- Email: [email protected]
Effects of hypoxia on thyroid function tests
602
Brief clinical and laboratory observations
particular reference to testicular activity, J Clin Endocrinol Metab 49:40, 1979. 4. Garnier PE, Chaussain JL, Binet E, Schlumberger A, and Job JC: Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotrophins in children and adolescents. VI: Relations to age, sex and puberty, Acta Endocrinol 77:422, 1974. 5. Albert A, Rosemberg F. Ross GT, Paulsen CA, and Ryan
The Journal of Pediatrics October 1980
RJ: Report of the National Pituitary Agency Collaborative study on the radioimmunoassay of FSH and LH, J Clin Endocrinol Metab 28:1214, 1968. Leymarie P, Strauss N, and Scholler R: Dosage radioimmunologique rapide de la testostdrone plasmatique chez l'adulte et l'enfant. Vtrification de la sptcificit6 par dosage en spectromttrie de masse, Pathol Biol 22:877, 1974.
Effects of hypoxia on thyroid function tests Thomas Moshang, Jr., M.D.,* Katherine H. Chance, M.D., Philadelphia, Pa., Michael M. Kaplan, M.D., Boston, Mass., Robert D. Utiger, M.D., Chapel Hill, N. C., and Osahiro Takahashi, M.D., Philadelphia, Pa.
THE RELATIONSHIP between thyroid hormones and oxygen consumption has long been recognized. In animals, hypoxia decreases thyroid function and peripheral deiodination of T4.1 This study was undertaken to evaluate the effects of hypoxia in children upon the production of thyroid hormones. PATIENTS
AND M E T H O D S
Thyroid function tests were obtained in normal healthy children, children with acute hypoxia, and children with chronic hypoxia. The control group consisted of 49 children, 2 to 16 years of age, who were free of any acute or chronic disease at the time of study; the majority of these patients were referred to the pediatric endocrine clinic because of genetic short stature or constitutional delay of growth and development. The acutely hypoxic group included seven children, 1% to 13 years of age, with status asthmaticus; studies were performed within six hours after admission. All of these patients were inpatients, having been clinically ill for less than 24 hours before admission. None was febrile or subsequently diagnosed to have a respiratory infection. All had received various sympathomimetic and/or theophylline derivatives prior to admission. None had received glucocortiFrom the Department of Pediatrics, Hahnemann Medical College, and Department of Medicine, the University of Pennsylvania. Supported in part by a grant from the National Institutes of Health (AM14039). Presented in part at the meetings of the Society for Pediatric Research and the American Pediatric Society, New York, April, 1978. *Reprint address: Department of l~ediatrics, Hahnemann Medical College, Philadelphia, PA 19102:.
coids. Arterial blood gas values were obtained on these patients because of clinical indications. The partial pressure of arterial oxygen (Pao~) ranged from 63 to 74 mm Hg (mean of 66). The group with chronic hypoxia consisted of seven children, 2% to 16 years of age, with congenital cyanotic heart disease. None of these children had congestive heart failure or failure to thrive. Blood for thyroid function tests and arterial blood gas measurements were obtained at the time of cardiac catherization, performed with the patient under local anesthesia because of clinical indications. This group of children had Pa% levels between 30 and 65 mm Hg (mean of 4 6 ) . Abbreviations used T4: thyroxine Pa%: partial pressure of arterial oxygen T3: tri-iodothyronine rT3: reverseY~ TSH: thyrotropin Serum T4, T3, reverse T:, (3, 3', 5'-tri-iodothyronine) and thyrotropin concentrations were all measured by radioimmunoassays previously described. 2' 3 Assessment of protein binding of thyroid hormones was determined by resin uptake of radiolabeled T3 using a commercial kit (Nuclear Medical Labs, Dallas, Texas) and expressed as a ratio of the patient's value as compared to the value in a control sample consisting of pooled sera from normal adults and children (T3RU). The normal ranges for the various tests in children in this laboratory are 5.0 to 13.0/~g/dl for T4, 70 to 150 ng/dl for T3, 20 to 40 ng/dl for rT3, < 1.5 to 8 /~U/ml for TSH, and 0.8 to 1.2 for T~RU ratio, This study was approved by the Hahnemann Institutional Review Board and Committee on Human Research.
0022-3476/80/100602+03500.30/0 9 1980 The C. V. Mosby Co.
