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

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Dexamethasone: A Case ReportIatrogenic Cushing's Syndrome Due to Intranasal Usage of Ophthalmic

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