Lithium Toxicity Research Articles

Lithium use in the elderly demands caution and vigilance

Lithium is a popular drug in the field of psychiatry, used widely as a mood stabilizer in bipolar affective disorder. However, it has a narrow therapeutic index, between 0.6 and 1.5 mEq/L. Toxicity can occur at levels >1.5 mEq/L, hence thus monitoring of serum drug level is vital. Furthermore, the range of Lithium's therapeutic index can be further lower in the elderly, especially in the presence of renal disease, as the drug metabolism in this age group has considerable variation from an average adult. Following is a case report to exemplify Lithium Intoxication and of its narrow therapeutic index; and to develop further understanding on and the clinical implications of the age related changes that affect the pharmacokinetics and pharmacodynamics of the drug.

“But the lithium level is normal!” SILENT Syndrome: A rare diagnosis of irreversible lithium toxicity to consider in cases of irreversible neurotoxicity

“But the lithium level is normal!” SILENT Syndrome: A rare diagnosis of irreversible lithium toxicity to consider in cases of irreversible neurotoxicity

Lithium Toxicity in an Elderly Women within Normal Therapeutic Range : A Case Report

Toxic effects of lithium are usually related to high serum levels. However, several cases of significant toxicity have occurred in patients whose serum levels fell within the normal therapeutic range. Such cases are rare, but individual variations may occur and clinical judgment rather than serum levels must determine the management. A 67 years old female with bipolar disorder on lithium was admitted with an acute confusional state, tremor, restlessness, increased nausea, slurred speech, polyuria and diarrhoea. Lithium level found to be 0.6 mmol/L that is in normal range. Neurotoxicity could be suspected at serum lithium levels which are considered therapeutic in young adults.Chatt Maa Shi Hosp Med Coll J; Vol.14 (2); Jul 2015; Page 78-79

Treatment of lithium intoxication: facing the need for evidence.

Lithium has been used as the gold standard in the treatment of major depressive and bipolar disorders for decades. Due to its narrow therapeutic index, lithium toxicity is a common clinical problem. Although risk factors for lithium intoxication seem to be well-described, lacking patient education and inexperience of treatment are assumed to contribute to the probability of lithium intoxication. A review of literature shows that the treatment of lithium intoxication has not been adequately studied or standardized. The aim of this literature review is to compile and present current evidence on the treatment of lithium intoxication and contribute to a standardization regarding general treatment recommendations as well as evidence on indication for extracorporeal methods. Against the background of this common and potentially life-threatening condition, the standardization of the treatment of lithium intoxication is definitely a task for the future.

Long-term effect of lithium maintenance therapy on estimated glomerular filtration rate in patients with affective disorders: a population-based cohort study

