Lithium Associated Hyperparathyroidism: An Evidence Based Surgical Approach

Abstract

Background: Long-term lithium use in psychiatric patients may lead to lithium associated hyperparathyroidism (LAH). Although anecdotal case reports have appeared, an evidence based algorithm for management of LAH is lacking. Methods: A comprehensive literature search was performed using PubMed with keywords; "lithium" "hypercalcemia" "hyperparathyroidism" "sestamibi" "intra-operative parathyroid hormone (IOPTH) monitoring" "parathyroidectomy" and "medical management". All English language publications addressing etiology and clinical management issues concerning LAH were critically analyzed. Results: Lithium associated hyperparathyroidism occurs in 4.3% -6.3% of chronic lithium users compared to the general population which has an incidence of 0.5% -1%. 194 cases of LAH have been reported which includes 10 patients (5%) treated medically and 170 patients (88%) who underwent parathyroidectomy. No details were available for 14 patients (7%). Among parathyroidectomy patients, 104 (59%) had adenomatous disease and 66 (39%) had multiglandular hyperplasia. Preoperative localization studies were utilized in only 22 patients (13%) and IOPTH monitoring was reported in only 3 studies (32 patients, 19%). Among surgical patients, bilateral neck exploration (BNE) was the most common approach performed in 162 patients (95%); focused neck exploration was utilized in only 8 patients (5%). Parathyroidectomy normalized LAH biochemical changes in nearly all patients (90% -97%) in the early post-operative period, but recurrent hyperparathyroidism occurred in 8% -42% of patients. Conclusion: LAH is an under appreciated and poorly understood endocrine disorder. LAH has a higher incidence of multiglandular disease and bilateral neck exploration is mandatory in majority for disease control. Nonsurgical approaches may be useful in select patients on short-term lithium therapy.

The Prevalence of Lithium-Associated Hyperparathyroidism in a Large Swedish Population Attending Psychiatric Outpatient Units

“…In its compendium of medicines, the representatives for the pharmaceutical industry in Sweden (www.lif.se) modestly comment that lithium "could possibly interact with the turnover of calcium and magnesium" (translation by A.M.). 39 This uncertainty is reflected in researchers' alternating usage of "lithium-associated" 3,4,8,25,26,29,33 versus "lithium-induced" 5,15,34 HPT, although to what extent lithium induces or is merely associated with HPT is unresolved. The exact histopathological background of LHPT remains contested.…”

“…40 As explained earlier, lithium's interaction with calcium homeostasis is not fully understood; but theoretically, lithium should affect all parathyroid glands, which might then lead either to "demasking" a gland, which has a predisposition to be an adenoma or even to multigland hyperplasia. 16,25,33 Whatever the mechanism, today there exists no consensus about the underlying histopathology; studies give divergent reports as to whether singular gland disease (SGD) or multiglandular disease (MGD) predominates. [4][5][6][7][8][9]33,34 Interestingly, the rather unusual diagnosis of double adenoma is not uncommonly reported.…”

“…16,25,33 Whatever the mechanism, today there exists no consensus about the underlying histopathology; studies give divergent reports as to whether singular gland disease (SGD) or multiglandular disease (MGD) predominates. [4][5][6][7][8][9]33,34 Interestingly, the rather unusual diagnosis of double adenoma is not uncommonly reported. 5,7,9 These observations have a direct impact on recommendations for surgical treatment.…”

“…7,9,[32][33][34] Hitherto, to our knowledge, few studies in English have calculated the level of prevalence of LHPT based on a larger population treated with lithium. 5,[23][24][25][26][27][28][29][30][31][32][33][34][35] In this study, we present a working definition for LHPT and have aimed to determine the prevalence of LHPT in 2 geographically defined, equivalent populations in central Sweden.…”

Single Centre Experience in Patients with Primary Hyperparathyroidism: Sporadic, Lithium-associated and in Multiple Endocrine Neoplasia

“…Other authors affirmed that biochemical changes in LIHPT are similar but not exactly the same compared to sporadic pHPT (spHPT): Serum calcium in LIHPT is usually only mildly elevated [28] and in contrast to spHPT it may be associated with hypocalciuria [17,18,22,28]. LIHPT has been reported predominantly among women [29]. Although the elevation of calcium and/or PTH can be observed about 25 % of patients with long-term use of lithium medication [24,30], studies regarding surgically treated patients with pHPT could only find a small percentage from 1.3-2.2 % with a history of lithium use amongst them [20,26,31].…”