THE
TREATMENT
OF
HYPERTHYROIDISM
IN CHILDHOOD
WITH
THIOURACIL
DRUGS
By Judson J. Van Wyk, M.D., Melvin M. Grumbach, M.D., Thomas H. Shepard, II,
and Lawson Wilkins, M.D.
Department of Pediatrics, Johns Hopkins University School of Medicine and
Endocrine Clinic of Harriet Lane Home of Johns Hopkins Hospital
(Submitted August 20, accepted September 12, 1955.)
Investigatioils were made possible by grants from the American Cancer Society upon recommendation
of the Committee on Growth of the National Research Council and from the Division of Research
Grants and Fellowships of the National Institutes of Health, U.S. Public Health Service.
Dr. Van \Vvk and Dr. Grumbach were Post Doctoral Fellows of the National Foundation for Infantile
Paralysis.
PRESENT ADDRESS: (J.J.Van W.) Department of Pediatrics, University of North Carolina School of
Medicine, Chapel Hill, North Carolina.
221
I
N THE 12 ears since thiouracil was intro-duce(l for the treatment of hyperthy-roidism it has been amply demonstratedthat a remission from the thyrotoxic state can he induced regularly and maintained
indefinitely by the antithyroid drugs. By proper adjustlnent of dosage any desired level of thyroid function can be achieved. In unselected adult patients with toxic goiters the incidence of prolonged remis-sion after treatment is discontinued has
ranged between 45 per cent and 75 per cent in most series.’ Since only about 1 per cent of the cases of hvperthyroidism occur be-fore the age of 14 years,5 there has been
far less opportunity to evaluate medical
therapy with these agents in children. Al-though satisfactory remissions by the use of
these drugs in children have been reported by several authors, more long-term fol-low-ups are needed to assess the effect of puberty and adolescence on children in whom remissions have been obtained. If remissions can be sustained through this
period of physiologic adjustment it may he
Presumed that patients will have an excel-lent chance of remaining well thereafter.
During the Past 10 years all children with hvperthvroidism in the Endocrine Clinic of
the Harriet Lane Home have been treated medically with the aim of avoiding surgery if possible. Follow-tips are available on 16 children whose disease began before the age of 13 years. The clinical course in these children will be reviewed.
PATIENT MATERIAL AND PLAN
OF
TREATMENT
In Figure 1 is shown the age distribution of
patients, the upper bar indicating the period from the age of onset to the end of the follow-up period. The crosshatched areas represent
the duration of symptoms or objective signs of
hyperthyroidism; the lower solid bar indicates
treatment with antithyroid drugs.
Propvl-thiouracil was used exclusively except in tile
earliest cases where thiouracil was employed.
Although the imidazole drugs have a more rapid action they have not been used in this
series as it was desirable to keep the group as
uniform as possible.
The diagnosis was unequivocal in every case, although the severity and
symptomatol-ogy varied. All had diffusely enlarged thyroid glands and the characteristic cardiovascular
manifestations of rapid bounding pulse and
wide pulse pressure. All in this group had
definite eye signs varying from separation of
the eyelids to frank proptosis. Confirmation of
the diagnosis was obtained with radioactive iodine-uptake studies in every case so studied and in more recent years with serum protein-bound iodine measurements. Twelve of the six-teen cases occurred in females and in 6 cases there was a familial history of hyperthyroidism.
In 2 instances the disease had recurred in
3
successive generations. Half of the patients were taller than the ninetieth percentile for age when first seen.
-IIII
B. B.
M.L
T. L
D. E
E.J.
V. E
L.0.
C. S.
H.J.
MW.
wE
J.F
J.M.
E.W.
J.T
B L.
(DIED)
222 VAN WYK - HYPERTHYROIDISM iN CHILDHOOD
Li,,,
ri
--i
__
-Ii
Li::i Li T:L_ .i
OP
U
EJ EUTHYROID HYPERTHYROID N-PROPYL THIOURACIL
DOSAGE SCALE: 300
iIiI
AGE 4 5 6 7 8 9 10 U 2 14 5 16 17 I8J
FI;. 1. Course of 16 patients with juvenile hyperthyroidism from onset of symptoms to end of follow-up period. Thiouracil was used before N-propylthiouracil became available.
euthyrcid status was usually not achieved for
2 to 4 months. The subsequent assessment of thyroid status was based on clinical appraisal,
and the dosage regulated accordingly.
