Case Study Evaluation February 29, 2016 CASE HISTORY: An 11-year-old female with no significant past medical history presented with symptoms suggestive of hyperthyroidism (weight loss, heat intolerance). She has also experienced a decline in grades at school. Family history is significant for thyroid disease in both grandmothers (both on thyroid replacement therapies). The clinician ordered thyroid function tests including Free T4, T3, TSH, anti-TSH receptor antibodies, antithyroglobulin and antithyroid peroxidase antibodies. The results for the tests follow: Free thyroxine (FT4)     2.87 ng/dL (Prepubertal 0.73-1.77 Pubertal/Adult 0.73-1.84) Total triiodothyronine pediatric (T3)     374.00 ng/dL (123-211) Thyroid-stimulating hormone (TSH)     <0.018 uU/ml Thyroxine (T4)     18.2 ug/dL (5.0-12.0) Antithyroglobulin antibodies     >3000 IU/ml (Negative <60 IU/mL Equivocal 60-100IU/mL Positive >100 IU/mL) Antithyroid peroxidase antibodies     2667 IU/mL (<60) Anti-TSH receptor antibodies     69.6 % Inhibit. (<=16.0 Unit: %) The laboratory findings confirmed the clinical impression and a diagnosis of Graves's disease (hyperthyroidism with thyrotoxicosis) was made. The patient was started on methimazole right away but after approximately two weeks of treatment she developed severe adverse reaction to it with significant joint pain and swelling over her upper and lower extremities with hives; Methimazole was stopped immediately and she was started on Benadryl and Advil ; her symptoms improved after few days, although she did have some residual intermittent hives that were transient. She has been given some brief course of Prednisone as well, and Atenolol 50 mg twice a day was also started. After approximately two weeks, due to the fact that the medical management for hyperthyroidism failed, the patient was considered to have radioiodine ablation of her thyroid next day and for that she underwent a thyroid imaging with uptake showing enlarged thyroid gland, with homogeneous increased uptake, consistent with Graves disease with 24-hour uptake equaling 86%. The patient underwent radio-iodine ablation as scheduled and she was stable on Atenolol 50 mg twice a day. She was discharged home. At her next follow-up appointment in 2 weeks her thyroid functions tests lab values were as follows: T4,     Free, >12.00 ng/dl (Prepubertal 0.73-1.77 Pubertal/Adult 0.73-1.84)  T3,     1173.00 ng/dL (123-211 ng/dL) TSH,     <0.018 uIU/mL DISCUSSION: "Thyrotoxicosis in a Pre-adolescent Patient with Averted Thyroid Storm Following Radio-pharmaceutically Induced Therapeutic Lysis of Thyroid Gland" Laboratory evaluation of thyroid function in various clinical situations. Adapted from The Merck Manuals, Online Medical Library, Endocrine and Metabolic Disorder, November 2005 revision Graves' disease is the most common cause of thyrotoxicosis in children. The disorder is rare before the age of 3 and increases progressively ...

1. Case Study Evaluation
February 29, 2016
CASE HISTORY:
An 11-year-old female with no significant past medical history
presented with symptoms suggestive of hyperthyroidism (weight
loss, heat intolerance). She has also experienced a decline in
grades at school. Family history is significant for thyroid
disease in both grandmothers (both on thyroid replacement
therapies). The clinician ordered thyroid function tests
including Free T4, T3, TSH, anti-TSH receptor antibodies,
antithyroglobulin and antithyroid peroxidase antibodies.
The results for the tests follow:
Free thyroxine (FT4) 2.87 ng/dL (Prepubertal 0.73-1.77
Pubertal/Adult 0.73-1.84)
Total triiodothyronine pediatric (T3) 374.00 ng/dL (123-211)
Thyroid-stimulating hormone (TSH) <0.018 uU/ml
Thyroxine (T4) 18.2 ug/dL (5.0-12.0)
Antithyroglobulin antibodies >3000 IU/ml (Negative <60
IU/mL Equivocal 60-100IU/mL Positive >100 IU/mL)
Antithyroid peroxidase antibodies 2667 IU/mL (<60) Anti-
TSH receptor antibodies 69.6 % Inhibit. (<=16.0 Unit: %)
The laboratory findings confirmed the clinical impression and a
diagnosis of Graves's disease (hyperthyroidism with
thyrotoxicosis) was made.
The patient was started on methimazole right away but after
approximately two weeks of treatment she developed severe
adverse reaction to it with significant joint pain and swelling
over her upper and lower extremities with hives; Methimazole
was stopped immediately and she was started on Benadryl and
Advil ; her symptoms improved after few days, although she did
have some residual intermittent hives that were transient.
She has been given some brief course of Prednisone as well, and
Atenolol 50 mg twice a day was also started.

