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CONGENITAL GOITRE AND HYPOTHYROIDISM PRODUCED BY MATERNAL INGESTION OF IODIDES
Saturday
CONGENITAL GOITRE AND HYPOTHYROIDISM PRODUCED BY MATERNAL INGESTION OF IODIDES F. CARSWELL
J.
M. M. KERR H. HUTCHISON
8
of
congenital goitre and hypothyroidism due to maternal ingestion of iodide are reported. There were 4 deaths, 2 due to unrelated causes. 2 of the survivors are mentally retarded, presumably owing to fetal hypothyroidism. It is recommended that iodide-containing preparations should not be used during pregnancy and that they should cease to be available without prescription. cases
Introduction
MATERNAL ingestion of iodide has been implicated in the causation of congenital goitre since 1940 when Parmelee et al.i reported 3 cases of newborn infants with goitre. All three mothers had taken iodide-
containing preparations throughout pregnancy; none of the mothers had goitres. Sporadic cases of similar goitres have been reported since then.2-4 This congenital goitre is due to prolonged maternal ingestion of iodide-containing preparations. The infant’s goitre usually regresses within months of birth. Iodide goitre has also been reported in adults. Begg and Hall5 reviewed 52 reported adult cases and added 23 of their own. Despite these reports congenital iodide goitres, often with hypothyroidism, are still occurring and iodide-containing preparations are still freely available to the general public. We report 8 cases seen in the past fourteen years in Glasgow (table i). The diagnosis was made when there was a demonstrable goitre at birth and a good maternal history of ingestion of iodides in infants either born in or admitted to the Royal Maternity Hospital, the Royal Hospital TABLE I-DATA ON
*
8
Clinical Material ILLUSTRATIVE CASE-REPORTS
Case 1 A male infant
was
born in
a
local cottage
hospital
on
May 22, 1955, after 40 weeks’ gestation. Birth-weight 2-60 kg. The infant was cyanosed at birth and the umbilical cord was tight round his neck. He had frequent cyanotic attacks in the first 24 hours, for which he was given oxygen. He was noted to have a goitre and hypospadias and on May 26 was transferred to the Royal Hospital for Sick Children, where he was thought to be cretinous. This was confirmed by the absence of the femoral, tibial, and cuboid epiphyses in X-rays of the knees and ankles. Tracer studies with 1311 on June 7 showed a 24-hour uptake of 87% and protein-bound (P.B.) 1311 at 48 hours of 4 72% dose per litre. The butanol-extractable 1311 was 3-08% dose per litre. p.B.1 on July 7 was 8-0 g. per 100 ml. The goitre was not detectable clinically by Aug. 25, although no specific therapy had been given. The mother was an asthmatic on ’Caifedrin ’ (table II) during both her pregnancies. The first child was normal at birth. When the
patient was last seen on July 22, 1959, his thyroid gland was still visible and thought possibly to be a little enlarged. Psychomotor development had been normal and the child’s bone age was normal. The mother now gave a history of swelling of her own thyroid gland during her pregnancy. Case 8
During the pregnancy this infant’s mother took ephedrine compound elixir for her chronic bronchitis. The infant was born in the Queen Mother’s Hospital, at 40 weeks’ gestation, on Sept. 19, 1969. Birth-weight 2-79 kg. The Apgar score was 6 at 2 minutes and the baby was noted to be limp and gasping with an obvious large goitre and a cretinous appearance. The clinical syndrome of idiopathic respira-
CASES OF CONGENITAL GOITRE
Serum-protein-bound-iodine. t Idiopathic respiratory distress syndrome.
7659
1970
for Sick Children, or the Queen Mother’s Hospital, Glasgow. All the cases reported were born between 1955 and 1969. Several other cases, seen by one of us (J. H. H.) only after treatment had been started elsewhere, have been excluded from consideration.
