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T4 TOXICOSIS
660 evoked response, which corresponded with the fall in serumcopper and did not improve after copper infusion.9 We suggest, therefore, that there is as yet no conclusive objective evidence supporting the efficacy of parenteral copper in Menkes’ syndrome. On the contrary, our findings suggest that intravenous copper is not taken up and utilised normally by either liver or central nervous tissue. Indeed, parenteral cupric salts may even be toxic to other tissues, as our patient developed transient aminoaciduria during the infusion period, which resolved gradually after the infusions were discontinued. Department of Pediatrics, University of Florida,
ADOLFO D. GARNICA STEVEN R. FLETCHER
Gainesville 32610.
T4 TOXICOSIS
SIR,-We find difficulties in accepting the suggestion of Dr Britton and his colleagues (July 26, p. 141) that "T4 toxicosis" may be
a normal biochemical finding in elderly women. Heartof 90-100 in 5 patients (presumably resting) may indicate early hyperthyroidism that will be confirmed by further follow-up. 24 h 131I uptake and thyrotrophin-releasing-hormone tests might have provided evidence that these patients were not normal. To assess the relevance of the findings of Britton et al. for patients in our area, we compared the mean free-thyroxine index (F.T.I.) values for 50 consecutive euthyroid non-goitrous women under 65 (19±0.45) with values for 100 consecutive clinically euthyroid women age 65 and over-50 non-goitrous (2.0±0.54), and 50 with diffuse goitre (20±052). Values for the three groups were almost identical. Only 1 patient over 65 had an F.T.I. value above normal (3-6-normal 11-34). She had a diffuse goitre, tremor, and an unexplained 10 lb weightloss. Iodine uptake was 27%; the serum-T3 concentration by radioimmunoassay (T3 [R.I.A.]) value was 142 ng/dl (normal 50-150 ng/dl). We believe she has early hyperthyroidism and are observing her for the present. In addition, we reviewed records of 29 consecutive women, aged 65 and older, treated for hyperthyroidism since the T3 (R.I.A.) assay became available in our laboratory, to determine whether any had only physiological T4 elevations. All had definite clinical features of hyperthyroidism. All had elevated F.T.I. values, and 23 had elevated T3 (R.I.A.) values. The remaining 6 patients had T3 (R.I.A.) values of 130-148 ng/dl. Iodine uptake was compatible with hyperthyroidism for 3 of these patients (30%, 47%, and 57%). The remaining 3 patients had iodine-uptake values of 15%, 22%, and 24%. 2 of these patients had toxic nodular goitre (commonly seen without elevated iodine-uptake), and the final patient had had a recent
rates
gallbladder X-ray. Since Britton et al. seem to doubt the existence of T4 toxiwe offer data on such a patient. A 35-year-old woman had a diffuse goitre three times normal size and classical clinical features of hyperthyroidism. The F.T.I. was 5.5, and iodineuptake was 52%. The T3 (R.I.A.) values were 78 ng/dl and 100 ng/dl on two separate specimens. Clinical and laboratory abnormalities abated three months after 131I therapy. In conclusion, our experience suggests that elevated F.T.I. values in elderly women are seldom, if ever, physiological in our area. We reiterate the warnings of generations of thyroidologists that elderly patients, particularly with long-standing goitre, may have masked hyperthyroidism, presenting primarily with manifestations of cardiac decompensation. An aged cardiovascular system is likely to have reduced tolerance for even modest increases in thyroid secretory activity.
cosis,
Suite 300, Northland Medical Building, 20905 Greenfield, Southfield, Michigan 48075, U.S.A. 9.
N. S., Dawson, W. W., Rhodes, 1974, 77, 1974.
Levy,
SHELDON S. STOFFER JOEL I. HAMBURGER B.
J., Garnica, A. Am. J. Ophthal.
SIR,—We have followed the correspondence on this subject with continued interest since the first letter of Turner et al.’ We agree with the suggestion of Britton et al. that caution should be exercised in interpreting a raised serum-thyroxme (T 4) in an elderly patient with slight symptoms and chnical signs of hyperthyroidism. In one elderly debilitated female patient with hypertension, arteriosclerosis, and a persistent tachycardia, a repeatedly raised serum-thyroxine ranging from 120 to 138 nmol/1 (normal range 55-105) and a subnormal serum-triiodothyronine (T3) of 05nmol/1 (11-26) raised the possibility of a diagnosis of T4 thyrotoxicosis. The problem was solved by time (the serum- T level gradually fell from 138 to 91 nmol/l) and by a thyrotrophin-releasing hormone (T.x.n.) infusion, demonstrating a normal plasma-T.s.H. response. In this situation in euthyroid elderly female patients, the raised serum-T4 level presumably compensates for a lowered peripheral conversion of T to T3 due to concomitant chronic disease or
drug interference.
