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Hypothyroidism in Early Childhood
Hypothyroidism in Early Childhood B. H. WILLIAMS, M.D., F.A.C.P.
CARL J. CRAMM, M.D.
WHEN a pediatrician or physician who treats children reads modern treatises on endocrine disorders of childhood, he learns that he cannot, within the resources of his practice, diagnose and manage all patients with endocrine disorders who may come to him. Among these patients, however, is a large group for whom early diagnosis is imperative and specific treatment is available. By reference to Wilkins' data, I this group can be defined. During a 13 year period, approximately 73,000 new patients were examined at Harriet Lane Home, the Johns Hopkins Hospital, and 997 of these patients were referred to the Endocrine Clinic of the Pediatric Department. Among these 997 patients, 233 endocrinopathies were diagnosed. Of the 233 cases, the thyroid gland was involved in 146 instances (approximately 62 per cent). Of these 146 cases of thyroid dysfunction, 77 were cases of congenital hypothyroidism (approximately 52 per cent). Of all the cases of endocrine gland disease diagnosed, congenital hypothyroidism represented more than 33 per cent. If one includes the cases of acquired hypothyroidism, hypothyroidism represents more than 42 per cent of all endocrinopathies diagnosed. I Since it is unlikely that there were selective factors in the assemblage of these data, it is suggested that one must maintain alertness for the diagnosis of hypothyroidism.
HYPOTHYROIDISM AND NEURAL GROWTH
Figure 171 is reproduced for direct reference to the normal growth curve of the central nervous system. The child is born with its full component of neurons but it is obvious that structural differentiation, maturation and myelinization of the central nervous system have precedence in the growth of a child during the preschool years, since intellectual function such as memory and habit patterns are functions of mature structures. The thyroid hormone is a sine qua non for the normal development of a child's nervous system. If there is thyroid functional deficiency within the time limit set by nature for the maturation of the nervous system, adequate replacement therapy is mandatory at the earliest possible time in order to minimize mental retardation. 1135
B. H. Williams, Carl J. Cramm
1136
Let us say for emphasis that antibiotics and gamma globulin may beguile us if the lymphoid system is disturbed by hypothyroidism and that there is much more time for the recognition and treatment of disturbed peripheral somatic growth. In congenital or early acquired hypothyroidism, thyroid hormone must be administered adequately through the preschool years if the child's natural mental age potential is to be maintained. Data published by Talbot2 indicate that a very large number of children who develop hypothyroidism at an early age have I.Q.'s under 80. Wilkins states, "When thyroid failure occurs after six years, LYMPHOID TYPE ,.,
, I
180
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Q.
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::: 120
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GENERAL TYP.
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GENtrAi. TYPE
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4
8
/
//
12
16
20
AGE IN YEARS
Fig. 171. The neural curve reveals the progress of the growth of the brain, the dura, the optic apparatus and the spinal cord. Fifty per cent of the postnatal growth of the brain is attained during the first year of life. Twenty per cent more is attained during the second year of life. (After Scammon; The Measurement of the Body in Childhood, the Measurement of Man. University of Minnesota Press, 1930.)
the mental development is usually normal, although the reactions are sluggish."l Hypothyroidism may occur in a child destined naturally to be mentally retarded, but Wilkins' illustrated cases emphasize the importance of early diagnosis and adequate therapy to preserve the patient's mentality: CASE I. At the beginning of treatment, the patient had a chronological age of 2 years, 4 months, and a mental age of 1 year, 6 months. At the age of 5 years, 10 months, the patient had a mental age of 5 years, 9 months. An increase of 4 years, 3 months in mental age thus occurred during 3 years, 6 months of therapy. Normal intelligence was preserved.
