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Therapeutic Apheresis and Dialysis 15(6):522531


doi: 10.1111/j.1744-9987.2011.01003.x
2011 The Authors
Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

Review Article

Role of Plasma Exchange in the Thyroid Storm


Clotilde Muller1, Peggy Perrin1, Bernadette Faller2, Sarah Richter3, and Francois Chantrel2
1

Department of Nephrology, Nouvel Hpital Civil, Strasbourg, 2Department of Nephrology, Hopital Civil,
Colmar, and 3Department of Nephrology, Clinique Sainte Anne, Strasbourg, France

Abstract: Inadequately treated thyroid storm can lead to


death. Therapeutic plasma exchange (TPE) is a suggested
treatment when conventional treatments fail, but its indication is not well codified. We report our experience
through three explicit cases. Three elderly patients were
admitted to our hospital for cardiac or neurologic symptoms due to thyroid storm. After initiation of conventional
therapy, TPE was performed with clinical and biological
improvement. The speed of symptom resolution varies
depending on the severity. This technique must be carried
out by experienced medical staff as many complications
can occur; nevertheless, in our patients with severe comorbidities, no complications occurred. The action of TPE

mainly results from plasma removal of cytokines, putative antibodies, and thyroid hormones and their bound
proteins. TPE has a transitory effect and thus should be
associated with other thyroid blockers. When there are
threatening symptoms, TPE should be done early, without
waiting for the efficiency of conventional treatment, since it
is the fastest method known for the improvement of the
clinical condition. We also suggest starting TPE in case of
neurologic symptoms because of very slow and incomplete
regression. The Burch and Wartofsky score seems to be
a helpful tool in establishing the diagnosis of thyroid
storm and for deciding on when to initiate TPE. Key
Words: Endocrinology, Plasma exchange, Thyroid storm.

Therapeutic plasma exchange (TPE) is a potential


therapeutic option for thyroid storm, but its indication is not clearly defined. The literature contains
fewer than 100 reported cases and no randomized
studies, and clear guidelines about indication criteria,
the best time to start and duration of this procedure
are lacking.
The thyroid storm is an abnormal state, characterized biologically by extremely elevated serum levels
of circulating hormones leading to multisystem
involvement with specific appearances in every
organ. Its contributing factor is often a physical stress,
such as infection or surgery. Even with treatment,
thyroid storm-related mortality stays high at approximately 30% (1), mainly due to cardiac arrhythmias,
intractable heart failure, and progressive cardiomyopathy. In 1993, Burch and Wartofsky (2) created a
scoring system to standardize the diagnosis of thyroid

storm using the following parameters: body temperature, central nervous system involvement,
gastrointestinalhepatic dysfunction, heart rate, and
the presence or absence of congestive heart failure
and/or atrial fibrillation. The severity of each
symptom correlates with a number of points, with a
maximum score of 140.A score of 2544 is considered
high risk for an imminent storm, and a score >45 is
defined as being diagnostic of thyroid storm.
The three most common treatments for hyperthyroidism are antithyroid drugs, radioactive iodine, and
thyroidectomy. TPE is an alternative treatment that
has been proposed since the 1970s for hyperthyroidism and, more precisely, for the thyroid storm, whatever the etiology (3). TPE has been shown to have a
clear benefit in the thyroid storm induced by Graves
disease, the most common cause of hyperthyroidism
and found especially in the life-threatening forms. Its
efficiency here can be explained by the rapid decline
of plasma hormones and antibodies responsible for
Graves disease (4). Its use was also reported in cases
of amiodarone-induced hyperthyroidism, inefficiency
or toxicity of conventional treatments (such as
leukopenia due to propylthiouracil), Hashimotos

Received March 2011; revised July 2011.


