Vitamin D Thyroid Eye Disease

Blue Light Therapy Another Winter Tool

If you find yourself feeling worse in the winter than you do in the summer , vitamin D may help, but you would likely have the best outcomes if you combined it with blue light therapy.

A recent study published in Scientific Report suggests that exposure to sunlight may be beneficial to our immune system, via mechanisms that are separate from vitamin D. The researchers noted that blue light, in particular, which is produced naturally by the sun, may activate key immune cells and boost immune function. In their study, blue light exposure triggered the synthesis of hydrogen peroxide, which inactivated pathways that signaled an increase of motility of the T cells , in both mouse and human T lymphocytes.

Blue light is known to reach the second layer of the skin, where there is a higher concentration of T lymphocytes compared to those found in the bloodstream. The study, therefore, suggests that there could be a separate pathway through which sunlight specifically blue light exposure may boost the immune system.

Blue light therapy devices have also been studied in seasonal affective disorder , aka the winter blues, with great success.

Adenovirus Preparation Mouse Strains Vitamin D

Adenovirus expressing the TSHR A-subunit have been described. Both adenoviruses were propagated in HEK293 cells , purified on CsCl density gradients, and viral particle concentration was determined by measuring the absorbance at 260 nm .

Female BALB/cJ and C57BL/6J mice were divided into two groups for each strain, one group was maintained on vitamin D-deficient chow , and the other group received regular mouse chow. After 6 wk, blood was drawn from mice of both strains, and 7 d later, when the animals were 13 wk old, mice were immunized three times at three weekly intervals with A-sub-Ad or Con-Ad . Blood was drawn 1 wk after two injections, and mice were euthanized 1 month after the third injection . All animal studies were approved by the Institutional Animal Care and Use Committee at Cedars-Sinai Medical Center and performed with the highest standards of care in a pathogen-free facility.

Schedule for investigating BALB/c and C57BL/6 mice maintained on vitamin D-deficient or normal diet and immunized three times with A-sub-Ad or Con-Ad. Also shown are the time intervals at which blood was drawn and mice were euthanized. Splenocytes were analyzed for lymphocyte subsets by flow cytometry and responses to A-subunit protein and mitogens. Sera were characterized for vitamin D and its active metabolite, T4, and TSHR antibodies.

The Benefits Of Vitamin D For Your Thyroid

Medically reviewed and written by Izabella Wentz, PharmD, FASCP

In January, I like to focus on immune support for my family.

Do you ever feel worse in the winter than you do in the summer? A deficiency in vitamin D and a certain spectrum of light may hold the key to feeling better.

Autoimmune conditions are more likely to cluster in regions farther from the equator, and scientists have suggested that one of the potential reasons for this may be due to inadequate vitamin D levels, as vitamin D is primarily absorbed via sunshine on skin that is free of sunscreen.

Although those who live in warm climates are more likely to be absorbing enough of the sunshine vitamin, I often find that even people who live in warm climates such as Southern California, Florida, and Arizona, are vitamin D deficient at similar rates to people living in Wisconsin or Minnesota!

This is because our absorption of the vitamin from food sources is minimal, and is often further compromised by digestive enzyme deficiencies and gut conditions that lead to malabsorption of nutrients .

As a result, vitamin D is one of the most under-recognized deficiencies in our society, and an estimated 85 percent of Americans may be deficient in it.

Many diseases have also been connected to low vitamin D levels, including heart disease, autoimmune disease, depression, and recently, thyroid conditions, including Hashimotos.

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In The Second Installment Of This Two

Management of thyroid eye disease has shifted dramatically from conservative measuresobservation and surgeryto targeted biologic therapy with a focus on cosmesis and quality of life. Surgical innovations have also allowed for more profound results with significantly less risk of complications. Treatments for active-phase disease have also multiplied, which significantly affects quality of life for these afflicted patients.

Last month, in part one of this two-part series on TED, I discussed the keys to diagnosing TED. Here, in part two, Ill discuss the best techniques for managing patients with TED.

Medical Therapies

Medical therapy can be a good initial, noninvasive way to manage certain patients with TED. Following are the pros and cons of the various medical approaches.

