization

Thyroid Control (MANDATORY)

• Restart methimazole immediately and delay surgery until euthyroid state is achieved (typically 6-8 weeks) 1
• Target TSH >0.4 and FT4 within normal range before proceeding 1
• Consider beta-blockade (propranolol or atenolol) for symptomatic control and to reduce perioperative cardiac risk 1
• Endocrinology consultation is essential for perioperative management 1

Coagulation Correction

• Continue vitamin K supplementation and recheck PT/INR; target INR <1.2 before major orthopedic surgery with hardware placement 2

Infection Workup

• Investigate source of leukocytosis with inflammatory markers (CRP, ESR) and blood cultures if indicated 2
• Ensure no local infection at tumor site 2

Calcium and Metabolic Optimization

• Maintain calcium and vitamin D supplementation (already prescribed) throughout denosumab treatment 1, 3
• Check parathyroid hormone level to exclude brown tumor as differential diagnosis 1, 4
• Monitor calcium closely perioperatively, as denosumab-treated patients are at risk for hypocalcemia 1, 3

Giant Cell Tumor Management Considerations

Denosumab Treatment Duration

• The patient has completed 6 weeks of denosumab, which is relatively short 1
• Optimal preoperative denosumab duration is up to 6 months for responding tumors to achieve cytoreduction and facilitate surgical resection 1
• However, curettage after denosumab is associated with higher local recurrence risk; complete resection (wide excision) is preferred after denosumab treatment 1

Surgical Approach

• Wide excision is appropriate given the extensive tumor (distal femur extending to mid-diaphysis) and prior denosumab treatment 1
• Wide excision has 0-12% local recurrence rates compared to 12-65% for intralesional curettage 1
• Intramedullary nailing is a reasonable reconstruction option for this location 2, 5

Post-Operative Denosumab Considerations

• Denosumab discontinuation carries risk of rebound hypercalcemia due to osteoclast reactivation, typically occurring 5-9 months after last dose 3
• Close calcium monitoring is essential if denosumab is discontinued post-operatively 3
• For unresectable disease, denosumab may require lifelong administration 1

Clinical Decision Algorithm

Step 1: Postpone surgery immediately due to uncontrolled hyperthyroidism 1

Step 2: Restart methimazole and refer to endocrinology 1

Step 3: Correct INR with vitamin K and investigate leukocytosis 2

Step 4: Check parathyroid hormone to exclude brown tumor 1, 4

Step 5: Reassess in 6-8 weeks when euthyroid (TSH >0.4, FT4 normal) 1

Step 6: Confirm INR <1.2, WBC normalized, calcium adequate before clearing for surgery 2, 3

Critical Pitfall to Avoid

Do not proceed with elective orthopedic surgery in uncontrolled hyperthyroidism, even for oncologic indications, as the risk of thyroid storm and cardiac complications outweighs the benefit of immediate tumor resection 1. Giant cell tumor, while locally aggressive, rarely metastasizes (5% rate), and a 6-8 week delay for medical optimization will not significantly compromise oncologic outcome 1.