Address correspondence and reprint requests to Dr Clotilde
Muller, Department of Nephrology, Nouvel Hpital Civil, 1 Place
de lHpital, Strasbourg 67000, France. Email: clotilde-muller@
hotmail.fr

522

Role of PE in the Thyroid Storm


encephalopathy (5), hyperthyroidism caused by
molar pregnancy (6) and Graves ophthalmopathy
(713). Thyroid storm can be also caused by surgery
or through the use of radioiodine therapy in unprepared hyperthyroid patients, and TPE is efficient in
preparing for emergency surgery in severe cases (14).
This technique is not indicated when hyperthyroidism is well-tolerated.
We report herein three patients hospitalized at
Colmar Hospital who developed a thyroid storm and
were treated with TPE. We used the filtration mode
with a dialyzer and a central venovenous access. The
replacement solution was mainly albumin. After
describing our experience in the resolution of these
cases and reviewing the literature (Table 1), we
propose some recommendations.
PATIENTS AND METHODS
Patient 1
A 61-year-old man was hospitalized in Colmar Hospital for thoracic pain and dyspnea on June 2009. He
had a past history of ischemic cardiomyopathy and
had undergone double by-pass graft surgery and multiple stenting. An episode of recurrent ventricular
tachycardia two years before was treated by amiodarone, with a normal TSH level at this time. A few
weeks before hospitalization, a flutter appeared while
on bisoprolol and amiodarone. Hyperthyroidism was
detected and treated with carbimazole 20 mg three
times a day and potassium perchlorate 600 mg per day.
On admission, the arterial pressure was 150/
78 mm Hg, the heart rate was 87/min with arrhythmia, and he was afebrile. His cardiac symptoms
were related to hyperthyroidism. The serum concentrations for free triiodothyronine (FT3) were
10.78 pmol/L (laboratory reference range (RR), 3.1
6.2) and for free thyroxine (FT4) 99.8 pmol/L (RR,
921.9) (Immunochemiluminescence; Beckmann,
Palo Alto, CA, USA). He had no renal insufficiency
or electrolyte abnormalities, and echocardiography
showed a ventricular ejection fraction of 66% (using
Teichholzs formula). His score according to Burch
and Wartofsky (2) was 20 to 140, so he was not considered to be at risk of a thyroid storm.
Since admission, antithyroid drugs were optimized
with carbimazole 20 mg six times a day, potassium
perchlorate 1000 mg per day, corticosteroid 30 mg
per day, and propranolol was given instead of bisoprolol.TPE was started 16 days after admission as the
conventional treatment was showing no efficiency in
controlling his life-threatening and crippling cardiac
symptoms (that is, the severe arrhythmia). The score
was 30140 at this time, as a moderate hepatic dys 2011 The Authors
Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

523

function had appeared. Four successive TPE sessions


were performed in eight days (Fig. 1). The FT4 level
decreased sharply after each session, with a total
reduction of 65% at the end of the treatment,
whereas the TSH increased progressively. No complications occurred. Two weeks later, his clinical state
was stable without any cardiac arrhythmias, and a
thyroidectomy was performed under good conditions
and without complications. The entire thyroid was
removed and found to be slightly increased in size,
hard, and fibrous.
This patient presented with type 2 amiodaroneinduced hyperthyroidism without an admission score
considered at risk. Nevertheless, he developed a
thyroid storm with cardiac symptoms in the foreground. Because of failure of conventional therapy,
TPE was performed and succeeded in significantly
reducing the thyroid hormone serum concentrations
and in controlling the cardiac symptoms. Thanks to
this technique, a stable state was quickly obtained,
which enabled the radical surgical treatment to be
performed safely.
Patient 2
A 74-year-old man with a past history of hypertension, atrial fibrillation treated with amiodarone,
and two ischemic strokes was admitted on February
2001 for a confusional state with anorexia and
insomnia. A cerebral CT scan at admission showed
only the sequelae of his previous strokes. Several
days later he developed fever and loss of consciousness. Despite antibiotic therapy, his temperature
increased to 39.5C and he also developed dyspnea
with a respiratory rate of 44 breaths/min, tachyarrhythmia at 150 beats/min, clinical signs of dehydration, and blood pressure of 105/75 mm Hg. The
neurological examination showed amyotrophia,
absent reflexes, hypotonia, and minimal response to
pain stimuli.
Biological investigations revealed the following:
TSH < 0.01 mIU/L (RR 0.343.80), FT4 > 103 pmol/L,
FT3 > 38.5 pmol/L, hypernatremia (Na+ 158 meq/L),
hyperkalemia (K+ 5 mmol/L), acute renal insufficiency (serum creatinine 1.6 mg/dL, urea 84.5 mg/dL),
cytolysis at twice the normal level, and respiratory
acidosis (pH 7.31, pCO2 55 mm Hg). The Burch and
Wartofsky score was high at 100140. Since thyroid
antibodies were negative and the ultrasound was
normal, type 2 amiodarone-induced hyperthyroidism
was suspected.
Mechanical ventilation was required due to his
respiratory distress and neurological problems.
Carbimazole was introduced after admission (as
methimazole is not available in France) and TPE