University Department of Child Health, Royal Hospital for Sick Children, Glasgow C.3 Summary
June
13
1242 TABLE II-IODINE-CONTAINING PREPARATIONS INGESTED BY MOTHERS OF INFANTS WITH CONGENTIAL GOITRE
tory distress developed rapidly. Despite controlled oxygen therapy, maintenance of acid-base status with intravenous sodium bicarbonate and fructose, intramuscular ampicillin and cloxacillin, and oral tri-iodothyronine 25 g. daily from 8 hours of age, his condition deteriorated. Endotracheal intubation and aspiration with initial positivepressure ventilation and subsequent negative-pressure ventilation proved unsuccessful and the child died on 1969.
Sept. 21,
A chest X-ray done on Sept. 19 showed an extensive bilateral airbronchogram and granular opacification of the lung fields. Bone age was estimated to be 34 weeks. P.B. 1271 was 15.4 tg. per 100 ml. on Sept. 19. Blood-culture was sterile. Necropsy revealed pronounced atelectasis and wellformed hyaline membranes. The appearance was characteristic of idiopathic respiratory distress syndrome. The thyroid histological structure was reported as normal although the gland was enlarged. CASE SUMMARIES
finding in all 8 patients. 5 of the thyroid replacement therapy. This patients given consisted ofL-thyroxine sodium (0-025 increasing to 0-mg. a day). One patient a day) or tri-iodothyronine (25 jj<.g. (case 2) who was not treated with thyroid replacement therapy had his thyroid isthmus divided to relieve tracheal obstruction from a huge goitre but died shortly after the operation when 28 hours old. 3 other patients (cases 6, 7, and 8) died when 56, 216, and 64 hours old-all 3 had been treated with thyroxine or tri-iodothyronine for 30, 14, and 56 hours respectively. Necropsy examination showed intrauterine pneumococcal pneumonia, no obvious cause, and idiopathic respiratory distress syndrome respectively. Histological examination of the thyroid glands showed hyperplasia (case 2), increased follicle size and increase in colloid (cases 6 and 7), and normal appearances (case 8). Of the 2 patients who survived after thyroxine therapy, 1 patient (case 4), who was first given thyroxine 2 weeks after birth, had an l.Q. of 64 at 4 years of age; the other (case 5), given thyroxine at 3 days after birth, had a normal intelliTable
I
8
summarises the were
clinical examination at 13 months. Of the 2 who survived without thyroxine therapy, 1 (case 1) patients was clinically of normal intelligence at 4 years of age and 1 (case 3) had an l.Q. of 66 at 2 years of age. Only 1 of the survivors (case 1) still had a possible goitre when last seen at 4 years of age. This child had no family history of thyroid disease. In the other surviving children the goitres completely disappeared over a variable period of time. Radioiodine (1311) tests were performed in case 1 (see illustrative case-report) and in case 3 at the age of 2 years. In case 3 the 1311 uptake at 24 hours was 30% of dose and p.B.1 at 48 hours was 0-15% dose per litre. An attempt to do 131 studies on the mother of case 7, 3 months after the birth of her baby, was unsuccessful as her thyroidal uptake of 131J was absent owing to continued ingestion of iodide. In the only infant (case 7) in whom the immunofluorescent test for antibody to thyroid microsomes was gence
on
performed, it was weakly positive although the thyroglobulin-precipitin test and the tanned-red-cell tests were negative. This child died and subsequent histological examination of the thyroid gland showed no evidence of Hashimoto’s thyroidits. The form in which the mothers ingested the iodides varied (table n). Six of the eight mothers had taken the iodide-containing preparation throughout pregnancy. Four of the mothers had small goitres and another mother had a history of goitre in the pregnancy. One of the patients (case 4) had 2 sibs who had small goitres at the ages of 4 and 5 years, but none of the other patients had family histories of thyroid disease. Discussion The intake of elemental iodine producing a goitre in the adult has been reported as between 18 and 2010 mg. a day 5; but Saxena et al. reported that 1-2 mg. elemental iodine a day suppressed 131 uptake in children. In the present series (using minimal estimates of elemental iodine intake) maternal intakes of 12-1650 mg. elemental iodine a day produced
