D.C. (S.M.H. l03781). This white male
child WdS found to have a large ileIls and
some Ul)iC hair tt the age of 5 sears, when examined I)y 1 sCl)(Ol physician. He was then referred to another hospital where the
diag-110515 of congenital a(lrenal hyperplasis was
macic. An increasc(l urinary excretion of
17-ketosteroids \‘as found aiul short courses of
cortisone and 17-methyl-androstenediol were
given. .At the age of 72 ‘ears he was
ad-mitted to Syracuse Memorial Hospital for
sttl(lV prior to re-institution of cortisone therapy.
Family history revealed no evidence of
endocrine (lisor(ler. However a male half-first cousin was exl)lore(l surgically in this hospital at 14 years of age and found to have a per-forated duoclenal ulcer. His chief complaint
This study was supported in part by a research Health, Public Health Service.
l)r. Gonzales is recipient of a fellowship from the New York State Division, American Cancer Society.
ADDRESS: (L.I.G.) Upstate Medical Center, 766 Irving Avenue, Syracuse 10, New York.
524
By Romulo F. Gonzales, M.D., and Lytt I. Gardner, M.D.
Department of Pediatrics, Upstate Medical Center, State University of New York,
Syracuse, New York
T
HIS I)h1)er describes a case ofcongeni-tat adrenal hyperplasia in a boy,
corn-plicated by episodes of flushing,
hyper-thermia, )aiii in head and/or abdomen and
prostration. Rare reports exist of patients
with congeiu tal adrenal hvperplasia who
ha-’e hv1)ertensioll’ ai-icl vho lllt\e
hypogly-cemia.2 There appears to l)e no reported
instance of a Pltie1lt with congenital
adrenal hyperplasia showing the symptoms
descril)ed above. Observations on this child have I)een inide over a period of years, and it seems justifiable to report them, both be-cause of the unusual nature of the symptoms and the possibility that the adrenocortical
disease is metabolically related to the
)arOXysIl1al episodes.
History
CASE REPORT
had been nocturnal abdominal pains.
The parents’ history of the patient stated
that he had been born normally, and that they
considered his development to be normal up
to 3 years of age when he manifested
ab-normally large musculature. After the age of
4 years he began to have bouts of headache
and/or abdominal pain and fever. Two of
these episodes were diagnosed as
“pneu-monia” but did not respond to antibiotic
therapy. These episodes occurred as frequently
as 3 times a month. There had been no
convul-SiOns or epileptiform seizures prior to
admis-sion here.
Physical Examination
On physical examination, he had the same
findings as previously mentioned. His
chrono-logical age was 79’i2 years, height-age 133k
years, weight-age 14 years and bone-age be-tween 14 and 15 years.
Laboratory Findings
(
See Appendix for methods.) Serum sodiumconcentration was 150 mEq./1. Urinary excre-tion of 17-ketosteroids averaged 25 mg./24 hours. He was given 50 rng. of cortisone
intra-muscularly daily for 3 days and then
main-tamed on 25 mg. orally twice daily. He was
observed as an outpatient, and the excretion of
17-ketosteroids fell to values of 12 and 6 mg./ 24 hours, as shown in Figure 1. The figure also shows a fall in the 17-ketosteroid level in the plasma from a mean value of 82 i.g./1O0 ml. before cortisone therapy to 17 p.g./lOO ml.,
1 1 days after treatment was begun. After 43 days of therapy the level of 17-ketosteroids in the plasma was too low to estimate by the
method used.
D C.
URINE
7-KS
MG.PER DA
THERAPY
Course, with Comments
Subsequent developmental progress on a
maintenance dose of 20 mg. of hydrocortisone
Orally twice daily is shown ill Figure 2. In
this figure the oblique dotted line indicates the normal mean for bone-age, height-age and
A- CORTISOW[ ‘1 BEGUN
B- AXILLARY HAIR NOCTURNAL EMISSIONS
Fic. 2. Developmental pattern of patient before and during cortisone therapy.
Average normal growth is indicated by the oblique dotted line.
0 5 10
CHRONOLOGIC AGE
MALE
PLASM A
7- KS
.JJG. PER
CENT
CLINICAL NOTES
CONGENITAL ADRENAL HYPERPLASIA
DAY OFEXPT. 5
7
34 49CONTROL CORTISONE5OMG. P.O. Q.D.
