Transcript Treatment of Graves` Disease with Combination Therapy: A Chart

Treatment of Graves’ Disease with Combination Therapy:
A Chart Review
Reba Leonard
Introduction
Graves’ Disease is the most common autoimmune disorder and affects
approximately 1% of the United States population. An autoimmune disorder is when
the immune system, the body’s main defense against pathogens, mistakes healthy
body tissue as a foreign invader and attacks the tissue. In the case of Graves’
disease, the immune system attacks the thyroid gland. The thyroid gland, a part of
the endocrine system, releases hormones, which control metabolism, heart rate,
and mood. In most cases, when the thyroid gland is attacked by the immune
system, the antibodies attach to the thyrotropin receptors and activate the thyroid
gland (Weetman, 2000, 1236). This causes the hypertrophy of the thyroid gland and
excess hormones to be released. When excess thyroid hormones are released the
body’s metabolism speeds up, causing one of the most common symptoms of
Graves’ disease, weight loss. Other symptoms include fatigue, anxiety, depression,
heat intolerance, palpitations (irregular heartbeat), goiter (swelling of the thyroid
gland), fertility problems, and ophthalmopathy, which is characterized by swelling of
the muscles of the eye and results in double vision and can sometimes lead to
blindness (Scharf, 2006, 902).
Graves’ Disease is treated by first correcting the hyperthyroidism associated with
Graves’ disease. This can be done by a thyroidectomy, radioactive iodine, or antithyroid medication (Cinemre, 2009, 199). However, both surgery and radioactive
iodine have been known to increase ophthalmopathy. Surgery is an invasive
procedure, and potentially risky because it can cause laryngeal nerve injury, leading
to difficulty speaking (Scharf, 2006, 902). Radioactive iodine, the favored therapy in
the United States, is ingested orally and absorbed by the thyroid gland, because the
thyroid gland uses iodine to make hormones. The radioactive iodine then irradiates
the cells that take it in, thus killing them (Ogbera, 2008, 212). Radioactive iodine, as
well as surgery, can render a patient hypothyroid, because they no longer have a
thyroid gland to produce hormones (Scharf, 2006, 902). As a result, they will have to
be on thyroid medications for the rest of their life (Scharf, 2006, 902). Anti-thyroid
medications are more likely to improve the condition due to a blocking of antibodies.
However, because the medication reduces the amount of thyroid hormones,
sometimes the patient still becomes hypothyroid, which can exacerbate the
ophthalmopathy. Also, once the patients terminate treatment, they can experience
recurrent hyperthyroidism, which can also worsen ophthalmopathy (Lowery, 2009,
292).
This project studied the combination therapy of two medications, methimazole,
an anti-thyroidal/immunosuppressive medication, and L-thyroxine, a thyroid
hormone replacement medication. It is expected that the combination therapy will
be more beneficial than the other treatment options for Graves’ Disease.
Advisor: Dr. Hancock
Figure 1: A box plot of white blood cell counts in the different treatment types. The
shaded box represents the normal range of white blood cells. There was a
significant difference between the combination therapy treatment and the rest of the
treatment groups, and between the thyroidectomy treatment and the rest of the
treatment groups. However, the majority of patients in each treatment type were
within the recommended ranges for white blood cell count, which means that the
treatments are not negatively affecting the numbers of immune cells in the body.
Figure 3: A box plot of the levels of free T4, which is a hormone released from
the thyroid gland, for each treatment type. There was a significant difference
between the combination therapy treatment and the rest of the treatment groups,
between the thyroidectomy treatment and the rest of the treatment groups, and
between the synthyroid treatment and the rest of the treatment groups. All
treatment types were within the normal range, which means that the treatments
are regulating the synthesis and release of thyroid hormones.
Conclusions
In conclusion, the obtained results partially support the hypothesis that combination
therapy will result in a significantly different outcome than the other treatment options
for Graves’ Disease. Combination therapy had a significantly different white blood cell
count, thyroid stimulating hormone levels, and free T4 levels than the other treatment
types, although none were out of the recommended levels. However, combination
therapy resulted in relatively the same outcomes as the other treatment types, for
neutrophil count, TSI and TBI.
General Methodology
The effect of combination therapy was investigated by conducting chart reviews
at outpatient offices at Ohio University and Belpre Endocrinology Center. The data
that was recorded was patient number, treatment type, white blood cell count,
neutrophil count, thyroid-stimulating hormone, free T4, thyroid-stimulating
immunoglobulin, and thyrotropin binding inhibitor for 7 different treatment types:
combination therapy, thyroidectomy, radioactive iodine, synthyroid (hormone
replacement medication), anti-thyroid medication, no treatment and remission.
Each variable was compared between treatment groups using a one way ANOVA.
Any variables that did result in a significant difference were then analyzed with
post hoc t-tests to determine which treatment groups differed.
Table 1: The results of the comparisons of each variable between treatment types.
Literature Cited
Cinemre H, Bilir C, Gokosmangolu F, Akdemir N, Erdogmus B, Buyukkaya R. 1999.
Predictors of time to remission and treatment failure in patients with Graves’ disease
treated with propylthiouracil. Clinical and Investigative Medicine, 32(3): 199-205.
Lowery AJ, Kerin MJ. 2009. Graves’ Opthalmopathy: The case for thyroid surgery. Surgeon,
7(5): 290-296.
Ogbera AO, Ekpebegh C, Eregie A, Kuku SF. 2008. The Role of radioactive iodine usage in
the management of thyroid disorders with emphasis on Sub-Saharan Africa. The West
African Journal of Medicine, 27(4): 211-217.
Scharf JL, Ahmad SM, Gaughan JP, Soliman AMS. 2006. Thyroidectomy for Graves’
Disease: A Case-Control Study. Annals of Otology, Thinology & Laryngology, 115(12):
902-907.
Weetman AP. 2010. Medical Progress: Graves’ Disease. The New England Journal of
Medicine, 343(17): 1236-48.
Results
Results
Figure 2: A box plot of thyroid-stimulating hormone (TSH) levels in the different
treatment types. There was a significant difference between the combination therapy
treatment and the rest of the treatment groups, and between the thyroidectomy
treatment and the rest of the treatment groups. Most of the treatment types were not
within the recommended range (shaded box) of TSH. This is expected since the
main objective of each treatment is to decrease the level of thyroid hormones
released, and a decrease in thyroid hormones causes an increase in TSH.
Variable
Significant Difference?
Which Treatments are
Different?
WBC
Yes (p=0.02)
1 differed from 2-7
2 differed from 1, 3-7
Neutrophils
TSH
No
Yes (p<0.001)
Free T4
Yes (p<0.001)
TSI
No
None
1 differed from 2-7
2 differed from 1, 3-7
1 differed from 2-7
2 differed from 1, 3-7
4 differed from 1-3, 5-7
None
TBI
No
None
Treatment types: 1 = Combination therapy, 2 = thyroidectomy, 3 = I-123
(radioactive iodine), 4 = Synthyroid, 5 = Antithyroid, 6 = None, 7 = Remission
Acknowledgments
I would like sincerely thank all of those who helped me in this project. I greatly
appreciate all that Dr. Hancock has done for me and this project. She has been a
wonderful advisor. I would also like to thank Dr. McShaffrey for being a great
capstone class advisor. Also, a thanks is due to my capstone classmates for their
support, direction, and constructive criticism. Most importantly, a thanks goes out
to my friends and family for supporting me through it all!