congenital iodide goitres. It is known that goitre develops in only a small proportion of those who take iodides. Thus Palliers7 reported that 197 children received iodides for asthma at the Jewish National Home for Asthmatic Children in Denver, and only 4 of these patients developed goitre. The duration of therapy or the dosage did not seem to be the factor determining those who developed goitre. In addition, Croughs and Vissier8 produced evidence that in their patients who had developed congenital iodide goitre the pituitary-thyroid control abnormal in that the raised iodide intake did not inhibit thyroid iodide uptake. These workers postulated that the presence of excess thyroid-stimulating hormone (T.s.H.) and iodide in these patients produced excessive iodide uptake which blocked the organification of iodide. They showed that, if iodide and T.S.H. were given to normal children, a goitre developed; but it did not develop if iodide alone was given. This work confirmed the significance of the earlier observation of Morgans and Trotter 9 that iodide-induced goitre is associated with a failure of organification of iodide as shown by the marked discharge of thyroidal iodide on administration of perchlorate. Our patients with congenital iodide-induced goitres showed both clinical and X-ray evidence of hypothyroidism. It could be expected by analogy with athyreotic cretins that those not treated with thyroid replacement therapy might later show signs of mental retardation.lO With this expectation it seems important to apply thyroid replacement therapy as soon after birth as possible and to continue it until the thyroid was
1243
gland is functioning normally. None the less, of the 4 survivors in our own series, 2 were mentally retarded. One had therapy; the other did not. Of the mentally normal survivors, 1 had therapy; the other did not. Cases of congenital iodide-induced goitre have been reported to develop normally despite the fact that no thyroid replacement therapy had been given.11,9,11 This may well be related to the severity of the fetal hypothyroidism.10 The goitre usually disappears with Of the 4 or without thyroid replacement therapy. deaths in the present series, 3 were in patients who had received thyroid replacement therapy; but in the 2 cases
in which
a cause
of death
was
established
at
(idiopathic respiratory distress syndrome and intrauterine pneumococcal pneumonia) it is hardly possible that the therapy altered the prognosis. The child who died of idiopathic respiratory distress syndrome was of 40 weeks’ gestational age (maternal dates) although the bone age was only 34 fetal weeks. Neurological immaturity may have contributed to these deaths. Probably thyroid replacement therapy is still advisable if it can be given shortly after birth. 5 deaths have been reported in neonates with iodideinduced goitres.12-14 Some of these deaths may have been due to inadequate or too late operation for massive goitres obstructing the trachea. Packard et al.4 reviewed the treatment of extreme thyroid enlargenecropsy
birth in 31 North American cases. Of the 18 infants treated expectantly, 10 died; of the 13 operated on, all 10 who had thyroid resection survived while the 3 who died did not have thyroid resection. Accordingly Packard et al.suggested that any patient with a congenital goitre who shows evidence of obstruction should have the thyroid resected to relieve the obstruction. One of our patients died after simple division of the thyroid isthmus; perhaps more radical surgery would have been effective.
ment at
The 4 deaths in our series were directly related to the mother’s ingestion of iodides. Iodine-containing compounds have been recommended as expectorants in the treatment of asthma.15.16 Mims 17 lists four for use in asthma. Two iodine-containing compounds are in the expeclisted iodine-containing compounds torant and cough suppressant section of Proplist 1969.1a (They are classified as consisting of acceptable preparations containing more than one drug: A3). These preparations are usually available without a prescription (table II). We agree with Klevit 19who suggested that these goitres have arisen commonly enough to discourage the use of iodide preparations in pregnancy. We suggest that such preparations should not be available without a prescription. REFERENCES 1.
2. 3. 4. 5. 6.
