RARE AND FATAL ADVERSE EFFECTS OF LITHIUM INTOXICATIONA. de Falco, V. Scarano, G. Cicarelli, L. Ciccone, S. Cella, D. Spitaleri

U.O.C. di Neurologia e Stroke Unit – A.O.R.N. San G. Moscati - Avellino

IntroduzioneLithium is considered the first-line maintenance treatment forbipolar affective disorder and as a mood stabilizer in thetreatment of schizoaffective disorder. Despite its therapeuticsuperiority and versatility, lithium has a very narrow therapeuticindex and toxicity is common in patients taking this agent.Lithium intoxication (LI) generally affects the central nervoussystem but less frequently can affect kidneys, thyroid andparathyroid. Here we report a patient who showed neurotoxicsymptoms due to LI complicated by parathyroid and renaladverse effects.

Bibliografia1.Ott, M., et al., Lithium intoxication: Incidence, clinical course and renal function - a population-based retrospective cohort study. J Psychopharmacol, 2016. 30(10): p. 1008-19.

2.Ott, M., B. Forssen, and U. Werneke, Lithium treatment, nephrogenic diabetes insipidus and the risk of hypernatraemia: a retrospective cohort study. Ther Adv Psychopharmacol, 2019. 9: p. 2045125319836563.

3.Shapiro, H.I. and K.A. Davis, Hypercalcemia and "primary" hyperparathyroidism during lithium therapy. Am J Psychiatry, 2015. 172(1): p. 12-5.

50°CONGRESSO NAZIONALE12 - 15 OTTOBRE 2019 – BOLOGNA

Caso ClinicoThe patient was a 52 year-old woman with a history ofschizoaffective disorder on treatment with carbolithium 300 mgbid, Olanzapine 10 mg qd and clonazepam 0,5 mg qd. She alsohad hypertension, dyslipidemia and recent finding ofhyperparathyroidism and hypercalcemia associated withparathyroid adenoma. She was admitted to our Neurology Unitfor severe agitation, confusion, disorientation, akathisia,uncooperativeness and diffuse tremor. Laboratory tests showedhigh serum lithium (1,3 mmol/L; therapeutic range 0.6-1.2),hypercalcemia (11,6 mg/dl; normal range 8.6-10.2) and normalNa+ (138 mmol/L). EEG showed disorganization of backgroundactivity with periodic and diffuse complex of sharp waves. BrainMRI and MR-angiography were normal. Cerebrospinal fluidanalysis including virologic DNA finding, bacterial antigens andcultures were unremarkable. Screening for autoimmuneencephalitis was negative. Lithium was discontinued and serumcalcium normalized. Agitation ceased but patent showed apersistent consciousness impairment evolving in a coma state.Laboratory revealed a gradual rise of serum Na+ up to 180mmol/L despite a high intake of glucose 5% solutions and freewater by naso-gastric tube. Diagnosis of nephrogenic diabetesinsipidus (NDI) was made and patient started hemodialysis. Afterthe first treatment Na+ serum level decreased but patient diedfor cardiac arrest.

DiscussioneNeurological symptoms of LI are common and they can occuralso at dosage close to therapeutic range, as in our patient, oreven in the normal therapeutic range. Parathyroid and renalinvolvement is rare. LI can lead to hyperparathyroidism oftensecondary to parathyroid adenoma causing hypercalcemia whichcan overlap LI neurological symptoms as in our patient.Moreover, lithium toxicity can affect kidneys causing an NDIwhich can generate a life-threatening hypernatremia.Hemodialysis is indicated for lithium serum level > 3.5mmol/Lbut in case of adverse effects or poor clinical outcome it shouldbe performed independently from lithium serum level.

ConclusioniIn patients with LI clinicians should identify not only neurotoxicsymptoms but also rare and life-threatening adverse effects suchas hypercalcemia and NDI and immediately start specifictreatments.

Complicanze Neurologiche

Atassia, tremori, rallentamento ideo-motorio, confusione,

agitazione, disturbo di coscienza

Crisi epilettiche

Anomalie EEG

Sindrome irreversibile da tossicità da litio (SILENT)

Complicanze non neurologiche

Gastrointestinalinausea, vomito, diarrea

Cardiachealterazioni ECG,

allungamento QTc, bradicardia, aritmie

RenaliInsufficienza renale, Diabete

insipido nefrogenico

Tiroidedistiroidismo,

iperparatiroidismo, ipercalcemia

Lithium intoxication – case series with a sample size >50 after the year 2000.