Download Congenital Adrenal Hyperplasia

Marissa Hampton RN, BSN, SNNP
University of Texas Medical Branch at Galveston
School of Nursing
NNP III/IV
GNRS 5633/5434
Dr. Debra Armentrout PhD, RN, MSN, NNP-BC
Dr. Leigh Ann Cates PhD, APRN, NNP-BC,RRT-NPS,CHSE

Objectives
› Define Congenital Adrenal Hyperplasia
(CAH)
› Define fetal pathophysiology
› Describe clinical features of CAH
› Discuss diagnostic evaluation of the
neonate
› Discuss therapeutic approach and
treatment options for the infant with CAH

Definition
› A group of inherited disorders of the adrenal glands
that cause improper production or synthesis of the
hormones cortisol (glucocorticoid) and/or
aldosterone (mineralcorticoid).
 Autosomal recessive disorder
 Cortisol helps the body respond to stress
 Infections
 Aldosterone helps body maintain normal electrolyte
balance.
 Sodium and potassium regulation
› In common forms of CAH, overproduction of
androgens occur simultaneously.
 Leads to virilization
(Merck Manuals, 2012)
(Mayo Clinic, 2014)

Definition
› Common forms of CAH
 90 % of CAH
 21- Hydroxylase deficiency
 overall incidence is 1 in 16,000
 Autosomal recessive
 Remaining 10 % of CAH:
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17 Alpha- Hydroxylase deficiency
11 Beta- Hydroxylase deficiency
3 Beta- Hydroxylase deficiency
20, 22 Desmolase deficiency
(Merck Manuals, 2012)
(Mayo Clinic, 2014)

Pathophysiology
› Multiple steps in synthesis of cholesterol to
cortisol
› Defects in enzyme metabolism lead to impaired
cortisol production
 Impaired cortisol production causes a secondary
increase in Adrenocorticotropic hormone(ACTH)
 Elevated ACTH increases adrenocortical activity
to normalize cortisol production.
 Impaired synthesis of adrenal hormones results from
enzymatic blocks.
 Overproduction of steroids
(Palmert& Dhams, 2013)
Pathophysiology
 Simply:

› Errors or deficiencies in metabolic pathways
in the synthesis of cortisol from cholesterol
cause:
 Increased hormone stimulation
 Improper hormone stimulation

Mnemonic to remember
› Use A and T for each hormone level affected
› Separate each number under each hormone
› Whichever hormone the number one falls under indicates
an increased level
Hormone
(A)
Aldosterone
(T)
Testosterone
Diagnostic
test
21Hydroxylase
2
1
increased
17-OH
Progesterone
17AHydroxylase
1
Increased
7
11BHydroxylase
1
Increased
1
Increased
Lets focus on the most common form of CAH
21- hydroxylase deficiency
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
Pathophysiology
Hormones:
The adrenal glands (cortex) are responsible for the production of
glucocorticoids, mineralcorticoids and androgens.
› Cortisol:
›



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Normal regulation of these hormones involves pituitary and adrenal glands.
ACTH activates the adrenal glands to produce cortisol.
ACTH and cortisol work to balance each other.
Cortisol main function to maintain blood sugars, fluid and electrolyte status
and protects the body from stress
›
Aldosterone:
›
Adrenal Androgens:
 Secreted under angiotensin (produced by renin in the kidneys)
 Regulates serum sodium, total body water and blood pressure in body.
 Secreted in both males and females prior to birth
 Production decreases after birth then resurges during puberty
(Migeon & Wisniewski, 2014)


Pathophysiology
21- Hydroxylase deficiency
 Caused by deletion or mutation in 21- hydroxylase
gene (CYP21)
› 2 Forms
 Classic
 Severe form
 Virilization form: partial enzyme deficiency
 Mild salt lost: Adrenal insufficiency does not occur
 Not life threatening
 Classic salt wasting: complete enzyme deficiency
 Life threatening form
 Mild form
 Presents later in life without salt wasting or virilization
(Gomella, Eyal & Cunningham, 2013)
(Thomas, 2014)


