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Biomarkers in a majority of Cushing’s syndrome patients with surgically induced disease remission showed a high rate of bone turnover and greater bone mineral density one and two years later, a study reports.

Before treatment, these patients were found to have greater bone degradation and poorer bone formation, as can be common to disease-related bone disorders. 

Researchers believe their work is the first study of its kind, “and the data obtained will be instrumental for clinicians who care for patients with Cushing’s syndrome.”

The study, “The Effect of Biochemical Remission on Bone Metabolism in Cushing’s Syndrome: A 2‐Year Follow‐Up Study,” was published in the Journal of Bone and Mineral Research. 

Two common co-conditions of Cushing’s syndrome are osteopenia, a loss of bone mass, and osteoporosis, in which the body makes too little bone, loses too much bone, or both. Studies suggest up to 80% of people with Cushing’s have evidence of reduced bone mineral density affecting the entire skeleton. 

However, few risk factors to predict bone health have been identified so far, and guidelines for osteoporosis management due to Cushing’s are lacking. Uncertainty as to the natural course of osteoporosis once a diagnosis of Cushing’s syndrome has been made is also still evident.

Investigators at the University of Munich, reportedly for a first time, analyzed the natural course of bone mineral density and bone turnover (recycling) in a group of people with endogenous Cushing’s syndrome — which refers to the disease caused by excess cortisol in the bloodstream, often due to a tumor in the adrenal or pituitary glands. 

They examined medical records of 89 Cushing syndrome patients with a mean age of 44, of which 74% were women. Of these, 65% had pituitary Cushing’s (Cushing’s disease), 28% had adrenal, and 7% had ectopic Cushing’s, which is caused by tumors outside the adrenal or pituitary glands. ...

$$$ Attention Cushing's Patients ~ Patient Advisory Board $$$

Novel genetic associations could pave the way for early interventions and personalized treatment of an incurable condition.

Scientists from the University of Bergen (Norway) and Karolinska Institutet (Sweden) have discovered the genes involved in autoimmune Addison's disease, a condition where the body's immune systems destroys the adrenal cortex leading to a life-threatening hormonal deficiency of cortisol and aldosterone.

Groundbreaking study

The rarity of Addison's disease has until now made scanning of the whole genome for clues to the disease's genetic origins difficult, as this method normally requires many thousands of study participants. However, by combining the world's two largest Addison's disease registries, Prof. Eystein Husebye and his team at the University of Bergen and collaborators at Karolinska Institutet in Sweden (prof. Kämpe) were able to identify strong genetic signals associated with the disease. Most of them are directly involved in the development and functioning of the human immune system including specific molecular types in the so-called HLA-region (this is what makes matching donors and recipients in organ transplants necessary) and two different types of a gene called AIRE (which stands for AutoImmune REgulator).

AIRE is a key factor in shaping the immune system by removing self-reacting immune cells. Variants of AIRE, such as the ones identified in this study, could compromise this elimination of self-reacting cells, which could lead to an autoimmune attack later in life.

Knowing what predisposes people to develop Addison's disease opens up the possibilities of determining the molecular repercussions of the predisposing genetic variation (currently ongoing in Prof. Husebye's lab). The fact that it is now feasible to map the genetic risk profile of an individual also means that personalised treatment aimed at stopping and even reversing the autoimmune adrenal destruction can become a feasible option in the future.

I thought I had moved on from this terrible disease. I leaned on this website through the hard times and am sad to see there is little traffic on here. Anyway, I'm Jenny, was a member between 2003 and 2010ish. I have had two unsuccessful put surguries, a bla 2x (due to ectopic adrenal tissue) and fear I may be having a recurrence. Anyway, I do hope more newbies make there way here.

Jenny

Central hypothyroidism is prevalent in about 1 in 2 adults with Cushing’s syndrome, and thyroid function can be restored after curative surgery for most patients, according to study findings.