For more than 40 years, the long-term effect of lithium maintenance therapy on renal function has been debated. We aimed to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eFGR) in patients with affective disorders, and explore predictors for a decrease in eGFR. This population-based cohort study included adult patients (18-65 years of age at baseline) in Tayside (Scotland, UK) who had recently started on lithium maintenance treatment between Jan 1, 2000, and Dec 31, 2011 (retrospectively assigned to the lithium group) or those with exposure to other first-line drugs used in the treatment of affective disorders (quetiapine, olanzapine, and semisodium valproate) during the same period (retrospectively assigned to the comparator group). Patients had to have at least 6 months of (incidence) exposure to lithium or any of the comparator drugs, at least two eGFR values available in the observation period (one at baseline and at least one after ≥6 months post baseline). We excluded patients with previous exposure to lithium or one of the comparator drugs, those with a previous diagnosis of schizophrenia or other psychotic disorder, those with glomerular disease, tubulo-interstitial disease, or chronic kidney disease stages 4-5 at baseline, and those who had undergone renal transplant before exposure. Maximum follow-up was 12 years. Data were provided by the University of Dundee Health Informatics Centre, who have access to health-related population-based datasets containing data for every patient registered with a regional family doctor. Each patient has a unique ten-digit identifier, the Community Health Index, enabling us to link laboratory tests, dispensed community prescriptions, Scottish Morbidity Records, and mortality records to the patient. All data were anonymised according to Health Informatics Centre standard operating procedures. The primary outcome was the change per year in the eGFR, adjusted for age, sex, and baseline eGFR, and analysed by random coefficient models. 1120 patients (305 exposed to lithium and 815 to comparator drugs) qualified for inclusion, providing 13 963 eGFR values over 12 years. The mean duration of exposure to lithium was 55 months (SD 42; range 6-144). Mean annual decline in eGFR (adjusted for age, sex, and baseline eGFR) was 1·3 mL/min per 1·73 m(2) (SE 0·2) in the lithium group, which did not differ significantly to that in the comparator group (0·9 mL/min/1·73 m(2) [SE 0·15]). After adjustment for additional confounders, the monthly decline in eGFR attributable to lithium exposure amounted to 0·02 mL/min per 1·73 m(2) (SE 0·02, p=0·30). As a post-hoc secondary outcome, we estimated the annual decline in eGFR for the lithium group to be 1·0 mL/min per 1·73 m(2) (SE 0·2), which again did not differ significantly to that in the comparator group (0·4 mL/min/1·73 m(2) [SE 0·2]. Modelling identified significant predictors for eGFR decline as age, baseline eGFR, comorbidities, co-prescriptions of nephrotoxic drugs, and episodes of lithium toxicity; however, duration of exposure to lithium and mean serum lithium level were not significant predictors for eGFR decline. Our analysis suggests no effect of stable lithium maintenance therapy (lithium levels in therapeutic range) on the rate of change in eGFR over time. Our results therefore contradict the idea that long-term lithium therapy is associated with nephrotoxicity in the absence of episodes of acute intoxication and that duration of therapy and cumulative dose are the major determinants of toxicity. None.

Hemodialysis for lithium poisoning.

Lithium salts, particularly lithium carbonate, are frequently used to treat bipolar disorder and mania. Lithium poisoning, which can occur as a result of reduced renal elimination, prescribing error, drug-drug interactions, or deliberate overdosage, produces neurologic injury that can be permanent. Hemodialysis is often recommended to treat lithium poisoning. Although hemodialysis clearly enhances the elimination of lithium, it is unclear whether this translates into improved patient outcomes. Evidence from observational studies, generally of low methodological quality, shows similar outcomes in patients managed with or without the use of hemodialysis. To determine whether hemodialysis, applied in addition to standard therapy, reduces the likelihood, severity, or duration of neurological sequelae following lithium poisoning. We ran the search on 15 May 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), CINAHL Plus, clinical trials registers and four other databases. We screened the reference lists of relevant studies, textbook chapters, and review articles, and performed a Google search to identify grey literature. In the context of this review, hemodialysis was defined as any extracorporeal technique to filter and extract toxicants from the serum, including all forms of hemodialysis, hemofiltration, and continuous renal replacement techniques, but not peritoneal dialysis. We included any clinical trials in which patients were randomly allocated to receive, or not receive, hemodialysis in addition to standard care for lithium poisoning. Two authors reviewed the abstracts of all identified articles. If either author identified an article as potentially meeting the inclusion criteria, both authors reviewed the full text of the article. No randomized controlled trials of hemodialysis therapy for lithium poisoning were identified. Although the use of hemodialysis to enhance the elimination of lithium in patients with lithium poisoning appears logical, there is no evidence from randomized controlled trials to support nor refute the use of hemodialysis in the management of patients with lithium poisoning.

Diagnostic Accuracy of Tests for Polyuria in Lithium-Treated Patients.

In lithium-treated patients, polyuria increases the risk of dehydration and lithium toxicity. If detected early, it is reversible. Despite its prevalence and associated morbidity in clinical practice, it remains underrecognized and therefore undertreated. The 24-hour urine collection is limited by its convenience and practicality. This study explores the diagnostic accuracy of alternative tests such as questionnaires on subjective polyuria, polydipsia, nocturia (dichotomous and ordinal responses), early morning urine sample osmolality (EMUO), and fluid intake record (FIR). This is a cross-sectional study of 179 lithium-treated patients attending a general adult and an old age psychiatry service. Participants completed the tests after completing an accurate 24-hour urine collection. The diagnostic accuracy of the individual tests was explored using the appropriate statistical techniques. Seventy-nine participants completed all of the tests. Polydipsia severity, EMUO, and FIR significantly differentiated the participants with polyuria (area under the receiver operating characteristic curve of 0.646, 0.760, and 0.846, respectively). Of the tests investigated, the FIR made the largest significant change in the probability that a patient experiences polyuria (<2000 mL/24 hours; interval likelihood ratio, 0.18 and >3500 mL/24 hours; interval likelihood ratio, 14). Symptomatic questioning, EMUO, and an FIR could be used in clinical practice to inform the prescriber of the probability that a lithium-treated patient is experiencing polyuria.

