Novel Insights from Clinical Practice

HOR MON E
RE SE ARCH I N
PDIATRIC S

Horm Res Paediatr 2014;82:415418

DOI: 10.1159/000363517

Received: February 25, 2014

Accepted: May 5, 2014
Published online: October 8, 2014

Exogenous Cushing Syndrome: A Lesson

of Diaper Rash Cream
Cindy Wei-Li Ho a Kah Yin Loke a, b Yvonne Yi-Juan Lim a Yung Seng Lee ac
a

Khoo Teck Puat National University Childrens Medical Institute, National University Hospital, National University
Health System, b Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore,
and c Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore

Established Facts
Prolonged use of topical corticosteroids can result in Cushing syndrome with systemic adverse effects.

Novel Insights
We highlight how severe cushingoid features can develop rapidly in the span of 12 months with just
the use of topical potent steroids.
Many doctors failed to recognize the importance of specifically asking parents about the use of creams
and check the creams as parents may not recognize creams as medication.
Doctors and parents should be aware that such high-potency topical steroids could be easily obtained
without a prescription overseas.

Key Words
Cushing syndrome Steroid cream Pericardial effusion
Hypertension

Abstract
A prolonged use of topical corticosteroids can result in Cushing syndrome, though this is less common than with oral or
parenteral steroids. Most pediatric cases were due to application of topical steroids for diaper dermatitis. Adverse cardiovascular effects can occur in Cushing syndrome with significant long-term morbidity and mortality, though so far
there have been no reports of cardiovascular complications
due to excessive usage of topical steroids. We report a

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2.5-month-old boy who rapidly developed severe Cushing

syndrome induced by the misuse of topical clobetasol, a very
potent steroid, without a doctors prescription as a diaper
rash cream, and developed moderate left ventricular hypertrophy and pericardial effusion.
2014 S. Karger AG, Basel

Introduction

Prolonged use of topical corticosteroids can result in

Cushing syndrome, though it is less common than oral or
parenteral steroids [1]. Young children have greater risks
of local and systemic side effects of topical steroids due to
Yung Seng Lee
1E Kent Ridge Road
NUHS Tower Block, Level 12
Singapore 119228 (Singapore)
E-Mail yung_seng_lee@nuhs.edu.sg

Color version available online

Color version available online

Fig. 1. Marked cushingoid facial appearance with hirsutism over

the boys forehead and side of face.

Fig. 2. Cushingoid features gradually resolved over a 2-month pe-

riod.

their thin skin and higher body surface area. There were
several reports of iatrogenic Cushing syndrome in children as young as 3 months from the use of topical steroids
for diaper dermatitis. Two of these cases had started topical application at a very early age and died from disseminated cytomegalovirus infection [2, 3]. Cardiovascular
side effects are known to occur with Cushing syndrome
but these have largely been reported with systemic steroids. We report a 2.5-month-old boy who developed severe cushingoid features rapidly through the misuse of
topical clobetasol for less than 2 months.
416

Horm Res Paediatr 2014;82:415418

DOI: 10.1159/000363517

Case Report
The patient, a 2.5-month-old Chinese boy, presented with excessive weight gain. He was born full term by cesarean section with
a birth weight of 2.9 kg. A rapid weight gain was noticed by his
parents from 4 weeks of life. At 2 months of age, his pediatrician
noted his round facies and hirsutism during vaccination, and referred him to our tertiary center for assessment of suspected Cushing syndrome.
Initially the parents denied the use of supplements or drugs that
could contribute to the cushingoid appearance, and the use of topical steroid was not elicited by several doctors in the referral system
during history-taking. On further specific questioning about
cream application, his parents first denied topical medication but
later gave information about a diaper barrier cream they had been
applying. We asked to see the cream and discovered they had been
using clobetasol propionate 0.05% cream that had been obtained
without a prescription from a foreign country, applying it with every change of diapers to treat and prevent diaper dermatitis. This
had been ongoing since the 3rd week of life.
On examination the boy was 6.2 kg (7590th percentile) and
56.2 cm long (10th percentile). He was afebrile and noted to be
hypertensive with blood pressure (BP) ranging from 99130 to 62
82 mm Hg (95th percentile BP for age is 99/55 mm Hg) [4], with a
heart rate of 150 beats/min. There was a marked cushingoid facial
appearance with hirsutism over his forehead and side of face
(fig.1). The scrotal skin was thin but not hyperpigmented. This
could be explained by the application of steroid cream causing skin
thinning. He had hypotonia with moderate head lag at 3 months
of life, but the deep tendon reflexes were normal.
With the history of use of clobetasol, the most likely diagnosis
is iatrogenic Cushing syndrome secondary to excessive use of potent steroids. Confirmatory tests showed suppressed random cortisol of 10 nmol/l (normal 8 a.m. level 123626 nmol/l) and suppressed random ACTH <2 pmol/l (normal <10.2 pmol/l). Urinary
free cortisol was also clearly suppressed at <9 nmol/l, hence no
calculation was made for the 24-hour urinary cortisol. These were
consistent with adrenal suppression from exogenous steroids.
There was no evidence of increased mineralocorticoid activity
from hypercortisolism as serum potassium was 4.9 mmol/l (normal 3.55.0). The urinary calcium:creatinine ratio was 1.65 (normal for age 1 month to 1 year 0.092.2) indicating no hypercalciuria which can occur with severe Cushing syndrome. Renal ultrasound did not demonstrate any nephrocalcinosis or evidence of
urinary tract dilatation that can occur with renal calculi secondary
to hypercalciuria. Eye review did not reveal any cataracts. In view
of his hypertension, a two-dimensional echocardiography was arranged which showed moderate left ventricular hypertrophy
(LVH) with a small pericardial effusion. This is very surprising to
us given the relatively short duration of steroid use and ensuing
hypertension.
As he was at risk of adrenal insufficiency with the withdrawal
of the steroid cream, he was started on low-dose hydrocortisone at
1 mg b.d. (6.25 mg/m2/day). On subsequent follow-up in the clinic, the cushingoid features gradually resolved over a period of 2
months (fig.2). His weight had decreased from the 90th to the 75th
percentile and his height had increased from the 50th to the 75
90th percentile. His BP remained high with persistence of LVH on
repeated two-dimensional echocardiography until 10 months of
age when it finally resolved. The last BP reading at the age of 2 years

