Carbimazole-Induced abnormalities of liver damage.
This "surprising" lack of reports1,2
Cholestatic Hepatitis
To the Editor.\p=m-\Inthe August 1985
issue of the Archives, Blom et al1
reported a case of carbimazole-induced
intrahepatic cholestasis and stated
that this condition has been reported
on only three previous occasions.2-4
We have found two additional reports5,6
on cholestatic effects of carbima-
zole, probably because carbimazole is
mainly used in Europe, as is methima-
zole in the United States. In this re-
port, we describe a case of cholestatic
hepatitis induced by carbimazole.
Report of a Case.\p=m-\Ourpatient was a 45\x=req-\
year-old woman with a toxic thyroid nod-
ule. Carbimazole therapy, 20 mg/d, was
started before thyroidectomy. Ten days
later, jaundice developed. Physical exami-
nation revealed hepatomegaly (2 cm below
the costal margin) and laboratory evalua-
tion disclosed the following values: total
bilirubin, 1.8 mg/dL (30.78 \g=m\mol/L (con-
jugated, 0.8 mg/dL [13.68 \g=m\mol/L]); alka-
line phosphatase, 241 IU/L (normal, 30 to
140 IU/L; \g=g\-glutamyltransferase, 157 IU/L
(normal, 12 to 25 IU/L); aspartate ami-
notransferase, 370 IU/L (normal, 1 to
60 IU/L); and alanine aminotransferase,
560 IU/L (normal, 1 to 60 IU/L). Tests for
hepatitis virus were negative. Ultraso-
nography provided normal images of the
liver and upper abdomen. Carbimazole
therapy was withdrawn, and 15 days after
the onset of symptoms, the liver function
test values have returned to normal.
Two months later, her family physician
prescribed carbimazole therapy again. Six
hours after the first dose (5 mg), nausea,
vomiting, and pain in the hepatic region
developed, and, approximately 48 hours
later, she noticed progressive jaundice.
The bilirubin level was 2.8 mg/dL
(47.88 µ /L) (conjugated, 1.6 mg/dL
[27.36 µ /L]); alkaline phosphatase,
196 IU/L; 7-glutamyltransferase, 119 IU/L;
aspartate aminotransferase, 355 IU/L; and
alanine aminotransferase, 490 IU/L. A per¬
cutaneous liver biopsy was performed on
the tenth day after starting carbimazole
treatment. Histopathology of the liver
showed mild intracanalicular cholestasis
and ceroid-loaded macrophages around the
central intralobular vein; portal tracts
were widened by an inflammatory infiltrate
in which lymphocytes, neutrophils, eosin¬
ophils, and periodic acid-Schiff diastase-
resistant macrophages were present. At
day 17 after the onset of this second epi¬
sode, the patient was asymptomatic and
biochemical evidence of liver damage re¬
solved.
Comment.—The diagnosis of he¬
patic injury induced by carbimazole is
supported either by positivity of lym¬
phocyte transformation test1,2 or by
histopathologic study of the liver after
administration of the drug.36 In our
patient, there was a clear relationship
between the use of carbimazole and the
appearance of clinical and biochemical
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now
was confirmed by the effect of re-
challenge with 5 mg of carbimazole
that precipitated jaundice and dis¬
turbed liver function once more, sug¬
gesting hypersensitivity mechanisms
in the pathogenesis of the hepatotoxic
reaction.
Liver lesions seen in our biopsy ma¬
terial were comparable with those no¬
ticed by other authors7,8 in cases of
carbimazole-induced cholestatic hepa¬
titis. The picture of hepatocellular cho¬
lestasis and ceroid-loaded macro¬
phages around the central vein was
consistent with drug toxicity. It is
interesting that hepatitis due to meth-
imazole, a metabolite of carbimazole,
is more common and severe than car¬
bimazole-induced cholestatic hepati¬
tis.3,5
C. Aynsa, MD
R. Diaz de Otazu, MD
J. M. Cia, MD
Vitoria, Spain
1. Blom H, Stolk J, Schreuder HB, et al: A case
of carbimazole-induced intrahepatic cholestasis:
An immune-mediated reaction? Arch Intern Med
1985;145:1513-1515.
