Month: March 2025

What is the role of measuring serum uric acid level in my patient with hyponatremia suspected of having syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

The utility of checking serum uric acid (SUA) in hyponatremia primarily stems from the fact that it helps distinguish SIADH from volume contraction as the cause of hyponatremia.1 Whereas hyperuricemia commonly accompanies volume contraction, hypouricemia is found in the majority (70%) of patients with SIADH.2 This finding is caused by increased urinary excretion of SUA in patients with SIADH.3

There are several potential mechanisms for the association of SIADH with hypouricemia. First, the expanded vascular volume in these patients enhances UA clearance by decreasing its reabsorption, as supported by improved UA serum levels in SIADH patients on fluid restriction.4 Of note, UA normalization with fluid restriction is more pronounced in chronic SIADH patients compared to healthy individuals acutely volume overloaded via treatment with synthetic ADH (i.e. desmopressin).5 This may be due to the fact that, unlike endogenous ADH, desmopressin is a selective agonist of vasopressin 2 receptors (V2R), promoting water reabsorption in the collecting duct without binding to vasopressin 1 receptors (V1R), which promotes UA secretion and inhibits UA reabsorption in the proximal tubule.5,6  To make things worse, there is also evidence that chronic hyponatremia induced by SIADH can directly promote UA excretion!7

Last, keep in mind that salt-wasting disease, a less common cause of hyponatremia, may also be associated with hypouricemia. However, in contrast to patients with SIADH, UA excretion remains high and serum UA levels remain low in these patients even after their hyponatremia is corrected. 8

Bonus Pearl: Did you know that tolvaptan, a selective ADH (V2R) antagonist, has been shown to be effective in raising serum sodium and UA levels in SIADH patients with the caveat that its chronic use may also cause hyperuricemia? 9,10

Contributed by Stella Hoft, PhD, Medical Student, St. Louis University Medical School, St. Louis, Missouri

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References

  1. Liamis G, Christidis D, Alexandridis G, Bairaktari E, Madias NE, Elisaf M. Uric acid homeostasis in the evaluation of diuretic-induced hyponatremia. J Investig Med. 2007 Jan;55(1):36-44. doi: 10.2310/6650.2007.06027. PMID: 17441410. https://journals.sagepub.com/doi/10.2310/6650.2007.06027?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
  2. Decaux G, Musch W. Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol. 2008 Jul;3(4):1175-84. doi: 10.2215/CJN.04431007. Epub 2008 Apr 23. PMID: 18434618. https://journals.lww.com/cjasn/abstract/2008/07000/clinical_laboratory_evaluation_of_the_syndrome_of.38.aspx
  3. Li R, Wu B, Han M, Li M, Yang X, Zhang J, Zhang Y, Liu Y. Uric Acid Metabolic Disorders in Pituitary-Target Gland Axis. Diabetes Metab Syndr Obes. 2024 Feb 7;17:661-673. doi: 10.2147/DMSO.S448547. PMID: 38343584; PMCID: PMC10859102. https://www.dovepress.com/uric-acid-metabolic-disorders-in-pituitary-target-gland-axis-peer-reviewed-fulltext-article-DMSO
  4. Beck LH. Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med. 1979 Sep 6;301(10):528-30. doi: 10.1056/NEJM197909063011005. PMID: 460306. https://www.nejm.org/doi/abs/10.1056/NEJM197909063011005
  5. Decaux G, Namias B, Gulbis B, Soupart A. Evidence in hyponatremia related to inappropriate secretion of ADH that V1 receptor stimulation contributes to the increase in renal uric acid clearance. J Am Soc Nephrol. 1996 May;7(5):805-10. doi: 10.1681/ASN.V75805. PMID: 8738818. https://journals.lww.com/jasn/abstract/1996/05000/evidence_in_hyponatremia_related_to_inappropriate.23.aspx
  6. Taniguchi K, Tamura Y, Kumagai T, Shibata S, Uchida S. Stimulation of V1a receptor increases renal uric acid clearance via urate transporters: insight into pathogenesis of hypouricemia in SIADH. Clin Exp Nephrol. 2016 Dec;20(6):845-852. doi: 10.1007/s10157-016-1248-x. Epub 2016 Mar 2. PMID: 26935049. https://link.springer.com/article/10.1007/s10157-016-1248-x
  7. Decaux G, Prospert F, Soupart A, Musch W. Evidence that chronicity of hyponatremia contributes to the high urate clearance observed in the syndrome of inappropriate antidiuretic hormone secretion. Am J Kidney Dis. 2000 Oct;36(4):745-51. doi: 10.1053/ajkd.2000.17623. PMID: 11007676. https://www.ajkd.org/article/S0272-6386(00)08495-X/ppt
  8. Momi J, Tang CM, Abcar AC, Kujubu DA, Sim JJ. Hyponatremia-what is cerebral salt wasting? Perm J. 2010 Summer;14(2):62-5. doi: 10.7812/TPP/08-066. PMID: 20740122; PMCID: PMC2912080. https://www.thepermanentejournal.org/doi/10.7812/TPP/08-066
  9. Nagamine T. Uric acid levels with tolvaptan treatment for syndrome of inappropriate antidiuretic hormone secretion. Endocrine. 2024 Mar;83(3):826-827. doi: 10.1007/s12020-023-03612-3. Epub 2023 Nov 20. PMID: 37982946. https://link.springer.com/article/10.1007/s12020-023-03612-3
  10. Bondanelli M, Aliberti L, Gagliardi I, Ambrosio MR, Zatelli MC. Long-term low-dose tolvaptan efficacy and safety in SIADH. Endocrine. 2023 Nov;82(2):390-398. doi: 10.1007/s12020-023-03457-w. Epub 2023 Jul 28. PMID: 37507553; PMCID: PMC10543144. https://link.springer.com/article/10.1007/s12020-023-03457-w