However, in
a recent study of 101 healthy volunteers, we have been unable to confirm that serum-T3 levels fall with age as reported by Rubenstein et a1.3 The serum-total-T) was determined by radioimmunoassay using the technique supplied by Endocrine Sciences* which uses A.N.S. (8-anilino-l-naphthalene sulphonic acid) as the thyroxine-binding globulin (T.B.G.) blocking agent and ammonium-sulphate precipitation to separate the bound T3 from the unbound T3. The T3 antisera is raised in our own laboratory rabbits. Lipxmic sera are carefully monitored in the assay procedure, since, in a few instances, the lipaemia has interfered with the ammonium-sulphate precipitation of the bound T3 leading to falsely raised T3 levels. 52 male subjects ranged in age from 21 to 88 years with a mean of 39 years. The mean T3 level was 1.80±0.28 (s.D.) nmol/1. A regression of T3 on age showed a slope of -0003 nmoll-1 y’, which is not significantly different from zero. 42 female subjects ranged in age from 18 to 82 years with a mean of 39 years. The mean T3 level was 1.65±0.34 (S.D.) nmoll. In this case the regression coefficient was -0001 nmol/l/year, again not significantly different from zero. The difference between males and females was statistically significant (t=337p<0001) although in our view of little practical concern in an individual patient. G. H. MCLELLAN Department of Biochemistry, W. J. RILEY Royal Perth Hospital, Perth, C. P. DAVIES Western Australia.
SCREENING FOR CONGENITAL HYPOTHYROIDISM
SIR,-Klein et al. 4pointed out that analysis of serum thyrotropin is preferable to thyroxine analysis in the screening for hypothyroidism in the neonate. X-ray examination of ossification centres in the distal femoral epiphysis, a method previously recommended for this purpose, appears to be too insensitive. 56 Serum-triiodothyronine assay would also be expected to be unsuitable, at least for cord-blood samples.’ To our knowledge, no case of congenital hypothyroidism has been reported in which all these examinations have been performed. We have had the opportunity to study two cases of congenital
hypothyroidism. CASE 1—The patient, a girl, was delivered at full term after an uneventful pregnancy. Her birth-weight was 3400 g, and the crown-heel length was 51 cm-mean values for normal children. The Apgar score *18418 Oxnard Street, Tarzana, California, U.S.A. 91356. 1. Turner. J. G., Brownlie, B. E. W., Sadler, W. A. Lancet, 1975, i, 407 2. Britton, K. E., Quinn, V., Ellis, S. M., Cayley, A. C. D., Miralles, J M Brown, B. L., Ekins, R. P. ibid. July 26, 1975, p. 141. 3. Rubenstein, H. A., Butler, V. P., Werner, S. C. J. clin Endocr 1973. 34. 247. 4. Klein, A. H., Agustin, A. V., Foley, T. P. Lancet, 1974, ii, 77 5. Taranger, J., Berglund, G., Clæsson, I., Victorin, L. ibid. 1973,i, 487 6. Ehrlich, R. M., McKendry, J. B. J. ibid. p. 1121. 7. Larsen, P. R. Metabolism, 1972, 21, 107.
ADOLFO D. GARNICA STEVEN R. FLETCHER
Gainesville 32610.
T4 TOXICOSIS
SIR,-We find difficulties in accepting the suggestion of Dr Britton and his colleagues (July 26, p. 141) that "T4 toxicosis" may be
a normal biochemical finding in elderly women. Heartof 90-100 in 5 patients (presumably resting) may indicate early hyperthyroidism that will be confirmed by further follow-up. 24 h 131I uptake and thyrotrophin-releasing-hormone tests might have provided evidence that these patients were not normal. To assess the relevance of the findings of Britton et al. for patients in our area, we compared the mean free-thyroxine index (F.T.I.) values for 50 consecutive euthyroid non-goitrous women under 65 (19±0.45) with values for 100 consecutive clinically euthyroid women age 65 and over-50 non-goitrous (2.0±0.54), and 50 with diffuse goitre (20±052). Values for the three groups were almost identical. Only 1 patient over 65 had an F.T.I. value above normal (3-6-normal 11-34). She had a diffuse goitre, tremor, and an unexplained 10 lb weightloss. Iodine uptake was 27%; the serum-T3 concentration by radioimmunoassay (T3 [R.I.A.]) value was 142 ng/dl (normal 50-150 ng/dl). We believe she has early hyperthyroidism and are observing her for the present. In addition, we reviewed records of 29 consecutive women, aged 65 and older, treated for hyperthyroidism since the T3 (R.I.A.) assay became available in our laboratory, to determine whether any had only physiological T4 elevations. All had definite clinical features of hyperthyroidism. All had elevated F.T.I. values, and 23 had elevated T3 (R.I.A.) values. The remaining 6 patients had T3 (R.I.A.) values of 130-148 ng/dl. Iodine uptake was compatible with hyperthyroidism for 3 of these patients (30%, 47%, and 57%). The remaining 3 patients had iodine-uptake values of 15%, 22%, and 24%. 2 of these patients had toxic nodular goitre (commonly seen without elevated iodine-uptake), and the final patient had had a recent
rates
gallbladder X-ray. Since Britton et al. seem to doubt the existence of T4 toxiwe offer data on such a patient. A 35-year-old woman had a diffuse goitre three times normal size and classical clinical features of hyperthyroidism. The F.T.I. was 5.5, and iodineuptake was 52%. The T3 (R.I.A.) values were 78 ng/dl and 100 ng/dl on two separate specimens. Clinical and laboratory abnormalities abated three months after 131I therapy. In conclusion, our experience suggests that elevated F.T.I. values in elderly women are seldom, if ever, physiological in our area. We reiterate the warnings of generations of thyroidologists that elderly patients, particularly with long-standing goitre, may have masked hyperthyroidism, presenting primarily with manifestations of cardiac decompensation. An aged cardiovascular system is likely to have reduced tolerance for even modest increases in thyroid secretory activity.
cosis,
Suite 300, Northland Medical Building, 20905 Greenfield, Southfield, Michigan 48075, U.S.A. 9.
