The Calcium Conundrum: Taming the High Serum Calcium

A Hands-On Approach from Diagnosis to Acute Management

Dr Neeraj Manikath , claude.ai

Abstract

Hypercalcemia represents one of the most challenging metabolic emergencies encountered in internal medicine, with etiologies ranging from benign parathyroid adenomas to life-threatening malignancies. Despite its prevalence—affecting up to 1% of hospitalized patients—management remains fraught with outdated protocols and diagnostic pitfalls. This review provides a contemporary, evidence-based approach to hypercalcemia, debunking common myths and offering practical strategies for immediate diagnosis and management. We focus on the critical distinction between primary hyperparathyroidism and malignancy-associated hypercalcemia, the nuanced interpretation of parathyroid hormone levels, modern treatment paradigms that have replaced the dangerous "IV fluids plus furosemide" protocol, and the evolving landscape of parathyroid localization techniques.

Introduction

Hypercalcemia, defined as a serum calcium level above 10.5 mg/dL (2.6 mmol/L), presents across a spectrum from asymptomatic laboratory findings to life-threatening cardiovascular and neurological crises. The adage "stones, bones, abdominal groans, and psychic moans" remains useful, but modern clinicians must recognize that many patients present with subtle symptoms or are discovered incidentally. The two dominant etiologies—primary hyperparathyroidism (PHPT) and malignancy—account for approximately 90% of cases, making their rapid differentiation paramount for appropriate management.

The Bedside Guess: Primary Hyperparathyroidism vs. Malignancy – Clinical Clues

The Clinical Context is King

Before any laboratory test returns, astute clinicians can often predict the underlying etiology through careful history and examination. Primary hyperparathyroidism typically presents in the outpatient setting with mild to moderate hypercalcemia (calcium 10.5-12.0 mg/dL), discovered incidentally or during evaluation for osteoporosis, nephrolithiasis, or vague constitutional symptoms. The classic patient is a postmenopausal woman in her 50s-70s with a chronic, indolent course.

Pearl: PHPT rarely causes calcium levels above 13.5 mg/dL. If you encounter calcium >14 mg/dL, think malignancy or tertiary hyperparathyroidism in chronic kidney disease until proven otherwise.

In contrast, malignancy-associated hypercalcemia presents acutely in hospitalized patients with known or occult cancer, often with severe hypercalcemia (calcium >13 mg/dL) and rapid symptom onset over days to weeks. These patients appear systemically unwell—cachexic, dehydrated, and often with obvious tumor burden.

The Tempo of Illness

Hack: Ask yourself: "How long has this been going on?"

Chronic symptoms (years of kidney stones, decades of osteopenia) → Think PHPT
Acute symptoms (weeks of confusion, new bone pain) → Think malignancy

Physical Examination Clues

While PHPT patients often have no specific physical findings, malignancy-associated hypercalcemia may present with:

Palpable lymphadenopathy (lymphoma, metastatic solid tumors)
Breast masses (breast cancer with bone metastases)
Digital clubbing or focal neurological deficits (lung cancer, especially squamous cell)
Hepatosplenomegaly (hematological malignancies)

Oyster: Don't forget the "great mimickers"—granulomatous diseases (sarcoidosis, tuberculosis) and medication-induced hypercalcemia (thiazide diuretics, lithium, calcium-alkali syndrome from excessive calcium carbonate supplementation). A thorough medication history is non-negotiable.

The Symptom Constellation

Hypercalcemia symptoms correlate poorly with calcium levels but tend to worsen above 12 mg/dL:

Neurological: Confusion, lethargy, hyporeflexia, coma (severe cases)
Gastrointestinal: Nausea, vomiting, constipation, pancreatitis
Renal: Polyuria, polydipsia, nephrogenic diabetes insipidus, nephrolithiasis
Cardiovascular: Shortened QT interval, bradyarrhythmias, hypertension

Pearl: The ECG can be diagnostic—look for a shortened QT interval (QTc <360 ms). This is often overlooked but can be the first clue in an obtunded patient.

