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The Role of Lithium in Management of Endocrine Tumors-A Comprehensive Review.

ABSTRACT: Background: Epidemiological data reveal that treatment with lithium, a mood stabilizer, is associated with decreased incidence and mortality of certain cancer types, such as melanoma. Therefore, repositioning of lithium as an anticancer agent has emerged as a promising strategy in oncology. Since lithium affects the physiology of several endocrine tissues, the goal of this study was to analyze the role of lithium in the pathogenesis and treatment of tumors of the endocrine system. Methods: The databases of PubMed, EMBASE, MEDLINE, were searched from January 1970 through February 2019 for articles including the keywords "lithium and"-"thyroid cancer," "thyroid nodule," "parathyroid adenoma," "parathyroid carcinoma," "pituitary adenoma," "pituitary neuroendocrine tumor," "neuroendocrine tumor," "carcinoid," "adrenal adenoma," "adrenal carcinoma," "pheochromocytoma/paraganglioma." Preclinical in vitro and in vivo studies as well as case series, retrospective cohort studies and prospective trials were selected for the analysis. Results: Treatment with lithium has been associated with a higher prevalence of thyroid enlargement, hypothyroidism and increased calcium levels due to parathyroid adenoma or hyperplasia, as one of the mechanisms of its action is to stimulate proliferation of normal follicular thyroid and parathyroid cells via activation of the Wnt signaling pathway. Supratherapeutic concentrations of lithium decrease the activity of glycogen synthase kinase-3? (GSK-3?), leading to cell cycle arrest in several in vitro cancer models including medullary thyroid cancer (TC), pheochromocytoma/paraganglioma and carcinoid. Growth inhibitory effects of lithium in vivo have been documented in medullary TC xenograft mouse models. Clinically, lithium has been used as an adjuvant agent to therapy with radioactive iodine (RAI), as it increases the residence time of RAI in TC. Conclusion: Patients chronically treated with lithium need to be screened for hypothyroidism, goiter, and hyperparathyroidism, as the prevalence of these endocrine abnormalities is higher in lithium-treated patients than in the general population. The growth inhibitory effects of lithium in medullary TC, pheochromocytoma/paraganglioma and carcinoid were achieved with supratherapeutic concentrations of lithium thus limiting its translational perspective. Currently available clinical data on the efficacy of lithium in the therapy of endocrine tumors in human is limited and associated with conflicting results.

SUBMITTER: Thakur S

PROVIDER: S-EPMC6842984 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Role of Lithium in Management of Endocrine Tumors-A Comprehensive Review.

Thakur Shilpa S Tobey Andrew A Klubo-Gwiezdzinska Joanna J

Frontiers in oncology 20191018

<b>Background:</b> Epidemiological data reveal that treatment with lithium, a mood stabilizer, is associated with decreased incidence and mortality of certain cancer types, such as melanoma. Therefore, repositioning of lithium as an anticancer agent has emerged as a promising strategy in oncology. Since lithium affects the physiology of several endocrine tissues, the goal of this study was to analyze the role of lithium in the pathogenesis and treatment of tumors of the endocrine system. <b>Meth ...[more]

PMID: 31750236

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Project description:Unlabelled: In recent years, immune checkpoint inhibitors have emerged as effective therapies for advanced neoplasias. As new checkpoint target blockers become available and additional tumor locations tested, their use is expected to increase within a short time. Immune-related adverse events (irAEs) affecting the endocrine system are among the most frequent and complex toxicities. Some may be life-threatening if not recognized; hence, appropriate guidance for oncologists is needed. Despite their high incidence, endocrine irAEs have not been fully described for all immunotherapy agents available. This article is a narrative review of endocrinopathies associated with cytotoxic T lymphocyte-associated antigen-4, blockade of programmed death receptor 1 and its ligand inhibitors, and their combination. Thyroid dysfunction is the most frequent irAE reported, and hypophysitis is characteristic of ipilimumab. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for clinical management are suggested. Heterogeneous terminology and lack of appropriate resolution criteria in clinical trials make adequate evaluation of endocrine AEs difficult. It is necessary to standardize definitions to contrast incidences and characterize toxicity patterns. To provide optimal care, a multidisciplinary team that includes endocrinology specialists is recommended.Implications for practiceImmune checkpoint inhibitors are already part of oncologists' therapeutic arsenal as effective therapies for otherwise untreatable neoplasias, such as metastatic melanoma or lung cancer. Their use is expected to increase exponentially in the near future as additional agents become available and their approval is extended to different tumor types. Adverse events affecting the endocrine system are among the most frequent and complex toxicities oncologists may face, and some may be life-threatening if not recognized. This study reviews endocrinopathies associated to immune checkpoint inhibitors available to date. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for management are proposed.

Project description:Incidence of endocrine cancers is rising every year. Over the last decade, evidence has accumulated that demonstrates the anti-cancer effects of an anti-diabetic drug, metformin, in endocrine malignancies. We performed a literature review utilizing the PubMed, Medline and clinicaltrials.gov databases using the keyword 'metformin' plus the following terms: 'thyroid cancer', 'thyroid nodules', 'parathyroid', 'hyperparathyroidism', 'adrenal adenoma', 'Cushing syndrome', 'hyperaldosteronism', 'adrenocortical cancer', 'neuroendocrine tumor (NET)', 'pancreatic NET (pNET)', 'carcinoid', 'pituitary adenoma', 'pituitary neuroendocrine tumor (PitNET)', 'prolactinoma', 'pheochromocytoma/paraganglioma'. We found 37 studies describing the preclinical and clinical role of metformin in endocrine tumors. The available epidemiological data show an association between exposure of metformin and lower incidence of thyroid cancer and pNETs in diabetic patients. Metformin treatment has been associated with better response to cancer therapy in thyroid cancer and pNETs. Preclinical evidence suggests that the primary direct mechanisms of metformin action include inhibition of mitochondrial oxidative phosphorylation via inhibition of both mitochondrial complex I and mitochondrial glycerophosphate dehydrogenase, leading to metabolic stress. Decreased ATP production leads to an activation of a cellular energy sensor, AMPK, and subsequent downregulation of mTOR signaling pathway, which is associated with decreased cellular proliferation. We also describe several AMPK-independent mechanisms of metformin action, as well as the indirect mechanisms targeting insulin resistance. Overall, repositioning of metformin has emerged as a promising strategy for adjuvant therapy of endocrine tumors. The mechanisms of synergy between metformin and other anti-cancer agents need to be elucidated further to guide well-designed prospective trials on combination therapies in endocrine malignancies.

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The Role of Lithium in Management of Endocrine Tumors-A Comprehensive Review.

Publications

The Role of Lithium in Management of Endocrine Tumors-A Comprehensive Review.

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