Frederic M. Kenny, M.D., Chawalit Preeyasombat, M.D., and
Claude J. Migeon, M.D.; with the technical assistance of
Betty Lawrence and Catherine Richards, B.S.
University of Pittsburgh School of Medicine and the Children’s Hospital of Pittsburgh; 071(1 the I!arrk’t
Lane Service of the Children’s Medical and Surgical Center,
Johns Hopkins Hospital and University
Ftc. 1. Cortisol production rate in normal newborn
infants delivered by the vaginal route.
34
CORTISOL
PRODUCTION
RATE
II.
Normal
Infants,
Children, and
Adults
I
N A previous communication, we pne-sented data on the production of cor-tisol in a small series of newborn 2Subsequently, Aarskog3 and Bertrand, et al.
published data on newborns utilizing in vivo isotope dilution techniques similar to those which we employed. All of these data suggest that at least during the first few days of life, the newborn infant produces more contisol relative to his total body sun-face area than does the adult.
In an effort to define more precisely the
normal range of cortisol secretion in the
newborn period, and to attempt to deter-mine when the production rate more nearly approaches the adult level, we have studied an additional 15 full-term and 4 premature babies delivered by vaginal delivery, bring-ing the total of these babies to 31. In addi-tion, we have compared this group with a group of 13 cesanean section babies; this latter group was chosen because Migeon,
et al. had earlier shown that the level of
17-hydnoxycorticosteroids in the cord blood
of cesanean section babies was significantly lower than the level in vaginal deliveries.
Finally, cortisol production rate studies
were done in a group of 17 normal older children and young adults, ranging in age from 4 months to 20 years. There is no
pre-vious report of the cortisol production rate
in normal subjects in this age group.
METHODS
Experimental Sublects
INFANTS DELIVERED BY THE VAGINAL
Roui’i: A group of 15 full-term and 4 pre-mature infants was studied (Cases 1-19 of Table I). Data obtained previously2 on 7 full-term and 5 premature infants are in-eluded in the results presented in Figure 1. This brings the total number of full-term in-fants to 22 and that of premature infants to 9.
INFANTS DELIVERED BY CESAREAN
SEC-TION:
A
group of 8 infants delivered byelective and 1 infant delivered by indicated section (after 6 hours of labor) was studied
(Cases 20-28 of Table II). Data obtained
CP R NORMAL INFANTS I FULL TERM
VAGINAL DELIVCRY 0 PREMATURE
U
I
0 , S , 0 ,
, , ,
AG IN DAYS
(Submitted April 12; accepted for publication August 2, 1965.)
This work was supported by U. S. Public Health Service Research Grants NB 04963-01, FR 84-01,
and AM-00180, and the Renziehausen Fund. Dr. Preeyasombat was a Renziehausen Fellow.
ADDRESS: (F.M.K.) Children’s Ilospital of Pittsburgh, 125 De Soto Street, Pittsburgh, Pennsylvania
15213.
ubjee1s Sex Age Case No. height Weight (cm) (gm) Dose (c/rn) Specific Activities Unconjugatcd 4 5 6 7 8 9 10 11 ‘V 13 ‘4 15’ 16’ 17 18 ‘9’ I1 11 11 11 F Is1 M F 11 11
M
11 i1 FM
F M 11 1 hr 4 hr 36 hr 48 hr 48 hr 60 hr 7 hr 96 hr 61 da 8da 8da 8da 9da , da 14 do 16 da 17 do 18 do 20 do 53 49 50 48 49 48 51 51 50 51 53 43 54 48 47 55 54 49 3,200 2,6002,800 2,770
2,950
3,080 3,190 3,390
3,520 3,200 3,610 2,150 3,850 3,640
2,685
2,400
4,450
4,250 3,350
110,500
1 12,300
I10,900
1 11,600
109, 800
75,800 76,600 74,900
111,400 7 ‘100 112,100
76,100
1 10, 800 1 1 1,600 77,000
75,900
109, 500
I 1 1,000 110,700
6-OHF10.8THE 11.5
THE 12.5
63-OHF 17.0 6$-OHF 19.9
IW-OHF 9.8THE 13.8
6,9-OHF8.7 THE 18.2
6-OHF 17.4
69-OHF 14.5THE 15.2
65-OIIF 23.2
6-OHF 17.4
6-oH24.oTHE 19.9 63-O11 17.3
Glucuronides
Th1,’ Allo THE
. . . . 13.7 ..
