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The measurement of aberrant developmental growth
THE
MEASUREMENT
OF A B E R R A N T
DEVELOPMENTAL
GROWTH I. THE IV[ANAGEiKENT OF PREADOLESCENT DISTURBANCE THEODORE T. ZUCK, A.B., M . D . CLEVELAND, 0HIO THE SUBTHYROID STATE
N O M A L I E S of h u m a n stature, p r o p o r t i o n a t e g r o w t h and m a t u r i t y level, m o r e especia 11 y g 1' go a n t l"s m a n d dwarfism, h a v e a l w a y s fascinated the investigator. Quite recently, with the accumulating knowledge of ductless g l a n d u l a r physiology, disturbed metabolic states have been c a r e f u l l y studied and n u m e r o u s theories h a v e been a d v a n c e d to explain the effects of altered metabolism on the progress and endresult of g r o w t h and development. Recent experience emphasizes the value of skeletal assessment in t h e diagnosis and t r e a t m e n t of disorders which involve g r o w t h in size or p r o g r e s s t o w a r d t h e m a t u r e condition. I n o u r l a b o r a t o r y m o r e t h a n t w o t h o u s a n d complete h u m a n skeletons a n d m o r e t h a n t h i r t y - s i x h u n d r e d living individuals below the ag'e of twenty-five, studied roentgraphically, h a v e been used to elaborate s t a n d a r d s of p r o g r e s s in m a t u r a t i o n . Todd 1, 2, 3, ~, a n d Stevenson '~ h a v e r e p o r t e d this work. These s t a n d a r d s h a v e been utilized in the: assessments to follow since t h e y h a v e been w o r k e d out and tested m o r e fully t h a n other' devices of similar nature. I t is possible b y this m e t h o d to estimate the stage of ossific d e v e l o p m e n t within a six-month range. I n the s t u d y and t r e a t m e n t of a b e r r a n t g r o w t h it is i m p o r t a n t to evaluate the. anomalous p r o g r e s s t o w a r d m a t u r i t y in the individual. I n d e e d it is in this aspect of d e v e l o p m e n t a l g r o w t h t h a t the first evidence of a d i s t u r b e d m e t a b o l i s m is to be found. E n g e l b a c h and McMahon 6 and Shelton ~ h a v e r e c e n t l y emphasized the r e t a r d i n g effect of hypothyroidism. The current tendency, however, to speak of matur a t i o n solely in t e r m s of sexual m a t u r i t y does not a d e q u a t e l y interp r e t the m a t u r a t i o n process. Differentiation of f e a t u r e s indicates, as clearly as g r o w t h in stature, a constant s t r u c t u r a l change just as significant in its assessment before adolescence as at t h a t precise phase of life. The W. 1%. U. s t a n d a r d s evaluate these s t r u c t u r a l changes t h r o u g h o u t childhood a n d adolescence a n d are proving' valuable in the u n d e r s t a n d i n g of all t y p e s of f a i l u r e in the a t t a i n m e n t of a v e r a g e d e v e l o p m e n t a l progress. I n the first volume of the W h i t e From the Laboratory of Anatomy and Associated Foundations "Western Reserve University.
494
ZUCK:
M E A S U R E M E N T OF G R O W T I {
~25
House Conference reports on G r o w t h and Development s some of the conditions which lead to a severe lag in maturation are discussed. Diabetes, for example, as well a s h y p o t h y r o i d i s m and o t h e r altered metabolic conditions, handicaps the growing child in that it retards his progress toward maturity as well as the attainment of his average family stature. I N D I R E C T D E V E L O P M E N T A L GROWTI~ P R O M O T I O N
In these special cases we have studied both r e t a r d a t i o n in growth and retardation in development, using, for this purpose, anthropometrie, clinical, developmental, and psychometric technics, and bringing each
SS 1257-M.W.
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1~ig. 1 . - - C h a l ' t of g r o w t h a n d m a t u r a t i o n p r o g r e s s of SS 1257, m a l e , w h i t e , f r o m t h e a g e of t h i r t e e n y e a r s t e n m o n t h s to s i x t e e n y e a r s five m o n t h s . T r e a t m e n t only a f t e r third e x a m i n a t i o n at fifteen y e a r s eleven mdnths. In skeletal r a n g e d o w n w a r d l y d i r e c t e d lines s i g n i f y r e t a r d a t i o n ; u p w a r d l y d i r e c t e d lines, p r o g r e s s i v e m a t u r a t i o n .