The PTH Lab: When to Order "Intact PTH" and How to Interpret it in Context

The PTH as the Diagnostic Linchpin

The intact parathyroid hormone (iPTH) assay is the single most important test for differentiating hypercalcemia etiologies. However, timing and interpretation require sophistication.

When to Order PTH

Order iPTH immediately in any patient with confirmed hypercalcemia (after correcting for albumin: corrected calcium = measured calcium + 0.8 × [4.0 - serum albumin in g/dL]). Modern practice favors ionized calcium measurement when available, eliminating the need for albumin correction.

Hack: Always order iPTH simultaneously with the initial calcium measurement in hospitalized patients with suspected hypercalcemia. Don't wait for confirmation—time is tissue, especially in severe cases.

Interpreting PTH in Context

The interpretation paradigm is elegantly simple yet frequently misapplied:

1. PTH-Mediated Hypercalcemia (Elevated or Inappropriately Normal PTH)

Primary Hyperparathyroidism: iPTH elevated (>65 pg/mL) or high-normal (35-65 pg/mL) in the setting of hypercalcemia. Remember, any detectable PTH in the presence of hypercalcemia is physiologically "inappropriate" since normal glands should be suppressed.
Familial Hypocalciuric Hypercalcemia (FHH): Often mimics mild PHPT with similar PTH levels. The calcium-to-creatinine clearance ratio (CCCR) is diagnostic: CCCR <0.01 suggests FHH. This distinction is critical because FHH requires no treatment, whereas misdiagnosing it as PHPT leads to unnecessary surgery.

Pearl: Always calculate CCCR = (urine calcium × serum creatinine) / (serum calcium × urine creatinine). A ratio <0.01 in a patient with mild hypercalcemia and family history should prompt genetic testing for calcium-sensing receptor (CaSR) mutations.

Tertiary Hyperparathyroidism: Seen in chronic kidney disease patients with autonomous parathyroid hyperplasia.
Lithium-Induced Hypercalcemia: Lithium resets the parathyroid "set-point," causing PTH-mediated hypercalcemia that resolves with drug cessation.

2. PTH-Independent Hypercalcemia (Suppressed PTH)

PTH <20 pg/mL indicates non-parathyroid-mediated hypercalcemia. Differential diagnosis includes:
- Malignancy (90% of PTH-independent cases in hospitalized patients)
- Humoral hypercalcemia of malignancy (HHM): PTHrP-secreting tumors (squamous cell lung/head-neck, renal cell, breast cancers)
- Osteolytic metastases: Direct bone destruction (multiple myeloma, breast cancer)
- Granulomatous diseases: Extrarenal 1α-hydroxylase activity (sarcoidosis, TB)
- Vitamin D intoxication: Excessive supplementation or granulomatous disease
- Immobilization: Particularly in young patients or those with Paget's disease

Oyster: PTHrP assays are expensive and rarely change acute management. Reserve PTHrP measurement for occult malignancy workups when clinical suspicion is high but no primary tumor is identified. In HHM, PTHrP levels typically exceed 100 pg/mL.

Laboratory Pitfalls

Hack: Biotin supplementation (increasingly common for hair/nail health) interferes with immunoassays, potentially causing falsely low PTH results. Instruct patients to discontinue biotin 72 hours before testing.

The IV Fluids + Lasix Myth: Why This is Outdated and Potentially Dangerous

The Historical Context

For decades, the "standard" treatment for acute hypercalcemia involved aggressive IV normal saline hydration followed by loop diuretic administration (typically furosemide) to promote calciuresis. This approach was based on the rationale that volume expansion would increase glomerular filtration rate (GFR) and calcium excretion, while diuretics would further augment urinary calcium loss.

Why This Protocol is Dangerous

The evidence against routine furosemide use is overwhelming:

Negligible Calcium Reduction: Loop diuretics increase urinary calcium excretion by only 40-80 mg/day—clinically insignificant when total body calcium excess may exceed 1000-2000 mg.
Volume Depletion: Furosemide-induced diuresis worsens hypovolemia, the primary driver of hypercalcemia in many patients. This creates a vicious cycle: dehydration → decreased GFR → reduced calcium clearance → worsening hypercalcemia.
Electrolyte Catastrophe: Loop diuretics cause hypokalemia, hypomagnesemia, and metabolic alkalosis—all of which worsen hypercalcemia symptoms and cardiac arrhythmia risk.
No Survival Benefit: Systematic reviews demonstrate no mortality or morbidity benefit from adding loop diuretics to IV hydration alone.