“Our study findings have confirmed and greatly extended previous smaller studies that suggested a link between hypercortisolism and thyroid dysfunction but were inconclusive due to smaller sample size and short follow-up,” Skand Shekhar, MD, an endocrinologist and clinical investigator in the reproductive physiology and pathophysiology group at the National Institute of Environmental Health Sciences, NIH, told Healio. “Due to our large sample and longer follow-up, we firmly established a significant negative correlation between hypercortisolemia measures — serum and urinary cortisol, serum adrenocorticotropic hormone — and thyroid hormones triiodothyronine, free thyroxine and thyrotropin.”

Shekhar and colleagues conducted a retrospective review of two groups of adults aged 18 to 60 years with Cushing’s syndrome. The first group was evaluated at the NIH Clinical Center from 2005 to 2018 (n = 68; mean age, 43.8 years; 62% white), and the second group was evaluated from 1985 to 1994 (n = 55; mean age, 37.2 years; 89% white). The first cohort was followed for 6 to 12 months to observe the pattern of thyroid hormone changes after surgical cure of adrenocorticotropic hormone-dependent Cushing’s syndrome. The second group underwent diurnal thyroid-stimulating hormone evaluation before treatment and during remission for some cases.

Urinary free cortisol and morning thyroid hormone levels were collected for all participants. In the second group, researchers evaluated diurnal patterns of TSH concentrations with hourly measurements from 3 to 7 p.m. and midnight to 4 p.m. In the first group, adrenocorticotropic hormone and serum cortisol were measured...

The cancer medicine bexarotene may hold promise for treating Cushing’s disease, a study suggests.

The study, “Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT‐20 cells,” was published in the Journal of Cellular and Molecular Medicine.

Cushing’s disease is caused by a tumor on the pituitary gland, leading this gland to produce too much adrenocorticotropic hormone (ACTH). Excess ACTH causes the adrenal glands to release too much of the stress hormone cortisol; abnormally high cortisol levels are primarily responsible for the symptoms of Cushing’s.

Typically, first-line treatment is surgical removal of the pituitary tumor. But surgery, while effective in the majority of cases, does not help all. Additional treatment with medications or radiation therapy (radiotherapy) works for some, but not others, and these treatments often have substantial side effects.

“Thus, the development of new drugs for CD [Cushing’s disease] treatment is extremely urgent especially for patients who have low tolerance for surgery and radiotherapy,” the researchers wrote.

Recent research has shown that a protein called testicular receptor 4 (TR4) helps to drive ACTH production in pituitary cancers. Thus, blocking the activity of TR4 could be therapeutic in Cushing’s disease.

Cushing's syndrome is a rare entity in children. Adrenal tumour is the common cause of this syndrome in young children, whereas, iatrogenic causes are more common among older children. We report a 4 year old male child diagnosed with Cushing syndrome due to a right adrenal adenoma; the child presented with obesity and increase distribution of body hair. After thorough investigation and control of hypertension and dyselectrolytemia, right adrenalectomy was performed. The patient had good clinical recovery with weight loss and biochemical resolution of Cushing's syndrome.

Researchers conducted this retrospective cohort study to investigate acute and life-threatening complications in patients with active Cushing syndrome (CS). Participants in the study were 242 patients with CS, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. In patients with benign pituitary CS, the prevalence of acute complications was 62%, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Infections, thromboembolic events, hypokalemia, hypertensive crises, cardiac arrhythmias and acute coronary events were complications reported in patients with benign CS. The whole spectrum of acute and life-threatening complications in CS and their high prevalence was illustrated in this study both before disease diagnosis and after successful surgery.

Read the full article on Journal of Clinical Endocrinology and Metabolism.

Thyroid cancer survival rates are 84 percent for 10 years or more if diagnosed early. Early diagnosis is crucial therefore and spotting the unusual signs could be a matter of life and death. A sign your thyroid cancer has advanced includes Cushing syndrome.

What is it?

What is Cushing syndrome?

