Improved early diagnosis and treatment for Graves' orbitopathy

September 14, 2018, CORDIS
Improved early diagnosis and treatment for Graves’ orbitopathy
Credit: Perception7, Shutterstock

Despite Graves' disease and Graves' orbitopathy affecting around 3 million Europeans and costing billions of euros, treatments can only control symptoms. INDIGO identified risk factors, studied microbiota composition and tested probiotics to improve health outcomes.

Graves' disease (GD)—the commonest cause of an overactive thyroid gland—is a chronic autoimmune condition characterised by the body's defence mechanism attacking itself, as it would an infection. Graves' orbitopathy (GO) is a disorder, occurring most frequently in people with GD, which produces orbital tissue inflammation and protruding eyes leading to double vision and even blindness. Despite a recognised impairment to quality of life, current treatment remains unsatisfactory.

To improve for people with GO, the EU-funded INDIGO project used human and animal trials to better understand the development of GO. The team were able to identify , devise approaches for early diagnosis and offer novel and safe interventions.

The good, the bad and the ugly in the gut's microbiota

From participating hospitals, INDIGO recruited 65 with GD, 56 with GO and a control group of 42. The group supplied blood samples, nasal swabs, tears and stool samples which were used for DNA extraction. The samples were collected at diagnosis, after several months of treatment (when thyroid hormone levels had normalised) and later when some patients might have relapsed. Participants also completed a questionnaire about their diet.

The first objective was to explore the link between microbiota and GD/GO. As project coordinator Professor Marian Ludgate explains, "To identify the different types of bacteria present in the stool DNA, we sequenced a gene called 16S rRNA to provide a unique biomarker for individual members of the gut's microbiota. We then identified those present in people with GD and GO, compared with healthy controls. This determined specific microbiota associated with autoantibodies, thyroid hormone levels or eye disease severity."

The study found an increased quantity of bacteria known as bacteroidetes in the control group (38.5 %) against the GD (24.2 %) and GO (27.3 %) groups. Conversely, a noted amount of bacteria called firmicutes, were more abundant in GD and GO patients. Additionally, a pathobiont – a pathological organism known as Enteroccoccus gallinarum – reported to be involved in triggering autoimmunity, was significantly higher in GD and GO groups, than in the control.

INDIGO also conducted a pilot study into the effects of a probiotic (live microorganisms) which may have beneficial effects by modifying the host microbiota in GD/GO patients. Participating patients were randomly assigned a probiotic or placebo with the same sampling procedure.

The results showed some evidence that microbiota composition was stabilised in the receiving patients, who also displayed a significant reduction in firmicutes counts, compared to the placebo group.

These findings broadly found support from the team's experiments with female mice (GD/GO being more prevalent in women) injected with the relevant autoantigen, for the identity of the receptor which is the on/off switch for the thyroid gland.

Getting from treatment to cure

For GD, drugs inhibit the production of thyroid hormones and work for about 50 % of patients. Those who relapse can have their thyroid removed, either using radio-active iodine or surgery, having to take thyroxine replacement drugs for life.

In the case of GO, sufferers can use steroids to reduce inflammation. Although it is possible to arrest GO in more than 80 % of patients, complete remission is rare, with surgery often necessary and rehabilitation lasting for months.

If INDIGO's work is to contribute to an improved quality of life for GD/GO sufferers, an additional control group is required to help distinguish the effects of hyperthyroidism and autoimmunity on the observed changes in gut microbiota composition. Professor Ludgate adds, "We also need to go beyond association, by actually looking at the RNA in the immune cells in the intestine involved in the activation or remission of GD and how they interact with the composition." Additionally, the probiotic trial needs to be conducted on a larger scale to clarify health outcomes.

Further down the line to improve diagnosis Professor Ludgate foretells, "The biomarkers identified by INDIGO need to be confirmed with further studies, then we can envisage simple disease prediction tests rather than conducting protein and genomic profiling."

Explore further: Breakthrough model holds promise for treating Graves' disease

Related Stories

Breakthrough model holds promise for treating Graves' disease

September 3, 2013
Researchers have developed the first animal model simulating the eye complications associated with the thyroid condition Graves' disease, a breakthrough that could pave the way for better treatments, according to a recent ...

Chronic fatigue syndrome possibly explained by lower levels of key thyroid hormones

March 20, 2018
New research demonstrates a link between chronic fatigue syndrome (CFS) symptoms and lower thyroid hormone levels. Published in Frontiers in Endocrinology, the study indicates that CFS, a condition with unknown causes, can ...

Research finds orbital radiotherapy should not be used to treat thyroid eye disease

March 26, 2018
The first NHS-led clinical trial for thyroid eye disease (TED) - also called Graves' orbitopathy (GO) – a disfiguring condition causing protruding eyes, double vision and swelling around the eyes affecting mostly women ...

The gut microbiota plays a key role in treatment with classic diabetes medication

June 1, 2017
A clearer picture of how the classic diabetes medication metformin works has emerged. A recent study at Sahlgrenska Academy and University of Girona indicates that the clinical effect – control of blood glucose – is achieved ...

Gastric bypass surgery alters gut microbiota profile along the intestine

July 10, 2012
Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that gastric bypass surgery ...

Researchers discover link between gut and type 1 diabetes

February 19, 2018
Scientists have found that targeting micro-organisms in the gut, known as microbiota, could have the potential to help prevent type 1 diabetes.

Recommended for you

Drugs that stop mosquitoes catching malaria could help eradicate the disease

September 18, 2018
Researchers have identified compounds that could prevent malaria parasites from being able to infect mosquitoes, halting the spread of disease.

Vaccine opt-outs dropped slightly when California added more hurdles

September 18, 2018
In response to spiking rates of parents opting their children out of vaccinations that are required to enroll in school—and just before a huge outbreak of measles at Disneyland in 2014—California passed AB-2109. The law ...

New evidence of a preventative therapy for gout

September 17, 2018
Among patients with cardiovascular disease, it's a common complaint: a sudden, piercing pain, stiffness or tenderness in a joint that lasts for days at a time with all signs pointing to a gout attack. Gout and cardiovascular ...

"Atypical" virus discovered to be driver of certain kidney diseases

September 14, 2018
An international research team led by Wolfgang Weninger has discovered a previously unknown virus that acts as a "driver" for certain kidney diseases (interstitial nephropathy). This "atypical" virus, which the scientists ...

Flu shot rates in clinics drop as day progresses, but nudges help give them a boost

September 14, 2018
Primary care clinics experienced a significant decline in influenza vaccinations as the day progressed, researchers from Penn Medicine report in a new study published in JAMA Open Network. However, "nudging" clinical staff ...

Cancer drug and antidepressants provide clues for treating brain-eating amoeba infections

September 13, 2018
The amoeba Naegleria fowleri is commonly found in warm swimming pools, lakes and rivers. On rare occasions, the amoeba can infect a healthy person and cause severe primary amebic meningoencephalitis, a "brain-eating" disease ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.