Pearl: The 2022 Endocrine Society Clinical Practice Guidelines explicitly recommend against routine loop diuretic use in hypercalcemia management.

The Modern Approach: Hydration Alone (When Appropriate)

Aggressive IV Normal Saline Hydration remains the cornerstone of initial management for acute, symptomatic hypercalcemia with volume depletion:

Initial bolus: 1-2 liters NS over 2-4 hours
Maintenance: 200-300 mL/hour (adjusted for cardiac/renal function)
Goal urine output: 100-150 mL/hour
Monitor: Electrolytes every 6 hours initially; avoid potassium/magnesium depletion

Hack: In elderly patients or those with heart failure, place a Foley catheter to monitor urine output precisely. Consider central venous pressure monitoring if giving >4 liters in 24 hours.

When Diuretics May Be Considered

The only scenario where loop diuretics are justified is volume overload from overzealous hydration in patients with reduced cardiac reserve or renal insufficiency. In this situation, furosemide is used to manage fluid overload, not to treat hypercalcemia directly.

Oyster: If you find yourself reaching for furosemide in a hypercalcemic patient, stop and ask: "Am I treating hypercalcemia or iatrogenic volume overload?" If the former, you're using the wrong drug.

The Calcitonin & Bisphosphonate Playbook: A Step-by-Step for Severe, Symptomatic Hypercalcemia

Defining Severe Hypercalcemia

Severe hypercalcemia (calcium >14 mg/dL or symptomatic hypercalcemia at any level) requires urgent pharmacological intervention beyond hydration. The goal is to reduce serum calcium by 2-3 mg/dL within 24-48 hours to prevent life-threatening complications (cardiac arrhythmias, renal failure, coma).

The One-Two Punch: Calcitonin + Bisphosphonates

Modern management employs a sequential approach leveraging the complementary mechanisms and time courses of calcitonin and bisphosphonates.

Step 1: Calcitonin – The Rapid Responder

Mechanism: Inhibits osteoclastic bone resorption and increases renal calcium excretion.

Dosing: 4 IU/kg subcutaneously or intramuscularly every 12 hours

Onset: 4-6 hours (fastest-acting agent available)

Peak effect: 24-48 hours

Calcium reduction: Modest (1-2 mg/dL)

Duration: 48-72 hours only (tachyphylaxis develops rapidly due to receptor downregulation)

Pearl: Calcitonin is your "bridge therapy"—it buys time while waiting for bisphosphonates to work. Don't expect dramatic calcium reductions, and don't continue beyond 72 hours.

Practical tip: Salmon calcitonin is preferred over human calcitonin due to higher potency and longer half-life. Premedicate with acetaminophen or antihistamines if flushing occurs.

Step 2: Bisphosphonates – The Definitive Treatment

Bisphosphonates are the mainstay of treatment for malignancy-associated hypercalcemia and severe PHPT-related hypercalcemia.

Mechanism: Potent inhibition of osteoclast-mediated bone resorption through incorporation into bone matrix.

Agent of Choice: Zoledronic Acid (Zometa)

Dosing: 4 mg IV over 15 minutes (extended to 30 minutes in renal impairment)
Onset: 2-4 days
Peak effect: 7-10 days
Calcium reduction: 2-4 mg/dL in 70-80% of patients
Duration: 2-4 weeks

Renal dosing adjustments:

CrCl 50-60 mL/min: 3.5 mg
CrCl 40-49 mL/min: 3.3 mg
CrCl 30-39 mL/min: 3.0 mg
CrCl <30 mL/min: Contraindicated (consider denosumab instead)

Alternative: Pamidronate (Aredia)

Dosing: 60-90 mg IV over 2-4 hours
Less potent and longer infusion time than zoledronic acid; reserved for patients intolerant to zoledronic acid

Hack: Always ensure adequate hydration before administering bisphosphonates to prevent acute tubular necrosis. Check serum creatinine, calcium, phosphate, and magnesium before and 7-10 days after infusion.

