The Effect Of Biochemical Remission on Bone Metabolism in Cushing’s Syndrome

Braun LT, Fazel J, Zopp S
Journal of Bone and Mineral Research

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May 22, 2020

This study was attempted to assess bone mineral density and fracture rates in 89 patients with confirmed Cushing’s syndrome at the time of diagnosis and 2 years after successful tumor resection.

Researchers ascertained five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. Via chemiluminescent immunoassays, they assessed bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide, alkaline bone phosphatase, CrossLaps, and TrAcP 5b in plasma or serum. For comparison, they studied 71 gender‐, age‐, and BMI‐matched patients in whom Cushing’s syndrome had been excluded.

The outcomes of this research exhibit that the phase immediately after surgical remission from endogenous CS is defined by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients.

Read the full article on Journal of Bone and Mineral Research.

Predicting Prolonged Length of Stay After Endoscopic Transsphenoidal Surgery for Pituitary Adenoma

First published:03 May 2020
Read the entire article at https://doi.org/10.1002/alr.22540

Potential conflict of interest: None disclosed.

Presented at the 65th Annual Meeting of the American Rhinologic Society, on September 14, 2019, in New Orleans, LA.

Abstract

Background

Endoscopic transsphenoidal surgery (ETS) for the resection of pituitary adenoma has become more common throughout the past decade. Although most patients have a short postoperative hospitalization, others require a more prolonged stay. We aimed to identify predictors for prolonged hospitalization in the setting of ETS for pituitary adenomas.

Methods

A retrospective chart review as performed on 658 patients undergoing ETS for pituitary adenoma at a single tertiary care academic center from 2005 to 2019. Length of stay (LoS) was defined as date of surgery to date of discharge. Patients with LoS in the top 10th percentile (prolonged LoS [PLS] >4 days, N = 72) were compared with the remainder (standard LoS [SLS], N = 586).

Results

The average age was 54 years and 52.5% were male. The mean LoS was 2.1 days vs 7.5 days (SLS vs PLS). On univariate analysis, atrial fibrillation (p = 0.002), hypertension (p = 0.033), partial tumor resection (p < 0.001), apoplexy (p = 0.020), intraoperative cerebrospinal fluid (ioCSF) leak (p = 0.001), nasoseptal flap (p = 0.049), postoperative diabetes insipidus (DI) (p = 0.010), and readmission within 30 days (p = 0.025) were significantly associated with PLS. Preoperative continuous positive airway pressure (CPAP) (odds ratio, 15.144; 95% confidence interval, 2.596‐88.346; p = 0.003) and presence of an ioCSF leak (OR, 10.362; 95% CI, 2.143‐50.104; p = 0.004) remained significant on multivariable analysis.

Conclusion

For patients undergoing ETS for pituitary adenomas, an ioCSF leak or preoperative use of CPAP predicted PLS. Additional common reasons for PLS included postoperative CSF leak (10 of 72), management of DI or hypopituitarism (15 of 72), or reoperation due to surgical or medical complications (14 of 72).

From https://onlinelibrary.wiley.com/doi/abs/10.1002/alr.22540?af=R

Patients With Cushing Have New Nonsurgical Treatment Option

Cushing syndrome, a rare endocrine disorder caused by abnormally excessive amounts of the hormone cortisol, has a new pharmaceutical treatment to treat cortisol overproduction.

Osilodrostat (Isturisa) is the first FDA approved drug who either can’t undergo pituitary gland surgery or have undergone the surgery but still have the disease. The oral tablet functions by blocking the enzyme responsible for cortisol synthesis, 11-beta-hydroxylase.

“Until now, patients in need of medications…have had few approved options, either with limited efficacy or with too many adverse effects. With this demonstrated effective oral treatment, we have a therapeutic option that will help address patients’ needs in this underserved patient population,” said Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health Sciences University.

Cushing disease is caused by a pituitary tumor that releases too much of the hormone that stimulates cortisol production, adrenocorticotropin. This causes excessive levels of cortisol, a hormone responsible for helping to maintain blood sugar levels, regulate metabolism, help reduce inflammation, assist in memory formulation, and support fetus development during pregnancy.