Fi;. 1. Reduction of 17-ketosteroids in plasma an(l urine when patient was treated with cortisone. The dotted column at the upper right indicates that tile plasma concentration of 17-ketosteroids of the
sample was less than 16 tg./ 100 ml.
(1)
L’J
0
-J
z LU
0
0
-J
LU
>
LU
Fic. 3. Temperature, blood pressure and sodium and potassium in serum during an episode. The data at
the extreme right of the chart were recorded when the patient was symptom-free. The bone-age curve may be seen considerably
above and approximately parallel to the
isodevelopmentat level before and during the
course of treatment. This chart also shows a
rise in 17-ketosteroids in the plasma at the
onset of “puberty,” while the patient was on
suppressive doses of hydrocortisone. It is
sug-gested that this is due to the elaboration of
normal testicular androgens as a result of
maturation of tile pituitary-gonadal axis.
Wil-kins and Cara have described the relationship between osseous maturation and the onset of gonadal maturation in boys with congenital adrenal hyperplasia who are treated with
corti-sone.3 These authors found that the effects of
cortisone therapy on sexual development
de-pend upon the level of general somatic
de-velopment attained before treatment is begun.
In addition to this typical picture of
con-genital adrenal hyperplasia in a male there
occurred, during our period of observation of
this patient, more than a dozen episodes of
headache and/or abdominal pain, fever,
only once. Their duration was from 1 day to
2 weeks.
In one instance an episode was clearly
re-lated to bilateral otitis media, and in another instance an episode directly followed a blow
on the head from a basketball. No such
obvi-ous stimuli could be incriminated for the great majority of this patient’s episodes. It was the
impression of some observers that the patient
was more likely to have an episode following
emotional excitement. On 1 occasion his
mother mentioned that the patient’s younger
brother had been pestering him a great deal
just before an episode. In 1954 an episode
began on December 23 and progressively
be-came worse, culminating in hospital admission
on Christmas morning.
Such an episode is depicted in Figure 3,
which shows subnormal diastolic pressures
during the febrile period. This was noted on
2 occasions. During an attack the patient
showed generalized muscular contracture,
527
No abnormal funduscopic or localizing
neuro-logical findings were made at any time. The
face of the patient became suffused with
blood, especially the malar eminences and the
ears. The ears were reminiscent of the “rose-petal” ears of magnesium-deficient rats. There
was marked flushing of the conjunctivae, and
a sensation of irritation and itching was de-scribed there by the patient. There was
some-times vomiting. At the height of such an
attack the patient complained of dizziness if
he sat up. On 1 occasion the patient turned
pate and became unresponsive when placed
in the erect position, and at another time
stopped breathing when placed in the erect
position during general anesthesia for a
pneu-moencephatogram. It is very possible that
postural hypotension was the cause of these
2 spells but no blood pressure data are
availa-ble to confirm this.
Additional Laboratory Findings
Hematological studies were normal. The
urine was negative on routine examination.
Concentrations of sodium, potassium and
chloride in the serum were normal on several occasions. No coproporphyrin, uroporphyrin,
porphobilinogen or 5-hydroxy-indoles could
be detected in the urine. Blood sugar
de-terminations, repeated 6 times in a period of
16 hours during an attack, ranged between 78
and 115 mg./100 ml. Serum amylase activity was normal. A gastrointestinal series revealed
no roentgenotogic evidence of ulcer. Skull
roentgenograms were normal.
Electroen-cephalograms were taken on 5 different
oc-casions and all were described as showing cerebral dysrhythmia without focal features. The degree of dysrhythmia was greater in
trac-ings taken during an attack than in those
taken before or after the attack.
Pneu-moencephalography was attempted but was
not successful for the reason previously noted.
Therapy
Treatment during these attacks was
symp-tomatic, antipyretics and sedatives. Dilantin#{174},
0 Bartter et al. have reported electroencephal-ographic studies on 3 females with congenital adrenal hyperptasia.42 Tracings on all 3 showed
asymmetry, elevation of voltages and abnormal
slow waves. The finding was unexplained. No
episodes of flushing, hyperthermia, etc., were
described.
Tridione#{174}, and chlorpromazine have been tried
at different times on a prophylactic basis. It has not yet been possible to assess whether or not any one of these agents has been helpful.