Hypothyroidism in Early Childhood
1137
CASE Il. The patient had a chronological age at the beginning of treatment of 5 years, 9 months, and a mental age of 3 years. At 10 years, 8 months, the patient's mental age was 6 years, 6 months. An increase of 3 years, 6 months in mental age occurred during a period of 4 years, 11 months of therapy; but the patient remained mentally retarded. CASE Ill. The patient's chronological age at the beginning of treatment was 8 years, 9 months, and the mental age was 3 years, 6 months. At 11 years, 9 months, the patient's mental age was 4 years, 5 months. An increase of only 11 months in mental age occurred during 3 years of therapy. The patient remained definitely retarded mentally.
A recent study 3 of a family of five adult siblings describes three cretins without goiters. One had an LQ. of 56; thyroid therapy was first administered at age ten. One had an LQ. of 36; treatment was started at age five. The third had an LQ. of 42; and was first treated at age 14. There is no doubt on examination of available data that early treatment of hypothyroidism is required for the preservation and elaboration of the nervous system. Bronstein and Shadakharaffa4 describe the brain of a ten month old completely athyreotic infant at autopsy as follows: "The brain externally appeared to be normal and looked like that of a newborn infant. Microscopically, the cortical neurons show very markedly vacuolated cytoplasm, like that of an acute anoxia. The cerebellum was normal." The child expired before adequate therapy could be established. AN ILLUSTRATIVE CASE. Figure 172, A, is a photograph of a child, 3 years and 10 months of age, an obvious cretin. The baby had been taken to a physician at the age of 1 year because the mother realized that the child was not developing normally. The mother was assured that the child would "grow out of it." It is ironical that, thus assured, the mother brought the child, as photographed, to a Well Child Conference almost three years later. Figure 172, B, shows the child after 14 months of treatment with adequate doses of desiccated thyroid. Somatic development has been impressive. Height increased from 27 to 34 inches; that is, from the ninety-seventh percentile of the 6 month old group to the tenth percentile of the 27-'2 year old group. Figures 173 and 174 depict the epiphysial development of this child. The roentgenograms suggest that bone development was completely stopped during the first month or so of life. For example, in a normal child, the head of the humerus will appear during the first 3 weeks of life. 6 It is apparent that the patient has experienced more than 2 years increase in bone age during a period of 14 months' therapy. Mentally, the child has progressed from a state of apathy and physical helplessness to that of a bright-eyed happy child who is able to stand alone but cannot walk. She cannot feed herself, and is not toilet trained. Her vocabulary is presently limited to "mama," "papa" and "agua" (water). It is impossible at present to examine her with standardized mental tests such as the "Draw a Man" or the Seguin form board. One can only say that at present the patient is grossly . retarded mentally.
B. H. Williams, Carl J. Cramm
1138
RECOGNITION OF THE HYPOTHYROID STATE
In 1941, Wilkins and Fleischmann 6 published a classic description of "The Diagnosis of Hypothyroidism in Childhood," to which Wilkins still refers. 7 Because it is evident that children with hypothyroidism do not "grow out of it" and with the desire to promote critical analysis and enthusiasm on the part of the clinician for early diagnosis, we quote: "Great differences of opinion have arisen as to what constitutes the signs of hypothyroidism in cases not presenting the frank, typical picture. In recent
A
B
Fig. 172. A, Photograph of a cretin, aged 3 years, 10 months. No previous treatment with thyroid hormone had been administered. B, The same ·child after 14 months of optimum continuous treatment with desiccated thyroid. years there have been a lack of critical analysis and an excess of enthusiasm, so that the diagnosis of hypothyroidism has been made often on the finding of some one suggestive sign. If a child's eyes are widely spaced or his nose is flat or if he is mentally retarded or physically stunted, he may be diagnosed a cretin. In fact, almost any infant who is retarded in development or who is peculiar or ugly runs a chance of being branded as having hypothyroidism. Since most physicians are aware that epiphysial ossification is delayed in hypothyroidism, roentgenograms of the bones are usually made. If retardation of osseous development is found, the physician considers that the diagnosis of hypothyroidism is proved. Dryness and coarseness of the skin and hair or a dull, phlegmatic disposition likewise may lead to uncritical diagnoses .. . . The existence of "border-
Hypothyroidism in Early Childhood
1139
Fig. 173. Roentgenograms showing epiphysial development of the heads of the humerus and femur before and after administration of desiccated thyroid. line" forms of hypothyroidism or of mixed endocrine disturbances should not be denied, nor should the therapeutic trial of thyroid be discouraged in doubtful cases. However, the limitations of our present knowledge should be frankly recognized and the need for diagnostic humility emphasized."6
It is our thesis that an early diagnosis of hypothyroidism is imperative in order that adequate treatment may minimize impaired development of the central nervous system. Therefore, one must watch for the first suggestive sign of deficiency. By its nature, hypothyroidism results in disturbed homeostasis which will give rise to various signs and symp•toms. Talbot 2 lists, in order of approximate frequency, the first suggestive symptoms of primary hypothyroidism with onset before two years
1140
B. H. Williams, Carl J. Cramm
Fig. 174. Roentgenograms showing epiphysial development of the carpus, distal femur, proximal tibia and tarsus before and after administration of desiccated thyroid.
