How is lithium-induced hyperparathyroidism managed?

Management of Lithium-Induced Hyperparathyroidism

Lithium-induced hyperparathyroidism should be managed with surgical intervention (parathyroidectomy) for cases with symptomatic hypercalcemia or resistant hyperparathyroidism, while cinacalcet can be used as an alternative for patients who are not surgical candidates. 1, 2, 3

Pathophysiology and Clinical Presentation

• Lithium-induced hyperparathyroidism is an underrecognized side effect of long-term lithium carbonate therapy, characterized by elevated parathyroid hormone (PTH) levels, hypercalcemia, and hypocalciuria 2, 4
• The condition may develop after several months to years of lithium therapy, with approximately 15% of lithium-treated patients becoming hypercalcemic 5, 4
• Lithium causes a shift in the set-point for inhibition of PTH secretion by calcium and directly stimulates PTH secretion, leading to parathyroid hyperplasia or adenoma formation 4
• Unusual metabolic features include low urinary calcium excretion, absence of nephrolithiasis, and normal urinary cyclic AMP excretion 4

Diagnostic Approach

• Measure serum calcium, phosphorus, and PTH levels in patients on long-term lithium therapy 1, 5
• Obtain 25-OH Vitamin D levels to exclude hypovitaminosis D as a concomitant secondary cause of hyperparathyroidism 6
• Consider imaging with ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT to localize parathyroid adenomas if surgical intervention is being considered 6
• Assess renal function (BUN, creatinine) to rule out chronic kidney disease as a contributing factor 7

Treatment Algorithm

Medical Management

• For mild hypercalcemia without complications and well-controlled psychiatric symptoms:
  • Consider cinacalcet hydrochloride as a first-line medical therapy, starting at 30 mg/day and titrating as needed 2, 3
  • Cinacalcet has been shown to normalize serum calcium levels and reduce intact PTH secretion in patients with lithium-induced hyperparathyroidism 2
  • Monitor serum calcium and PTH levels monthly until target levels are achieved 1

Surgical Management

• Indications for parathyroidectomy include:

  • Severe hypercalcemia that precludes medical therapy 1
  • Symptomatic hypercalcemia 8
  • Resistant hyperparathyroidism unresponsive to medical management 3, 8

• Surgical options include:

  • Total parathyroidectomy (TPTX)
  • Total parathyroidectomy with autotransplantation (TPTX+AT)
  • Subtotal parathyroidectomy (SPTX) 1

• TPTX+AT has become the preferred surgical approach in many clinical centers due to lower risk of permanent hypoparathyroidism 1

• However, TPTX may be superior to TPTX+AT in terms of lower recurrence rates of secondary hyperparathyroidism 9

Post-Treatment Monitoring

• For patients on medical therapy:

  • Monitor serum calcium and phosphorus monthly
  • Measure intact PTH every 1-3 months until target levels are achieved, then every 3 months 1

• For post-parathyroidectomy patients:

  • Monitor ionized calcium every 4-6 hours for the first 48-72 hours after surgery
  • Continue monitoring twice daily until stable 6, 1
  • Provide calcium supplementation if hypocalcemia develops 1

Special Considerations

• Cessation of lithium therapy usually does not correct the hyperparathyroidism and associated hypercalcemia 2
• Coexistence with hypothyroidism is not uncommon in lithium-induced hyperparathyroidism 4
• Regular post-operative follow-up is needed for early identification of recurrence in patients who undergo parathyroidectomy 8
• In patients with multiglandular disease (which is common in lithium-induced hyperparathyroidism), the issue of routine four-gland exploration versus intraoperative PTH-guided excision remains unresolved 3

Prevention

• Measure serum calcium levels before initiating lithium therapy 4
• If elevated values are obtained, defer lithium treatment and evaluate for hyperparathyroidism 4
• Monitor serum calcium periodically during lithium treatment to detect hypercalcemia early 5, 4