Evaluation of Neurotoxicity in Lithium Treated Patients Admitted to Poison Control Center-Ain Shams University Hospitals during the Years (2011-2014)

Lithium has been the first line drug in treating bipolar disorder. It has a low therapeutic index and toxic levels are frequently seen in clinical practice. Chronic lithium intoxication due to progressive accumulation of lithium was found to be more common. Symptoms are primarily neurologic; mental status is often altered and can progress to coma. The aim of the study is to evaluate the neurotoxicity among lithium intoxicated patients and its association with serum lithium levels through a cross sectional hospital based study over four years in the Poison Control Center, Ain Shams University Hospitals (PCC-ASUH). Factors affecting the outcome of lithium intoxicated patients were deduced. Subjects and methods: Lithium intoxicated patients presented to the PCC-ASUH during the period from January 2011 to January 2015 were prospectively evaluated. For every patient we recorded the duration of lithium intake, comorbidities and concomitant use of medications. Clinical manifestations, serum lithium level, renal function (serum urea and creatinine) and serum electrolytes (sodium and potassium) in addition to the treatment characteristics were also recorded. Patients were divided according to their outcome into two groups: (Survivors and Non survivors). Results: Twenty five lithium intoxicated patients were enrolled in our study; the mean duration of lithium therapy was similar in both groups (more than 12 years). The main clinical presenting sign of lithium intoxicated patients was coma with its different grades. Glasgow Coma Score (GCS) was significantly lower among non survivors. Relevant history of diabetes mellitus and hypertension was found in 15 patients and 13 patients respectively. Non psychotropic medications (including angiotensin converting enzyme inhibitors and diuretics) that interact with lithium clearance were more prevalent among non survivors. Neuroleptics were used by 22 patients and this was of no significant difference between survivors and non survivors. There was no significant difference between serum lithium levels in survivors and non survivors. Rehydration therapy with intravenous fluids was significantly more prevalent among the survivors. While no significant difference was found between both groups as regards the use of hemodialysis. Conclusion: The serious morbidity suffered by lithium intoxicated patients might be reduced by careful monitoring and awareness of factors that might predict their outcomes including altered conscious level or drug interactions (diuretics or angiotensin converting enzyme inhibitors). Clinicians should seriously maintain a high level of suspicion in treating patients maintained on lithium noting that serum lithium levels do not accurately predict toxicity and they should not solely rely on it.

Enhance Your Understanding of Lithium Neurotoxicity.