DISCUSSION
The natural history of congenital adrenal
hyperplasia in the male has been
ade-quately described eIsewhere. The patient responded to cortisone therapy by a reduc-tion in urinary excretion of 17-ketosteroids.5
A fall in the level of 17-ketosteroids in the
plasma was also demonstrated when
corti-sone was given. It had been hoped that
long-term cortisone therapy might postpone
the early fusion of epiphyses which
ordi-narily takes place in patients with this disease. Figure 2 shows that this result was
not accomplished, and repeated
measure-ments of height indicate that he has
stopped growing. Because his bone-age was
over 14 years at the onset of therapy, it may
have come too late. Secondly, the oral route
of therapy may not have provided a
suffi-ciently uniform suppression of androgen
production, a disadvantage of oral therapy
which has been pointed out by Wilkins et
al.’
The patient’s episodes bear some
re-semblance to a disturbance in the
hypo-thalamus. Various mechanisms have been
offered to explain periodic massive
dis-charge of hyperactivity from the hypothal-amus. Riley and colleagues have described
48 cases of “familial dysautonomia.
“
Inthese cases, attacks were provoked by
an-tagonizing the child. There was defective lacrimation, ease of perspiration,
erythema-tous blotches on excitement, inadequate temperature control and postural
hpoten-sion. In addition there was interference of
growth, speech defects and neurological
findings such as absent or diminished deep
tendon reflexes. These authors proposed a
vicious cycle starting with a functional
de-rangement of the central nervous system
re-sulting in the autonomic attacks.
.In a study of more than 100 schizophrenic
children Bender noted disturbances in
manifesta-invasion of the brain. Aring and Engel
have described another variation on this
theme in a hyperphagic dwarf with
tha-lamic lesions who had autonomic attacks.#{176}
In this case attacks were provoked by
emo-tional excitement of any sort or by illness.
The author suggested that the lesions in the
thalamus acted as an interruption to the
higher cortical controt of hypothalamic
functions. By this hypothesis emotional stimuli, thus released from higher control,
would! provoke autonomic changes to an
exaggerated extent. Penfield has described
a syndrome of “diencephalic autonomic
epilepsy.” His first case, reported in 1929,
was due to a ball-valve tumor of the third
ventricle. In this patient the severity and
duration of the seizures apparently
de-pended upon the degree and duration of
pressure on the thalamus. Penfield and
Jasper iii subsequent reports of other cases
showed that individual sym)tOmS shown
by the patients could be reproduced by
stimulation of certain cortical areas.’2 It
was thought that these cortical areas had
pathways through the hypothalamus. When
Bauer Surveyed! 60 cases of hypothalamic
disease with various endocrine
manifesta-tions, hypothalamic changes found at
nec-ropsy consisted of 51 neoplasms, 7
inflam-matory lesions and 2 degenerative ones.’3
Several elements of our patient’s
paroxys-mal episodes : headache, facial flushing,
lowered diastolic blood pressure, vomiting
and 1)rostration resellible histamine
poison-ing.’4 The attacks were more generalized
than the syndrome of intense unilateral
headache, lacrimation, salivation and
sweat-ing described! by Horton and theorized by
him as due to histamine.’7 Whether the
symptomatology of our patient is due, in
fact, to the endogenous liberation of
hista-mine or a histamine-like substance must
await further study. Nevertheless this
in-teresting )ossibility perniits the proposal
of an hypothesis interrelating congenital
siderable evidence that histamine metabo-lism is influenced by adrenal corticosteroids.
The adrenalectomized rat is more
suscepti-ble to histamine intoxication, and its tissue
histamine concentration has been found
to be very high.lH The administration of
adrenal cortical extract to adrenalectomized
rats has been found to restore the ability
of the animal to inactivate injected
hista-mine.0 The hypophysectomized rat is also
quite Susce1)tible to histamine intoxication,
and this lowered resistance is brought hack
to normal by treatment with
adrenocorti-cotropin (ACTH).” Following
adrenalec-toniy the rat lung shows a marked
diminu-tion of histaminase activity, which can be
restored by treatment with adrenal cortical
extract.” Urinary excretion of histamine
rises in the normat and allergic human
sub-ject when ACTH or cortisone is
The administration of cortisone to guinea
pigs, dogs and human beings causes a fall
in histamine concentration in the
As most histamine in the blood is in the
formed leukocytes,” changes in
concentra-tion of histamine in the whole blood more
nearly reflect shifts intracellularly than
extracellularly. The foregoing data suggest
that the level of circulating
corticoster-oids profoundty affects the intracellular
con-centration of histamine. Increased levels of
corticosteroids in plasma are associated
with increased renal excretion of histamine
and lower intracellular concentration of
histamine, whereas lower levels of
corti-costeroids in plasma are associated with
higher intracellular concentration of
hista-mine.