 

Cushing syndrome occurs when your body is exposed to high levels of the hormone cortisol for a long time, said the Mayo Clinic.

The health site continued: “Cushing syndrome, sometimes called hypercortisolism, may be caused by the use of oral corticosteroid medication.

“The condition can also occur when your body makes too much cortisol on its own.

“Too much cortisol can produce some of the hallmark signs of Cushing syndrome — a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks on your skin.”

In a study published in the US National Library of Medicine National Institutes of Health, thyroid carcinoma and Cushing’s syndrome was further investigated.

The study noted: “Two cases of thyroid carcinoma and Cushing's syndrome are reported.

“Both of our own cases were medullary carcinomas of the thyroid, and on reviewing the histology of five of the other cases all proved to be medullary carcinoma with identifiable amyloid in the stroma.

“A consideration of the temporal relationships of the development of the carcinoma and of Cushing's syndrome suggested that in the two cases with papillary carcinoma these conditions could have been unrelated, but that in eight of the nine cases with medullary carcinoma there was evidence that thyroid carcinoma was present at the time of diagnosis of Cushing's syndrome.

“Medullary carcinoma of the thyroid is also probably related to this group of tumours. It is suggested that the great majority of the tumours associated with Cushing's syndrome are derived from cells of foregut origin which are endocrine in nature.”

A young healthcare worker who contracted COVID-19 shortly after being diagnosed with Cushing’s disease was detailed in a case report from Japan.


While the woman was successfully treated for both conditions, Cushing’s may worsen a COVID-19 infection. Prompt treatment and multidisciplinary care is required for Cushing’s patients who get COVID-19, its researchers said.


The report, “Successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia,” was published in Endocrine Journal.


Cushing’s disease is caused by a tumor on the pituitary gland, which results in abnormally high levels of the stress hormone cortisol (hypercortisolism). Since COVID-19 is still a fairly new disease, and Cushing’s is rare, there is scant data on how COVID-19 tends to affect Cushing’s patients.


In the report, researchers described the case of a 27-year-old Japanese female healthcare worker with active Cushing’s disease who contracted COVID-19.


The patient had a six-year-long history of amenorrhea (missed periods) and dyslipidemia (abnormal fat levels in the body). She had also experienced weight gain, a rounding face, and acne.


After transferring to a new workplace, the woman visited a new gynecologist, who checked her hormonal status. Abnormal findings prompted a visit to the endocrinology department.


Clinical examination revealed features indicative of Cushing’s syndrome, such as a round face with acne, central obesity, and buffalo hump. Laboratory testing confirmed hypercortisolism, and MRI revealed a tumor in the patient’s pituitary gland.


She was scheduled for surgery to remove the tumor, and treated with metyrapone, a medication that can decrease cortisol production in the body. Shortly thereafter, she had close contact with a patient she was helping to care for, who was infected with COVID-19 but not yet diagnosed.

Dr. Theodore Friedman will host a webinar on COVID-19 Vaccines for Endocrine Patients

Dr. Friedman will discuss topics including:

How do the vaccines work?


What did the New England Journal of Medicine article say about the Pfizer vaccine?


What are the different vaccine options?


What are the side effects?


Who should and shouldn’t get a vaccine?


What about Dr. Friedman’s vaccine studies?


Sunday • December 27 • 6 PM PST
Click here on start your meeting or
https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m5085619c25d8a2417d9316b56fe7830b
 
OR
Join by phone: (855) 797-9485
 
<br clear="ALL">
      Meeting Number (Access Code): 177 542 2496 Your phone/computer will be muted on entry. 
Slides will be available on the day of the talk here 
There will be plenty of time for questions using the chat button. Meeting Password: pcos
For more information, email us at mail@goodhormonehealth.com