.
. 16.111.9 . 16.4
. . . . 14.9
13.5 . . 10.6
15.8 14.0 12.4
. . 8.9 11.0 .
.
.
. 7.6. .
.
. 21.6. . . . 15.0
18.5 . . 13.6
. . . . 22.4
. . . . 18.0
. . . . 27.6
. .
. 14.6 . . . . 15.814.1 . . 12.1
24.3 . 20.5
.
.. .
19.7Cortisol
Production
mg/24 hr
mg/MI/24
hr
4.6 (22) 3.9 (21) 3.7 (19.5) 3.2 (17.8) 4.5(23.6) 2.7 (13.9) 3.5 (17.5)
4.6 (21. 9)
2.8 (13.5) 2.4 (12) 3.4 (15.5) 1.7 (11.0) 3.5 (15.0) 2.2 (10) 2.4 (13) 2.4 (14) 4.2 (17) 2.5 (10.5) 3.0 (15) Are,-age 12.0 14.3 15.1 17.4 12.1 14. 1 10.9 8. 15 19.9 15.0 16.5 22.4 15.9 25.4 16.0 15.8 13.1 22.2 18.5 Urinary 17-OHCS mg/24 hr mg/M’/4 hr 0.2 (0.95) 0.2 (1.1)
0. 15 (0. 8)
0.3 (1.66) 0.3(1.58) 0. 15 (0.77)
0.25 (1.25) 0.55 (2.61) 0.2 (0.95) 0.3 (1.5) 0.5 (2.26) 0.3(2.0) 0.6 (2.6)
0.5 (2.27)
0.3 (1.66)
0.35 (2.0)
0.75 (3.0)
0.35 (1.46) 0.6 (3.0)
. Premature by weight.
previously on 5 infants (3 full-term and 2 maphnodite (ambiguous external genitalia,
premature) delivered by elective cesarean buccal smear chromatin negative, but other-section are included in the results presented wise normal)2 and on 4 young adultsa were in Figure 2, bringing the total number of included in the results presented in Figures
elective cesarean sections to 13, and that of 3 and 4, bringing the total number of
sub-indicated sections to 1. jects in this group to 20.
NORMAL SUBJECTS, 4 MONTHS TO 20 YEARS NORMAL SUBJECTS, 21 TO 48 YEARS OF
OF AGE: A group of 15 normal subjects was AGE: Data obtained previously0 on 26
nor-studied (Cases 29-43 of Table III). Data ob- mal subjects and those obtained on 2 other tamed previously on 1 male pseudoher- individuals (Cases 44 and 45) are presented
TABLE II
CouTIso1 PuoDuc-rIoN RATE IN NouIAL, FULL-TERM, NEWBORN INFANTS 1)ELIYERED BY
ELECTIVE CESAHEAN SEc’rIoN
Specific. Actirities (Glucvronides) Case No. 20 21 22 23 24’ 25 26 27 28 Sex F M F F 11 M F “I F Cortisol Production .4ge 3 hr 8hr 8hr 22 hr 22hr 25 hr 27 hr 27 hr 27 hr height (cm) 43 52 48 51 49 52 53 50 46 Weigh! (gm) 2,055
3,800
3,900 2,900
2,600
3,000 3,000 3, 000
2,600
Urinary 17-OJICS Doie
89,320
86 ,210
94,965
85, 120
28, 850
45,290
93,960
94,363 93,595
mg/MI/4 zng/JfI/t
rng/4 hr hr mg/24 hr hr
Alto 27.7 6.3 THE 22.6 8.8 12.3 18.0 3.7 5.6 10.0 10.2 20.5 A‘erage 25.2 8.8 12.3 18.0 3.7 5.6 8.15 10.2 20.5 1.8 4.9 3.9 2.4 3.9 4.0 5.8 4.6 2.3 11.8 21.4 18.6 11.7 21.7 19.0 28.8 23.0 13.8 0.05 0.75 0.1 0.32 0.1 0.4 0.2 0.15 0.15 0.33 3.25 0.48 1.6 0.56 I .1) 1.0 0.75 0.88
*Indicated eeaarean section.
