Download Iodine-induced hyperthyroidism, or Jod-Basedow

CASE REPORT
Iodine-Induced Hyperthyroidism
(Jod-Basedow Phenomenon)
in the Elderly
Llanyee Liwanpo, MD, Raymond Tang, MD,
and Michael Br yer-Ash, MD, FRCP(Lond), FRCP(C)
I
this phenomenon may be an increasing but underrecognized consequence of modern imaging procedures, which entail larger iodine loads, in the geriatric population.
odine-induced hyperthyroidism, or Jod-Basedow
phenomenon, a thyrotoxic condition caused by
exposure to increased amounts of iodine, has historically been reported in regions deficient in
iodine.1 However, with advances in contrast imaging, this hyperthyroidism has more recently been
reported in patients following studies that require
administration of iodine-containing contrast
media,2-5 but has received little attention in the elderly,6,7 who frequently undergo such studies. The
increasing application of these imaging techniques
to evaluate and prognosticate diseases of advanced
age, in combination with our growing life expectancy, make the geriatric population especially susceptible to the development of Jod-Basedow hyperthyroidism under this clinical setting. We report a case
of Jod-Basedow hyperthyroidism in an elderly
patient with no known prior thyroid disease who
was exposed to iodinated contrast media for cardiac
computed tomography (CT) imaging. Given that
weight loss was the only clinical manifestation of
hyperthyroidism in our patient, we contend that
CASE PRESENTATION
An 83-year-old Caucasian man was referred to the
Endocrinology Clinic of the University of California,
Los Angeles, Healthcare System, complaining of a 7pound weight loss over one week. On initial presentation to his primary care physician, the patient
reported losing approximately one pound per day
with only a modest reduction in his appetite. He
denied insomnia, heat intolerance, or diaphoresis,
nor did he complain of tremor, palpitations, or
change in bowel habit. Approximately 10 days prior
to the visit, the patient underwent elective coronary
imaging, which involved a thin-section CT scan and
administration of an iodinated contrast media. Two
doses (20 mL, then 140 mL) of a contrast agent,
iohexol, were given intravenously. The patient’s medications included dipyridamole/aspirin 200/25 mg 1
tablet daily, atorvastatin 10 mg nightly, tamsulosin
0.4 mg daily, and aspirin 81 mg daily. His past medical history was significant for hypertension, hyperlipidemia, and a right-sided cerebrovascular accident
3 years previously, from which he had recovered full
Drs. Liwanpo and Tang are from the Department of
Medicine, and Dr. Bryer-Ash is from the Department
of Medicine and the Gonda (Goldschmied) Diabetes
Center, Division of Endocrinology, Diabetes and
Hypertension, David Geffen School of Medicine,
University of California, Los Angeles.
Clinical Geriatrics Volume 14, Number 3
33
March 2006
TA B L E I
CASE REPORT
Serial Thyroid Function Test Values
Days after iohexol administration
TSH (0.3-4.7 μIU/mL)
Free T4 by dialysis (0.7-2.2 ng/dL)
Free T3 (210-440 pg/dL)
Total T3 (60-181 ng/dL)
5
0.02
…
…
…
16
<0.02
2.9
454
150
54*
19.2
0.5
172
80
77*
16.9
1.1
237
106
93
8.4
…
…
…
147
6.1
1.2
221
96
188
4.1
…
…
…
TSH = thyroid-stimulating hormone; T4 = thyroxine; T3 = triiodothyronine.
* Patient taking methimazole.
Numbers in bold indicate abnormal values.
… Indicates not performed.
