Lithium-induced hypercalcemia with normal parathyroid hormone: A case report

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Abstract

Long-term use of lithium is a known risk factor for hypercalcemia often due to involvement of the parathyroid gland. Because of this, lithium-induced hypercalcemia typically occurs simultaneously with abnormal parathyroid hormone concentrations. This case report describes a 54-year-old white male who has received lithium therapy intermittently for more than 10 years. During admission to an acute inpatient psychiatric unit, the patient experienced hypercalcemia with normal parathyroid hormone concentrations and no other discernible cause. Based on the Naranjo algorithm, lithium was determined to be the probable cause of hypercalcemia. Current literature suggests that lithium-induced hypercalcemia occurs secondary to hyperparathyroidism; however, this case may provide evidence of another, unidentified cause.

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Primary Hyperparathyroidism

John Bilezikian (2018)

Background Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management. Methods In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease. Results PHPT is now recognized to include three clinical phenotypes: overt target organ involvement, mild asymptomatic hypercalcemia, and high PTH levels with persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is used, vitamin D deficiency is present, and whether parathyroid hormone levels are routinely measured in the evaluation of low bone density or frank osteoporosis. Guidelines for parathyroidectomy apply to all three clinical forms of the disease. If surgical guidelines are not met, parathyroidectomy can also be an appropriate option if no medical contraindications are present. If either the serum calcium or bone mineral density is of concern and surgery is not an option, pharmacological approaches are available and effective. Conclusions Advances in our knowledge of PHPT have guided new concepts in diagnosis and management. This article presents a summary of our current knowledge of the diagnosis, evaluation, management, and natural and interventional history of primary hyperparathyroidism.

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Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D.

Geoffrey N. Hendy, Lucie Canaff (2002)

The calcium-sensing receptor (CASR), expressed in parathyroid chief cells, thyroid C-cells, and cells of the kidney tubule, is essential for maintenance of calcium homeostasis. Here we show parathyroid, thyroid, and kidney CASR mRNA levels increased 2-fold at 15 h after intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in rats. Human thyroid C-cell (TT) and kidney proximal tubule cell (HKC) CASR gene transcription increased approximately 2-fold at 8 and 12 h after 1,25(OH)2D3 treatment. The human CASR gene has two promoters yielding alternative transcripts containing either exon 1A or exon 1B 5'-untranslated region sequences that splice to exon 2 some 242 bp before the ATG translation start site. Transcriptional start sites were identified in parathyroid gland and TT cells; that for promoter P1 lies 27 bp downstream of a TATA box, whereas that for promoter P2, which lacks a TATA box, lies in a GC-rich region. In HKC cells, transcriptional activity of a P1 reporter gene construct was 11-fold and of P2 was 33-fold above basal levels. 10(-8) m 1,25(OH)2D3 stimulated P1 activity 2-fold and P2 activity 2.5-fold. Vitamin D response elements (VDREs), in which half-sites (6 bp) are separated by three nucleotides, were identified in both promoters and shown to confer 1,25(OH)2D3 responsiveness to a heterologous promoter. This responsiveness was lost when the VDREs were mutated. In electrophoretic mobility shift assays with either in vitro transcribed/translated vitamin D receptor and retinoid X receptor-alpha, or HKC nuclear extract, specific protein-DNA complexes were formed in the presence of 1,25(OH)2D3 on oligonucleotides representing the P1 and P2 VDREs. In summary, functional VDREs have been identified in the CASR gene and provide the mechanism whereby 1,25(OH)2D up-regulates parathyroid, thyroid C-cell, and kidney CASR expression.

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Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

Shonni J. Silverberg, E. Lewiecki, Leif Mosekilde … (2009)

At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after 8-10 yr, regular monitoring (serum calcium and three-site BMD) is essential in those followed without surgery. Patients may present with normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism). Data on the incidence and natural history of this phenotype are limited. 4) In the absence of kidney stones, data do not support the use of marked hypercalciuria (>10 mmol/d or 400 mg/d) as an indication for surgery for patients. 5) Patients with bone density T-score -2.5 or less at the lumbar spine, hip, or distal one third radius should have surgery.

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Journal

Journal ID (nlm-ta): Ment Health Clin

Journal ID (iso-abbrev): Ment Health Clin

Journal ID (publisher-id): mhcl

Journal ID (pmc): Ment Health Clin

Title: The Mental Health Clinician

Publisher: College of Psychiatric & Neurologic Pharmacists

ISSN (Electronic): 2168-9709

Publication date Collection: September 2019

Publication date (Electronic): 4 September 2019

Volume: 9

Issue: 5

Pages: 318-321

Author notes

[1 ] Postgraduate Year-1 Pharmacy Practice Resident, VA Northeast Ohio Healthcare System, Cleveland, Ohio, cdorflinger@ 123456neomed.edu

² National Pharmacy Benefits Management Clinical Pharmacy Program Manager – Psychiatry and Geriatrics, VA Pharmacy Benefits Management Services, Cleveland, Ohio

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Charles Dorflinger https://orcid.org/0000-0001-9686-5452

Matthew Fuller https://orcid.org/0000-0002-9404-1713

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Serial Item and Contribution ID: mhcl-09-05-02 Publisher ID: MHC-D-18-00065

DOI: 10.9740/mhc.2019.09.318

PMC ID: 6728121

PubMed ID: 31534874

SO-VID: e64c8dc7-ebab-4bd7-afaa-9e3af70b4776

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Citation How to cite: Dorflinger C, Fuller M. Lithium-induced hypercalcemia with normal parathyroid hormone: A case report. Ment Health Clin [Internet].

Lithium-induced hypercalcemia with normal parathyroid hormone: A case report

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Most cited references 15

Primary Hyperparathyroidism

Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D.

Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

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