1642

N 52
SA MEDICAL JOURNAL
(Supplement-South African Journal of Nutrition)
20 September 1975
Cortisol and Growth Hormone
and Marasmus

In Kwashiorkor
J. M. VANDER WESTHUYSEN, J. J. JONES, C. H. VAN NIEKERK, P. C. BELONJE
SUMMARY
Cortisol and growth hormone concentrations in the plasma
were determined in 26 children with kwashiorkor, 13 with
marasmus, and 21 controls. Cortisol levels were high in
babies with kwashiorkor and marasmus, but higher in the
former, in relation to a constant body mass. The concen-
tration of plasma cortisol correlated positively with the
body mass deficit in kwashiorkor (r = 0,66) and in children
with low mass for age (r = 0,75). Growth hormone levels
were elevated in both kwashiorkor and marasmus. The
proposed role of these hormones in metabolic adaptation to
malnutrition is discussed.
S. Afr. med. J., 49, 1642 (1975).
Adaptation to deficient nutrition depends primarily on
the endocrine control of the metabolic processes involved.
The two ultimate forms of protein energy malnutrition,
namely kwashiorkor and marasmus, have been described
as forms of failure of adaptation and successful adaptation
to protein energy malnutrition, respectively.'"
Failure of adaptation involves the inability of hormones
to maintain normal metabolism because the malnutrition
is too severe,'" or the individual is physiologically unable
to adapt to the dietary deficiency. Hormonal changes, such
as increases in cortisol and growth hormone, have been
reported by many workers."" Some workers' ascribe the
increase in plasma cortisol to the general stress of
malnutrition, whereas others' attribute it to infection.
The increase in growth hormone is also related to changes
in plasma amino acid concentration:'l1 particularly ala-
nine" and valine: Recently, Rao
13
proposed that mal-
adaptation to protein energy malnutrition (kwashiorkor)
results from an inability of the adrenal cortex to respond
sufficiently to mobilise enough amino acids for use by
an abnormally high secretion of growth hormone. The
successful adaptation in marasmus results from an ade-
quately responsive adrenal and relatively low growth
hormone. This experiment was performed to test this
hypothesis, by comparing these hormonal concentrations
in non-fatal and fatal kwashiorkor and marasmus, and
to attempt to relate them to the severity of malnutrition.
Department af Physiology, Godfrey Huggins School of
Medicine. University of Rhodesia, Salisbury, Rhodesia
J. M. VA J DER WESTH YSEN*, M.se., PH.D.
J. J. JONES, PH.D., M.B. B.S., B.se., M.R.e.S.. Professor ill
Preclinical Studies
C. H. VAN NlEKERK*, B.\'.SC., D.\.SC., Professor
P. C. BELONJE*, B.V.se., M.MED.VET.
Date received: 6 May 1975.
Preseot address: Department of Human and Animal PhYSiology. University
of Stellenbosch. CP.
PATIENTS AND METHODS
Thirty-nine patients between the ages of 12 and 48 months
with protein energy malnutrition were studied. They were
admitted to Harari Hospital, Salisbury, between December
1972 and March 1973 and were all underweight for age
(Boston 50th percentile).H Twenty-six patients with oedema
and less than 80% of the expected body mass for age,
were classified as kwashiorkor, and 13 without oedema
and less than 60% of the expected body mass for age,
marasmus."
It is customary to take a venous blood sample from
all children admitted to this hospital before treatment
is started. The blood is collected between 08hOO and 09hOO
in plastic syringes containing lithium sequestrene as an
anticoagulant. Immediately after collection, blood samples
are placed in ice and spun down in a refrigerated centrifuge
within 2 hours of collection. Plasma is stored at -20C,
until it is analysed. Another venous blood sample is taken
for analysis 1 week after the patient has been admitted
to hospital and again during the patient's last week in
hospital.
In this study, at each blood sampling, the child
examined and the age, body mass and height were
recorded. Any signs of gastro-intestinal disturbance or
of other infections were noted. Measurements were made
of skinfold thickness over the triceps, using Harpenden
skinfold calipers, and the mid-arm circumference was
measured with a tape measure. From these measurements
the 'mid-arm muscle circumference' was determined,'"
Oedema was measured as the pitting depth, in millimetres,
obtained after pressure for 15 seconds on the dorsum
of the foot and by scoring (0 - 9) for the total degree of
oedema in the limbs (0 - 3), face (0 - 3) and abdomen
(0 - 3). Further observations included skin, hair and liver
changes. Liver enlargement was measured in centimetres,
in the right midclavicular line by palpation, with the child
supine. Skin lesions and stomatitis were graded by
inspection from 0 - 3.