Hypothyroidism in Early Childhood
114-1
of age as: dwarfism, slowness or apathy, slow motor development, dry skin, constipation, slow teething, poor appetite, large tongue, hernia, pot belly, deep voice, cold extremities, cold intolerance, myxedema, fat pads, and yellow skin. With onset after two years of age, the findings may be the same with the addition of easy fatigability and abnormal hair. If these symptoms and findings suggest hypothyroidism, the serum protein bound iodine should be determined since it represents the iodine of the circulating thyroid hormone. When this procedure is not available, the simpler but less reliable serum cholesterol may be obtained. In hypothyroidism, the cholesterol level usually is elevated, but in young children it may not be elevated. l With reference to the "borderline" forms of hypothyroidism postulated by Wilkins and Fleischmann in 1941, it is now possible to demonstrate the absence of, or the relative deficiency of thyroid gland function by the use of radioiodine. 8 Therapeutic Test
In the case where several signs and symptoms of hypothyroidism exist and where the more definitive diagnostic aids such as protein bound iodine or radioiodine uptake determinations cannot be obtained, a therapeutic trial of thyroid administration should be made. The administration of therapeutic doses of thyroid hormone over a limited period of time is not harmful to a euthyroid individual, and is tolerated usually without noticeable effects. On the other hand, the hypothyroid patient under treatment will be relieved of subjective and objective symptoms jf given adequate amounts. Should there be doubt regarding the efficacy of treatment, it may be discontinued. In this instance, if the patient has hypothyroidism, the serum cholesterol level rises to abnormal values within six to twelve weeks following the cessation of treatment. l Wilkiils advocates the following thyroid sensitivity test. In a hypothyroid individual, a single intramuscular injection of thyroxin, 2 mg., will lower the level of serum cholesterol from its preinjection level, and the cholesterol will not return to the previous concentration for 30 to 40 days. In the normal individual, this response is slight and transient. 1 TREATMENT OF HYPOTHYROIDISM
We have followed Wilkins' recommendations with respect to the dosage of desiccated thyroid. l Give 15 mg. (~ gr.) of desiccated thyroid daily initially, and every three weeks increase the daily dosage by 15 mg., until the optimum dosage is established. Indications of overdosage are excitability, tremulousness, jitteriness, tachycardia and hypertension. Usually, one must expect an initial weight loss in an untreated hypothyroid child during the regression of the myxedema. Amounts of desiccated thyroid adequate
1142
B. H. Williams, Carl J. Cramm
to restore physiologic homeostasis must be given. In small children, this amount generally will range from 60 to 180 mg. (1 to 3 grains) daily. SUMMARY
We have directed attention to the growth curve of the central nervous system and its relationship to hypothyroidism. Since recent research suggests that hypothyroidism may exist in all degrees, from complete athyreosis up to euthyroidism, it is recommended that the clinician should not defer judgment until the frank symptoms of hypothyroidism develop. Positive or negative evidence is valuable as obtained by the techniques of radioiodine uptake and protein bound iodine determinations. Should these procedures be unavailable, complete evaluation by a therapeutic trial of desiccated thyroid is indicated in a suspected case. If the diagnosis of hypothyroidism is established, early treatment will allow maximal growth of the central nervous system. REFERENCES 1. Wilkins, L.: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. Springfield, Ill., Charles C Thomas, 1950. 