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524

C Muller et al.
TABLE 1.

Authors

Review of the literature: black citations concern systemic manifestations, blue citations concern
ophthalmologic manifestations
Number
of cases

Median number of
TPE/median volume
replacement per patient

Indication

Ashkar et al.
1970 (3)
Herrmann 1973 (15)

6/3 L

Cardiac symptoms

5/2.65 L

Cardiac and neurological


symptoms

Horn 1976 (16)

1/5 L

Neurological symptoms

Gabry 1981 (17)


Martin 1981 (18)

1
1

2/2.5 L
1/4 L

Ogriseg 1981 (19)

3/8.1 L

Before surgery
Cardiac, neurological and
ophthalmological
symptoms after surgery
Cardiac and neurological
symptoms

Van de Vyver 1982


(20)

3/8.4 L

Cardiac and neurological


symptoms

Shigematsu 1982
(21)

1/3.8 L

May 1983 (22)

1/4.8 L

Resistance to conventional
antithyroid drugs,
agranulocytosis
Thyroid hormone
intoxication

Patte et al.
1983 (23)

2/3.4 L

Newcomer 1983
(24)

1/4 L

Tajiri 1984 (25)

2/7.2 L

Cardiac and
ophthalmological
symptoms

Sprenger 1985 (26)

3.5/2.63.8 L
per exchange

Thyrotoxicosis

Schlienger et al.
1985 (27)

2.75/40 mL/kg

Thyrotoxicosis

Braithwaite 1986
(28)

3/5.5 L

Geissler 1987 (29)

2/6 L

Binimelis et al.
1987 (30)

3.25/3.84.5 L

Thyrotoxicosis after
thyroid iodine
irradiation and
conventional drugs
Hematological symptoms
and before surgery
Thyrotoxicosis with
neurological and cardiac
symptoms

Segers 1988 (31)

4.6/2.5 L each time

Thyrotoxicosis

De Rosa et al.
1991 (4)