Steroids. Steroids are excellent for reducing symptoms in TED, but arent disease-modifying rather, they improve soft-tissue symptoms in the active phase until the body can pass into the stable phase of the disease.

Surgical Therapies

Future Directions

Demographics According To Vitamin D Supplementation Status

The clinical characteristics of the participants were described according to vitamin D supplementation : 60 patients took vitamin D supplements and 150 patients did not take vitamin D supplements. The two groups had similar baseline parameters in terms of age and thyroid function at diagnosis and ATD discontinuation however, sex and TBII levels at the time of ATD discontinuation were different between two groups at baseline. In the vitamin D supplementation group, the mean vitamin D level increased from 10.6 ng/mL to 25.7 ng/mL. The vitamin D supplementation group took vitamin D supplements for a mean duration of 31 months and at a mean dose of 1383 IU per day 28 patients took 1000 IU vitamin D per day, 18 patients took 1500 IU per day, and 14 patients took 2000 IU per day. The time to recurrence was delayed in the supplementation group compared to the time to recurrence of the no supplementation group . However, the difference in recurrence rate within one year was similar with borderline significance .

Table 1 Clinical characteristics according to vitamin D supplementation status.

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What To Limit When You Have Graves’ Disease

• Caffeine: Foods that contain caffeinecoffee, soda, tea, and chocolatecan aggravate Graves disease symptoms, such as anxiety, nervousness, rapid heart rate, and weight loss. Although you may not need to completely eliminate caffeine from your diet, talk to your doctor about whether youll need to limit foods with caffeine. If you enjoy a cup of coffee in the morning, and you don’t feel awful, then you don’t have to eliminate it.

• Food allergens: If you have a food allergyeven if its a mild food allergyyou may want to avoid that food to lessen any adverse effects. The effect that some food allergens have on the body can mimic Graves disease symptoms, so eliminating those foods may help your doctor figure out what exactly your Graves disease symptoms are. Common food allergens include dairy products, , soy, corn, and nuts.

Vitamin D Deficiency And Thyroid Disease

There’s increasing evidence to suggest that low levels of vitamin D may play a role in thyroid disorders. For instance, research has suggested a possible link between vitamin D deficiency and autoimmune thyroid disorders, namely Hashimoto’s thyroiditis, the most common cause of hypothyroidism , and Grave’s disease, characterized by an overactive thyroid.

In one study, 72% of subjects with autoimmune thyroid disease were deficient in vitamin D, whereas just under 31% of healthy subjects had low levels of vitamin D. Similarly, a study of people in Greece with Hashimoto’s thyroiditis revealed that more than 85% of them had low levels of vitamin D, as well as high levels of anti-thyroid antibodies.

Vitamin D supplementation also has shown promise as a way to help treat thyroid disease. In the same Greek study, for example, the Hashimoto thyroiditis patients who were deficient in vitamin D took 1,200 to 4,000 international units of vitamin D every day for four months, after which time they had significantly lower levels of anti-thyroid antibodies.

In yet another study, people with hypothyroidism who took extra vitamin D supplements for 12 weeks had improvements in blood levels of thyroid stimulating hormone .

Aleksandra Jankovic / Stocksy United

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Vitamin D Its Active Metabolite And Cyp27b1

Compared with mice on regular mouse chow, BALB/c and C57BL/6 mice on the deficient diet had virtually undetectable serum levels of 25D3, the major circulating form of vitamin D . As expected, levels of the active metabolite, 1,252D3, were also lower in mice of both strains on the deficient chow. Nevertheless, 1,252D3 was still detectable in mice on vitamin D-deficient chow. It was also noted that 1,252D3 levels were significantly lower in BALB/c than in C57BL/6 mice, regardless of diet . To investigate this issue further, we analyzed expression in the kidney of Cyp27b1, the gene that encodes the enzyme 1-hydroxylase that catalyzes synthesis of 1,252D3. Levels of Cyp27b1 mRNA were approximately 17-fold lower in BALB/c than in C57BL/6 mice, regardless of diet . These findings provide a potential explanation for the lower serum levels of 1,252D3 in BALB/c vs. C57BL/6 mice . Overall, these differences suggested that any effects of diet were more likely to be seen in BALB/c than in C57BL/6 mice.