Throughout the period of therapy the children attended school and led normal lives.
RESULTS AND COMMENTS
ON TREATMENT
Of these 16 patients, 8 are now in a period of remission without therapy,
4
have come to surgery, and 4 are still receivingtreatment.
Patients Now in Remission Without Therapy
The 8 patients who have remained in
remission after cessation of treatment are
summarized in Table I. Seven have been
off treatment for periods ranging between
23 months and 6 years 10 months. Although
the last patient has been completely ofi
treatment for only 4 months lie has actually been receiving only 50 mg. daily for the
past 3#{189}years due to the reluctance on the
part of the referring physician to
discon-tinue it completely as had been
recom-mended. Six of the patients have passed
through adolescence and a seventh (B.B.) is well into puberty. In no case have we
seen any tendency to relapse during this
period.
In none of these patients are there any residual signs or symptoms of thyrotoxicosis
with the exception of slight prominence of
the eyes in a few cases. Considerable
im-provement in the eye signs has occurred in all of the patients in which the treatment
was exclusively medical. Since 85 per cent
‘rABLE I
PATIENTS Now IN REMIssIoN WITHOUT FUI4TIIER ThERAPY
T ?%arne
: Age of j Present
Onset Age
yr., mo. yr., mo.
. Duratwn
of Treatment
yr., mo.
. Enlargement of Gland
Period
. - --- --
--Since
Treatment Before Lad of
#{163}ow yr., ma. Ireatment Treatment
‘r.i.
BR. V.E. H..J. M.L. B.L. J.M. J.F. 4’ 4 7 8’#{176} 4 1’2’ Ii’ 106 15 1i2’ 152 16 94 196 16 18 ‘2 8 44 l’#{176} 1 6 )‘ 49 610 57 410 4 34 6 1” 4 ++ + + ++ +++ j 0 + SL. SL. s1. SL. + 1) (1 (I U SL. SL. (I Sb.that most or all of this group will remain this may take. We feel that 2 years should
well. be the minimal period of treatment in any
In Astwood’s experience the single, most case. favorable prognostic sign has been the
re-duction in size of the gland during the Patients Subsequently
Subjected
to
course of treatment.1 Although temporary Thyroidectomyenlargement frequently occurred after treat- Table II summarizes the 4 patients in ment was started, the gland eventually be- whom surgery was carried out. J.T. dis-came smaller in each of these 8 patients continued the drug on her own initiative before treatment was stopped. At the pres- after she had become euthyroid for a short ent time no significant thyroid enlargement period. During the ensuing relapse her is present in any of this group. Excluding gland enlarged considerably. Although she
the last case the average duration of treat- again became euthyroid during a second ment in this group was 28 months. Our course of treatment her gland remained present policy is to carry out therapy until enlarged. Finally she developed an illness
the thyroid gland has been reduced con- characterized by fever and leukopenia. Al-siderably in size, regardless of how long though recovery was rapid with penicillin
TABLE II
PATIENTS SUBSEQUENTLY SUBJE-rED TO TIIYROIDECTOMY
.
Patient Age of Onset
yr., nto.
Duration of Treatment
yr., ml).
,
Reason for 7 hyroidectamy I osloperative) (ondiiicn
J.T. 3
(‘2 courses)
Persistent goiter Leucopenia
Increase in exophthalnlos ilypothyroid
W.F. 101 l)rug Rash Hypothyroid
Ilypoparathyroid
MW. 101 41
(Intermittent)
Persistent toxicity Failure to co-operate
hypothyroid
E.W. 1’2
(Intermittent)
Age of
Patient Onset
yr. me.
Present Age yr. mo.
. Duration of
Treatment yr. mo.
Enlargement of Gland Response of Goiter
-Before To PT(’+
Now To PT(
.ireatment Inyrol
E.J. 5’
(‘S.
L().
I).E. 49
1’26
1O
‘26
6’#{176}
73
1
4
++++ ++++ ++++
+
+ + ++
.(After
-( yr.)
.1J,1.
111
HJ.
I I
224 VAN WYK - HYPERTHYROIDISM IN CHILDHOOD
TABLE III
PATIENTS STILL RECEIVING N-PROPYLTHIOURACIL (PTU)
and cortisone and there was some question
as to whether the illness was actually a manifestation of drug toxicity, it was con-sidered that medical management had had an adequate trial in her case and surgery
was carried out.