3/6.3 L

Thyrotoxicosis with
ophthalmopathy, and
before surgery

Ther Apher Dial, Vol. 15, No. 6, 2011

Cardiac and neurological


symptoms with
conventional drug
resistance
Cardiac and neurological
symptoms

Response
Clinical improvement in 4872 h and
diminution of TT3 by 2280%
Clinical and biological amelioration,
patients successfully treated by the last
plasma exchange; 40% decrease in TT3
and 56.6% decrease in TT4
Clinical improvement and biological
improvement with significant fall in the
free hormones (633 mg FT4 and 13.6 mg
T3)
Clinical improvement in 48 h
Clinical improvement in less than 24 h; 25%
decrease in TT4
Clinical and biological improvement with a
decrease of 18.5 mg and 10 mg of TT3 and
TT4, respectively
Clinical and biological improvement with
the extraction of 530 mg of T4 and 2.8 mg
of T3
Clinical improvement after TPE, but no
change observed in TT3 or TT4
Clinical improvement immediately after
TPE and biological improvement (43%
decrease in TT4 and 68% decrease in
TT3)
No amelioration, plasma exchange not well
tolerated, with underlying cardiac disease
threatening
Biological improvement (decrease of 64%
TT3 and 54% TT4) and clinical
improvement in 24 h
Clinical improvement in 48 h, biological
improvement (decreases of 8.5% FT4,
27.4% FT3, and 15% TT3, but no
decrease in TT4)
39% decrease in TT4 in the first case; 53%
decrease in TT4 immediately after TPE in
the second case, with 80% after a few
days
7/8 showed clinical improvement, biological
improvement with almost no
improvement in FT3 or FT4, but
amelioration with decreases of 43% of
TT3 and 37% of TT4
Clinical improvement with cure in four days
and biological improvement (decreases of
76% of T3, 56% of T4, and 39% of FT4)
Clinical and biological amelioration;
decreases of 25% of TT3 and 17% of TT4
Biological and clinical improvement; thyroid
hormone normalization in
approximately15 days; >50% decreases in
TT3 and TT4
Clinical and biological improvement:
approximately 63.5% decrease in FT3
and 57.8% in FT4; one relapse after one
week
Biological improvement with decreases of
51% FT3, 47% FT4, 60% TT3, and 53%
of TT4

2011 The Authors


Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

Role of PE in the Thyroid Storm


TABLE 1.

Authors

Number
of cases

Median number of
TPE/median volume
replacement per patient

Continued

Indication

Response
Biological improvement: decreases of 75%
TT4, 75% FT4, 78% FT3 (nothing for
TT3); amiodarone rate decreased too, but
then it rose again after TPE stopped
Biological amelioration with decreases of
40% TT3, 31% FT3, 27.2% TT4, and
14.4% FT4
Controls were six euthyroid patients:
decreases in TT4 and TT3 blood levels
(39% and 47%, respectively), more marked
for TT3, related to the removal of TBG
(thyroxine-binding globulin); FT3 and FT4
remained unchanged (6% decrease in FT4)
Transient clinical improvement, decreases of
approximately 7075% FT3, and 30% FT4,
no range normalization; and decreases of
60% TT3 and 4045% TT4
No clinical or biological improvement;
decreases of 84% FT4 and 58.5% FT3
immediately after TPE, but with
subsequent rises afterwards
Failure of treatment due to the death of the
patient; at first biological amelioration of
TT3 and TT4 was experienced, but
afterwards the rate rose again to levels
higher than previously
Little effect on plasma level (0% and 33%
decreases in FT4, and 7% and 18%
decreases in FT3) and no effect on the
hyperthyroid state
Clinical and biological improvement, with a
subsequent relapse; no FT3, FT4, TT3, or
TT4 samples taken

Uzzan 1991 (32)

5/22.5 L

Thyrotoxicosis with cardiac


and muscular symptoms

Puy et al. 1992 (33)

3/3.5 L

Severe hyperthyroidism
and cardiac failure

Schlienger 1992 (34)

11

2.9/ND

Thyroid storm or
persistent thyrotoxicosis

Aghini-Lombardi
et al. 1993 (35)

2/4 L

Thyrotoxicosis

Henderson et al.
1994 (36)

2/4 L

Thyroxine overdose

Samaras and Marel


1996 (37)

5/ND

Thyrotoxicosis with cardiac


symptoms

Ligtenberg et al.
1999 (38)

ND/ND

Before surgery and


tachycardia

Boers and
Colebatch
2001 (5)

3/21 L

Nieuwenhuis 2004
(39)

3/ND

Resistance to conventional
antithyroid drugs
with neurological
manifestations
Severe neurological
symptoms

Diamond 2004 (40)

2.3/7.5 L

Before surgery, TIA

Kokuho et al.
2004 (41)
Ozbey 2004 (42)

1/3.4 L

Guvenc 2004 (43)

