Low Vitamin D levels linked to upper respiratory tract infections

Research about the values of Vitamin D has been in the news a lot lately. A new study reinforces its value. According to this study, the lower the levels of serum 25(OH)D levels the higher the prevalence of flu and colds in the patients studied.

"The findings of our study support an important role for vitamin D in prevention of common respiratory infections, such as colds and the flu," says Adit Ginde, MD, MPH, UC Denver Division of Emergency Medicine and lead author of the study in a recent news release. "Individuals with common lung diseases, such as asthma or emphysema, may be particularly susceptible to respiratory infections from vitamin D deficiency."

Information from approximately 19,000 subjects who participated in the Third National Health and Nutrition Examination Survey (NHANES III) was analyzed for this study.

Compared with individuals with serum 25(OH)D levels of 30 ng/mL or more, those with levels less than 10 ng/mL or 10 to less than 30 ng/mL had 55% and 27% higher odds of recent URTI, respectively (Table 2, model 1). In further stratification of the group with 25(OH)D levels of 30 ng/mL or more, those with levels of 30 to less than 40 ng/mL had similar odds of recent URTI compared with those with levels of 40 ng/mL or more (OR, 0.99; 95% CI, 0.81-1.21). After adjusting for season, lower serum 25(OH)D levels were still associated with a significantly higher URTI (Table 2, model 2). Indeed, the 25(OH)D-URTI association was consistent across all seasons.

"A respiratory infection in someone with otherwise healthy lungs usually causes a few days of relatively mild symptoms," explains Carlos Camargo, MD, DrPH, MGH Department of Emergency Medicine and senior author of the study. "But respiratory infections in individuals with an underlying lung disease can cause serious attacks of asthma or COPD that may require urgent office visits, emergency department visits or hospitalizations. So the impact of preventing infections in these patients could be very large."

The authors stress that the study's results need to be confirmed in clinical trials before vitamin D can be recommended to prevent colds and flu.

...randomized controlled trials are valuable for determining the causal nature of an observed association. Reverse causation (ie, lower serum 25[OH]D levels due to recent URTI and, thus, decreased outdoor activity) seems unlikely because the half-life of serum 25(OH)D is 2 to 3 weeks11 and URTIs last only 3 to 4 days,3 but it may affect the enhanced vitamin D–URTI association in participants with asthma and COPD owing to longer symptom duration in those individuals....Randomized controlled trials are warranted to explore the direct effect of vitamin D supplementation and to establish optimal levels of serum 25(OH)D in the prevention of RTI.

Previous articles about which I've blogged, Vitamin D and the thyroid gland... and Vitamin D: "Normal" isn't normal anymore support greater daily intake of Vitamin D.


To read more:

• Assay Variation Confounds the Diagnosis of Hypovitaminosis D: A Call for Standardization
• Assessment of dietary vitamin D requirements during pregnancy and lactation
• Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define

Adit A. Ginde, MD, MPH; Jonathan M. Mansbach, MD; Carlos A. Camargo Jr, MD, DrPH (2009). Association Between Serum 25-Hydroxyvitamin D Level and Upper Respiratory Tract Infection in the Third National Health and Nutrition Examination Survey Archives of Internal Medicine, 169(4)

Urinary tract infections full of iron thieves

Research in the differences between E. Coli in the gut and in these UTIs help target treatment options.


Bacteria need iron, and as soon as they invade the human body, they are on the hunt for it. There is a limited supply of iron inside the human body where it is stored by the proteins tranferrin and ferritin.

Disease-causing bacteria have evolved by producing siderophores which are iron-chelating molecules. These molecules can bind to iron stored in ferritin and transferrin and "steal" it for the bacteria.

