Steroids In Pediatrics By Dr. Piyush 2018

PRESENTED BY : DR. PIYUSH RANJAN SAHOO
JUNIOR RESIDENT
STEROIDS IN PEDIATRICS

We Will Cover…
 Briefly About The Adrenal Glands
 Steroid Biosynthesis
 Mechanism Of Action
 Regulation Of Secretion
 Comparison Among Preparations
 Actions
 Adverse Effects & C/I
 Prevention & Therapy of S/E
 Uses In Neonates
 Uses In Older Children
 Take Home Message
 References
Biochemistry
Physiology
Anatomy
Pediatrics
Pharma
Pathology
Of Steroids

Adrenal Glands: Anatomy
 Lie immediately antero-superiorly
to the upper pole of each kidney.
 Surrounded by perinephric fat
enclosed within the renal fascia of
Gerota, and separated from the
kidneys by fibrous tissue.
Each gland possesses two
functionally and structurally
distinct areas:
Outer Cortex
Inner medulla
Gray’s Anatomy 41/e Chapter 71

Outer Cortex Microstructure Responsible For
Steroid Secretion
Ref - Gray’s Anatomy 41/e Chapter 71
Capsule
ZG
ZF
ZR

Outer Cortex Microstructure Responsible For
Steroid Secretion
• Narrow region of small polyhedral cells arranged in rounded clusters.
• Cells have deeply staining nuclei and a basophilic cytoplasm abundant of
smooth endoplasmic reticulum (typical of steroid-synthesizing cells).
Zona
glomerulosa
• Large polyhedral basophilic cells arranged in straight columns.
• Also contain large amounts of SER.
Zona
fasciculata
• Branching interconnected columns of rounded cells with cytoplasm containing
SER, numerous lysosomes and aggregates of brown lipofuscin pigment that
accumulate with age.
Zona
reticularis
Ref -- Gray’s Anatomy 41/e Chapter 71

Adrenal Glands: Histology
Ref -- Ross’s Histology 7/e

Adrenal Glands: Physiology
Ref – Ganong Physiology 25/e

HPA Axis: Regulation Of Steroid Production
& Response To Stress
Ref – KDT Pharmacology 7/e

Adrenal Steroidogenesis : Biochemistry
Mnemonic = 3  2  1

Q. Where Does The Rate Limiting Step Take Place?
A. Nucleus
B. Mitochondria
C. SER
D. RER
The Rate Limiting Step takes place in Adrenal
Mitochondria. Rest steps take place in
Adrenal/Gonadal SER.
Mnemonic - STEROIDS

Biochemistry of Steroidogenesis
StAR Protein
Mitochondrial P450SCC
RATE LIMITING
STEP
Lipoid CAH :
Most Severe
Ref – Nelson 20/e

Diurnal Variation
Source -- Web
 What’s the cause?
 What’s the importance?

Q. Why There Is Evening Rise Of Temp. In TB?
---Ward Round Question by Kedar Sir---
Diurnal Relationship between Cortisol, Melatonin and Body temp.

Two Possible Explanations
Diurnal Variation of Body
Temperature:
Body temp varies
according to activity and
there is a 0.5◦ variation
normally -- highest in the
evening and lowest in the
morning.
Diurnal Variation of
Cortisol Secretion:
Higher during the day
time, lower in the evening.
Being an antiinflammatory
hormone, it keeps the
inflam. markers in check
during day.
TB = chronic low level inflammation. Hence, evening rise
temperature more marked.

Regulation, Response And Defects

Preparations, Potency & Classification

Relative Efficacy Of Preparations
---Potency relative to Hydrocortisone

Inference From The Relative Efficacy
Maximum glucocorticoid activity Dexamethasone
Maximum mineralocorticoid activity Aldosterone
Glucocorticoid with maximum mineralocorticoid
activity
Hydrocortisone
Least potent glucocorticoid Cortisone
Most potent glucocorticoid Dexa ≈ Betamethasone
Selective mineralocorticoid action (zero glucocorticoid) DOCA
Selective glucocorticoid action (zero mineralocorticoid ) Methylprednisolone,
Triamcinolone, Dexa,
Beta
Maximum topical activity Triamcinolone

Pharmacological Actions
 Direct (Intended) Actions
 Anti-inflammatory
 Anti-allergy
 Immunosuppressive
 Permissive Actions
 Lipolytic effects
 Effect on BP
 Effect on bronchial smooth muscles
They do not themselves
produce these effects, rather
their presence facilitates
other hormones to exert that
action.

Anti-inflammatory & Immunosuppressive Effects
Source – Medscape

Anti-inflammatory Effect
 Most important
mechanism 
Inhibition of
chemotaxis.
 Also induce
production of
Annexins (formerly
Lipocortins):
Inhibit Phospholipase A2
that is involved in the
production of PG and LT.

Immunosuppressive Effect
 Q. Suppress more?
A. Cell-mediated immunity
B. Humoral immunity
 Most important mechanism  Inhibition of recruitment of
immune cells.
 Also inhibit release of IL-1 & IL-2.
 At high doses  Antibody production is affected.
 Continuous administration of GCs  Catabolism of IgG.
 Basis of use in graft rejection and various HSRs.