To the Editor: Lithium is a drug established for treatment of affective disorder and is intended to mitigate and prevent depressive or manic episodes and diminish suicidal tendencies. However, lithium can induce neurologic sequelae following overdose or during maintenance therapy.1,2 Neurotoxicity. Lithium neurotoxicity can be reversible or irreversible and may even be observed at therapeutic serum levels.3 Acute lithium toxicity initially affects fast-acting neurons controlling coordination, resulting in tremor and extremity dyscoordination. Increased toxicity may cause progressive development of slurred speech, muscular fasciculation, seizures, nystagmus, and extrapyramidal features.4 Delirium can be another manifestation, with obtundation in severe neurotoxicities. Sustained serum lithium levels > 1.5 mEq/L can be associated with toxicity risk, but may not be at concentrations consistently high enough to induce nerve injury.4 Persistent concentrations > 2.5 mEq/L often induce neurologic complications, especially convulsions and cerebellar impairment. Permanent lithium neurotoxicity is clinically documented.1,2,5,6 The syndrome of irreversible lithium-effectuated neurotoxicity is a permanent sequela of intoxication that presents with persistent cerebellar dysfunction.6 Other significant neurologic complications also can be observed.7 Demyelination occurs at various sites, especially the cerebellum, causing dystaxia and dysarthria.8 Permanent cerebellar and pyramidal cell dysfunction can result. Pharmacology. Lithium enters the circulation and is distributed widely and primarily intracellularly. The mechanisms of action include changes at cell membranes, alteration of serotonin and norepinephrine actions, and influences on phosphatidylinositol metabolism.4 However, when serum lithium levels are in overtly toxic ranges, lithium further accumulates in the brain and kidney, causing dysfunction, but does not always reflect degrees of neurotoxicity. Serum concentrations do not correlate well with neuronal levels. The implications of an individual assay must include a relation to the timing of previous lithium administrations, with standardized determinations based on approximately 12 hours after the last ingestion. Lithium is excreted by the kidney, and this process is strongly influenced by sodium and water excretion. The lithium half-life is approximately 18 hours in young adults and 36 hours in healthy elderly people,7 and it varies according to renal function and hydration. Some pharmaceutical interactions enhance lithium retention, most prominently the diuretics like hydrochlorothiazide, secondary to sodium wasting. Angiotensin converting enzyme inhibitors decrease glomerular filtration and increase tubular reabsorption of lithium. Nonsteroidal anti-inflammatory drugs interrupt renal prostaglandin synthesis, retarding lithium excretion.7 Lithium acts synergistically with neuroleptic drugs in the development of neuroleptic malignant syndrome.8 Clinical conditions involving dehydration and impaired renal status diminish lithium excretion and increase the risk of neurotoxicity. Management. Lithium toxicity is usually avoided through conservative prescribing, patient education, and close clinical and laboratory monitoring.9 Patients administered lithium should understand drug interactions, the need for adequate hydration, and how to contact their physician. Doctors must consider coexistent renal or cardiac failure and brain diseases that might predispose toward toxicity. Minor intoxications are mitigated by oral hydration and adequate electrolyte ingestion. In more severe cases, intravenous saline is instituted. At progressively greater toxicities, cathartics and lavage with charcoal are considered. When dangerous sequelae are feared, hemodialysis is indicated to forestall neurotoxicity.10 The serum lithium concentration may exhibit a rebound during treatment.11 Rebound in lithium toxicity cases means that serum levels that were once lower, often rise again, reflecting stores of higher lithium concentration within cells, including those of the central nervous system—that can result in later observing rising serum lithium levels and thus implies continued lithium neurotoxicity.

AAN and AAP meetings: Latest research in neurology, psychiatry

Emerging advances in neurology ranging from management of refractory status epilepticus to multiple sclerosis were the focus of numerous abstracts presented at the American Academy of Neurology‘s (AAN) 67th annual meeting, held April 18–25 in Washington, DC. At the American Psychiatric Association's (AAP) 168th meeting, held May 16–20 in Toronto, topics ranged from use of psychotropic medications in patients with dementia to lithium toxicity. Following are highlights from both conferences.

Psychiatric and medical adverse events for kidney transplant recipients with lithium induced kidney disease

Background: The purpose of this study is to describe post-transplant psychiatric and medical adverse events for kidney transplant (KT) recipients with a history of lithium induced kidney disease. According to the United Network for Organ Sharing (UNOS) as of January 2015 there have been 208 kidney transplantations done in the USA for this condition and 227 are currently waiting for a kidney. Considering the evidence that decompensated psychiatric conditionsmay interferewith post-transplant outcomes, there is a concern about the risk of posttransplant adverse events in this population. To our knowledge, at this time there is no information about medical or psychiatric course post transplantation for kidney recipients with a history of lithium toxicity. Method: Retrospective study of patients who received kidney transplantation for lithium induced kidney disease at Yale Transplantation Center. The following electronic documents were reviewed: discharge summaries, admission assessments, clinic visit notes, social work evaluations, psychiatric evaluations, counts of hospitalizations and clinic visits, and laboratory tests (immunosuppressant levels). We are presenting the descriptive analysis of this information. Results: We identified a total of 12 patients who received a KT for a primary diagnosis of lithium induced kidney disease at our center between 1/1/2004 and 12/31/2014. Eight (66%) were male and all were Caucasian. The most common co-occurring medical condition was hypertension 8 (66%) followed by hypothyroidism 4 (33.3%). Six (50%) had received hemodialysis before transplantation and 2 (16.5%) had received peritoneal dialysis, for an average dialysis duration of 2.35 years (±2.81). The post KT follow-up was 3.11 years (±2.26). Eleven (91.6%) had a diagnosis of Bipolar I disorder. The most commonly prescribed psychotropic medications were Lamotrigine (4 cases), followed by Quetiapine, Aripiprazole and Divalproex (3 cases each). One patient was continued on lithium through dialysis and after transplant. There were a total of 3 psychiatric hospitalizations corresponding to 0.08 hospitalizations per patient per year (PPY), 25 medical hospitalizations (average 2 per patient ±1.9) or 0.66PPY; infections 0.08 PPY, rejection 0.02PPY); instances of subtherapeutic medications level 0.21PPY. There was one death in the group. There were no instances of graft loss. Conclusion: Post-transplant exacerbations of psychiatric illness, psychiatric hospitalizations, graft loss, infections, and death were rare in patients receiving KT for lithium induced kidney disease at our center. Studying a higher number of patients with longer post-transplant follow-up, possible through multicenter registry, would provide more accurate information about the psychiatric and medical course of this group of KT recipients.