Parmelee, A. H., Allen, E., Stein, I. F., Buxbaum, H. Am. J. Obstet. Gynec. 1940, 40, 145. Bongiovanni, A. M., Eberlein, W. R., Thomas, P. Z., Anderson, W. B. J. clin. Endocr. 1956, 16, 146. Turner, H. H., Howard, R. B. ibid. p. 141. Packard, G. B., Williams, E. T., Wheelock, S. E. Surgery, St. Louis, 1960, 48, 422. Begg, T. B., Hall, R. Q. Jl Med. 1963, 32, 351. Saxena, K. M., Chapman, E. M., Pryles, C. V. Science, 1962, 138, 430.
7. Palliers, C. J. Am. J. Dis. Child. 1960, 99, 428. 8. Croughs, W., Vissier, H. K. A. J. Pediat. 1965, 67, 353. 9. Morgans, M. E., Trotter, W. R. Lancet, 1959, ii, 374.
References continued
at
foot of next column
CHRONIC LIVER DISEASE AND PRIMARY LIVER-CELL CANCER WITH HEPATITISASSOCIATED
(AUSTRALIA)
ANTIGEN
IN SERUM SHEILA SHERLOCK S. P. NIAZI
R. A. Fox P. J. SCHEUER
*
Departments of Medicine and Pathology, Royal Free Hospital, London W.C.1
Seventeen patients, all males, are described with chronic liver disease and a positive serological test for hepatitis-associated (H.A.) Australia antigen. Two came from the U.K., eight from Greece, three from North or South America, one from Belgium, one from Italy, and two from Africa. Seven presented during follow-up of a severe attack of virus hepatitis. All had received corticosteroid therapy. The other ten had no past history of the acute disease. Liver biopsy was done in sixteen patients. One patient showed only evidence of a recent viral hepatitis, and four showed persistent hepatitis or inactive post-necrotic scarring. These five patients are symptom-free and the prognosis is considered good. Six patients showed histological features of chronic aggressive hepatitis and in four there was also cirrhosis. They differed from classic active chronic (lupoid) hepatitis in being males of an older age-group. Serum bilirubin, aspartate transaminase, and globulin levels tended to be lower. The smooth-muscle antibody was absent from the serum or present only in low titre. Hepatic histological differences were not absolute although three of the H.A. group showed evidence of a recent acute hepatitis. Five patients had primary liver cancer, and in four of these, underlying cirrhosis was demonstrated. Serum-&agr;-fetoprotein was present in two of these five patients. These observations suggest, but do not prove, that acute hepatitis with positive H.A. antigen may be followed by chronic liver disease and cirrhosis and that this can proceed to livercell cancer.
Summary
Introduction
THE relationship between acute viral hepatitis and chronic hepatitis and cirrhosis has always been in doubt. In certain cases, serial liver biopsies have shown progression from acute viral hepatitis to cirrhosis This course is usually believed to com*
Present address: Fatimah Jinnah Medical
DR. CARSWELL AND OTHERS:
College, Lahore, Pakistan.
REFERENCES—continued
Blizzard, R. M., Wilkins, L. Pediatrics, Springfield, 1957, 19, 1011. 11. Martin, H. M., Rento, R. D. J. Pediat. 1962, 61, 94. 12. Bernard, W. G., Grubin, H., Scheller, G. A. Archs Path. 1955, 60, 10.
Smith,
D. W.,
635. 13. Anderson, G. S., Bird, T. Lancet, 1961, ii, 742. 14. Galina, M. P., Avnet, N. L., Einhorn, A. New Engl. J. Med. 1962, 267, 1124. 15. Todd, R. G. in Extra Pharmacopoiea: Martindale, p. 1147. London, 1967. 16. Welt, L. G., Blythe, W. B. in The pharmacological Basis of Therapeutics (edited by L. S. Goodman and A. Gilman); p. 814. London, 1965. 17. Mims: Monthly index of Medical Specialities; vol. 11, no. 10,
18. 19.
p. 134. London, 1969. Proplist; vol. v, p. 31. London, 1969. Klevit, H. D. in Endocrine and Genetic Diseases of Childhood (edited by L. I. Gardner); p. 243. London, 1969.