(h) Possible relation of histamine to an
error in corticosteroid metabolism in
con-genital adrenal hyperplasia. The relative
inability of patients with congenital adrenal
hyperplasia to maintain adequate levels of
corticosteroids in plasma is now well
docu-2627 Jf intracellular concentration of
concen-tration of circulating corticosteroids, then
these patients should have chronically
dc-vated levels of histamine in tissues. It is
possible that the mobilization of a
hista-mine-like substance from cells to plasma
during sudden stressful situations would
account for the systemic manifestations
of our patient. Because individuals with
congenital adrenal hyperplasia are unable
to raise their low plasma levels of
corti-costeroids, even when maximally stimulated
by ACTH, their adrenal mechanisms for
promoting urinary excretion of histamine
should be almost nonfunctional. Thus if
stress were to liberate histamine-like
sub-stances from the intracellular compartment,
the lack of an adrenal mechanism to
pro-mote its urinary excretion might result in
signs of histamine poisoning. Furthermore,
despite exogenous cortisone treatment the
patient with congenital adrenal hyperplasia
has little or no endocrine control over his
level of circulating corticosteroids, in
con-trast to the normal individual. It is not
possible for him to meet a sudden metabolic
demand for an increased plasma
concen-tration of corticosteroids. If the patient is
treated with oral cortisone, as was the
present case, another dimension of
non-homeostatic variability is added. Wilkins
has pointed out that the effects of oral
cortisone are transient and probably wear
off during each night.’
Why are there not more patients with
congenital adrenal hyperplasia who show
such episodes? This cannot be answered
at present, but it may be pointed out that
neither has it been explained why there are
not more cases of hypoglycemia in this
group of patients, yet the nature of the
metabolic defect involves chronically low
plasma level of corticosteroids (cf.
discus-sion by Bongiovanni et al.’). The possible
diagnoses of paroxysmal diencephalic
dis-charge versus endogenous liberation cf a
histamine-like substance are not necessarily
mutually exclusive. The relationship of
emo-tional stress to chronic urticaria,
angioneu-rotic edema and asthma is a case in point.
Paroxysmal episodes of flushing have
l)een reported
in
certain patients who have metastatic carcinoid. ‘ Since these patientshave abnormal indole metabolism and
cx-crete excessive amounts of
5-hydroxy-in-doles in the urine2, 30 the present patient’s
urine was tested for this class of compound.
No measurable amounts were detected. It
would thus seem unlikely that there is any
connection between the present patient’s
episodes of flushing and the syndrome of
paroxysmal flushing, nletastatic carcinoid
and abnorn at 5-hydroxy-inclole metabol iSm.
SUMMARY
Developmental and metabolic 01)5
tions are presented! on a boy with congenital
adrenal hyperplasia who also exhibited
paroxysmal episodes resembling histamine
These attacks were characterized
by hyperthermia, flushing of the head and
ears, abdominal and/or head pain, chilly
sensations, 1)rostratioil and sometimes
vomit-ing. Diastolic hypotension was observed
twice during the episodes. The patieiit corn-1)laiiled of marked dizziness if placed in the erect positioli. There was no eviclepce of cx-cessive toss of sodium.
Two possible explanations for the above
episodes are discussed: (1) that the
epi-sodes were dine to paroxysmal, massive
di-encephalic discharge, and (2) that the epi-sodes were due to the sudden liberation into
plasma of an intracellular histamine-like
substance. The interrelationships between
histamine metabolism and adrenocortical function are reviewed. It is hypothesized that the patient’s defect in corticosteroid
synthesis may be causally related to the
episodes resembling histamine shock.
APPENDIX
OF ANALYTIC
METHODS
The analytic procedures employed were
as follows: (a) Na and K in serum, method
of Wallace et al.;” (b) Cl in serum, method
of Schales and Schales;’2 (c) neutral
17-ketosteroids in plasma, method of Gardner;’’
(
d) blood sugar, method of Folin and Wti asmodified by Folin;’4 serum amylase activity,
method of Somogyi.0 Coproporphyrin,
tested for 5-hydroxy-indoles by the
tech-nique of Udenfriend et Bone-age was
estimated by the method of Todd.4’
Height-age and weight-age were estimated using
mean values from Englebach’s tables.4’
Twelve-lead electroencephalograms were
obtained using a Grass Ill-B machine.