A case of lithium toxicity with significant QT interval prolongation

Background Lithium toxicity has been associated with electrocardiographic abnormalities, such as QT interval prolongation.

Calculating lithium doses in mental health

L is licensed for the acute and long-term management of mania in bipolar affective disorder (electronic Medicines Compendium, 2014). Lithium has a narrow therapeutic index, and the National Institute for Health and Care Excellence (NICE, 2014) recommends regular therapeutic drug monitoring and that health professionals should aim to achieve a lithium plasma concentration between 0.6 and 0.8 mmol/litre in patients initially treated with lithium. For those already on lithium and who have relapsed, a plasma concentration between 0.8–1.0 mmol/litre is recommended. If a patient’s lithium plasma concentration is suboptimal, they are at risk of relapsing with either a manic or depressive episode. Concentrations above the therapeutic range can result in lithium toxicity. Each preparation of lithium differs in its pharmacokinetic properties and the amount of lithium contained, therefore it is important that lithium is prescribed by brand name (Joint Formulary Committee (JFC), 2015). In addition, when substituting different preparations, it is important to ensure the conversion is done correctly. A patient is diagnosed with bipolar affective disorder and is currently prescribed Priadel (lithium carbonate) tablets 600 mg at night as prophylaxis of manic episodes. He has relapsed and is currently secreting his tablets, and the prescriber wishes to convert him to a liquid preparation. Priadel tablets contain 5.4 mmol of lithium per 200 mg tablet. Priadel liquid (lithium citrate) has a strength of 520 mg per 5 ml, and each 5 ml contains approximately 5.4 mmol (JFC, 2015). Priadel 200 mg tablets cost £2.30 per pack (containing 100 tablets), and 400 mg tablets cost £3.35 per pack (also containing 100 tablets). Priadel liquid costs £5.61 per 150 ml bottle (JFC, 2015).

Lithium Toxicity Precipitated by Fluvoxamine: a Case Report

To report a case of Lithium toxicity resulting in haemodialysis, possibly caused by multiple drug interaction amongst Lithium, Enalapril and Fluvoxamine in a patient with Bipolar affective disorder with no history of renal disease. A 56 year-old man with bipolar affective disorder was stabilized on Lithium 400mg BD for 3 months with concurrent Enalapril therapy. He, however, developed Lithium toxicity after fluvoxamine was added. He was admitted due to poor sleep and increased anxiety. Upon admission, Lithium level was normal (0.88mmol/L). Fluvoxamine, Propranolol and Lorazepam were added subsequently with no changes in Lithium dose. No deterioration in mental status was observed. However, on Day 10, he developed significant tremors and lethargy. Repeated laboratory findings revealed deranged Lithium level (2.3 mmol/L), serum sodium (128mmol/L), serum creatinine (407 mcmol/L) and liver enzymes. Abnormal physical findings include hypotension and bradycardia. He was then admitted to the intensive care unit for close monitoring and underwent hemodialysis. Lithium was also discontinued. Subsequently, his Lithium level, renal function, and neurological signs improved. The interaction between Enalapril with Lithium is well established. However, reported interactions between Lithium and Fluvoxamine are mainly cases of serotonin syndrome. An objective causality assessment using the Naranjo Probability Scale revealed a score of 7 – probable relationship between concomitant use of the drugs and the resulting symptoms. This episode suggests that fluvoxamine- Lithium interaction may result in raised Lithium level. Clinicians should be aware of this severe adverse event and take steps to minimize its occurrence.