2. Talbot, N. B. and others: Functional Endocrinology from Birth through Adolescence. Cambridge, Harvard University Press, 1952. 3. N abney, J. B. C.: MUltiple Cretinism in a Family. Lancet 2: 1107 (Nov. 27) 1954. 4. Bronstein, 1. P. and Shadakharaffa, K. S.: The Thyroid Deficient Child. M. CLIN. NORTH AMERICA 34: 235-245 (Jan.) 1950. 5. Nelson, W. E.: Textbook of Pediatrics. 6th Ed. Philadelphia, W. B. Saunders Co., 1954. p. 13. 6. Wilkins, L. and Fleischmann, W.: The Diagnosis of Hypothyroidism in Childhood. J.A.M.A. 116: 2459-2465 (May 31) 1941. 7. Wilson, L., Clayton, G. W. and Berthrong, M.: Development of Goiters in Cretins . without Iodine Deficiency: Hypothyroidism Due to Apparent Inability of the Thyroid Gland to Synthesize Hormone. Pediatrics 13: 235-246 (March) 1954. 8. Silverman, S. H. and Wilkins, L.: Radioiodine Uptake in the Study of Different Types of Hypothyroidism in Childhood. Pediatrics 12: 288-299 (Sept.) 1953.
CARL J. CRAMM, M.D.
WHEN a pediatrician or physician who treats children reads modern treatises on endocrine disorders of childhood, he learns that he cannot, within the resources of his practice, diagnose and manage all patients with endocrine disorders who may come to him. Among these patients, however, is a large group for whom early diagnosis is imperative and specific treatment is available. By reference to Wilkins' data, I this group can be defined. During a 13 year period, approximately 73,000 new patients were examined at Harriet Lane Home, the Johns Hopkins Hospital, and 997 of these patients were referred to the Endocrine Clinic of the Pediatric Department. Among these 997 patients, 233 endocrinopathies were diagnosed. Of the 233 cases, the thyroid gland was involved in 146 instances (approximately 62 per cent). Of these 146 cases of thyroid dysfunction, 77 were cases of congenital hypothyroidism (approximately 52 per cent). Of all the cases of endocrine gland disease diagnosed, congenital hypothyroidism represented more than 33 per cent. If one includes the cases of acquired hypothyroidism, hypothyroidism represents more than 42 per cent of all endocrinopathies diagnosed. I Since it is unlikely that there were selective factors in the assemblage of these data, it is suggested that one must maintain alertness for the diagnosis of hypothyroidism.
HYPOTHYROIDISM AND NEURAL GROWTH
Figure 171 is reproduced for direct reference to the normal growth curve of the central nervous system. The child is born with its full component of neurons but it is obvious that structural differentiation, maturation and myelinization of the central nervous system have precedence in the growth of a child during the preschool years, since intellectual function such as memory and habit patterns are functions of mature structures. The thyroid hormone is a sine qua non for the normal development of a child's nervous system. If there is thyroid functional deficiency within the time limit set by nature for the maturation of the nervous system, adequate replacement therapy is mandatory at the earliest possible time in order to minimize mental retardation. 1135
B. H. Williams, Carl J. Cramm
1136
Let us say for emphasis that antibiotics and gamma globulin may beguile us if the lymphoid system is disturbed by hypothyroidism and that there is much more time for the recognition and treatment of disturbed peripheral somatic growth. In congenital or early acquired hypothyroidism, thyroid hormone must be administered adequately through the preschool years if the child's natural mental age potential is to be maintained. Data published by Talbot2 indicate that a very large number of children who develop hypothyroidism at an early age have I.Q.'s under 80. Wilkins states, "When thyroid failure occurs after six years, LYMPHOID TYPE ,.,
, I
180
/
~
Q.
