Jod-Basedow effect due to prolonged use of Lugol

Rev. Med. Chir. Soc. Med. Nat., Iaşi – 2014 – vol. 118, no. 4
INTERNAL MEDICINE - PEDIATRICS
CASE REPORTS
JOD-BASEDOW EFFECT DUE TO PROLONGED USE OF LUGOL
SOLUTION-CASE REPORT
Letiţia Leuştean¹, Cristina Preda¹, Maria-Christina Ungureanu¹*,
R. Dănilă², Voichiţa Mogoş¹, Cipriana Ştefănescu³, Carmen Vulpoi¹
University of Medicine and Pharmacy ˮGrigore T. Popaˮ- Iaşi
Faculty of Medicine
1. Department of Medical Specialties (II)
2. Department of Surgery
3. Department of Morpho-Functional Sciences
*Corresponding author. E-mail: [email protected]
JOD-BASEDOW EFFECT DUE TO PROLONGED USE OF LUGOL SOLUTION-CASE
REPORT (Abstract): Graves' disease is the most common form of hyperthyroidism, accoun ting for 60-80% of all cases of thyrotoxicosis. If left untreated, it may lead to severe thyrotoxicosis with cardiovascular, ocular, psychiatric complication, and in extreme cases thyr otoxic crisis with a high mortality rate. We present the case of a 50-years-old woman diagnosed in another service with Graves' disease and treated for many years with antithyroid
drugs (ATDs), admitted to our service for a relapse due to treatment discontinuation. The
surgical treatment was planned and the preoperative preparation with Lugol solution was in itiated. Due to a misunderstanding, the administration of iodine solution was extended for a
period of about 30 days, thus generating the so-called Jod-Basedow effect, with the exacerbation of the manifestations of thyrotoxicosis and risk of thyroid storm. The patient received
treatment with high ATDs doses, glucocorticoids, and beta-blockers, resulting in the progressive improvement of symptoms. She was discharged from hospital and given the risk of
thyrotoxic crisis the surgery was postponed. After a month, the patient underwent thyroide ctomy without preoperative preparation with iodine solution. The operative and postoperative
courses were uneventful. Keywords: GRAVES' DISEASE, SURGICAL TREATMENT,
LUGOL SOLUTION, THYROTOXIC CRISIS
Graves' disease is the most common
form of hyperthyroidism, accounting for
60-80% of all cases of thyrotoxicosis. Its
prevalence is estimated to be about 0.6% of
population, with a female-to-male ratio of
7:8/1. The disease mainly affects young
women, aged 30-60 years (1, 2).
It is an autoimmune disorder due to thyroid receptor autoantibodies (TRAb), also
named thyroid-stimulated immunoglobulins
(TSI), which stimulate growth of the thyroid
gland and overproduction of thyroid hormones. The main clinical manifestations are
hyperthyroidism, diffuse goiter, ocular signs,
and more rarely dermopathy and acropachy
(3). If left untreated it may lead to severe
thyrotoxicosis with cardiovascular, ocular,
psychiatric complication, and in extreme
cases thyrotoxic crisis, with a high mortality
rate of about 20% even in our days (4).
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Letiţia Leuştean et al.
The optimal therapy for Graves' disease
is still a subject of debate. The main treatment options are represented by antithyroid
drugs (ATDs) and ablation therapy: radioactive iodine (RAI) or surgery (5). The
used ATDs are methimazole, carbimazole,
and propylthiouracil. They are acting by
blocking thyroid hormone synthesis and
may also control hyperthyroidism by immune suppression (6). A major disadvantage of ATDs treatment, which has
traditionally been the first-line treatment in
Europe, is the high risk of relapse after
discontinuation (50-80% of patients) (5, 7).
Surgery is an alternative therapeutic option
for Graves' disease in many circumstances.
Total thyroidectomy has negligible recurrence rates and high cure rates (8, 9, 10).
