Endocrine

My hospitalized patient with acute kidney injury and type 2 diabetes is persistently hypoglycemic, likely related to sulfonylurea use. Is there a role for octreotide?

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

Yes, octreotide is indicated in the treatment of sulfonylurea-induced hypoglycemia1.

Sulfonylureas are widely used in the treatment of type 2 diabetes mellitus. Hypoglycemia is a known potential adverse effect which may be prolonged and recurrent, and last for days after ingestion.1,2 The risk is higher in elderly patients, renal or hepatic dysfunction, alcohol use, and polypharmacy, as observed with certain antibiotics.3,4

The mode of action of sulfonylureas is through binding to SUR1 receptors on the pancreatic β-cell membrane which leads to an inhibition of ATP-dependent potassium efflux channels. This results in membrane depolarization, opening voltage-gated calcium channels which in turn triggers insulin release.1 Sulfonylureas are metabolized in the liver and are renally cleared, thus hepatorenal dysfunction can increase the magnitude and duration their action.2  Octreotide binds to somatostatin receptors on pancreatic β-cells, which closes the voltage-gated calcium channels, preventing insulin release.1

Treatment for sulfonylurea-induced hypoglycemia begins with carbohydrate administration, with oral glucose or IV dextrose boluses and infusion.1 Octreotide should be used in acute overdose as well in refractory hypoglycemia.5 In fact, the administration of carbohydrates can cause a transient hyperglycemia which potentiates further insulin release, leading to recurrent rebound hypoglycemia.1

Octreotide can be given subcutaneously or IV with equivalent bioavailability. The typical dose is 50-100 micrograms every 6-12 hours, with 12-72 hours of therapy usually considered adequate. Serum glucose should be closely monitored during treatment and at least for 16-24 hours afterwards. The good news is that octreotide is generally well tolerated, and, in most cases, adverse effects are mild including hyperglycemia, injection site pain, and GI upset.1,2,5

Bonus Pearl:

Did you know that sulfonylureas are also widely used as herbicides? Herbicidal sulfonylureas disrupt the synthesis of branched chain amino acids via inhibition of AHAS, an enzyme present in plants, bacteria, and fungi. There is low toxicity to humans and animals as our bodies lack this enzyme.6

Contributed by Tony Hiran, MD, Mercy Hospital, St. Louis, MO

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Dougherty PP, Klein-Schwartz W. Octreotide’s role in the management of sulfonylurea-induced hypoglycemia. J Med Toxicol 2010;6:199-206. doi: 10.1007/s13181-010-0064-z. PMID: 20352540; PMCID: PMC3550273.
  2. Gonzalez RR, Zweig S, Rao J, Block R, Greene LW. Octreotide therapy for recurrent refractory hypoglycemia due to sulfonylurea in diabetes-related kidney failure. Endocr Pract 2007;13:417-23. doi: 10.4158/EP.13.4.417. PMID: 17669721.
  3. Harrigan RA, Nathan MS, Beattie P. Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment. Ann Emerg Med 2001; 38:68-78. doi: 10.1067/mem.2001.114314. PMID: 11423816.
  4. Pearls4Peers. My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia — can it be related? Pearls4Peers. 2016 Jul 27. Available from: https://pearls4peers.com/2016/07/27/my-patient-is-being-treated-for-a-urinary-tract-infection-with-trimethoprim-sulfamethoxazole-tmp-smx-and-has-developed-hypoglycemia-can-it-be-related/ [Accessed 1st January 2026].
  5. Glatstein M, Scolnik D, Bentur Y. Octreotide for the treatment of sulfonylurea poisoning. Clin Toxicol (Phila) 2012;50:795-804. doi: 10.3109/15563650.2012.734626. Epub 2012 Oct 10. PMID: 23046209.
  6. Lonhienne T, Garcia MD, Pierens G, Mobli M, Nouwens A, Guddat LW. Structural insights into the mechanism of inhibition of AHAS by herbicides. Proc Natl Acad Sci U S A. 2018;115:E1945-E1954. doi: 10.1073/pnas.1714392115. Epub 2018 Feb 13. PMID: 29440497; PMCID: PMC5834681.

