Presenting manifestations

Presenting manifestations

• Watery Stools• Vomiting• Drowsy• Generalized

tonic-clonic seizures

• Vital Signs• T: afebrile• CR: 180• RR: 50-60

• LAB results• Na 120• K 6.0• Hgt low

• Symptom, sign or laboratory finding pathognomonic of a disease

• Symptom, sign or laboratory finding pointing to an organ or part of an organ system

• Symptom, sign or laboratory finding pointing to a group of diseases

• Symptom, sign or laboratory finding whose mechanism is well understood

• Symptom, sign, or laboratory finding found in the least number of diseases

2

Approach to Diagnosis

Approach to DiagnosisSeizures

Neurologic Metabolic Infectious

Metabolic

Electrolyte Imbalance

Diabetic Ketoacidosis Intoxication Adrenal

Crisis

Severe salt wasting:- vomiting, - Watery stools- electrolyte

changes- cardiac

arrhythmia

Acute adrenal crisis

• An acute form of adrenal insufficiency characterized by salt loss, circulatory collapse and hypoglycemia due to inadequate secretion of glucocorticoids and or mineralocorticoids

Handbook of Medical and Surgical Emergencies, 6th ed

Physiology• The two adrenal glands are located on top of the kidneys. They consist of the

outer portion, called the cortex, and the inner portion, called the medulla. The cortex produces three types of hormones, all of which are called corticosteroids.

• Cortisol is a glucocorticoid -- a corticosteroid that:– Helps regulate blood sugar (glucose)– Holds back the immune response– Is released as part of the body's response to stress

• Cortisol production is regulated by a small gland just below the brain called the pituitary gland. Cortisol is essential for life.

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Adrenal crisis occurs when

• Primary adrenal insufficiency– Congenital adrenal hypoplasia or aplasia– Congenital adrenal hyperpalsia due to enzymatic defect

(21-hydroxylase-most common; cholesterol 20, 22 desmolase, 17-hydroxylase, 11-B hydroxylase deficiency)

– Adrenal hemorrhage (Waterhouse Friderichsen syndrome)– ACTH unresponsiveness– Acute illness– Adrenoleukodystrophy

Handbook of Medical and Surgical Emergencies, 6th ed

• Secondary adrenal insufficiency– Anencephaly– Hypopituitarism– Isolated ACTH deficiency– Iatrogenic

• Prolonged steroid therapy

Handbook of Medical and Surgical Emergencies, 6th ed

Adrenal crisis occurs when

Etiologies• Primary Adrenal Insufficiency

– Congental Adrenal Hypoplasia• Hypoadrenalism usually presents acutely in the neonatal period but may

be delayed until later childhood or even adulthood with a more insidious onset

– Adrenal Hemorrhage (waterhouse Friedrichsen Syndrome)• Neionatal Period (Difficult labor, causing trauma) An abdominal mass, anemia,

unexplained jaundice, or scrotal hematoma may be the presenting sign. Often, the hemorrhage is asymptomatic initially and is identified later by calcification of the adrenal gland.

• Infection– Tuberculosis was a common cause of adrenal destruction in the past but is much less

prevalent now

– Adrenoleukodystrophy• associated with demyelination in the central nervous system• appearing in childhood or adolescence and progressing to severe

dementia and deterioration of vision, hearing, speech, and gait, with death occurring within a few years

Risk factors for adrenal crisis include:

• Dehydration• Infection and other physical stress• Injury to the adrenal or pituitary gland• Stopping treatment with steroids such as

prednisone or hydrocortisone too early• Surgery• Trauma

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Clinical manifestations

• Newborn and infant– Vomiting– Diarrhea– Weight loss higher than approved fluid loss– Cardiorespiratory distress– Hypotension– Seizure

Handbook of Medical and Surgical Emergencies, 6th ed

• Children over 1 year– Vomiting– Diarrhea– Dehydration and fever– Hypotension– Vascular collapse– Coma