Splenocyte Responses To Tshr Protein And Mitogens

Splenocytes were incubated in round-bottomed 96-well plates with or without purified TSHR A-subunit protein . Recombinant A-subunit protein secreted by Chinese hamster ovary cells with an amplified transgenome was purified from culture supernatants by affinity chromatography . Responses to the mitogens and pokeweed mitogen were also tested. Culture medium was RPMI 1640, 10% heat-inactivated fetal bovine serum, 2 mm glutamine, 1 mm sodium pyruvate, 50 m -mercaptoethanol, 50 g/ml gentamicin, and 100 U/ml penicillin . After 56 d , the plates were centrifuged to remove cell debris and supernatants stored . Interferon- was measured by ELISA using capture and biotinylated detection-antibodies .

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Vitamin B9 And Vitamin B12

General Pathology and Causes

Vitamin B9, also known as folate acid, serves as a coenzyme and is involved in various reactions including DNA and purine synthesis, and amino acid catabolism, specifically the conversion of homocysteine to methionine. Folate is found in green leafy vegetable, fruits, fortified cereals, and meats. A serum folate concentration of less than 3ng/mL and an increased plasma homocysteine level of greater than 16 mol/L indicates deficiency. Folate deficiency can develop in the setting of malabsorptive diseases, excess alcohol, medications , and pregnancy.11

Vitamin B12, also known as cobalamin, serves as a coenzyme in reaction that converts homocysteine to methionine and in the production of succinyl-CoA. Therefore, solely measuring plasma homocysteine levels would not differentiate between a folate or cobalamin deficiency. Cobalamin is absorbed with intrinsic factor, a glycoprotein of stomach cells, in the terminal ileum. Cobalamin deficiency most typically develops in patients following a vegetarian or vegan diet, with a history of bariatric surgery, and those with malabsorptive diseases. Elevated serum homocysteine and methylmalonic acid are an indicator of cobalamin deficiency.11

Disease and Treatment

Defining Vitamin D Deficiency

According to some reports, around 40% of adults have insufficient levels of vitamin D, although estimates vary. Certain risk factors are associated with lower levels, including race , obesity, lack of college education, and lack of daily milk consumption.

Vitamin D levels are measured with a simple blood test called the 25-hydroxyvitamin D test. Results of this test are measured in nanograms per milliliter , which the National Institutes of Health categorizes as follows:

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Correlation Of Vitamin D Levels With Laboratory And Clinical Parameters In Gd Patients

We did not observe any correlation between the vitamin D levels and levels of fT4, fT3, TRAb, and TPOAb and relapse within 1 year after terminating treatment with antithyroid drugs. When comparing subjects with a vitamin D level < 25 nmol/L to those with higher levels, we could not see any differences in the fT4, fT3, TRAb, and TPOAb levels or the frequency of GO. Regarding GO, GD patients without GO at diagnosis had the same vitamin D levels as those with GO . Logistic regression adjusting for sex, age, ethnicity, and smoking did not show any association between the vitamin D levels and GO at diagnosis of GD . We further analyzed the impact of vitamin D levels on the outcome of patients treated with antithyroid drugs , defined as relapse of GD within 1 year of completing an 18-month course of antithyroid drugs. There was no difference in the vitamin D levels at baseline between individuals who achieved remission and those who relapsed . Logistic regression, adjusting for sex, age, smoking, GO at diagnosis, and TRAb at diagnosis, did not show any association between the vitamin D levels at diagnosis and relapse after antithyroid drugs .

Do Low Vitamin D Levels Play A Role

What relationship does vitamin D deficiency have with thyroid eye disease among patients with Graves disease?

Take Note

• Graves disease patients with TED were found to have lower levels of vitamin D than Graves disease patients without TED or matched controls.
• Vitamin D supplementation may help lessen the risk of developing thyroid eye disease , and thus potential eye damage, in patients with Graves disease. Future study is needed.
• Certain TED treatments, such as prolonged use of corticosteroids, may have an effect on vitamin D levels.

