Identification Of Potential Markers For Cushing’s Disease

Endocr Pract. 2016 Jan 20. [Epub ahead of print]

Abstract

OBJECTIVE:

Cushing’s disease (CD) causes a wide variety of nonspecific symptoms, which may result in delayed diagnosis. It may be possible to uncover unusual combinations of otherwise common symptoms using ICD-9-CM codes. Our aim was to identify and evaluate dyads of clinical symptoms or conditions associated with CD.

METHODS:

We conducted a matched case-control study using a commercial healthcare insurance claims database, designed to compare the relative risk (RR) of individual conditions and dyad combinations of conditions among patients with CD versus matched non-CD controls.

RESULTS:

With expert endocrinologist input, we isolated 10 key conditions (localized adiposity, hirsutism, facial plethora, polycystic ovary syndrome, abnormal weight gain, hypokalemia, deep venous thrombosis, muscle weakness, female balding, osteoporosis) with RR varying from 5.1 for osteoporosis to 27.8 for hirsutism. The RR of dyads of these conditions ranged from 4.1 for psychiatric disorders/serious infections to 128.0 for hirsutism/fatigue in patients with vs. without CD. Construction of uncommon dyads resulted in further increases in RR beyond single condition analyses, such as osteoporosis alone had RR of 5.3, which increased to 8.3 with serious infections and to 52.0 with obesity.

CONCLUSION:

This study demonstrated that RR of any one of 10 key conditions selected by expert opinion was ≥5 times greater in CD compared to non-CD, and nearly all dyads had RR≥5. An uncommon dyad of osteoporosis and obesity had an RR of 52.0. If clinicians consider the diagnosis of CD when the highest-risk conditions are seen, identification of this rare disease may improve.

KEYWORDS:

Cushing’s disease; delay in diagnosis; disease markers; insurance claims; relative risk

PMID:
26789346
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/26789346

Case study shows chronic marijuana use associated with hypopituitarism

PHOENIX — Results of a case study presented here at the American Association of Clinical Endocrinologists 22nd Scientific and Clinical Congress demonstrate that smoking marijuana may result in serious endocrine complications.

Hormone feedback cycles

Hormone feedback cycles (Photo credit: Wikipedia)

“We really feel that the evidence to-date shows this is a much more serious health problem than we’ve given credit to,” Pinsker said during a press conference. “Marijuana’s always been laughed off: ‘it’s a kid’s drug; they’ll outgrow it.’ In certain communities, it’s so common that people look at it as if they’re having a glass of beer. I think it’s time that physicians start having their antenna up for all the difficulties that come with this drug.”

The patient presented to the emergency department with dyspnea on exertion, increasing fatigue and loss of libido with no previous radiation exposure or head trauma. He had bibasilar rales, gynecomastia and bilateral atrophied testis.

His hormonal evaluation demonstrated low Luteinizing Hormone (0.2 mIU/mL); FSH (1.8 mIU/mL) and testosterone (22 ng/dL), as well as high prolactin (53.3 ng/mL).

Additionally, the patient had ACTH of 6 pg/mL and cortisol of 6.4 ug/dL at 0 minutes and 9.3 ug/dL at 60 minutes following cosyntropin administration.

Further labs revealed low total T3 (30 ng/dL); high T3 resin reuptake (49%); low total T4 (3.94 ng/dL); normal free T4 (0.97 ng/dL) and low TSH (0.22 uIU/mL). Growth hormone was within normal range (5.0 ng/mL) and IGF-I was low (75 ng/mL; Z-score of -1.3). An MRI revealed a slightly enlarged protuberant pituitary gland, but no identified mass lesion.

After being started on cortisone 25 mg in the morning and 12.5 mg at bedtime, as well as levothyroxine 25 mcg daily, the patient’s fatigue and edema improved significantly, according to the abstract.

In this case, severe hypopituitarism occurred from interference between THC, the psychoactive ingredient in marijuana which has the ability to alter neural transmitters in the hypothalamus, and hypothalamic function.

Additionally, studies show that marijuana impairs the release of gonadotropin-releasing hormone (GnRh), resulting in reduced production of testosterone.

Other symptoms seen with prolonged use include cognitive decline in school children and older people, according to Pinsker. “The public will become more attuned to looking for these things. We’re going to have what we call a surveillance bias and we’re going to start discovering that it’s a lot higher than we gave it credit for, both because of increased use and because we’re going to be looking for it.”