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!

My hospitalized patient with acute kidney injury and type 2 diabetes is persistently hypoglycemic, likely related to sulfonylurea use. Is there a role for octreotide?

“My patient with severe hypothyroidism developed a large pericardial effusion. What is the pathophysiology underlying this process?”

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

Pericardial effusion in hypothyroidism—responsible for up to 14% of all pericardial effusions¹⁻²—is thought to be related to an increase in permeability of the pericardial capillaries to serum proteins (eg, albumin) resulting in an exudative effusion.³   Increased capillary permeability may in turn be due to the release of histamine by mastocytes or a direct effect of thyroid hormone deficiency on vascular endothelial integrity. ¹⁻³ In addition, hypothyroidism can be associated with pulmonary hypertension and a decrease in catecholamines, both of which can impair lymphatic drainage and further exacerbate the effusion.¹

Of note, myxedema — the accumulation of acid mucopolysaccharides causing fluid retention –– by itself does not explain the accumulation of pericardial fluid, as there is a lack of acid mucopolysaccharide buildup in the pericardial space.¹⁻² Autoimmune processes also do not appear to play a role in this context as pericardial disease can occur in both autoimmune (eg, Hashimoto thyroiditis) and non-autoimmune hypothyroidism.¹ Thus, the pericardial effusion in hypothyroidism seems to be a direct consequence of the metabolic effects of thyroid hormone deficiency itself. 

Occasionally, pericardial effusion in hypothyroidism is not so “benign” and can be complicated by tamponade.¹ In addition to timely percutaneous or surgical drainage of the effusion, thyroid hormone supplementation should be initiated without delay. ¹⁻² Although most pericardial effusions resolve over several months with adequate thyroid supplementation, they may recur in severe or chronically untreated hypothyroidism due to persistent alterations in the pericardial vascular permeability and impaired lymphatic drainage. ¹⁻³ This is another reason to remind patients to not go off their thyroid supplementation!

Bonus pearl: Did you know that the attendant increase in metabolic demands, plasma volume and higher levels of thyroxine-binding globulin in pregnancy necessitates routine upward titration of levothyroxine in pregnant patients with hypothyroidism? ⁵

Contributed by: Sarah de la Serna, Ponce Health Sciences University, St. Louis, MO and Tony Hiran, MD, Mercy Hospital, St. Louis, MO

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Chahine J, Ala CK, Gentry JL, Pantalone KM, Klein AL. Pericardial diseases in patients with hypothyroidism. Heart. 2019 Jul;105(13):1027-1033. doi: 10.1136/heartjnl-2018-314528. Epub 2019 Apr 4. PMID: 30948517. Pericardial diseases in patients with hypothyroidism – PubMed
  2. Chaker L, Papaleontiou M. Hypothyroidism: A Review. JAMA. Published online September 03, 2025. doi:10.1001/jama.2025.13559. Hypothyroidism: A Review | Endocrinology | JAMA | JAMA Network
  3. González Vílchez F, Castillo L, Pi J, Ruiz E. Manifestaciones cardíacas del hipotiroidismo primario. Factores determinantes y respuesta al tratamiento [Cardiac manifestations of primary hypothyroidism. Determinant factors and treatment response]. Rev Esp Cardiol. 1998 Nov;51(11):893-900. Spanish. PMID: 9859712. [Cardiac manifestations of primary hypothyroidism. Determinant factors and treatment response] – PubMed
  4. Kerber RE, Sherman B. Echocardiographic evaluation of pericardial effusion in myxedema. Incidence and biochemical and clinical correlations. Circulation. 1975 Nov;52(5):823-7. doi: 10.1161/01.cir.52.5.823. PMID: 126121. Echocardiographic evaluation of pericardial effusion in myxedema. Incidence and biochemical and clinical correlations – PubMed
  5. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid : Official Journal of the American Thyroid Association. 2017;27(3):315-389. doi:10.1089/thy.2016.0457. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum – PubMed

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!

“My patient with severe hypothyroidism developed a large pericardial effusion. What is the pathophysiology underlying this process?”