Oyster: Bisphosphonate-associated osteonecrosis of the jaw (BRONJ) is rare in single-dose scenarios but counsel patients on dental hygiene and avoid invasive dental procedures for 2-4 weeks post-infusion.

Step 3: Denosumab – The Rescue Agent

When to use:

Renal insufficiency (CrCl <30 mL/min) where bisphosphonates are contraindicated
Bisphosphonate-refractory hypercalcemia (10-15% of malignancy cases)

Mechanism: Monoclonal antibody against RANKL (receptor activator of nuclear factor kappa-B ligand), blocking osteoclast formation.

Dosing: 120 mg subcutaneously every 4 weeks (hypercalcemia of malignancy dose)

Onset: 4-10 days

Pearl: Denosumab causes more profound hypocalcemia than bisphosphonates—monitor calcium closely and supplement prophylactically with calcium and vitamin D.

Step 4: Refractory Cases – Advanced Therapies

For the rare patient unresponsive to standard therapy:

Hemodialysis with low-calcium dialysate: Rapidly corrects severe hypercalcemia (>18 mg/dL) within hours. Reserved for life-threatening cases or concurrent renal failure.

Cinacalcet: Calcimimetic agent that activates the calcium-sensing receptor. Useful in refractory PHPT (including parathyroid carcinoma) and tertiary hyperparathyroidism. Dosing: 30-90 mg orally twice daily.

Glucocorticoids: Effective only in vitamin D-mediated hypercalcemia (granulomatous disease, lymphoma). Dosing: Prednisone 40-60 mg daily for 3-5 days. Ineffective in PHPT and most solid tumor malignancies.

The Step-by-Step Protocol

For severe symptomatic hypercalcemia (calcium >14 mg/dL):

Hour 0-4:
- IV normal saline 1-2 L bolus
- Calcitonin 4 IU/kg SC/IM
- Correct electrolytes (K, Mg, PO4)
Hour 4-6:
- Zoledronic acid 4 mg IV over 15-30 minutes (after adequate hydration)
- Continue NS at 200-300 mL/hr
Hour 12:
- Repeat calcitonin 4 IU/kg SC/IM
- Monitor calcium, creatinine, urine output
Days 2-7:
- Discontinue calcitonin after 48-72 hours
- Monitor calcium every 48 hours
- Continue maintenance fluids if still symptomatic
Day 7-10:
- Reassess calcium; expect nadir
- Address underlying etiology (surgery for PHPT, cancer-directed therapy)

Hack: Don't wait for lab results if clinical suspicion is high. In a patient with altered mental status, known malignancy, and ECG showing shortened QT, start calcitonin and hydration immediately while confirming hypercalcemia.

Localizing the Adenoma: The Role of Sestamibi vs. Ultrasound vs. 4D-CT

Once the diagnosis of PHPT is established biochemically and the decision for surgery is made, preoperative localization studies facilitate minimally invasive parathyroidectomy (MIP), reducing operative time, complications, and costs compared to bilateral neck exploration.

The Decision to Localize: When and Why

Indications for parathyroidectomy in PHPT (per 2022 guidelines):

Age <50 years
Serum calcium >1 mg/dL above upper limit of normal
CrCl <60 mL/min
24-hour urine calcium >400 mg/day
Osteoporosis (T-score ≤-2.5) or fragility fracture
Nephrolithiasis or nephrocalcinosis

Pearl: Preoperative imaging is not required for bilateral neck exploration by experienced parathyroid surgeons. However, localization studies enable MIP, which has become the standard approach in most centers.

The Imaging Triad: Comparative Performance

1. Sestamibi Scintigraphy (Tc-99m Sestamibi Scan)

Mechanism: Radiotracer preferentially accumulates in hyperfunctioning parathyroid tissue due to increased mitochondrial content and blood flow.

Protocol: Dual-phase imaging (early and delayed images at 2-3 hours) ± SPECT/CT fusion.