ng/dL (reference range, 1.0-4.4), and suppressed thyrotropin, or thyroid-stimulating hormone (TSH), of
0.02 μIU/mL (reference range, 0.34-5.6). Laboratory
tests obtained at the initial visit to the endocrinology
clinic showed a normal serum chemistry panel and
complete blood cell count, while serum TSH was
undetectable at < 0.02 μIU/mL (reference range, 0.34.7 μIU/mL). Serum free T4 by dialysis was elevated
at 2.9 ng/dL (reference range, 0.7-2.2) and serum free
triiodothyronine (T3) was high at 454 pg/dL (reference range, 210-440). Thyroid-stimulating
immunoglobulin was normal at 92% of basal activity
(reference range, 0-129), but antithyroperoxidase
antibody was elevated at 32.7 IU/mL (reference
range, < 2.0). Thyroid scintigraphy was not performed due to the recent iodine load. Approximately
3 weeks after the initial presentation, TSH determined at an outside laboratory remained undetectable, and methimazole 10 mg daily was prescribed. Serial thyroid function tests (TFTs) are
shown in Table I. On a follow-up visit 7 weeks later,
the patient had returned to his previous weight. At
that time, TSH was elevated at 19.2 μIU/mL, with
both free T4 and T3 levels low, at 0.5 ng/dL and 172
pg/dL, respectively. Therefore, the dosage of methimazole was reduced to 5 mg daily, and later discontinued entirely on day 93. His thyroid function then
gradually returned to the normal range (Table I).
motor function. He denied any family history of
thyroid or other endocrine disease. He had grown
up in Hungary and immigrated to the United States
as a young man.
On physical exam, the patient was a healthyappearing gentleman who was alert and in no apparent distress. His weight was 160 pounds, and height
was 5 feet 4 inches. He was afebrile, with a temperature of 96.7 degrees Fahrenheit. Pulse rate was 80
beats per minute, and blood pressure was 140/60
mm Hg. There was no eyelid lag, stare, exophthalmos, or scleral icterus. Oropharynx was clear. There
was no palpable thyroid goiter, and the gland was
nontender without bruits. Cardiovascular exam was
significant for a grade II over VI systolic murmur
radiating to the axilla and a soft mid-systolic murmur at the upper-left and -right sternal borders. Respiratory and abdominal examinations were unremarkable. Assessment of extremities showed a trace
of pitting edema at both ankles, with no cyanosis or
clubbing. His hands were warm, without tremor or
diaphoresis. Neuromuscular exam revealed symmetrical and normal power and tone, with grossly normal coordination and reflexes.
Laboratory data obtained at an outside laboratory
five days after the cardiac imaging study showed an
elevated total thyroxine (T4) level of 12.8 μg/dL (reference range, 4.5-12.5), elevated free T4 index of 4.9
Clinical Geriatrics Volume 14, Number 3
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CASE REPORT
DISCUSSION
iodine-deficient regions, as well as in individuals
with underlying thyroid pathology, such as
autonomous hyperfunctioning nodules. Therefore, excess iodine does not directly cause thyroid
dysfunction; rather, in the setting of abnormalities, which prevent the gland’s normal adaptation
to excess iodine, it conditions the development of
disease.17 Clinical symptoms of iodine-induced
hyperthyroidism occur days or weeks after exposure. Upon removal of the source of excess iodine,
the condition usually resolves spontaneously.
Anti-thyroid medication may be indicated in
patients severely affected or subjected to a large
iodine load.
Although patients with Jod-Basedow phenomenon are likely to manifest in a clinically similar
manner to those with Graves’ disease, our patient,
who was 83 years of age at the time of diagnosis,
complained only of a 7-pound weight loss during
his initial hyperthyroid phase. Indeed, the lack of
typical symptoms and signs of hyperthyroidism,
also known as apathetic hyperthyroidism, occurs in
about 15% of the elderly population with hyperthyroidism.18 In 1986, Tibaldi et al19 investigated
the condition of thyrotoxicosis in 25 elderly
patients with a mean age of 81.5 years. They
reported the average number of thyrotoxic symptoms to be only two per patient, with the most
common presenting symptom being weight loss,
which occurred in 44%. Martin and Deam18
TA B L E I I
Iodine-induced hyperthyroidism was first described
in 1821 by Jean-François Coindet, at a time when
iodine prophylaxis became widely used for prevention of goiter.8 The term Jod-Basedow was later
coined by Emil Theodor Kocher in 1910.9 Prevalence of this phenomenon has often reflected developments in industry and diet. In 1976, Stewart and
Vidor10 reported an increased incidence of thyrotoxicosis in Tasmania when the dairy industry began use
of iodine-containing disinfectants, thus increasing