Adverse Effects & C/I
 G – Glaucoma (topical use)
 L – Limb muscle atrophy
 U – Ulcer (peptic) is a C/I
 C – Cushing’s habitus
 O – Osteoporosis
 C – Cataract [PSC in children on long-term systemic use]
 O – Osteonecrosis (AVN, Mostly of Hip joint)
 R – Renal failure is a C/I*
 T – Tuberculosis is a C/I (mainly Ileo-cecal)
 I – Impair wound healing & scar formation
 C – CHF is a C/I*, Convulsions are C/I
 O – Oedema
 I – Infections (d/t immunosuppression)
 D – Diabetes mellitus
 S – Suppression of HPA axis
Routine prescription of
antacids or H2 blockers is
discouraged in patients
taking steroids.
* For Mineralocorticoids

Glaucoma Versus PSC
 Topical steroid use is typically more closely associated with increase in
IOP than PSC.
 Systemic glucocorticoid-induced gene transcription events in lens
epithelial cells causes PSC.
Does NOT revert back even after
stoppage of steroid therapy

Risk of S/E Depends On
 Dose
– Low dose (< 10 mg/day of prednisone)
– Medium dose (10-20 mg/day)
– High dose (> 20 mg/day)
 Type of steroid
– Long-acting
– Short-acting
 Length of treatment: (Long-term treatment > 3 months)
 Other medical problems

S/E
• Hyperglycemia
• Hyperlipidemia
• Peptic ulcer disease
• Psychosis
Dose Dependent Duration Dependent
• GI intolerance
• Increased infections
• Delayed wound healing
• Raised appetite
• Sodium, water retention
• Mood changes
Musculoskeletal
• Growth retardation
• Osteoporosis
• Myopathy
• AVN
HPA Axis
• Adrenal suppression
• SWS
• Adrenal crisis
Ophthalmologic
• Cataracts
• Glaucoma
GI
• Gastritis, PUD
• Pancreatitis
• Perforation/bleeding risk
Metabolic
• Hyperglycemia
• Hyperlipidemia
• Hypokalemia
• Hypocalcemia
Cutaneous
• Hirsutism
• Atrophy
• Hyperpigmentation
• Acne
CNS
• Personality changes
• Psychosis
• Seizures
• Pseudotumor cerebri
Long Term GC Therapy
Short Term GC Therapy

Before Starting A Steroid…
Full History including psychiatric evaluation and other medication history
Measure Blood pressure
Measure Blood sugar
Varicella – H/O Chickenpox, Check Antibodies if necessary, advise against
contact with chickenpox and shingles cases.
Tuberculosis – H/O TB, Contact history, Mantoux, CXR
Osteoporosis – DEXA scan maybe needed. Ensure sufficient intake of Calcium &
Vit. D3. Hormone replacement if necessary.
Peptic Ulcer Disease – H/O PUD. Give PPx if high risk group.

Follow Up Protocol
EXAMINATION:
At 1 mo – thereafter every 2-3 mo 
 BP, Wt.
 Ht & Wt plotted on growth curve
 Thorough H/O at each visit for S/E
Every 6 mo initially, then annually 
 Ophthalmological examination
LABORATORY:
At 1 mo – thereafter every 3-4 mo 
 K+ level
 FBS
 TGL
Near time of cessation of long term CS
therapy 
 8-9 am Cortisol level

Prevention & Therapy Of S/E
1. Hyperglycemia:
 Prevention: Dietary measures (low in saturated fat & calories), regular
monitoring of BGL & HbA1c during therapy is important.
 Diagnosis: Fasting glucose level.
 Management: Proper diet, Insulin, Oral hypoglycemics, Insulin
sensitizers, reduction in glucocorticoid dose.
 If steroid is stopped - hyperglycemia may fully reverse over many
months.
Persistent Hyperglycemia:
 Blood glucose levels < 250 mg/dL  addition of insulin-sensitizing
drugs (TZD, Metformin) and/or insulin secretagogues
 Blood glucose levels > 250 mg/dL (especially if pt is symptomatic) 
Consider insulin therapy.

2. HTN:
 Mech: MC effect induced Na+ retention + d/t GC effect induced
vasoconstriction.
 Prevention: Na restriction,choose CS with low MC effect
 Diagnosis: Monitor BP
 Management:
 1. Na+ restriction.
 2. Anti-hypertensives (Thiazides) or by blocking MC receptors
with Spironolactone.

3. Hyperlipidemia:
 Mech: GC Effect-catabolic state, initiated by elevated Lipoprotein lipase.
 Prevention: Low calorie, low saturated fat diet
 Diagnosis: Triglycerides level
 Management: Gemfibrozil, Statins
4. Cushingoid Changes:
 Mech: Altered fat distribution, result of overall fat catabolism
 Addl. Effect: Moon facies, Truncal obesity, Buffalo hump
 Prevention: Dietary measures, exercise
 Diagnosis: Low ACTH level, High Cortisol level, Hypokalemia, Low bone
density as measured by DEXA scan, High cholesterol particularly high TG &
low HDL.

Cushing’s Habitus & Striae
 Characteristic appearance d/t redistribution of fat

4. Glucocorticoids induced Osteoporosis: Mechanism

 Observation: Bone loss occurs early within first 3 to 6 months
 Bone loss that has occurred is usually never fully regained even
after steroids are discontinued
 Prevention & T/t: Bisphosphonates (Alendronate, Etidronate or
Risedronate) are recommended first-line therapy for the
prevention & t/t of GIOP.

5. HPA Axis Effects:
 Mech: Reduced GC & MC reserves
 Pathophysiology: CS administration results in a negative feedback effect via
GC receptors in ant. hypothalamus which in turn suppresses production of
CRH & ACTH. Prolonged suppression of ACTH levels leads to atrophy of
adrenal cortex & secondary adrenal insufficiency.
 Addl risk factors: Major surgery, trauma, illness, severe gastroenteritis with
fluid & electrolyte loss.
 Prevention: Appropriate CS tapering / withdrawal
 Diagnosis: By History of patient
 Therapeutic glucocorticoid administration is MCC of secondary AI.