W.F. developed a skin rash after 4 months
of treatment with propyithiouracil. No
ef-fort was made to change medication to
another antithyroid drug and after a period during which Lugol’s solution was adminis-tered a subtotal thyroidectomy was per-formed.
M.W. came from a poor social back-ground and failed to take her medication regularly. Return visits were irregular and
at one time she failed to return for a year
and a half. Hyperthyroidism persisted due to her failure to follow the prescribed treat-ment.
E.W. was the first patient of our series
and achieved an excellent remission with thiouracil. She returned to her home in Bermuda where she was unable to secure the drug. Within a short time she relapsed and developed auricular fibrillation. She died following a thyroidectomy, probably performed while she was in a thyroid crisis. This patient and M.W. emphasize that medical management should be abandoned
early in any patient who cannot be followed closely or who fails to co-operate.
The 3 surviving postoperative patients are all hypothyroid and require substitution therapy. One of them (W.F.) also has hypo-parathyroidism which has improved but has not disappeared after 2 years. J.T. had
a measurable and obvious increase in cx-ophthalmos postoperatively.
Patients Still Undergoing Treatment
The 4 patients still requiring treatment are summarized in Table III.
E.J. was the most severely toxic patient in this series and was the slowest to be-come euthyroid. Therapy has been dis-continued twice with relapses occurring promptly on each occasion. The gland re-mained enlarged for 61/2 years but has re-cently undergone rapid spontaneous in-volution. This is regarded as an excellent prognostic sign and therapy is now being discontinued. Despite the prolonged
therapy for nearly 7 years the patient has remained in an excellent state of health
and
has been in no manner handicapped by her illness or treatment. Indeed, it would have been difficult at any point in her therapy to convince the parents that medi-cal management should have been aban-doned in favor of surgery.
L.O. and D.E. are of particular interest in that the goiters underwent progressive enlargement during therapy. This is most apt to occur when a patient is overtreated and allowed to become hypothyroid. Under these conditions the gland is heavily stimu-lated by pituitary thyrotropin. Various
in-vestigators have suggested that the
com-bination of desiccated thyroid or thyroxine
hor-24
HYPERTHYROID
I
D.E. W.
49/YRS. AT ONSET
HYPOTHYROID
EUTHYROID ZONE
RELATIVE
SIZE OF
GOITER
I
I
II
Iii
i
THYROID 3
(GRAINS)
2
I
600
N- PROPYL
THIOURACI L #{176}#{176}
(MG.) 200
LU GOL’ S
2 4 6 8 I 0 2 14 16 8 20 22
MONTHS AFTER ONSET
Fic. 2. The effect of thyroid extract in combination with propvlthiouracil on size of goiter in Cllil(l prs’iotmsly treated with iodine. The estimates of thyroid status are based on clinical appraisal. The
relative size of the gland is only approximate but is based on measurement of serial tracings. The glahi(i was only slightly enlarged at the time of this report.
mone.TM’ 1, U This combined treatment
proved to be most effective in causing
in-volution of the thyroid gland in patients L.O. and D.E. The efficacy in the case of C.S. is more difficult to evaluate since her gland had already become considerably smaller before desiccated thyroid was
started.
The effect of combined thyroid and pro-pylthiouracil therapy is illustrated by the clinical course of D.E. as shown in Figure 2. This 4 9/12-year-old girl developed marked thyrotoxicosis and was treated elsewhere with Lugol’s solution for 1 year. Although she became euthyroid her gland increased
in size after a year of this therapy. Her
physician abruptly discontinued the iodine
and started methylthiouracil in a dosage of
600 mg. daily. We first saw her after she
had received this medication for 6 weeks.
She had become hyperthyroid after the
abrupt cessation of iodine therapy and was
not as yet controlled by the
methylthioura-cil. Nevertheless, the dosage was changed
to 300 mg. of propylthiouracil daily. When next examined 2 months later she had
be-come myxedematous and the goiter had
increased enormously in size. Three grains of thyroid daily were added to the regimen, and the 300 mg. of propylthiouracil daily was continued. Within 3 days the mother noted a definite decrease in the size of her neck and within 3 months the goiter was
only one-third as large as previously. At this time the referring physician abruptly
discon-tinued the thyroid and in the ensuing period
of hypothyroidism the gland again
en-larged. The subsequent addition of thyroid
to her therapy caused further reduction in
the size of the gland. After a period of
sta-bility stepwise reduction in the medication
will be carried out.