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

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

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?

What are the proven benefits and side effects of testosterone therapy in my elderly male patient with hypogonadism?

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

The benefits and side-effects of testosterone therapy (TTh) in male hypogonadism, a common condition among elderly men, have been explored in several trials, demonstrating variable health benefits without significant side effects.1-4

A large 2016 randomized placebo-controlled trial of testosterone replacement for one year in elderly men found that TTh modestly improves muscle mass and strength (by 5%) without significant reduction in falls or frailty.1 This study also showed significant improvement in sexual desire and erectile dysfunction, but the effect of TTh on erections was weaker than that of phosphodiesterase inhibitors. Of interest, TTh did not improve fatigue in this study.1 This is important because lack of energy is probably the commonest complaint by men in ambulatory setting requesting that a serum testosterone level be checked.

Interestingly, in one study, cognition was not improved by TTh.2 Additionally, although TTh has been shown to improve bone density,3  it is not known if it has any impact on the risk of fractures due to lack of proper studies.  Hence, TTh should not be considered for treatment of osteoporosis at this time.  

TTh has been shown to be associated with a rise in hemoglobin by ~1 g/dl.4 However, some men may develop polycythemia, especially if they achieve supranormal levels of serum testosterone with therapy. Testosterone and hemoglobin concentrations should be monitored during TTh.3

Although there have been concerns about risks of cardiovascular events and prostate cancer with TTh, a recent randomized placebo controlled cardiovascular trial showed no effect of TTh on the incidence of major adverse cardiovascular events.4 TTh also does not appear to increase the risk of prostate cancer in the short term (up to 3 years), but long- term prospective trials have not yet been conducted to exclude this possibility.3

Feel free to use the above summary while discussing the pros and cons of TTh with your patients.

Bonus Pearl: Did you know that, according to the Endocrine Society Clinical Practice Guideline,3 in men with symptoms and signs consistent with testosterone deficiency, measuring fasting morning total testosterone concentrations followed by repeat testing for confirmation is recommended.  In men whose total testosterone is near the lower limit of normal or who have condition that alters sex hormone binding globulin, a free testosterone concentration using either equilibrium dialysis or estimating it using an accurate formula is recommended. 3

Contributed by Sandeep Dhindsa, MD, Director, Division of Endocrinology, Diabetes and Metabolism, St. Louis University Medical School, St. Louis, Missouri

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older Men. N Engl J Med. 2016;374(7):611-24. Epub 2016/02/18. doi: 10.1056/NEJMoa1506119. PubMed PMID: 26886521.
  2. Snyder PJ, Bhasin S, Cunningham GR, et al. Lessons from the testosterone trials. Endocr Rev. 2018;39(3):369-86. Epub 2018/03/10. doi: 10.1210/er.2017-00234. PubMed PMID: 29522088; PMCID: PMC6287281.
  3. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-44. Epub 2018/03/22. doi: 10.1210/jc.2018-00229. PubMed PMID: 29562364.
  4. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107-17. Epub 2023/06/16. doi: 10.1056/NEJMoa2215025. PubMed PMID: 37326322.

 

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 are the proven benefits and side effects of testosterone therapy in my elderly male patient with hypogonadism?

Should I consider treating my patient with heart failure with an SGLT2 inhibitor?

FA Manian MD, MPH, , , , , , , , , , , , , , 1 Comment

Absolutely! Although sodium glucose cotransporter 2 (SGLT2) inhibitors are often used for their antidiabetic properties, more recently they have been shown to have extraordinary benefits in patients with heart failure.

 In 2015, a large randomized controlled trial, EMPA-REG OUTCOME, showed that empagliflozin significantly lowered overall death, death from cardiovascular events, and hospitalizations for heart failure in patients who had type II diabetes (T2DM) and cardiovascular disease1.

Later, 2 other randomized controlled trials showed that patients with heart failure with reduced ejection fractions (HFrEF), irrespective of a diagnosis of T2DM, had lower rates of death from cardiovascular causes and better heart failure outcomes when treated with SGLT2 inhibitors2,3.