TABLE I
(‘ORTISOL Pitoovt’rtox RATE IN NoIsMAI, FuII-Tne5I, NEVB015N INFANTS
6
0 vi
14
N
(A
25I
I
. FULL TERM
0 PREMATURE
INDICATED
MEAN ±2 SD
VAGINAL DEL.
MEAN ±2 SD
VAGINAL DEL.
AGE IN DAYS ____________________________________
FIG. 2. Cortisol production rate in normal newborn Fic. 3. Cortisol production rate (mg/24 hr.) in
infants delivered by elective cesarean section. normal children and adults.
TABLE III
(ouTISoI PIaool’erIoN IN No1ta1AI SUBJECTS, 4 \LONTHS TO () EAIIS OF
Case
No. ex .ige
. height
(m)
. . JJ eight
. (kg)
(‘or/leo! Production
I
rinary 1 7-OII(’S-sng/2. hr iiig/JI2/2!g hr mg/.14 hr mg/M2/24hr
29 F 4mon 66 6.7 5.5 16.2 (1.95 2.8
30 i1 6mon 61 5.1 1.8 6.3 (1.44 1.6
31 1Sf 2125 yr 89 13.() 3.5
t;.
0.5
0.93
F
4yr 101 16.() 7.9 8.5 0.9 1.033
F
4yr 101 1.5.5 6.5 10.() 1.6 .534
11 5yr 1U 19.0 12.1 13.7 tL7 3.53.5 M 7yr 131 26.() 8.7 9.0 2.3 2.4
36 F 8yr 1li 3.() 11.9 13.5 3.3 3.7
37 ii: iflyr H9 23.8 9.0 9.6 i.5 2.6
38 M 11 yr 140 32.() 16.6 15.0 3.9 3.5
39 F 1yr 131) 1’1.H 14.1 15.2 3.1 3.4
40 M l3yr 15l 39.6 13.3 FL5 4.’t 3.2
41 F l4yr 15’2 44.5 21.2 15.5 4.5
4 M 20yr 16i 59.2 24.6 14.5 6.4 ‘3.8
43 F 2Oyr 165 .57.0 26.6 16.5 6.1 ‘3.8
(Figs. 3 and 4) for the purpose of compar-ing the results found in adults with those of infants and children.
PERMISSION FOR SnjDY: In every study,
verbal permission was obtained from the subjects, if adult, or from the parents when infants or children were injected. In
addi-tion, written permission was obtained from
parents of infants studied at the Magee Women’s Hospital. The isotope safety corn-mittees of both our institutions had
previ-CPR ELECTIVE
CESAREAN SECTION
ously approved our studies. The procedure was considered safe because (a) the labeled steroid can be quantitatively recovered in urine and stool within 48 hours, and (b)
during the time that labeled steroid was present in the body of the infant, the amount of total body radiation received
from 4ChIcortisol and 1,2-H#{176}-contisol
amounted to less than that derived from na-tural radiation during 48 hours.
Body Surface Area
The various subjects were carefully
weighed and measured and their surface
CPR NORMAL CHILDREN I MALE
AND ADULTS 0 PEMALE
. S 0
25 S #{149}OS
S S S
2O 5 05 OS
0 05 5 0
I 0
S#{149} 0 S 0
1
Eu 0
..‘ S 0 0
10 0
0
5 5
I
- 5I 0 5 20 25 30I 35 40 45
37
CPR NORMAL CHILDREN S MALE
AND ADULTS 0 FEMALE
25 m
I
20
w
i5
MEAN
±230
#{149}0 0
2 0 5 20 25 30 35 40 45
AGE IN YEARS
Fic. 4. Cortisol production rate (mg/M2/24 hr) in
normal children and adults.
area was obtained from these measure-rnents by means of the nomogram of DuBois.