The authors conclude that, as many states consider the legalization of marijuana, more study should be conducted with regard to the effects of chronic use of the drug on the endocrine system.

“Of course this is one case report, but I think it should alert further research that needs to be done, “ said Pinsker. “Something prospectively should be done to map this out more scientifically, but this would be difficult in what, to-date, has been an illegal substance.”

For more information:

Pinsker R. Abstract #825. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.

Disclosure: The authors report no relevant financial disclosures.

 From Healio.com

Connecting Canine and Human Health to Fight Cushing’s Disease

Cushing’s Disease is common in dogs but rare and hard to diagnose in people. That’s why University of Georgia researchers are leveraging canine treatments to find new solutions to battle the condition in humans. This collaboration between veterinary medicine and human health care is just one example of how UGA uses a Precision One Health approach to find and tailor new medical treatments for people and animals.

~~~

Imagine your body as a well-run newsroom. Each day, the editor-in-chief—in this case, the pituitary gland—provides assignments, keeping everything running smoothly. One day, however, the editor’s role is usurped by a rogue reporter who declares breaking news nonstop, flooding the newsroom with bulletins and sending everyone into overdrive.

This is a bit like Cushing’s Disease. The rogue reporter is a tiny, usually benign tumor, the stress bulletins cortisol. The newsroom—your body—responds with metabolic fluctuations, burnt out muscles, emotional distress, and more. Over the long haul, Cushing’s Disease can cause lasting deterioration of the body: osteoporosis, muscle weakness, high blood pressure and heart disease, diabetes, memory and mood issues, fatigue, and more.

It’s a common disease and easier to detect in canines. In people, however, it is rare and difficult to diagnose. University of Georgia researchers are leveraging canine treatments to find new solutions to battle the condition in humans.

This collaboration between veterinary medicine and human health is just one example of how UGA uses a Precision One Health approach to find and tailor new medical treatments for people and animals.

From https://research.uga.edu/news/connecting-canine-human-health-to-fight-cushings-disease/

Day 13, Cushing’s Awareness Challenge

UVA 2004
Cushing’s Conventions have always been special times for me – we learn a lot, get to meet other Cushies, even get referrals to endos!

As early as 2001 (or before) my pituitary function was dropping.  My former endo tested annually but did nothing to help me with the symptoms.

In the fall of 2002 my endo refused to discuss my fatigue or anything at all with me until I lost 10 pounds. He said I wasn’t worth treating in my overweight condition and that I was setting myself up for a heart attack. He gave me 3 months to lose this weight. Those 3 months included Thanksgiving, Christmas and New Years.  Needless to say, I left his office in tears, again.

Fast forward 2 years to 2004.  I had tried for a while to get my records from this endo. He wouldn’t send them, even at doctors’ or my requests.

I wanted to go see Dr. Vance at UVa but I had no records so she wouldn’t see me until I could get them.

Finally, my husband went to the former endo’s office and threatened him with a court order. The office manager managed to come up with about 13 pages of records. For going to him from 1986 to 2001 including weeks and weeks at NIH and pituitary surgery, that didn’t seem like enough records to me.

In April of 2004, many of us from the message boards went to the UVa Pituitary Days Convention. That’s where the picture above comes in.  Other pictures from that convention are here.

By chance, we met a wonderful woman named Barbara Craven. She sat at our table for lunch on the last day and, after we learned that she was a dietitian who had had Cushing’s, one of us jokingly asked her if she’d do a guest chat for us. I didn’t follow through on this until she emailed me later. In the email, she asked how I was doing. Usually I say “fine” or “ok” but for some reason, I told her exactly how awful I was feeling.

Barbara emailed me back and said I should see a doctor at Johns Hopkins. I said I didn’t think I could get a recommendation to there, so SHE referred me. The doctor got right back to me, set up an appointment. Between his vacation and mine, that first appointment turned out to be Tuesday, Sept 14, 2004.

Just getting through the maze at Johns Hopkins was amazing. They have the whole system down to a science, moving from one place to another to sign in, then go here, then window 6, then… But it was very efficient.

My new doctor was wonderful. Understanding, knowledgeable. He never once said that I was “too fat” or “depressed” or that all this was my own fault. I feel so validated, finally.