Volume 97 Number 4
Brief clinical and laboratory observations
603
Table. Serum thyroid hormone and TSH concentrations in normal children and in children with acute or chronic hypoxia
Normal Acute hypoxia Chronic hypoxia
T, (,g / al)
T. (ng/ dl)
rT~ (~g/ al)
TSH (#U/ml)
8.5 _+_0.3 (49) 8.1 + 0.9 (6) 6.3 _+ 1.0" (7)
111 + 4 (49) 112 + 25 (7) 71 • 13t (6)
22 _+ 1 (37) 34 _+ 6"~ (7) 54 + 27t (7)
3.9 + 0.4 (44) 1.7 • 0.2* (5) 5.2 • 1.3 (6)
(
T3 RU % pa,ie
,
% control~
0.99 + 0.01 (45)
1.0l + 0.03 (7)
Values are mean -+SEM; ( ) represents number. *P = < 0.02 as compared to controls. tP ~ < 0.01 as compared to controls.
RESULTS The findings in the various groups Of children are shown in the Table. Mean serum T4 and T~ concentrations were not altered in the acutely hypoxic children, but m e a n serum rT~ concentration was significantly elevated (P < 0.01). In the chronically hypoxic children, not only was the mean serum rT3 concentration significantly increased (P < 0.01) but the mean serum T4 and T3 concentrations were both significantly lower than those found in the control group (P < 0.02 and P < 0.01, respectively). TaRU, as an index of thyroid hormone binding, was not altered by hypoxia, indicating that the alterations in serum T4, T~, and rT3 concentrations in these patients were not secondary to changes in binding of thyroid hormones. Despite the lower serum T~ and T3 concentrations in the chronically hypoxic children, serum TSH values were not significantly altered. In the acutely hypoxic children, the mean serum TSH value was significantly lower than in normal children (P < 0.02). DISCUSSION The results of this study indicate that acute or chronic hypoxia results in alterations in serum thyroid hormone concentrations. Since production of both T~ and rT3 is largely extrathyroidal, the altered serum concentrations of T3 and rT~ during hypoxia are most likely due to alterations in extrathyroidal hormone metabolism. In the acutely hypoxic patients, who were studied within 24 hours after the onset of their illness, only elevated serum rT~ concentrations were found, indicating either increased rT~ production from T4 or decreased rT~ metabolism. Kinetic studies in several other situations, such as cirrhosis or starvation, have shown that decreased rT~ degradation is the predominant cause of increased serum rT3 concentration in such patients. 4 In the chronically hypoxic patients, not only elevated
serum rT~ concentrations but also decreased serum T~ concentrations were found. The latter finding most likely represents decreased extrathyroidal T4 conversion to T~. These results are compatible with in vitro data suggesting that T4 conversion to Ta, and rT3 deiodination to 3-Y-di-iodothyronine may be catalyzed by the same enzyme? Thus, in acute hypoxia, inhibition is less marked and only serum rT~ concentrations are elevated, whereas chronic hypoxia results in both elevated serum rT~ and decreased serum T3 concentrations. Whether the changes described are the result of hypoxia per se, rather than some other concomitant of the acute or chronic illness of these patients, cannot be stated with certainty. The low serum TSH levels in patients with acute hypoxia and the normal serum TSH levels despite lower serum T4 concentrations in those with chronic hypoxia suggest the existence of adaptation by the hypothalamus a n d / o r pituitary to hypoxia. The sequence of events proposed is that hypoxia acutely suppresses TSH production, and further prolonged hypoxia results in a new steady state of lowered T4 production with normal TSH levels. An alternate explanation for the lower serum T~ concentrations in the chronically hypoxic patients is that more rapid degradation of T4 to rT3 occurs during chronic hypoxia. However, with intact neuroendocrine feedback mechanisms, more rapid degradation of thyroid hormones should stimulate TSH production. Kinetic studies are needed to distinguish between these possibilities. Croxon et al 6 have suggested a similar adaptive phenomenon to explain the decreased TSH levels noted in acute fasting and the normal TSH levels with low serum T4 concentrations documented during chronic fasting?' 7 Whether the drugs given to the acutely hypoxic (asth matic) children prior to admission could have been responsible for their increased serum rT3 concentrations is not known. In animals, catecholamines increase T~ deiod-
604
B r i e f clinical and laboratory observations
ination? However, epinephrine does not appear to have any effect on T4 deiodination in h u m a n beings? Thyroid hormones are thermogenic, increase oxygen consumption, and have anabolic and catabolic effects. The reduction in extra-thyroidal T3 production that occurs in many illnesses would be expected to reduce the rate of m a n y of these processes. In this context, it is not surprising that hypoxia should have a similar effect on extrathyroidal thyroid hormone metabolism. In this setting, reduced oxygen consumption in tissues sensitive to thyroid hormone, e.g., liver, would spare oxygen for those tissues in which oxygen consumption is not regulated by thyroid hormones, e.g., brain. Almost 30 years ago, it was demonstrated that experimentally induced hypothyroidism in the rat increased the animal's resistance to anoxia.' ~ REFERENCES
1. Galton VA: Some effects of altitude on thyroid function, Endocrinology 91:1393, 1972. 2. Kaplan MM, Schimmel M, and Utiger RE: Changes in serum 3, 3', 5'-triiodothyronine (reverse T3) concentrations
The Journal of Pediatrics October 1980
3.