In this new study, the authors compared Escherichia coli taken from it's natural habitat in the gut and compared it to E. coli found in the urinary tracts of subjects suffering from urinary tract infections (UTIs). They found "epigenetic optimization" of the E. coli from the urinary tract:

Urinary tract infections (UTIs) are among the most common bacterial infections treated by physicians worldwide. Although symptoms of acute infection are often resolved with a course of antibiotics, the same bacterial strain often causes subsequent bouts of symptomatic infection. Escherichia coli are the most common bacteria causing UTI and the infecting strains are widely believed to originate from the gastrointestinal tract where multiple E. coli strains reside. Here, we use a novel mass spectrometric technique in a population of patients with recurrent UTI to identify how strains that cause UTI differ from other strains that were present in the gastrointestinal tract at the same time. We found that urinary E. coli strains preferentially expressed two small molecules called yersiniabactin and salmochelin. These molecules are called siderophores, meaning they are able to scavenge iron to support bacterial survival and growth. Synthesis and transport of these small molecules requires a coordinated network of proteins encoded by a collection of different genes. These findings suggest that new antibiotics directed against yersiniabactin or salmochelin-producing E. coli strains may be an improved, and more targeted, strategy to prevent recurrent UTIs.

Since some iron-transport systems also naturally transport antibiotics into the cell it is important to understand the molecular mechanism of iron transport here. Understanding these pathogenic bacteria may lead to new ways of either delivering or designing drugs which exploit this difference.

Many of us with Cushing's Syndrome/Disease (even if in remission) suffer from low ferritin. When we have an infection, due to our compromised immune system, we often have a difficult time recovering. When accounting for the iron-depleting nature of our infections, we are doubly plagued.

To read more:

• How some bacteria may steal iron from their human host
• Acquisition of siderophores in Gram-negative bacteria
• Pathogenic E. coli
  

Jeffrey P. Henderson, Jan R. Crowley, Jerome S. Pinkner, Jennifer N. Walker, Pablo Tsukayama, Walter E. Stamm, Thomas M. Hooton, Scott J. Hultgren (2009). Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli PLoS Pathogens, 5 (2) DOI: 10.1371/journal.ppat.1000305

In the News: Protein in pituitary critical to women's health...

Discovery In Pituitary Of Protein That Regulates Hormones Critical To Women's Health:

University of Wisconsin-Madison researchers have solved the mystery surrounding
a 'rogue protein' that plays a role in the release of neurotransmitters and hormones in the brain.

The scientists found abundant amounts of the puzzling protein - whose main location and function were unknown until now - in a specific area of the pituitary gland. Like someone at a control knob, the protein may adjust the release of the two hormones that come almost exclusively from the posterior pituitary: oxytocin, which controls many reproductive functions, and vasopressin, which controls fluid balance.

---

Wal-Mart's $4 Generic Prescription Drug List Added to Epocrates' Drug Reference Application

What does this mean for you, the patient? It means your physician should be able to readily see what drugs you can get through this program and prescribe accordingly.

Physicians will now be better equipped to help identify lower cost medication options available for their patients at Walmart, Neighborhood Market and Sam's Club pharmacies nationwide.

---

Discovery of a compound strong enough to fight off some of the most deadly bacterial infections seen in human beings.

Important in many ways, including those who suffer MRSA and other hard-to-treat infections, a compound isolated while searching for a reason so many coral reefs were dying may help treat resistant infections.

Scientists isolated the compound from the thriving sponge. What they found was a compound that was originally discovered in the late 1990s by scientists searching for anticancer chemicals. Back then it was overlooked. Today, scientists think they may have hit an underwater jackpot.

"We have yet to have a failure. We have yet to find resistant bacteria. We're limited only by our imagination in what we're going to get out of the ocean for human health. It's a big world out there."

Pasireotide showed promise as an effective pituitary-targeted treatment for Cushing’s disease and other news....

Pasireotide showed promise as an effective pituitary-targeted treatment for Cushing’s disease

After 15 days of treatment with pasireotide, 76% of patients with Cushing’s disease experienced a decrease in urinary free cortisol levels.... Safety analysis revealed that pasireotide was well tolerated; the most common adverse events were gastrointestinal disorders (54%), such as diarrhea (44%), nausea (23%) and abdominal pain (18%).

Paper sheds new 'light' on fascinating rhythms of the circadian clock

...It turns out that many of the cells throughout our bodies have an intrinsic circadian clock mechanism and that jet lag and shift work can produce internal asynchrony between each of our tissue-specific clocks.

Our brains, on a daily basis, generate the hormonal and neuronal signals that influence the cellular clocks in the peripheral tissues. If this communication line is disrupted, the liver, for example, ends up on one time zone, and the brain on another.