:patient i n t o the l a b o r a t o r y at three-month intervals for s t u d y while u n d e r active treatment. N e a r l y 200 cases of disturbed development have been r e c o r d e d and more t h a n 35 cases are b e i n g studied and t r e a t e d at the present time. We have observed t h a t when a nutritional disorder occurs in a growing child, t h e r e is a disturbance of development M g r o w t K In the m a j o r i t y of children this i n t e r r n p t i o n is temp o r a r y and the normal progress is again resumed d u r i n g the period of convalescence, In a few children, following such a disturbance, there is no resumption of the original tempo of progress, as though the mechanisms which control growth and development had been definitely nut.flared. In these eases a progressive developmental lag be-
426
THE JOURNAL OF PEDIATRICS
comes a p p a r e n t and adult proportions or.complete m a t u r i t y m a y never be reached. A dwarfism or at best a defective m a t u r a t i o n results 9 In the t r e a t m e n t of these conditions the administration of certain endocrine substances appears to rectify the metabolic functions of the organism and thus promote developmental growth. It is, however, essential to govern the dose by a serial study of developmental growth progress d u r i n g the treatment. The following eases illustrate how progress u n d e r t h e r a p y is studied and indicate the promotion of growth at a r a t e g r e a t e r than t h a t shown in normal children u n d e r our obser~zation or in eases of a b e r r a n t growth not u n d e r treatment. SS 1257 shows a tag both in stature increment and in maturat:ion, with the progress in stature following growth promotion. (Fig. 1,
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}Pig'. 2.--Chart of growth and maturation progress of SS 1351, male, white, from the age of fourteen years ten months to seventeen years four months. Treatment only after fourth examination at seventeen years one month. In skeletal range downwardly directed lines signify retardation; upwardly directed lines, progressive m a t u r a -
tion.
Table I.) D u r i n g the first two years while the boy was being studied but not treated, height, weight, and m a t u r a t i o n showed much less than the average y e a r l y increments, so t h a t on his sixteenth b i r t h d a y the boy was r e t a r d e d the. equivalent o f f o u r years eight months in height, t h r e e years seven months in weight on the Baldwin-Wood standards, and two year's nine. months in m a t u r a t i o n on W.R..U. standards. D u r i n g the. n e x t six months A r m o u r ' s desiccated t h y r o i d (4 grains) and A r m o u r ' s desiccated a n t e r i o r p i t u i t a r y (2 grains) were administered daily by mouth. Assessments t h e n registered a height increase equivalent to eleven months on the Baldwin-Wood standards, a stationary weight., and a maturation (or developmental) increment
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JOURNAL
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equivalent to three months on the W.I~.U. standards. This case is recorded merely as an example of the encouragement of s t a t u r e increase in retarded adolescence. SS 1851 is a similar ease in which the d e v e l o p m e n t a l p r o g r e s s was materially modified following t r e a t m e n t (Fig. 2, Table I1). A f t e r two years of simple obser~eation, when this boy was sixteen years ten raonths of age he was still retarded the equivalent of three years six months in height, f o u r years four months in weight on the Baldwin-Wood s*andards, and three, years seven months in developm e n t on the W.R.U. standards. F u r t h e r , the retardation was progressive d u r i n g the two p r e c e d i n g y e a r s when no t r e a t m e n t was given. In SS 2 8 9 5 - M.W.
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~ i g . 3 . - - C h a r t o f g r o w t h a n d m a t u r a t i o n p r o g r e s s o f SS ~895, m a l e , w h i t e , f r o m t h e a g e Of f i f t e e n y e a r s f o u r m o n t h s to s e v e n t e e n y e a r s . Treatment throughout entire eight examinations. In skeletal range downwardly directed lines signify retardation; u p w a r d l y d i r e c t e d lines, p r o g r e s s i v e m a t u r a t i o n .
the six months following the institution of t r e a t m e n t the p a t i e n t grew the equivalent of twelve months in height and nine months in weight. H e also progressed the equivalent of twelve months in development. D u r i n g this time he received 2 grains of desiccated thyroid and 2 grains os desiccated anterior p i t u i t a r y for three months,, t h e n r grains of each for three months. This is again an illustration of developmental growth encouragement in retarded adolescence. The detailed relationship of endocrine dosage to progress in developmenta ! growth is presented in the following case (SS 2895), the features of which clearly indicate t h a t a therapeutic p r o g r a m for the promotion of specific effect either of increase in dimensions or of pro-
ZUCK
:
.-MEASUREMENT
OF
GROWTI~
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430
THE JOURNAL OF PEDIATRICS
gressive maturation can indeed be worked out. This ease particularly illustrates the adjustment of endocrine dosage for the promotion of growth and emphasSzes the significance of a serial maturation study. (Fig. 3, Table III.) SS 2895 was first studied in this l a b o r a t o r y on ]Yiay 9~ 1931. The boy had been a feeding problem during t h e first two years of his life, a f t e r which time he failed to grow normally. At the age of f o u r he had measles, at five ehickenpox and at six