4.
5. 6.
7.
8. 9.
10.
with altered thyroid hormone secretion and metabolism, J Clin Endocrinol Metab 45:447, 1977. Utiger RD: Thyrotropin, in Jaffe B, and Behrman H, editors: Methods of hormone radioimmunoassay, New York, 1974, Academic press, Inc, p 161. Chopra IJ: An assessment of daily production and significance of thyroidat secretion of 3,3',5'-triiodothyronine (reverse T3) in man, J Clin Invest 58:32, 1976. Kaplan MM, and Utiger RD: Iodothyronine metabolism in rat liver homogenates, J Clin Invest 61:459, 1978. Croxon MS, Hall TD, Kletzky OA, Jaramillo JE, and Nicoloff JT: Decreased serum thyrotropin induced by fasting, J Clin Endocrinol Metab 45:560, 1977. Moshang T Jr, and Utiger RD: Low triiodothyronine euthyroidism in anorexia nervosa, in Vigersky R, editor: Anorexia nervosa, New York, 1977, Raven Press, p 263. Galton VA: Thyroid hormone-catecholamine interrelationships, Endocrinology 77:278, 1965. Hays MT, and Solomon DH: Effect of epinephrine on the peripheral metabolism of thyroxine, J Clin Invest 48:1114, 1969. Zarrow MX, Hiestand WA, Stemler FW, and Wiebers SE: Comparison of effects of experimental hyperthyroidism and hypothyroidism on resistance to anoxia in rats and mice, Am J Physiol 167:171, 1951.
Blood spot thyroxine-binding globulin: A means to reduce recall rate in a screening strategy for neonatal hypothyroidism Evelyn F. Robertson, F.R.A.C.P.,* Anthony C. Wilkins, B.Se., Robert K. Oldfield, F.A.I.M.L.S., and Anthony C. Pollard, F.R.C.Path., North Adelaide, South Australia
T H E N E O N h T AL hypothyroidism screening strategy currently employed in South Australia and elsewhere has been fully described.', 2 We estimate the blood thyroxine level from the dried blood spots provided on the regular Guthrie test papers obtained from infants on the fifth day of life, and then repeat the T4 assay and measure the thyroid-stimulating hormone on a selected (handpunched) blood spot of those samples in the lowest 10% of T, values on first assay. The few infants who appear to have low T4 and high TSH values on blood spot screening have a very high probability of having congenital hypothyroidism. In these it is easy to justify their urgent recall From the Department of Chemical Pathology, The Adelaide Children's Hospital Inc. *Reprint address: Department of Chemical Pathology, The Adelaide Children's Hospital, In'c, North Adelaide, 5006, South Australia, Australia.
for definitive investigation. On the other hand, m a n y more infants (1.8% of the whole) appear to have low T4 and normal TSH values. In this group the individual risk of clinically significant thyroid abnormality is very low; nevertheless, they include 6% of all neonatal hypothyroid Abbreviations used T~: thyroxine TSH: thyroid-stimulating hormone TBG: thyroxine-binding globulin patients? Thu s the problem is to recognize efficiently this latter, small n u m b e r of infants with the m i n i m u m disturbance (recall a n d / o r re-investigation etc.) of the rest of the group. We describe here a solution to this problem by the additional measurement of thyroxine-binding globulin in the blood spots, and discrimination .for the purposes of
0022-3476/80/100604 + 04500.40/0 9 1980 The C. V. Mosby Co.