These peripheral clocks in the body's organ systems cannot themselves receive information directly. To know what time of day it is in relation to the external environment, these tissues depend on signals originating in the suprachiasmatic nucleus: every day the brain sends signals that inform the peripheral cells to adjust the phase of their rhythms, like the pin of a wrist watch being moved a little bit forward or backward.

If we could somehow tinker with this system in the adult human, it might be possible to reduce the effects of jet-lag and shift work by rapidly adjusting our internal clock. Duffield and the team of researchers may have uncovered an important target for such remedies by identifying the Id2 gene, which appears to in some way regulate the magnitude of response of the circadian clock to light signals.

BackTrack: Dynamic MR Imaging of the Pituitary: Same tools, different technique (but wow, what a difference!)

(This article was first posted on July 29, 2008. It's worth repeating.)

Those of us who have suffered or still suffer with pituitary adenomas have heard way too many times "your MRI is normal". I did, for years. Yet, I ultimately did have a proven adenoma which caused my Cushing's disease. If the MRI had shown even an inkling of the tumor to the trained eye, perhaps a doctor would have taken my symptoms more seriously.

So, what makes a difference, then?

Two things made a huge difference for me. First, my current endocrinologist insisted on a dynamic MRI. Secondly, I sent the films and/or CDs to neurosurgeons who remove a lot of pituitary adenomas. What my local radiologist called a "normal" MR image of my pituitary was actually deemed NOT NORMAL by three world-renowned neurosurgeons.

(My local hospital is excellent, but they had never done a dynamic protocol with MR imaging. However, the Taper Imaging Center at Cedars-Sinaii Hospital in Los Angeles bent over backwards to prepare them through phone calls, emails, and reading materials. What a good group of folks! I've met several of them.)

What is a dynamic MRI?

In order to understand that, you need to first understand what an MRI is. Typically, pituitary MRI's are done "without contrast" and "with contrast". The Magnetic Resonance Imaging is done with no radioactivity (aka x-rays). It uses a strong magnetic field produced by a large magnet to send radio waves through the body which "jiggle" the body's atoms. When these atoms move back into place, they send out radio waves of their own which are picked up by the scanner and fed into a computer. This computer then uses programmed algorithms to turn them into pictures. To learn more about it, visit How Stuff Works.

A contrast is often used with MR imaging, especially of the head, to enhance the images. Solutions of gadolinium compounds are typically used as contrast agents. Tumors enhance after gadolinium is given because they tend to absorb the contrast agent either more quickly or less quickly than "normal" tissue. This leads to a "contrast" between the two types of tissue.

What makes a dynamic MRI different from any MRI using contrast?

Typically, a series of images are taken prior to contrast and then the MR imaging is stopped while contrast is injected. Once that is finished, the MRI proceeds with another series of images. With the dynamic protocol, the contrast is infused over a period of time while the MR imaging is taking place. In one study the gadolinium solution was injected via IV over a period of 180 seconds. In another study the gadolinium was dripped via IV between 2 and 3 minutes.

Why does that make a difference?

Pituitary tumors and normal gland tissue absorb the gadolinium at different speeds. The contrast between the normal tissue and tumor may be easier to see in the earlier images when compared to the later ones. Usually the pituitary adenoma enhances slower than the gland. (However, there have been documented cases of just the reverse if the tumor encases a blood supply.) When the tumor enhances slower, a "dark spot", in layman terms, shows up on the pituitary. These are called areas of "hypointensity". This is transitory and if not imaged as it happens, the tumor will enhance to match the gland. (In the picture, the upper image does not clearly show a tumor. The lower image shows the tumor well including its contact with the right internal carotid artery.)

Although I did not mention the strength of the MRI scanners being used, it's probably obvious that the stronger they are (measured in Tesla), the better they work. A 3T scanner is preferable if available, but the authors of the studies used scanners as low as 0.5T in their studies. A scanner is only as good as those operating it, those reading the scans, and the protocols used not matter how strong it is.

Pretty dynamic, huh?