the iodine content in milk. From 1965 to 1985,
iodine supplementation in the United States resulted
in increased prevalence of iodine-induced thyroid
dysfunction.11-13 While Jod-Basedow hyperthyroidism still occurs upon ingestion of large quantities
of iodine by persons in iodine-deficient regions,
including Eastern Europe,14 new concerns have arisen in patients undergoing radiographic imaging with
iodine-containing contrast agents, particularly in
those with pre-existing thyroid pathology.2-5 Some
iodide-containing agents that may cause Jod-Basedow hyperthyroidism are shown in Table II.15
Normally, when the thyroid gland is subjected
to a sudden large iodine load, biosynthesis of T4
and T3 decreases due to the inhibitory effect of
iodine on organification and thyroid hormone
formation. This self-regulatory mechanism,
known as the Wolff-Chaikoff effect, temporarily
protects against the production of excess thyroid
hormone.16 Over time, the thyroid gland either adapts to the
Commonly Used Iodide-Containing Contrast Media
increased iodine concentration
Radiographic Contrast Agents
Iodide Content
or escapes from the self-regulatIohexol
140 mg/mL to 350 mg/mL
ing mechanism, resulting in a
Diatrizoate meglumine and sodium
370 mg/mL
Iodized oil
380 mg/mL
rise in thyroid hormone producIopanoic acid
333 mg/tablet
tion. The latter phenomenon
Ipodate
308 mg/capsule
most commonly occurs in
Iothalamate
480 mg/mL
Metrizamide
Clinical Geriatrics Volume 14, Number 3
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483 mg/mL before dilution
March 2006
CASE REPORT
CONCLUSION
examined 60 Australian patients with a mean age of
80.2 years for clinical features of hyperthyroidism.
They also found that weight loss, present in 83% of
patients, was the most common clinical manifestation. All patients in both of these reports had
underlying thyroid disorders, such as Graves’ disease, multinodular goiter, or toxic adenoma.
Indeed, increased susceptibility to iodine-induced
hyperthyroidism has been reported in patients from
iodine-sufficient areas who have autonomous thyroid nodules.2-5,20 Nevertheless, there is also evidence that iodine-induced hyperthyroidism may
occur in patients with no apparent thyroid dysfunction residing in an iodine-sufficient area.21
The course of Jod-Basedow hyperthyroidism
often depends on the underlying thyroid disorder.22 Duration of the hyperthyroid state is usually, though not always, self-limited and generally
resolves within 12 weeks of iodine withdrawal in
patients with or without underlying thyroid
pathology.20,21 Management is directed both at
reduction of symptoms and inhibition of hormone synthesis. Beta-blocking agents, such as propranolol, are indicated when patients exhibit overt
clinical manifestations. Anti-thyroid medications,
such as methimazole, may shorten recovery time if
the load of iodine is large, or if symptomatic
hyperthyroidism does not resolve in a short space
of time. Approaches such as 131iodine ablative
therapy and surgery should be reserved for
patients with large multinodular goiters or recurrent Graves’ disease after the iodine-induced component of the hyperthyroid state has subsided,22 as
such treatment will then be more effective. Prophylactic use of thionamide drugs may be useful
in patients with evidence of thyroid autonomy
prior to contrast administration,23,24 but their use
is not yet routinely recommended.
In this case of iodine-induced hyperthyroidism in
the setting of exposure to iodinated contrast media,
the only symptom of hyperthyroidism exhibited by
this elderly patient was weight loss. Considering the
current trend towards more elective contrast imaging, this condition may become increasingly common. If left undetected, especially in the geriatric
population, iodine-induced hyperthyroidism can
lead to serious cardiac arrhythmias or complications
such as congestive heart failure or embolic stroke. In
these patients, thyroid function evaluation both
prior to and after imaging is recommended. Patients
found to have subclinical autonomy may benefit
from short-term prophylactic therapy. In general,
after administration of a large dose of iodinated contrast media, elderly patients should be monitored for
hyperthyroidism. Treatment is warranted for overt
symptoms and signs of hyperthyroidism or markedly elevated thyroid hormone levels. Given that the
course of this disease depends on the underlying
thyroid pathology, management with anti-thyroid
medications is necessary in certain individuals.
Acknowledgments
This case report was supported by funds from the Leslie
and Susan Gonda (Goldschmied) Family Endowment.
Dr. Inder J. Chopra kindly reviewed and commented
on this manuscript.
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