Routine treatment included feeding fortified milk
(containing skimmed milk, oil, eggs, a multivitamin syrup,
folic acid and potassium cWoride). Intravenous transfusion!
of plasma or half-strength Darrow's solution (containing
2,5% glucose) were used only when there was evidence of
low-output circulatory failure, and antibiotics were given
when indicated. Most deaths occurred during the first
3 days in hospital and were usually associated with an
overwhelming Gram-negative bacteraemia" or with severe
gastro-enteritis. Patients who recovered remained in
hospital for 2 - 5 weeks. A healthy control group consisted
of 21 children, aged 12 - 24 months, of the same community.
20 September 1975 SA MEDIESE TYDSKRIF
(Byvoegsel-S/lid-Ajrikaanse Tydskrij vir Voeding)
1643
V 53
Plasma cortisol concentration was determined by com-
petitive protein binding," and plasma growth hormone"
was estimated by radio-immunoassay. The antibodies were
supplied by CEA-CIA Sorin. Total pia ma protein was
determined by the biuret method'" and albumin by cellulo t;
acetate electrophoresis" followed by fiying- pot den i-
tometry.
they differed ignificantly (P<O,OI) in the y intercept.
An analy i of covariance howed that kwa hiorkor
patients had a significantly higher (P<O,OI) plasma corti 01
concentration than malnouri hed children without oedema,
when the effect of body mas deficit was made constant.
'OD
Fig. 1. Correlations and regressions of plasma cortisol
concenlr-ations (ng/mJ) and body mass deficit (%) in
malnourished children with oedema (kwashiorkor) and
in those without oedema.
During the first week of recovery in ho pital, cortisol
concentrations of kwashiorkor and mara mus p t i n ~
decreased significantly (P<O,OI), but not thereafter, so that
they were significantly higher (P<0,05) during the week
'0
lOW BODY MASSI AGE: , ; 0.75
y = 23,50 + 6,79x
20 30
BODY MASS DEfiCIT
10
400
KWASHIORKOR: ,; 0,66
Y:: 159,61" 6,30x
'" c
_ 300
o
~
100
'" .-'
0200 .......
u .-'
'"
The mean plasma hormone concentrations of children
suffering from protein energy malnutrition on admission to
hospital, are summarised in Table 1. Changes occurring
in these concentrations during recovery in hospital, are
presented in Table n.
m both kwashiorkor and marasmus, the mean plasma
cortisol concentrations were significantly greater (P<O,OI)
in the controls, but did not differ from each other. m
addition, kwashiorkor and marasmus patients who sub-
sequently died in hospital had cortisol concentrations
significantly greater (P<0,05) than those who recovered.
m Table ill the correlations of plasma cortisol with the
severity of the clinical features are presented. It can be
seen that severe clinical features are associated with
higher concentrations of cortisol in the plasma. Fig. I
presents the relationships of plasma cortisol and body
mass deficit of children with a low body mass for age,
but without oedema (r = 0,754), and of those with
kwashiorkor (r = 0,658). Although the two regression
lines did not differ in slope (low body mass/ age: y =
23,50 + 6,788 x; kwashiorkor: y = 159,607 + 6,301 x),
RESULTS
TABLE I. PLASMA ENDOCRINE CONCENTRATIONS IN KWASHIORKOR AND MARASMUS PATIENTS ON ADMISSION
TO HOSPITAL AND IN CONTROLS
Kwashiorkor Marasmus
Lived Died Lived Died Controls
Number 12 14 9 4 21
Cortisol (ng/ml) 127,0
-+-
13,13' 163,3
-+-
10,99
b
120,5 -+- 10,41' 185,3
-+-
14,00b 54,1 -+- 5,24
c
Growth hormone (ng/ml) 71,45 -+- 1,79' 70,00 -+- 2,58' 76,00 -+- 7,45' 62,75 -+- 2,58' 28,47 -+- 3,45
b
Plasma albumin (g/100 ml) 2,31 -+- 0,10' 1,99 -+- 0,09' 2,72 -+- O,10
b
2,31
-+-
0,41'b 3,97 -+- 0,15
c
,.b,c. Figures with the same superscript are not significantly (P<O.Ol) different from each other.
TABLE 11. PLASMA ENDOCRINE CONCENTRATIONS IN CONTROLS AND IN KWASHIORKOR AND MARASMUS
PATIENTS ON ADMISSION AND DURING RECOVERY IN HOSPITAL
Kwashiorkor Marasmus
112,3 -+- 11,66' 86,57 -+- 7,32
b
82,00 -+- 20,12
b
120,5 -+- 9,01' 88,67 -+- 11,08
b
81,67 -+- 6,45
b
75,67 -+- 5,97' 36,67 -+- 7,23
b
34,33 -+- 5,70
b
76,00 -+- 6,45' 31,33 -+- 5,53
b
27,50 -+- 8,92
b
2,19 -+- 0,15' 3,18 -+- 0,22
b
3,95 -+- 0,12
b
2,55 -+- 0,17' 3,70 -+- 0,24
b
3,81 -+- 0,29
b
Controls
21
3,97 -+- 0.15"
28,47 -+- 3,45
b
54,1 -+- 5,24'
Discharge
8
7 days
8
Admission
8
Discharge
11
7 days
11
Admission
11 Number
Cortisol
(ng/ml)
Growth
hormone
(ng/ml)
Plasma
albumin
(g/loo ml)
'.b.c Figures with the same superscript are not significantly (P<O,05) different from each other.