Preoperative preparation with iodine is
used by most surgeons in order to prevent
thyrotoxic crisis and complications during
thyroidectomy (11, 12).
CASE REPORT
We present the case of a 50-years-old
woman, living in an urban area, nonsmoker, diagnosed in 2006 in another service
with Graves' disease. She was treated with
variable doses of methimazole. The patient
was admitted to our service in January
2014 for agitation, sinus tachycardia, significant weight loss, and diarrhea. The
patient discontinued the treatment with
ADTs for 10 months without consulting her
physician. Hormone profile revealed severe
thyrotoxicosis: TSH < 0.004 µUI/ml, FT4 =
4.88 ng/dl, FT3 = 21.1 pg/ml, positive
antithyroid antibodies (AAT) and TRAb.
Thyroid ultrasound: increased thyroid volume (40 ml), intense hypoechoic appearance “hell-likeʺ vascularization. ECG:
sinus tachycardia. Given the long course of
Graves' disease, high thyroid volume and
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high TRAb levels, surgery was recommended. The preoperative preparation with
Lugol solution 20 drops x 3/day for 9 days
was initiated. Due to intercurrent respiratory infection surgery was delayed, but without discontinuing the administration of
Lugol solution; the patient continued the
administration of iodine solution at home
for 30 more days. Readmitted for surgical
treatment, the patient developed more severe symptoms of thyrotoxicosis (pulse =
140/min, intense sweating, agitation), the
surgery being once again delayed, and the
patient transferred to the Endocrinology
Department. Clinical and laboratory assessments confirmed the diagnosis of
Graves' disease; thyroid scan demonstrated
the characteristic features of Jod-Basedow
effect (large thyroid, highly increased thyroid uptake). Cardiac assessment: hyperkinetic heart, without signs of ventricular
dysfunctions (fig. 1, 2).
The patient received treatment with
high
methimazole
doses
(Thyrozol
60mg/day), glucocorticoids (Prednisone 30
mg/day) and beta-blockers (Propranolol 40
mg x 2/day). Due to leukopenia (white
blood cell count to 2730/µl) with neutropenia (neutrophil count to 920/ µl) methimazole administration was temporary discontinued and continued the administration
of corticosteroids with gradual return to
normal of leukocyte formula that allowed
resumption of high ATDs doses. The clinical signs had progressively improved and
the patient was discharged after 14 days.
The surgical treatment was once again
postponed, given the risk of thyrotoxic
crisis. The patient was ambulatory monitored every 2 weeks. In April 2014 thyroidectomy was performed without preoperative preparation with iodine solution. The
operative and postoperative courses were
Jod-Basedow effect due to prolonged use of Lugol solution-case report
uneventful. The patient developed postoperative hypothyroidism, and currently she
is under thyroid replacement therapy. Histopathology confirmed the Graves' disease.
Fig. 1. Thyroid ultrasound showing
an increased thyroid volume (63 ml), intense hypoechoic appearance, ʺhell-likeʺ
vascularization
Fig. 2. Thyroid scan: characteristic features
of Jod-Basedow effect, large thyroid and
highly increased thyroid uptake
DISCUSSION
In patients with Graves' disease treated
for many years with ATDs, with an increased number of relapses, large goiter and
high TRAb level, surgery may be a safe
therapeutic option. Also, surgery provides
rapid treatment and permanent cure of hyperthyroidism in most patients (8). Preoperative preparation of patients with hyperthyroidism to achieve euthyroid state is
extremely important for avoiding perioperative complications due to severe thyrotoxicosis (13). This can be done using a combination of ATDs, beta-blockers and sometimes glucocorticoids (11). Thyroid storm is
an exaggerated state of thyrotoxicosis that
occurs in patients who have an inadequately
treated thyrotoxicosis and a precipitating
event such as thyroid surgery, with a mortality rate that has decreased over time from
nearly 100% to approximately 20% in our
days (4). Most surgeons administer iodine
(as Lugol solution) to provide ≥ 30 mg of
iodine/day for 10 days before surgery to
decrease thyroid vascularity, the rate of
blood flow, and intraoperative blood loss
during thyroidectomy (12). These actions
are explained by the Wolff-Chaikoff effect
of excess iodine, an autoregulatory phenomenon that directly inhibits thyroid hormone
synthesis and release. This effect lasts
around 10 days, after which it is followed by
an ”escape phenomenon”, with resumption
of normal organification of iodine and normal thyroid function (14, 15).