,4 B Fig. 4.--A. l=~oentgenogram of left hand SS 2895 before treatment, aged fifteen y e a r s four months. B. l~oentgenogram of left hand SS, 2895 after twenty months' treatment, aged seventeen years. mumps. Other t h a n this his history was uneventful, t I i s p a r e n t s a r e b o t h above the average s t a t u r e and his f a m i l y history is negative. I n 1926 he h a d a course of b o t h thyroid, and a n t e r i o r p i t u i t a r y substance by mouth and became so nervous t h a t a f t e r two m o n t h s t r e a t m e n t was discontinued. I n 1928 he had another course of t h y r o i d t r e a t m e n t b u t this was also discontinued because of nervousness and irritability. W h e n first examined in our l a b o r a t o r y he was a f a i r l y well-proportioned boy, s o m e w h a t lethargic~ fifteen~ years f o u r m o n t h s t h i r t e e n clays o f age. I I i s voice
ZUCK:
]V][EASUREMENT
OF GROWTH
431
h a d not changed. There was no axillary, pubic, or f a c i a l hair. The skin a n d hair were very d r y a n d t h e s u b c u t a n e o u s t i s s u e s were u n u s u a l l y firm. The g e n i t a l i a were u n d e r d e v e l o p e d : testicles a b o u t one a n d o n e - h a l f c e n t i m e t e r s i n d i a m e t e r a n d penis f o u r c e n t i m e t e r s in l e n g t h . T h e r e was also a n u n d e r d e v e l o p m e n t of t h e m a x i l l a r y p a r t of t h e f a c e with a n a s s o c i a t e d constriction of t h e p o s t e r i o r n a s a l p a s s a g e s . The b a s a l metabolic ra~e r e g i s t e r e d m i n u s 19 per cent a n d m i n u s 17 p e r cent on two e s t i m a t i o n s . Other l a b o r a t o r y chemical t e s t s revealed n o t h i n g u n u s u a l . The p h y s i c a l a s s e s s m e n t at t h i s time ( E x a m . 1, Table I I I ) g a v e t h e b o y a h e i g h t a g e of e i g h t y e a r s e i g h t m o n t h s , w e i g h t age of eleven y e a r s six m o n t h s on t h e B a l d w i n - W o o d s t a n d a r d s , a n d a skeletal age of nine y e a r s eleven m o n t h s on our
Fig. 5.--A. R o e n t g e n o g r a m of left knee before t r e a t m e n t SS 2895. fifteen y e a r s f o u r months. B. 1%oentgenogram of left knee a f t e r t r e a t m e n t SS 2895, seventeen years. /Vote t r a n s f o r m a t i o n of cauliflower-like mineralization os patella into n o r m a l ossification a f t e r t w e n t y m o n t h s . s t a n d a r d s . T h e r e was a m a r k e d osteochondritis of t h e p a t e l l a a n d of t h e n a v i c u l a r b o n e of t h e foot. A t t h i s t i m e A r m o u r ' s t h y r o i d g l a n d t a b l e t s were prescribed, 2 g r a i n s each day, a n d A r m o u r ' s a n t e r i o r lobe p i t u i t a r y tablets, 4 g r a i n s a day. Two weeks l a t e r t h e dose was i n c r e a s e d to thyroid, 4 g r a i n s , a n d p i t u i t a r y , 6 g r a i n s . T h i s d o s a g e produced h e a d a c h e , sleeplessness, a n d a m i l d glycosuria. I t w a s t h e r e f o r e reduced to 2 g r a i n s of t h y r o i d a n d 6 g r a i n s of p i t u i t a r y a day. Two weeks later t h e g l y c o s u r i a a n d other d i s t u r b a n c e s h a d d i s a p p e a r e d a n d t h e 4 - g r a i n thyroid, 6 - g r a i n p i t u i t a r y dosage was resumed. N o f u r t h e r d i s t u r b a n c e s occurred. A f t e r two m o n t h s of t h i s r 6 g i m e ( E x a m . 2, T a b l e I I I ) t h e boy h a d lost t e n p o u n d s in w e i g h t a n d h a d n o t i n c r e a s e d i n height. T h e skin w a s t h e n n o t so d r y a n d the s u b c u t a n e o u s t i s s u e s h a d lost t h e i r u n h e a l t h y firmness.
432
THE JOURNAL OF PEDIATRICS
A f t e r five months on this dosage (Exam. 3, Table tI~) it was found t h a t the skin and hair had become quite normal in appearance. The height had incre~tsed the value of ten months and skeletal development twelve months. Weight on the other hand showed no change since the previous examination (Exam. 2). The dosage was now increased to 8 grains of thyroid and 8 grains of anterior pituitary substance a day. Three months later (Exam. 4, Table I I I ) the height had increased the equivalent of an additional ten months, weight two months, and skeletal development eighteen months. There was a beginning of the sexual development and a nearly complete healing of the osteochendritis originally noted. In view of the greater progress ~n physical development over height increase the pituitary medication was stopped and the thyroid decreased to 2 grains a day. After another three-month interval (Exam. 5, Table I I I ) it was found that the height had increased the value of ten months and weight sixteen months but skeletal development had remained praatically stationary. There was an unhealthy firmness of the subcutaneous tissues as when the boy was first seen and his skin was quite dry. The genitalia~ however, had begun to increase in size and there was now a scant amount of pubic hair. Because of the reappearing hypothyroidism the dosage of thyroid was raised to 4 grains a day and the pituitary substance again started at 2 grains a day, A f t e r three months on this dosage (Exam. 6, Table I I I ) the height had progressed the value of ten months and the weight four months. The skeletal development had also progressed the value of four months. The dosage was continued and after another inYervaI of three months (~xam. 7, Table IXI) the height had progressed the equivalent of an