Health Care Expenditure Burden High in Adrenal Insufficiency

Patients with adrenal insufficiency may accrue substantial health care costs and have more hospital stays and outpatient visits compared with healthy controls, according to findings published in the Journal of the Endocrine Society.

Candace Gunnarsson, PhD, vice president of health economics and outcomes research at CTI Clinical Trial and Consulting in Cincinnati, and colleagues evaluated data from a U.S.-based payer database on 10,383 patients with adrenal insufficiency to determine the estimated annual health care burden among them.

Participants were divided into groups based on their type of adrenal insufficiency: primary adrenal insufficiency (n = 1,014), adrenal insufficiency secondary to pituitary disease (n = 8,818) or congenital adrenal hyperplasia (n = 551). A group of matched controls was also evaluated for comparison.

Total annual health care expenditures were significantly higher in the primary adrenal insufficiency group ($18,624 vs. $4,320), adrenal insufficiency secondary to pituitary disease group ($32,218 vs. $6,956) and the congenital adrenal hyperplasia group ($7,677 vs. $4,203) compared with controls. The adrenal insufficiency secondary to pituitary disease group had the highest health care expenditure estimated with an incremental health care burden of $25,262, followed by the primary adrenal insufficiency group ($14,304) and the congenital adrenal hyperplasia group ($3,474).

Compared with controls, participants with adrenal insufficiency spent eight to 10 times more days in the hospital and had up to twice as many outpatient visits per year.

“When comparing [adrenal insufficiency] patients within each cohort based on their drug regimen, patients receiving prednisone therapy vs. hydrocortisone therapy had significantly higher total annual expenditures in the [primary adrenal insufficiency] and [congenital adrenal hyperplasia] and significantly lower total expenditures in the [pituitary disease] cohort,” the researchers wrote. “Patients taking only hydrocortisone and meeting the threshold of 50% adherence were found to have lower expenditures when medication adherence was 75% or higher.” – by Amber Cox

Disclosure: Gunnarsson reports being an employee of CTI Clinical Trial and Consulting. Please see the full study for a list of all other authors’ relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B8f92bd0c-0c72-4902-beb5-663c356a61cb%7D/health-care-expenditure-burden-high-in-adrenal-insufficiency

Osilodrostat maintained cortisol control in Cushing’s syndrome

Osilodrostat, a drug that normalized cortisol in 89% of patients with Cushing’s syndrome who took it during a phase II study, continued to exert a sustained benefit during a 31-month extension phase.

In an intent-to-treat analysis, all of the 16 patients who entered the LINC-2 extension study responded well to the medication, with no lapse in cortisol control, Rosario Pivonello, MD, said at the annual meeting of the Endocrine Society.

“We also saw significant improvements in systolic and diastolic blood pressure and decreases in fasting plasma glucose,” said Dr. Pivonello of the University of Naples Federico II, Italy. “Surprisingly, after 31 months, we also observed declines in body mass index and weight.”

Osilodrostat, made by Novartis, is an oral inhibitor of 11 beta–hydroxylase. The enzyme catalyzes the last step of cortisol synthesis in the adrenal cortex. The drug was granted orphan status in 2014 by the European Medicines Agency.

In the LINC-2 study, 19 patients took osilodrostat at an initial dose of either 4 mg/day or 10 mg/day, if baseline urinary-free cortisol exceeded three times the upper normal limit. The dose was escalated every 2 weeks to up to 60 mg/day, until cortisol levels were at or below the upper limit of normal. In this study, the main efficacy endpoint was normalization of cortisol, or at least a 50% decrease from baseline at weeks 10 and 22.

Overall response was 89%. Osilodrostat treatment reduced urinary-free cortisol in all patients, and 79% had normal cortisol levels at week 22. The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. New or worsening hirsutism and/or acne were reported among four female patients, all of whom had increased testosterone levels.

The LINC-2 extension study enrolled 16 patients from the phase II cohort, all of whom had responded to the medication. They were allowed to continue on their existing effective dose through the 31-month period.

Dr. Pivonello presented response curves that tracked cortisol levels from treatment initiation in the LINC-2 study. The median baseline cortisol level was about 1,500 nmol per 24 hours. By the fourth week of treatment, this had normalized in all of the patients who entered the extension phase. The response curve showed continued, stable cortisol suppression throughout the entire 31-month period.