3/11.5 L
per exchange
3/7.5 L

Resistance to conventional
antithyroid drugs
Before surgery

Erbil 2006 (44)

3/ND

Resistance to conventional
antithyroid drugs and
heart failure
Preparation for surgery

Azezli 2006 (45)

3/6 L

Preparation for surgery

Pasimeni 2008 (46)

2/6 L

Resistance to conventional
antithyroid drugs

Adali et al. 2009 (6)

2/ND

Ezer et al. 2009 (14)

11

Resistance to conventional
antithyroid drugs, major
bleeding
Before surgery

3.3/

2011 The Authors


Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

525

Clinical and biological improvement (ND);


six months recuperation; reduction in the
level of antibodies to normal
Clinical stabilization before surgery; one
patient had no biological amelioration, the
other two had average decreases of 40%
FT3 and 35% FT4 (TT3 and TT4 ND)
Clinical amelioration in 3 h, with decreases of
25% FT4 and 15% FT3
Biological amelioration: mean decreases of
65% TT3 and 75% FT4
Clinical and biological amelioration;
decreases of 58% FT3 and 67% FT4
Biological improvement, with decreases of
43% FT3 and 26% FT4
Biological improvement, with decreases of
75% FT3, 64% FT4, 66% TT3, and 51%
TT4
Clinical and biological amelioration: decrease
of 29% FT4, but no amelioration of FT3
(TT3 and TT4 ND)
Biological amelioration: decreases of 33%
FT3 and 17.5% FT4
Improvement in thyroid symptoms; safe
preparation of patients before surgery, with
mean decreases of 76% FT3 and 44% FT4
(TT3 and TT4 ND)

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C Muller et al.
TABLE 1.

Authors

Number
of cases

Muller 2011

Glinoer and
Schrooyen
1987 (11)
Glinoer et al.
1988 (12)

11

Median number of
TPE/median volume
replacement per patient
4.6/2.5 L
per exchange
4/510 L

4/8.510 L

Dandona et al.
1979 (7)
Glinoer 1981 (47)

34/23 L

4/10 L

De Rosa 1982 (48)

4/8 L

Kuzuya and
Degroot
1982 (10)
Sawers et al.
1981 (8)
Yamamoto et al.
1982 (9)

15/ND

3/ND

4/5 L

Continued

Indication
Resistance to conventional
drugs, cardiac and
neurological symptoms
Severe ophthalmopathy
with no response to
traditional treatment
Severe Graves
ophthalmopathy
Ophthalmological
symptoms
Ophthalmological
symptoms
Ophthalmological
symptoms
Ophthalmological
symptoms
Ophthalmological
symptoms
Severe ophthalmological
symptoms

Response
Biological and clinical amelioration: mean
decreases of 55% FT4 and 26% FT3
immediately after TPE sessions
Clinical improvement in 91% of the
patients; four relapsed at six months
8/9 clinical improvement; three relapses one
year after treatment, successfully treated
again by TPE
Clinical amelioration in 48 h
Clinical amelioration in 15 days
Clinical improvement, but three relapsed at
six months
No clinical improvement
Clinical improvement with adjuvant
immunosuppressive therapy
Clinical improvement soon after the end of
TPE, but with a further increase in pain
two weeks later

TIA, transient ischemic attack; FT3, free triiodothyronine; FT4, free thyroxine; ND, not determined; TPE, therapeutic plasma exchange;
TT3, total triiodothyronine; TT4, total thyroxine.