In 2021, the EMPEROR Preserved trial showed that SGLT2 inhibitors provide significant clinical benefit for patients with heart failure with preserved ejection fraction (HFpEF), irrespective of the presence of T2DM4. In addition, multiple studies have shown substantial benefit to starting SGLT2 inhibitors during or shortly after a hospitalization for heart failure.5,6,7

 The effectiveness of SGLT2 inhibitors in heart failure is also reflected in the updated guidelines from the American College of Cardiology/American Heart Association8  that recommend  use of SGLT2 inhibitors in patients with chronic symptomatic HFrEF.  In addition,  the guidelines state that SGLT2 inhibitors can be beneficial in decreasing heart failure hospitalizations and cardiovascular mortality for patients mildly reduced ejection fraction and those with HFpEF.

 Potential mechanisms of action of SGLT2 inhibitors in heart failure include reduction in myocardial oxidative stress, decrease cardiac preload and afterload, increase endothelial function, decrease arterial stiffness, and increase muscle free fatty acid uptake which leads to increased availability of ketones during times of stress.9 

So the data to date suggest that we should consider SGLT2 inhibitors as part of our armamentarium for treatment of heart failure unless, of course, there are contraindications, including pregnancy/risk of pregnancy, breastfeeding, eGFR <30mL/min/1.73 m2, symptoms of hypotension, systolic blood pressure <95mmHg, or a known allergic/other adverse reactions. 10

Bonus Pearl: Did you know that SGLT 2 inhibitors are derived from phlorizin, a naturally occurring phenol glycoside first isolated back in 1835 from the bark of apple tree in 1835? 11

Contributed by Yisrael Wallach, MD, St. Louis, Missouri

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., … & Inzucchi, S. E. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine, 373(22), 2117-2128. https://pubmed.ncbi.nlm.nih.gov/26378978/
  2. McMurray, J. J., Solomon, S. D., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., … & Langkilde, A. M. (2019). Dapagliflozin in patients with heart failure and reduced ejection fraction. New England Journal of Medicine, 381(21), 1995-2008. https://pubmed.ncbi.nlm.nih.gov/31535829/
  3. Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., … & Zannad, F. (2020). Cardiovascular and renal outcomes with empagliflozin in heart failure. New England Journal of Medicine, 383(15), 1413-1424. https://pubmed.ncbi.nlm.nih.gov/32865377/
  4. Anker, S. D., Butler, J., Filippatos, G., Ferreira, J. P., Bocchi, E., Böhm, M., … & Packer, M. (2021). Empagliflozin in heart failure with a preserved ejection fraction. New England Journal of Medicine, 385(16), 1451-1461. https://pubmed.ncbi.nlm.nih.gov/34449189/
  5. Cunningham, J. W., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Desai, A. S., Jhund, P. S., … & Solomon, S. D. (2022). Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction. Journal of the American College of Cardiology. https://pubmed.ncbi.nlm.nih.gov/36041912/
  6. Voors, A. A., Angermann, C. E., Teerlink, J. R., Collins, S. P., Kosiborod, M., Biegus, J., … & Ponikowski, P. (2022). The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nature medicine, 28(3), 568-574. https://pubmed.ncbi.nlm.nih.gov/35228754/
  7. Bhatt, D. L., Szarek, M., Steg, P. G., Cannon, C. P., Leiter, L. A., McGuire, D. K., … & Pitt, B. (2021). Sotagliflozin in patients with diabetes and recent worsening heart failure. New England Journal of Medicine, 384(2), 117-128. https://pubmed.ncbi.nlm.nih.gov/33200892/
  8. Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., … & Yancy, C. W. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure: Executive summary: a report of the American College of Cardiology/American heart association joint Committee on clinical practice guidelines. Journal of the American College of Cardiology, 79(17), 1757-1780. https://pubmed.ncbi.nlm.nih.gov/35379504/
  9. Muscoli, S., Barillà, F., Tajmir, R., Meloni, M., Della Morte, D., Bellia, A., … & Andreadi, A. (2022). The New Role of SGLT2 Inhibitors in the Management of Heart Failure: Current Evidence and Future Perspective. Pharmaceutics, 14(8), 1730. https://pubmed.ncbi.nlm.nih.gov/36015359/
  10. Aktaa, S., Abdin, A., Arbelo, E., Burri, H., Vernooy, K., Blomström-Lundqvist, C., … & Gale, C. P. (2022). European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing: developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology. EP Europace, 24(1), 165-172. https://pubmed.ncbi.nlm.nih.gov/34455442/
  11. Petersen, C. (1835). Analyse des phloridzins. Annalen der pharmacie, 15(2), 178-178. 