Four patients dropped out during the course of the study. Dr. Pivonello didn’t discuss the reasons for these dropouts. He did break down the results by response, imputing the missing data from these four patients. In this analysis, the majority (87.5%) were fully controlled, with urinary-free cortisol in the normal range. The remainder were partially controlled, experiencing at least a 50% decrease in cortisol from their baseline levels. These responses were stable, with no patient experiencing loss of control over the follow-up period.

The 12 remaining patients are still taking the medication, and they experienced other clinical improvements as well. Systolic blood pressure decreased by a mean of 2.2% (from 130 mm Hg to 127 mm Hg). Diastolic blood pressure also improved, by 6% (from 85 mm Hg to 80 mm Hg).

Fasting plasma glucose dropped from a mean of 89 mg/dL to 82 mg/dL. Weight decreased from a mean of 84 kg to 74 kg, with a corresponding decrease in body mass index, from 29.6 kg/m2 to 26.2 kg/m2.

Serum aldosterone decreased along with cortisol, dropping from a mean of 168 pmol/L to just 19 pmol/L. Adrenocorticotropic hormone increased, as did 11-deoxycortisol, 11-deoxycorticosterone, and testosterone.

Pituitary tumor size was measured in six patients. It increased in three and decreased in three. Dr. Pivonello didn’t discuss why this might have occurred.

The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. These moderated over time in both number and severity.

However, there were eight serious adverse events among three patients, including prolonged Q-T interval on electrocardiogram, food poisoning, gastroenteritis, headache, noncardiac chest pain, symptoms related to pituitary tumor (two patients), and uncontrolled Cushing’s syndrome.

Two patients experienced hypokalemia. Six experienced mild events related to hypocortisolism.

Novartis is pursuing the drug with two placebo-controlled phase III studies (LINC-3 and LINC-4), Dr. Pivonello said. An additional phase II study is being conducted in Japan.

Dr. Pivonello has received consulting fees and honoraria from Novartis, which sponsored the study.

Prednisolone May Raise Cholesterol in Adrenal Insufficiency

Prednisolone treatment of patients with adrenal insufficiency is associated with significantly elevated total-and low-density-lipoprotein (LDL) cholesterol levels compared with use of an alternative glucocorticoid, hydrocortisone, new data suggest.

Real-world data from the European Adrenal Insufficiency Registry (EU-AIR) were presented on April 2 here at ENDO 2017: The Endocrine Society Annual Meeting by Robert D Murray, MBBS, consultant endocrinologist and honorary associate professor at Leeds Teaching Hospitals NHS Trust, United Kingdom.

In an interview, Dr Murray told Medscape Medical News, “In addition to previous data showing that prednisolone can cause lower bone mass, we’ve now shown that it may raise cholesterol to a higher degree than hydrocortisone.”

Asked to comment, session moderator Constantine A Stratakis, MD, chief medical officer of the National Institute of Child Health & Human Development, Bethesda, Maryland, said: “These are significant findings. I think that the difference he’s seeing may be mostly due to the differences in how glucocorticoids are metabolized locally in the liver and fat tissues.”

Regarding clinical implications, Dr Stratakis said, “These data point to the need for using hydrocortisone. Clearly, at these doses anyway, you have increases in LDL and cholesterol with prednisolone.”

Indeed, the new findings support recent recommendations from the Endocrine Society to use hydrocortisone as first-line glucocorticoid replacement therapy for primary adrenal insufficiency.

But the huge cost difference between the two generic medications has led some to suggest otherwise. In 2014, the BMJ published editorials arguing both for and against the preferred use of prednisolone.

During his presentation, Dr Murray reported that in the United Kingdom, an annual supply of 5-mg prednisolone (one tablet a day) costs about £16 and 3 mg (three 1-mg tablets a day) about £48, compared with £1910 for a year’s supply of twice-daily 10-mg hydrocortisone.

(Hydrocortisone is also considerably more expensive than prednisolone in the United States, although the differential isn’t quite as dramatic.)

Dr Murray pointed out that about 75% of the patients in the database were taking 5 mg/day of prednisolone and that although that’s within the recommended range (3–5 mg/day), it might be too much. “I suspect this isn’t related to the steroid use, but that we may actually have gotten the doses wrong, and we may need a smaller dose of prednisolone. I think probably in reality the ideal dose is probably nearer to 3.5 to 4 mg. Therefore, I think we may be slightly overtreating these people and both the bone mass and the cholesterol may be a reflection of that.

“I think for now we have to stay with hydrocortisone as our mainstay of treating adrenal insufficiency, but I think more studies need to be done in patients taking 3.5 to 4.0 mg to then look at the effects on cholesterol, bone mass, and other markers….It would be quite a significant saving if we were able to move patients to prednisolone,” he added.