Determination of Urinary 17,21 -dihydroxy-20-ketosteroids
(17-OHCS)
The urinary excretion of 17-OHCS was measured by a modification#{176} of the method of Glenn and Nelson.7 Ten to 50 ml aliquots of the 48-hour urine pool were incubated overnight with -glucuronidase (7,500 units per 10 ml of urine) at pH 4.6. The urine was extracted three times with twice its volume of chloroform. The chloroform extracts were washed with 0.1 N NaOH and 0.1 N HCI, and then evaporated to dryness. One aliquot of the residue was treated with the Porter-Silber Reagent, and the color developing after overnight incubation was read on a Beckman DU spectrophotometer against a blank made of a similar aliquot of the
resi-due but in which the phenylhydrazine was omitted.
Cortisol Production Rate (CPR)
Some of the studies were performed in
Baltimore, Maryland, and some in Pitts-burgh, Pennsylvania. A few were performed in both cities as a check on the reproduci-bility of the results, with good agreement. In the studies performed in Pittsburgh, 4-C1-cortisol (specific activity 25 c/milli-mole) was obtained from the New England Nuclear Company. Its purity was tested by paper chromatography. It was
chromato-graphed in a Bush B5 system for 4 hours alongside non-radioactive cortisol, which
was used as a marker. The 4-C’-cortisol was 96% pure and was not purified further.
In the studies performed in Baltimore, 1,2-H#{176}-cortisol (specific activity 50 y.c per
1 .g) was graciously provided by the
En-docrinology Study Section, Division of Re-search Grants, National Institute of Health, Bethesda, Maryland. This material was re-chromatographed and the eluted material was injected.
In Pittsburgh, a Nuclear Chicago C115 low background gas flow counter was used to measure radioactivity. Background was about 1.6 counts per minute, and the count-ing efficiency was about 30%. In Baltimore, a Nuclear-Chicago Liquid Scintillation
counter was used, the counting efficiency of
tritium being about 40%.
Factors Affecting the Accuracy and Validity of the In Vivo Isotope Dilution Technique
in Newborn Subjects
POOL SizE: Among the factors that influ-ence the accuracy of cortisol production estimations is the constancy of the various body pools such as the outer pool (plasma volume, extracellular volume and liver inter-cellular volume) and inner pool
(intracellu-lar volume and liver intracellular volume) during the period that the test is in
prog-ress.8 When delayed clamping of the cord
is employed, a significant decrease in blood volume occurs during the first 4 hours of life.9 However, after that time, no marked alteration in blood volume occurs, whether immediate or delayed cord clamping is practiced. Our test was started before the age of 4 hours in only one infant. This baby, delivered by cesarean section, was
started on the study at 3 hours of age. It is possible that in this infant, the estima-tion of cortisol production may have been less valid than in those studied after the blood volume became stabilized.
38
CORTISOL PRODUCTIONthe first year of life, pfl)bablV too small to affect our results.#{176} It is possible that a significant shift in intracellular volume might occur during the first few days of life, but we are unaware of data to support
such a shift.
VARIABILITY IN SPECIFIC Aci-ivrnis
AMONG VARIOUS METABOLITES: EFFECT ON
RELIABILITY OF FINAL CALCULATED VALUES:
For each patient, the average of the specific activities of the metabolites was deter-mined. The dose administered was divided by the average specific activity. The result-ing figure was the estimated cortisol pro-duction per 48 hours, expressed in
micro-grams.2
The discrepancies in values from one metabolite to another, when several were measured in a given individual, was of great magnitude in some cases (e.g., sub-jects 2, 3, 7, 18, and 26). Had the cortisol production rate been calculated from the specific activity furthest from the mean, a disparity in the final results of 0.6, 1.0, 0.8, 0.3, and 1.6 mg per day respectively would have been obtained in those subjects. The discrepancies between specific activities probably result from the limitations im-posed by working with small amounts of
metabolites.