The condition is most common among adults aged 30-50 and affects women 3 times more than men.

Cushing disease can lead to a number of medical issues including high blood pressure, obesity, type 2 diabetes, blood clots in the arms and legs, bone loss and fractures, a weakened immune system, and depression. Patients with Cushing disease may also have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks), or weak muscles.

Side effects of osilodrostat occurring in more than 20% of patients are adrenal insufficiency, headache, nausea, fatigue, and edema. Other side effects can include vomiting, hypocortisolism (low cortisol levels), QTc prolongation (heart rhythm condition), elevations in adrenal hormone precursors (inactive substance converted into hormone), and androgens (hormone that regulated male characteristics).

Osilodrostat’s safety and effectiveness was evaluated in a study consisting of 137 patients, of which about 75% were women. After a 24-week period, about half of patients had achieved normal cortisol levels; 71 successful cases then entered an 8-week, double-blind, randomized withdrawal study where 86% of patients receiving osilodrostat maintained normal cortisol levels, compared with 30% who were taking a placebo.

In January 2020, the European Commission also granted marketing authorization for osilodrostat.

From https://www.ajmc.com/newsroom/patients-with-cushing-have-new-nonsurgical-treatment-option

Patients on Steroids With COVID-19 Might Need Rescue Steroids

 

Endocrinologists have underlined the importance that physicians consider “a stress dose” of glucocorticoids in the event of severe COVID-19 infection in endocrine, and other, patients on long-term steroids.

 

People taking corticosteroids on a routine basis for a variety of underlying inflammatory conditions, such as asthma, allergies, and arthritis, are at elevated risk of being infected with, and adversely affected by, COVID-19.

 

This also applies to a rarer group of patients with adrenal insufficiency and uncontrolled Cushing syndrome, as well as secondary adrenal insufficiency occurring in hypopituitarism, who also rely on glucocorticoids for day-to-day living.

 

In the event of COVID-19, all of these individuals may be unable to mount a normal stress response, and “in the case of adrenal suppression…such patients may run into severe difficulties, particularly if on intensive care units,” warns Paul Stewart, MD, University of Leeds, UK, and editor-in-chief of the Journal of Clinical Endocrinology & Metabolism (JCEM).

 

As such, it is vitally important to recognize that “Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case,” Stewart and colleagues emphasize in a newly published editorial in JCEM.

 

They note this advice must be considered alongside World Health Organization (WHO) guidance against prescribing therapeutic glucocorticoids to treat complications of COVID-19, based on prior experience in patients with acute respiratory distress syndrome, as well as those affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).

 

The key difference here is not to use pharmacologic doses of glucocorticoids as treatment for COVID-19 (where they have no effect), but rather to prevent death from adrenal failure by using “stress” doses of replacement glucocorticoid, Stewart explained to Medscape Medical News.

 

“No patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months)…should die without consideration” for a stress dose of replacement glucocorticoid therapy.

“The intent here is to ensure that no patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months) by whatever route should die without consideration for parenteral glucocorticoid therapy,” the editorialists write.

 

He advises using physiological stress doses of hydrocortisone (50-100 mg intravenously tid).

 

Specific Advice for Adrenal Insufficiency: Follow Sick Day Rules

 

separate statement by the American Association of Clinical Endocrinologists (AACE) also emphasizes that it is particularly important for patients with adrenal insufficiency to follow advice from the Centers for Disease Control and Prevention (CDC) or similar guidance on preventing COVID-19 infection, including social distancing and frequent hand washing.

 

Such patients should continue to take medications as prescribed and ensure they have appropriate supplies of oral and injectable steroids, ideally for 90 days, AACE advises.

And if there is a shortage of hydrocortisone, the statement advises patients ask a pharmacist or physician about replacement hydrocortisone with different doses that might be available.