2. After approximately two weeks, due to the fact that the medical
management for hyperthyroidism failed, the patient was
considered to have radioiodine ablation of her thyroid next day
and for that she underwent a thyroid imaging with uptake
showing enlarged thyroid gland, with homogeneous increased
uptake, consistent with Graves disease with 24-hour uptake
equaling 86%.
The patient underwent radio-iodine ablation as scheduled and
she was stable on Atenolol 50 mg twice a day. She was
discharged home.
At her next follow-up appointment in 2 weeks her thyroid
functions tests lab values were as follows:
T4, Free, >12.00 ng/dl (Prepubertal 0.73-1.77 Pubertal/Adult
0.73-1.84)
T3, 1173.00 ng/dL (123-211 ng/dL)
TSH, <0.018 uIU/mL
DISCUSSION:
"Thyrotoxicosis in a Pre-adolescent Patient with Averted
Thyroid Storm Following Radio-pharmaceutically Induced
Therapeutic Lysis of Thyroid Gland"
Laboratory evaluation of thyroid function in various clinical
situations. Adapted from The Merck Manuals, Online Medical
Library, Endocrine and Metabolic Disorder, November 2005
revision
Graves' disease is the most common cause of thyrotoxicosis in
children. The disorder is rare before the age of 3 and increases
progressively with age thereafter. Hyperthyroidism accounts for
10- 15% of all pediatric thyroid disorders and children
constitute 1-5% of all Graves' disease patients. In Graves'
disease, autoantibodies stimulate the thyrotropin receptor and
lead to excess thyroid hormone production.
Thyroid storm is a potentially fatal, though uncommon
condition that affects 1% of individuals with thyrotoxicosis (1),
and accounts for between 1 and 10% of patients hospitalized for
thyrotoxicosis (2,3). It is an exaggerated state of thyrotoxicosis

3. involving decompensation of one or more organ systems and
carries a mortality rate of between 20 and 30% (2).
CAUSES OF THYROID STORM:
Besides thyroid surgery, thyroid storm is triggered by
radioactive iodine therapy, uncontrolled diabetes, emotional
stress, abrupt withdrawal of antithyroid medication, excessive
palpation of the thyroid gland in hyperthyroid patients, thyroid
hormone overdose, pulmonary thromboembolism, toxemia of
pregnancy, labor, trauma, acute infection, severe drug reaction
or myocardial infection (Basic & Clinical Endocrinology, 3rd
Edition, 1991, Greenspan, Francis p. 260-272).
SYMPTOMS:
The clinical manifestations of thyroid storm are those consistent
with marked hypermetabolism. Patients in thyroid storm may
complain of chest pain, palpitations, shortness of breath,
tremor, nervousness, increased sweating, disorientation, fatigue
and fever. Usually there is marked tachycardia, often with atrial
fibrillation and high pulse pressure. On rare occasions
symptoms may progress to heart failure. Central nervous system
symptoms include marked agitation, restlessness, delirium,
psychosis, and coma. Gastrointestinal symptoms include nausea,
vomiting, diarrhea and jaundice. Fatal outcomes, which usually
occur in the elderly, are associated with heart failure and shock.
BIOCHEMICAL CHANGES:
Previously it was thought that the release of stored thyroid
hormone is responsible for thyroid storm. Nowadays it is known
that the blood levels of thyroid hormone are no different from
thyrotoxic patients who are free of thyroid storm symptoms.
Evidence suggests that in thyroid storm the number of binding
sites for catecholamines (epinephrine, norepinephrine, etc.)
increases. Therefore, the heart and nervous tissue have
increased sensitivity to circulating catecholamines. (Greenspan,
1991, p. 252).
Also, there is decreased binding to TBG, the protein which
normally binds with thyroid hormone. Thus there is more
available thyroid hormone in the circulation. The combined

4. effect of excess free thyroid hormone along with increased
catecholamine receptors causes an exaggerated response to
illness, infection or surgical stress that precipitates the acute
symptoms seen in thyroid storm.
RADIOACTIVE IODINE (RAI) therapy and withdrawal of
antithyroid medications are two well described causes of
thyroid storm (4). Thyroid storm following RAI therapy has
generally been attributed to increased thyroid hormone release
from degenerating follicles. Brooks et al. (5, 6) showed that
patients with thyroid storm and uncomplicated thyrotoxicosis
had comparable T4 and T3 levels, but that free T4 was
significantly higher in the patients with thyroid storm. Studies
have shown that after RAI therapy patients pretreated with
antithyroid medications have lower serum T4 and T3 levels than
non pretreated patients (7, 8). These studies also show that
serum T4 and T3 levels increase significantly after withdrawal
of antithyroid medication in preparation for RAI therapy.
Retrospective studies have shown a lower success rate of RAI
therapy in patients pretreated with PTU, but not methimazole (9
-11). In addition, studies have also demonstrated lower RAI
efficacy in patients treated with PTU and methimazole after
RAI therapy (9, 12). Treatment with methimazole before RAI
therapy is beneficial because it does not affect the overall
efficacy of RAI and pretreated patients have lower thyroid
hormone levels than patients treated with RAI alone.
Allahabadia et al. (13) determined that male gender and younger
age of onset of Graves' disease are associated with a higher
failure rate of treatment with antithyroid medication. They also
found that male gender, independent of radioiodine dose and
treatment with antithyroid medication before and after RAI, is
associated with a higher failure rate after a single dose of RAI
therapy.
The dose of 131I is calculated by a standard formula that uses
the estimated weight of the thyroid gland and the 24-h RAI
uptake to determine the dose required for the delivery of 50-200
mCi 131I/g thyroid tissue (14). Hamburger's (15) retrospective

5. study showed that within 6 months of receiving a single dose of
200 mCi 131I/g thyroid tissue, 88% of the children were
euthyroid or hypothyroid. Rivkees et al. (16) recommend that a
single dose of 150-200 mCi