...
Dr. Friedman completely supports efforts to limit the spread of the virus, including wearing masks, social distancing, handwashing and staying at home. Listening to government officials including the CDC is crucial. Dr. Friedman agrees with data showing gatherings are much safer outside and encourages his patients to err on the side of safety and caution. Dr. Friedman is spearheading efforts at Charles R. Drew University to be a site for a vaccine study and after some delays, it looks like his University will be a site for the Sanofi vaccine in December 2020. Dr. Friedman is very excited about the promising results from the Moderna and Pfizer trials and thinks vaccines along with mask-wearing and social distancing will curtail the pandemic, hopefully in the latter half of 2021. He does think that COVID-19 will be with us for a long time. Dr. Friedman anticipates that changes due to COVID-19, including telemedicine and working from home will remain with us after the pandemic subsides. 
 
As mentioned in the March update, patients with endocrine problems such as Cushing’s syndrome, Addison’s Disease, hypopituitarism and diabetes have slightly impaired immune systems, making them potentially susceptible for a more severe infection by COVID-19. He would recommend those patients to be especially vigilant about mask-wearing/social distancing and to get a vaccine when it comes out. ..

Dr. Friedman wishes everyone to stay healthy

From message board member @sharm - Sharmyn McGraw:

Hi All, I hope you can join us on Zoom this Saturday, Nov. 14, 2020 starting at 9:00 a.m. (PST). For those that can't make it, I will record the meeting and post it later on our Facebook page. I look forward to seeing you!

Contact @sharm if you have questions or email her here:  pituitarybuddy@hotmail.com

We have an opportunity for you to take part in a Cushing's Disease study(IPS_4636) for Patients. Our project number for this study is IPS_4636.

Project Details:

Web- Camera Interview


There is a homework component


Interview is 75-minutes long


125 Reward + 100 homework


Things to Note:

Patient study only, Caregivers please pass the link along


Unique links, please do not pass along for 2nd use


One Participant per household


Want to share this opportunity? Let us know and we can provide a new link


Preliminary questions are Mobile Friendly!


Save this email to reference if you have any questions about the study!


If you have any problems, email pm3@rarepatientvoice.com and reference the project number.  If you hit reply, you will get an auto do-not-reply email.


If you are interested in this study, please click the link below to answer a few questions to see if you qualify.

Study Link: Link

OR if the Study Hyperlink is not clickable above, please copy/paste this URL below.
https://panel.rarepatientvoice.com/newdesign/site/rarepatientvoice/surveystart.php?surveyID=hld5jbejublj&panelMemberID=trfnbc7mvduh1gseff1h&invite=email


Thanks as always for your participation! Please be aware that by entering this information you are not guaranteed that you will be selected to participate. As always, we do not share any of your contact information without your permission.

The treatment of adrenal insufficiency with hydrocortisone granules in children with congenital adrenal hyperplasia (CAH) was associated with an absence of adrenal crises and normal growth patterns over a 2-year period, according to study findings published in The Journal of Clinical Endocrinology and Metabolism.

The study included a total of 17 children with CAH and 1 child with hypopituitarism. All included participants were <6 years old who were receiving current adrenocortical replacement therapy, including hydrocortisone with or without fludrocortisone. Hydrocortisone medications used in this population were converted from pharmacy compounded capsules to hydrocortisone granules without changing the dose.

These study participants were followed by study investigators for 2 years. Glucocorticoid replacement therapy was given three times a day for a median treatment duration of 795 days. Treatment was adjusted by 3 monthly 17-hydroxyprogesterone (17-OHP) profiles in children with CAH.

There were a 150 follow-up visits throughout the study. At each visit, participants underwent assessments that measured hydrocortisone dose, height, weight, pubertal status, adverse events, and incidence of adrenal crisis.

 



A total of 40 follow-up visits had changes in hydrocortisone doses based on salivary measurements (n=32) and serum 17-OHP levels (n=8).

At time of study entry, the median daily doses of hydrocortisone were 11.9 mg/m2 for children between the ages of 2 to 8 years, 9.9 mg/m2 for children between 1 month and 2 years, and 12.0 mg/m2 for children <28 days of age. At the end of the study, the respective doses for the 3 age groups were 10.2, 9.8, and 8.6.
...