In order for the technique employed to be valid, it is necessary for radioactive
cor-tisol to be metabolized in the same manner as endogenous cortisol; the metabolites con-sidered must be derived exclusively from cortisol; and all the radioactivity in the form of the metabolite analyzed must be col-lected. It is unnecessary for the rates of
pro-duction and excretion of each measured metabolite to be identical in the period of urine collection. That these postulates were probably fulfilled is shown by the generally good agreement among specific activities of different metabolites, excluding those cited above. The finding by Aarskog3 of rather close agreement between paired spe-cific activities of tetrahydrocortisol and
tetrahydrocortisone (less than
±
8.5% devia-lion from the mean) in five newborn babies,lends support to the validity of the
tech-nique, as both Aarskog’s method and ours
are modifications of the method of Cope
and Black.hl
INTERPRETATION OF THE RESULTS OF Oun
STUDIES IN NEWBORNS LESS THAN 48 HOURS
OF AGE: At present, there is no method by which one can measure separately cortisol produced by the newborn infant and that produced by the mother. Therefore, when our studies were initiated under 48 hours of age, it is likely that maternal
contribu-tion of steroids played a role in the findings presented. After 48 hours of age, it is
un-likely that maternally derived steroid af-fected our studies, since it is well
docu-mented that even very early in 2 12 only
negligible amounts of isotope are excreted later than 48 hours following an injection.
RESULTS
Normal Full-Term and Premature Newborn
Infants Delivered by the Vaginal Route
The data obtained in the 19 infants studied in the present paper (Table I) and those reported earlier on 12 other infants2
are shown in Figure 1.
Although the number of premature
in-fants was small, it would appear that their
CPR fell in the range of the values of the
CPR of the full-term infants.
As seen in Figure 1, when the study was started prior to 5 days of age, the values of the CPR in mg/day were higher than when started between 5 and 20 days of age. The difference between the two means (Table IV) is statistically significant (p = 0.01).
This was also true when the values were corrected for body surface area (p = 0.01).
Normal Full-Term and Premature Newborn
Infants Delivered by Cesarean Section
The data obtained in the 9 infants studied in the present paper (Table II) and those reported earlier on 5 other infants2 are
shown in Figure 2. In all cases the study was started prior to or at 5 days of age. The
MEAN STANDA1ID l)EvIATION OF TIlE CORTI.SOL PRODUCTION RATES IN THE VARIOUS GROUPS OF NoR1AI SUBJECTS OF THE PRESENT STUDY
Subjects
-__________________________
4ge NiL umber
of Cases
Mean and Standard Deviation of
Cortisol Production Rate
mg/day iiig/312/day
-_________________
5
days 5days 5 days3.7±0.8 3.6
3.7±0.8
3.1±1.7
) .4±0.6
2.8±1).7
3.3±1.3
18 .3
±
3.61.4
18 .7±3.7
14 .0
± ‘2
.9 13.8± ‘2 .9 13.9 ±‘2 .917.’2±3.8
14
0
16
8
15
14
11 9
20 14 14 28
48
had a birth weight less than 2,500 gm. The
CPR of these 4 infants fell in the range of the CPR of the 10 cases of full term, elec-tive cesarean section. The mean CPR ex-pressed either in mg/day or in mg/M2/day for this group (Table IV) was not statis-tically different from that obtained in in-fants less than 5 days of age delivered by the vaginal route.
Subjects 4 Months to 20 Years of Age
In this group CPR increased with age, from a low of 1.8 mg/day in a 6 month old baby to 26.6 mg/day in a 203 year old (Figure 3). When corrected for body sur-face area, the values ranged from 6.3 mg/
42 to 16.5 mg/M#{176}, with a mean of 12.1
±
2.9 (Figure 4).
