History

Fact Explanation
Abnormalities of genitalia Usually in the steroid biosynthesis, pathway, conversion of progesterone into deoxycorticosterone and 17-alfahydroxyprogesterone into deoxycortisol is mediated by 21-hydroxylase. [4] Then deoxycorticosterone is converted to aldesterone and deoxycortisol is converted to cortisol by 11-betahydroxylase. In patients with congenital adrenal hyperplasia, there is a defect in the 21-hydroxylation in the biosynthesis of the cortisol and aldesterone in the adrenal gland. [1] This defective hydroxylation is mainly due to the deficiency of 21-hydroxylase enzyme. There are 2 types of congenital adrenal hyperplasia: salt losing and non salt losing. Reduced cortsol, stimulate the pituitary to release adreno corticotrophin hormone (ACTH) and causes increased production of adrenal androgens. [2] These excess androgens cause virilization of the external genitalia. (Abnormalities will be dealt in detail in the examination section)
Vomiting and weight loss Abscence of aldesterone causes reduction in sodium and water reabsorption. Salt losing adrenal crisis may present with vomiting and weight loss. [4]
Family history of same problem As this is an inherited condition as an autosomal recessive manner, there can be affected persons with the same problem in the family. [5]
Consanguinity Due to the autosomal recessive inheritance, [6] it is more common in consanguineous marriages.
Family history of neonatal death Due to the salt losing adrenal crisis. [7]
Dry skin, excessive thirst and reduced urine output Dehydration [4] may be due to reduced sodium and water retention associated with reduction in the level of aldesterone.
Irregular menstruation and subfertility These are some associated problems. [3]
References
  1. KOBAYASHI A, IGARASHI Y. Serum magnesium level in the salt-losing type of congenital adrenal hyperplasia. Arch Dis Child [online] 1968 Apr, 43(228):223-228 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2019827
  2. QAZI QH, THOMPSON MW. Incidence of salt-losing form of congenital virilizing adrenal hyperplasia. Arch Dis Child [online] 1972 Apr, 47(252):302-304 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648069
  3. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  4. BARTTER FC. Salt-losers and non salt-losers in congenital adrenal hyperplasia. Arch Dis Child [online] 1969 Feb, 44(233):138-139 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2020228
  5. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193
  6. DESSINIOTI C, KATSAMBAS A. Congenital adrenal hyperplasia Dermatoendocrinol [online] 2009, 1(2):87-91 [viewed 23 September 2014] Available from: doi:10.4161/derm.1.2.7818
  7. KNOWLES RL, KHALID JM, OERTON JM, HINDMARSH PC, KELNAR CJ, DEZATEUX C. Late clinical presentation of congenital adrenal hyperplasia in older children: findings from national paediatric surveillance Arch Dis Child [online] 2014 Jan, 99(1):30-34 [viewed 23 September 2014] Available from: doi:10.1136/archdischild-2012-303070

Examination

Fact Explanation
Virilization of external genitalia in female: clitoral hypertrophy, labial fusion [2] Reduced cortisol, stimulate the pituitary to release adrenocorticotrophic hormone (ACTH) and causes increased production of adrenal androgens. [1,2] These excess androgens cause virilization of the external genitalia.
Abnormalities of male genitalia: enlarged penis, pigmented scrotum As mentioned above, due to the excess androgens. [5]
Floppy baby Salt losing adrenal crisis may present with floppiness. Congenital adrenal hyperplasiacan be occasionally a manifestation of the lysosomal storage disorders and may cause of floppy baby syndrome. [6]
Hypotension Salt losing adrenal crisis may be associated with circulatory collapse. [4]
Dehydration [1] :sunken eyes, reduced skin turgor, reduced urine output Due to reduced sodium and water retention associated with reduction in the level of aldesterone. [2]
Rapid linear growth with normal testicular size Due to the increased androgens from the peripheral site which is not under the control of central control. [3]
Acne, hirsuitism, striae, hypertension Effects of steroids. [3]
References
  1. QAZI QH, THOMPSON MW. Incidence of salt-losing form of congenital virilizing adrenal hyperplasia. Arch Dis Child [online] 1972 Apr, 47(252):302-304 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648069
  2. NEW MI, MILLER B, PETERSON RE. Aldosterone excretion in normal children and in children with adrenal hyperplasia. J Clin Invest [online] 1966 Mar, 45(3):412-428 [viewed 29 August 2014] Available from: doi:10.1172/JCI105356
  3. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  4. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193
  5. STARETZ-CHACHAM O, LANG TC, LAMARCA ME, KRASNEWICH D, SIDRANSKY E. Lysosomal Storage Disorders in the Newborn Pediatrics [online] 2009 Apr, 123(4):1191-1207 [viewed 23 September 2014] Available from: doi:10.1542/peds.2008-0635