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What is the role of measuring serum uric acid level in my patient with hyponatremia suspected of having syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

Why should I check serum magnesium level in my patient with hypokalemia in need of potassium replacement?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Short answer: Potassium and magnesium are highly intertwined in their physiological roles and magnesium is critical for renal retention of potassium.

Hypomagnesemia increases the release of renin from the kidney, leading to elevated levels of angiotensin II, which stimulates the adrenal cortex to secrete aldosterone. 1,2 The resulting secondary hyperaldosteronism contributes to refractory hypokalemia through increased sodium reabsorption via epithelial sodium channels (ENaC) in the distal nephron.  Increased sodium reabsorption in turn increases the expression and activity of the renal outer medullary potassium (ROMK) channels, which increases potassium secretion into the tubular lumen.1,3 Interestingly, magnesium also directly inhibits ROMK channels which, in the setting of hypomagnesemia, further leads to potassium loss.1,4

Parenthetically, most patients with mild to moderate hypomagnesemia are asymptomatic or have non-specific symptoms such as lethargy, muscle weakness or cramps. So don’t rely on symptoms to decide who should have their serum magnesium checked in the setting of hypokalemia. 5

Last, hypomagnesemia is not uncommon. It is found in 3-10% of general population, 10-30% of patients with type 2 diabetes, 10-60% of hospitalized patients and over 65% of those in the intensive care unit.5   What’s more concerning is that hypomagnesemia is also associated with an elevated risk of death from any cause and death from cardiovascular diseases.5

So, don’t forget to check serum magnesium level in your patient with hypokalemia in need of potassium replacement!

Bonus Pearls: Did you know that many drugs such as proton pump inhibitors (PPIs), thiazide and loop diuretics, aminoglycosides and chemotherapeutic agents are associated with magnesium wasting and hypomagnesemia, while sodium-glucose cotransporter-2 (SGLT2) inhibitors may be associated with increased renal magnesium reabsorption? 5

Contributed by Andy Wu, PhD, Medical Student, St. Louis University Medical School, St. Louis, Missouri

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References

  1. Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007 Oct;18(10):2649-52. doi: 10.1681/ASN.2007070792. Epub 2007 Sep 5. PMID: 17804670. https://pubmed.ncbi.nlm.nih.gov/17804670/
  2. AlShanableh Z, Ray EC. Magnesium in hypertension: mechanisms and clinical implications. Front Physiol. 2024 Apr 10;15:1363975. doi: 10.3389/fphys.2024.1363975. PMID: 38665599; PMCID: PMC11044701. https://pubmed.ncbi.nlm.nih.gov/38665599/
  3. Valinsky WC, Touyz RM, Shrier A. Aldosterone, SGK1, and ion channels in the kidney. Clin Sci (Lond). 2018 Jan 19;132(2):173-183. doi: 10.1042/CS20171525. PMID: 29352074; PMCID: PMC5817097. https://pubmed.ncbi.nlm.nih.gov/29352074/
  4. Rodan AR, Cheng CJ, Huang CL. Recent advances in distal tubular potassium handling. Am J Physiol Renal Physiol. 2011 Apr;300(4):F821-7. doi: 10.1152/ajprenal.00742.2010. Epub 2011 Jan 26. PMID: 21270092; PMCID: PMC3074996. https://pubmed.ncbi.nlm.nih.gov/21270092/
  5. Touyz RM, de Baaij JHF, Hoenderop JGJ. Magnesium Disorders. N Engl J Med. 2024 Jun 6;390(21):1998-2009. doi: 10.1056/NEJMra1510603. PMID: 38838313. https://pubmed.ncbi.nlm.nih.gov/38838313/

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why should I check serum magnesium level in my patient with hypokalemia in need of potassium replacement?