Clinical manifestations

Laboratory

• Low cortisol level• Hypoglycemia• Hyperkalemia• Hyponatremia• Metabolic acidosis

• Hypoglycemia :often accompanied by ketosis as the body attempts to utilize fatty acids as an alternative energy source. – Ketosis is aggravated by anorexia, nausea, and vomiting, all of which

occur frequently.• Hypovolemia due to decreased resorption of sodium in the

distal nephron.• Hyponatremia, due to decrease plasma osmolality

– Hypotension and decreased cardiac output decrease glomerular filtration and thus decrease the ability of the kidney to excrete free water. Vasopressin (AVP) is secreted by the posterior pituitary in response to hypotension and also as a direct consequence of lack of inhibition by cortisol.

• Hyperkalemia, decreasing potassium excretion in the distal nephron

What is CAH? It is a familial disorder of adrenal steroid

biosynthesis with autosomal recessive mode of inheritance.

The defect is expressed as adrenal enzyme deficiency.

5 major Enzymes deficiency are clinically important

• 21-Hydroxylase• 11-b-Hydroxylase• 17-a-Hydroxylase• 3-b-Hsteroid hydrogenese• 20,22 Desmolase deficiency

CAHThe enzyme deficiency causes

reduction in end-products, accumulation of hormone precursors & increased ACTH production.

The clinical picture reflects the effects

of inadequate production of cortisol & aldosterone and the increased production of androgens & steroid metabolites.

21-Hydroxylase Deficiency

Most common type, accounts for >80% of cases.

Incidence is 1:5000 to 1:15000 live birth. Gene is located on the short arm of

chromosome 6 near the C4 locus in close association with HLA genes.

Heterozygous carriers can be detected by ACTH stimulation test.

21-Hydroxylase deficiency/2

It is characterized by reduced production of cortisol and aldosterone and increased production of progesterone; 17-OH-progesterone, and sex steroids.

The urinary steroid metabolites (17-ketosteroids and pregnanetriol) are elevated above normal levels.

21-Hydroxylase deficiency/3

Decreased secretion of aldosterone results in salt loss with hyponatremia and hyperkalemia; plasma renin activity is therefore elevated.

In partial enzyme deficiencies, the aldosterone deficiency is not expressed, and patients remain normonatremic and normokalemic.

The excess androgens causes virilization of girls & ambiguous genitalia & dark scrotum in boys.

21-Hydroxylase Deficiency/4

2 forms, classic early virilization type with or without salt-losing crisis and non-classic type with late-onset virilization.

Male babies with non salt-losing non-classic type remains asymptomatic till late childhood when they may show signs of sexual precocity.

Pathophysiology

Anatomically, the adrenal gland can be divided into 3 zones: Zona glomerulosa, which

produces predominately mineralocorticoid

Zona fasciculata, which produces predominately glucocorticoid

Zona reticularis, which produces predominately androgens

Enzyme pathway

•

Result of a 21-Hydroxylase Deficiency

ESSENTIALS OF DIAGNOSIS

Increased linear growth with advanced bone age and eventual short stature

Pseudohermaphorditism in girls due to androgen virilizing effect

Isosexual precocity in boys with small infantile testes.

ESSENTIALS OF DIAGNOSIS/2

Adrenal crisis with salt-loss & metabolic acidosis or Hypertension & hypokalemic alkalosis.

Low cortisol with high androgens, ACTH and steroid precursors e.g. 17-OH-Progest. or 11-Deoxycortisol.

ESSENTIALS OF DIAGNOSIS/3

Diagnosis is confirmed by measurement of ACTH, Cortisol, Aldosterone, 17-OH-progesterone, Testosterone & urinary 17-ketosteroids.

Needs alertness for the possibility in all babies with Diarrhea & Vomiting, hypoglycemia or BP.

CLINICAL COURSEThe clinical phenotype depends upon

the nature and severity of the enzyme deficiency.

Approximately 50% of patients with classic congenital adrenal hyperplasia due to 21-hydroxylase (CYP21) deficiency have salt wasting due to inadequate aldosterone synthesis.