Pathophysiology
Simple virilizing CAH
› Partial deficiency of 21- Hydroxylase enzyme
 Increased ACTH produced near normal levels of
cortisol
 Increased production of 17- OHP as cortisol
precursors
 Increased 17-OHP produces minor salt wasting
 Increased salt loss causes increased aldosterone
levels
 Aldosterone levels able to compensate for salt loss
 Increased androgens lead to female virilization
 Ambiguous genitalia of female infants
(Migeon & Wisniewski, 2014)


Pathophysiology
Salt wasting form of CAH
› Total or near total deficiency of 21-Hydroxylase enzyme
› Inability to produce cortisol and aldosterone
 Inability to produce cortisol
 May lead to hypoglycemia
 Increase in ACTH to regulate cortisol levels
 Build up of cortisol precursors due to improper metabolism
 17-OHP
 Androgens
› No aldosterone production
 Extreme serum sodium and water loss
› Increased androgens lead to female virilization
 Ambiguous genitalia of female infants
(Migeon & Wisniewski, 2014)

Clinical Manifestations
› Signs and symptoms of CAH have different
clinical presentations
 Clinical presentation differs according to:
 Chromosomal sex of infant
 Form of CAH
 Classic form
 Salt wasting form

Classic CAH (21-OH)
› Females
 Severe form
 Excessive adrenal androgen secretion leads to prenatal
virilization
 Ambiguous genitalia at birth
 Fusion of labioscrotal folds: Partial
 Phallic urethra
 Clitoromegaly
 Mild form

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Often identified later on in life due to subtle clinical manifestations
Precocious pubic hair
Clitoromegaly
Accelerated growth and skeletal maturation
Also present with similar findings with 3- beta hydro:
oligomenorrhea, hirsutism, infertility
(Antal, Z. & Zhou, P, 2009)

Classic CAH (21-OH)
› Males
 External genitalia are unaffected
 Subtle penile enlargement
 Without testicular enlargement
 Early overt signs of puberty:
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May occur as early as age 2-3
Axillary/pubic hair
Acne
Body odor
Continued surge in androgens cause accelerated
excessive growth
 Final adult heights are reached early
 Shorter then average male due to premature epiphyseal
bone closure
(Antal, Z. & Zhou, P, 2009)
(Stresing, 2014)

Salt wasting CAH (21-OH)
› Both Male and Female
 Salt wasting due to inadequate aldosterone levels
 Can lead to:
 Poor feeding
 Vomiting and Dehydration
 Hyponatremia
 Hyperkalemia
 Hypovolemia
 Long term effects of salt wasting CAH
 Learning disabilities
 Behavioral problems
 Death
(Androgen Excess Society, 2012)
(Stresing, 2014)
(Van der Kamp & Wit, 2004)

Diagnostic evaluation
› Assessment
 Identify female infants with external masculine
features
 Identify males with impalpable gonads
 Infants who develop signs of adrenal
insufficiency or severe crisis
 Family history of CAH
 Unexplained death in infancy
(Palmert & Dahms, 2013)

Diagnostic evaluation
› Newborn screening
 Conducted within 24-48 hours of birth before
potential salt wasting crisis
 However may have false positive result if sampled in
first 36 hours after birth
 Identifies increased 17 OHP concentration in
blood
 Term newborns must exceed a 99% range of 17 OHP
for a positive screen
 Preterm infant levels of 17 OHP are scaled based on
birth weight and gestational age.
 Higher incidence of false positive results
(Van der Kamp & Wit, 2004)
Diagnostic evaluation
 Positive newborn screen for CAH

› For confirmation, send:
 17 OHP
 Serum/urine electrolytes
 Serum: Hyponatremia, Hyperkalemia
 Urine: Hypernatremia
 Patients with mild salt wasting CAH may have
normal electrolytes without hypovolemia!
(Palmert & Dahms, 2013)
Treatment
 Goals of treatment include normalizing
ACTH secretion and providing
replacement of hormone deficiencies