In our patient, the preoperative preparation with Lugol solution was extended for a
period of about 30 days (due to a misunderstanding), thus providing excessive amounts
of iodine to the thyroid gland for a long
period of time, and generating the so-called
Jod-Basedow effect, with the exacerbation
of thyrotoxicosis and risk of thyroid storm.
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Letiţia Leuştean et al.
This condition has a steep onset with fever,
marked tachycardia, and arrhythmias, which
may be accompanied by pulmonary edema,
congestive heart failure, gastrointestinal
dysfunction, and central nervous system
involvement (16,17). Knowledge of these
aspects and careful monitoring of the patient
are extremely important because the diagnosis is mostly clinical, the point at which
thyrotoxicosis becomes thyroid storm being
subjective (17). Even though some authors
have proposed a clinical score to confirm the
diagnosis, in current practice patients presenting with significant symptoms of thyrotoxicosis should be considered as being at
risk for thyroid storm and undergo aggressive treatment, rather than waiting for a
specific score threshold (17, 18). In our
case, the patient presented an impaired general condition with aggravation of the cardiovascular, digestive and mental manifestations of thyrotoxicosis, thus prompt treatment with high doses of ATDs, betablockers, glucocorticoids and sedatives was
initiated in an attempt to block the synthesis
and peripheral conversion of thyroid hormones, and to control the clinical symptoms.
Besides minor adverse effects such as
pruritus, skin rash, arthralgias, and slight
elevations in liver enzymes levels, ATDs
may rarely cause an aggravation of mild
leukopenia that is common in Grave's
disease, with risk of agranulocytosis
(granulocyte count below 500/mm³).
Agranulocytosis may occur even in patients who previously tolerated ATDs, and
multiple exposures may represent a risk
factor for developing hematological disturbances (19, 20). This situation was met
in our patient, who presented under methimazole a worsening of initial leukopenia, with granulocytopenia and risk of
agranulocytosis, which forced us to tem-
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porarily discontinue the administration of
ATDs, and continue only with glucocorticoids, which gradually normalized the
absolute neutrophil count. Normalization
of white blood count allowed us to resume
the treatment with high doses of methimazole, in order to obtain a more rapid improvement of symptoms, by blocking the
synthesis of thyroid hormones.
The clinical symptoms and hormone parameters gradually improved, and the patient was discharged after 14 days of hospital stay.
It is important to know that in thyrotoxicosis ATDs are blocking the thyroid hormone
synthesis, not the release of preformed thyroid hormones. Euthyroidism is obtained only
when intrathyroidal hormone and iodine
stores are depleted, and this process requires
up to 6 weeks. Large goiters with abundant
deposits of thyroid hormone, especially when
iodine excess is present, often show a delayed
response to thioanmides (19, 21). In these
circumstances, knowing the history of massive thyroid iodine load, confirmed by the
increased scintigraphic uptake and the ultrasonographic aspect of the thyroid gland with
high volume and intense vascularization, the
surgical intervention was postponed again,
due to the high risk of thyrotoxic crisis.
CONCLUSIONS
Our case highlights that although preoperative preparation with iodine solution
is preferred by most surgeons in order to
prevent complications during thyroidectomy, this treatment must be performed in
hospital under close supervision by medical
personnel, in order to avoid such complications like Jod-Basedow phenomenon and
thyroid storm. Thus, surgery remains a safe
therapeutic option for Graves' disease in
many circumstances.
Jod-Basedow effect due to prolonged use of Lugol solution-case report
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