Male Hypothyroidism-Clinical Relevance Including Role in Reproduction

Purpose: Overt Hypothyroidism is defined as arise of S.TSH>10mIU/L. Since its incidence is more common in females one generally tends to ignore this diagnosis in males and usually the diagnosis is made in an emergency situation when the patient presents either with coma or with a severe form of Hashimoto’s thyroiditis (HT) like IgG4 related thyroiditis. Methods: A systemic literature search was performed using PubMed for all English articles till Sept 2014 regarding male hypothyroidism using MeSH terms like congenital hypothyroidism, male hypothyroidism and reproduction; subclinical hypothyroidism; Hoffmann’s syndrome; myxedemic coma. Results: To eradicate congenital hypothyroidism all over the world many countries have incorporated in their neonatal screening programme (NNSP), yet occasional cases of cretinism still get diagnosed .Important causes being genes encoding Transcription factor TTX1, TTX2 presenting as Bamforth syndrome, Thyroglobulin gene, Thyroid peroxidase (TPO), TSHR gene abnormalities, Pendreds syndrome coexisting with thyroid developmental abnormalities etc. Context Ig superfamily1deficiency (IGSF1), Fryns Anophthalmia Plus syndrome (APS), TSHβ gene deletion, frame shift mutation in first exon of Fibroblast growth factor8 (FGF8) can present as Central hypothyroidism. The first presentation maybe a neurological emergency like myxedemic coma either secondary to neurofibromatosis, lithium toxicity which responds to L-thyroxin or occasionally may not, responding only to steroids. Some patients may present as different forms of Hoffmann’s syndrome or stiff leg syndromes. Subclinical hypothyroidis, (SH) and its aetiology along with TSH R mutations R109 Qreported as causation in 2 brothers and importance of treatment is highlighted. Importance of treatment of SH in children and adults is discussed. Mechanism of reversible kidney dysfunction in hypothyroidism is highlighted along with discussing its relationship with treatment. Changes in serum testosterone and gonadotropins are discussed in a patient of male hypothyroidism and the way it may affect reproduction. Conclusion: Hypothyroidism may be the primary cause of a male presenting with Hypogonadotropic hypogonadism (HH) and should be suspected in a man presenting with delayed puberty. Untreated hypothyroidism should be suspected as the cause of presentation of myopathies like Hoffmann Syndrome or other myopathies or myxedema coma. SH may warrant treatment in young males with known adverse affects on cardiovascular system although its affect on cognitive function has not been found especially in elderly.

A Patient with Neuropsychiatric Manifestations and Thyrotoxicosis in a background of Lithium Toxicity

Neuropsychiatric manifestations are well known to occur in thyrotoxicosis. In many cases, these manifestations occur in conjunction with the systemic features of the disease, but may be the presenting symptom in some patients. We report on an elderly gentleman with, neuropsychiatric manifestations and thyrotoxicosis in the background of lithium toxicity who presented as a diagnostic dilemma. Case report: A-70 year old man awaiting coronary artery bypass graft was detected to have thyrotoxicosis with FT4 of 2.7 ng/l(0.7-1.8) and TSH levels of 0.03 μIU/mL (0.4-4.3). A Tc 99 thyroid scan showed <1% iodine uptake suggestive of thyroiditis. He had no prior history of thyroid disorders, but has had a recent coronary angiogram. He was commenced on thioamides, lithium and small doses of prednisolone. One week after initiation of medication he presented with ataxia, dysarthria, choreiform movements and altered level of consciousness following a bout of diarrhea and vomiting and was found to have elevated levels of lithium 2.57 mmol/l(0.6-1.2) with serum creatinine of 219 µmol/l(80-120). In spite of adequate hydration, hemodialysis and normalization of lithium levels he did not show any clinical improvement. Blood and cerebrospinal fluid analysis for a possible infectious etiology were negative. This prompted an alternative diagnosis of Hashimoto’s encephalopathy (HE). Treatment with high doses of steroids led to a remarkable clinical resolution. HE also known as steroid responsive encephalopathy associated with autoimmune thyroiditis is an autoimmune thyroid disease with neuropsychiatric manifestations. Although almost all cases of HE have positive thyroid antibodies, these were repeatedly negative in our patient. This case posed a diagnostic challenge in differentiating between acute lithium toxicity and thyroiditis with encephalopathy. The dramatic response to high dose steroids in the presence of negative thyroid antibody highlights the possible rare existence of an antibody negative steroid responsive encephalopathy associated with thyroiditis.