Ultimately such patients with large
goiters may require surgery, but the suc-cess to date in causing involution of the
gland by simultaneously blocking the
syn-thesis of thyroid hormone with
226 VAN WYIC -
HYPERTHYROIDISM
IN CHILDHOODthyrotropin by the administration of desic-cated thyroid, would prompt us to extend this form of treatment to all patients whose glands fail to decrease promptly with anti-thyroid drugs alone.
Toxicity
In larger series of adults the reported in-cidence of adverse reactions to propyl-thiouracil has varied between 1.5 per cent
and 10 per cent.’24 Fortunately toxic re-‘ictions are usually mild. Urticaria and der-matitis usually occur early in the course of of treatment and in some instances it may be possible to change to one of the
imida-zole group of drugs. However, cross-sensi-tivity, occurs in a significant percentage of
sensitive patients.15
Granulocytopenia occurred in 2 of the pa-tients and was accompanied by buccal ulceration and sore throat. This complica-tion may occur late in the course of treat-ment. Although periodic blood counts are advisable in all patients, they do not offer
adequate warning as hematologic complica-tions may occur suddenly. Patients should report all minor illnesses or sore throats and then a blood count should be performed.
Fortunately, leukopenia due to propyl-thiouracil is usually mild and often
disap-pears even though the drug is continued.
Even in more severe cases it is usually re-versible after the drug is withdrawn. Cor-tisone is a valuable adjunct in this situation; an increase of neutrophils was demonstrated
in patient J.T. within 12 hours after it was started. Fatal agranulocytosis from propyl-thiouracil has been reported but is ex-tremely rare.
DISCUSSION
Our experience with the medical manage-ment of an unselected group of children with hyperthyroidism is entirely compa-rable with that derived from larger series of unselected cases in adults14 and with the group of cases reported by Kunstadter and
Stein8 and Allen
et
al.9
A number
of
our patients who obtained remissions in early childhood have passed through thevulner-able period of adolescence without relapses. The complete subsidence of thyroid enlarge-ment is probably the best indication that
the remissions will be permanent.
There has been considerable debate con-cerning the relative merits of surgical versus medical management of thyrotoxicosis. Neither the medical nor the surgical
treat-ment of childhood thyrotoxicosis presents
any serious hazard to life. Provided a pa-tient is not sensitive to antithyroid drugs, is co-operative and can be kept under observa-tion, the choice between a surgical opera-tion and a 2- or 3-year period of medical therapy should depend upon which method offers the greatest likelihood of restoring the patient to a permanent state of health re-quiring no further treatment.
Because of the high percentage of relapses when the more conservative thyroidec-tomies were performed, surgeons have re-sorted to more and more radical removal of the gland, in spite of the probability of caus-ing permanent hypothyroidism. Thus every child managed surgically requires a long period of postoperative observation. A certain number of them will require thy-roid therapy under medical supervision for the rest of their lives. The risk of surgical damage to the parathyroid glands becomes greater with more radical operations. Hy-poparathyroidism, although a less frequent complication, is far more serious and
diffi-cult to manage than hypothyroidism. In
adults progression of exophthalmos is not an infrequent sequel to thyroidectomy.’T
Irradiation of the thyroid gland either by x-rays or 1-131 is generally not recommended for patients under 40 years of age because of the theoretical danger of predisposing to later neoplastic changes. Duffy has given credence to this possibility by observing that 10 of 28 youthful patients with thyroid cancer had received thymic irradiation in in-fancy.18
Because of these disadvantages of treat-ment by surgery or irradiation, we believe that in children with hyperthyroidism sur-gery should be reserved for those who are
227
to co-operate. In the remainder, careful medical management over 2 or 3 years offers “cures” to at least 50 per cent, or per-haps to a much larger number, which will be
permanent after the drug is withdrawn. It is possible that the combined use of thyroid extract with antithyroid drug in those pa-tients whose glands remain large may
in-crease the number who obtain a permanent
remission.
SUMMARY
During the past 10 years thiouracil and propyithiouracil have been used to treat all children with hyperthyroidism in the Har-riet Lane Home Endocrine Clinic.
Follow-ups are available on 16 children whose dis-ease began before 13 years of age. Eight of this group are now in a period of pro-longed remission; 4 have required subse-quent surgery, and 4 are still under treat-ment. The occurrence of adolescence has not been found to induce a relapse in any child who was previously in remission.
Reduction in the size of the goiter while the patient is receiving treatment has been
found to be the best prognostic sign. The combined use of thyroid with antithyroid drugs has caused involution of the gland
in those patients whose goiters remained
large after treatment with propyithiouracil
alone. The ultimate value of this combined treatment remains to be determined.
It is recommended that surgery be
re-served for those children who are sensitive
to antithyroid drugs, who fail to co-operate
or cannot be followed closely. In the re-mainder, treatment with antithyroid drugs should be continued until there is
sub-st4intial reduction in the size of the gland. A period of 2 years of continuous therapy is suggested as the minimal period of
treat-ment.
REFERENCES
1. Solomon, D. H., Beck,
J.
C., VanderLaan,W. P. and Astwood, E. B.: Prognosis of hyperthyroidism treated by antithy-roid drugs. J.A.M.A., 152:201, 1953. 2. Wing, E. S., and Asper, S. P., Jr.:
Obser-vations on the use of propylthiouracil
in hyperthyroidism with especial
refi-ence to long term treatment. Bull. Johns Hopkins Hosp., 90:201, 1952.
3. Beierwaltes, W. H., and Sturgis, C. C.: Current methods of treating thyrotoxico-sis. M. Clin. North America, 53:497, 1949.
4. McCullagh, E. P., Humphrey, D. C., Mc-Garvey, C.
J.,
and Sundgren, V.: Re-sults of propylthiouracil therapy for hy-perthyroidism. J.A.M.A. 147:106, 1951.5.
Kennedy, R. L.J.:
Surgical and medical treatment of exophthalmic goiter in chil-dren; late results. Am.J.
Dis. Child., 60:677, 1940.6. Williams, L. P., and Janney, F. R.: Thion-racil in childhood hyperthyroidism.
J.
Pediat., 30:370, 1947.7. Jackson, A. S., and Haley, H. B.: Exoph-thalmic goiter in children; treatment with propylthiouracil. Am.
J.
M. Sc., 218:493, 1948.8. a. Kunstadter, R. H., and Stein, A. F.: Treatment of thyrotoxicosis in children with thiourea derivatives. PEDIATRICS,
6:244, 1950.
b.
Ibid.:
Treatment of thyrotox.ic childrenwith thiourea derivatives. Am.
J.
Dis. Child., 90:373, 1955.9. Allen, R. F., Rose, E., and Rose, E. K.: Juvenile thyrotoxicosis; results of treat-ment in 30 cases. PEDIATRICS, 14:38, 1954.
10. Fraser, R., and Wilkinson, M.: Simplified method of drug treatment for thyrotoxi-cosis using a uniform dosage of methyl-thiouracil and added thyroxine. Brit. M.
J.,
1:481, 1953.11. Poate, H. R. G.: Long-term therapy in thyrotoxicosis with methylthiouracil. M.
J.
Australia, 2:677, 1948.12. Goodman, L. S., and Gilman, A.: The Pharmacological Basis of Therapeutics, 2nd Ed. New York, Macmillan, 1955, p. 1551.
13. Bartels, E. C., and Kohn, M. M.: Large doses of propylthiouracil in the treat-ment of hyperthyroidism.
J.
Clin.Endocrinol., 14:1403, 1954.
14. Irwin, C. W., Van Vactor, H. D., and
Norris, M. S.: Propylthiouracil and
methimazole therapy; comparative ex-periences. J.A.M.A., 149:1637, 1952. 15. Asper, S. P., Jr.: Personal communications. 16. Bartlett, W., Jr.: Recurrent and persistent
hyperthyroidism.
J.
Clin. Endocrinol., 11:1179, 1951.228 VAN WYK -
HYPERTHYROIDISM
INCHILDHOOD
in the guinea pig and in man. Surg.,
Gynec. & Obst., 80:526, 1945. 18. Duffy, B.
J.,
Jr., and Fitzgerald, P.J.
:Thy-roid cancer in childhood and adoles-cence. Cancer, 3:1018, 1950.
SPANISH ABSTRACT
Tratamiento
del
Hipertiroidismo
en
la
Infancia
con
Tiouracil
y sus
Derivados.
Evoluci#{243}n de
16 Casos
Durante los tiltimos diez a#{241}ostodos los
niflos con hipertiroidismo vistos en Ia Clinica de Endocrinologla de Ia Instituci#{243}n Harriet
Lane han sido tratados medicamente con el fin
de evitar al m#{225}ximo el tratamiento quirtirgico.
Los autores presentan Ia evoluci#{243}n de 16 ni#{241}os cuya enfermedad apareci#{243} antes de los trece aiios de edad, y revisan su curso dlinico.
Generalmente el propiltiouracil se inici#{243}a Ia
dosis de 30 mgrs. diarios; al paciente se le mantuvo en reposo en cama y sedado hasta
observarse una mejorla definida. Esto por lo com#{252}nrequiri#{243}alrededor de tres semanas; sin embargo, el estado eutiroideo generalmente se lograba hasta dos o cuatro meses despu#{233}s. La
valorizaci#{243}n del estado tiroideo subsecuente se bas#{243}en el examen clInico; Ia dosificaci#{243}n fu#{233} regulada de acuerdo con #{233}l.Los ni#{241}osasistlan a
Ia escuela y vivian una vida normal durante
todo el perIodo de tratamiento.
De estos 16 pacientes, 8 han remitido y no est#{225}nsujetos a tratamiento, 4 han requeridn
tratamiento quiriirgico y los otros 4 ann est#{225}n
bajo tratamiento. Seis de los 8 pacientes con
remisiones y sin tratamiento han cruzado Ia adolescencia y el s#{233}ptimo va pasando Ia pubertad; en ningnn caso los autores han ob-servado tendencia a recaer durante este perlodo.
Con excepci#{243}n del (iltimo caso, Ia duraci#{243}n
promedio de tratamiento en este grupo ha sido de 28 meses. Los autores consideran como politica adecuada sostener Ia terap#{233}utica hasta
que Ia gl#{225}ndula tiroides se haya reducido con-siderablemente de tamaflo, sin importar Ia du-raci#{243}ndel perlodo; creen que en cualquier caso dos aflos es el perIodo minimo de sostenimiento.
Cuatro de los pacientes tratados m#{233}dicamente
fueron sujetos subsecuentemente a
tiroidecto-mia; uno por presentar manifestaciones cut#{225}neas de intoxicaci#{243}n a Ia droga despu#{233}sde cuatro meses, otro por persistencia de hipertrofia
tiroidea e instalaci#{243}n de leucopenia a los tres a#{241}osy medio del tratamiento; los otros dos
pacientes no fueron vigilados adecuadamente
y al v#{233}rseles nuevamente continuaban con
hipertiroidismo. Uno de estos ni#{241}ossali#{243}del
pals y muri#{243}despu#{233}s de Ia operaci#{243}n. Los 3
que sobreviven desarrollaron hipotiroidismo
posteriormente y uno adem#{225}s hipoparatiroi-dismo.
Cuatro de los pacientes que ann reciben
drogas antitiroideas est#{225}nen condiciones euti-roideas. En dos de ellos persisti#{243}Ia hipertrofia glandular o bien la gl#{225}ndula
creci#{243}progresiva-mente. Una reducci#{243}n dram#{225}ticadel tama#{241}o de estas gl#{225}ndulas sigui#{243}a Ia administraci#{243}n de
tiroide desecada en dosis hasta de 20 cgr. al dIa, simult#{225}neas a grandes dosis de N-propiltiouracil. Ann cuando estos pacientes se encuentran asintom#{225}ticos actualmente no puede
predecirse el resultado final.
Se observ#{243} granulocitopenia en dos de los
pacientes, que se acompafl#{243} de ulceraciones
bucales y dolor faringeo, complicaci#{243}n que puede presentarse tardlamente en el curso del
tratamiento. Aunque Ia biometria hem#{225}tica
peri#{243}dica es recomendable en todos los pa-cientes, Ia protecci#{243}n que ofrece no es del todo completa. Los pacientes deben informar todos los procesos menores y dolor de garganta, a Io
que se practicar#{225} cuenta hem#{225}tica de inmediato.
Los autores recomiendan el tratamiento
quirnrgico para aquellos ni#{241}ossensibles a la medicaci#{243}n antitiroidea, que no cooperen, o
bien que no puedan vigilarse estrechamente. En el resto debe sostenerse un tratamiento a base de drogas antitiroideas hasta que haya reducci#{243}n definida del tamaflo de Ia gl#{225}ndula.
Por #{241}ltimo, sugieren como perlodo mlnimo de tratamiento 2 a#{241}osde terapia sostenida.
INTERLINGUA ABSTRACT
Le
Uso
de
Drogas
Thiouracilic
in
Ic
Tractamento
de
Hyperthyroidismo
in
Juveniles.
Observationes
Ulterior
in
16 Casos
Durante le passate 10 annos, cmne juveniles
con hyperthyroidismo presentate al Clinica Eu-docrin del “Harriet Lane Home” esseva tractate
medicalmente con le objectivo de evitar
inter-ventiones chirurgic in tanto que possibile. Ob-servationes ulterior es disponibile pro 16 juve-niles in qui le morbo comenciava ante le etate de 13 annos. Nos presenta un revista del curso
clinic in iste casos.
ORIGINAL
ARTICLES
229generalmente comenciate in closes diurne de 300 mg, e le patiente esseva retenite al hospital
sub allectamento e sedation usque al occurren-tia de melioration inequivoc. Isto requireva usu-almente circa 3 septimanas, ben que usualmente un stato completemente euthyroide non esseva attingite in minus que 2 o 4 menses. Le subse-quente evalutation del stato thyroide esseva ba-sate super observationes clinic, e le dosage
esse-va regulate correspondentemente. Perdurante le periodo therapeutic le juveniles vadeva aI schola e viveva vitas normal.
Ex iste gruppo de 16 patientes, 8 es nunc in un periodo de remission sin therapia; 4 esseva presentate al chirurgia; e 4 continua reciper
tractamento.
Sex del 8 patientes in remission sin therapia ha passate le adolescentia; un septime es ben avantiate in le pubertate. Durante iste periodo nulle tendentia recidival esseva observate in nile caso del serie.
Si nos exclude le ultime caso, le duration median del tractamento in iste gruppo esseva 28 menses. Al tempore presente nos seque le principio de continuar le therapia usque le dimensiones del glandula thryroide es conside-rabilemente reducite, sin reguardo al longor del tempore que es requirite pro attinger iste ob-jectivo. Nos opina que tin periodo de 2 annos de tractamento debe esser considerate como le minimo in omne casos.
Quatro patientes esseva subjicite a thyroidec-tomia post reciper un tractamento medical. In
un de iste casos le ration esseva que le patiente
disveloppava manifestationes cutanee de toxi-citate medicamentose post un curso therapeu-tic de 4 menses. In le secunde caso il habeva un persistente allargamento thyroide e le dis-veloppamento de leucopenia post 33 annos de
tractamento. Le tertie e le quarte caso concer-neva patientes qui esseva subtrahite ab nostre
supervision. Lor hyperthyroidismo se provava
persistente. Un de iste juveniles quitava le pais
e moriva post-operativemente. Le 3
supervi-ventes disveloppava hypothyroidismo post-operative; un de illes disveloppava hypopara-thyroidismo.
Le 4 patientes qui continua reciper drogas antithyroide es mantenite in stato euthyroide. In 2 de illes le glandula thyroide remaneva al-largate o deveniva progressivemente plus large.
Un frappante reduction del dimensiones de iste
glandulas occurreva quando thyroide desiccate
in quantitates diume de 3 granos esseva
admini-strate conjunctemente con grande doses de
N-propylthiouracil. Iste patientes es nunc mante-nite in un stato asymptomatic sed le resultado
final non es cognoscite.
Granulocytopenia occurreva in 2 de nostre
l)atientes e esseva accompaniate de ulceration buccal e mal de gurgite. Iste complication pote occurrer tarde in le curso del tractamento. Ben
que periodic contos sanguinee es
recommen-dabile in omne patientes, illos non offere un pro-tection complete. Le patientes deberea reportar
omne maladias minor e accessos de mal de
gur-gite, e a tal tempores contos sanguinee deberea
esser executate.
Ii es a recommendar que interventiones
chi-rurgic es reservate pro juveniles qui es sensibile
a drogas antithyroide, qui non coopera, o qui non pote esser surveliate strictemente. In omne
altere casos, le tractamento con drogas antithy-roide deberea esser continuate usque un
con-siderabile reduction es attingite in le
dimen-siones del glandula. Un periodo de 2 annos de
therapia ininterrumpite es recommendate como
le minimo del tractamento medical.
His’roeLAsMosls, Frederic N. Silverman et at. (Am.
J.
Med., 19:410, September, 1955.)A comprehensive review of the available information concerning histoplasmosis is