CONGENITAL GOITRE AND HYPOTHYROIDISM PRODUCED BY MATERNAL INGESTION OF IODIDES F. CARSWELL
J.
M. M. KERR H. HUTCHISON
8
of
congenital goitre and hypothyroidism due to maternal ingestion of iodide are reported. There were 4 deaths, 2 due to unrelated causes. 2 of the survivors are mentally retarded, presumably owing to fetal hypothyroidism. It is recommended that iodide-containing preparations should not be used during pregnancy and that they should cease to be available without prescription. cases
Introduction
MATERNAL ingestion of iodide has been implicated in the causation of congenital goitre since 1940 when Parmelee et al.i reported 3 cases of newborn infants with goitre. All three mothers had taken iodide-
containing preparations throughout pregnancy; none of the mothers had goitres. Sporadic cases of similar goitres have been reported since then.2-4 This congenital goitre is due to prolonged maternal ingestion of iodide-containing preparations. The infant’s goitre usually regresses within months of birth. Iodide goitre has also been reported in adults. Begg and Hall5 reviewed 52 reported adult cases and added 23 of their own. Despite these reports congenital iodide goitres, often with hypothyroidism, are still occurring and iodide-containing preparations are still freely available to the general public. We report 8 cases seen in the past fourteen years in Glasgow (table i). The diagnosis was made when there was a demonstrable goitre at birth and a good maternal history of ingestion of iodides in infants either born in or admitted to the Royal Maternity Hospital, the Royal Hospital TABLE I-DATA ON
*
8
Clinical Material ILLUSTRATIVE CASE-REPORTS
Case 1 A male infant
was
born in
a
local cottage
hospital
on
May 22, 1955, after 40 weeks’ gestation. Birth-weight 2-60 kg. The infant was cyanosed at birth and the umbilical cord was tight round his neck. He had frequent cyanotic attacks in the first 24 hours, for which he was given oxygen. He was noted to have a goitre and hypospadias and on May 26 was transferred to the Royal Hospital for Sick Children, where he was thought to be cretinous. This was confirmed by the absence of the femoral, tibial, and cuboid epiphyses in X-rays of the knees and ankles. Tracer studies with 1311 on June 7 showed a 24-hour uptake of 87% and protein-bound (P.B.) 1311 at 48 hours of 4 72% dose per litre. The butanol-extractable 1311 was 3-08% dose per litre. p.B.1 on July 7 was 8-0 g. per 100 ml. The goitre was not detectable clinically by Aug. 25, although no specific therapy had been given. The mother was an asthmatic on ’Caifedrin ’ (table II) during both her pregnancies. The first child was normal at birth. When the
patient was last seen on July 22, 1959, his thyroid gland was still visible and thought possibly to be a little enlarged. Psychomotor development had been normal and the child’s bone age was normal. The mother now gave a history of swelling of her own thyroid gland during her pregnancy. Case 8
During the pregnancy this infant’s mother took ephedrine compound elixir for her chronic bronchitis. The infant was born in the Queen Mother’s Hospital, at 40 weeks’ gestation, on Sept. 19, 1969. Birth-weight 2-79 kg. The Apgar score was 6 at 2 minutes and the baby was noted to be limp and gasping with an obvious large goitre and a cretinous appearance. The clinical syndrome of idiopathic respira-
CASES OF CONGENITAL GOITRE
Serum-protein-bound-iodine. t Idiopathic respiratory distress syndrome.
7659
1970
for Sick Children, or the Queen Mother’s Hospital, Glasgow. All the cases reported were born between 1955 and 1969. Several other cases, seen by one of us (J. H. H.) only after treatment had been started elsewhere, have been excluded from consideration.