Should I discontinue the glucagon-like peptide-1 receptor agonist (GLP-1RA) perioperatively in my patient with an upcoming elective surgery?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Despite initial concerns, GLP-1RAs need not be categorically discontinued in patients undergoing surgery and, in fact, may be continued safely in most patients.

A December 2024 clinical practice “guidance”—not “guidelines” due to lack of firm evidence—involving several professional societies, including the American Society of Anesthesiologists (ASA) and the American Gastroenterological Association suggests that GLP-1RA therapy may be continued perioperatively in the absence of the following high risk factors: escalation phase of GLP-1RA (vs maintenance phase),1 higher dose, weekly dosing, presence of GI symptoms suggestive of delayed gastric emptying (eg, nausea, vomiting, abdominal pain, dyspepsia, constipation) and medical conditions associated with delayed gastric emptying (eg, gastroparesis, Parkinson’s disease).2

In the presence of one or more of the above risk factors that may contribute to delayed gastric and aspiration perioperatively, withholding GLP-1RAs should be considered.  When balancing the risks and benefits of withholding these drugs, shared decision making involving the patient and members of the care team including the procedural, anesthesia and prescribing providers is prudent.  For example, with discontinuation of GLP-1RAs, one should also consider the possibility of hyperglycemia in patients with diabetes with its potential adverse effects on surgical outcome .1

As far as the timing of discontinuation of GLP1-RAs, ASA recommends holding such drugs on the day of surgery for daily formulations and a week prior to surgery for weekly formulations while maintaining glycemic control. The above “guidance” also recommends assessment for symptoms of delayed gastric emptying on the day of surgery with use of point of care ultrasound (POCUS), if available, to assess degree of delayed gastric emptying.1

It’s worth noting that despite early case reports of pulmonary aspiration of gastric contents in patients on GLP-1RAs undergoing procedural sedation and/or general anesthesia, (3,4) recent larger studies have not substantiated such claims. Interestingly, a 2024 retrospective observational cohort of over 13,000 adults with diabetes found a lower risk of perioperative and postoperative delayed gastric emptying and antiemetic use among patients treated with GLP1-RA compared to non-users; aspiration/pneumonitis and ileus risks within 7 days were not significantly different between the 2 groups. 5

Bonus Pearl: Did you know that scintigraphy via ingestion of a radio-labelled meal is the gold standard for diagnosis of gastroparesis with the 13 C breath test using a solid meal as an acceptable alternative?6

Contributed by Shirley Joo, MD, Internal Medicine Associate Program Director, Mercy Hospital, St. Louis, Missouri

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References

  1. van Zuylen ML, Siegelaar SE, Plummer MP, et al. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration. Br J Anaesth. 2024;132:644-648. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration – PubMed
  2. Kindell TL, Wang AY, Wadhwa A, et al. Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period. Surgery for Obesity and Related Diseases 2024;20:1183-1186. Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period
  3. Klein SR, Hobai    Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: a case report.   Can J Anaesth. 2023;70(8):1394-1396.  Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: a case report – PubMed
  4. Silveira SQ, da Silva  LM, de Campos Vieira Abib  A,  et al.  Relationship between perioperative semaglutide use and residual gastric content: a retrospective analysis of patients undergoing elective upper endoscopy.   J Clin Anesth. 2023;87:111091.  Relationship between perioperative semaglutide use and residual gastric content: A retrospective analysis of patients undergoing elective upper endoscopy – PubMed
  5. Klonoff DC, Kim SH, Galindo RJ, et al. Risks of peri- and postoperative complications with glucagon-like peptide-1 receptor agonists. Diabetes Obes Metab 2024; 26:3128-3138. Risks of peri- and postoperative complications with glucagon-like peptide-1 receptor agonists – PubMed
  6. Ghazanfar H, Allena N, Javed N, Ponnachan D, Narasimhadevara S, Komadur T, et al. Diagnostic Modalities Used in Diagnosing Gastroparesis: A Clinical Review. Cureus. 2022 Oct 21;14(10):e30540. https://pmc.ncbi.nlm.nih.gov/articles/PMC9675943/ 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should I discontinue the glucagon-like peptide-1 receptor agonist (GLP-1RA) perioperatively in my patient with an upcoming elective surgery?