Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Case Study
  • Published:

Hypercalcemia and diabetes insipidus in a patient previously treated with lithium

Nature Clinical Practice Nephrology volume 3, pages 397–404 (2007)Cite this article

Abstract

Background A 65-year-old woman presented with decreased oral intake, a reduced level of consciousness, hypercalcemia and hypernatremia. She had previously received lithium for 20 years for a schizoaffective disorder, but this treatment had been discontinued 3 years before presentation.

Investigations Physical examination, laboratory studies including measurement of serum calcium and parathyroid hormone levels, measurement of urine and serum osmolalities before and after desmopressin administration, blood and urine cultures, and a CT scan of the abdomen.

Diagnosis Urosepsis, dehydration, kidney stone disease, hyperparathyroidism, and nephrogenic diabetes insipidus.

Management Hydration, antibiotics, intravenous pamidronate for rapid control of hypercalcemia, parathyroidectomy, surgical removal of the large kidney stones, a low-protein and low-sodium diet, and initiation of treatment with a thiazide diuretic.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Relationship between serum PTH concentration and serum total calcium concentration in various disease states
Figure 2: Evaluation and management of hypercalcemia
Figure 3: iPTH dynamics in lithium-treated and control groups
Figure 4: Hypothetical mechanisms that might coordinate systemic calcium and water homeostasis in humans

References

  1. Brown EM and MacLeod RJ (2001) Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81: 239–297

    Article  CAS  Google Scholar 

  2. Garofeanu CG et al. (1998) Causes of reversible nephrogenic diabetes insipidus: a systematic review. Am J Kidney Dis 45: 626–637

    Article  Google Scholar 

  3. Livingstone C and Rampes H (2006) Lithium: a review of its metabolic adverse effects. J Psychopharmacol 20: 347–355

    Article  Google Scholar 

  4. Presne C et al. (2003) Li-induced nephropathy: rate of progression and prognostic factors. Kidney Int 64: 585–592

    Article  CAS  Google Scholar 

  5. Timmer RT and Sands JM (1999) Lithium intoxication. J Am Soc Nephrol 10: 666–674

    CAS  PubMed  Google Scholar 

  6. Mallette LE and Eichhorn E (1986) Effects of lithium carbonate on human calcium metabolism. Arch Intern Med 146: 770–776

    Article  CAS  Google Scholar 

  7. Mak TW et al. (1998) Effects of lithium therapy on bone mineral metabolism: a two-year prospective longitudinal study. J Clin Endocrinol Metab 83: 3857–3859

    CAS  PubMed  Google Scholar 

  8. El-Hajj Fuleihan G et al. (2002) The familial benign hypocalciuric hypercalcemic syndromes. In Principles of Bone Biology, 1031–1045 (Eds Bilezikian JP et al.) San Diego: Academic Press

    Chapter  Google Scholar 

  9. Haden ST et al. (1997) Alterations in parathyroid dynamics in lithium-treated subjects. J Clin Endocrinol Metab 82: 2844–2848

    CAS  PubMed  Google Scholar 

  10. Bendz H et al. (1996) Hyperparathyroidism and long-term lithium therapy—a cross-sectional study and the effect of lithium withdrawal. J Intern Med 240: 357–365

    Article  CAS  Google Scholar 

  11. Nordenstrom J et al. (1992) Hyperparathyroidism associated with treatment of manic-depressive disorders by lithium. Eur J Surg 158: 207–211

    CAS  PubMed  Google Scholar 

  12. Hundley JC et al. (2005) Revisiting lithium-associated hyperparathyroidism in the era of intraoperative parathyroid hormone monitoring. Surgery 138: 1027–1032

    Article  Google Scholar 

  13. Awad SS et al. (2003) Parathyroid adenomas versus four-gland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy. World J Surg 27: 486–488

    Article  Google Scholar 

  14. Boton R et al. (1987) Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis 10: 329–345

    Article  CAS  Google Scholar 

  15. Oksche A and Rosenthal W (1998) The molecular basis of nephrogenic diabetes insipidus. J Mol Med 76: 326–337

    Article  CAS  Google Scholar 

  16. Schrier RW (2006) Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol 17: 1820–1832

    Article  CAS  Google Scholar 

  17. Christensen S et al. (1985) Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats. J Clin Invest 75: 1869–1879

    Article  CAS  Google Scholar 

  18. Christensen BM et al. (2004) Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI. Am J Physiol Cell Physiol 286: C952–C964

    Article  CAS  Google Scholar 

  19. Hensen J et al. (1996) Lithium induced polyuria and renal vasopressin receptor density. Nephrol Dial Transplant 11: 622–627

    Article  CAS  Google Scholar 

  20. Bendz H (1983) Kidney function in lithium-treated patients: a literature survey. Acta Psychiatr Scand 68: 303–324

    Article  CAS  Google Scholar 

  21. Earm JH et al. (1998) Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats. J Am Soc Nephrol 9: 2181–2193

    CAS  PubMed  Google Scholar 

  22. Mangat H et al. (1997) Hypercalcemia stimulates expression of intrarenal phospholipase A2 and prostaglandin H synthase-2 in rats: role of angiotensin II AT1 receptors. J Clin Invest 100: 1941–1950

    Article  CAS  Google Scholar 

  23. Kim GH et al. (2004) Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J Am Soc Nephrol 15: 2836–2843

    Article  CAS  Google Scholar 

  24. Bichet DG (2007) Treatment of nephrogenic diabetes insipidus. In UpToDate (Ed. Rose BD) Waltham, MA: UpToDate

    Google Scholar 

  25. Bilezikian JP et al. (2002) Summary statement from a workshop on asymptomatic hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 87: 5353–5361

    Article  CAS  Google Scholar 

  26. Sloand JA and Shelly MA (2006) Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride. Am J Kidney Dis 48: 832–837

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the valuable contirbutions of Dr Kamal Badr, Dr Walid Medawar and Dr Ghassan Awar.

Author information

Authors and Affiliations

  1. W Khairallah is a Specialist Endocrinologist at the Joslin Diabetes Center Affiliate, Gulf Diabetes Specialist Center, Bahrain.,

    Walid Khairallah

  2. A Fawaz is a second-year Fellow in the Division of Nephrology, American University of Beirut, Beirut, Lebanon.,

    Ahmad Fawaz

  3. EM Brown is Professor of Medicine and Director of the Calcium Unit of the Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,

    Edward M Brown

  4. Division of Endocrinology and Metabolism, G El-Hajj Fuleihan is Professor of Medicine and Director of the Calcium Metabolism and Osteoporosis Program, American University of Beirut, Beirut, Lebanon.,

    Ghada El-Hajj Fuleihan

Authors
  1. Walid Khairallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmad Fawaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edward M Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ghada El-Hajj Fuleihan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ghada El-Hajj Fuleihan.

Ethics declarations

Competing interests

EM Brown receives royalties related to the calcimimetic cinacalcet (Sensipar® Amgen).

The other authors declared they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khairallah, W., Fawaz, A., Brown, E. et al. Hypercalcemia and diabetes insipidus in a patient previously treated with lithium. Nat Rev Nephrol 3, 397–404 (2007). https://doi.org/10.1038/ncpneph0525

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneph0525

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing