Primary Hyperparathyroidism

55 y/o F with h/o neck radiation, nephrolithiasis, long-bone fractures presents, bipolar disorder for health maintenance exam. Reports intermittent lethargy/fatigue, weakness, epigastric pain, nausea/vomiting, insomnia, and forgetfulness. Medications include lithium. Hypertension, irregular heartbeat, abdominal tenderness, flank pain, muscle weakness, and lower extremity edema on exam.

• CMP shows hypercalcemia

  • Repeat CMP and re-evaluate serum calcium and creatinine levels

  • If repeat serum calcium elevated, obtain serum ionized calcium

• Obtain serum vitamin D, magnesium, and lithium levels

• PTH > 65 mg/dL in setting of hypercalcemia: Obtain 24-hour urine calcium:urine creatinine ratio

  1. Ratio > 0.01: Primary hyperparathyroidism confirmed

     • Obtain Sestamibi scan to confirm hyperparathyroidism due to excess parathyroid activity and refer for surgical removal of parathyroid glands pending positive scan

     • Consider genetic analysis for MEN syndrome

  2. Ratio 0.01 or less: Diagnose familial hypocalciuric hypercalcemia (see notes below)

Notes

• Risk factors include female sex, age > 50 years, and h/o neck radiation

• Presentation

  • Most patients are asymptomatic at diagnosis

  • Elements of the classic stones (nephrolithiasis), bones (osteitis fibrosa cystica), groans (abdominal pain due to pancreatitis), and psychiatric overtones (lethargy/fatigue, weakness, insomnia, impaired memory) may be present

  • Hyperparathyroidism is sometimes associated with hypertension, arrhythmia, heart failure, and muscle weakness

• Diagnosis

  • Primary hyperparathyroidism is most commonly an incidental diagnosis

    • Low vitamin D and/or calcium levels may cause hypoglycemia and lead to elevated parathyroid hormone in the setting of low to normal calcium values

    • Lithium can raise PTH levels, thereby causing hypercalcemia; chronic use may also lead to renal failure and associated hypocalcemia due to decreased vitamin D production

  • Familial hypocalciuric hypercalcemia

    • This condition is due a “calcium sensor that reads low.” In other words, a normal sensor shuts off PTH when the calcium level reaches ~9.0 mg/dL, i.e. normal. In patients with familial hypocalciuric hypercalcemia, the sensor doesn’t activate until calcium levels reach ~11.0 or higher, i.e. elevated.

    • Patients may not need surgical removal of parathyroid glands if they are not displaying signs/symptoms of hyperparathyroidism

  • If PTH is low, primary hyperparathyroidism is ruled out: Obtain 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, and PTH-rP level to evaluate for parathyroid-independent causes of hypercalcemia

Secondary Hyperparathyroidism

Pt with h/o chronic kidney disease, bipolar disorder controlled with lithium, and h/o gastric bypass surgery presents with hypocalcemia. Reports recent paresthesias, emotional lability, anxiety/depression, and difficulty focusing. Hypotension, cataract, lower extremity edema, positive Chvostek/Trousseau sign, and dry skin on exam.

• Labs

  • CMP shows hypocalcemia with normal albumin

    • Obtain repeat CMP

    • If repeat CMP shows hypocalcemia, obtain serum ionized calcium

  • PTH > 65 mg/dL

  • Obtain 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels

• Obtain EKG and evaluate QTc

• Start vitamin D and/or calcium supplementation as needed to prevent osteomalacia

• Pt counseled about importance of vitamin supplementation s/p bariatric surgery

Notes

• Etiology

  • Renal failure = most common etiology

    • May occur due to chronic lithium use

    • Decreases conversion of 25-hydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3

  • May be related to decreased vitamin D and/or calcium absorption, e.g. due gastric bypass surgery

  • Insufficient calcium intake is rare in developed nations

• Normal values

  • PTH 10-65 mg/dL

  • 25-hydroxyvitamin D > 10 ng/mL