additional six months and weight six months~ but skeletal development now remained almost stationary. At this time it was noted that there was a mild osteoporosis developing in the texture of the bones, particularly in the hands. Consequently vitanfins A, B (with G), and D were prescribed and calcium lactate was given in a dosage of 10 grains a day; the thyroid dosage was raised to 6 grains a day and pituitary to 3 grains a day. A month later the boy had a moderately severe attack of influenza during which time the endocrine preparations were discontinued for three weeks and then resumed. At the next examination (Exam. 8, Table I I I ) height had progressed the equivalent of seven months~ welglff, th~'ee month~ and maturation nine months. B y this date the osteoporosis had again disappeared. Thus, in twenty months weight had progressed 73~ pound% the value of one year five months (i.e., eleven year's six months to twelve years eleven m o n t h s ) ; height 212 mm. (8% in.) the equivalent of four years five months (eight years eight months to thirteen years one m o n t h ) ; and skeletal development the equivalent of three years ten months (nine years eleven months to thirteen years nine months). The change in the skeletal age is well shown by the penetration of bone into the epiphyseal cartilages of the left hand (]pig. ~-A, B). The evaluation of the former is nine years three months whereas that of the latter is thirteen years. (For the criteria of evaluation see Reference 3.) The. ~r~n,~for~t~on of cauliflower-like mine~-a~izat~on of the patella ~n~o e. healthy ossificas during this period of treatment is evident in ]Pig; 5 which s h o w s the left knee at fifteen years four months and at seventeen years respectively. SUMMARY
1. Serial examinations in growth studies of children should include as,sessments of physical maturation as well as of physdeal growth. 2. I n the cases here reported, the W.I%.U. standards of physical maturation, assessed on roentgenograms of the skeleton, are e m p l o y e d be-
ZUCK:
MEASUREMENT OF GROWTH
433
cause t h e y p e r m i t g r e a t e r p r e c i s i o n of assessment t h a n t h e s t a n d a r d s put forward by other workers. 3. I l l u s t r a t i v e i n s t a n c e s f r o m o u r s t u d i e s of a b e r r a n t , g r o w t h a r e h e r e Pres.ented to d e m o n s t r a t e the. t e m p o of p r o g r e s s b e f o r e a n d d u r ing treatment for developmental growth promotion. 4. T w o b o y s a r e chosen f r o m our series of r e t a r d e d adolescence. T h e i r p r o g r e s s i n d e v e l o p m e n t a l g r o w t h f o r two years, p r e c e d i n g active i n t e r v e n t i o n is p r e s e n t e d a n d w i t h t h i s is p r e s e n t e d t h e i r progres.s d u r i n g s i x m o n t h s of e n d o c r i n e t r e a t m e n t d e v i s e d to hass a n adolescence a l r e a d y c o n s i d e r a b l y d e l a y e d . I t is. n o t i n t e n d e d to s u g g e s t t h a t , l a c k i n g t r e a t m e n t , these b o y s w o u l d n o t u l t i m a t e l y have. m a t u r e d b u t i t is c o n t e n d e d t h a t d e v e l o p m e n t a l g r o w t h m e t a b o l i s m has. been f a v o r e d and stature probably increased by treatment. 5. A t h i r d ease is p r e s e n t e d i n some. d e t a i l to i l l u s t r a t e how a d j u s t m e n t of d o s a g e a n d p r o p e r c a r e i n t h e u t i l i z a t i o n o f e x t r a c t s f r o m t h e d i f f e r e n t e n d o c r i n e g l a n d s p e r m i t one to p r o m o t e i n c r e a s e of s t a t u r e or p r o g r e s s i v e m a t u r a t i o n a s s e r i a l a s s e s s m e n t os t h e ease m a y r e q u i r e . T h e case chosen ( S S 2895) is a r e l a t i v e l y s i m p l e f o r m of r e t a r d e d d e v e l o p m e n t a l g r o w t h in w h i c h t h y r o i d a n d p i t u i t a r y s u b s t a n c e s w e r e a d e q u a t e to p r o m o t e saris,factory r e s u l t s s i n c e t h e deficiency w a s u n c o m p l i c a t e d b y a c t u a l d e f e c t s d u e to c h r o n i c d i s t u r b a n c e of' g r o w t h , to long' c o n t i n u e d f o c a l i n f e c t i o n , or o t h e r c o n s t i t u t i o n a l m u t i l a t i o n . I t m u s t n o t b e a s s m n e d t h a t e v e r y ease t r e a t e d w i l l r e s o l v e so r e a d i l y or d i s p l a y so m a r k e d a s e n s i t i v i t y to m o d i f i c a t i o n s in t h e r 6 g i m e of t r e a t m e n t a s is so b e a u t i f u l l y d e m o n s t r a t e d i n S S 2895. REFERENCES
1. Todd, T. Wiugas Child Development 1: 298, 1930. 2. Todd, T. Wingate" Child Development 1: 186, 1930. 3. Todd, T. Wingate: "l~oentgenographic Appraisement of DevelopmentM Growth in the Skeleton" in White House Conference on Child Health and Protection - - " G r o w t h and Development of the Child--Part IV--ApprMsement of the Child," New York, 1932, Century Co., pp. 258-279. 4. Todd, T. Wingate: Child Development 2: 49~ 1932. 5. Stevenson, Paul H.: Am. J. Phys. Anthropol. 7: 53, I924. 6. Engelbach, W., and 1YfciYiahon, A.: Endocrinology 8: 1, 1924. 7. She]ton, E. I~iost: J . A . M . A . 96: 759, 1931. 8. Todd, T. Wingate: "C~'owth and Development of the Skeleton" in White House Conference on Child I~Iea]th and Protection--" Growth and Development of the Child--Part I I ~ A n a t o m y and Physiology," New York, 1933, Century Co., pp. 26-130. 9. Baldwin, Bird T., and Wood, Thomas D. : Weight-Height-Age Tables in English Units of American-born Boys (Girls) (Clothed) of School Age. Iowa City: Iowa Child Welfare Research Station, 1927, pp. 4.