Replacement Therapy
 Aim  To resemble the endogenous secretory rate of Cortisol.
 Overtreatment  Causes S/S of Cushing syndrome & can impair
the growth of children.
 Undertreatment  Will cause the S/S of Adrenal Insufficiency
& may impair the individual’s capacity to respond to stress.
Q. Physiological Cortisol secretory rate?
 Ans. 6 - 8 mg/m2/day in children and adults.
 A patient with a body surface area of 1 m2 will have a
secretory rate of about 8 mg/day.
Ref - Sperling 2014 ed P.522

Q. Then same treatment for all?
 Ans. No.
 For infants and children < 5 yrs, the range of normal values
varies widely, so, therapy must be individualized for each patient
to achieve optimal results.
Q. Why steroids so unique?
 Ans. In contradictinction to many other drugs, orally
administered steroids are absorbed rapidly but incompletely,
whereas intramuscularly administered steroids are absorbed
slowly but completely.

Withdrawal Of GC Therapy
GC therapy for only
1 wk or 10 days
Therapy can be discontinued abruptly,
even if high doses have been used. How?
Logic: Although only one or two doses of GC are needed to
suppress the HPA axis, this axis recovers very rapidly from short-
term suppression.
GC therapy for 2
wks or longer
Recovery of HPA axis is slower, and
tapering of GC dose indicated. Why?
Logic: Acute discontinuation of therapy in such patients will lead
to symptoms of Adrenal Insufficiency (Steroid Withdrawal
Syndrome).

Q. Reducing higher doses directly to “physiologic replacement
doses" won't work too. Why?
Logic: Even pharmacologic doses of GC for a long-term inhibits
synthesis of GC receptors, so physiologic doses of GC will elicit
sub-physiologic cellular responses, resulting in SWS.
Q. Does the symptom complex of SWS include salt loss and low
BP?
 Ans. Salt loss doesn't occur. ZG function is regulated principally
by RAS system, hence remains normal.
 BP can fall abruptly, as GC are required for the action of
catecholamines in maintaining vascular tone.

Successful Steroid Tapering Predicted By…
 Length of t/t 
Long term < Short term.
 Type of steroid 
Long acting < Short acting.
 Mode of t/t 
Daily therapy < AD therapy.
 Individual patient responses 
Morning Sr. Cortisol value ≥ 10 mcg/dL indicates that the dose
can be reduced safely.

Prednisone Tapering Steps For Children
Ref - AACI Journal 2013 Issue Page 19
Taper GC dose as guided by underlying
condition until 30 mg/m2/day of
Hydrocortisone equivalent is reached
Logic: At 30 mg/m2/day, the adrenal cortex must
begin to produce its own Cortisol again, and the
weaning process needs to progress more slowly
to minimize withdrawal symptoms.
Then taper by 10-20% every 3–7 days until
patient is on physiological GC dose (8–10
mg/m2/day H.E.)
H.E. = Hydrocortisone Equivalent

Switch to Hydrocortisone 8–10 mg/m2/day,
given in the morning or AD therapy. Now
proceed more slowly.
Logic: At this point, the adrenal glands need to
produce natural Cortisol, as the drug is no longer
providing enough corticosteroid to keep the body
functioning properly.
Discontinue/continue Hydrocortisone based
on assessment of morning Cortisol.
Ref - AACI Journal 2013 Issue Page 19

Morning Cortisol
> 20 µg/dL or 500
nmol/L: HPA axis has
recovered
------------------------------
• Discontinue daily and
stress Hydrocortisone
3-20 µg/dL or 171-500
nmol/L: Sufficient GC
production for day-to-day
functioning
---------------------------------
Further evaluation needed to
determine if stress dose
required:
→ Discontinue daily
hydrocortisone
→ Continue stress dosing as
needed
→ Low-dose ACTH stimulation
testing
< 3 µg/dL or 171 nmol/L:
HPA axis has not
recovered
--------------------------------
→ Continue daily
Hydrocortisone
→ Continue stress
Hydrocortisone as
needed
→ Re-evaluate patient in
4–6 weeks
If with ACTH testing:
 Peak Cortisol > 500 nmol/L: HPA axis is intact and GC can be discontinued.
 Peak Cortisol < 500 nmol/L: Steroids required at times of stress until normal ACTH
response is noted.

After Successful Withdrawal
 Even after successful withdrawal from a long term high dose
GC therapy, HPA axis remains incapable of responding to
severe stress for = 6 to 12 mo.
 What to do?
 CRF or Metyrapone test  Evaluation of the hypothalamus
and pituitary.
 IV low-dose ACTH test  Evaluation of adrenal
responsiveness to pituitary stimulation, done at the
conclusion of a withdrawal program and 6 mo thereafter.
 The results of these tests will indicate if there is a need for
“steroid coverage” in acute surgical stress or illness.

