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Iatrogenic Cushing’s Syndrome Due to Intranasal Usage of Ophthalmic Dexamethasone: A Case ReportSarah Orton, MD, Marisa Censani, MD
Division of Pediatric Endocrinology, Department of
Pediatrics, Weill Cornell Medicine, New York Presbyterian
Hospital, New York, New York
Dr Orton diagnosed and treated the patient,
contributed to the concept and design of the case
report, drafted the manuscript, and critically
revised the manuscript for important intellectual
content; Dr Censani diagnosed and treated the
patient, contributed to the concept and design
of the case report, drafted the manuscript, and
critically revised the manuscript for important
intellectual content; and both authors approved
the fi nal manuscript as submitted and agree to be
accountable for all aspects of the work.
DOI: 10.1542/peds.2015-3845
Accepted for publication Feb 17, 2016
Address correspondence to Marisa Censani,
Division of Pediatric Endocrinology, Department
of Pediatrics, Weill Cornell Medicine, 525 East 68th
St, Box 103, New York, NY 10065. E-mail: mac9232@
med.cornell.edu
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
Copyright © 2016 by the American Academy of
Pediatrics
FINANCIAL DISCLOSURE: The authors have
indicated they have no fi nancial relationships
relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors
have indicated they have no potential confl icts of
interest relevant to this article to disclose.
Iatrogenic Cushing’s syndrome (ICS)
is caused by exogenous corticosteroid
administration and has been
commonly described with oral and
topical steroid use.1–4 There has been
a limited number of reported cases of
intranasal steroid use leading to ICS in
children.5–9 Specifically, there is only
1 previously reported case involving
intranasal use of a dexamethasone
ophthalmic solution leading to ICS.6
This case described a 6-year-old child
receiving ocular drops for epistaxis
for 3 months with apparent excess
administration of the product. In
this article, we present a case of a
4-month-old infant who developed ICS
after 6 weeks of prescribed intranasal
use of a dexamethasone ophthalmic
solution for nasal obstruction. Written
informed consent was obtained
from the patient’s mother for
publication of this case report and any
accompanying images.
CASE PRESENTATION
A 4-month-old male was admitted
to the pediatric ICU for respiratory
distress. He was a product of a twin
pregnancy and was born prematurely
at 26 weeks gestation. His medical
history was complicated by chronic
lung disease, retinopathy of
prematurity, patent ductus arteriosus
requiring indomethacin for closure,
and a 3 month NICU admission.
Nasal Ciprodex (ciprofloxacin/
dexamethasone) was initiated 1 week
after his initial NICU discharge when
he was readmitted for an apparent
life-threatening event secondary
abstractIatrogenic Cushing’s syndrome (ICS) is caused by exogenous corticosteroid
administration with suppression of the hypothalamic–pituitary–adrenal
axis. It has been commonly described with oral and topical steroid use, but
scarce reports have documented intranasal steroid usage as the etiology
in infancy. In this article, we describe a case of a 4-month-old infant who
developed ICS after 6 weeks of intranasal dexamethasone ophthalmic
solution administration for nasal obstruction. To our knowledge, this is the
youngest patient reported with ICS due to intranasal use of a prescribed
dose of an ophthalmic steroid. His hypothalamic–pituitary–adrenal axis
recovered fully 4.5 months after steroid discontinuation. Because of the
small body surface area and supine position during administration, infants
are particularly susceptible to ICS. Given that intranasal steroids are
commonly prescribed to infants and children for a variety of diagnoses,
this case highlights the risks inherent in the use of intranasal steroid drops,
particularly in young infants, for both adrenal suppression and linear
growth deceleration, even with short-term use. Close monitoring of these
patients’ height and weight should occur while on steroid treatment, with
every effort made to decrease or discontinue steroid use when possible.
CASE REPORTPEDIATRICS Volume 137 , number 5 , May 2016 :e 20153845
To cite: Orton S and Censani M. Iatrogenic
Cushing’s Syndrome Due to Intranasal Usage
of Ophthalmic Dexamethasone: A Case Report.
Pediatrics. 2016;137(5):e20153845
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ORTON and CENSANI
to severe nasal congestion. His
congestion improved, but treatment
was changed to dexamethasone
ophthalmic solution after 1 week
due to a rash that was thought to
be caused by Ciprodex. The patient
was readmitted to the hospital 4
weeks later for respiratory distress
with a 1-week history of lethargy,
decreased appetite, and increased
facial swelling.
On initial presentation, the patient
weighed 4.1 kg with a length of 49
cm (corrected for gestational age:
5% and 0% respectively). He had
a normal, age-adjusted heart rate
of 155 bpm and blood pressure of
86/40 mm Hg. Review of growth
charts revealed he had gained 24 g
per day since starting steroids, but
his growth velocity had markedly
decreased from 5 cm per month
to 1 cm per month after steroid
introduction (Fig 1). On exam, he was
noted to have large, ruddy cheeks
with moon facies (Fig 2). He did
not have striae, edema, acanthosis
nigricans, or hypertrichosis.