MEASUREMENT
OF A B E R R A N T
DEVELOPMENTAL
GROWTH I. THE IV[ANAGEiKENT OF PREADOLESCENT DISTURBANCE THEODORE T. ZUCK, A.B., M . D . CLEVELAND, 0HIO THE SUBTHYROID STATE
N O M A L I E S of h u m a n stature, p r o p o r t i o n a t e g r o w t h and m a t u r i t y level, m o r e especia 11 y g 1' go a n t l"s m a n d dwarfism, h a v e a l w a y s fascinated the investigator. Quite recently, with the accumulating knowledge of ductless g l a n d u l a r physiology, disturbed metabolic states have been c a r e f u l l y studied and n u m e r o u s theories h a v e been a d v a n c e d to explain the effects of altered metabolism on the progress and endresult of g r o w t h and development. Recent experience emphasizes the value of skeletal assessment in t h e diagnosis and t r e a t m e n t of disorders which involve g r o w t h in size or p r o g r e s s t o w a r d t h e m a t u r e condition. I n o u r l a b o r a t o r y m o r e t h a n t w o t h o u s a n d complete h u m a n skeletons a n d m o r e t h a n t h i r t y - s i x h u n d r e d living individuals below the ag'e of twenty-five, studied roentgraphically, h a v e been used to elaborate s t a n d a r d s of p r o g r e s s in m a t u r a t i o n . Todd 1, 2, 3, ~, a n d Stevenson '~ h a v e r e p o r t e d this work. These s t a n d a r d s h a v e been utilized in the: assessments to follow since t h e y h a v e been w o r k e d out and tested m o r e fully t h a n other' devices of similar nature. I t is possible b y this m e t h o d to estimate the stage of ossific d e v e l o p m e n t within a six-month range. I n the s t u d y and t r e a t m e n t of a b e r r a n t g r o w t h it is i m p o r t a n t to evaluate the. anomalous p r o g r e s s t o w a r d m a t u r i t y in the individual. I n d e e d it is in this aspect of d e v e l o p m e n t a l g r o w t h t h a t the first evidence of a d i s t u r b e d m e t a b o l i s m is to be found. E n g e l b a c h and McMahon 6 and Shelton ~ h a v e r e c e n t l y emphasized the r e t a r d i n g effect of hypothyroidism. The current tendency, however, to speak of matur a t i o n solely in t e r m s of sexual m a t u r i t y does not a d e q u a t e l y interp r e t the m a t u r a t i o n process. Differentiation of f e a t u r e s indicates, as clearly as g r o w t h in stature, a constant s t r u c t u r a l change just as significant in its assessment before adolescence as at t h a t precise phase of life. The W. 1%. U. s t a n d a r d s evaluate these s t r u c t u r a l changes t h r o u g h o u t childhood a n d adolescence a n d are proving' valuable in the u n d e r s t a n d i n g of all t y p e s of f a i l u r e in the a t t a i n m e n t of a v e r a g e d e v e l o p m e n t a l progress. I n the first volume of the W h i t e From the Laboratory of Anatomy and Associated Foundations "Western Reserve University.
494
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M E A S U R E M E N T OF G R O W T I {
~25
House Conference reports on G r o w t h and Development s some of the conditions which lead to a severe lag in maturation are discussed. Diabetes, for example, as well a s h y p o t h y r o i d i s m and o t h e r altered metabolic conditions, handicaps the growing child in that it retards his progress toward maturity as well as the attainment of his average family stature. I N D I R E C T D E V E L O P M E N T A L GROWTI~ P R O M O T I O N
In these special cases we have studied both r e t a r d a t i o n in growth and retardation in development, using, for this purpose, anthropometrie, clinical, developmental, and psychometric technics, and bringing each
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1~ig. 1 . - - C h a l ' t of g r o w t h a n d m a t u r a t i o n p r o g r e s s of SS 1257, m a l e , w h i t e , f r o m t h e a g e of t h i r t e e n y e a r s t e n m o n t h s to s i x t e e n y e a r s five m o n t h s . T r e a t m e n t only a f t e r third e x a m i n a t i o n at fifteen y e a r s eleven mdnths. In skeletal r a n g e d o w n w a r d l y d i r e c t e d lines s i g n i f y r e t a r d a t i o n ; u p w a r d l y d i r e c t e d lines, p r o g r e s s i v e m a t u r a t i o n .