Stress Doses of Glucocorticoids
 Cortisol secretory rate increases significantly during
physiologic stress e.g. trauma, major surgery or severe
illness.
 Candidates: Patients receiving GC replacement therapy or
those recently withdrawn from pharmacologic therapy.
 Stress Dose = Doses 3-10 times physiologic replacement.
 Preferred = Hydrocortisone (Logic: Short duration of
action + Mineralocorticoid effect) 30-100 mg/m²/day [in
divided doses] during stress.
 Rate of tapering = Taper by 50% daily
 Equivalent oral dose of Prednisone = 0.5-0.8 mg/kg/day
Ref - Sperling 2014 ed P.522 & Bagga Pediatric Nephrology 6/e

iPhone & Android Apps For Steroid
Tapering

Steroids & Vaccines
Live Virus Vaccines NOT C/I:
 Short term steroid therapies (< 2 wks)
 Alternate-day steroid therapy
 Physiologic replacement dose
 Topical (skin or eyes), Aerosol or Intra-articular, Bursal, or Tendon injection
Not Safe To Give Live Virus Vaccines:
 Dose equivalent to either 2 mg/kg (or a total of 20 mg/day) of
Prednisone for ≥ 2 wks is sufficiently immunosuppressive.
 After discontinuation of therapy or reduction of dose after high doses of
CS for ≥ 2 wks: Wait at least for 1 mo.
Inactivated Vaccines And Toxoids:
 Can be administered to all immunocompromised patients in usual doses
and schedules, but the response to these vaccines may be suboptimal.
Ref - Pan-American Health Organization 2010, ACIP Guidelines 2018

Specific Recommendations
 If feasible, vaccines should be given before planned immunosuppression.
 Live vaccines should be given at least 4 wks before immunosuppression and
should be avoided within 2 wks of initiating immunosuppression.
 Inactivated vaccines should be given at least 2 wks before immunosuppression.
 Most immunocompromised patients at least 6 mo of age should receive annual
influenza vaccination as an injection, but they should not receive LAIV
administered as a nasal spray.
 Immunocompetent persons living in a household with immunocompromised
patients can safely receive inactivated vaccines based on the CDC-ACIP
recommendations.
 Persons living in a household with immunocompromised pts at least 6 months of
age should annually receive influenza vaccine, either inactivated or LAIV, provided
they’re healthy, not pregnant, and aged 2-49 yrs.
Ref - IDSA Guidelines Updated in 2013, Reviewed in 2018

Steroids Use In Neonates
1. RDS Prevention
2. BPD
3. Planned Extubation
4. Resistant Hypotension
5. CAH
6. Refractory Hypoglycemia
Index

1. Prevention Of RDS
 Basis = Maternal hormones, specifically glucocorticoids,
enhance surfactant maturation.
 Administration of antenatal corticosteroids (ANC) modifies
surfactant readiness as well as lung structure (including
thinning of alveolar walls).
 Target population = Pregnant women at 24-34 wks of gestation
with PTL.
 Complete course of ANC:
Ref - Cloherty 8/e P439
Inj. Betamethasone 12 mg IM
OD × 2 doses OR
Inj. Dexamethasone 6 mg
IM q12h × 4 doses

Ref – Ministry Of Health & Family Welfare, GOI

Postnatal Corticosteroids in BPD
 T/t with GCs (usually Dexamethasone) in infants who remain ventilator
-dependent for 2-3 wks results in:
 Increased dynamic compliance (Crs)
 Decreased Resp. system resistance (Rrs)
 Diminished O2 requirement
 Facilitated earlier extubation
 Dexamethasone:
 Short-term S/E = HTN, hyperglycemia, GI perforation
 Long-term S/E = impaired neurodevelopment and growth. Routine
use of Dexamethasone is discouraged.
 Hydrocortisone use is not asso. with the neurodevelopmental
concerns described with dexamethasone.

1.25 mg/kg/dose IV/PO q6h × 7 days
1.25 mg/kg/dose q8h × 5 days
If the risk of developing BPD is estimated at 2 weeks of age as
≥60%, a preventive course of Hydrocortisone is given:

3. Planned Extubation
 Post-extubation airway edema, with stridorous obstruction
leading to respiratory failure, may be attenuated with
Dexamethasone.
 Q. How many doses desired?
 Edema also may be acutely diminished with nebulized racemic
epinephrine.
 Prone positioning.
Ans. 3 doses Dexamethasone at 0.25 mg/kg/dose every 12
hours starting 8 to 12 hours before a planned extubation.

4. Vasopressor-Resistant Hypotension
 Hydrocortisone replacement: Useful in infants with hypotension refractory to
volume expansion & vasopressors, especially premature infants.
 Hydrocortisone stabilizes BP through following mechanisms:
 It induces the expression of the adrenergic receptors that are
downregulated by prolonged use of sympathomimetic agents.
 It inhibits catecholamine metabolism.
 Rapidly increases intracellular Calcium availability, resulting in enhanced
responsiveness to adrenergic agents.
 The BP response is evident as early as 2 hours
after Hydrocortisone t/t.
Ref - Cloherty 8/e P.A1071 & P507

 Day 1 initial dose = 1 mg/kg/dose q8h × 3 doses
 Day 2 follow in 12 hours with = 0.5 mg/kg/dose q12h × 2 doses
 Day 3 follow in 12 hours with = 0.25 mg/kg/dose q12h × 2 doses
 Day 4 follow in 24 hours with = 0.125 mg/kg/dose × 1 dose
 If BP improves and other pressors have been weaned off, may stop
after 24 hours.
 Final conc. for infusion = 1 mg/mL in dextrose or saline.
 Use preservative-free Hydrocortisone sodium succinate
formulation for IV dosing.
Ref - Cloherty 8/e P.A1071 & P507

5. Congenital Adrenal Hyperplasia (CAH)
 In an infant suspected of 21-OHase deficiency, t/t should be started as
soon as the lab tests have been obtained.
 Glucocorticoids: Hydrocortisone 20 mg/m2/day 8 hrly, should be
given to all infants suspected of 21-OHase deficiency. Stress dose = 30
to 50 mg/m2/day.
 Mineralocorticoids: In cases of salt-wasting CAH, Fludrocortisone
acetate 0.1 to 0.2 mg daily is given.
 Q. Salt-wasting crises usually develop between?
o Ans. 5th-14th day of life (but can occur as late as 1 month).
 Weight, fluid balance, and electrolytes must be monitored closely, with
blood samples at least every 2 days during the first few weeks of life
to detect hyponatremia or hyperkalemia.