80
\ \
J J
::: 120
...
\
I I
140
lOO
\
I I
160
~\)
I
\
\ \
\
I
\
\ \\
"
I / __ ~--~liEtiRAL-rr;;i----,
It
"
,/ /
60 I
40
"
/
I
/
/1
1
"
eo if.: I
I
I
/'f'
"
/
/
/
I
I
GENERAL TYP.
" '
I ___ ~_~_-
GENtrAi. TYPE
I
4
8
/
//
12
16
20
AGE IN YEARS
Fig. 171. The neural curve reveals the progress of the growth of the brain, the dura, the optic apparatus and the spinal cord. Fifty per cent of the postnatal growth of the brain is attained during the first year of life. Twenty per cent more is attained during the second year of life. (After Scammon; The Measurement of the Body in Childhood, the Measurement of Man. University of Minnesota Press, 1930.)
the mental development is usually normal, although the reactions are sluggish."l Hypothyroidism may occur in a child destined naturally to be mentally retarded, but Wilkins' illustrated cases emphasize the importance of early diagnosis and adequate therapy to preserve the patient's mentality: CASE I. At the beginning of treatment, the patient had a chronological age of 2 years, 4 months, and a mental age of 1 year, 6 months. At the age of 5 years, 10 months, the patient had a mental age of 5 years, 9 months. An increase of 4 years, 3 months in mental age thus occurred during 3 years, 6 months of therapy. Normal intelligence was preserved.
Hypothyroidism in Early Childhood
1137
CASE Il. The patient had a chronological age at the beginning of treatment of 5 years, 9 months, and a mental age of 3 years. At 10 years, 8 months, the patient's mental age was 6 years, 6 months. An increase of 3 years, 6 months in mental age occurred during a period of 4 years, 11 months of therapy; but the patient remained mentally retarded. CASE Ill. The patient's chronological age at the beginning of treatment was 8 years, 9 months, and the mental age was 3 years, 6 months. At 11 years, 9 months, the patient's mental age was 4 years, 5 months. An increase of only 11 months in mental age occurred during 3 years of therapy. The patient remained definitely retarded mentally.
A recent study 3 of a family of five adult siblings describes three cretins without goiters. One had an LQ. of 56; thyroid therapy was first administered at age ten. One had an LQ. of 36; treatment was started at age five. The third had an LQ. of 42; and was first treated at age 14. There is no doubt on examination of available data that early treatment of hypothyroidism is required for the preservation and elaboration of the nervous system. Bronstein and Shadakharaffa4 describe the brain of a ten month old completely athyreotic infant at autopsy as follows: "The brain externally appeared to be normal and looked like that of a newborn infant. Microscopically, the cortical neurons show very markedly vacuolated cytoplasm, like that of an acute anoxia. The cerebellum was normal." The child expired before adequate therapy could be established. AN ILLUSTRATIVE CASE. Figure 172, A, is a photograph of a child, 3 years and 10 months of age, an obvious cretin. The baby had been taken to a physician at the age of 1 year because the mother realized that the child was not developing normally. The mother was assured that the child would "grow out of it." It is ironical that, thus assured, the mother brought the child, as photographed, to a Well Child Conference almost three years later. Figure 172, B, shows the child after 14 months of treatment with adequate doses of desiccated thyroid. Somatic development has been impressive. Height increased from 27 to 34 inches; that is, from the ninety-seventh percentile of the 6 month old group to the tenth percentile of the 27-'2 year old group. Figures 173 and 174 depict the epiphysial development of this child. The roentgenograms suggest that bone development was completely stopped during the first month or so of life. For example, in a normal child, the head of the humerus will appear during the first 3 weeks of life. 6 It is apparent that the patient has experienced more than 2 years increase in bone age during a period of 14 months' therapy. Mentally, the child has progressed from a state of apathy and physical helplessness to that of a bright-eyed happy child who is able to stand alone but cannot walk. She cannot feed herself, and is not toilet trained. Her vocabulary is presently limited to "mama," "papa" and "agua" (water). It is impossible at present to examine her with standardized mental tests such as the "Draw a Man" or the Seguin form board. One can only say that at present the patient is grossly . retarded mentally.
