Primary Adrenal

Insufficiency
 Primary Adrenal Insufficiency

Deficiency in the secretion of cortisol by the adrenal

glands

Most frequently caused by genetic conditions that are

often but not always manifested in infancy and less
often by acquired problems such as autoimmune
conditions
ETIOLOGI
ES
 EPIDEMIOLOGY
▪ Age:
– Addison disease is uncommon in children and usually presents between
the ages of 20 and 50 years. In the pediatric population, it is most often
seen in late childhood and adolescence.
– Adrenoleukodystrophy typically presents late in the 1st decade of life
with neurologic symptoms. Signs and symptoms of adrenal insufficiency
may present at any age.
– Adrenocorticotropic hormone (ACTH) unresponsiveness presents in
late infancy or the toddler period.
– Adrenal hypoplasia congenita presents in infancy or early childhood.
– Adrenal insufficiency associated with congenital adrenal hyperplasia
 EPIDEMIOLOGY

▪ Sex:
– Addison disease is more common in girls.

– Adrenoleukodystrophy, an X-linked disorder, predominantly affects boys.

– ACTH unresponsiveness and CAH affect both sexes equally.
– Adrenal hypoplasia congenita, an X-linked disorder, predominantly
affects boys.
 PATHOPHYSIOLOGY
Addison disease:
– Primary hypoadrenalism due to bilateral destruction of the adrenal cortices; this can
be due to autoimmune destruction (isolated or associated with APS), tuberculosis,
hemorrhage, fungal infection, neoplastic infiltration, or AIDS.

Adrenoleukodystrophy:
– Inherited disorders of impaired peroxisomal degradation of very-long-chain fatty
acids, resulting in adrenal insufficiency and progressive neurologic deterioration

ACTH unresponsiveness:
– Inherited defect in the ACTH receptor, resulting in isolated glucocorticoid deficiency
with hypoglycemia in infancy and hyperpigmentation
 PATHOPHYSIOLOGY
Adrenal hypoplasia congenita:
A defect in adrenal organogenesis

CAH:
A group of enzymatic disorders of steroid metabolism, of which 21-
hydroxylase deficiency is the most common

Waterhouse-Friderichsen syndrome:
Bilateral adrenal gland hemorrhage classically associated with fulminant
meningococcemia, but also reported with Staphylococcus aureus and
Streptococcus pneumoniae
 DIAGNOSIS
HISTORY
The symptoms of primary adrenal insufficiency are nonspecific and similar to those
found in many disease processes. The electrolyte picture of adrenal insufficiency can
be seen in renal disorders, obstructive uropathy, and isolated aldosterone deficiency:

• Weakness and fatigue • Emotional lability

• Anorexia, weight loss • Salt craving
• Headache • Hyperpigmentation
• Nausea, vomiting, diarrhea, • Decreased axillary or pubic
abdominal pain hair in females due to lack of
• Orthostatic symptoms adrenal androgens
• Muscle or joint pains • Amenorrhea in females
 DIAGNOSIS

PHYSICAL EXAM
 Hyperpigmentation, especially on lip borders, buccal mucosa, nipples,
and over skin creases
 Weight loss
 Hypotension
 Evaluate for other signs of autoimmune disease (e.g., thyromegaly,
vitiligo).
 Pubertal staging
 Signs of virilization in females
 DIAGNOSTIC TESTS

Specific:
 Cosyntropin (Cortrosyn) stimulation test:
Administer cosyntropin (synthetic ACTH) 250 mcg IV and measure cortisol at 30 and 60
minutes. An insufficient cortisol response is diagnostic of adrenal insufficiency

 Serum adrenal antibodies may be positive in autoimmune Addison

disease.
 Very-long-chain fatty acids are elevated in adrenoleukodystrophy.
 Low gonadotropin and sex steroid levels suggesting hypogonadotropic
hypogonadism may be seen with adrenal hypoplasia congenita.
 Adrenal steroid precursors (17-hydroxyprogesterone ) will be elevated in
 DIAGNOSTIC TESTS

Nonspecific:
Electrolytes:
◦ Hyponatremia: Result of the mineralocorticoid defect and glucocorticoid deficiency;
combination sodium loss from kidneys, and the inability to excrete a water load
◦ Hyperkalemia and acidosis: Chronic mineralocorticoid deficiency with the inability to
excrete potassium and acid
◦ Hypercalcemia: Most likely a result of increased calcium absorption due to the lack of
glucocorticoid effect on the gut
◦ Hypoglycemia: Glucocorticoids have permissive effects on gluconeogenesis.
◦ Renin levels are elevated when a mineralocorticoid deficiency is present.
 DIFFERENTIAL DIAGNOSIS
 Autoimmune adrenal cortical destruction
 Infectious adrenal cortical destruction:
– Tuberculous
– Fungal
– HIV

 Adrenal hemorrhage
 Neoplastic adrenal infiltration
 Adrenoleukodystrophy
 ACTH unresponsiveness
 Adrenal hypoplasia congenita
 TREATMENT
Acute adrenal insufficiency
• A blood sample should be obtained before therapy to determine
electrolytes, glucose, ACTH, cortisol, aldosterone, and plasma renin
activity.
• Intravenous solution of 5% glucose in 0.9% saline should be
administered to correct hypoglycemia, hypovolemia, and hyponatremia.
• Hypotonic fluids (e.g., 5% glucose in water or 0.2% saline) must be
avoided because they can precipitate or exacerbate hyponatremia.
 TREATMENT
Correct hyperkalemia:
Calcium:
Calcium gluconate 100 mg/kg/dose IV of 10% solution over 3–5 min
Insulin and glucose:
Insulin 0.1 units/kg IV over 30 min
Dextrose 0.5 g/kg IV over 30 min
Sodium bicarbonate:
1–2 mEq/kg IV
 TREATMENT
Hydrocortisone
Given intravenously. As much as
• 10 mg for infants
• 25 mg for toddlers
• 50 mg for older children
• 100 mg for adolescents
should be administered as a bolus .
A similar total amount given in divided doses at 6 hr intervals for the 1st 24
hr. These doses may be reduced during the next 24 hr if progress is
satisfactory.
 TREATMENT
chronic replacement therapy
Hydrocortisone
orally in daily doses of 10 mg/m2/24 hr in 3 divided doses;
some patients require 15 mg/m2/24 hr to minimize fatigue, especially in the morning
During situations of stress, such as periods of infection or minor operative procedures,
the dose of hydrocortisone should be increased 2-3–fold.
Fludrocortisone
a synthetic mineralocorticoid is given orally in doses of 0.05-0.2 mg daily.
 Patient Monitoring

• Clinical status
• Reduction in hyperpigmentation
• Electrolytes, ACTH, and renin levels
• Screen for polyautoimmune disorders.
• Growth
• Very-long-chain fatty acid levels and neurologic function in
adrenoleukodystrophy
• Pubertal development
Thank
you