CAH: Prenatal Dx & Treatment
Confirmation of
pregnancy
At risk pregnancy:
H/O prev. CAH
Start Dexamethasone (20
mcg/kg/day PO 2-3 div. doses)
as soon as pregnancy is
diagnosed i.e. 6 wks
(Before 9th wk GA)
Sex & Genotype
Determination
By CVS: at the 9 – 11th
weeks GA
Search for mutations
and/or deletions in the
CYP21 gene
Continue Dexa until
the results have
arrived
 If Male: STOP Dexa
 If unaffected Female: STOP
 If affected Female: Continue
till delivery
If the family is unwilling /
unable for CVS or if the
results of CVS are
contradictory,
Amniocentesis at 15 - 18
wks GA
COUNSELLINGCONSENT

6. Refractory Hypoglycemia After GIR @
12-15 mg/kg/min
 Inj. Hydrocortisone, 10 mg/kg/day IV in two divided doses.
 Q. Correct Mechanism?
 A. Reduces peripheral glucose utilization
 B. Increases gluconeogenesis
 C. Increases the effects of glucagon
 After attaining stable glucose levels, and it can then be rapidly
tapered over the course of a few days.
 Before administering hydrocortisone, ideally we should test
cortisol level.
 Do not use hydrocortisone routinely for hypoglycemia.

Critical Lab Sample
 Diagnosing hyperinsulinemia requires measuring an insulin level that is
inappropriately high for a simultaneous sr. glucose.
 Evaluation requires drawing the Critical Lab Sample at a time when the
glucose level is <40 mg/dL.
 The typical Critical Lab Sample includes the following:
i. Glucose
ii. Insulin
iii. Cortisol: to screen for the integrity of the HPA axis.
iv. β -hydroxybutyrate and free fatty acid levels:
[Logic: Their Measurement in plasma can be useful because decreased
levels of these substances can indicate excessive insulin action even if
insulin levels are not significantly elevated.]
Mnemonic: B.I.G. College

Steroids Use In Pediatrics
1. Replacement Therapy
2. Pharmacotherapy
3. Diagnostic Use
As Per KDT Pharmacology

Adrenal Insufficiency
Primary Secondary
Etiologies:
1. CAH (59%)
2. Autoimmune (16%)
3. Adrenoleukodystrophy (4%)
4. Idiopathic (4%)
5. Hemorrhage (1%)
Etiologies:
1. Drug-induced (GC administration)
2. Abrupt stoppage of GC
3. Hypothalamic or pituitary tumors
4. Trauma/ Surgery/Irradiation
5. Pituitary apoplexy /Sheehan synd.
6. Isolated ACTH deficiency
7. Prader-Willi syndrome
Ref – Nelson 20/e P2707

Adrenal Insufficiency: C/F
Clinical Manifestations and Biochemical Findings :
 Most Prevalent Symptoms = N/V, Fatigue, Anorexia, Wt. loss (90%)
 Most Prevalent Signs = Low BP, Orthostatic HypoTN (70-100%)
 MC Lab Findings:
- Hyponatremia (90%),
- Hyperkalemia (50%),
- Hypoglycemia (30%),
- Low random Cortisol level (80%),
- High ACTH level (primary adrenal insufficiency only) (100%)
- High plasma renin activity (primary adrenal insufficiency only) (100%)

Adrenal Insufficiency: Ix
Most Definitive Test: “ACTH STIMULATION TEST”
i.e. Measurement of Sr. Cortisol levels before & after ACTH administration.
 We measure Cortisol levels before and 30 or 60 min after giving 250 µg of
ACTH by rapid IV infusion.
 Resting levels are low and do not increase normally after administration of
ACTH = Primary A.I.
 A low initial level f/b a significant response to ACTH indicates = Secondary A.I.
Drawback & Solution:
 Occasionally, normal resting levels that don’t increase after administration of
ACTH may indicate = Absence of adrenocortical reserve.
 Low-dose test (1 μg ACTH 1-24/1.73 m2) is more sensitive test for AC reserve.

Adrenal Insufficiency
Suspected
A.I. is Possible
8 AM Sr. Cortisol
Sr. Cortisol ≤ 15 µg/dLSr. Cortisol > 15 µg/dL
250 µg ACTH Stimulation
Test
A.I. is Unlikely
Sr. Cortisol ≥ 18 µg/dLSr. Cortisol < 18 µg/dL
A.I. is UnlikelyA.I. is Possible

8 AM Sr. ACTH
Increased ACTH Decreased or Normal ACTH
Primary A.I. Secondary A.I.

1. Acute Adrenal Insufficiency
 Medical emergency.
 IV solution of 5%D in 0.9% saline should be administered to correct
hypoglycemia, hypovolemia and hyponatremia.
 Hydrocortisone sodium succinate (a water-soluble form) is given IV.
 Dose: 10 mg for infants, 25 mg for toddlers, 50 mg for older children, and
100 mg for adolescents administered as a bolus and a similar total amount
given in divided doses at 6 hrly for the 1st 24 hr.
 If progress satisfactory: Doses may be reduced over next 24 hr.
 Amount of fluid infused IV is guided by monitoring CVP, because these
patients have reduced capacity to excrete water load.
 Short-term IV infusion of a vasopressor (Dopamine) may be needed.
 Chronic replacement therapy: Hydrocortisone 10 mg/m2/day PO in 3
divided doses.

