112
4.2 Stepwise Analysis
This 16-year-old girl presented with weight gain, menstrual abnormalities, and hir-
sutism. On evaluation, though she was overweight for age, her height age was less
than the chronological age which suggests underlying endocrine disorder for her
growth failure, as opposed to children with exogenous obesity, who usually grow
taller due to hyperinsulinemia-mediated increased IGF1 generation. However, the
attained height in the index patient was within 1.5 SD of her target height, which
indicates relatively recent onset of the disease. She had wide violaceous striae,
proximal myopathy, and cuticular atrophy, which are the specifi c features of
Cushing’s syndrome and represent the manifestations of protein catabolism. Though
the children of younger age with Cushing’s syndrome usually present with growth
failure and delayed puberty and do not have features of protein catabolism, the
index patient had manifestations of protein catabolism. The presence of features of
protein catabolism in the index patient distinguishes it from polycystic ovarian syn-
drome which usually presents in the peripubertal age with weight gain and men-
strual irregularities. Though the patient denied history of use of steroid preparations
or alternative medications, 0800h serum cortisol was estimated to exclude the exog-
enous Cushing’s syndrome as inadvertent use of steroids is not uncommon in chil-
dren and adolescents. In addition, 0800h serum cortisol is also useful to establish
the loss of diurnal rhythm and for the interpretation of HDDST. The presence of
hypercortisolemia in the index patient was confi rmed by elevated urinary free corti-
sol, midnight salivary cortisol, and non-suppressible ONDST. However, at least two
tests are required to establish the presence of hypercortisolemia in a patient with
suspected Cushing’s syndrome to increase sensitivity of the screening tests.
Additional screening test like midnight serum cortisol may be useful in a situation
where the results of the screening tests are discordant or negative, and the clinical
suspicion of Cushing’s syndrome is strong. A 2300h serum cortisol >207 nmol/L in
awake state has a sensitivity and specifi city of 94 % and 100 %, respectively, or in
sleeping state >50 nmol/L has a sensitivity and specifi city of 100 % and 20 %,
respectively. Further, 2300h serum cortisol <207 nmol/L in awaken state or
<50 nmol/L in sleeping state virtually excludes the diagnosis of Cushing’s syn-
drome with a negative predictive value of 96 % and 100 %, respectively. The LDDST
should be preferred over other screening tests in those who have subtle features of
Cushing’s syndrome (pseudo-Cushing’s syndrome). Nevertheless, it should be
remembered that the doses of dexamethasone used for performing the dynamic tests
are different in children and adolescents as compared to adults (ONDST, LDDST,
and HDDST – 15 μg/Kg, 30 μg/Kg/day for 2 days, and 120 μg/Kg/day for 2 days,
respectively, in children weighing <40 Kg). After confi rmation of hypercortisolemia,
measurement of plasma ACTH is recommended to establish the etiological diagno-
sis of Cushing’s syndrome. A 2300h plasma ACTH >22 pg/ml has highest discrimi-
natory value to establish the diagnosis of ACTH-dependent Cushing’s syndrome.
An 0800h plasma ACTH <5 pg/ml supports the diagnosis of ACTH-independent
4 Childhood Cushing’s Syndrome