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Emergency And Acute Medicine: Hyperparathyroidism
Basics
Description Hyperparathyroidism is characterized by excess parathyroid hormone (PTH) leading to metabolic effects including decreased urinary calcium excretion, increased urinary phosphate loss, increased renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, and increased calcium and phosphate release from bone. Hypercalcemia is the primary metabolic abnormality. Despite reduced renal calcium excretion, hypercalciuria occurs due to elevated serum calcium, often accompanied by urinary magnesium loss. Magnesium is essential for both PTH secretion and peripheral PTH action; hypomagnesemia may blunt PTH effects. Genetic associations include multiple endocrine neoplasia (MEN) syndromes: MEN 1 (hyperparathyroidism, pancreatic islet tumors, pituitary disease) and MEN 2 (hyperparathyroidism in MEN 2A, medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas in MEN 2B).
Etiology Primary hyperparathyroidism results from parathyroid adenoma (≈85%), hyperplasia (≈14%), or rarely carcinoma (<1%). Secondary hyperparathyroidism is a compensatory response to vitamin D deficiency or chronic kidney disease with hyperphosphatemia; calcium levels are low or normal with elevated PTH.
Diagnosis
Signs and symptoms Classic features include renal stones, bone pain, gastrointestinal complaints, and neuropsychiatric changes. Alert Hypercalcemic crisis presents with anorexia, nausea, vomiting, and progressive mental status depression.
History Symptoms correlate with severity and rapidity of hypercalcemia.
Pediatric considerations Neonates born to hypoparathyroid mothers may present with hypotonia, weakness, and lethargy; hypercalcemic infants may have distinctive facial features including broad forehead, epicanthal folds, underdeveloped nasal bridge, and prominent upper lip.
Physical exam Findings may include dehydration, hypertension despite volume depletion, cardiac conduction abnormalities (bradyarrhythmias, bundle branch block, complete heart block, asystole), shortened QT interval, potentiation of digoxin toxicity, neurologic deficits (decreased reflexes, proximal weakness, lethargy, coma), psychiatric symptoms (depression, anxiety, psychosis), gastrointestinal symptoms (anorexia, constipation, peptic ulcer disease, pancreatitis), musculoskeletal pain, gout or pseudogout, and renal manifestations including nephrolithiasis and nephrocalcinosis.
Essential workup Measure serum calcium and albumin to assess corrected calcium. Evaluate for symptoms of severe hypercalcemia or impending parathyroid crisis. If asymptomatic with normal ECG and corrected calcium <14 mg/dL, no further ED testing is required. If symptomatic or calcium ≥14 mg/dL, obtain ionized calcium, electrolytes, BUN/creatinine, phosphorus, magnesium, alkaline phosphatase, ESR, TSH, CBC, and chest radiograph.
Diagnosis tests and interpretation
Laboratory Correct calcium for albumin: corrected Ca (mg/dL) = measured Ca + 0.8 × (4 − albumin). Acidosis increases ionized calcium by reducing albumin binding. Phosphorus is typically low in primary hyperparathyroidism and elevated in secondary disease. Chloride-to-phosphate ratio >33 favors hyperparathyroidism; <30 suggests malignancy. Alkaline phosphatase is elevated in ~50% of cases. ESR and anemia are usually normal in hyperparathyroidism but elevated in malignancy or granulomatous disease. Magnesium is often low or low-normal. PTH is elevated in primary and secondary hyperparathyroidism. PTH-related peptide suggests malignancy-associated hypercalcemia.
Imaging Chest radiograph evaluates volume status and screens for malignancy or granulomatous disease.
Diagnostic procedures Definitive diagnosis and treatment are established with parathyroidectomy.
Differential diagnosis PTH-mediated causes include primary or secondary hyperparathyroidism and familial hypocalciuric hypercalcemia. Non-PTH causes include malignancy, vitamin D excess or granulomatous disease, immobilization (e.g., Paget disease), and drug-induced hypercalcemia (thiazides, lithium, vitamin A, aluminum antacids, estrogens, androgens, tamoxifen).