Girls are usually recognized at birth because of ambiguous genitalia.

CLINICAL COURSE/2Non salt losing CAH present late in

childhood with precocious pubic hair and/or clitoromegaly, often accompanied by accelerated growth and advanced bone age.

Those individuals with mild deficiencies of the enzyme present in adolescence or adulthood with varying virilizing symptoms ranging from oligomenorrhea to hirsutism and infertility.

Laboratory Findings Demonstration of inadequate production of

cortisol and/or aldosterone in the presence of accumulation of excess concentrations of precursor hormones is diagnostic.

In 21-hydroxylase deficiency, very high serum 17-hydroxyprogesterone is characteristic together with very high urinary pregnanetriol (metabolite of 17-hydroxyprogesterone).

Laboratory Findings/2 11-b-hydroxylase deficiency is characterized

by high serum 11-deoxycorticosterone and 11-deoxycortisol concentrations with elevation of its urinary metabolites (tetrahydrocompound-S).

Both are accompanied by elevated 24-hour urinary 17-ketosteroids, the urinary metabolites of adrenal androgens.

Laboratory Findings/3Salt wasting forms of adrenal

hyperplasia are accompanied by low serum aldosterone, hyponatremia, hyperkalemia and elevated plasma renin activity indicating hypovolemia.

In contrast hypertensive forms of

adrenal hyperplasia (11-b-hydroxylase deficiency and 17-a-hydroxylase deficiency) are associated with suppressed plasma renin activity and hypokalemia.

Other TestsA karyotype is essential in the evaluation

of the infant with ambiguous genitalia in order to establish the chromosomal sex.

Prenatal diagnosis of adrenal hyperplasia is possible through biochemical and genetic tests.

TREATMENT PRINCIPLESTreatment is life-long Treatment goals are:

to maintain growth velocity & skeletal maturation.

to normalize electrolytes & hormone levels using the smallest dose of glucocorticoids that will suppress the ACTH to normal. Mineralocorticoid replacement may be needed to sustain normal electrolyte homeostasis.

MODES OF TREATMENTSteroid replacementSupportive therapy when

neededTreatment is life-longPlastic surgery for ambiguous

genitalia at early ageGenetic counseling Psychological support

Acute Medical Management

Fluid therapy in babies with salt losing crisis 0.9% sodium chloride 20 ml/kg as IV bolus, followed by a continuous IV infusion of 0.9% or 0.45% saline 3200 ml/m2/day.

If the patient is hypoglycemic, 2-4 ml of 10% dextrose will correct the hypoglycemia.

Patients with 11-b-hydroxylase and 17-alpha-hydroxylase deficiency, may be hypokalemic and require potassium.

Long Term Therapy Glucocorticoid Replacement

Hydrocortisone 10-15 mg/m2/day divided in 3 oral doses. Dose should doubled during crisis & stressful conditions. The goals of therapy are:

To replace the body's requirement under normal conditions and during stress.

To suppress ACTH secretion, which drives the adrenal gland to overproduce adrenal androgens in virilizing forms of congenital adrenal hyperplasia.

Long Term Therapy/2• Mineralocorticoids Treatment

– Fludrocortisone acetate • 0.05-0.2 mg once daily orally is indicated for

patients who have salt-wasting forms of CAH to replace the aldosterone that is insufficiently produced by the adrenal cortex.

• It will restore the sodium- potassium balance.

PROGNOSISIs good and complications like short

stature, sexual precocity & metabolic effects are not seen with early adequate therapy.

However, children with CAH are at risk of developing mesodermal tumours e.g. osteogenic sarcoma, pulmonary liposarcoma, uterine leiomyomata and brain tumours.

PROGNOSIS /2• Late diagnosis & inadequate

therapy may cause: Death of newborns with salt-

losing types & if patients are not provided with stress doses of glucocorticoid in times of illness, trauma, or surgery.

Psychological problems in girls with ambiguous genitalia.

Short stature and infertility.