2. Chronic Adrenal Insufficiency
 Hydrocortisone given orally is the MCnly used drug along with
adequate salt and water allowance.
 Iatrogenic secondary A.I. (caused by chronic glucocorticoid
administration) is best avoided by use of the smallest effective doses
of systemic GCs for the shortest period of time.
 For at-risk patients: Taper the dose rapidly to a level equivalent to or
slightly less than the physiologic replacement (~10 mg/m2/day) and
further taper over several week.
 Patients with anatomic lesions of the pituitary: Treat indefinitely
with glucocorticoids.
 Some patients in addition need a mineralocorticoid: Fludrocortisone is
added.

3. Congenital Adrenal Hyperplasia
(Adrenogenital Syndrome)

CAH Mnemonic
Enzyme Deficiency A T
21-Hydroxylase Deficiency
17 α-Hydroxylase Deficiency
11β-Hydroxylase Deficiency
2
7

1. Steroids in Tuberculosis
Q. What are the indications for t/t with steroids in TB?
 TBM (reduced mortality and morbidity)
 TB pericarditis (risk of cardiac tamponade & constrictive pericarditis
reduced)
 TB pleural effusion (when large with severe symptoms)
 Adrenal insufficiency (TB of adrenal glands)
 TB laryngitis (with life-threatening airway obstruction)
 Severe hypersensitivity reactions to anti-TB drugs
 Renal tract TB (to prevent ureteric scarring)
 Massive LN enlargement with pressure effects
 Endobronchial TB
 Miliary TB with alveolocapillary block
---Ward Round Question by Kedar Sir--

 Preferred steroid preparations = Prednisolone
 Dose of Prednisolone = 1 to 2 mg/kg/day × 2-4 wks  gradual
tapering over next 4-6 wks.

Why This Clinical Confusion?
Immunosuppressant
May reduce the inflammation of
the meninges
May suppress the immune
response to M.Tb  systemic
effects may worsen
Drug penetration to the
subarachnoid space reduced
Paradoxical reactions, mainly
in CLHA
Clinical or radiological worsening
of pre-existing TB lesions or
development of new lesions in pts
on ATT who initially improved
with t/tIRIS (Immune Reconstitution
Inflammatory Syndrome)

2. Rheumatic fever
 Antiinflammatory Therapy:
Q. In a suspected case of ARF with arthralgia or atypical arthritis,
antiinflammatory agents (e.g. salicylates, corticosteroids)
should be?
A. Started immediately
B. Withheld immediately
C. Started with higher dose and then tapered
D. Started with lower dose and then escalated
• Premature t/t with these agents may interfere with the development of the
characteristic migratory polyarthritis and thus obscure the diagnosis of ARF.
• PCM can be used to control pain and fever during this period.
Ref – Nelson 20/e

 Patients with typical migratory polyarthritis + carditis without
cardiomegaly or CCF  treat with Oral salicylates.
 Usual dose of Aspirin is 50-70 mg/kg/day in 4 div. doses PO × 3-5 days,
 --f/b--> 50 mg/kg/day in 4 div. doses PO × 3 wk and half that dose for
another 2-4 wk.
 Patients with carditis + more than minimal cardiomegaly
and/or CCF  Give Corticosteroids.
 Usual dose of Prednisone is 2 mg/kg/day in 4 divided doses × 2-3 wk
 --f/b--> half the dose for 2-3 wk and then tapering of the dose by 5 mg/24
hr every 2-3 days.
 When prednisone is being tapered, aspirin should be started at 50
mg/kg/day in 4 div. doses for 6 wk to prevent rebound of inflammation.
Ref – Nelson 20/e

Rx Of Childhood Rheumatic Diseases
Ref – Nelson 20/e

 IV steroids are used to treat severe, acute
manifestations of systemic rheumatic
diseases such as SLE, dermatomyositis
and vasculitis.
 IV route allows for higher doses to obtain
an immediate, profound
antiinflammatory effect.
 Inj. Methylprednisolone 10-30
mg/kg/dose (max dose 1 g) given IV over
1 hr daily × 1-5 days is the preparation of
choice.
Ref – Nelson 20/e
Inj. Methyl-Pred
 500 mg = 550 INR
 1000 mg = 1080 INR

3. JIA
 No role in pharmacologic t/t. Systemic
steroids are recommended only for --
 (i) M/m of severe systemic illness,
 (ii) For bridge therapy before response to a DMARD
 (iii) For control of uveitis.
 Candidates: No or partial response after 4-6 wk t/t
with NSAIDs or functional limitations + (e.g. joint
contracture or leg-length discrepancy).
 Suitable preparation: Intra-articular
Triamcinolone hexacetonide
 Logic: Long-lasting preparation, provides a
prolonged response.
 S/E: Myopathy [Avoided in NM disorders]
Ref – Nelson 20/e
Inj. Kenacort
 10 mg / 1 mL = 30 INR
 40 mg/ 1 mL = 55 INR

4. SLE
 Steroids are mainstay for t/t of significant manifestations of
SLE and work quickly to improve acute deterioration.
 First line: High doses of Inj. Methylprednisolone 30
mg/kg/day IV × 3 days --f/b--> weekly pulses.
 Alternative: High doses of oral prednisone (1-2 mg/kg/day).
 On improvement: Taper corticosteroid dosages gradually
over months.
Ref – Nelson 20/e

Dx is JDM
A characteristic, violaceous rash is
present over the eyelids with
periorbital edema
Gottron papules are present over
the metacarpophalangeal joints and
proximal interphalangeal joints.