University Department of Child Health, Royal Hospital for Sick Children, Glasgow C.3 Summary
June
13
1242 TABLE II-IODINE-CONTAINING PREPARATIONS INGESTED BY MOTHERS OF INFANTS WITH CONGENTIAL GOITRE
tory distress developed rapidly. Despite controlled oxygen therapy, maintenance of acid-base status with intravenous sodium bicarbonate and fructose, intramuscular ampicillin and cloxacillin, and oral tri-iodothyronine 25 g. daily from 8 hours of age, his condition deteriorated. Endotracheal intubation and aspiration with initial positivepressure ventilation and subsequent negative-pressure ventilation proved unsuccessful and the child died on 1969.
Sept. 21,
A chest X-ray done on Sept. 19 showed an extensive bilateral airbronchogram and granular opacification of the lung fields. Bone age was estimated to be 34 weeks. P.B. 1271 was 15.4 tg. per 100 ml. on Sept. 19. Blood-culture was sterile. Necropsy revealed pronounced atelectasis and wellformed hyaline membranes. The appearance was characteristic of idiopathic respiratory distress syndrome. The thyroid histological structure was reported as normal although the gland was enlarged. CASE SUMMARIES
finding in all 8 patients. 5 of the thyroid replacement therapy. This patients given consisted ofL-thyroxine sodium (0-025 increasing to 0-mg. a day). One patient a day) or tri-iodothyronine (25 jj<.g. (case 2) who was not treated with thyroid replacement therapy had his thyroid isthmus divided to relieve tracheal obstruction from a huge goitre but died shortly after the operation when 28 hours old. 3 other patients (cases 6, 7, and 8) died when 56, 216, and 64 hours old-all 3 had been treated with thyroxine or tri-iodothyronine for 30, 14, and 56 hours respectively. Necropsy examination showed intrauterine pneumococcal pneumonia, no obvious cause, and idiopathic respiratory distress syndrome respectively. Histological examination of the thyroid glands showed hyperplasia (case 2), increased follicle size and increase in colloid (cases 6 and 7), and normal appearances (case 8). Of the 2 patients who survived after thyroxine therapy, 1 patient (case 4), who was first given thyroxine 2 weeks after birth, had an l.Q. of 64 at 4 years of age; the other (case 5), given thyroxine at 3 days after birth, had a normal intelliTable
I
8
summarises the were
clinical examination at 13 months. Of the 2 who survived without thyroxine therapy, 1 (case 1) patients was clinically of normal intelligence at 4 years of age and 1 (case 3) had an l.Q. of 66 at 2 years of age. Only 1 of the survivors (case 1) still had a possible goitre when last seen at 4 years of age. This child had no family history of thyroid disease. In the other surviving children the goitres completely disappeared over a variable period of time. Radioiodine (1311) tests were performed in case 1 (see illustrative case-report) and in case 3 at the age of 2 years. In case 3 the 1311 uptake at 24 hours was 30% of dose and p.B.1 at 48 hours was 0-15% dose per litre. An attempt to do 131 studies on the mother of case 7, 3 months after the birth of her baby, was unsuccessful as her thyroidal uptake of 131J was absent owing to continued ingestion of iodide. In the only infant (case 7) in whom the immunofluorescent test for antibody to thyroid microsomes was gence
on
performed, it was weakly positive although the thyroglobulin-precipitin test and the tanned-red-cell tests were negative. This child died and subsequent histological examination of the thyroid gland showed no evidence of Hashimoto’s thyroidits. The form in which the mothers ingested the iodides varied (table n). Six of the eight mothers had taken the iodide-containing preparation throughout pregnancy. Four of the mothers had small goitres and another mother had a history of goitre in the pregnancy. One of the patients (case 4) had 2 sibs who had small goitres at the ages of 4 and 5 years, but none of the other patients had family histories of thyroid disease. Discussion The intake of elemental iodine producing a goitre in the adult has been reported as between 18 and 2010 mg. a day 5; but Saxena et al. reported that 1-2 mg. elemental iodine a day suppressed 131 uptake in children. In the present series (using minimal estimates of elemental iodine intake) maternal intakes of 12-1650 mg. elemental iodine a day produced