Disclosures: 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 consider treating my patient with heart failure with an SGLT2 inhibitor?

What’s the connection between severe hypoglycemia and hypothermia?

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

The association of severe hypoglycemia and low body temperatures has been well documented at least since 1960s.  Hypothermia is thought to be caused by low blood glucose in the brain (neuroglucopenia) which may serve as a protective mechanism for decreasing energy demand during glucose deprivation.1-2

A 2012 retrospective study involving mostly patients with diabetes mellitus with severe hypoglycemia (majority with serum glucose 18-54 mg/dl) found that 23% of patients had hypothermia (defined as body temperature < 95◦F or 35◦C). The incidence of hypothermia was not affected by age, diabetes, season or time of day.  Two patients had extremely low temperatures (<90◦F).  There was an association between hypothermia and severity of hypoglycemia.1

An older experimental study (1974) involving 36 recumbent nude men in thermoneutral environment found that that insulin-induced hypoglycemia was associated with rectal temperatures below 96.2◦F (36◦C) in 33%.  Cooling was attributed to reduction in heat production and to secretion of sweat, peripheral vasodilatation and hyperventilation.2

But before you attribute hypothermia to hypoglycemia, make sure other causes of hypothermia such as sepsis, hypoadrenalism, hypothyroidism, alcohol and stroke are ruled out.3  

Bonus Pearl: Did you know that heat production is accomplished by shivering, which can increase the normal basal metabolic rate by 2-5 times as well as via non-shivering thermogenesis through increased levels of thyroxine and epinephrine?3

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Tran C, Gariani K, Hermann FR, et al. Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes. Diab Metab 2012;38:370-72. https://www.sciencedirect.com/science/article/abs/pii/S1262363612000535?via%3Dihub
  2. Strauch BS, Felig P, Baxter JD, et al. Hypothermia in hypoglycemia. JAMA 1969;210:345-46. https://jamanetwork.com/journals/jama/article-abstract/349081
  3. McCullough L, Arora S. Diagnosis and treatment of hypothermia. Am Fam Physician 2004;70:2325-2332. https://www.aafp.org/afp/2004/1215/p2325.html

Disclosures: 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 or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. 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’s the connection between severe hypoglycemia and hypothermia?

Why is my diabetic patient complaining of arm pain and localized edema for couple of weeks without an obvious cause?

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

Aside from the usual suspects associated with a painful extremity (eg, trauma, deep venous thrombosis and soft tissue infections), think of spontaneous diabetic myonecrosis (DMN), also known as diabetic muscle infarction (1-3).

DMN is characterized by abrupt onset of painful swelling of the affected muscle, most often of the lower extremities, but also occasionally upper extremities. DMN occurs in patients with longstanding DM whose blood glucose control has deteriorated over time, often with nephropathy, retinopathy and/or neuropathy (1-3).

Couple of things to remember when considering DMN in your differential of a painful extremity. First, except for localized edema and tenderness over the involved muscle, the exam may be unremarkable. Specifically, there is no erythema or signs of compartment syndrome and fever is absent in the great majority of patients (~90%) (2). Even white blood cell count and creatine kinase (CK) are usually normal. The reason for normal CK at presentation is not clear but CK might have already peaked by the time of patient presentation (3). In contrast, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are usually elevated (>80%) (1).

MRI (without contrast in patients with renal insufficiency) is the imaging of choice with muscle enlargement and edema with hyperintense signal on T2-weighted images and other changes, including perifascial, perimuscular and or subcutaneous edema (1-3). Muscle biopsy is not currently recommended because of its adverse impact on time to symptomatic improvement. Non-surgical therapy, with rest, analgesia and glycemic control is usually recommended (1-3).