Stewart agrees that patients with adrenal insufficiency need to be hypervigilant, but says that “if they do become ill, for the most part they are well counseled to respond appropriately to intercurrent infections.”

Nevertheless, it is “invaluable to reiterate ‘sick day rules'” for suspected COVID-19 infection.

“Any patient who develops a dry continuous cough and fever should immediately double their daily oral glucocorticoid dose and continue on this regimen until the fever has subsided.”

If a patient still deteriorates on this regimen, develops diarrhea or vomiting, or is unable to take oral glucocorticoids for other reasons, they should contact their physicians or seek urgent medical care to receive parenteral treatment with a glucocorticoid.

J Clin Endocrinol Metab. Published online March 31, 2020. Position statement

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From https://www.medscape.com/viewarticle/928072?nlid=134869_3901&src=wnl_newsalrt_200404_MSCPEDIT&uac=295048SY&impID=2335560&faf=1&fbclid=IwAR1zZe6fqDS3tKuHUYoFpbvBMkQYJ4JN59RzC93xdzVcGGkJIz5bnmmE4LY

AACE Position Statement: Coronavirus (COVID-19) and People with Adrenal Insufficiency and Cushing’s Syndrome

With the novel COVID-19 virus continuing to spread, it is crucial to adhere to the advice from experts and the Centers for Disease Control and Prevention (CDC) to help reduce risk of infection for individuals and the population at large. This is particularly important for people with adrenal insufficiency and people with uncontrolled Cushing’s Syndrome.

Studies have reported that individuals with adrenal insufficiency have an increased rate of respiratory infection-related deaths, possibly due to impaired immune function. As such, people with adrenal insufficiency should observe the following recommendations:

  • Maintain social distancing to reduce the risk of contracting COVID-19
  • Continue taking medications as prescribed
  • Ensure appropriate supplies for oral and injectable steroids at home, ideally a 90-day preparation
    • In the case of hydrocortisone shortages, ask your pharmacist and physician about replacement with different strengths of hydrocortisone tablets that might be available. Hydrocortisone (or brand name Cortef) tablets have 5 mg, 10 mg or 20 mg strength
  • In cases of acute illness, increase the hydrocortisone dose per instructions and call the physician’s office for more details
    • Follow sick day rules for increasing oral glucocorticoids or injectables per your physician’s recommendations
      • In general, patients should double their usual glucocorticoid dose in times of acute illness
      • In case of inability to take oral glucocorticoids, contact your physician for alternative medicines and regimens
  • If experiencing fever, cough, shortness of breath or other symptoms, call both the COVID-19 hotline (check your state government website for contact information) and your primary care physician or endocrinologist
  • Monitor symptoms and contact your physician immediately following signs of illness
  • Acquire a medical alert bracelet/necklace in case of an emergency

Individuals with uncontrolled Cushing’s Syndrome of any origin are at higher risk of infection in general. Although information on people with Cushing’s Syndrome and COVID-19 is scarce, given the rarity of the condition, those with Cushing’s Syndrome should strictly adhere to CDC recommendations:

  • Maintain social distancing to reduce the risk of contracting COVID-19
  • If experiencing fever, cough, shortness of breath or other symptoms, call both the COVID-19 hotline (check your state government website for contact information) and your primary care physician or endocrinologist

In addition, people with either condition should continue to follow the general guidelines at these times:

  • Stay home as much as possible to reduce your risk of being exposed
    • When you do go out in public, avoid crowds and limit close contact with others
    • Avoid non-essential travel
  • Wash your hands with soap and water regularly, for at least 20 seconds, especially before eating or drinking and after using the restroom and blowing your nose, coughing or sneezing
  • If soap and water are not readily available, use an alcohol-based sanitizer with at least 60% alcohol
  • Cover your nose and mouth when coughing or sneezing with a tissue or a flexed elbow, then throw the tissue in the trash
  • Avoid touching your eyes, mouth or nose when possible

From https://www.aace.com/recent-news-and-updates/aace-position-statement-coronavirus-covid-19-and-people-adrenal

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