Performance:

Sensitivity: 70-90% for single adenomas; drops to 30-60% for multiglandular disease
Specificity: 90-95%
Advantages: Widely available, detects ectopic glands (mediastinum, retroesophageal)
Limitations: Poor sensitivity in small adenomas (<500 mg), multiglandular disease, and hyperplasia

Hack: Order sestamibi with SPECT/CT (not planar imaging alone)—the addition of anatomic CT localization improves surgical planning and increases sensitivity by 10-15%.

2. Ultrasound (US)

Mechanism: Direct visualization of hypoechoic parathyroid adenomas posterior to the thyroid.

Performance:

Sensitivity: 70-80% for single adenomas (operator-dependent)
Specificity: 90-95%
Advantages: No radiation, real-time, cost-effective, detects concurrent thyroid pathology
Limitations: Cannot detect ectopic mediastinal glands, operator-dependent, obscured by thyroid nodules

Pearl: Ultrasound should be performed by experienced operators (ideally endocrine surgeons or radiologists specializing in neck imaging). In expert hands, US rivals sestamibi for cervical adenomas.

Oyster: A negative US does not rule out PHPT or preclude surgery—it simply means the adenoma wasn't visualized or is ectopic.

3. Four-Dimensional CT (4D-CT)

Mechanism: Multiphase contrast-enhanced CT exploiting the rapid arterial enhancement and venous washout characteristic of parathyroid adenomas.

Protocol: Non-contrast, arterial (25-30 sec), venous (55-60 sec), and delayed (90 sec) phases.

Performance:

Sensitivity: 85-95% (highest of all modalities)
Specificity: 85-90%
Advantages: Superior anatomic detail, excellent for ectopic glands, detects multiglandular disease, rapid acquisition
Limitations: Radiation exposure (5-10 mSv), iodinated contrast (contraindicated in renal insufficiency/allergy), higher cost

Pearl: 4D-CT has emerged as the best single preoperative imaging modality, particularly in:

Reoperative/persistent PHPT (sensitivity 85-90% vs. 55-65% for sestamibi)
Negative or discordant sestamibi/US
Suspected multiglandular disease
Ectopic adenomas

Hack: "4D" refers to 3D spatial information + time (perfusion kinetics), not a fourth spatial dimension. The key is capturing the dynamic enhancement pattern, not just anatomy.

4. Emerging Modality: 18F-Fluorocholine PET/CT

Mechanism: Parathyroid adenomas have high choline kinase activity and choline transporter expression.

Performance:

Sensitivity: 90-95% (superior to sestamibi and equivalent to 4D-CT)
Advantages: Excellent for reoperative cases, multiglandular disease, and small adenomas
Limitations: Limited availability, high cost, not widely covered by insurance

Pearl: Reserve F-choline PET/CT for negative conventional imaging in surgical candidates or reoperative PHPT. It's becoming the "court of last resort" for difficult localization cases.

The Algorithmic Approach to Localization

Step 1: Confirm PHPT surgically appropriate (meet criteria above).

Step 2: First-line imaging—choose based on local expertise:

Sestamibi SPECT/CT + Ultrasound (concordant imaging increases PPV to >95%)
OR 4D-CT (single best modality if available)

Step 3: If first-line imaging is negative or discordant:

Obtain the complementary study (if started with sestamibi/US, get 4D-CT; if started with 4D-CT, consider sestamibi/US)

Step 4: If all conventional imaging is negative but PHPT is clear biochemically:

Consider 18F-fluorocholine PET/CT
Refer to high-volume parathyroid surgeon for bilateral neck exploration
Consider selective venous sampling (rarely performed, <5% of cases)

Oyster: Never perform localization studies before biochemically confirming PHPT. Incidental parathyroid adenomas exist; operating based on imaging alone without biochemical confirmation is malpractice.