5. Juvenile Dermatomyositis (JDM)
 Mainstay of t/t: Steroids
 T/t of choice in a clinically stable child: Oral Prednisone 2 mg/kg/ day
(maximum 60 mg daily).
 Children with GI involvement (d/t decreased absorption of oral
steroids) & in severe cases with respiratory or oropharyngeal
weakness: High-dose pulse Inj. Methylprednisolone 30 mg/kg/day IV
× 3 days (maximum dose 1 g/day) with ongoing weekly or monthly IV
dosing along with daily oral corticosteroids as needed.
 Dose tapered over a period of: 12 mo
Ref – Nelson 20/e

6. Acute Urticaria
 Self-limited illness.
 Best T/t: Avoidance of any identified trigger.
 Antihistamines:
 Hydroxyzine and Diphenhydramine (S/E = sedation)
 Loratadine, Fexofenadine and Cetirizine: preferable because of less
frequency of drowsiness and longer duration of action.
 Epinephrine: 1 : 1,000, 0.01 mL/kg (maximum: 0.3 mL) IM provides rapid
relief of acute, severe urticaria/angioedema.
 Oral corticosteroids: Short course, only for very severe episodes of urticaria
and angioedema that are unresponsive to antihistamines.
Ref – Nelson 20/e

7. Bronchial Asthma
Inhalational CS:
 ICSs are available in MDIs, in dry powder inhalers (DPIs), or in
suspension for nebulization.
 The selection of the initial ICS dose is based on = Disease severity.
 MCnly encountered S/E of ICSs = local: oral candidiasis (thrush)
and dysphonia (hoarse voice) [Dose dependent]
Systemic CS:
 Oral corticosteroids are used primarily to treat asthma
exacerbations.
Ref – Nelson 20/e

Systemic CS in Status Asthmaticus
Ref – Nelson 20/e
Drug Class MOA Cautions & S/E
• Preferred: Inj. Hydrocortisone 10 mg/kg IV STAT --f/b-->
5 mg/kg/dose IV 6 hourly

• ICS therapy used for severe persistent asthma.
• Budesonide DPI / suspension for nebulization.
• AS per NIH guidelines:
• Step 2 –low dose ICS (0.25-.5 mg/day)
• Step 3 & 4 –medium dose ICS (>0.5-1 mg/day)
• Step 5 & 6 – high dose ICS ( 1-2 mg/day)
Severe
chronic
asthma
• Decreases the edema in the laryngeal mucosa through anti-
inflammatory action.
• Inj. Dexamethasone 0.6 mg/kg IV single dose or nebulized
with budesonide for 8 days.
Croup
• Decreases edema of laryngeal mucosa through
antiinflammatory action.
Pulmonary
edema
following
drowning

8. ITP
 Education and counseling of the family & patient.
IVIG: Single dose of IVIG 0.8-1.0 g/kg × 1-2 days  Induces rapid rise in TPC (usually
> 20 × 103/mm3) in 95% of patients within 2 days.
Q. Headaches and vomiting after IVIG infusion suggests?
 Ans. IVIG induced Aseptic Meningitis
Prednisone: 1-4 mg/kg/day induces rapid rise in TPC.
 Usually continued for short course until a rise in TPC to > 20 × 103/mm3
IV Anti-D therapy: For Rh+ve patients, 50-75 µg/kg causes a rise in platelet count
to > 20 × 103/mm3 in 80-90% of patients within 48-72 hr.
 Ineffective in Rh-negative patients.
Ref – Nelson 20/e

9. Atopic Dermatitis
 Skin hydration: Moisturizers are first-line
therapy.
 Lukewarm soaking baths for 15-20 min f/b -->
ointment.
 (i) Retains moisture to provide symptomatic
relief and (ii) helps in transepidermal
penetration of topical glucocorticoids.
 Topical CS: 7 GROUPS according to potency.
 Topical CNI: Tacrolimus ointment 0.1% &
0.03% for moderate to severe AD in children
>/= 2 yrs.
 Antihistamines: H1 blockers (Hydroxyzine).
Pruritus is severe at night, so the sedative S/E
is utilized by prescribing it at bedtime.

Finger Tip Unit
Ref – AAP Ped. Dermatology Quick Reference Guide 3/e 2016
 Defn: Amount of ointment, cream or other semi-
solid dosage form expressed from a tube with a 5 mm
diameter nozzle, applied from the distal skin-crease to the
tip of the index finger of an adult.
 One FTU i.e. 0.5 gm is enough to treat an area of skin
twice the size of a handprint.
 Two FTUs are approx. equivalent to 1g of topical steroid.

Selecting & Prescribing A Topical Steroid
 Age of the patient?
 E.g. For m/m of flares of Atopic Dermatitis
In infant: Low potency – Oint. Hydrocort 1% or 2.5% is enough.
In adolescent: Mid-potency – Oint. Triamcinolone 0.1% is needed.
 Area to be treated?
 E.g. Thickness of skin. Potency for Feet > Face
 Vehicle used?
 E.g. Ointments (most effective) >
Creams > Lotions > Gels

10. CNS Disorders
Cerebral Edema:
 CS limits the production of inflammatory mediators thereby
reducing the addl. neurologic injury.
 Preferred: Inj. Dexamethasone 0.15 mg/kg/dose IV 6 hrly.
Multiple Sclerosis:
 Preferred: Inj. Methylprednisolone 20-30 mg/kg/day x 5 days
followed with or w/o by Prednisolone.