Dr Stratakis commented, “I have to say the price difference to me is amazing.” Asked about Dr Murray’s dose hypothesis, he responded, “It is possible we may be giving more prednisolone than we should. Also, there might be important differences in the handling of glucocorticoids at the tissue level, in fat and liver, specifically, that we don’t account for.”

Hydrocortisone vs Prednisolone

Beginning his presentation, Dr Murray noted that data on risk factors for cardiovascular disease in patients with adrenal insufficiency treated with prednisolone are scarce, despite this condition being the predominant cause of excess mortality, and so in this analysis he and his colleagues aimed to address this gap in the literature.

EU-AIR is a prospective, observational study, initiated in August 2012 to monitor the long-term safety of glucocorticoids in patients with adrenal insufficiency, and of 946 enrolled — in Germany, the Netherlands, Sweden, and the United Kingdom — 91.8% were using hydrocortisone for glucocorticoid replacement therapy compared to just 6.8% using prednisone, with marked heterogeneity in doses and frequency and timing of dosing (Endocrine Abstracts. 2015: DOI:10.1530/endoabs.37.EP39).

Other previous studies have found lower bone mass at the hip and spine with prednisolone compared with hydrocortisone-treated patients, but no quality-of-life difference between the two treatments, Dr Murray said.

The current study is the first patient-matched analysis of cardiovascular-risk-factor differences for the two glucocorticoid therapies. Patients were excluded if they were receiving more than one glucocorticoid, had congenital adrenal hyperplasia, were receiving modified-release hydrocortisone, or were receiving prednisolone or hydrocortisone doses outside the Endocrine Society’s recommended ranges.

Prior to matching, the 909 hydrocortisone patients were significantly more likely to be female, to have primary adrenal insufficiency, to be older, and to have longer disease duration. After matching three hydrocortisone patients for every one taking prednisolone, the 141 hydrocortisone and 47 prednisolone patients were similar for those factors: 62% were female, 40% had primary adrenal insufficiency, average age was around 59 years, and disease duration 23 years.

Both total cholesterol and LDL levels were significantly higher, at 6.3 and 3.9 mmol/L, respectively, in the prednisolone group compared with 5.4 and 3.2 mmol/L for hydrocortisone (both P < .05). However, there were no significant differences in rates of hypertension, diabetes (of either type), blood pressure, triglycerides, or HDL cholesterol.

In subgroup analysis, both total and LDL cholesterol were elevated among patients with primary adrenal insufficiency taking prednisolone, but among those with only secondary adrenal insufficiency, just total cholesterol was elevated with prednisolone.

Dr Stratakis told Medscape Medical News, “It is peculiar for me to see that the only difference he found from all the parameters he measured were in lipids, and specifically total cholesterol and LDL. I think the difference is tissue-specific.”

Dr Murray said it’s certainly plausible that the current prednisolone dosing is too high for two reasons: First, in the United Kingdom prednisolone comes in 1-mg and 5-mg tablets, so taking 5 mg/day is simpler than taking the lower end of the recommended range.

Second, “hydrocortisone is cortisol, so you know what the body produces and about what your levels should be, but you can’t do that with prednisone because it’s an analog. So, we’re guessing, and I think we’ve guessed too high.”

Dr Murray is a speaker and consultant to Shire. Disclosures for the coauthors are listed in the abstract. Dr Stratakis has no relevant financial relationships.   

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

ENDO 2017. April 2, 2017; Orlando, Florida. Abstract OR03-5

 

From http://www.medscape.com/viewarticle/878097

What I’m doing for Rare Disease Day

rare disease day

 

Each and every day since 1897,  I tell anyone who will listen about Cushing’s.  I pass out a LOT Cushing’s business cards.

Adding to websites, blogs and more that I have maintained continuously since 2000 – at mostly my own expense.

Posting on the Cushing’s Help message boards about Rare Disease Day.  I post there most every day.

Tweeting/retweeting info about Cushing’s and Rare Disease Day today.

Adding info to one of my blogs about Cushing’s and Rare Disease Day.

Adding new and Golden Oldies bios to another blog, again most every day.

Thinking about getting the next Cushing’s Awareness Blogging Challenge set up for April…and will anyone else participate?