Treatment
Prehospital May present primarily with psychiatric manifestations.
Initial stabilization/therapy Place on cardiac monitor if symptomatic or calcium >14 mg/dL. Begin IV hydration with 0.9% normal saline and correct acidosis.
Emergency department management Treat hypercalcemia with aggressive isotonic saline hydration (≥250 mL/hr unless limited by heart failure) targeting urine output ≥100 mL/hr. After adequate hydration, add loop diuretics to enhance calciuresis; avoid thiazides. Consider glucocorticoids in vitamin D–mediated or granulomatous disease. Initiate bisphosphonates in coordination with endocrinology. Treat dysrhythmias conventionally and use extreme caution with digoxin. Stop contributing medications and monitor closely for heart failure and electrolyte disturbances. Use calcitonin when hydration is contraindicated and initiate dialysis for refractory hypercalcemia with renal failure.
Medication First line Normal saline infusion; furosemide 40 mg IV q2–4h after rehydration; prednisone 40–60 mg PO or hydrocortisone 100 mg IV. Second line (with endocrinology) Calcitonin salmon 4 U/kg SC q12h; pamidronate 60–90 mg IV depending on calcium level; zoledronic acid 4 mg IV; cinacalcet 30 mg PO daily or BID for secondary hyperparathyroidism or carcinoma.
Follow-up and disposition
Admission criteria Corrected calcium >14 mg/dL, symptomatic hypercalcemia, or cardiac conduction abnormalities.
Discharge criteria Asymptomatic patients with calcium <14 mg/dL who can maintain hydration.
Issues for referral Endocrinology referral for PTH evaluation and definitive management.
Follow-up recommendations Arrange outpatient PTH testing, reinforce hydration, and discontinue medications that increase calcium levels.
Key points Hyperparathyroid-related hypercalcemia is often mild and rarely exceeds 14 mg/dL; higher levels suggest malignancy. Measure ionized or albumin-corrected calcium. Administering loop diuretics before adequate hydration worsens hypercalcemia and is a common management error.
Basics
Description Hyperparathyroidism is characterized by excess parathyroid hormone (PTH) leading to metabolic effects including decreased urinary calcium excretion, increased urinary phosphate loss, increased renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, and increased calcium and phosphate release from bone. Hypercalcemia is the primary metabolic abnormality. Despite reduced renal calcium excretion, hypercalciuria occurs due to elevated serum calcium, often accompanied by urinary magnesium loss. Magnesium is essential for both PTH secretion and peripheral PTH action; hypomagnesemia may blunt PTH effects. Genetic associations include multiple endocrine neoplasia (MEN) syndromes: MEN 1 (hyperparathyroidism, pancreatic islet tumors, pituitary disease) and MEN 2 (hyperparathyroidism in MEN 2A, medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas in MEN 2B).
Etiology Primary hyperparathyroidism results from parathyroid adenoma (≈85%), hyperplasia (≈14%), or rarely carcinoma (<1%). Secondary hyperparathyroidism is a compensatory response to vitamin D deficiency or chronic kidney disease with hyperphosphatemia; calcium levels are low or normal with elevated PTH.
Diagnosis
Signs and symptoms Classic features include renal stones, bone pain, gastrointestinal complaints, and neuropsychiatric changes. Alert Hypercalcemic crisis presents with anorexia, nausea, vomiting, and progressive mental status depression.
History Symptoms correlate with severity and rapidity of hypercalcemia.
Pediatric considerations Neonates born to hypoparathyroid mothers may present with hypotonia, weakness, and lethargy; hypercalcemic infants may have distinctive facial features including broad forehead, epicanthal folds, underdeveloped nasal bridge, and prominent upper lip.
Physical exam Findings may include dehydration, hypertension despite volume depletion, cardiac conduction abnormalities (bradyarrhythmias, bundle branch block, complete heart block, asystole), shortened QT interval, potentiation of digoxin toxicity, neurologic deficits (decreased reflexes, proximal weakness, lethargy, coma), psychiatric symptoms (depression, anxiety, psychosis), gastrointestinal symptoms (anorexia, constipation, peptic ulcer disease, pancreatitis), musculoskeletal pain, gout or pseudogout, and renal manifestations including nephrolithiasis and nephrocalcinosis.