Subjects 21 to 48 Years of Age
When corrected for surface area, the CPR
of the females were not significantly differ-ent from those of the males. Furthermore, there were no significant differences be-tween these values and those obtained in subjects 4 months to 20 years of age (Table
IV). The average CPR in mg/M#{176}/24 hr for the 48 males and females 4 months to 48
years of age was 11.8
±
2.5.This mean was significantly lower than those of the 16 full-term and premature in-fants delivered by the vaginal route and less than 5 days of age (p > 0.001) and
the 14 full-term and premature infants
de-livered by elective cesarean section and less than 5 days of age (p > 0.001). The mean of the 15 full-term and premature infants delivered by the vaginal route and 5 to 20 days of age (13.9
±
2.9 mg/M#{176}/24 hr) was higher than that of the 4 month to 48-year-old subjects but the difference was not statistically significant.TABLE IV
Vaginal delivery Full term
Premature
Full term & premature
Vaginal delivery
Full term Premature
Full term & Premature
Cesarean sectioti
Full term & premature
Older subjects Males
Females
Males & females Males
Females Males & females Males & feniales
5 to 20 (laSS
5 to 20 days 5 to 10 (layS
5days
4mon to O yr
4mon to 0 yr
4 mon to O yr
21 to 48 yr
21 to 48 yr ‘21 to 48 yr
4 mon to 48 yr
.. H.±S.1
.. 13.1±i2.8 ..
21.9±3.7 11.3±1.9
17.3±3.9 1’2.0±2.2
Urinary 17-OHCS
In the normal vaginally delivered in-fants under 5 days of age, urinary 17-OHCS ranged from 0.15 to 0.55 mg/day, with a mean value of 0.255 mg/day. For those over age
5
days, the range was from 0.16 to 0.75 mg/day, with a mean value of 0.44 mg/day. On the basis of calculated body surface area, those under age 5 days had a mean value of 1.2 mg/M2/day; those over 5 days had a mean value of 2.2 mg/M2/ day. Ratios of CPR to urinary 17-OHCSranged from 3.7 to 26.5.
In the group of older subjects (4% to 20
years of age) the ratio of CPR to urinary
17-OHCS averaged 4.0 (range 3.5-4.7).
COMMENTS
Full-Term and Premature Infants
Delivered Vaginally
Aarskog,3 utilizing a modification of the method of Cope and Black,u1 studied 5 nor-mal newborns and 8 newborns of diabetic mothers, all under 5 days of age; the mean
CPR were 21.96 and 26.89 mg/M2/24 hr respectively, the difference between the two
groups being not statistically significant. This author concluded that on the basis of surface area, cortisol production of infants is greater than that of adults. Bertrand, Loras, and Gilly4 found higher rates in new-boms under 5 days of age than in older newborns; the mean CPR for 8 infants in the former group was 21.9 mg/M2/day and
for 13 infants in the latter group was 16.4
mg/M2/day. In the present study, during
the first 5 days of life, CPR, both in mg/day and in mg/M2/day, were significantly higher than those of babies 5 to 20 days of age.
Full-Term and Premature Infants
Delivered by Cesarean Section
Cortisol crosses the “placental barrier”
from the mother to the fetus as well as from the fetus to the mother.3 Usually, an equilibrium is established so that the ma-ternal plasma concentrations are several
times higher than the fetal concentrations.13
References in the older literature suggested that the stress of labor and vaginal delivery might increase the plasma levels of
17-OHCS of mother and infant. On the other hand, the surgery of an elective cesarean section up to the time of delivery was thought to be only a mild stress, which did
not increase markedly the plasma 17-OHCS levels of the mother, the levels in cord blood being hl5
Even though cord plasma 17-OHCS are
higher in infants delivered by the vaginal
route than in infants delivered by elective cesarean section, CPR begun during the first 5 days of life was similar in both groups. This suggests that if adrenal stim-ulation occurs during labor with resulting
increase in plasma 17-OHCS, these are
transient changes as far as the babies are concerned. In addition, it would appear that the stress of labor is not the cause of the elevated CPR in babies delivered by
the vaginal route and under 5 days of age.
The data referred to above is in rather close agreement with those recently ob-tamed by more specific measurements of total plasma cortisol plus cortisone. Using a double isotope derivative assay, Hillman
and Giroud#{176} have found a mean value of 21.4 lLg% for the sum of cord cortisol plus
cortisone at the time of delivery; the figure
for the mother was 57.6 i.g%. Similar fig-ures of 27 .g% for cord 17-OHCS and
62 .g% for the mother were found by Mi-geon and colleagues15 9 years earlier.