And updating https://www.facebook.com/CushingsInfo with a bunch of info today (and every day!)

~~~

Today is Rare Disease Day.

I had Cushing’s Disease due to a pituitary tumor. I was told to diet, told to take antidepressants and told that it was all my fault that I was so fat. My pituitary surgery in 1987 was a “success” but I still deal with the aftereffects of Cushing’s and of the surgery itself.

I also had another Rare Disease – Kidney Cancer, rare in younger, non-smoking women.

And then, there’s the adrenal insufficiency…

If you’re interested, you can read my bio here https://cushingsbios.com/2013/04/29/maryo-pituitary-bio/

 

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8 Things You Should Know About Addison’s Disease

adrenal-insufficiency

 

Cortisol gets a bad rap these days. (Guilty!) Yes, this hormone surges when you’re stressed. And yes, chronic stress is bad news for your health. But while too much cortisol can lead to all sorts of stress-related side effects, too little cortisol is equally debilitating.

Just ask someone with Addison’s disease. If you suffer from this condition, your adrenal glands fail to make adequate amounts of cortisol, says Betul Hatipoglu, MD, an endocrinologist at Cleveland Clinic.

Cortisol plays a role in regulating your blood pressure, heart function, digestion, and a lot else, Hatipoglu explains. So if your adrenal glands poop out and your cortisol levels plummet, a lot can go wrong. (In as little as 30 days, you can be a whole lot slimmer, way more energetic, and so much healthier just by following the simple, groundbreaking plan in The Thyroid Cure!)

Here’s what you need to know about this condition—starting with its craziest symptom.

It can make your teeth appear whiter.

Hatipoglu once met with a patient who was suffering from fatigue, belly pain, and mild weight loss. “Her doctors thought she was depressed,” Hatipoglu recalls. Toward the end of their appointment, Hatipoglu noticed the woman’s teeth looked very white. She realized they looked white because the woman’s skin was tan. “I asked her if she’d been on vacation, and she said she hadn’t been in the sun, and that’s when I knew,” Hatipoglu says. Some Addison’s-related hormone shifts can make the skin appear darker, almost like a tan. “Addison’s is the only disease I know of that can cause darkening of the skin,” she says.

Its (other) symptoms are popular ones.

 Along with darker skin, other symptoms of Addison’s include nausea, mild-to-severe abdominal or bone pain, weight loss, a lack of energy, forgetfulness, and low blood pressure, Hatipoglu says. Of course, those same symptoms are linked to many other health issues, from thyroid disease to cancer. “It’s very easy to confuse with other disorders, so many people see a lot of doctors before finally receiving a proper diagnosis,” she says. (One exception: For young women who develop Addison’s disease, loss of body hair is a warning sign, Hatipoglu adds.)
It’s rare.
Doctors also miss or misinterpret the symptoms of Addison’s disease because it’s very uncommon. “I’m not sure if it’s quite one in a million, but it’s very rare,” Hatipoglu says. “It makes sense that many doctors don’t think of it when examining a patient with these symptoms.”
It’s often confused with adrenal insufficiency.

A lot of online resources mention Addison’s disease and adrenal insufficiency as though they were two names for the same condition. They’re not the same, Hatipoglu says. While a thyroid issue or some other hormone-related imbalance could mess with your adrenal function, Addison’s disease refers to an autoimmune disorder in which your body attacks and destroys your adrenal glands.

That destruction can happen quickly.

While it takes months or even years for some Addison’s sufferers to lose all hormone production in their adrenal glands, for others the disease can knock out those organs very rapidly—in a matter of days, Hatipoglu says. “That’s very uncommon,” she adds. But compared to other less-severe adrenal issues, the symptoms of Addison’s tend to present more dramatically, she explains. That means a sufferer is likely to experience several of the symptoms mentioned above, and those symptoms will continue to grow worse as time passes.

Anybody can get it.

Addison’s is not picky. It can strike at any age, regardless of your sex or ethnicity, Hatipoglu says. While there’s some evidence that genetics may play a role—if other people in your family have the disease or some other endocrine disorder, that may increase your risk—there’s really no way to predict who will develop the disease, she adds.

Screening for Addison’s is pretty simple.

If your doctor suspects Addison’s, he or she will conduct a blood test to check for your levels of cortisol and another hormone called ACTH. “Usually the results of that screening are very clear,” Hatipoglu says. If they’re not, some follow-up tests can determine for sure if you have the condition.

There are effective treatments.

Those treatments involve taking oral hormone supplements.  In extreme cases, if the patient’s body does not properly absorb those supplements, injections may be necessary, Hatipoglu explains. “But patients live a normal life,” she adds. “It’s a treatable disease, and the treatments are effective.”

From http://www.prevention.com/health/addisons-disease-symptoms

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