B. H. Williams, Carl J. Cramm
1138
RECOGNITION OF THE HYPOTHYROID STATE
In 1941, Wilkins and Fleischmann 6 published a classic description of "The Diagnosis of Hypothyroidism in Childhood," to which Wilkins still refers. 7 Because it is evident that children with hypothyroidism do not "grow out of it" and with the desire to promote critical analysis and enthusiasm on the part of the clinician for early diagnosis, we quote: "Great differences of opinion have arisen as to what constitutes the signs of hypothyroidism in cases not presenting the frank, typical picture. In recent
A
B
Fig. 172. A, Photograph of a cretin, aged 3 years, 10 months. No previous treatment with thyroid hormone had been administered. B, The same ·child after 14 months of optimum continuous treatment with desiccated thyroid. years there have been a lack of critical analysis and an excess of enthusiasm, so that the diagnosis of hypothyroidism has been made often on the finding of some one suggestive sign. If a child's eyes are widely spaced or his nose is flat or if he is mentally retarded or physically stunted, he may be diagnosed a cretin. In fact, almost any infant who is retarded in development or who is peculiar or ugly runs a chance of being branded as having hypothyroidism. Since most physicians are aware that epiphysial ossification is delayed in hypothyroidism, roentgenograms of the bones are usually made. If retardation of osseous development is found, the physician considers that the diagnosis of hypothyroidism is proved. Dryness and coarseness of the skin and hair or a dull, phlegmatic disposition likewise may lead to uncritical diagnoses .. . . The existence of "border-
Hypothyroidism in Early Childhood
1139
Fig. 173. Roentgenograms showing epiphysial development of the heads of the humerus and femur before and after administration of desiccated thyroid. line" forms of hypothyroidism or of mixed endocrine disturbances should not be denied, nor should the therapeutic trial of thyroid be discouraged in doubtful cases. However, the limitations of our present knowledge should be frankly recognized and the need for diagnostic humility emphasized."6
It is our thesis that an early diagnosis of hypothyroidism is imperative in order that adequate treatment may minimize impaired development of the central nervous system. Therefore, one must watch for the first suggestive sign of deficiency. By its nature, hypothyroidism results in disturbed homeostasis which will give rise to various signs and symp•toms. Talbot 2 lists, in order of approximate frequency, the first suggestive symptoms of primary hypothyroidism with onset before two years
1140
B. H. Williams, Carl J. Cramm
Fig. 174. Roentgenograms showing epiphysial development of the carpus, distal femur, proximal tibia and tarsus before and after administration of desiccated thyroid.