The researchers concluded that “hydrocortisone granules are an effective treatment for childhood adrenal insufficiency providing the ability to accurately prescribe pediatric appropriate doses.”

Dr. Friedman wants to update his patients about natural desiccated thyroid (NDT) recalls based on new information from the FDA. Dr. Friedman prescribes various thyroid hormone preparations to his patients with hypothyroidism. This includes natural desiccated thyroid (NDT) of which two preparations are WP Thyroid and Nature-Throid, both made by RLC Labs. On August 25, 2020, RLC Labs announced a voluntary, consumer-level recall of all lots of Nature-Throid and WP Thyroid tablets because some lots contain less than the required 90% of the active ingredient as determined by the FDA. The RLC spokesperson said to Dr. Friedman that one lot of WP Thyroid and 5 lots of Nature-Throid contained between 87% and 90% of the labeled amount of levothyroxine (T4) or liothyronine (T3). Recently the FDA announced which lots are recalled that are listed below. According to the recall, if a patient receives a sub-potent tablet, hypothyroid symptoms may not be controlled. To date, there have been no reports of adverse events related to this recall. Patients who have had an adverse event should contact RLC Labs. The lot numbers are listed on the bottles of Nature-Throid and WP Thyroid.
 
With this information about which lots are recalled, Dr. Friedman is only recommended those taking the effective lots to discontinue them. Currently no lots of Nature-Throid and WP Thyroid tablets are commercially available, so a replacement with the same product is not an option. It is unknown how long it will be before Nature-Throid and WP Thyroid become commercially available.
 
 
 

Presented by

Dr. Magge, Assistant Professor of Neurology at Weill Cornell Medical College and an Assistant Attending Neurologist at New York-Presbyterian Hospital.

Dr. Ranakrishna, Chief of Neurological Surgery at NewYork-Presbyterian Brooklyn Methodist Hospital, Associate Professor of Neurological Surgery at Avina and Willis Murphy at Weill Cornell Medicine

Click here to attend.

Date: Tuesday, October 13, 2020

Time: 10:00 AM Eastern Daylight Time

Learning objectives:

-          the basic characteristics of the different types of pituitary adenomas

-          the potential predictors of recurrence and aggressiveness in pituitary adenomas

-          the surgical and radiotherapy options for recurrent pituitary adenomas

-          the potential medical interventions, including chemotherapy, for recurrent pituitary adenomas

Health Condition: All Conditions

Demographics: Ages 18+, United States Resident

Special Request(s): Everyone who has taken part in a clinical trial is asked to share. We are interested in learning why you decided to take part in a clinical trial and how your experience went.

Honoraria: Some respondents may be asked to participate in a clinical trial awareness network where there are paid opportunities to tell their stories.

 Apply to learn more. 

Michael P Catalino 1 2, David M Meredith 3 4, Umberto De Girolami 3 4, Sherwin Tavakol 1 5, Le Min 6, Edward R Laws 1 4

PMID: 32886921
DOI: 10.3171/2020.5.JNS201514

Abstract

Objective: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes.

Methods: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups.

Results: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma)...


Keywords: ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; Cushing disease; HPA = hypothalamic-pituitary-adrenal; HR = hazard ratio; IPSS = inferior petrosal sinus sampling; ROC = receiver operating characteristic; UFC = urinary free cortisol; corticotroph adenoma; corticotroph hyperplasia; diagnosis; pathology; pituitary surgery; surgical outcomes.

From https://pubmed.ncbi.nlm.nih.gov/32886921/

Presented by

Ahmad Sedaghat, MD, PhD - Associate Professor and Director of the Division of Rhinology, Allergy and Anterior Skull Base Surgery in the Department of Otolaryngology - Head and Neck Surgery at the University of Cincinnati College of Medicine and UC Health.

