Introduce on anatomy and physiology of the adrenal gland. Brief on etiologies and Classification of adrenal insufficiency. Brief on clinical manifestations, diagnosis, and treatment of adrenal insufficiency.

1. Adrenal Insufficiency
Prepared by Dr. Abinet Takele (pediatrician)
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2.  Objectives
 Introduction
 Etiologies
 Clinical features
 Investigations
 Treatments
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Out lines

3. Objectives
 Introduce on anatomy and physiology of adrenal gland.
 Brief on etiologies and Classification of adrenal insufficiency.
 Brief on clinical manifestations, diagnosis and treatment of
adrenal insufficiency.
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4. Introduction
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5. Regulation of Adrenal Cortex
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6. Regulation of aldosterone
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7. Adrenal insufficiency
 Is impaired synthesis and release of adrenocortical hormones.
 It is classified as
 primary, results from disease intrinsic to the adrenal cortex .
 Secondary, caused by either impaired release or effect of
adrenocorticotropic hormone (ACTH) from the pituitary gland.
 Tertiary adrenal insufficiency ,impaired release or effect of
corticotrophin releasing factor (CRH) from the hypothalamus.
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8. Etiologies of primary AI
 INHERITED ETIOLOGIES
o Inborn Defects of Steroidogenesis (eg. CAH)
o Adrenal Hypoplasia Congenita
o Adrenoleukodystrophy (ALD)
o Familial Glucocorticoid Deficiency
o Type I Autoimmune Poly-endocrinopathy Disorders
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9.  ACQUIRED ETIOLOGIES
o Autoimmune Addison Disease
o Infection (TB, Meningococcemia (waterhouse Friderichsen
syndrome), Fungal infection, AIDS)
o Drugs (Ketoconazol , Mitotane , Etomidate, anesthesia)
o Hemorrhage into Adrenal Glands
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10.  Meningococcemia ( Waterhouse-Fridericsen
syndrome)
 Is adrenal gland failure due to bleeding in to the adrenal glands
and caused by Neisseria meningitides.
 C/F: - Petechial and purpuric rash,
- Hypotension, Septic shock,
- Hypoglycemia, Hyponatremia ,
- Acute adrenal failure
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12. Inborn Defects of Steroidogenesis
• Defects within the biosynthetic pathways of
glucocorticoids and/or mineralocorticoids lead to impaired
synthesis of cortisol and/or aldosterone.
• Steroidogenic disorders of cortisol (congenital adrenal
hyperplasia,CAH) are major causes of primary adrenal
insufficiency in children.
• There are various forms of CAH based upon their enzymatic
defects.
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13. CYP21A2 (21-hydroxylase) deficiency,
• Accounts > 95 % of adrenal steroidogenic defects.
• Two major phenotypes are recognized with this enzyme
deficiency:
I. Classic form
Females present with genital ambiguity
 Salt losing form: failure to thrive, dehydration, hyponatremia, and
hyperkalemia typically at 7 to 14 days of life males.
 Simple virilization: present at 2-4 years of age with early
virilization (pubic hair, growth spurt, adult body odor) in males.
II. Non-classic form:
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14. Hyperpigmentation of
skin
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Clitoromegaly

15. 15
A, A 6-yr-old girl with congenital
virilizing adrenal hyperplasia. The
height age was 8.5 yr, and the bone
age was 13 yr.
B, Notice the clitoral enlargement
and labial fusion.
C, Her 5 yr old brother was not
considered to be abnormal by the
parents. The height age was 8 yr,
and the bone age was 12.5 yr.

16. Non classic form
Produce normal amount of cortisol and aldosterone at the
expense of mild to moderate overproduction of sex
hormones.
Irregular or absent menstrual periods
Masculine characteristics ( facial hair, excessive body hair
and a deepening voice)
Severe acne, decreased fertility
 There may be no symptoms
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17. Autoimmune Addison Disease
• The most common cause of Addison disease is autoimmune
destruction of the glands.
• It accounts for up to 15% of pediatric patients with PAI.