was carried out two days later for a total of six


exchangesevery day for three days and then every
48 h. The level of FT4, which was initially very high,
decreased under the superior threshold only after six
TPE sessions. A rapid FT3 reduction was also seen
(Fig. 1). Steroids and potassium perchlorate were
introduced, as well as propranolol, after the exchange
procedure to control mild tachycardia. The patient
left the intensive care unit (ICU) on 5 mg prednisone
per day and propranolol; the potassium perchlorate
and carbimazole were discontinued.
His clinical picture slowly improved; the patient
recovered consciousness within three weeks after
TPE and his muscle tone returned one month later.
Nevertheless, his respiratory status required a tracheostomy one month after admission. No radical
treatment was planned after this event. The normalization of the thyroid hormone serum concentrations
was obtained after more than one month and thyroid
treatments were stopped. No more complications
occurred during this period.
In this second case of amiodarone-induced thyroid
storm with a very high risk score,TPE was initiated as
first-line therapy in conjunction with conventional
treatment. It offered benefits with a rapid resolution
of cardiac symptoms and a slow (over one month)
but effective recovery of his initially severe neurologic state.

Ther Apher Dial, Vol. 15, No. 6, 2011

Patient 3
An 85-year-old woman was admitted for hyperthyroidism on September 2002. She had a history of
giant cell arteritis, polymyalgia rheumatica, hypertension, and valvular and ischemic cardiomyopathy with
conduction and rhythm impairment. A multinodular
goiter with hyperthyroidism had been treated with
radioactive iodine in 1992 with stable hormonal
levels thereafter.
One month before admission, an aortic valve
replacement and a mitral valvuloplasty were performed because of recurrent pulmonary edema. In
the postoperative days, the patient became asthenic
and blood tests revealed a high FT4 at 42.3 pmol/L
and a low TSH concentration at 0.005 mU/L. Despite
the introduction of carbimazole, she presented with
tachycardia (120 beats/min) and severe amyotrophia.
Propranolol was introduced; however, her clinical
status worsened with the onset of confusion, requiring admission to the ICU nine days later.
In the ICU, she was found to be thin with mild
exophthalmia. She presented with atrial fibrillation,
tachypnea (50/min), with rales in the right lung.
Her blood pressure was 130/80 mm Hg. Neurologic
examination found an isolated confusion. Biologically, there was no acidosis or electrolyte imbalance.
FT4 was increased to 80 pmol/L and FT3 to
14.3 pmol/L; TSH was undetectable; thyroid antibod 2011 The Authors
Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

Role of PE in the Thyroid Storm

527

FIG. 1. Free triiodothyronine (FT3) and free thyroxine (FT4) serum concentrations during hospitalization
in the intensive care unit for each patient. B, before
a session of therapeutic plasma exchange (TPE);
and A, after TPE. RR: FT3: 3.16.2 pmol/L; FT4:
921.9 pmol/L.

ies were negative. The Burch and Wartofsky score


was high at 75140. Because of history of multinodular goiter and discrete exophthalmia, a recurrence of
the goiter or Graves disease was suspected.
As her respiratory state worsened, with severe
hypoxemia and persistent tachyarrhythmia, daily
TPE was started with four exchanges. Ten days
after admission, as the levels of thyroid hormone
normalized and the clinical outcome was favorable,
2011 The Authors
Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

treatment with carbimazole was switched for propylthiouracil with a tapering dose (Fig. 1). No radical
treatment was performed.
In this case, TPE was justified by the high score, the
failure of one months conventional therapy, and the
appearance of precarious respiratory and cardiac
states. In this elderly patient with severe cardiomyopathy, TPE allowed a favorable outcome without
complications.