 
Though its exact cause is still unclear, atherosclerosis, diabetic microangiopathy, vasculitis with thrombosis and ischemia-reperfusion injury have been posited as potential precipitants for DMN. The role of anti-phospholipid syndrome, particularly in patients with type I DM, is unclear (1,2).

 
Bonus pearl: Did you know that symptoms of DMN may last for weeks with at least one-third of patients having a recurrence in the same muscle or elsewhere (1)?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Reference
1. Horton WB, Taylor JS, Ragland TJ, et al. Diabetic muscle infarction: a systematic review. BMJ Open Diabetes Research and Care 2015;3:e000082.
2. Trujillo-Santos AJ. Diabetic muscle infarction. An underdiagnosed complication of long-standing diabetes. Diabetes Care 2003;26:211-15.
3. Diabetes muscle infarction in end-stage renal disease:A scoping review on epidemiology, diagnosis and treatment. World J Nephrol 2018;7:58-64.

Why is my diabetic patient complaining of arm pain and localized edema for couple of weeks without an obvious cause?

Can hypothyroidism be associated with hypertension?

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

Short answer: Yes! Just as hyperthyroidism, hypothyroidism is also associated with hypertension (1-5). Compared to normal subjects, patients with hypothyroidism have a 3-fold increased prevalence of hypertension, usually diastolic (2). In fact, hypothyroidism has been identified as a cause of hypertension in 3% of patients with high blood pressure and is the most common cause of secondary hypertension after renovascular hypertension (1-3).

 
High systemic vascular resistance and increased arterial stiffness are among the important mechanisms explaining hypothyroid-induced hypertension (1). High systemic vascular resistance is thought to be due to the absence of the vasodilator effects of T3 on vascular smooth muscle and decreased response to beta-adrenergic stimulation, which in turn leads to increased alpha-adrenergic responses. Increased arterial stiffness may also contribute due to the myxedema involvement of the arterial wall. Other potential factors include free water retention due to an inappropriate secretion of anti-diuretic hormone (ADH) and obesity in hypothyroid patients (1,4).

 
Similar to its prevalence in hypothyroidism, hypertension is about 3-fold higher in patients with overt hyperthyroidism compared to normal subjects (1). However, in contrast to hypothyroid patients, the hypertension in hyperthyroidism is primarily “cardiogenic”, where the increased blood pressure levels are mainly maintained by the increased cardiac output due to high stroke volume and heart rate (1).

 
Thus, both hypothyroidism and hyperthyroidism can be associated with hypertension!

 
Bonus pearl: Did you know that hypertension due to hypothyroidism is typically associated with a low-renin state, is particularly sensitive to salt intake, and may not respond as well to angiotensin -converting enzyme inhibitors (1)?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 
References
1. Mazza A, Beltramello G, Armigliato M, et al. Arterial hypertension and thyroid disorders: what is important to know in clinical practice? Annales d’Endocrinologie 2011;72:296-303. https://www.sciencedirect.com/science/article/abs/pii/S0003426611000886
2. Dernellis J, Panaretou M. Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism 2002; Am Heart J 2002;143:718-24. https://www.ncbi.nlm.nih.gov/pubmed/11923811
3. Anderson GH, Blakeman N, Steeten DHP. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. J Hypertension 1994;12:609-15. https://insights.ovid.com/hypertension/jhype/1994/05/000/effect-age-prevalence-secondary-forms-hypertension/15/00004872
4. Saito I, ITO K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension 1983;5:112-15. https://www.ahajournals.org/doi/10.1161/01.hyp.5.1.112
5. Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet 2017;390:1550-62. https://www.ncbi.nlm.nih.gov/pubmed/28336049

Can hypothyroidism be associated with hypertension?

Does my patient on chronic prednisone need stress doses of corticosteroids perioperatively?