Laboratory evaluation revealed
a cortisol level of <0.4 ug/dL
(reference range: 6.7–22.6 ug/dL)
obtained at 6:30 AM, and the diagnosis
of ICS was made.
At the time of the endocrinology
consultation, the patient had been on
intranasal steroids at an equivalent
hydrocortisone dose of 28 mg/m2
per day for 6 weeks (conversion
used: 1 mg of dexamethasone
equivalent to 40 mg hydrocortisone;
this is based on the concentration of
the ophthalmic dexamethasone of 1
mg/mL with 20 drops/mL and a total
daily dose of 3 drops).
On hospital discharge, otolaryngology
felt that the patient should continue
with dexamethasone treatment
because of continued respiratory
distress and improvement of
the patient's respiratory status
on treatment. At diagnosis, a
dexamethasone taper was initiated
with a decrease to 2 drops daily (18
mg/m2 per day of hydrocortisone),
followed by a decrease to 1
drop daily (8 mg/m2 per day of
hydrocortisone) by 3 months,
and discontinuation by 4 months
post–ophthalmic steroid initiation
(Fig 1). During the dexamethasone
taper, the patient received 1 2-day
course of stress-dose hydrocortisone
for an upper respiratory infection
with fever, but otherwise remained
off additional steroid use for the
remainder of his clinical care. His
mother was instructed on stress
dosing and emergency Solu-Cortef
administration. His growth improved
once the dexamethasone dose was
weaned to 1 drop (8 mg/m2 per day
of hydrocortisone) with a consistent
velocity of 4 cm per month thereafter
(Fig 1). One month post–steroid
use, his morning cortisol level was
e2
FIGURE 1Patient growth chart with correction for gestational age and dexamethasone taper as follows: (A) 28 mg/m2 per day; (B) 18 mg/m2 per day; (C) 8 mg/m2 per day; and (D) discontinuation.
FIGURE 2Patient at the time of diagnosis with Cushingoid appearance.
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PEDIATRICS Volume 137 , number 5 , May 2016
1.6 ug/dL. By 2.5 months post–
steroid use, his Cushingoid facies
resolved, and a low-dose, 1 mcg
adrenocoricotropic hormone (ACTH)
stimulation test was performed,
revealing a baseline cortisol level of
6.2 ug/dL, with levels at 14.9 ug/dL
and 15.7 ug/dL at 30 min and
60 min, respectively. At 4.5 months
post–steroid use, a low-dose ACTH
stimulation test showed a baseline
cortisol level of 6.0 ug/dL, with levels
at 17.9 ug/dL and 19.2 ug/dL at
30 min and 60 min, respectively.
DISCUSSION
To our knowledge, this is the
youngest patient reported with ICS
due to intranasal use of a prescribed
dose of an ophthalmic steroid. Our
patient was diagnosed after only a
6-week course of dexamethasone
ocular drops compared with a
previously prescribed 3-month
course.6 Given that intranasal
steroids are commonly prescribed
to infants and children for a variety
of diagnoses, this case highlights
the risks inherent in the use, even
short-term, of intranasal steroid
drops, particularly in young infants,
for both adrenal suppression and
linear growth deceleration. Because
oral and topical glucocorticoids are a
more common cause of ICS, there are
limited reports of intranasal steroids
as the etiology, 5–9 with patients being
diagnosed with ICS anywhere from
2 to 4 months to several years after
steroid initiation.
Infants given intranasal
dexamethasone drops may be at
higher risk for systemic absorption
through the gastrointestinal tract
because they are often supine during
administration and may swallow a
significant portion of each drop. They
also have a smaller body surface area
than older children and adults.1–5, 9
Although some publications report
ICS caused by prescription errors or
parents using excessive doses and
prolonged courses of therapy, 6, 7, 10 our
patient was receiving the appropriate
prescribed dose for a short duration.
Patients with ICS due to various
etiologies have presented with a
spectrum of signs and symptoms
ranging from excessive weight
gain and growth delay to posterior
cervical fat pad, hypertrichosis, and
violaceous striae.1–10 Our patient
presented with Cushingoid facies
and poor growth. Once our patient
was weaned to physiologic dosing
of steroids, his growth improved
dramatically and his Cushingoid
features resolved.
Our patient was weaned to
physiologic hydrocortisone dosing
by 3 months post–steroid initiation,
with discontinuation by 4 months.
To determine hypothalamic–
pituitary–adrenal axis recovery, a
low-dose ACTH stimulation test with
a goal peak cortisol level of 18–20
ug/dL was implemented.11, 12 Our
patient's cortisol level of 19.2 ug/
dL documented adrenal recovery
from suppression 4.5 months after
discontinuation of steroid treatment,
with a noted improvement in height
velocity and an appropriate weight
gain and energy level.