---

For more information in prior threads, see:

Recent Advances in Neuroendocrine Imaging Lead to Improved Diagnosis

Testing 101: Imaging

Central actions of glucocorticoids in the control of body fluid homeostasis

Cushing's patients have a lot of problems with fluid regulation. Since the hypothalamic-pituitary-adrenal (HPA) axis is involved in the control of body fluid, it isn't surprising glucocorticoids are involved. This research indicates glucocorticoids play a role.

The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity.

To read more, the full-text article may be found here:

Central actions of glucocorticoids in the control of body fluid homeostasis: Review

S.G. Ruginsk, A. Lopes da Silva, R.R. Ventura, L.L.K. Elias, J. Antunes-Rodrigues (2009). Central actions of glucocorticoids in the control of body fluid homeostasis: Review Brazilian Journal of Medical and Biological Research, 42 (1) DOI: 10.1590/S0100-879X2009000100010

Amazing Kimberly: A video tracing her journey with Cushing's Syndrome

"For five years the doctors found nothing wrong"


On her blog, Cushing's and Cancer, MaryO shares the story of Kimberly, a Cushing's Syndrome survivor. She says:

This video was kindly sent to me by Kimberly's husband. He did such a beautiful job putting her images into a video with music. This is another great way to help get the word out about Cushing's. Thanks, Randall!

On the YouTube site Kimberly's husband, Randal, says:

The amazing story of Kimberly, whose health began to deteriorate in 1999. A number of unrelated symptoms, including substantial weight gain and fatigue, baffled doctors for over 5 years. She was finally diagnosed with Cushings syndrome in 2005. This video shows her miraculous transition battling through this disease, regaining her health and beauty.

Kimberly, you go, girlfriend!!! Randal, thank you for sharing. I hope this will help others to be diagnosed sooner and easier.

I heart you! <3 <3 <3 <3 <3 <3

Almost two years ago, I was participating in an online art "class" with some of my fellow "Cushies" (Cushing's Disease/ Syndrome survivors), and I did this variation of a heart. I love quilts, and my mother makes gorgeous works of art called quilts. I'm not quite so handy or patient, so my "quilts" are done with art.

For everyone reading here who is suffering from an endocrine disorder, I wish you a quick diagnosis and treatment. For all others who read here, I wish you well.

Happy Valentine's Day.

Bariatric surgery: Not the answer for obesity and "hidden" Cushing's Syndrome

Although I'm posting this as research (which it is), this is also personal for me. I was told by multiple doctors to have bariatric surgery. This included endocrinologists. I even went as far as making an appointment with a bariatric surgeon, going through the pre-surgical "talk" and consult, and asking a lot of questions. I didn't find him cognizant of the endocrine problems that might hinder recovery with bariatric surgery. Frankly, he dismissed my questions and walked out on me.

I'm glad I did my research. And now, the medical community is looking at the repercussions of bariatric surgery to control weight without first testing for endocrine-related causes, especially Cushing's Syndrome.

The first article cited below is a plea for screening of obese patients prior to bariatric surgery. Dr. Ludlam is well-known in the Cushing's patient community because of his stringent protocol for diagnosis and treatment of Cushing's. He and the others who authored this article have dealt with Cushing's patients for a very long time.

In this article, the authors cite two cases where bariatric surgery caused the CS to be overlooked, resulting in a poor outcome. "One patient had progression of obesity, multiple vertebral compression fractures, poorly controlled diabetes and HTN during a 10-year period, and the second patient ultimately died." The second patient was 27 years old. His death is a tragedy.

The second patient had a rapid weight-gain at the age of 20. By the age of 24 he had undergone a Roux-en-Y gastric bypass to control the weight. After losing 170 pounds and with a BMI of 20 kg/m² he still presented with "symptoms suggestive of hypercortisolism. These included
lower extremity edema, facial plethora, facial rounding, a dorsocervical hump, acne, proximal muscle weakness, and neuropsychiatric symptoms." These had been present prior to bariatric surgery, also.

