Lithium-Associated Hyperparathyroidism: Surgical Strategies in the Era of Minimally Invasive Parathyroidectomy

Lithium remains an effective treatment of bipolar affective disorder. The long-term use of lithium is associated with an alteration in parathyroid function that may culminate in hyperparathyroidism. The long-term effects of lithium use are variable due to its complex effects on calcium homeostasis and bone metabolism, and as a consequence the indications for surgery remain poorly defined. The optimal surgical strategy for lithium-associated hyperparathyroidism in the era of minimally invasive surgery is also the subject of debate. The aim of the present study was to evaluate the variable findings of lithium-associated parathyroid disease.

A retrospective review was performed of patients undergoing parathyroid surgery presenting with lithium-associated hyperparathyroidism from July 1999 until July 2009 at the university hospital La Timone, Marseille, and from October 2005 to July 2009 at Hammersmith Hospital, Imperial College, London. Fifteen patients underwent surgery for lithium-associated hyperparathyroidism. Clinical data including patient demographics, duration of lithium use, clinical manifestations of hyperparathyroidism, indications for surgery, and biochemical parameters preoperatively and postoperatively were reviewed. Preoperative imaging, the surgical procedure performed, operative findings, and histopathology were also analyzed.

All 15 patients had preoperative imaging: sestamibi scanning showed that 10 patients had localized single-gland disease, 1 had multiple hot spots, and 4 had a negative scan. Ultrasonography demonstrated a single abnormal gland in 8 patients and multiple enlarged glands in 1 patient; the test was negative in 6. As a consequence of concordant preoperative imaging a minimally invasive approach (endoscopic or a focused lateral approach) was adopted in 3 patients. Focused surgery demonstrated an enlarged hyperplastic gland in 3 cases and resulted in normocalcemia in the immediate postoperative period. However, one patient has a serum calcium at the upper limit of normal and elevated parathyroid hormone (PTH) levels, suggestive of possible recurrence of disease at 15 months follow-up. One patient has permanent hypoparathyroidism. In those patients who had open procedures, final histology showed hyperplastic multiglandular disease in 10 patients (83.3%) of patients and single-gland disease in 2 patients (16.7%). None of these patients show evidence of recurrence at follow-up.

Lithium hyperparathyroidism is predominantly a multiglandular disease characterized by asymmetrical hyperplasia that is frequently associated with misleading or discordant localization studies. Bilateral neck exploration is therefore recommended in order to minimize the risk of disease recurrence.