N. S., Dawson, W. W., Rhodes, 1974, 77, 1974.
Levy,
SHELDON S. STOFFER JOEL I. HAMBURGER B.
J., Garnica, A. Am. J. Ophthal.
SIR,—We have followed the correspondence on this subject with continued interest since the first letter of Turner et al.’ We agree with the suggestion of Britton et al. that caution should be exercised in interpreting a raised serum-thyroxme (T 4) in an elderly patient with slight symptoms and chnical signs of hyperthyroidism. In one elderly debilitated female patient with hypertension, arteriosclerosis, and a persistent tachycardia, a repeatedly raised serum-thyroxine ranging from 120 to 138 nmol/1 (normal range 55-105) and a subnormal serum-triiodothyronine (T3) of 05nmol/1 (11-26) raised the possibility of a diagnosis of T4 thyrotoxicosis. The problem was solved by time (the serum- T level gradually fell from 138 to 91 nmol/l) and by a thyrotrophin-releasing hormone (T.x.n.) infusion, demonstrating a normal plasma-T.s.H. response. In this situation in euthyroid elderly female patients, the raised serum-T4 level presumably compensates for a lowered peripheral conversion of T to T3 due to concomitant chronic disease or
drug interference.
However, in
a recent study of 101 healthy volunteers, we have been unable to confirm that serum-T3 levels fall with age as reported by Rubenstein et a1.3 The serum-total-T) was determined by radioimmunoassay using the technique supplied by Endocrine Sciences* which uses A.N.S. (8-anilino-l-naphthalene sulphonic acid) as the thyroxine-binding globulin (T.B.G.) blocking agent and ammonium-sulphate precipitation to separate the bound T3 from the unbound T3. The T3 antisera is raised in our own laboratory rabbits. Lipxmic sera are carefully monitored in the assay procedure, since, in a few instances, the lipaemia has interfered with the ammonium-sulphate precipitation of the bound T3 leading to falsely raised T3 levels. 52 male subjects ranged in age from 21 to 88 years with a mean of 39 years. The mean T3 level was 1.80±0.28 (s.D.) nmol/1. A regression of T3 on age showed a slope of -0003 nmoll-1 y’, which is not significantly different from zero. 42 female subjects ranged in age from 18 to 82 years with a mean of 39 years. The mean T3 level was 1.65±0.34 (S.D.) nmoll. In this case the regression coefficient was -0001 nmol/l/year, again not significantly different from zero. The difference between males and females was statistically significant (t=337p<0001) although in our view of little practical concern in an individual patient. G. H. MCLELLAN Department of Biochemistry, W. J. RILEY Royal Perth Hospital, Perth, C. P. DAVIES Western Australia.
SCREENING FOR CONGENITAL HYPOTHYROIDISM
SIR,-Klein et al. 4pointed out that analysis of serum thyrotropin is preferable to thyroxine analysis in the screening for hypothyroidism in the neonate. X-ray examination of ossification centres in the distal femoral epiphysis, a method previously recommended for this purpose, appears to be too insensitive. 56 Serum-triiodothyronine assay would also be expected to be unsuitable, at least for cord-blood samples.’ To our knowledge, no case of congenital hypothyroidism has been reported in which all these examinations have been performed. We have had the opportunity to study two cases of congenital
hypothyroidism. CASE 1—The patient, a girl, was delivered at full term after an uneventful pregnancy. Her birth-weight was 3400 g, and the crown-heel length was 51 cm-mean values for normal children. The Apgar score *18418 Oxnard Street, Tarzana, California, U.S.A. 91356. 1. Turner. J. G., Brownlie, B. E. W., Sadler, W. A. Lancet, 1975, i, 407 2. Britton, K. E., Quinn, V., Ellis, S. M., Cayley, A. C. D., Miralles, J M Brown, B. L., Ekins, R. P. ibid. July 26, 1975, p. 141. 3. Rubenstein, H. A., Butler, V. P., Werner, S. C. J. clin Endocr 1973. 34. 247. 4. Klein, A. H., Agustin, A. V., Foley, T. P. Lancet, 1974, ii, 77 5. Taranger, J., Berglund, G., Clæsson, I., Victorin, L. ibid. 1973,i, 487 6. Ehrlich, R. M., McKendry, J. B. J. ibid. p. 1121. 7. Larsen, P. R. Metabolism, 1972, 21, 107.