There has been only 1 other
documented case where physiologic
dosing was not used during the
recovery period for intranasal
steroid–induced ICS.7 The patient
was a 19-month-old male who
developed ICS after 3 months of
excessive intranasal betamethasone
nasal drops for rhinorrhea and
snoring. He was weaned off the
steroid drops over 3 weeks and had
a normal cortisol level 3 months
later. He was not given physiologic
dosing of glucocorticoids, but he
did require 3 days of stress dosing
for pharyngitis 2 weeks after
discontinuing the intranasal steroids.
Our patient was given instruction on
stress dosing steroids during times
of illness or surgery and received
stress-dose steroids for an upper
respiratory illness without issue. Our
case supports the notion that it is safe
and effective to supply steroids only
at times of illness and stress during
axis recovery. However, although it
may not be necessary to supplement
with physiologic hydrocortisone,
close monitoring and clear stress-
dosing instructions are required in
these patients because ICS has been
reported to result in death.4
In conclusion, this case presents
the youngest patient to date who
developed ICS through intranasal
use of ophthalmic dexamethasone
drops. The diagnosis of ICS in
our patient was made after only
6 weeks of therapy, the shortest
reported course of intranasal steroid
treatment. This case emphasizes the
potential risk of ICS for any infant
with poor growth and Cushingoid
features regardless of the duration
of steroid use or the route of
administration. Given the small body
surface area and supine position
during administration, infants are
particularly susceptible to ICS. Close
monitoring of these patients’ height
and weight should occur while
on steroid treatment, and every
effort should be made to decrease
or discontinue steroid use when
possible. This case also suggests that
physiologic dosing during the time
of hypothalamic–pituitary–adrenal
axis recovery may not be required
and that patients can be safely
monitored and provided with stress-
dose steroids as long as appropriate
education and management plans
are provided to the patients’
families.
ACKNOWLEDGMENTS
We thank Dr. Oksana Lekarev for
her expert review of and suggestions
regarding this manuscript.
ABBREVIATIONS
ACTH: adrenocorticotropic
hormone
ICS: iatrogenic Cushing’s
syndrome
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ORTON and CENSANI
REFERENCES
1. Buluş AD, Andıran N, Koçak M.
Cushing’s syndrome: hidden risk
in usage of topical corticosteroids.
J Pediatr Endocrinol Metab.
2014;27(9-10):977–981
2. Ozdemir A, Bas VN. Iatrogenic
Cushing’s syndrome due to overuse
of topical steroid in the diaper area.
J Trop Pediatr. 2014;60(5):404–406
3. Ozon A, Cetinkaya S, Alikasifoglu
A, Gonc EN, Sen Y, Kandemir N.
Inappropriate use of potent topical
glucocorticoids in infants. J Pediatr
Endocrinol Metab. 2007;20(2):219–225
4. Semiz S, Balci YI, Ergin S, Candemir
M, Polat A. Two cases of Cushing’s
syndrome due to overuse of topical
steroid in the diaper area. Pediatr
Dermatol. 2008;25(5):544–547
5. Baş VN, Cetinkaya S, Aycan Z.
Iatrogenic Cushing syndrome due to
nasal steroid drops. Eur J Pediatr.
2012;171(4):735–736
6. Dutta D, Shivaprasad KS, Ghosh
S, Mukhopadhyay S, Chowdhury
S. Iatrogenic Cushing’s syndrome
following short-term intranasal steroid
use. J Clin Res Pediatr Endocrinol.
2012;4(3):157–159
7. Oluwayemi IO, Oduwole AO, Oyenusi E,
et al. Iatrogenic Cushing’s syndrome in
children following nasal steroid. Pan
Afr Med J. 2014;17:237
8. Perry RJ, Findlay CA, Donaldson
MD. Cushing’s syndrome, growth
impairment, and occult adrenal
suppression associated with
intranasal steroids. Arch Dis Child.
2002;87(1):45–48
9. Rottenstreich A, Wexler ID, Abu-
Libdeh A, Berkun Y. Iatrogenic
Cushing Syndrome due to Intranasal
Dexamethasone. Clin Pediatr (Phila).
2015;54(12):1215–1217
10. Kimmerle R, Rolla AR. Iatrogenic
Cushing’s syndrome due to
dexamethasone nasal drops. Am J
Med. 1985;79(4):535–537
11. Grinspoon SK, Biller BM. Clinical review
62: Laboratory assessment of adrenal
insuffi ciency. J Clin Endocrinol Metab.
1994;79(4):923–931
12. Tordjman K, Jaffe A, Trostanetsky
Y, Greenman Y, Limor R, Stern
N. Low-dose (1 microgram)
adrenocorticotrophin (ACTH)
stimulation as a screening test for
impaired hypothalamo-pituitary-
adrenal axis function: sensitivity,
specifi city and accuracy in
comparison with the high-dose (250
microgram) test. Clin Endocrinol (Oxf).
2000;52(5):633–640
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Dexamethasone: A Case ReportIatrogenic Cushing's Syndrome Due to Intranasal Usage of Ophthalmic
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