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

There are wide-ranging opinions on stress doses of corticosteroids (CS) in patients on chronic prednisone undergoing surgery, largely due to lack of adequately-sized randomized controlled studies.  Most experts seem to agree, however, that the age-old practice of routinely administering very high doses of hydrocortisone (eg, 100 mg IV every 8 hours) with prolonged taper postoperatively is excessive. 1-7

Couple of questions to consider before you decide on stress doses of CS for your patient with CS-induced (not primary) adrenal suppression. First, is your patient likely to have a suppressed adrenal function? And if so, what type of surgery is he or she about to undergo?

As for the first question, keep in mind that exogenous CS suppress the production of corticotropin (ACTH) and can induce adrenal atrophy that may persist for up to 12 months, an effect that’s dependent not only on their dose but also on their duration and may vary greatly from person to person. 2,4

Generally, a daily prednisone dose of 5 mg or less —irrespective of the duration— is considered unlikely to cause adrenal suppression (unless it’s given at bed time) and therefore should not require stress doses of CS.1 Conversely, clinical features of Cushing’s syndrome and prednisone doses of 20 mg or more daily for more than 3 weeks are likely to be associated with hyphothalamic-pituitary-adrenal (HPA) axis suppression.  Due to possible delay in the recovery of the HPA axis after discontinuation of exogenous CS, you should review not only your patient’s current dose and duration of CS but his or her regimen during the previous year. 2

When in doubt, particularly in patients receiving intermediate doses (eg, between 5 to 20 mg of prednisone daily) or duration of CS, testing the HPA axis (eg, by cosyntropin stimulation) has been suggested by some with the caveats that it’s a grade 2C (weak recommendation, low quality evidence) recommendation,7 and the results may not necessarily predict clinical adrenal insufficiency or be available before surgery. 4  

Once you have decided that your patient may be at risk of adrenal insufficiency during the perioperative period, the stress dose and duration of CS will likely depend on the type of surgery: “minor” (eg, inguinal herniorrhaphy); “moderate” (eg, total joint replacement, peripheral vascular surgery) and “major” (eg, pancreatoduodenectomy, cardiac surgery with cardiopulmonary bypass). 

A popular online resource suggests the following:4

  • Minor surgery or local anesthesia: Give only the morning maintenance dose of CS without any stress doses
  • Moderate surgery: Give the usual morning dose plus hydrocortisone IV 50 mg (or equivalent) just before the procedure followed by 25 mg IV every 8 hours for 24 hours, followed by the maintenance regimen
  • Major surgery: Give the usual morning dose plus hydrocortisone 100 mg IV before anesthesia induction, followed by 50 mg IV every 8 hours for 24 hours, tapering the dose by half each day to maintenance.

Alternatively, for minor and moderate procedures, other authors suggest usual daily dose plus hydrocortisone 50 mg IV before incision, followed by hydrocortisone 25 mg IV every 8 h for 24 h, then the usual daily dose.1  Yet others have recommended giving IV hydrocortisone 25 mg/day for 1 day for minor surgeries, 50-75 mg/day x 1-2 days for moderate surgeries, and 100-150 mg/day for 2-3 days for major surgeries.2-4 Whichever regimen you chose, make sure to give the morning maintenance dose.  

Why is less aggressive stress dosing being favored in these patients? Several reasons come to mind, including:

  •  In normal subjects, endogenous cortisol production rarely rises above 150-200 mg /day even in response to major surgery 2-4   
  • High doses of CS, particularly with long taper, may unnecessarily subject patients to adverse effects, such as hyperglycemia and poor wound healing 3,4
  • Published reports of CS-treated patients having complications such as hypotension or even death in the postoperative period have generally only implicated, not proven, adrenal insufficiency as a cause. 1-4

 

Bonus pearl: Did you know that the hypotension of secondary adrenal insufficiency in patients treated with CS is not caused by mineralocorticoid deficiency? Instead, it may in part be related to the action of CS in enhancing vascular responsiveness to vasopressors (eg, catecholamines).2 

If you like this post, download the P4P app on your smartphone and sign up

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

to catch future pearls right into your inbox, all for free!