congenital iodide goitres. It is known that goitre develops in only a small proportion of those who take iodides. Thus Palliers7 reported that 197 children received iodides for asthma at the Jewish National Home for Asthmatic Children in Denver, and only 4 of these patients developed goitre. The duration of therapy or the dosage did not seem to be the factor determining those who developed goitre. In addition, Croughs and Vissier8 produced evidence that in their patients who had developed congenital iodide goitre the pituitary-thyroid control abnormal in that the raised iodide intake did not inhibit thyroid iodide uptake. These workers postulated that the presence of excess thyroid-stimulating hormone (T.s.H.) and iodide in these patients produced excessive iodide uptake which blocked the organification of iodide. They showed that, if iodide and T.S.H. were given to normal children, a goitre developed; but it did not develop if iodide alone was given. This work confirmed the significance of the earlier observation of Morgans and Trotter 9 that iodide-induced goitre is associated with a failure of organification of iodide as shown by the marked discharge of thyroidal iodide on administration of perchlorate. Our patients with congenital iodide-induced goitres showed both clinical and X-ray evidence of hypothyroidism. It could be expected by analogy with athyreotic cretins that those not treated with thyroid replacement therapy might later show signs of mental retardation.lO With this expectation it seems important to apply thyroid replacement therapy as soon after birth as possible and to continue it until the thyroid was
1243
gland is functioning normally. None the less, of the 4 survivors in our own series, 2 were mentally retarded. One had therapy; the other did not. Of the mentally normal survivors, 1 had therapy; the other did not. Cases of congenital iodide-induced goitre have been reported to develop normally despite the fact that no thyroid replacement therapy had been given.11,9,11 This may well be related to the severity of the fetal hypothyroidism.10 The goitre usually disappears with Of the 4 or without thyroid replacement therapy. deaths in the present series, 3 were in patients who had received thyroid replacement therapy; but in the 2 cases
in which
a cause
of death
was
established
at
(idiopathic respiratory distress syndrome and intrauterine pneumococcal pneumonia) it is hardly possible that the therapy altered the prognosis. The child who died of idiopathic respiratory distress syndrome was of 40 weeks’ gestational age (maternal dates) although the bone age was only 34 fetal weeks. Neurological immaturity may have contributed to these deaths. Probably thyroid replacement therapy is still advisable if it can be given shortly after birth. 5 deaths have been reported in neonates with iodideinduced goitres.12-14 Some of these deaths may have been due to inadequate or too late operation for massive goitres obstructing the trachea. Packard et al.4 reviewed the treatment of extreme thyroid enlargenecropsy
birth in 31 North American cases. Of the 18 infants treated expectantly, 10 died; of the 13 operated on, all 10 who had thyroid resection survived while the 3 who died did not have thyroid resection. Accordingly Packard et al.suggested that any patient with a congenital goitre who shows evidence of obstruction should have the thyroid resected to relieve the obstruction. One of our patients died after simple division of the thyroid isthmus; perhaps more radical surgery would have been effective.
ment at
The 4 deaths in our series were directly related to the mother’s ingestion of iodides. Iodine-containing compounds have been recommended as expectorants in the treatment of asthma.15.16 Mims 17 lists four for use in asthma. Two iodine-containing compounds are in the expeclisted iodine-containing compounds torant and cough suppressant section of Proplist 1969.1a (They are classified as consisting of acceptable preparations containing more than one drug: A3). These preparations are usually available without a prescription (table II). We agree with Klevit 19who suggested that these goitres have arisen commonly enough to discourage the use of iodide preparations in pregnancy. We suggest that such preparations should not be available without a prescription. REFERENCES 1.
2. 3. 4. 5. 6.
