1. Congenital Adrenal Hyperplasia
A Clinical Presentation
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

2. Congenital Adrenal Hyperplasia
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

3. Congenital Adrenal Hyperplasia
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)

4. Congenital Adrenal Hyperplasia
Definition
Common forms of CAH
90 % of CAH
21- Hydroxylase deficiency
overall incidence is 1 in 16,000
Autosomal recessive
Remaining 10 % of CAH:
17 Alpha- Hydroxylase deficiency
11 Beta- Hydroxylase deficiency
3 Beta- Hydroxylase deficiency
20, 22 Desmolase deficiency
Most common form of CAH involves a deficiency in 21-Hydroxylase. Other Hydroxylase deficiencies compose the remaining 10% of the disorder.
(Merck Manuals, 2012)
(Mayo Clinic, 2014)

5. Congenital Adrenal Hyperplasia
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)

6. Congenital Adrenal Hyperplasia
Pathophysiology
Simply:
Errors or deficiencies in metabolic pathways in the synthesis of cortisol from cholesterol cause:
Increased hormone stimulation
Improper hormone stimulation

7. Congenital Adrenal Hyperplasia
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
21- Hydroxylase 2 1
increased
17-OH Progesterone
17A- Hydroxylase
Increased 7
11B- Hydroxylase
Here is an easy way to remember which hormone level is affected in each deficiency.

8. Congenital Adrenal Hyperplasia
Lets focus on the most common form of CAH
21- hydroxylase deficiency

9. Congenital Adrenal Hyperplasia
Pathophysiology
Hormones:
The adrenal glands (cortex) are responsible for the production of glucocorticoids, mineralcorticoids and androgens.
Cortisol:
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:
Secreted under angiotensin (produced by renin in the kidneys)
Regulates serum sodium, total body water and blood pressure in body.
Adrenal Androgens:
Secreted in both males and females prior to birth
Production decreases after birth then resurges during puberty
(Migeon & Wisniewski, 2014)

10. Congenital Adrenal Hyperplasia
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)

11. Congenital Adrenal Hyperplasia
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)

12. Congenital Adrenal Hyperplasia
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)

13. Congenital Adrenal Hyperplasia
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

14. Congenital Adrenal Hyperplasia
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
Often identified later on in life due to subtle clinical manifestations
Precocious pubic hair
Accelerated growth and skeletal maturation
Also present with similar findings with 3- beta hydro: oligomenorrhea, hirsutism, infertility
(Antal, Z. & Zhou, P, 2009)

15. Congenital Adrenal Hyperplasia
Classic CAH (21-OH)
Males
External genitalia are unaffected
Subtle penile enlargement
Without testicular enlargement
Early overt signs of puberty:
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)

16. Congenital Adrenal Hyperplasia
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)

17. Congenital Adrenal Hyperplasia
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)

18. Congenital Adrenal Hyperplasia
Diagnostic evaluation
Newborn screening
Conducted within 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)

19. Congenital Adrenal Hyperplasia
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)

20. Congenital Adrenal Hyperplasia
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)

21. Congenital Adrenal Hyperplasia
Treatment
Simple Virilization CAH
NOT salt wasting
Goal is to normalize ACTH
Replacement with cortisol
Hydrocortisone PO in 3 divided doses
Dose usually 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)

22. Congenital Adrenal Hyperplasia
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)

23. Congenital Adrenal Hyperplasia
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 mg PO Q hours
Also manage:
Acidosis
Hypoglycemia
Hyperkalemia
Treatment for acute salt wasting crisis is identified.
(Palmert & Dahms, 2013)

24. Congenital Adrenal Hyperplasia
Conclusion
Impaired synthesis of adrenal hormones may lead to multiple forms of CAH, two of which include virilization and salt wasting crisis.

25. References
Androgen Excess Society. (2012). Congenital adrenal hyperplasia: Definition, treatment, symptoms, diagnosis. Retrieved from
Antal, Z. & Zhou, P. (2009). Congenital adrenal hyperplasia: Diagnosis, evaluation and management. Pediatrics in Review, 30 (7), e doi: /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 hyperplasia/basics/definition/con
Merck Manuals (2012). Congenital adrenal hyperplasia. Retrieved from hildren/congenital_adrenal_hyperplasia.html
Migeon, C. J. & Wisniewski, A. B. (2014). Congenital adrenal hyperplasia due to 21- hydroxylase deficiency: A guide for patients and their families. Retrieved from
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 Philadelphia, PA: Mosby Elsevier.

26. References
Stresing, D. (2014). Congenital adrenal hyperplasia. Retrieved from hyperplasia
Thomas, T. A. (2014). Congenital adrenal hyperplasia. Retrieved from
Van de Kamp, H. & Wit, J. M. (2004). Neonatal screening for congenital adrenal hyperplasia. European Journal of Endocrinology, 151, (pg71-75).