He looked through my records, especially at my 2 previous Insulin Tolerance Tests (ITT). From those, he determined that my growth hormone has been low since at least August 2001 and I’ve been adrenal insufficient since at least Fall, 1999 – possibly as much as 17 years! I was amazed to hear all this, and astounded that my former endo not only didn’t tell me any of this, he did nothing. He had known both of these things – they were in the past records that I took with me. Perhaps that was why he had been so reluctant to share copies of those records. He had given me Cortef in the fall of 1999 to take just in case I had “stress” and that was it.

The new endo took a lot of blood (no urine!) for cortisol and thyroid stuff. I went back on Sept. 28, 2004 for arginine, cortrosyn and IGF testing.

He said that I would end up on daily cortisone – a “sprinkling” – and some form of GH, based on the testing the 28th.

For those who are interested, my new endo is Roberto Salvatori, M.D.
Assistant Professor of Medicine at Johns Hopkins

Medical School: Catholic University School of Medicine, Rome, Italy
Residency: Montefiore Medical Center
Fellowship: Cornell University, Johns Hopkins University
Board Certification: Endocrinology and Metabolism, Internal Medicine

Clinical Interests: Neuroendocrinology, pituitary disorders, adrenal disorders

Research Interests: Control of growth hormone secretion, genetic causes of growth hormone deficiency, consequences of growth hormone deficiency.

Although I have this wonderful doctor, a specialist in growth hormone deficiency at Johns Hopkins, in November, 2004, my insurance company saw fit to over-ride his opinions and his test results based on my past pharmaceutical history! Hello??? How could I have a history of taking GH when I’ve never taken it before?

Of course, I found out late on a Friday afternoon. By then it was too late to call my case worker at the drug company, so we had to appeal on Monday. My local insurance person also worked on an appeal, but the whole thing was  just another long ordeal of finding paperwork, calling people, FedExing stuff, too much work when I just wanted to start feeling better by Thanksgiving.

As it turned out the insurance company rejected the brand of hGH that was prescribed for me. They gave me the ok for a growth hormone was just FDA-approved for adults on 11/4/04. The day this medication was approved for adults was the day after my insurance said that’s what is preferred for me. In the past, this form of hGH was only approved for children with height issues. Was I going to be a ginuea pig again?

The new GH company assigned a rep for me, submitted info to pharmacy, and waited for insurance approval, again.

I finally started the Growth Hormone December 7, 2004.

Was the hassle and 3 year wait worth it?

Stay tuned for April 15, 2016 when all will be revealed.

Read

Read Dr. Barbara Craven’s Guest Chat, October 27, 2004

Thanks for reading 🙂

MaryO

Day 3: Cushing’s Awareness Challenge

me-tired

Sleep.  Naps.  Fatigue, Exhaustion.  I still have them all.  I wrote on my bio in 1987 after my pituitary surgery “I am still and always tired and need a nap most days. I do not, however, still need to take whole days off just to sleep.

That seems to be changing back, at least on the weekends.  A recent weekend, both days, I took 7-hour naps each day and I still woke up tired. That’s awfully close to taking a whole day off to sleep again.

In 2006, I flew to Chicago, IL for a Cushing’s weekend in Rockford.  Someone else drove us to Lake Geneva, Wisconsin for the day.  Too much travel, too Cushie, whatever, I was too tired to stay awake.  I actually had put my head down on the dining room table and fallen asleep but our hostess suggested the sofa instead.  Amazing that I traveled that whole distance – and missed the main event 😦

This sleeping thing really impacts my life.  Between piano lessons, I take a nap.  I sleep as late as possible in the mornings and afternoons are pretty much taken up by naps.  I nod off at night during TV. One time I came home between church services and missed the third service because I fell asleep.

I only TiVo old tv shows that I can watch and fall asleep to since I already know the ending.

Since  mid-February, I have been doing physical therapy twice a week for 2 hours at a time for a knee injury (read more about that in Bees Knees).  I come home from that exhausted – and in more pain than I went.  I know it’s working and my knee is getting better, but it’s such a time and energy sapper.  Neither of which I can really spare.

Maybe now that I’m nearly 10  years out from my kidney cancer (May 9, 2006) I could theoretically go back on Growth Hormone again.  My surgeon says he “thinks” it’s ok.  I’m sort of afraid to ask my endo about it, though.  I want to feel better and get the benefits of the GH again but I don’t want any type of cancer again and I certainly can’t afford to lose another kidney.

I’ll probably just muddle through without it.  I always laugh when I see that commercial online for something called Serovital.  I saw it in Costco the other day and it mentions pituitary right on the package.  I wish I could take the people buying this, sit them down and tell them not to mess with their pituitary glands.  But I won’t.  I’ll take a nap instead because I’m feeling so old and weary today, and yesterday.

And tomorrow…