Abstract
To The Editor
Lithium is a well established and important component of the psychiatric armoury. As such, it is often necessary to manage complications that arise from lithium therapy. Hyperparathyroidism is a relatively uncommon complication, occurring in perhaps 4.3–6.3% of patients, most of whom have taken lithium for many years (Rizwan and Perrier, 2009). Reports as to the pathology and course of this condition vary, and this case demonstrates the continued uncertainty regarding its psychiatric management.
We describe here a 55-year-old patient with a history of bipolar disorder who had been taking lithium for 25 years, most recently at a dose of 750 mg per day with levels in the mid-therapeutic range. Used in combination with valproate and dosulepin, their mood had remained stable for a number of years, although some depressive symptoms persisted.
A routine screen detected hyperparathyroidism (13.8 pmol/l) complicated by hypercalcaemia (2.82 mmol/l, ionized calcium 1.4 mmol/l) and renal impairment (creatinine 132 umol/l). As a consequence, their lithium was stopped but these problems persisted until they underwent a subtotal parathyroidectomy during which three-and-a-half of the four hyperplastic glands were removed. Parathyroid hormone and calcium levels then returned to the normal range, although creatinine remained elevated.
In the post-operative period the patient became significantly more depressed and anxious, symptoms that have continued despite further treatment. They were reluctant to restart lithium given the complications that it had caused, and the paucity of information regarding subsequent risks of lithium limited the capacity for informed decisions.
It might be expected that the systemic distribution of lithium would cause it to affect all four parathyroid glands equally. However, the reported rate of multi-glandular disease varies dramatically from 27% to 75% (Broome and Solorzano, 2011; Rizwan and Perrier, 2009). This variation may support suggestions that lithium acts by increasing pre-existing vulnerabilities to parathyroid disease rather than acting independently.
There is also conflicting data on the outcomes of surgical treatment (Broome and Solorzano, 2011). One study suggested an eventual failure rate of 50% post-surgery, regardless of the number of glands excised (Järhult et al., 2010). There are several reports of patients continuing lithium after the excision of an adenoma, but it has also been suggested that this may later lead to multi-glandular disease (Järhult et al., 2010). For widespread hyperplasia, the surgical treatment is often excision of most of the glands, as occurred for this patient. It could be assumed that continuing lithium therapy in this situation may risk an adenoma in the remaining tissue but there is no evidence regarding this.
The calcimimetic drug cinacalcet is used to treat hyperparathyroidism and may be effective in lithium-induced disease. It was found to be effective in two case studies with a total of five patients, four of whom continued taking lithium (Broome and Solorzano, 2011; Szalat et al., 2009). From the psychiatric standpoint, this may be preferable to surgery if it allows continuation of lithium without further risks, but clearly this requires further investigation.
Lithium-associated hyperparathyroidism (LAH), though relatively uncommon, perhaps warrants monitoring of serum calcium (Malhi et al., 2012). This case demonstrates that the complexity and uncertainty of its management is partly due to the lack of consistent information about its pathophysiology and treatment outcomes. Surgery remains the main treatment for LAH. However, for those who are not suitable candidates for surgery and who need to continue lithium there is promise in the use of calcimimetics.