ACKNOWLEDGMENTS
The authors are indebted to Drs. Stanley
Batkin, Pierre Brodeur, Julius B. Richmond
and Martin Schulman for advice and
assist-ance. The patient was kindly referred to us
by Dr. Thomas H. Shepard,
II. Thanks
aredue to Salty Merrick, Artelissa Tice and
Sylvia Saarnijoki for technical assistance.
Cortisone and hydrocortisone were
pro-vided by Merck and Company.
REFERENCES
1. (a) Shepard, T. H., II, and Clausen, S. W.:
Case of adrenogenital syndrome
. with hypertension treated with
corti-sone. PEDIATRICS, 8:805, 1951. (b) Wilkins, L. and others: Further studies
on the treatment of congenital adrenal hyperplasia with cortisone. I.
J.
Gun. Endocrinol. & Metab., 12:257, 1952; II. Ibid., 12:277, 1952;
III. ibid., 12:1015, 1952.
(c) Wilkins, L. : The diagnosis of the
adrenogenital syndrome and its
treatment with cortisone.
J.
Pediat., 41:860, 1952.2. White, F. P., and Sutton, L. E. :
Adreno-genital syndrome with associated
epi-sodes of hypoglycemia.
J.
Clin. Endo-crinol., 11:1395, 1951.“3. \Vilkins, L., and Cara,
J.
: Further studies on the treatment of congenital adrenal hyperplasia with cortisone. V. Effects of cortisone therapy on testicular develop-ment.J.
Clin. Endocrinol. & Metab., 14: 287, 1954.4.
Gardner, L. I., and others: Follow-upstudies in a boy with mixed adrenal
cortical disease. PEDIATRICS,
5:808,
1950.
5. Wilkins, L., and others: Cortisone therapy ill congenital adrenat hyperplasia. j. Cliii. Endocrinol., I I : 1, 1951.
7. Riley, C. M., and others: Further
observa-tions on familial dysautonomia.
PEDI-ATRICS, 14:75, 1954.
8. Bender, L. : Childhood schizophrenia. Clinical study of one hundred schizo-phrenic children. Am.
J.
Orthopsychiat.,17:40, 1947.
9. Ford, F. R. : Diseases of the Nervous Sys-tem in Infancy, Childhood and
Adoles-cence. Springfield, Thomas, 1946, p.
428.
10. Aring, C. D., and Engel, G. L. :
Hypothala-mic attacks with thalarnic lesions. I.
Physiological and psychological
con-siderations. II. Anatomical considera-tions. Arch. Neurol. & Psychiat., 54:37 (I); 54:44 (II), 1945.
1 1. Penfield, W. C. : Diencephalic autonomic
fits. Arch. Neurol. & Psychiat., 22:358, 1929.
12. Penfield, W. G., and Jasper, H. : Epilepsy
and the Functional Anatomy of the
Human Brain. Boston, Little, 1954, p.
412.
13. Bauer, H. G. : Endocrine and other clinical manifestations of hypothalamic disease.
J.
Ctin. Endocrinol. & Metab., 14:13, 1954.14. Dale, H. H., and Laidlaw, P. P. :
Hista-mine shock.
J.
Physiol., 52:355, 1919. 15. Weiss, S., and others: The systemic effectsof histamine in man; with special refer-ence to the responses of the
cardiovascu-lar system. Arch.
mt.
Med., 49:360,1932.
16. Pickering, G. W. : Observations on
mechanism of headache produced by
histamine. Clin. Sc., 1:77, 1933.
17. Horton, B. T. : Histamine cephalalgia.
Journal-Lancet, 72:92, 1952.
18. Rose, B., and Browne,
J.
S. L. : The effect of adrenalectomy on the histaminecon-tent of the tissues of the rat. Am.
J.
Phvsiol., 131 :589, 1940-41.
19. Rose: B. : The effect of cortin and desoxy-corticosterone acetate on the ability of the adrenalectomized rat to inactivate histamine. Am.
J.
Physiol., 127:780,1939.