11. Nephrotic Syndrome
 Adequate t/t of the initial episode, both in terms of dose
and duration of Prednisolone, is an imp. determinant of
the long-term course of the disease.
 Q. Which steroid(s) can be used instead?
A. Methylprednisolone
B. Hydrocortisone
C. Dexamethasone
D. Triamcinolone
Ref - Management of SSNS | Revised Guidelines IAP 2008
None of these preparations are recommended.

 Initial episode t/t with Prednisolone:
[Standard recommendation]
 Cochrane Renal Group
recommendation for
sustained remission
& reduction in relapse rates:
2 mg/kg/day (max.
60 mg in single or
divided doses) for 6
wks
1.5 mg/kg (maximum
40 mg) as a single
morning dose on AD for
the next 6 wks
Therapy
discontinued
Steroid tapered
over the next 2-4
months

 Q. A 4 yr MCH, K/C/O – NS. Presented with edema. diagnosed as first relapse
case. Urine RE ME shows pus cells = 10-12/HPF. After treatment with
antibiotics, the edema subsided. Next step?
A. Start steroids at 2 mg/kg/day
B. Discharge with advice for F/U
C. Start steroids with lower dose
D. Start steroids with stress dose
Confirm remission by – nil/trace urine albumin in 3 cons. early morning samples.
Relapse With Spontaneous Remission:
 The patient should be examined for infections, which should be treated
before initiating steroid therapy.
 Appropriate therapy of an infection might result in spontaneous remission,
thereby avoiding the need for t/t with steroids.

 Q. A first relapse patient did NOT attain remission after 2 wks of steroid
therapy at 2 mg/kg daily. What to do?
A. Continue daily regimen for 2 wks more
B. Start the alt. day regimen anyway
C. Proceed for renal biopsy
D. Tag it as a case of steroid resistant NS
 In case the patient is not in remission despite 2 wks t/t with daily
Prednisolone, the t/t is extended for 2 more weeks.
 Patients showing no remission despite 4 wks’ t/t with daily Prednisolone
should be referred for evaluation.

12. Pyogenic Meningitis
Why to give?
 Rapid killing of bacteria in the CSF effectively sterilizes the meningeal
infection but releases toxic cell products after cell lysis (cell wall endotoxin)
that precipitates the cytokine-mediated inflammatory cascade.
 The resultant edema formation and neutrophilic infiltration may
produce additional neurologic injury with worsening of CNS signs and
symptoms.
Dose:
 Inj. Dexamethasone 0.15 mg/kg/dose IV 6 hrly x 2 days, in children older
than 6 wk with acute bact. meningitis caused by H. influenzae type b.
---Ward Round Question by Kedar Sir---

Benefits noticed:
 Among children with meningitis caused by H. influenzae type b, corticosteroid
recipients show –
 Shorter duration of fever,
 Lower CSF protein and lactate levels, and
 Reduction in SNHL incidences.
Ideal time:
 Maximum benefit if given 1-2 hr before antibiotics are initiated.
 May also be effective if given concurrently with or soon after the first dose of
antibiotics.
Ref – Nelson 20/e

Diagnostic Use
Dexamethasone Suppression Test:
 Purpose: To test the intactness of HPA axis function & Dx of
Cushing’s syndrome.
 Two step test – Low dose (1 mg) and High dose (8 mg)
 Q. For Cushing’s syndrome, DST is?
 A. Screening
 B. Confirmatory
 C. Prognostic
 D. None

Dexamethasone 1 mg
PO at 11 pm
Cushing’s
Syndrome
Plasma Cortisol
measurement at 8 am
Normal
> 5 µg/dL< 3 µg/dL

Cushing’s Syndrome
Dexamethasone 8 mg PO at 11 pm
Plasma Cortisol measurement
at 8 am
< 50% reduction in
Cortisol levels
Cushing’s Disease
(d/t Pituitary tumor)
> 50% reduction in
Cortisol levels
Plasma ACTH
measurement

Plasma ACTH
measurement
Low High
Adrenal Tumor Ectopic ACTH
production

Take Home Message
 A single dose (even excessive) is not harmful: can be used to tide over
mortal crisis, even when benefit is not certain.
 Short courses (even high dose) are not likely to be harmful in the absence
of C/I; starting doses can be high in severe illness.
 Long-term use is potentially hazardous: keep the duration of t/t and dose
to minimum.
 Initial dose depends on severity of the disease; start with a high dose in
severe illness—reduce gradually as symptoms subside. In mild cases start
with the lowest dose and titrate upwards to find the correct dose.

 No abrupt withdrawal after a long term use
for > 2 weeks: may precipitate
Acute Adrenal Insufficiency.
 Q. If infection, severe trauma or any stress during corticoid
therapy, steroid dose should be?
A. Unchanged
B. Increased
C. Decreased
D. Stopped abruptly
 Use local therapy (cutaneous, inhaled, intranasal etc) wherever
possible.
Never
Decreased

References
 Cloherty & Stark’s Manual of Neonatal Care 8/e
 Nelson Textbook of Pediatrics 20/e
 Rudolph’s Pediatrics 22/e
 Sperling Pediatric Endocrinology 2014 ed
 Brook’s Pediatric Endocrinology 6/e
 IAP 2008 Revised Guidelines For: Management of SSNS
 IAP Guidebook For Immunology 2013-14
 Bagga Pediatric Nephrology 6/e
 KDT Pharmacology 7/e
 IAP Journal Article On: “Management of Complications & Side
Effects of Steroids”

Steroids In Pediatrics By Dr. Piyush 2018

Steroids In Pediatrics By Dr. Piyush 2018

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