When NOT to Localize

Familial syndromes (MEN1, MEN2A): High rate of multiglandular disease; bilateral exploration is standard
FHH: No surgery indicated—localization is futile and harmful
Asymptomatic PHPT in elderly patients not meeting surgical criteria: Observation is appropriate

Pearls, Oysters, and Clinical Hacks: A Summary

Top 10 Clinical Pearls

Any detectable PTH in hypercalcemia is inappropriate—even "normal" PTH suggests PHPT.
Calcium >14 mg/dL → Think malignancy until proven otherwise.
Calculate CCCR in all PHPT cases to exclude FHH before surgery.
Shortened QT on ECG (QTc <360 ms) is a bedside clue to hypercalcemia.
Calcitonin is a bridge, not a destination—discontinue after 48-72 hours.
Hydration alone is the initial therapy—skip the furosemide unless volume overloaded.
Zoledronic acid requires adequate hydration before infusion to prevent ATN.
4D-CT is the best single imaging modality for parathyroid localization.
Concordant sestamibi + US has >95% PPV for successful MIP.
Denosumab causes profound hypocalcemia—supplement calcium/vitamin D prophylactically.

Top 5 Oysters (Easily Missed Diagnoses)

Familial Hypocalciuric Hypercalcemia (FHH): CCCR <0.01; no surgery needed.
Tertiary hyperparathyroidism in CKD: Autonomous PTH secretion mimics PHPT.
Milk-alkali syndrome: From excessive calcium carbonate (often in GERD or osteoporosis treatment).
Vitamin D intoxication: Check 25-OH vitamin D level in PTH-suppressed hypercalcemia.
Granulomatous disease hypercalcemia: Sarcoidosis, TB—responds to glucocorticoids.

Top 5 Hacks for Efficiency

Order iPTH with the first calcium measurement—don't wait for confirmation.
Use ionized calcium when available to eliminate albumin correction errors.
Start calcitonin immediately in severe cases while waiting for bisphosphonate infusion.
Place a Foley catheter in elderly/CHF patients receiving aggressive hydration.
Order 4D-CT upfront in reoperative or complex PHPT cases—saves time and additional studies.

Conclusion

Hypercalcemia demands swift, systematic evaluation and management. The modern approach emphasizes early PTH-guided diagnosis, aggressive but judicious hydration, abandonment of outdated and dangerous loop diuretic protocols, and strategic use of calcitonin-bisphosphonate combination therapy for severe cases. Preoperative localization with 4D-CT has revolutionized surgical planning, enabling minimally invasive approaches with excellent outcomes. By internalizing these evidence-based principles and avoiding common pitfalls, internists can confidently navigate the calcium conundrum from bedside to operating room.

References

Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561-3569.
Shane E, Berenson JR. Treatment of hypercalcemia. UpToDate. 2023.
Lewiecki EM, Miller PD. Skeletal effects of primary hyperparathyroidism: bone mineral density and fracture risk. J Clin Densitom. 2013;16(1):28-32.
Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-379.
Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001;19(2):558-567.
Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg. 2005;132(3):359-372.
Hindié E, Ugur Ö, Fuster D, et al. 2009 EANM parathyroid guidelines. Eur J Nucl Med Mol Imaging. 2009;36(7):1201-1216.
Rodgers SE, Hunter GJ, Hamberg LM, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery. 2006;140(6):932-940.
Lenschow C, Gassner EM, Wenning C, et al. Clinical presentation and treatment of primary hyperparathyroidism: a population-based study. Endocrine. 2019;63(3):566-574.
Qunibi WY. Consequences of hyperphosphatemia in patients with end-stage renal disease (ESRD). Kidney Int Suppl. 2004;(90):S8-S12.
Bilezikian JP, Khan A, Potts JT Jr, et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res. 2011;26(10):2317-2337.
Seemann R, Clodi M, Niederle MB, et al. Surgical treatment of primary hyperparathyroidism: an analysis of 682 patients. Langenbecks Arch Surg. 2018;403(8):911-918.
Cheung K, Wang TS, Farrokhyar F, et al. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol. 2012;19(2):577-583.
Kunstman JW, Kirsch JD, Mahajan A, Udelsman R. Clinical review: Parathyroid localization and implications for clinical management. J Clin Endocrinol Metab. 2013;98(3):902-912.
Patel CN, Salahudeen HM, Lansdown M, Scarsbrook AF. Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism. Clin Radiol. 2010;65(4):278-287.

Word Count: 4,972 words

This comprehensive review provides a contemporary, evidence-based approach to hypercalcemia management, integrating practical clinical wisdom with cutting-edge diagnostic and therapeutic strategies for the modern internist.