• The disease can occur as a component of 2 autoimmune
polyendocrinopathy syndromes.
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18. APS1, ( autoimmune polyendocrinopathy-
candidiasis-ectodermal dystrophy
(APECED),
 hypoparathyroidism
 chronic mucocutaneous candidiasis
 adrenal insufficiency
 primary hypogonadism
 malabsorption
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19. Type II autoimmune polyendocrinopathy
(APS-2)
 Characterized mainly by PAI
 Autoimmune thyroid disease (Schmidt syndrome)
 Type 1 diabetes (Carpenter syndrome)
 Others (Gonadal failure, Vitiligo, Alopecia, chronic
atrophic gastritis)
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20. Secondary and Tertiary Adrenal
Insufficiency
 Secondary adrenal insufficiency- dysfunction of the anterior
pituitary gland.
 Tertiary adrenal insufficiency is sometimes used to denote
cases arising from hypothalamic dysfunction.
 ETIOLOGY –
 prolonged administration of high doses of a potent glucocorticoid
(more than 5 mg of prednisolone a day or hydrocortisone >20mg /d for
more than three weeks)
 sudden withdrawal, tapered too quickly
 Tumors, brain injury, surgical removal, radiation, and congenital
lesions of pituitary
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21. Diagnosis
 The most definitive test is measurement of serum levels of
cortisol before and after administration of ACTH.
 It has 3 stage process
1, Confirmation AI: low cortisol
2, Determination of primary or secondary AI
 1° AI; low cortisol, high ACTH, ↑Renin
 2 ° &/or 3° AI; low cortisol & ACTH, low response to
ACTH
3, Evaluate the cause; Antiadrenal antibody levels
Others; Serum electrolytes: (↓Na, ↑K ),RBS, ECG, 24 hour Urine
(↑ Na, ↑ Cl and ↓ K), BUN (Acidosis) ,Aldosterone level
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22. Treatment
 In patients with primary adrenal insufficiency, treatment
includes physiologic replacement with glucocorticoid and
mineralocorticoid.
 Glucocorticoid dosing must be increased during times of
stress.
 Patients with secondary adrenal insufficiency require only
glucocorticoid replacement.
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23.  Glucocorticoid Replacement
• 15-20 mg/m2/24 hr of hydrocortisone daily administered
orally in 3 divided doses or oral prednisolone.
• close follow-up of somatic growth (weight, bone age, and
height and weight velocities) provides the most important
guidelines for dose adjustment.
 Mineralocorticoid Replacement
• fludrocortisone
• sodium supplementation (sodium chloride, 8 mmol/kg)
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24.  Surgical Management of Ambiguous Genitals
• usually undergo surgery between 2-6 mo of age.
• In adolescent and adult females with poorly
controlled 21-hydroxylase deficiency (hirsutism,
obesity, amenorrhea), bilateral laparoscopic
adrenalectomy (with hormone replacement).
 Prenatal treatment with dexamethasone for pregnant
mothers at risk.
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25. Treatment of Adrenal crisis in children and
adolescents
• Fluids: give bolus of 5 percent Dextrose with 0.9 percent
saline, without potassium (D5NS), 20 mg/kg over one hour
• Stress corticosteroids: administer hydrocortisone succinate
(SoluCortef) as a bolus
- Infants and toddlers, 0 to 3 years old: 25 mg IV
- Children 3 to 12 years: 50 mg IV
- Children and adolescents 12 years and older: 100 mg IV
• Treat electrolyte abnormalities.
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26.  STRESS CONDITIONS
 Minor infection and/or low-grade fever (sore throat,
rhinorrhea, fever up to 38ºC)- not require a change in dose.
 Moderate stress (eg, severe upper respiratory infections), -
double the usual glucocorticoid replacement dose.
 In major stress (eg, temperature above 38ºC and/or vomiting)-
increased the hydrocortisone dose to three to four times the
normal replacement.
 Surgical procedures IV bolus of stress dose then infusions are
given over 24 hrs and decrease dose by 50% each day as
patient respond.