Brief clinical and laboratory observations
particular reference to testicular activity, J Clin Endocrinol Metab 49:40, 1979. 4. Garnier PE, Chaussain JL, Binet E, Schlumberger A, and Job JC: Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotrophins in children and adolescents. VI: Relations to age, sex and puberty, Acta Endocrinol 77:422, 1974. 5. Albert A, Rosemberg F. Ross GT, Paulsen CA, and Ryan
The Journal of Pediatrics October 1980
RJ: Report of the National Pituitary Agency Collaborative study on the radioimmunoassay of FSH and LH, J Clin Endocrinol Metab 28:1214, 1968. Leymarie P, Strauss N, and Scholler R: Dosage radioimmunologique rapide de la testostdrone plasmatique chez l'adulte et l'enfant. Vtrification de la sptcificit6 par dosage en spectromttrie de masse, Pathol Biol 22:877, 1974.
Effects of hypoxia on thyroid function tests Thomas Moshang, Jr., M.D.,* Katherine H. Chance, M.D., Philadelphia, Pa., Michael M. Kaplan, M.D., Boston, Mass., Robert D. Utiger, M.D., Chapel Hill, N. C., and Osahiro Takahashi, M.D., Philadelphia, Pa.
THE RELATIONSHIP between thyroid hormones and oxygen consumption has long been recognized. In animals, hypoxia decreases thyroid function and peripheral deiodination of T4.1 This study was undertaken to evaluate the effects of hypoxia in children upon the production of thyroid hormones. PATIENTS
AND M E T H O D S
Thyroid function tests were obtained in normal healthy children, children with acute hypoxia, and children with chronic hypoxia. The control group consisted of 49 children, 2 to 16 years of age, who were free of any acute or chronic disease at the time of study; the majority of these patients were referred to the pediatric endocrine clinic because of genetic short stature or constitutional delay of growth and development. The acutely hypoxic group included seven children, 1% to 13 years of age, with status asthmaticus; studies were performed within six hours after admission. All of these patients were inpatients, having been clinically ill for less than 24 hours before admission. None was febrile or subsequently diagnosed to have a respiratory infection. All had received various sympathomimetic and/or theophylline derivatives prior to admission. None had received glucocortiFrom the Department of Pediatrics, Hahnemann Medical College, and Department of Medicine, the University of Pennsylvania. Supported in part by a grant from the National Institutes of Health (AM14039). Presented in part at the meetings of the Society for Pediatric Research and the American Pediatric Society, New York, April, 1978. *Reprint address: Department of l~ediatrics, Hahnemann Medical College, Philadelphia, PA 19102:.
coids. Arterial blood gas values were obtained on these patients because of clinical indications. The partial pressure of arterial oxygen (Pao~) ranged from 63 to 74 mm Hg (mean of 66). The group with chronic hypoxia consisted of seven children, 2% to 16 years of age, with congenital cyanotic heart disease. None of these children had congestive heart failure or failure to thrive. Blood for thyroid function tests and arterial blood gas measurements were obtained at the time of cardiac catherization, performed with the patient under local anesthesia because of clinical indications. This group of children had Pa% levels between 30 and 65 mm Hg (mean of 4 6 ) . Abbreviations used T4: thyroxine Pa%: partial pressure of arterial oxygen T3: tri-iodothyronine rT3: reverseY~ TSH: thyrotropin Serum T4, T3, reverse T:, (3, 3', 5'-tri-iodothyronine) and thyrotropin concentrations were all measured by radioimmunoassays previously described. 2' 3 Assessment of protein binding of thyroid hormones was determined by resin uptake of radiolabeled T3 using a commercial kit (Nuclear Medical Labs, Dallas, Texas) and expressed as a ratio of the patient's value as compared to the value in a control sample consisting of pooled sera from normal adults and children (T3RU). The normal ranges for the various tests in children in this laboratory are 5.0 to 13.0/~g/dl for T4, 70 to 150 ng/dl for T3, 20 to 40 ng/dl for rT3, < 1.5 to 8 /~U/ml for TSH, and 0.8 to 1.2 for T~RU ratio, This study was approved by the Hahnemann Institutional Review Board and Committee on Human Research.
0022-3476/80/100602+03500.30/0 9 1980 The C. V. Mosby Co.