Essential workup Measure serum calcium and albumin to assess corrected calcium. Evaluate for symptoms of severe hypercalcemia or impending parathyroid crisis. If asymptomatic with normal ECG and corrected calcium <14 mg/dL, no further ED testing is required. If symptomatic or calcium ≥14 mg/dL, obtain ionized calcium, electrolytes, BUN/creatinine, phosphorus, magnesium, alkaline phosphatase, ESR, TSH, CBC, and chest radiograph.
Diagnosis tests and interpretation
Laboratory Correct calcium for albumin: corrected Ca (mg/dL) = measured Ca + 0.8 × (4 − albumin). Acidosis increases ionized calcium by reducing albumin binding. Phosphorus is typically low in primary hyperparathyroidism and elevated in secondary disease. Chloride-to-phosphate ratio >33 favors hyperparathyroidism; <30 suggests malignancy. Alkaline phosphatase is elevated in ~50% of cases. ESR and anemia are usually normal in hyperparathyroidism but elevated in malignancy or granulomatous disease. Magnesium is often low or low-normal. PTH is elevated in primary and secondary hyperparathyroidism. PTH-related peptide suggests malignancy-associated hypercalcemia.
Imaging Chest radiograph evaluates volume status and screens for malignancy or granulomatous disease.
Diagnostic procedures Definitive diagnosis and treatment are established with parathyroidectomy.
Differential diagnosis PTH-mediated causes include primary or secondary hyperparathyroidism and familial hypocalciuric hypercalcemia. Non-PTH causes include malignancy, vitamin D excess or granulomatous disease, immobilization (e.g., Paget disease), and drug-induced hypercalcemia (thiazides, lithium, vitamin A, aluminum antacids, estrogens, androgens, tamoxifen).
Treatment
Prehospital May present primarily with psychiatric manifestations.
Initial stabilization/therapy Place on cardiac monitor if symptomatic or calcium >14 mg/dL. Begin IV hydration with 0.9% normal saline and correct acidosis.
Emergency department management Treat hypercalcemia with aggressive isotonic saline hydration (≥250 mL/hr unless limited by heart failure) targeting urine output ≥100 mL/hr. After adequate hydration, add loop diuretics to enhance calciuresis; avoid thiazides. Consider glucocorticoids in vitamin D–mediated or granulomatous disease. Initiate bisphosphonates in coordination with endocrinology. Treat dysrhythmias conventionally and use extreme caution with digoxin. Stop contributing medications and monitor closely for heart failure and electrolyte disturbances. Use calcitonin when hydration is contraindicated and initiate dialysis for refractory hypercalcemia with renal failure.
Medication First line Normal saline infusion; furosemide 40 mg IV q2–4h after rehydration; prednisone 40–60 mg PO or hydrocortisone 100 mg IV. Second line (with endocrinology) Calcitonin salmon 4 U/kg SC q12h; pamidronate 60–90 mg IV depending on calcium level; zoledronic acid 4 mg IV; cinacalcet 30 mg PO daily or BID for secondary hyperparathyroidism or carcinoma.
Follow-up and disposition
Admission criteria Corrected calcium >14 mg/dL, symptomatic hypercalcemia, or cardiac conduction abnormalities.
Discharge criteria Asymptomatic patients with calcium <14 mg/dL who can maintain hydration.
Issues for referral Endocrinology referral for PTH evaluation and definitive management.
Follow-up recommendations Arrange outpatient PTH testing, reinforce hydration, and discontinue medications that increase calcium levels.
Key points Hyperparathyroid-related hypercalcemia is often mild and rarely exceeds 14 mg/dL; higher levels suggest malignancy. Measure ionized or albumin-corrected calcium. Administering loop diuretics before adequate hydration worsens hypercalcemia and is a common management error.
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