The article goes into much more depth than I am presenting here. It is one which I believe all doctors who treat obese patients should read. The authors suggest who to screen , which can be summarized:

1. Anyone with an adrenal incidentaloma
2. Anyone presenting with HTN and Type II diabetes
3. Patients with a "history of easy bruising, evidence of proximal muscle weakness, the presence of reddish-purple striae 1 cm wide, and facial plethora"
4. Patients with rapid weight gain, especially in combination with other symptoms
5. Young patients with "old" symptoms (i.e. HTN, osteoporosis, kidney stones, multiple infections)
6. Any combination of the above.

The authors also suggest following the guidelines of research previously quoted in this blog.

The second article cited below is a response to the first article. In this article, the authors emphasize the need for screening of obese patients.

...a recently published meta-analysis reported a prevalence of hypercortisolism in ≤2–5% when Cushing syndrome is systematically screened for in patients with poorly controlled type 2 diabetes and adrenal incidentalomas [2]. Conversely, the prevalence of Cushing syndrome in those with simple obesity is largely unknown. Moreover, a condition of functional hypercortisolism with subtle alterations of hypothalamic-pituitary-adrenal axis is frequently evidenced in those with simple obesity...

...However, despite the probability that the diagnosis of Cushing syndrome might be overlooked, the possibility arises that Cushing syndrome might be unrecognized among obese patients.

This article outlines possible contra-indications of bariatric surgery for obese patients, especially those with possible Cushing's. Those, along with the delay in diagnosis may cause "irreversible sequelae in patients with undiagnosed Cushing syndrome".

M FLESERIU, W LUDLAM, S TEH, C YEDINAK, C DEVENEY, B SHEPPARD (2009). Cushing's syndrome might be underappreciated in patients seeking bariatric surgery: a plea for screening Surgery for Obesity and Related Diseases, 5 (1), 116-119 DOI: 10.1016/j.soard.2008.09.011


S SAVASTANO, R PIVONELLO, A COLAO (2009). Bariatric surgery for obesity and hidden Cushing syndrome Surgery for Obesity and Related Diseases, 5 (1), 121-122 DOI: 10.1016/j.soard.2008.07.006

CT imaging in the hunt for ectopic ACTH tumors

Once the biochemical evidence of excess ACTH production leads to the diagnosis of Cushing's Syndrome for a patient, the next step is determining the source of excess ACTH production. Usually the source for the excess ACTH is a tumor on the pituitary gland. However, ectopic sources may also be ACTH secreting tumors.

Eighty to 85% of Cushing’s syndrome is ACTH-dependent, of which 80–90% will be due to a pituitary adenoma—Cushing’s disease (CD) [1]. Ten to 15% will have a nonpituitary source, referred to as ectopic ACTH secretion (EAS) [2], of which 80% have an identified source within the chest and abdomen whilst 20% have no detected source and are referred to as occult [1].

This article talks about the use of computed tomography (CT) to locate the source of the EAS. According to the authors, a bilateral inferior petrosal venous sampling (BIPPS) is the first step in determining whether the source of excess ACTH is ectopic, with a 95% sensitivity. They say "false positives are extremely rare (<1%)> and there is a false negative rate of 2–4%".

The authors include information about imaging multiple tumors including the following:

Bronchial carcinoids

Thymic carcinoids

Gastrointestinal carcinoids

Pancreatic neuroendocrine tumours

Medullary thyroid carcinomas

Phaeochromocytomas

They also mention other tumors briefly:

Many tumours have been reported in the literature to result in EAS such asovarian carcinoid, ovarian adenocarcinoma, ovarian androblastoma, ovarian teratoma, ovarian Sertoli cell carcinoma, ovarian dermoid cyst, prostatic adenocarcinoma, prostatic small cell carcinoma, small cell carcinoma of the uterine cervix and olfactory neuroblastoma [6].

The authors recommend the use of ¹¹¹In-octreotide in some cases and mention the enlargement of the adrenals, as well as shape and hyperplasia depending on the type of EAS. They conclude that CT imaging can lead to earlier diagnosis and treatment of these excess ACTH sources.

(Picture is from the article)

Paul A. Sookur, Anju Sahdev, Andrea G. Rockall, Andrea M. Isidori, John P. Monson, Ashley B. Grossman, Rodney H. Reznek (2009). Imaging in covert ectopic ACTH secretion: a CT pictorial review European Radiology DOI: 10.1007/s00330-008-1274-5