2. Prost G, Dechavanne M, Levenq P, et al:
Ict\l=e`\recholestatique d\l=u^\au carbimazole. Nouv
Press Med 1973;2:2479.
3. Lunzer M, Huang S-N, Ginsburg J, et al:
Jaundice due to carbimazole. Gut 1975;16:913-917.
4. Dinsmore WN, O'Hara MD, Callender ME:
Postanesthetic carbimazole jaundice. N Engl J
Med 1983;309:438.
5. Jenkins RM, Evans DMD: Carbimazole hy-
persensitivity and liver damage. Br J Clin Pract
1981;35:415-417.
6. Efstratuadis N, Holzberg R, Schmidt W,
et al: Toxische cholestatische hepatose durch
Thiamazol und Carbimazol. Dtsch Med Woch-
enschr 1982;107:1531-1533.
7. Zimmerman HJ: Hormonal derivatives and
other drugs used to treat endocrine disease, in
Zimmerman HJ (ed): Hepatotoxicity: The Ad-
verse Effects of Drugs and Other Chemicals on
the Liver. New York, Appleton-Century-Crofts,
1978, pp 436-467.
8. Zimmerman HJ, Ishak KG: Hepatic injury
due to drugs and toxins, in MacSween RNM,
Anthony PP, Scheuer PJ (eds): Pathology of the
Liver. New York, Churchill Livingstone Inc,
1979, pp 335-386.
In Reply.\p=m-\ \p=m-\Weare obliged to Ayensa
et al for finding two recent references
concerning carbimazole-induced cho-
lestasis. The suggested mechanism of
a hypersensitivity reaction is sup-
ported by their case report and the
additional references. Histopathology
has been obtained in all cases and was
consistent with drug toxicity, be it still
unspecific. In their own case also re-
challenge was done, be it accidental.
We do not think the evidence avail-
able up to now warrants their state-
ment that hepatitis due to meth-
imazole is more common and severe.
We expect the same incidence and the
same severity for carbimazole. The
seems to be already equalized.
Harmjo Blom, MD
Hendrik B. Schreuder, MD, PhD
Amsterdam
1. Lunzer M, Huang S-N, Ginsburg J, et al:
Jaundice due to carbimazole N Engl J Med
1983;309:438.
2. Jenkins RM, Evans DMD: Carbimazole hy-
persensitivity and liver damage. Br J Clin Pract
1981;35:415-417.
Medical Identification
To the Editor.\p=m-\Wefrequently encoun-
ter patients with thoracic, abdominal,
or pelvic surgical scars who have no
recollection of what procedures have
been performed, or who the surgeon
was. Such information is often conve-
nient, and, occasionally, critical, to the
planning of another surgical proce-
dure. Given that the population of
America is both aging and mobile, and
that patients are surviving far long-
er postoperatively\p=m-\especiallyafter
gynecologic surgery for benign or for
malignant disease\p=m-\wehave a modest
proposal on behalf of surgeons practic-
ing in clinics, hospitals, or emergency
rooms.
A minute tattoo, only a dot or a bar,
or a combination of these, might be
placed by the operating surgeon on the
sides of a patient's toes, according to a
nationally agreed on designation. For
instance, a dot and a bar on the medial
aspect of the second right toe might
indicate "total abdominal hysterec-
tomy/salpingo-oophorectomy"; a simi-
lar tattoo without the dot might indi-
cate "hysterectomy without oophorec-
tomy." Any tattoo in red, as opposed to
blue, would indicate malignant find¬
ings at pathologic examination. A code
might easily be established for the 50
or 60 most commonly performed ab¬
dominal or pelvic operations. Such tat¬
tooing would, of course, be completely
voluntary. Precedent exists for this,
with tiny dots being tattooed on the
chests of young persons who have had
radiation ports for the treatment of
lymphomas.
Cosmesis would probably be of little
significance in patients of mature
years. One of us (J.R.) has been hap¬
pily married to a lovely woman (also a
physician) for over three years, and
has not, to this day, ever looked be¬
tween her toes. In addition, he bears
surgical scars from a radical orchiec-
tomy (to rule out testicular malig¬
nancy) and would not have objected to
the offer of a voluntary coded tattoo on
his toe.
John Rudoff, MD
David C. Daniels, MD
Charleston, SC