Volume 97 Number 4
Brief clinical and laboratory observations
603
Table. Serum thyroid hormone and TSH concentrations in normal children and in children with acute or chronic hypoxia
Normal Acute hypoxia Chronic hypoxia
T, (,g / al)
T. (ng/ dl)
rT~ (~g/ al)
TSH (#U/ml)
8.5 _+_0.3 (49) 8.1 + 0.9 (6) 6.3 _+ 1.0" (7)
111 + 4 (49) 112 + 25 (7) 71 • 13t (6)
22 _+ 1 (37) 34 _+ 6"~ (7) 54 + 27t (7)
3.9 + 0.4 (44) 1.7 • 0.2* (5) 5.2 • 1.3 (6)
(
T3 RU % pa,ie
,
% control~
0.99 + 0.01 (45)
1.0l + 0.03 (7)
Values are mean -+SEM; ( ) represents number. *P = < 0.02 as compared to controls. tP ~ < 0.01 as compared to controls.
RESULTS The findings in the various groups Of children are shown in the Table. Mean serum T4 and T~ concentrations were not altered in the acutely hypoxic children, but m e a n serum rT~ concentration was significantly elevated (P < 0.01). In the chronically hypoxic children, not only was the mean serum rT3 concentration significantly increased (P < 0.01) but the mean serum T4 and T3 concentrations were both significantly lower than those found in the control group (P < 0.02 and P < 0.01, respectively). TaRU, as an index of thyroid hormone binding, was not altered by hypoxia, indicating that the alterations in serum T4, T~, and rT3 concentrations in these patients were not secondary to changes in binding of thyroid hormones. Despite the lower serum T~ and T3 concentrations in the chronically hypoxic children, serum TSH values were not significantly altered. In the acutely hypoxic children, the mean serum TSH value was significantly lower than in normal children (P < 0.02). DISCUSSION The results of this study indicate that acute or chronic hypoxia results in alterations in serum thyroid hormone concentrations. Since production of both T~ and rT3 is largely extrathyroidal, the altered serum concentrations of T3 and rT~ during hypoxia are most likely due to alterations in extrathyroidal hormone metabolism. In the acutely hypoxic patients, who were studied within 24 hours after the onset of their illness, only elevated serum rT~ concentrations were found, indicating either increased rT~ production from T4 or decreased rT~ metabolism. Kinetic studies in several other situations, such as cirrhosis or starvation, have shown that decreased rT~ degradation is the predominant cause of increased serum rT3 concentration in such patients. 4 In the chronically hypoxic patients, not only elevated
serum rT~ concentrations but also decreased serum T~ concentrations were found. The latter finding most likely represents decreased extrathyroidal T4 conversion to T~. These results are compatible with in vitro data suggesting that T4 conversion to Ta, and rT3 deiodination to 3-Y-di-iodothyronine may be catalyzed by the same enzyme? Thus, in acute hypoxia, inhibition is less marked and only serum rT~ concentrations are elevated, whereas chronic hypoxia results in both elevated serum rT~ and decreased serum T3 concentrations. Whether the changes described are the result of hypoxia per se, rather than some other concomitant of the acute or chronic illness of these patients, cannot be stated with certainty. The low serum TSH levels in patients with acute hypoxia and the normal serum TSH levels despite lower serum T4 concentrations in those with chronic hypoxia suggest the existence of adaptation by the hypothalamus a n d / o r pituitary to hypoxia. The sequence of events proposed is that hypoxia acutely suppresses TSH production, and further prolonged hypoxia results in a new steady state of lowered T4 production with normal TSH levels. An alternate explanation for the lower serum T~ concentrations in the chronically hypoxic patients is that more rapid degradation of T4 to rT3 occurs during chronic hypoxia. However, with intact neuroendocrine feedback mechanisms, more rapid degradation of thyroid hormones should stimulate TSH production. Kinetic studies are needed to distinguish between these possibilities. Croxon et al 6 have suggested a similar adaptive phenomenon to explain the decreased TSH levels noted in acute fasting and the normal TSH levels with low serum T4 concentrations documented during chronic fasting?' 7 Whether the drugs given to the acutely hypoxic (asth matic) children prior to admission could have been responsible for their increased serum rT3 concentrations is not known. In animals, catecholamines increase T~ deiod-
604
B r i e f clinical and laboratory observations
ination? However, epinephrine does not appear to have any effect on T4 deiodination in h u m a n beings? Thyroid hormones are thermogenic, increase oxygen consumption, and have anabolic and catabolic effects. The reduction in extra-thyroidal T3 production that occurs in many illnesses would be expected to reduce the rate of m a n y of these processes. In this context, it is not surprising that hypoxia should have a similar effect on extrathyroidal thyroid hormone metabolism. In this setting, reduced oxygen consumption in tissues sensitive to thyroid hormone, e.g., liver, would spare oxygen for those tissues in which oxygen consumption is not regulated by thyroid hormones, e.g., brain. Almost 30 years ago, it was demonstrated that experimentally induced hypothyroidism in the rat increased the animal's resistance to anoxia.' ~ REFERENCES
1. Galton VA: Some effects of altitude on thyroid function, Endocrinology 91:1393, 1972. 2. Kaplan MM, Schimmel M, and Utiger RE: Changes in serum 3, 3', 5'-triiodothyronine (reverse T3) concentrations
The Journal of Pediatrics October 1980
3.