Minimizing negative outcomes associated with potentially harmful lithium levels by means of pharmacist-led educational interventions in an inpatient psychiatric facility

Introduction: Studies examining educational interventions led by pharmacists to minimize negative outcomes associated with elevated and potentially harmful lithium levels in inpatient psychiatric facilities are lacking. Other studies indicate a need for improvement of therapeutic drug monitoring for lithium. The aim of this article is to identify potential improvements in negative outcomes associated with harmful lithium blood levels after educational interventions are delivered by a clinical pharmacist to providers of an inpatient psychiatric facility. Methods: Medication reports were queried from the pharmacy database to identify all patients who were taking lithium within 1 year. Laboratory results, physician progress notes, nursing progress notes, and treatment plans were studied to detect any adverse events associated with lithium levels. Educational interventions created by pharmacy services were tailored toward medical staff and delivered over a 3 month period. Learning was assessed at pre-educational and posteducational interventions. Results: One hundred fifteen patients received lithium between March 2012 and March 2013. The most-frequent adverse effects reported associated with lithium included tremor, dizziness, slurred speech, and lethargy. Two patients were sent to the local emergency department for lithium toxicity and required dialysis. Fifty-two patients received lithium after educational interventions, and no adverse events were reported. A lithium drug-monitoring spreadsheet was created for pharmacy use, and drug-monitoring guidelines were revised and disseminated throughout the facility. Discussion: A reduction in negative outcomes associated with lithium was noted after educational interventions to medical staff occurred. The impact of pharmacist-led educational interventions demonstrated a high potential for success.

Lithium as an Alternative Option in Graves Thyrotoxicosis.

A 67-year-old woman was admitted with signs and symptoms of Graves thyrotoxicosis. Biochemistry results were as follows: TSH was undetectable; FT4 was >6.99 ng/dL (0.7–1.8); FT3 was 18 pg/mL (3–5); TSI was 658% (0–139). Thyroid uptake and scan showed diffusely increased tracer uptake in the thyroid gland. The patient was started on methimazole 40 mg BID, but her LFTs elevated precipitously with features of fulminant hepatitis. Methimazole was determined to be the cause and was stopped. After weighing pros and cons, lithium was initiated to treat her persistent thyrotoxicosis. Lithium 300 mg was given daily with a goal to maintain between 0.4 and 0.6. High dose Hydrocortisone and propranolol were also administered concomitantly. Free thyroid hormone levels decreased and the patient reached a biochemical and clinical euthyroid state in about 8 days. Though definitive RAI was planned, the patient has been maintained on lithium for more than a month to control her hyperthyroidism. Trial removal of lithium results in reemergence of thyrotoxicosis within 24 hours. Patient was maintained on low dose lithium treatment with lithium level just below therapeutic range which was sufficient to maintain euthyroid state for more than a month. There were no signs of lithium toxicity within this time period. Conclusion. Lithium has a unique physiologic profile and can be used to treat thyrotoxicosis when thionamides cannot be used while awaiting elective radioablation. Lithium levels need to be monitored; however, levels even at subtherapeutic range may be sufficient to treat thyrotoxicosis.