Hypothyroidism in Early Childhood
114-1
of age as: dwarfism, slowness or apathy, slow motor development, dry skin, constipation, slow teething, poor appetite, large tongue, hernia, pot belly, deep voice, cold extremities, cold intolerance, myxedema, fat pads, and yellow skin. With onset after two years of age, the findings may be the same with the addition of easy fatigability and abnormal hair. If these symptoms and findings suggest hypothyroidism, the serum protein bound iodine should be determined since it represents the iodine of the circulating thyroid hormone. When this procedure is not available, the simpler but less reliable serum cholesterol may be obtained. In hypothyroidism, the cholesterol level usually is elevated, but in young children it may not be elevated. l With reference to the "borderline" forms of hypothyroidism postulated by Wilkins and Fleischmann in 1941, it is now possible to demonstrate the absence of, or the relative deficiency of thyroid gland function by the use of radioiodine. 8 Therapeutic Test
In the case where several signs and symptoms of hypothyroidism exist and where the more definitive diagnostic aids such as protein bound iodine or radioiodine uptake determinations cannot be obtained, a therapeutic trial of thyroid administration should be made. The administration of therapeutic doses of thyroid hormone over a limited period of time is not harmful to a euthyroid individual, and is tolerated usually without noticeable effects. On the other hand, the hypothyroid patient under treatment will be relieved of subjective and objective symptoms jf given adequate amounts. Should there be doubt regarding the efficacy of treatment, it may be discontinued. In this instance, if the patient has hypothyroidism, the serum cholesterol level rises to abnormal values within six to twelve weeks following the cessation of treatment. l Wilkiils advocates the following thyroid sensitivity test. In a hypothyroid individual, a single intramuscular injection of thyroxin, 2 mg., will lower the level of serum cholesterol from its preinjection level, and the cholesterol will not return to the previous concentration for 30 to 40 days. In the normal individual, this response is slight and transient. 1 TREATMENT OF HYPOTHYROIDISM
We have followed Wilkins' recommendations with respect to the dosage of desiccated thyroid. l Give 15 mg. (~ gr.) of desiccated thyroid daily initially, and every three weeks increase the daily dosage by 15 mg., until the optimum dosage is established. Indications of overdosage are excitability, tremulousness, jitteriness, tachycardia and hypertension. Usually, one must expect an initial weight loss in an untreated hypothyroid child during the regression of the myxedema. Amounts of desiccated thyroid adequate
1142
B. H. Williams, Carl J. Cramm
to restore physiologic homeostasis must be given. In small children, this amount generally will range from 60 to 180 mg. (1 to 3 grains) daily. SUMMARY
We have directed attention to the growth curve of the central nervous system and its relationship to hypothyroidism. Since recent research suggests that hypothyroidism may exist in all degrees, from complete athyreosis up to euthyroidism, it is recommended that the clinician should not defer judgment until the frank symptoms of hypothyroidism develop. Positive or negative evidence is valuable as obtained by the techniques of radioiodine uptake and protein bound iodine determinations. Should these procedures be unavailable, complete evaluation by a therapeutic trial of desiccated thyroid is indicated in a suspected case. If the diagnosis of hypothyroidism is established, early treatment will allow maximal growth of the central nervous system. REFERENCES 1. Wilkins, L.: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. Springfield, Ill., Charles C Thomas, 1950. 2. Talbot, N. B. and others: Functional Endocrinology from Birth through Adolescence. Cambridge, Harvard University Press, 1952. 3. N abney, J. B. C.: MUltiple Cretinism in a Family. Lancet 2: 1107 (Nov. 27) 1954. 4. Bronstein, 1. P. and Shadakharaffa, K. S.: The Thyroid Deficient Child. M. CLIN. NORTH AMERICA 34: 235-245 (Jan.) 1950. 5. Nelson, W. E.: Textbook of Pediatrics. 6th Ed. Philadelphia, W. B. Saunders Co., 1954. p. 13. 6. Wilkins, L. and Fleischmann, W.: The Diagnosis of Hypothyroidism in Childhood. J.A.M.A. 116: 2459-2465 (May 31) 1941. 7. Wilson, L., Clayton, G. W. and Berthrong, M.: Development of Goiters in Cretins . without Iodine Deficiency: Hypothyroidism Due to Apparent Inability of the Thyroid Gland to Synthesize Hormone. Pediatrics 13: 235-246 (March) 1954. 8. Silverman, S. H. and Wilkins, L.: Radioiodine Uptake in the Study of Different Types of Hypothyroidism in Childhood. Pediatrics 12: 288-299 (Sept.) 1953.