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C Muller et al.
DISCUSSION

The therapeutic benefit of TPE results from the


removal of the potential pathological substances
from the thyroid storm: hormones, autoantibodies
(i.e. Graves disease), catecholamines (released by
the sympathetic system), cytokines (which mediate
inflammation), toxins, and so on. The metabolically
active part of the hormones is free, but over 99.5%
of T4 (Thyroxine) and T3 (Triiodothyronine) are
protein bound in the serum. TBG binds approximately 80% of circulating hormones; transthyretin
and albumin are minor protein binders (49); albumin
binds 10% of T4 and 20% of T3 (33). This technique
decreases the effects of thyroid hormones by removing free thyroid hormones and, moreover, by replacing carrier proteins by unsaturated bound proteins
of the replacement solution. TPE also removes
5-monodesiodase which converts T4 to T3 and this
removal lessens T3 production (50). Nevertheless
TPE has to be associated with an adjunct treatment
to stop the synthesis of these components.
These three cases illustrate the efficiency and
rapidity of action of plasma exchange in the thyroid
storm. TPE has allowed us to observe favorable biological and clinical effects. After analyzing these
examples and reviewing the literature (Table 1) we
are able to suggest several recommendations.
In the first and third cases, we noticed a dramatic
reduction of the free T3 and T4 serum concentrations
after the TPE procedures (with a total reduction of
65% of FT4 in the first case, and of 46% for FT4 and
27% for FT3 in the third case). In one study, Puy et al.
report a total extraction of FT4 and FT3 from
between 20 to 60% and between 20 to 40%, respectively, for TBG after three exchanges (33). Binimelis
et al., in a small study on six patients, depict a disappearance rate of total thyroxine (TT4) that is 30-fold
greater with TPE than with standard medical treatment. This effect was proportional to the serum level
of TT4 (30). In the same way, we saw in the second
patient that FT4 could not be quantified, hiding the
fact that FT4 was extremely high, thus explaining why
reaching normal levels and TPE efficacy need several
weeks.
In cases 1 and 2, with amiodarone-induced hyperthyroidism, the efficiency of TPE can also be
explained by the fact that it removes amiodarone
from the circulation. Amiodarone and its active
metabolite are highly bound to plasma proteins
and cannot be cleared by hemodialysis, but only by
plasma exchange.
In our observations, thyroid hormone levels have a
tendency to rise again in the next day after TPE. In

Ther Apher Dial, Vol. 15, No. 6, 2011

some cases the FT3, FT4, and TSH do not decrease


during the procedure and may even increase (30,33).
This phenomenon is explained by a mobilization
effect from the extravascular compartment and the
establishment of a new equilibrium between free and
intracellular rates (27). Nevertheless, even if the
T3 and T4 concentrations still stay high, clinical
improvement can be seen (1).
In our first and third cases we simultaneously
observed the biological and clinical amelioration of
cardiac and neurological symptoms at the end of the
TPE procedures. In all three cases reported herein
there were cardiac manifestations with problems in
reducing tachycardia and managing the arrhythmia.
TPE decreased both the thyroid rate and controlled
the cardiac symptoms within a few days, when conventional therapy had failed. We observed that
cardiac symptoms are more likely to regress faster
than the neurological ones.
In our patient who was in a coma (patient 2), we
observed slower recuperation requiring three weeks
for the coma to resolve. We hypothesize that thyroid
hormone removal is greater in the circulation, but
that the bloodbrain barrier could prevent intracerebral hormone removal. We speculate that in such
cases with severe neurological impairment, improvement requires a longer time after a TPE session.
The mechanisms underlying reversible neurological
symptoms are as yet unknown, and the recuperation
seems to be variable between patients. As was the
case with our patients, some authors describe very
late improvement, up to six months after the procedure (23).
An unexpected action of TPE with clinical
improvement a few hours after the first TPE session
is frequently reported (27,35). TPE improves the
clinical symptoms (especially cardiac ones) of the
thyroid storm rather than decreasing the thyroid
hormone rates (3). Kokuho et al. reported their experience with a woman with a thyroid storm that was
resistant to methimazole, Lugols solution, propranolol, and digoxin: as she had a body temperature of
39C and tachycardia, TPE was performed and
immediately, after 3 h, the cardiac rhythm slowed and
the fever decreased (41).
Some reports have described the failure of TPE
to control thyroid storm in different cases such as
Graves disease, amiodarone-induced thyroid storm,
or hormone overload (10,23,3638). TPE appears to
be inefficient in hormone overload in Henderson
et al.s study as it had removed only 7% of the
ingested dose (36). In Samara et al.s report, renal
and hepatic impairment would have played a role in
the failure of TPE (37), while in Kuzuya et al.s case,
2011 The Authors
Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