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27. SIADH versus adrenal insufficiency: a life-threatening misdiagnosis
Italian journal of pediatrics
puplished: 06 February 2019
 Case presentation
 A 12 year-old Caucasian boy was admitted to a pediatric emergency
department with repeated vomiting, malaise, excessive thirst,
dizziness on standing and one episode of syncope after drinking 1
liter of water.
 He has similar episode 3 weeks before and admitted to the local
hospital with diagnosis of gastroenteritis and marked hyponatraemia
(124 mEq/L) and discharged after correcting hyponatraemia with NS
infusion and remained symptom-free until the actual episode.
 At admission no fever, diarrhea, change in urinary output or change
in weight were reported. Physical examination showed an a pyretic,
euphonic, asthenic boy, with a tanned skin color. Heart rate was
63 bpm, blood pressure was 98/62 mmHg and SaO2 was 100%.
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28.  Lab; hyponatraemia (121 mEq/L), hypochloraemia (86 mEq/L) and mild
hyperkalaemia (5,91 mEq/L) with low plasmatic osmolarity
(248 mOsm/Kg). Urinary sodium was 163 mEq/L, potassium 48 mEq/L,
chlorine 119 mEq/L, with high urinary osmolarity (896 mOsm/L). Blood
and urinary glucose, white cell count, blood gas analysis and RFT were
normal.
 SIADH was suspected and fluid restricted with 2/3 of MF.
 After 4 hours, hyponatraemia worsened (119 mEq/L) despite fluid
restriction, while asthenia and inability to stand upright persisted, thus
adrenal insufficiency is suspected.
 Low cortisol (7.95 mcg/dl; 6.2–19.4), marked ACTH increase
(> 1250 pg/mL), high renin level (> 500 mUI/ml) and low aldosterone
(3.1 ng/dL; 3–30) confirmed the diagnosis of adrenal insufficiency.
 Rx: IV hydrocortisone (100 mg/day, then decreased to 50 mg each 6 h/day);
oral daily fludrocortisone, 0.15 mg, Maintenance therapy with oral
hydrocortisone was introduced after 3 days, while electrolyte and ACTH
values returned within normal limits in 48 h.
 The patient presented two further episodes of symptomatic orthostatic
hypotension in the first 72 h after diagnosis and recovered in the following
days. Anti-adrenal antibodies tested positive, confirming autoimmune
adrenalitis (Addison disease).
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29. References
• Perrin C. White, Adrenocortical Insufficiency, Nelson TEXTBOOK of PEDIATRICS EDITION
20, Chapter 575
• Perrin C. White, Physiology of the Adrenal Gland Nelson TEXTBOOK of PEDIATRICS
EDITION 20, Chapter 574
• Patricia A Donohoue, MD, Diagnosis of adrenal insufficiency in children,Uptodate 21.2
• Patricia A Donohoue, MD, Causes and clinical manifestations of primary adrenal
insufficiency in children,Uptodate 21.2
• Patricia A Donohoue, MD, treatment of adrenal insufficiency in children,Uptodate 21.2
• Patricia A Donohoue, MD, Causes and clinical manifestations of central adrenal insufficiency
in children,Uptodate 21.2
• Perrin C. White ,Congenital Adrenal Hyperplasia and Related Disorders Nelson TEXTBOOK
of PEDIATRICS EDITION 20, Chapter 576
• Moises Auron and Nouhad Raissouni,Adrenal Insufficiency,Pediatrics in Review March
2015, 36 (3) 92-103; DOI: https://doi.org/10.1542/pir.36-3-92
• Sasigarn A. Bowden, Pediatric Adrenal Insufficiency: Diagnosis, Management, and New
Therapies, International Jaurnal of Pediatrics, Published 01 Nov 2018,
https://doi.org/10.1155/2018/1739831
• Stefano Pintaldi,SIADH versus adrenal insufficiency: a life-threatening
misdiagnosis,Italian Journal of Pediatrics ,volume 45, Article number: 23 (2019)
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