4.
5. 6.
7.
8. 9.
10.
with altered thyroid hormone secretion and metabolism, J Clin Endocrinol Metab 45:447, 1977. Utiger RD: Thyrotropin, in Jaffe B, and Behrman H, editors: Methods of hormone radioimmunoassay, New York, 1974, Academic press, Inc, p 161. Chopra IJ: An assessment of daily production and significance of thyroidat secretion of 3,3',5'-triiodothyronine (reverse T3) in man, J Clin Invest 58:32, 1976. Kaplan MM, and Utiger RD: Iodothyronine metabolism in rat liver homogenates, J Clin Invest 61:459, 1978. Croxon MS, Hall TD, Kletzky OA, Jaramillo JE, and Nicoloff JT: Decreased serum thyrotropin induced by fasting, J Clin Endocrinol Metab 45:560, 1977. Moshang T Jr, and Utiger RD: Low triiodothyronine euthyroidism in anorexia nervosa, in Vigersky R, editor: Anorexia nervosa, New York, 1977, Raven Press, p 263. Galton VA: Thyroid hormone-catecholamine interrelationships, Endocrinology 77:278, 1965. Hays MT, and Solomon DH: Effect of epinephrine on the peripheral metabolism of thyroxine, J Clin Invest 48:1114, 1969. Zarrow MX, Hiestand WA, Stemler FW, and Wiebers SE: Comparison of effects of experimental hyperthyroidism and hypothyroidism on resistance to anoxia in rats and mice, Am J Physiol 167:171, 1951.
Blood spot thyroxine-binding globulin: A means to reduce recall rate in a screening strategy for neonatal hypothyroidism Evelyn F. Robertson, F.R.A.C.P.,* Anthony C. Wilkins, B.Se., Robert K. Oldfield, F.A.I.M.L.S., and Anthony C. Pollard, F.R.C.Path., North Adelaide, South Australia
T H E N E O N h T AL hypothyroidism screening strategy currently employed in South Australia and elsewhere has been fully described.', 2 We estimate the blood thyroxine level from the dried blood spots provided on the regular Guthrie test papers obtained from infants on the fifth day of life, and then repeat the T4 assay and measure the thyroid-stimulating hormone on a selected (handpunched) blood spot of those samples in the lowest 10% of T, values on first assay. The few infants who appear to have low T4 and high TSH values on blood spot screening have a very high probability of having congenital hypothyroidism. In these it is easy to justify their urgent recall From the Department of Chemical Pathology, The Adelaide Children's Hospital Inc. *Reprint address: Department of Chemical Pathology, The Adelaide Children's Hospital, In'c, North Adelaide, 5006, South Australia, Australia.
for definitive investigation. On the other hand, m a n y more infants (1.8% of the whole) appear to have low T4 and normal TSH values. In this group the individual risk of clinically significant thyroid abnormality is very low; nevertheless, they include 6% of all neonatal hypothyroid Abbreviations used T~: thyroxine TSH: thyroid-stimulating hormone TBG: thyroxine-binding globulin patients? Thu s the problem is to recognize efficiently this latter, small n u m b e r of infants with the m i n i m u m disturbance (recall a n d / o r re-investigation etc.) of the rest of the group. We describe here a solution to this problem by the additional measurement of thyroxine-binding globulin in the blood spots, and discrimination .for the purposes of
0022-3476/80/100604 + 04500.40/0 9 1980 The C. V. Mosby Co.