Lityumun Metabolik Yan Etkileri

Lityum 19. yüzyıldan bu yana tıpta kullanılan alkali bir iyondur. Lityumun psikiyatrik rahatsızlıklarda kullanımının yaygınlaşması ile birlikte yan etkilerin de gözlenmeye başlaması lityum kullanımı konusunda çekinceler doğurmuştur. Tüm bu çekincelere karşın lityumun bipolar bozukluk başta olmak üzere duygudurum bozukluklarında vazgeçilmez ilaçlardan birisidir. Lityumun halen özellikle bipolar bozuklukta altın standart sağaltım olarak kabul edilmesi yan etkilerinin iyi tanınması gerekliliğini de beraberinde getirmiştir. Lityumun süregen kullanımında çeşitli organ sistemleri üzerine olan etkileri iyi bilinmektedir. Bu yazıda metabolik yan etkiler olarak tiroid ve paratiroid bezleri ile vücut ağırlığı üzerine etkileri ve böbrekler üzerine olan etkilerinden söz edilirken bu yan etkilerin olası etki düzenekleri, klinik bulguları, olası risk etmenleri ve bu yan etkilere yönelik önlemler üzerinde durulacaktır. Lityumun tiroid üzerinde gözlenen en sık yan etkisi hipotiroididir. Klinik ve biyokimyasal özellikler bakımından primer hipotiroidi ile aynı özelliklere sahiptir ve en sık subklinik hipotiroidi olarak karşımıza çıkmaktadır. Hipotiroidi, subklinik de olsa sağaltıma yanıtsızlık veya yetersiz yanıtla ilişkili olabilir ve hızlı döngülük için bir risk etmeni olarak gösterilmektedir. Bu özellikleri nedeniyle hipotiroidi, şiddeti ne olursa olsun izleme alınmalı ve klinik hipotiroidi varlığında tiroid hormonu ile tedavi edilmelidir. Lityuma bağlı kilo artışı tedavi uyumunu bozmakta ve ruhsal rahatsızlığın seyrini olumsuz etkilemektedir. Kilo artışına bağlı gelişen diyabet, hipertansiyon, iskemik kalp hastalığı ve inme riskinde artış diğer sorun odaklarını oluşturmaktadır. Bu nedenlerle lityuma başlamadan önce risk etmenlerinin belirlenmesi, kilo takibi, beslenme alışkanlıklarının düzenlenmesi ve egzersiz programlarının önerilmesi önem taşımaktadır. Lityum kullanımı konusunda en çok sorun yaratan yan etkilerden birisi de böbrek işlev bozukluğudur. Lityuma bağlı gelişen böbrek işlevlerindeki bozulmanın çok önemli bir kısmı poliüri ve polidipsi ile karakterize nefrojen diyabetes insipidus şeklinde karşımıza çıkmaktadır. Nefrojen diayabetes insipidus, lityumun toplayıcı tübüller seviyesinde su ve sodyumun emilimini etkileyerek idrar konsantrasyon yeteneğini bozması sonucu gelişmektedir. Lityum kullanırken gelişebilecek böbrek hasarının önlenebilmesi için böbrek işlevlerinin yakın takibi önemlidir. Bununla birlikte lityum zehirlenmesi ataklarının böbrek hasarı riskini artırabileceğinden serum lityum düzeylerinin izlemi de büyük önem taşımaktadır. Sonuç olarak, lityum özellikle duygudurum bozukluklarında halen vazgeçilmezliğini korumaktadır. Bu kadar önemli bir tedavinin hastalardan esirgenmemesi için klinisyenlerin lityumun yan etkileri konusunda güncel bilgilere sahip olması ve gerekli önlemlerin alınması gerekmektedir.

Diabetes insípida nefrogénica

The anti-diuretic hormone arginine-vasopressin (AVP) is released from the pituitary and regulates water reabsorption in the principal cells of the kidney collecting duct. Binding of AVP to the arginine-vasopressin receptor type-2 in the basolateral membrane leads to translocation of aquaporin-2 water channels to the apical membrane of the principal cells of the collecting duct, inducing water permeability of the membrane. This results in water reabsorption in the collecting duct of the nephron following an osmotic gradient.Nephrogenic diabetes insipidus is caused by partial or complete renal resistance to the effects of AVP. Congenital nephrogenic diabetes insipidus is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their urine. Acquired nephrogenic diabetes insipidus can be caused by electrolyte imbalances (e.g., hypercalcemia, hypokalemia), renal/extra-renal diseases and drugs (e.g., lithium toxicity).This article reviews the causes, clinical manifestations, diagnosis and treatment of patients with nephrogenic diabetes insipidus. Based on more in-depth mechanistic understanding, new therapeutic strategies are current being explored.