› Replacement of cortisol, aldosterone and
androgens
› Each form has different treatment options.
(Palmert & Dahms, 2013)
Treatment
 Simple Virilization CAH

› NOT salt wasting
› Goal is to normalize ACTH
 Replacement with cortisol
 Hydrocortisone PO in 3 divided doses
 Dose usually 15-25 mg/m2
 Increase dose with period of stress usually 2-3x
maintenance dose for moderate to severe disease
 Simultaneous use of mineralcorticoid therapy may reduce
amount of cortisol used.
 Adequate replacement is monitored by serum
17OHP level
(Palmert & Dahms, 2013)


Treatment
Salt wasting CAH
› Normalizing ACTH levels includes management
of
 Sodium
 Replacement therapy in first years of life
 Renal tubules unable to conserve sodium
 Supplementation: 1-5 mEq/kg daily PO
 Fluid status
 Monitor for hypovolemia
 Replacement cortisol
 Hydrocortisone
 Mineralcorticoid therapy
(Palmert & Dahms, 2013)


Treatment
Acute salt wasting crisis
› Fluid replacement
 Give NS bolus at 20 ml/kg PRN
› Sodium replacement
› Continuous glucose infusion
 Dextrose 10% initially
› Glucocorticoid therapy
 Hydrocortisone at 3-6 x maintenance level IV
› Mineralcorticoid therapy
 Florinef Acetate 0.1-0.2 mg PO Q 12- 24 hours
› Also manage:
 Acidosis
 Hypoglycemia
 Hyperkalemia
(Palmert & Dahms, 2013)

Conclusion
› Impaired synthesis of adrenal hormones may
lead to multiple forms of CAH, two of which
include virilization and salt wasting crisis.
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Androgen Excess Society. (2012). Congenital adrenal hyperplasia: Definition, treatment,
symptoms, diagnosis. Retrieved from
http://www/ae-ociety.org/congenital_adrenal_hyperplasia
Antal, Z. & Zhou, P. (2009). Congenital adrenal hyperplasia: Diagnosis, evaluation and
management. Pediatrics in Review, 30 (7), e 49-57. doi: 10.1542/pir.30-7-e49
Gomella, T., Cunningham, M. D., & Eyal, F. G. (2013). Neonatology: Management,
procedures, on-call problems, diseases and drugs (7th ed.). New York, NY:
McGraw- Hill Education LLC.
Mayo Clinic (2014). Congenital adrenal hyperplasia. Retrieved from
http://www.mayoclinic.org/diseases-conditions/congenital-adrenalhyperplasia/basics/definition/con-20030910
Merck Manuals (2012). Congenital adrenal hyperplasia. Retrieved from
http://www.merckmanuals.com/professional/pediatrics/endocrine_disorders_in_c
hildren/congenital_adrenal_hyperplasia.html
Migeon, C. J. & Wisniewski, A. B. (2014). Congenital adrenal hyperplasia due to 21hydroxylase deficiency: A guide for patients and their families. Retrieved from
http://www.hopkinschildrens.org/cah/printable.html
Palmert, M. R. & Dhams, W. T. (2013). Metabolic and endocrine disorders: Abnormalities
of sexual differentiation. In R. J. Martin, A. A. Fanaroff, M.C. Walsh(Eds.),
Neonatal- Perinatal Medicine: Diseases of the fetus and the infant (9th ed.,
pp.1577-1600. Philadelphia, PA: Mosby Elsevier.
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Stresing, D. (2014). Congenital adrenal hyperplasia. Retrieved from
http://pediatrics.med.nyu.edu/endocrinology/patient-care/congenital-adrenalhyperplasia
Thomas, T. A. (2014). Congenital adrenal hyperplasia. Retrieved from
http://emedicine.medscape.com/article/919218-overview
Van de Kamp, H. & Wit, J. M. (2004). Neonatal screening for congenital adrenal
hyperplasia. European Journal of Endocrinology, 151, (pg71-75).