:patient i n t o the l a b o r a t o r y at three-month intervals for s t u d y while u n d e r active treatment. N e a r l y 200 cases of disturbed development have been r e c o r d e d and more t h a n 35 cases are b e i n g studied and t r e a t e d at the present time. We have observed t h a t when a nutritional disorder occurs in a growing child, t h e r e is a disturbance of development M g r o w t K In the m a j o r i t y of children this i n t e r r n p t i o n is temp o r a r y and the normal progress is again resumed d u r i n g the period of convalescence, In a few children, following such a disturbance, there is no resumption of the original tempo of progress, as though the mechanisms which control growth and development had been definitely nut.flared. In these eases a progressive developmental lag be-
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THE JOURNAL OF PEDIATRICS
comes a p p a r e n t and adult proportions or.complete m a t u r i t y m a y never be reached. A dwarfism or at best a defective m a t u r a t i o n results 9 In the t r e a t m e n t of these conditions the administration of certain endocrine substances appears to rectify the metabolic functions of the organism and thus promote developmental growth. It is, however, essential to govern the dose by a serial study of developmental growth progress d u r i n g the treatment. The following eases illustrate how progress u n d e r t h e r a p y is studied and indicate the promotion of growth at a r a t e g r e a t e r than t h a t shown in normal children u n d e r our obser~zation or in eases of a b e r r a n t growth not u n d e r treatment. SS 1257 shows a tag both in stature increment and in maturat:ion, with the progress in stature following growth promotion. (Fig. 1,
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}Pig'. 2.--Chart of growth and maturation progress of SS 1351, male, white, from the age of fourteen years ten months to seventeen years four months. Treatment only after fourth examination at seventeen years one month. In skeletal range downwardly directed lines signify retardation; upwardly directed lines, progressive m a t u r a -
tion.
Table I.) D u r i n g the first two years while the boy was being studied but not treated, height, weight, and m a t u r a t i o n showed much less than the average y e a r l y increments, so t h a t on his sixteenth b i r t h d a y the boy was r e t a r d e d the. equivalent o f f o u r years eight months in height, t h r e e years seven months in weight on the Baldwin-Wood standards, and two year's nine. months in m a t u r a t i o n on W.R..U. standards. D u r i n g the. n e x t six months A r m o u r ' s desiccated t h y r o i d (4 grains) and A r m o u r ' s desiccated a n t e r i o r p i t u i t a r y (2 grains) were administered daily by mouth. Assessments t h e n registered a height increase equivalent to eleven months on the Baldwin-Wood standards, a stationary weight., and a maturation (or developmental) increment
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equivalent to three months on the W.I~.U. standards. This case is recorded merely as an example of the encouragement of s t a t u r e increase in retarded adolescence. SS 1851 is a similar ease in which the d e v e l o p m e n t a l p r o g r e s s was materially modified following t r e a t m e n t (Fig. 2, Table I1). A f t e r two years of simple obser~eation, when this boy was sixteen years ten raonths of age he was still retarded the equivalent of three years six months in height, f o u r years four months in weight on the Baldwin-Wood s*andards, and three, years seven months in developm e n t on the W.R.U. standards. F u r t h e r , the retardation was progressive d u r i n g the two p r e c e d i n g y e a r s when no t r e a t m e n t was given. In SS 2 8 9 5 - M.W.
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~ i g . 3 . - - C h a r t o f g r o w t h a n d m a t u r a t i o n p r o g r e s s o f SS ~895, m a l e , w h i t e , f r o m t h e a g e Of f i f t e e n y e a r s f o u r m o n t h s to s e v e n t e e n y e a r s . Treatment throughout entire eight examinations. In skeletal range downwardly directed lines signify retardation; u p w a r d l y d i r e c t e d lines, p r o g r e s s i v e m a t u r a t i o n .
the six months following the institution of t r e a t m e n t the p a t i e n t grew the equivalent of twelve months in height and nine months in weight. H e also progressed the equivalent of twelve months in development. D u r i n g this time he received 2 grains of desiccated thyroid and 2 grains os desiccated anterior p i t u i t a r y for three months,, t h e n r grains of each for three months. This is again an illustration of developmental growth encouragement in retarded adolescence. The detailed relationship of endocrine dosage to progress in developmenta ! growth is presented in the following case (SS 2895), the features of which clearly indicate t h a t a therapeutic p r o g r a m for the promotion of specific effect either of increase in dimensions or of pro-
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gressive maturation can indeed be worked out. This ease particularly illustrates the adjustment of endocrine dosage for the promotion of growth and emphasSzes the significance of a serial maturation study. (Fig. 3, Table III.) SS 2895 was first studied in this l a b o r a t o r y on ]Yiay 9~ 1931. The boy had been a feeding problem during t h e first two years of his life, a f t e r which time he failed to grow normally. At the age of f o u r he had measles, at five ehickenpox and at six