14
I,
, ,
1644
N 54
SA MEDICAL JOURNAL
(Suppleme/lt-Solllh African Journal of NI/iriaon)
20 September 1975
DISCUSSION
TABLE Ill. CORRELATION COEFFICIENTS OF PLASMA
CORTISOL AND THE SEVERITY OF THE CLINICAL
FEATURES IN PROTEIN ENERGY MALNUTRITION
of discharge than those of the controls.
Growth hormone concentrations were significantly
elevated (P<O,Ol) in each child admitted to hospital with
protein energy malnutrition, compared with the controls
(Table I). Children with kwashiorkor or marasmus did
not differ from each other in this respect, nor did those
suffering from the fatal and non-fatal forms of the disease
differ in growth hormone concentrations. During recovery
in hospital, growth hormone concentration returned to
the normal level within the first week of treatment.
Adrenal function in protein energy malnutrition has been
the subject of investigation for many years. Owing to
contradictory reports between histological and
determinations of urinary steroid excretion,"'''' it was
concluded that urinary excretion may be an unreliable
guide to adrenal activity"'" and that the plasma cortisol
concentration should be used. In general, raised con-
centrations of plasma cortisol in protein energy malnutri-
tion, regardless of type have been reported,',.3l although
there have been conflicting results of adrenal activity
being generally low in kwashiorkor, but high in
marasmus:"
Recently, Rao" proposed that high adrenal activity may
be essential for adaptation to protein energy malnutrition
and that the main difference between the aetiology of
marasmus (successful adaptation) and kwashiorkor (failure
of adaptation) is not of dietary origin, but depends mainly
on the ability of the adrenal cortex to respond adequately
to maintain metabolic integrity. The results of this study
do not agree with this theory ner with the work of
Castellanos and Arroyave' and Lunn et al." but show that
plasma cortisol concentration is elevated in both types of
protein energy malnutrition. The significant increase in
cortisol levels of children with fatal protein energy mal-
nutrition above those of surviving children, also makes
it most unlikely for the magnitude of the adrenal response
to be valid as an indication of successful adaptation.
Moreover, high correlation was found between plasma
cortisol concentration and the severity of the clinical
features.
This study clearly showed that body mass deficit is
correlated with cortisol concentration which is more ele-
vated in kwashiorkor, the type of protein energy mal-
nutrition that represents maladaptation. Cortisol concen-
tration is higher in kwashiorkor than in marasmus, and
still higher when the disease is fatal. It was also found
that cortisol in experimental protein energy malnutrition
pigs) was related to the clinical severity of the syn-
drome." Therefore, cortisol concentration is not so much
an indication of an adaptive response, but imply represents
the severity of the stress of protein energy malnutrition,
a conclusion that is in marked contrast to Rao's" theory.
In agreement with Abassy' and with Rao et aL.,:n the
highest cortisol concentrations were found in children with
high body mass deficits, and more so in children with
kwashiorkor.
It is generally agreed that in severe kwashiorkor serum
growth hormone concentrations are raised.','33,,, In maras-
mus, growth hormone concentrations have been reported
as either normal" or raised.' The present results confirm
those of Pimstone et a/.' that growth hormone concen-
trations are elevated in both kwashiorkor and marasmus.
This elevated concentration of growth hormone is not
significantly related to body mass deficit or to plasma
concentrations of glucose or albumin. These results also
are at variance with the theory of Rao."
She reported growth hormone to be high in kwashiorkor
and low in marasmus, and that the plasma amino acids
showed opposite changes. The present study shows that
growth hormone concentration is markedly elevated in
both types of protein energy malnutrition.
From this it can be concluded that, although hypo-
proteinaemia, and particularly hypo-albuminaemia, are
expressions of the metabolic state during the maintenance
of plasma albumin concentration and metabolic integrity
in protein energy malnutrition, factors other than growth
hormone and cortisol concentrations are primarily
responsible for successful adaptation.
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Correlation coefficients
0,55*
0,61*
0,56*
0,41*
0,33t
Cortisol and:
Body mass deficit
Skinfold deficit
Dermatitis
Lethargy
Albumin
P<O.01.
tP<O.05.
,I