113Cushing’s syndrome. An 0800h plasma ACTH >90 pg/ml is suggestive of ectopic
source of ACTH secretion. After confi rmation of ACTH dependency, dynamic con-
trast-enhanced MRI sella should be performed to localize the source of ACTH
excess, as pituitary Cushing’s is the most common (98 %) cause of Cushing’s syn-
drome during peripubertal period. The index patient had 2300h ACTH value of
63.7 pg/ml and dynamic CEMRI sella localized the 4.8 × 4.0 mm tumor in the left
half of the pituitary gland. In adults, the pituitary tumor size ≥6 mm has a specifi city
of 98 %, whereas such data is not available for patients with childhood Cushing’s
syndrome. Therefore, additional investigations like HDDST and IV CRH stimula-
tion tests should be performed to substantiate the diagnosis of pituitary ACTH-
dependent Cushing’s syndrome. However, the data for ACTH and cortisol cutoffs in
response to IV CRH are limited in children. Therefore, this patient was subjected to
IPSS and it localized the source of ACTH to the pituitary gland but lateralized, con-
trary to the MRI fi ndings, to the right half of the pituitary gland. Basal central to
peripheral (C/P) ACTH ratio >2 and stimulated ratio >3 localizes the source of
ACTH to the pituitary, whereas a ratio of >1.4 between the right and left inferior
petrosal sinus lateralizes the source of ACTH excess. The index patient had basal
C/P ratio of 3.8 and stimulated peak of 54.3, which localized the source of ACTH
excess to the pituitary. The ratio of right to left inferior petrosal sinus ACTH after
CRH stimulation was 59.3, lateralizing the source of ACTH excess to the right side.
The discordance in lateralization of pituitary tumor between MRI and IPSS can be
explained by intercavernous venous mixing, right-sided dominance in pituitary
venous drainage pattern (in 40 % of healthy adults), or presence of the epicenter of
the tumor on one side with extension of the tumor to the contralateral side. The
pretest probability of fi nding a tumor during surgical exploration is approximately
92 % as lateralized by MRI, compared to 69 % as lateralized by IPSS. Therefore, a
decision was taken fi rst to explore the left half of the pituitary in the index patient,
and the tumor was found on the same side and was resected. Histopathology of the
tumor tissue was consistent with pituitary adenoma, but immunohistochemistry on
tumor tissue for ACTH was negative, which may be a poor predictor in achieving
long-term remission. Postoperatively, serum cortisol should be estimated at 0800h
from day 1 to day 5 and a serum cortisol value <100 nmol/L merits for immediate
replacement with hydrocortisone, whereas patients with serum cortisol level
450 nmol/L do not require supplementation with hydrocortisone. However, 0800h
serum cortisol between 100 and 450 nmol/L requires a close watch and, if symp-
tomatic, should be supplemented. Postoperative 0800h serum cortisol <50 nmol/L
predicts long-term remission; however, some studies have shown that 0800h serum
cortisol <140 nmol/L up to 6 weeks also predicts the similar long-term outcome.
The immediate postoperative hypocortisolemia (<50 nmol/L) is a result of peritu-
moral corticotropes suppression due to long-standing hypercortisolemia. The index
patient had day 1, 0800h serum cortisol <100 nmol/L and she was initiated with
hydrocortisone replacement. Postoperatively, she had desquamation which is the
earliest clue of curative surgery and occurs as a result of increased cuticular
4 Childhood Cushing’s Syndrome