Ho /Loke /Lim /Lee

was 101/69 mm Hg (95th percentile BP for age is 108/62 mm Hg)

[4]. Serial monitoring of his serum cortisol showed gradual improvement and his serum 8 a.m. cortisol level was 451 nmol/l (normal 8 a.m. level 123626 nmol/l) 1 year after the cessation of use
of topical steroids.

Discussion

Previous reports of affected cases in children were infants with diaper dermatitis, and the other primary diseases were psoriasis, burns, and skin dryness [1]. The steroid most commonly used was clobetasol and the other
was betamethasone. The median duration for application
was 2.75 (117) months. Typical Cushing features appeared in all cases with suppressed cortisol and ACTH
levels. The mean recovery of the HPA axis after discontinuation of topical steroids was 3.49 2.92 (112) months
[1].
Our patient had received a clobetasol application 89
times a day since the 3rd week of life when changing diapers. Topical steroids can be absorbed through normal
skin and the thin and delicate skin of neonates and infants
is particularly susceptible. As infants have a larger ratio of
body surface area to body weight, they are more prone to
develop systemic adverse effects. Clobetasol proprionate
is considered to be a very potent steroid in the UK classification and class I (super high potency) steroid in the
USA classification. It is estimated to be 1,000 times more
potent than 1% hydrocortisone [5, 6]. In some countries
these dermatological medications can be purchased at
drug stores without a doctors prescription. The infants
parents had many tubes of clobetasol purchased by a
friend who visited one of these countries. An important
learning point is to be vigilant of topical steroid and ask
to see any topical creams applied on infants and not to
assume that the diaper rash cream parents are using is the
standard diaper barrier cream. This was missed by several doctors who saw the child and he could have been
subjected to unnecessary investigations to delineate the
source of endogenous cortisol production.
Cardiovascular disease, in particular moderate diastolic hypertension, is a major cause of morbidity and death
in patients with Cushing syndrome [7]. The pathogenesis
of hypertension is multifactorial and not fully understood, involving various factors like increased peripheral
vascular sensitivity to adrenergic agonists, increased hepatic production of renin substrate (angiotensinogen)
[8], and possibly a direct cardiotoxic effect of cortisol [9].
A new cardiovascular finding in our patient, not previA Lesson of Diaper Rash Cream

ously reported, was that of pericardial effusion. It was

postulated to be most likely due to steroid use although
the mechanism is uncertain. The clinical impact of pericardial effusion if the Cushing syndrome goes untreated
remains unknown.
While the steroid-induced hypertension could be the
cause of the LVH in our patient, it is likely also a direct
steroid cardiotoxic effect. Given the short duration of
topical steroid use, we were surprised to see its deleterious
effects on the heart at such a young age. Fortunately the
LVH subsequently resolved.
The appropriate management to prevent adrenal insufficiency after the cessation of the suppressive exogenous steroid is to give a physiologic dose of steroids for
about 69 months and stress dose of steroids during intercurrent illness. To avoid the adverse effects of topical
corticosteroids, clinicians should be aware of such effects
and avoid these problems by prescribing topical corticosteroids of appropriate potency, especially during infancy, advising parents to apply only a thin layer to the affected skin and discontinuing them when no longer required. Parental education as to the possible adverse
effects should also be encouraged before the use of these
agents.

Conclusion

We report a case of iatrogenic Cushing syndrome with

severe cushingoid features that progressed rapidly within
a short span of less than 2 months and also highlight the
importance of specific direct questioning about topical
medications and looking at all creams used when trying
to elicit causes for iatrogenic Cushing syndrome, as parents often do not see creams as medications. The profound effect of the topical steroid on the infants appearance and heart is a lesson to all about the prolonged use
of topical steroids, especially those of high potency. We
should also be mindful that in some countries some of
these high-potency steroids could be available as overthe-counter medications and easily obtained by parents
unaware of the dangers.

Horm Res Paediatr 2014;82:415418

DOI: 10.1159/000363517

417

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Ho /Loke /Lim /Lee

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