CASE REPORT: SUCCESSFUL TREATMENT OF LITHIUM-INDUCED HYPERPARATHYROIDISM (LIH) THROUGH THE USE OF CINACALCET

CASE REPORT: SUCCESSFUL TREATMENT OF LITHIUM-INDUCED HYPERPARATHYROIDISM (LIH) THROUGH THE USE OF CINACALCET

Lithium carbonate has been used as first-line treatment of acute and maintenance manic episodes in bipolar disorders since its discovery by Dr. John Cade in 1949 and the prevalence of hyperparathyroidism in patients treated with lithium has been estimated between 4.3 and 6.3% versus 0.1 to 0.4% of the general population. Thyroid and kidney alterations are well-known side effects of the drug, while the action on the parathyroids is less studied and widespread. Lithium acts on signal transduction pathways by modulating the phosphorylation activity of intracellular proteins, which clinically stabilizes bipolar disorder. These actions occur via inhibition of inositol monophosphatase with a regulatory effect on cell growth and by inhibition of Glycogen synthase kinase 3 which inactivates anti-apoptotic transcription factors, brain energy regulation and oxidative stress. Both pathways are simultaneously involved in the effects of lithium on calcium metabolism, PTH synthesis and thyroid activity, as well as its actions at the level of the renal tubule are caused by dysfunction of G protein-coupled transmembrane receptor, the calcium sensing receptor (CaSR). [Graphic 1].

The history of a 65-year-old female patient is presented under long term treatment with lithium carbonate, which develops hypercalcemia and increased PTH who has been treated whith cinacalcet.

A a 65-year-old female patient diagnosed with schizoaffective disorder and severe manic-depressive was treated with lithium carbonate at a dose of 1200 mg/day for ten years prior to the discovery of hypercalcemia and increased PTH. Laboratory: serum creatinine 0.7 mg/dl, total calcium 10.7 mg/dl, Cai 5.6 mg/dl, PTH 140 pg/ml, 24-hour calciuria 59 mg. Renal and parathyroid ultrasounds were normal, and a parathyroid scan with TC-99m-SESTAMIBI did not demonstrate localized abnormal uptake on late images. Since reduction or interruption of the drug was not possible due to exacerbation of the condition including suicidal ideas, treatment with cinacalcet allowed long-term normalization of calcium and PTH without the need to interrupt treatment with lithium [Table 1]. Previous publications by Gregoor PS, de Jong GMT (Kidney Int. 2007; 71: 470.) and Sloand JA (Am J Kidney Dis 2006; 48: 832-7) demonstrated the successful use of cinacalcet for the lithium-induced hyperparathyroidism treatment.

Unlike primary hyperparathyroidism lithium-induced hyperparathyroidism is not associated with hypercalciuria or renal litiasis and is distinguished from hyperparathyroidism secondary to chronic kidney disease, because on LIH, kidney function generally is preserved, evolves with hypercalcemia and have normal levels of 1 -alpha, 25-dihydroxycholecalciferol. It should be taken into account when diagnosing that the spectrum of LIH is broad and includes cases of obvious hyperparathyroidism, as well as forms with isolated hypercalcemia and without elevated PTH levels, or elevated PTH without hipercalcemia and hypocalciura.

The reported case shows the effectiveness of pharmacological therapy based on the known modulating effects of calcimimetic drugs on the calcium sensing receptor, being of importance in patients without the possibility of reducing or definitive interreuption of lithium treatment.