 


Norberto Andaluz, MD, MBA, FACS - Professor of Neurosurgery and Otolaryngology/Head and Neck Surgery - Director, Division of Skull Base Surgery University of Cincinnati College of Medicine and University of Cincinnati Gardner Neuroscience Institute - UC Health


 

Click here to attend

Date: Wednesday, Sept 23, 2020

Time: 3:00 PM  Eastern Daylight Time

Learning objectives:

1.  To understand the surgical steps of endoscopic pituitary surgery
2.  To understand how the surgical steps of endoscopic pituitary surgery translate to post-operative outcomes
3.  To understand surgical factors that can modify post-operative outcomes after endoscopic pituitary surgery
4.  To understand post-operative care that can modify post-operative outcomes after endoscopic pituitary surgery

Patients with endogenous Cushing’s syndrome who stopped using Recorlev (levoketoconazole) and moved to a placebo in a study started having their urine cortisol levels rise in response to lack of treatment, compared with those who remained on Recorlev, according to top-line data from the Phase 3 LOGICS trial.

Based on these findings and data from a previous Phase 3 trial of Recorlev called SONICS (NCT01838551), the therapy’s developer, Strongbridge Biopharma, is planning to submit a new drug application requesting its approval to the U.S. Food and Drug Administration (FDA) early next year.

If approved, Recorlev could be available to patients in the U.S. in 2022.

“We are delighted to announce the positive and statistically significant top-line results of the LOGICS study, which add to the growing body of evidence supporting the potential of Recorlev (levoketoconazole) as an effective and well tolerated cortisol synthesis inhibitor to treat Cushing’s syndrome,” Fredric Cohen, MD, chief medical officer of Strongbridge Biopharma, said in a press release.

Recorlev, also known as COR-003, is an investigational oral treatment for endogenous Cushing’s syndrome that inhibits the production of cortisol, the glucocorticoid hormone that is overly produced in patients with the disorder.

The safety, tolerability, effectiveness, and pharmacological properties of Recorlev in people with endogenous Cushing’s syndrome are currently being assessed in the LOGICS trial (NCT03277690).

LOGICS enrolled patients who had never been treated with Recorlev, as well as those given the medication in SONICS.

...

Adults with adrenal insufficiency who are adequately treated and trained display the same incidence of COVID-19-suggestive symptoms and disease severity as controls, according to a presenter.

“Adrenal insufficiency is supposed to be associated with an increased risk for infections and complications,” Giulia Carosi, a doctoral student in the department of experimental medicine at Sapienza University of Rome, said during a presentation at the virtual European Congress of Endocrinology Annual Meeting. “Our aim was to evaluate the incidence of COVID symptoms and related complications in this group.”

In a retrospective, case-control study, Carosi and colleagues evaluated the incidence of COVID-19 symptoms and complications among 279 adults with primary or secondary adrenal insufficiency (mean age, 57 years; 49.8% women) and 112 adults with benign pituitary nonfunctioning lesions without hormonal alterations, who served as controls (mean age, 58 years; 52.7% women). All participants lived in the Lombardy region of northern Italy. Participants completed a standardized questionnaire by phone on COVID-19-suggestive symptoms, such as fever, cough, myalgia, fatigue, dyspnea, gastrointestinal symptoms, conjunctivitis, loss of smell, loss of taste, upper respiratory tract symptoms, thoracic pain, headaches and ear pain. Patients with primary or secondary adrenal insufficiency were previously trained to modify their glucocorticoid replacement therapy when appropriate.

From February through April, the prevalence of participants reporting at least one symptom of viral infection was similar between the adrenal insufficiency group and controls (24% vs. 22.3%; P = .788).

Researchers observed “highly suggestive” symptoms among 12.5% of participants in both groups.

No participant required hospitalization and no adrenal crisis was reported. Replacement therapy was correctly increased for about 30% of symptomatic participants with adrenal insufficiency.
...