20. Noble, R. L., and Collip,
J.
B. : The re-sponse of normal, hypophysectomised and adrenalectomised rats to histamine administration. Am.J.
Physiol., 133:623,1941.
CLINICAL NOTES
Decrease of histaminase in tissue by
adrenalectomy and its restoration by
cortico-adrenal extract. Am.
J.
Physiol.,130:539, 1940.
22. Rose, B., and others: Observations on the
metabolic changes resulting from the
administration of ACTH to patients with
asthma and allied conditions, in
Pro-ceedings of the Second Clinical ACTH Conference, vol. 1,
J.
R. Mote, editor.New York, Blakiston, 1951, pp. 515-525.
23. Grob, D. : The renal excretion of histamine and histidine in man, and the effect of
adrenocorticotropic hormone (ACTH)
and cortisone administration. Bull. Johns Hopkins Hosp., 90:341, 1952.
24. Mitchell, R. G., and Code, C. F. : Urinary excretion of histamine after administra-lion of cortisone.
J.
Clin. Endocrinol. & Metab., 14:707, 1954.25. Graham, H. T., and others: Distribution of histamine among leucocytes and plate-lets. Blood, 10:467, 1955.
26. Kelley, V. C., and others: Hormone
patterns in patients with congenital adrenal hyperplasia. PEDIATRICS, 12:541, 1953.
27. Bongiovanni, A. M., and others: Studies on
the metabolism of adrenal steroids in
the adrenogenital syndrome.
J.
Cliii. Endocrinol. & Metab., 14:409, 1954.28. Thorson, A., and others: Malignant
car-cinoid of the small intestine with
metastases to the liver, valvular disease of the right side of the heart, peripheral vasomotor symptoms, bronchoconstric-tion and an unusual type of cyanosis. Am. Heart
J.,
47:795, 1954.29. Lembeck, F. : 5-Hydroxytryptamine in a
carcinoid tumor. Nature, 172:910, 1953. 30. Sjoerdsma, A., and Udenfriend, S. : Studies
on indole metabolism in patients with
malignant carcinoid (argentaffinoma)
(abstract).
J.
Gun. Investigation, 34:914,1955.
:31. Wallace, W. M., and others: The
applica-tion of the internal standard flame
photometer to the analysis of biologic material.
J.
Lab. & Cliii. Med., 37:621, 1951.32. Schales, and Schales, Selma S. : Simple
and accurate method for determination of chloride in biological fluids.
J.
Biol. Chem., 140:879, 1941.33. Gardner, L. I. : Plasma iieii: rat
17-ketosteroids. I. Technique of estimation.
J.
Cliii. Endocrinol. & Metab., 13:941, 1953.:34. Folin, 0. : The determination of sugar in
blood and in normal urine.
J.
Biol.Chem., 67:357, 1926.
35. Somogyi, M. : Micromethods for the esti-mation of diastase.
J.
Bfol. Chem., 125: 399, 1938.36. Watson, C.
J.
: Porphyria, ill Christian,H. A. : Oxford Medicine, vol. 4. New
York, Oxford, 1938.
37. Watson, C.
J.,
and Schwartz, S. : A simple test for urinary porphobilinogen. Proc. Soc. Exper. Biol. & Med. 47::393, 1941.:38. Drekter, I.
J.,
and others: A rapid methodfor the determination of total urinary
17-ketosteroids.
J.
Clin. Endocrinol., 7:795, 1947.
:39. Udenfriend, S., Weissbach, H., and Clark,
C. T. : The estimation of 5-hdroxytryp-tamine (serotonin) in biological tissues.
J.
Biol. Chem., 215:337, 1955. 40. Todd, T. W. : Atlas of Skeletal Maturation.St. Louis, Mosby, 1937.
41. Englebach, W. : Tables as adapted by
Wilkins, L., The Diagnosis and Treat-ment of Endocrine Disorders in
Child-hood and Adolescence. Springfield,
Thomas, 1950, pp. 30-33.
42. Bartter, F. C., Albright, F., Forbes, A. P., Leaf, A., Dempsey, E., and Carroll, E.: The effects of adrenocorticotropic hor-mone and cortisone in the adrenogenital
syndrome associated with congenital
adrenal hvperplasia: An attempt to
cx-1,l,ii,i and correct its disordered hormonal pattern. j. Clin. Investigation, 30:2.37,