That was the question researchers from the Kellogg Eye Center in Ann Arbor, Mich., sought to answer in a retrospective case-control study. The results, recently published in Ophthalmic Plastic and Reconstructive Surgery, demonstrate lower levels of serum vitamin D in TED patients. The authors postulate that supplementation with vitamin D may potentially lessen the risk of developing TED and its associated visual impairment in patients with Graves disease.1

A shadowy disorder

How multiple groups of patients compared

The authors compared mean vitamin D levels across 4 groups: 89 patients with Graves disease and TED, 89 Graves disease patients without TED, and 2 healthy control groups matched 4:1 to the cases . Appropriate data were retrieved from the electronic medical records of patients who had visited the Kellogg Eye Center between April 1, 2016, and June 22, 2018.

A good start but not the final word

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What Is Vitamin D

Vitamin D is an essential nutrient and a precursor hormone that plays an important role in many biochemical functions within the body. The body produces vitamin D from cholesterol, when our skin is exposed to sunlight. Vitamin D is also found in certain foods, such as fatty fish and fortified dairy products. However, it is very difficult to get adequate amounts through diet alone.

Vitamin D has several important functions within the body, including the regulation of calcium and phosphorus absorption for bone and tooth growth.

This vitamin has also been shown to reduce ones risk of developing Multiple Sclerosis and heart disease. It plays an important role in regulating mood and preventing depression as well. In fact, researchers behind a 2013 meta-analysis observed that, statistically, people with low vitamin D were at a much greater risk of depression. Another study found vitamin D receptors in the same areas of the brain associated with depression, and concluded that vitamin D plays an important role in brain function and mental health.

Of note, vitamin D can also support the immune system. By enhancing the pathogen-fighting effects of monocytes and macrophages white blood cells that are important parts of immune defense and decreasing inflammation, vitamin D can help reduce the likelihood of contracting viruses, such as the seasonal flu.

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Clinical Presentation Of Ted

About 90% of patients with TED also have some thyroid dysfunction – usually the thyroid is overactive , but occasionally the thyroid is underactive . Most times, the diagnosis of TED and diagnosis of a thyroid dysfunction occur within the same year. Patients who are diagnosed with TED but have no known thyroid dysfunction should see their primary care physician for an evaluation of their thyroid function.

The disease course for TED involves 2 phases – active and stable. In the active phase there is active swelling and inflammation. This presents as redness in and around the eye, eye pain with or without eye movement, as well as swelling around the eyes and eyelids. The active phase of TED involves a waxing/waning period of these symptoms, and can last months to years. On average, the active phase of TED lasts about 1 year for non-smokers, and 2-3 years for smokers . The active phase of TED spontaneously transitions to the stable phase, but can recur. Active TED has a recurrence rate of about 5-10%, but is less likely to recur after 18 months in the stable phase.

Figure 3. Active vs. Stable TED. Active TED is characterized by signs of inflammation . TED activity waxes and wanes, and usually transitions to stable TED within 1-3 years.

Figure 4. Rundle’s curve. As seen in the representation of TED activity over time in Rundle’s curve, initiating therapy early is crucial to diminish the overall severity of the chronic disease.

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While There Is No Specific Diet To Prevent Or Treat Graves’ Disease There Are Certain Foods Best Avoided And Others That Are Best Chosen To Promote Health And Avoid Inflammation

Theres really not such a thing as a Graves disease diet, per se.

While what you eat can matter, it’s more about planning meals and filling your plate with foods that wont aggravate your Graves disease symptoms. In addition to selecting foods wisely, youll most likely need a combination of treatments, such as medications and radioactive iodine, as part of your Graves disease treatment plan so you can feel your best.

Graves disease is actually the most common cause of when your thyroid gland over-produces thyroid hormone. Although Graves disease cant be prevented or treated through diet alone, certain foods may help ease Graves disease symptoms. And, keep in mind that everybody is different so that which foods may exacerbate or worsen your symptoms will be a matter of trial and error.

More universal are the foods you should choose most often to help manage the symptoms of Graves disease.