The first ever prospective study to test the safety and efficacy of metyrapone in patients with Cushing’s Syndrome in a real-life setting has shown successful results.

HRA Pharma Rare Diseases SAS, of Paris, has presented data from PROMPT, the first ever prospective study designed to confirm metyrapone efficacy and good tolerance in patients with endogenous Cushing’s Syndrome, with results confirming that metyrapone controlled 80% of the patients at week 12 with either normalisation or at least 50% decrease of urinary free cortisol. These initial results are being published to coincide with HRA Pharma Rare Diseases’ participation in the e-ECE conference 2020.

Cushing’s Syndrome is a rare condition where patients have too much cortisol in their blood. Endogenous Cushing’s Syndrome is most often caused by hormone-releasing tumours of the adrenal or the pituitary glands. To manage this condition, controlling high cortisol levels in patients is important.

Successful results with metyrapone

Metyrapone is an inhibitor of the 11-beta-hydroxylase enzyme, which majorly contributes to cortisol synthesis and is approved in Europe for the treatment of endogenous Cushing’s Syndrome based on observational retrospective studies published over more than 50 years. As this prospective study took place over five years from April 2015 to April 2020, the longitudinal format reduced potential sources of bias and helped determine the risk factors of metyrapone when compared to the previous retrospective studies.

The first results of this study showed that at the end of the 12 weeks, metyrapone therapy is a rapid-onset, effective and safe medical treatment in patients living with the syndrome.

Evelina Paberze, COO of HRA Pharma Rare Diseases, said: “At HRA Pharma Rare Diseases, we are dedicated to building comprehensive evidence of our products. The first results of this prospective study clearly demonstrate the effectiveness of metyrapone in treating Cushing’s Syndrome.”...

Abnormally high levels of cortisol in the urine — one of the hallmarks of Cushing’s syndrome — seem to be associated with alterations in blood sugar metabolism in obese patients, a study found.

The study, “Hypercortisolism and altered glucose homeostasis in obese patients in the pre-bariatric surgery assessment,” was published in the journal Diabetes/Metabolism Research and Reviews.

Context



Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA-F) is a first-line screening test for Cushing’s syndrome (CS) with a reported sensitivity and specificity of >90%. However, liquid chromatography-tandem mass spectrometry, validated to measure salivary cortisol (LCMS-F) and cortisone (LCMS-E), has been proposed to be superior diagnostically.

Objective, Setting, and Main Outcome Measures



Prospectively evaluate the diagnostic performance of EIA-F, LCMS-F, and LCMS-E in 1453 consecutive late-night saliva samples from 705 patients with suspected CS.

Design



Patients grouped by the presence or absence of at least one elevated salivary steroid result and then subdivided by diagnosis.

Results



We identified 283 patients with at least one elevated salivary result; 45 had an established diagnosis of neoplastic hypercortisolism (CS) for which EIA-F had a very high sensitivity (97.5%). LCMS-F and LCMS-E had lower sensitivity but higher specificity than EIA-F. EIA-F had poor sensitivity (31.3%) for ACTH-independent CS (5 patients with at least one and 11 without any elevated salivary result). In patients with Cushing’s disease (CD), most non-elevated LCMS-F results were in patients with persistent/recurrent CD; their EIA-F levels were lower than in patients with newly diagnosed CD.

Conclusions



Since the majority of patients with ≥1 elevated late-night salivary cortisol or cortisone result did not have CS, a single elevated level has poor specificity and positive predictive value. LNSC measured by EIA is a sensitive test for ACTH-dependent Cushing’s syndrome but not for ACTH-independent CS. We suggest that neither LCMS-F nor LCMS-E improves the sensitivity of late-night EIA-F for CS.

Cushing’s disease, ectopic ACTH, adrenal Cushing’s syndrome, diagnosis, assay performance




Issue Section:



Clinical Research Article

From https://academic.oup.com/jes/advance-article/doi/10.1210/jendso/bvaa107/5876040