Role of PE in the Thyroid Storm


TPE was partially efficient, but exophthalmos was
certainly too much evolved (10), and in Patte et al.s
study, TPE was stopped because of cardiac instability
during the exchange (23). In several cases, TPE has
failed because of the great severity of symptoms
already present at diagnosis. TPE should be conducted as early as possible in order to be efficient.
The usual association with other drugs, such as glucocorticoids and/or cytotoxic medications, makes it
difficult to differentiate the contribution of TPE in
these clinical improvements. In the second patient,
we could speculate as to the particular extent of each
of the separate actions of TPE and carbimazole;
however, they were probably both effective and their
effects synergistic.
TPE is a recommendation of grade IIc and a category III in the last American Society for Apheresis
(ASFA) document (51). TPE should be performed in
the following indications: severe symptoms (such as
cardiothyrotoxicosis, as in the first case, neurological
manifestations, impairment of consciousness, as in
the second case, and severe myopathy), rapid clinical
degradation, contraindications to other therapies
(agranulocytosis, renal insufficiency, asthma, heart
failure, as so on), and failure of conventional therapeutics. Before emergency surgery, it can also be used
to stabilize the patient.
When treating a thyroid storm, we suggest calculating the Burch and Wartofsky score (2), and if it is
higher than 45, to envisage early TPE before the
emergence of life-threatening cardiac symptoms or
neurological symptoms, especially as regression is
slow and sometimes incomplete in the latter. If the
score is less than 45, conventional therapies can be
tried first. As in the first case, TPE was performed
after failure of conventional treatment and as the
score worsened. In our cases, TPE was beneficial,
even if the patients were elderly (patient 3 was
85 years old). The past history of the patient is not a
limiting factor and the technique, when well done,
seems to be safe no matter what the patients age and
comorbidities are.
As per the ASFA recommendations (51), we recommend that TPE should be performed daily until
clinical improvement is noted and with 4050 mL/kg
of replacement solution. FT3 and FT4 should be
sampled before and after each session, without stopping TPE if no decrease occurs, because of the
biologicoclinical dissociation.
The overall incidence of adverse effects of this
technique, which are mostly reversible, is about 5%.
Notable side effects include transfusion reaction,
citrate-related nausea and vomiting, vasovagal or
hypotensive reactions, respiratory distress, and
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Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

529

tetany or seizure. Death is rare and usually due to


the underlying disease (52). TPE remains a very
harsh technique (mainly infectious complications
are reported (30)) that can be implemented in case
of thyroid storm, and not in simple hyperthyroidism
cases.
CONCLUSIONS
We report herein three cases that emphasize the
efficiency and safety of TPE treatment in the case of
severe hyperthyroidism symptoms with cardiac or
neurological complications, even in an elderly
patient. Retrospectively, we calculated the Burch and
Wartofsky score, which seems to be a helpful tool in
making a diagnosis of thyroid storm and for deciding
when to initiate TPE. We suggest also starting TPE if
neurological symptoms are present because of their
very slow and incomplete regression, and, moreover,
if manifestations are severe.
It can, of course, be used as a rescue treatment if
traditional medical treatments are contraindicated or
ineffective. When there are threatening symptoms,
the efficiency of conventional treatments should not
be awaited, because TPE is the fastest method to
improve the patients clinical condition. It is also particularly useful in amiodarone-induced pathology.
TPE has a transitory effect and thus several sessions
should be performed, and it should be associated with
other thyroid hormone antagonists. It is a relatively
safe therapy, although it has a high associated cost.
Monitoring the thyroid hormones is interesting, but
clinical improvements are often dissociated from the
hormonal levels and must be mainly judged on the
patients condition. A randomized study is needed to
explore the benefits of initiating treatment earlier, at
diagnosis of a thyroid storm, according to the symptoms and the Burch and Wartofsky score.
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