Parmelee, A. H., Allen, E., Stein, I. F., Buxbaum, H. Am. J. Obstet. Gynec. 1940, 40, 145. Bongiovanni, A. M., Eberlein, W. R., Thomas, P. Z., Anderson, W. B. J. clin. Endocr. 1956, 16, 146. Turner, H. H., Howard, R. B. ibid. p. 141. Packard, G. B., Williams, E. T., Wheelock, S. E. Surgery, St. Louis, 1960, 48, 422. Begg, T. B., Hall, R. Q. Jl Med. 1963, 32, 351. Saxena, K. M., Chapman, E. M., Pryles, C. V. Science, 1962, 138, 430.
7. Palliers, C. J. Am. J. Dis. Child. 1960, 99, 428. 8. Croughs, W., Vissier, H. K. A. J. Pediat. 1965, 67, 353. 9. Morgans, M. E., Trotter, W. R. Lancet, 1959, ii, 374.
References continued
at
foot of next column
CHRONIC LIVER DISEASE AND PRIMARY LIVER-CELL CANCER WITH HEPATITISASSOCIATED
(AUSTRALIA)
ANTIGEN
IN SERUM SHEILA SHERLOCK S. P. NIAZI
R. A. Fox P. J. SCHEUER
*
Departments of Medicine and Pathology, Royal Free Hospital, London W.C.1
Seventeen patients, all males, are described with chronic liver disease and a positive serological test for hepatitis-associated (H.A.) Australia antigen. Two came from the U.K., eight from Greece, three from North or South America, one from Belgium, one from Italy, and two from Africa. Seven presented during follow-up of a severe attack of virus hepatitis. All had received corticosteroid therapy. The other ten had no past history of the acute disease. Liver biopsy was done in sixteen patients. One patient showed only evidence of a recent viral hepatitis, and four showed persistent hepatitis or inactive post-necrotic scarring. These five patients are symptom-free and the prognosis is considered good. Six patients showed histological features of chronic aggressive hepatitis and in four there was also cirrhosis. They differed from classic active chronic (lupoid) hepatitis in being males of an older age-group. Serum bilirubin, aspartate transaminase, and globulin levels tended to be lower. The smooth-muscle antibody was absent from the serum or present only in low titre. Hepatic histological differences were not absolute although three of the H.A. group showed evidence of a recent acute hepatitis. Five patients had primary liver cancer, and in four of these, underlying cirrhosis was demonstrated. Serum-&agr;-fetoprotein was present in two of these five patients. These observations suggest, but do not prove, that acute hepatitis with positive H.A. antigen may be followed by chronic liver disease and cirrhosis and that this can proceed to livercell cancer.
Summary
Introduction
THE relationship between acute viral hepatitis and chronic hepatitis and cirrhosis has always been in doubt. In certain cases, serial liver biopsies have shown progression from acute viral hepatitis to cirrhosis This course is usually believed to com*
Present address: Fatimah Jinnah Medical
DR. CARSWELL AND OTHERS:
College, Lahore, Pakistan.
REFERENCES—continued
Blizzard, R. M., Wilkins, L. Pediatrics, Springfield, 1957, 19, 1011. 11. Martin, H. M., Rento, R. D. J. Pediat. 1962, 61, 94. 12. Bernard, W. G., Grubin, H., Scheller, G. A. Archs Path. 1955, 60, 10.
Smith,
D. W.,
635. 13. Anderson, G. S., Bird, T. Lancet, 1961, ii, 742. 14. Galina, M. P., Avnet, N. L., Einhorn, A. New Engl. J. Med. 1962, 267, 1124. 15. Todd, R. G. in Extra Pharmacopoiea: Martindale, p. 1147. London, 1967. 16. Welt, L. G., Blythe, W. B. in The pharmacological Basis of Therapeutics (edited by L. S. Goodman and A. Gilman); p. 814. London, 1965. 17. Mims: Monthly index of Medical Specialities; vol. 11, no. 10,
18. 19.
p. 134. London, 1969. Proplist; vol. v, p. 31. London, 1969. Klevit, H. D. in Endocrine and Genetic Diseases of Childhood (edited by L. I. Gardner); p. 243. London, 1969.