References

  1. Liu MM, Reidy AB, Saatee S, et al. Perioperative steroid management: Approaches based on current evidence. Anesthesiology 2017;127:166-72. https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2626031
  2. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin N Am 2003;32:367-83. http://pggweb.com/doc/glucocorticoids.pdf
  3. Salem M, Tainsh RE Jr, Bromberg J, et al. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg 1997;219:416-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1243159/
  4. Shaw M. When is perioperative ‘steroid coverage’ necessary? Clev Clin J Med 2002;69:9-11. https://www.ncbi.nlm.nih.gov/pubmed/11811727
  5. Urmson K. Stress dose steroids: the dogma persists. Can J Anesthe 2019;September 23. https://www.ncbi.nlm.nih.gov/pubmed/31549340
  6. Wax DB. One size fits all for stress-dose steroids. Anesthesiology 208;128:674-87. https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2672525
  7. Hamrahian AH, Roman S, Milan S. The management of the surgical patient taking glucocorticoids. Uptodate 2019, accessed October 21, 2019. https://www.uptodate.com/contents/the-management-of-the-surgical-patient-taking-glucocorticoids
Does my patient on chronic prednisone need stress doses of corticosteroids perioperatively?

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?

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

You may have to!  That’s because patients with DM due to pancreatic disease (also known as “pancreatogenic [Type 3C] diabetes”) tend to have more labile blood glucoses with particular predisposition to severe hypoglycemic episodes due to the impairment of glucagon production by pancreatic alpha-cells. 1-3

This observation dates back to a 1977 study where a high rate of hypoglycemic episodes was found among 59 patients with chronic pancreatitis (most with insulin-dependent DM), including 3 deaths and 2 suffering from severe brain damage following hypoglycemic coma. Interestingly, low basal glucagon levels were found in the latter patients, supporting impairment in glucagon synthesis. Of note, while hypoglycemia is a serious problem in these patients, they are not spared from complications of chronic hyperglycemia, including retinopathy and kidney disease.2

As for the blood glucose management in type 3C DM, since the principle endocrine defect is insulin deficiency, insulin therapy is preferred for most patients, particularly those who are acutely ill or are hospitalized. For otherwise more stable patients with mild hyperglycemia, metformin is an ideal agent as it enhances hepatic insulin sensitivity without the risk of hypoglycemia. As a bonus, metformin may also decrease the risk of pancreatic cancer in chronic pancreatitis, based on observational studies. 4

Also, don’t forget that concurrent pancreatic exocrine insufficiency is common in patients with type 3C DM and requires oral pancreatic enzyme requirement with meals.

Fascinating Pearl: Did you know that in patients with type 3C DM, hyperglycemia is mediated not only by decreased production of insulin, but also by decreased synthesis of pancreatic polypeptide, a peptide that mediates hepatic insulin sensitivity and glucose production? 5

If you liked this post, download the app, sign up under MENU and catch future pearls right into your inbox, all for free!

References

  1. Linde, J, Nilsson LH, Barany FR. Diabetes and hypoglycemia in chronic pancreatitis. Scand J Gastroenterol. 2012;12, 369–373. https://www.ncbi.nlm.nih.gov/pubmed/867001
  2. Andersen D. The practical importance of recognizing pancreatogenic or type 3c diabetes. Diabetes Metab Res Rev. 2012;28:326-328. https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.2285
  3. Cui YF, Andersen DK. Pancreatogenic diabetes: Special considerations for management. Pancreatology. 2011;11(3):279-294. doi:10.1159/000329188. https://jhu.pure.elsevier.com/en/publications/pancreatogenic-diabetes-special-considerations-for-management-4
  4. Evans J, Donnelly L, Emsley-Smith A. Metformin and reduced risk of cancer in diabetic patients. Br Med J. 2005;330:1304-1305. https://www.researchgate.net/publication/7888859_Metformin_and_reduced_risk_of_cancer_in_diabetic_patients
  5. Rabiee A. Gafiatsatos P, Salas-Carnillo R. Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patents on insulin pump therapy. J Diabetes Sci Technol 2011;5:1521-28.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262724/

Contributed by Hugo Torres, MD, MPH, Hospital Medicine Unit, Mass General Hospital, Boston, Massachusetts

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?