,4 B Fig. 4.--A. l=~oentgenogram of left hand SS 2895 before treatment, aged fifteen y e a r s four months. B. l~oentgenogram of left hand SS, 2895 after twenty months' treatment, aged seventeen years. mumps. Other t h a n this his history was uneventful, t I i s p a r e n t s a r e b o t h above the average s t a t u r e and his f a m i l y history is negative. I n 1926 he h a d a course of b o t h thyroid, and a n t e r i o r p i t u i t a r y substance by mouth and became so nervous t h a t a f t e r two m o n t h s t r e a t m e n t was discontinued. I n 1928 he had another course of t h y r o i d t r e a t m e n t b u t this was also discontinued because of nervousness and irritability. W h e n first examined in our l a b o r a t o r y he was a f a i r l y well-proportioned boy, s o m e w h a t lethargic~ fifteen~ years f o u r m o n t h s t h i r t e e n clays o f age. I I i s voice
ZUCK:
]V][EASUREMENT
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h a d not changed. There was no axillary, pubic, or f a c i a l hair. The skin a n d hair were very d r y a n d t h e s u b c u t a n e o u s t i s s u e s were u n u s u a l l y firm. The g e n i t a l i a were u n d e r d e v e l o p e d : testicles a b o u t one a n d o n e - h a l f c e n t i m e t e r s i n d i a m e t e r a n d penis f o u r c e n t i m e t e r s in l e n g t h . T h e r e was also a n u n d e r d e v e l o p m e n t of t h e m a x i l l a r y p a r t of t h e f a c e with a n a s s o c i a t e d constriction of t h e p o s t e r i o r n a s a l p a s s a g e s . The b a s a l metabolic ra~e r e g i s t e r e d m i n u s 19 per cent a n d m i n u s 17 p e r cent on two e s t i m a t i o n s . Other l a b o r a t o r y chemical t e s t s revealed n o t h i n g u n u s u a l . The p h y s i c a l a s s e s s m e n t at t h i s time ( E x a m . 1, Table I I I ) g a v e t h e b o y a h e i g h t a g e of e i g h t y e a r s e i g h t m o n t h s , w e i g h t age of eleven y e a r s six m o n t h s on t h e B a l d w i n - W o o d s t a n d a r d s , a n d a skeletal age of nine y e a r s eleven m o n t h s on our
Fig. 5.--A. R o e n t g e n o g r a m of left knee before t r e a t m e n t SS 2895. fifteen y e a r s f o u r months. B. 1%oentgenogram of left knee a f t e r t r e a t m e n t SS 2895, seventeen years. /Vote t r a n s f o r m a t i o n of cauliflower-like mineralization os patella into n o r m a l ossification a f t e r t w e n t y m o n t h s . s t a n d a r d s . T h e r e was a m a r k e d osteochondritis of t h e p a t e l l a a n d of t h e n a v i c u l a r b o n e of t h e foot. A t t h i s t i m e A r m o u r ' s t h y r o i d g l a n d t a b l e t s were prescribed, 2 g r a i n s each day, a n d A r m o u r ' s a n t e r i o r lobe p i t u i t a r y tablets, 4 g r a i n s a day. Two weeks l a t e r t h e dose was i n c r e a s e d to thyroid, 4 g r a i n s , a n d p i t u i t a r y , 6 g r a i n s . T h i s d o s a g e produced h e a d a c h e , sleeplessness, a n d a m i l d glycosuria. I t w a s t h e r e f o r e reduced to 2 g r a i n s of t h y r o i d a n d 6 g r a i n s of p i t u i t a r y a day. Two weeks later t h e g l y c o s u r i a a n d other d i s t u r b a n c e s h a d d i s a p p e a r e d a n d t h e 4 - g r a i n thyroid, 6 - g r a i n p i t u i t a r y dosage was resumed. N o f u r t h e r d i s t u r b a n c e s occurred. A f t e r two m o n t h s of t h i s r 6 g i m e ( E x a m . 2, T a b l e I I I ) t h e boy h a d lost t e n p o u n d s in w e i g h t a n d h a d n o t i n c r e a s e d i n height. T h e skin w a s t h e n n o t so d r y a n d the s u b c u t a n e o u s t i s s u e s h a d lost t h e i r u n h e a l t h y firmness.
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A f t e r five months on this dosage (Exam. 3, Table tI~) it was found t h a t the skin and hair had become quite normal in appearance. The height had incre~tsed the value of ten months and skeletal development twelve months. Weight on the other hand showed no change since the previous examination (Exam. 2). The dosage was now increased to 8 grains of thyroid and 8 grains of anterior pituitary substance a day. Three months later (Exam. 4, Table I I I ) the height had increased the equivalent of an additional ten months, weight two months, and skeletal development eighteen months. There was a beginning of the sexual development and a nearly complete healing of the osteochendritis originally noted. In view of the greater progress ~n physical development over height increase the pituitary medication was stopped and the thyroid decreased to 2 grains a day. After another three-month interval (Exam. 5, Table I I I ) it was found that the height had increased the value of ten months and weight sixteen months but skeletal development had remained praatically stationary. There was an unhealthy firmness of the subcutaneous tissues as when the boy was first seen and his skin was quite dry. The genitalia~ however, had begun to increase in size and there was now a scant amount of pubic hair. Because of the reappearing hypothyroidism the dosage of thyroid was raised to 4 grains a day and the pituitary substance again started at 2 grains a day, A f t e r three months on this dosage (Exam. 6, Table I I I ) the height had progressed the value of ten months and the weight four months. The skeletal development had also progressed the value of four months. The dosage was continued and after another inYervaI of three months (~xam. 7, Table IXI) the height had progressed the equivalent of an additional