Large amounts of cortisone have been
detected in cord plasma’#{176}’17 In one study the ratio of cord cortisone to cortisol was
1.8.16 In another investigation,
4-C14-corti-sol was administered intravenously to a
ne-onate. Thirty minutes after the injection,
the plasma concentration of 4-C14-cortisone
exceeded that of 4Ch4.cortisol. It is likely that the newborn rapidly converts cortisol to cortisone, either in the liver or in the circulation. Although it is unlikely that the
41
Ratio Urinary 17-OHCS to Cortisol
Production Rate in Newborns
In contrast to the data on CPR, it was of interest that urinary 17-OHCS were lower in newborns under 5 days of age than in
infants 5 to 20 days of age, both on a mg/ day, and mg/M2/day basis. It is well estab-lished that the glucuronidation mechanism of the newborn is deficient and that other means of disposing of cortisol are used
during this period of life.hs,bo Since the
un-nary 17-OHCS method which we utilized measures largely glucuronide conjugates of
cortisol metabolites and not the highly
po-lar steroid fraction, such measurements will
be a poor index of adrenocortical function during the neonatal period. 6-hydroxy-cortisol is known to be excreted in large amounts in the newborn,18 and would not be measured by the method of Glenn and Nelson,7 or by modifications of that meth-od, which measure largely 17-OHCS less
polar than 6-hydroxycortisol.
Normal Subjects 4 Months to
48 Years of Age
The mean CPR corrected for body sur-face area for individuals from 43 to 20
years of age was similar to that for
sub-jects from 21 to 48 years. We did not study subjects over 20 days and less than 4
months of age and there were too few
sub-jects in the group 4 months to 4% years of
age to define the range of normal values in this age group. Except for two cases, un-nary 17-OHCS in the 4-month to 20-year
subjects bore a much more constant rela-lion to the CPR than did these values in the newborns.
SUMMARY
Newborn infants less than five days of
age secrete more cortisol per meter square of body surface area than do older infants, children, and adults. However, their
un-nary 17-hydroxycorticosteroids corrected for surface area are lower than those of in-fants 5-20 days of age. The difference
be-tween the data on contisol production and
urinary excretion is accounted for by the
utilization of different pathways for
meta-bolic disposal of cortisol. Between birth and age 5 days, vaginally delivered and cesarean section babies produce similar
amounts of cortisol (18.7
±
3.7 and 17.2±
5.8 mg/M2/24 hr, respectively).
When corrected for body surface area, the CPR of 20 subjects 4 months to 20 years of age and of 28 subjects 21 to 48 years of age fell in a similar range, the
mean and standard deviation for the 48
individuals being 11.8
±
2.5 mg/M2/24 hr.REFERENCES
1. Kenny, F. M., Malvaux, P., and Migeon, C.
J.: Cortisol production in newborns and
in-fants. Amer. Dis. Child., 104:592, 1962
(Abstract).
2. Kenny, F. NI., Malvaux, P., and Migeon, C. J.:
Cortisol production in newborn babies,
older infants, and children. PEDIATRICS, 31:
360, 1963.
3. Aarskog, D. : Cortisol production rate in new-born infants of diabetic mothers. J. Pediat.,
62:807, 1963.
4. Bertrand, J., Loras, B., and Cilly, R. :
Contribu-tion a l’#{233}tude de Ia secretion et du meta-bolisme du cortisol chez le nouveau-ne t
le nourrison de moms de trois mois. Pat.
Biol., 11:997, 1963.
5. Migeon, C. J.: Cortiol production and
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Acknowledgments
The authors wish to express their gratitude to Dr. Richard L. Day for his interest in this work, and to Drs. Paul Taylor and Ahmad Shoabi for
their co-operation. Thanks are also due to the staff
of the Magee Woman’s Hospital for assistance in collecting the specimens and to Mrs. Barbara
Goldsmith for her secretarial help.
CORRECTION
In the article “Whose Chromosomes to
Count in Mongolism?” by R. James McKay,
Jr., M.D. (PErnAmics, 36:620, 1965), item 6
on pages 622-623 should read:
6. If either parent is found to have a
chromosome count other than 46, idiograms