six months and weight six months~ but skeletal development now remained almost stationary. At this time it was noted that there was a mild osteoporosis developing in the texture of the bones, particularly in the hands. Consequently vitanfins A, B (with G), and D were prescribed and calcium lactate was given in a dosage of 10 grains a day; the thyroid dosage was raised to 6 grains a day and pituitary to 3 grains a day. A month later the boy had a moderately severe attack of influenza during which time the endocrine preparations were discontinued for three weeks and then resumed. At the next examination (Exam. 8, Table I I I ) height had progressed the equivalent of seven months~ welglff, th~'ee month~ and maturation nine months. B y this date the osteoporosis had again disappeared. Thus, in twenty months weight had progressed 73~ pound% the value of one year five months (i.e., eleven year's six months to twelve years eleven m o n t h s ) ; height 212 mm. (8% in.) the equivalent of four years five months (eight years eight months to thirteen years one m o n t h ) ; and skeletal development the equivalent of three years ten months (nine years eleven months to thirteen years nine months). The change in the skeletal age is well shown by the penetration of bone into the epiphyseal cartilages of the left hand (]pig. ~-A, B). The evaluation of the former is nine years three months whereas that of the latter is thirteen years. (For the criteria of evaluation see Reference 3.) The. ~r~n,~for~t~on of cauliflower-like mine~-a~izat~on of the patella ~n~o e. healthy ossificas during this period of treatment is evident in ]Pig; 5 which s h o w s the left knee at fifteen years four months and at seventeen years respectively. SUMMARY
1. Serial examinations in growth studies of children should include as,sessments of physical maturation as well as of physdeal growth. 2. I n the cases here reported, the W.I%.U. standards of physical maturation, assessed on roentgenograms of the skeleton, are e m p l o y e d be-
ZUCK:
MEASUREMENT OF GROWTH
433
cause t h e y p e r m i t g r e a t e r p r e c i s i o n of assessment t h a n t h e s t a n d a r d s put forward by other workers. 3. I l l u s t r a t i v e i n s t a n c e s f r o m o u r s t u d i e s of a b e r r a n t , g r o w t h a r e h e r e Pres.ented to d e m o n s t r a t e the. t e m p o of p r o g r e s s b e f o r e a n d d u r ing treatment for developmental growth promotion. 4. T w o b o y s a r e chosen f r o m our series of r e t a r d e d adolescence. T h e i r p r o g r e s s i n d e v e l o p m e n t a l g r o w t h f o r two years, p r e c e d i n g active i n t e r v e n t i o n is p r e s e n t e d a n d w i t h t h i s is p r e s e n t e d t h e i r progres.s d u r i n g s i x m o n t h s of e n d o c r i n e t r e a t m e n t d e v i s e d to hass a n adolescence a l r e a d y c o n s i d e r a b l y d e l a y e d . I t is. n o t i n t e n d e d to s u g g e s t t h a t , l a c k i n g t r e a t m e n t , these b o y s w o u l d n o t u l t i m a t e l y have. m a t u r e d b u t i t is c o n t e n d e d t h a t d e v e l o p m e n t a l g r o w t h m e t a b o l i s m has. been f a v o r e d and stature probably increased by treatment. 5. A t h i r d ease is p r e s e n t e d i n some. d e t a i l to i l l u s t r a t e how a d j u s t m e n t of d o s a g e a n d p r o p e r c a r e i n t h e u t i l i z a t i o n o f e x t r a c t s f r o m t h e d i f f e r e n t e n d o c r i n e g l a n d s p e r m i t one to p r o m o t e i n c r e a s e of s t a t u r e or p r o g r e s s i v e m a t u r a t i o n a s s e r i a l a s s e s s m e n t os t h e ease m a y r e q u i r e . T h e case chosen ( S S 2895) is a r e l a t i v e l y s i m p l e f o r m of r e t a r d e d d e v e l o p m e n t a l g r o w t h in w h i c h t h y r o i d a n d p i t u i t a r y s u b s t a n c e s w e r e a d e q u a t e to p r o m o t e saris,factory r e s u l t s s i n c e t h e deficiency w a s u n c o m p l i c a t e d b y a c t u a l d e f e c t s d u e to c h r o n i c d i s t u r b a n c e of' g r o w t h , to long' c o n t i n u e d f o c a l i n f e c t i o n , or o t h e r c o n s t i t u t i o n a l m u t i l a t i o n . I t m u s t n o t b e a s s m n e d t h a t e v e r y ease t r e a t e d w i l l r e s o l v e so r e a d i l y or d i s p l a y so m a r k e d a s e n s i t i v i t y to m o d i f i c a t i o n s in t h e r 6 g i m e of t r e a t m e n t a s is so b e a u t i f u l l y d e m o n s t r a t e d i n S S 2895. REFERENCES
1. Todd, T. Wiugas Child Development 1: 298, 1930. 2. Todd, T. Wingate" Child Development 1: 186, 1930. 3. Todd, T. Wingate: "l~oentgenographic Appraisement of DevelopmentM Growth in the Skeleton" in White House Conference on Child Health and Protection - - " G r o w t h and Development of the Child--Part IV--ApprMsement of the Child," New York, 1932, Century Co., pp. 258-279. 4. Todd, T. Wingate: Child Development 2: 49~ 1932. 5. Stevenson, Paul H.: Am. J. Phys. Anthropol. 7: 53, I924. 6. Engelbach, W., and 1YfciYiahon, A.: Endocrinology 8: 1, 1924. 7. She]ton, E. I~iost: J . A . M . A . 96: 759, 1931. 8. Todd, T. Wingate: "C~'owth and Development of the Skeleton" in White House Conference on Child I~Iea]th and Protection--" Growth and Development of the Child--Part I I ~ A n a t o m y and Physiology," New York, 1933, Century Co., pp. 26-130. 9. Baldwin, Bird T., and Wood, Thomas D. : Weight-Height-Age Tables in English Units of American-born Boys (Girls) (Clothed) of School Age. Iowa City: Iowa Child Welfare Research Station, 1927, pp. 4.