Differential Diagnoses

Fact Explanation
5-alpha-reductase type 2 deficiency 5-alpha-reductase type 2 deficiency is an autosomal recessive condition [4] that is associated with impaired conversion of testosterone to physiologically active dihydrotestosterone (DHT). [3] They will have ambiguous genitalia at birth due to defective DHT. [4] Males will have signs of virilization. Females will have delayed menarche, and minimal body hair. [4] Fertility is normal in females. Elevated ratio of testosterone to DHT is found in 5-alpha reductase deficiency.
Adrenal Hypoplasia X-linked congenital adrenal hypoplasia is due to mutation or deletion of the DAX1 (AHCH) gene. They will present with crisis with dehydration, hyponatremia, hyperkalemia, hypotension, or hypoglycemia. [2]
Androgen insensitivity syndrome This is an X-linked recessive condition presenting with failure of normal masculinization of the external genitalia in males.Main abnormality is defective androgen receptor protein due to a mutation of the androgen receptor gene. [1] Females may have virilized external genitalia and males may have undervirilized external genitalia with hypospadias and diminished penile size. Some will have precocious puberty as well.
Pyloric stenosis Salt losing crisis may be mistaken for pyloric stenosis on some occasions as both conditions can present at around 2-6 weeks after birth. [6] Test feed, ultrasound scan and electrolyte profile may be used to differentiate both.
References
  1. EVANS B, HUGHES I, BEVAN C, PATTERSON M, GREGORY J. Phenotypic diversity in siblings with partial androgen insensitivity syndrome Arch Dis Child [online] 1997 Jun, 76(6):529-531 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717223
  2. UTTLEY WS. Familial congenital adrenal hypoplasia. Arch Dis Child [online] 1968 Dec, 43(232):724-730 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2020170
  3. ANWAR R, GILBEY SG, NEW JP, MARKHAM AF. Male pseudohermaphroditism resulting from a novel mutation in the human steroid 5 alpha-reductase type 2 gene (SRD5A2). Mol Pathol [online] 1997 Feb, 50(1):51-52 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC379579
  4. MALEKI N, KALANTAR HORMOZI M, IRANPARVAR ALAMDARI M, TAVOSI Z. 5-Alpha-Reductase 2 Deficiency in a Woman with Primary Amenorrhea Case Rep Endocrinol [online] 2013:631060 [viewed 23 September 2014] Available from: doi:10.1155/2013/631060
  5. METRAKOS JD. Congenital Hypertrophic Pyloric Stenosis in Twins Arch Dis Child [online] 1953 Oct, 28(141):351-358 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1988616

Investigations - for Diagnosis

Fact Explanation
17-alfahydroxyprogesterone level Is markedly increased due to the deficiency of 21-hydroxylase. [3,4]
Urinary aldesterone level Is usually reduced. [1]
11-deoxy cortisol To diagnose the defects in the 11beta hydroxylase enzyme. [2]
ACTH level ACTH (Adrenocorticotrophine hormone) is increased [4] in the urine, but this is not routinely done. [2]
References
  1. NEW MI, MILLER B, PETERSON RE. Aldosterone excretion in normal children and in children with adrenal hyperplasia. J Clin Invest [online] 1966 Mar, 45(3):412-428 [viewed 29 August 2014] Available from: doi:10.1172/JCI105356
  2. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  3. QAZI QH, THOMPSON MW. Incidence of salt-losing form of congenital virilizing adrenal hyperplasia. Arch Dis Child [online] 1972 Apr, 47(252):302-304 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648069
  4. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193

Investigations - Fitness for Management

Fact Explanation
Serum electrolytes [2] Sodium and water retention is reduced due to associated low levels of aldesterone. [1] Low sodium and high potassium will be found in the serum. [4]
Random blood sugar They might have associated hypoglcaemia. [5]
Blood urea Dehydration is a well known complication of the disaese. [3] Blood urea will be elevated due to the dehydration.
References
  1. BARTTER FC, HENKIN RI, BRYAN GT. Aldosterone hypersecretion in "non-salt-losing" congenital adrenal hyperplasia J Clin Invest [online] 1968 Aug, 47(8):1742-1752 [viewed 29 August 2014] Available from: doi:10.1172/JCI105864
  2. NEW MI, MILLER B, PETERSON RE. Aldosterone excretion in normal children and in children with adrenal hyperplasia. J Clin Invest [online] 1966 Mar, 45(3):412-428 [viewed 29 August 2014] Available from: doi:10.1172/JCI105356
  3. QAZI QH, THOMPSON MW. Incidence of salt-losing form of congenital virilizing adrenal hyperplasia. Arch Dis Child [online] 1972 Apr, 47(252):302-304 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648069
  4. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193
  5. HINDE FR, JOHNSTON DI. Hypoglycaemia during illness in children with congenital adrenal hyperplasia. Br Med J (Clin Res Ed) [online] 1984 Dec 8, 289(6458):1603-1604 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1443900

Investigations - Followup

Fact Explanation
Growth assessment Failure to thrive is common in these children. [2] They need regular growth assessment during follow up. Tall stature is found in non salt losing variety.
Serum electrolytes [1] Electrolyte imbalance is a recognized feature of adrenal insufficiency. [2] Low sodium and high potassium will be come back to normal with the treatment.
Plasma renin level Regular assessment of plasma renin activity should be checked specially in a case of unfavourable clinical out come. [2]
References
  1. NEW MI, MILLER B, PETERSON RE. Aldosterone excretion in normal children and in children with adrenal hyperplasia. J Clin Invest [online] 1966 Mar, 45(3):412-428 [viewed 29 August 2014] Available from: doi:10.1172/JCI105356
  2. QAZI QH, THOMPSON MW. Incidence of salt-losing form of congenital virilizing adrenal hyperplasia. Arch Dis Child [online] 1972 Apr, 47(252):302-304 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648069

Investigations - Screening/Staging

Fact Explanation
Arterial blood gas analysis Features of metabolic acidosis such as low pH, reduced bicarbonate level may be present. [4]
Serum magnesium and potassium Aldesterone is important in regulating the metabolism of magnesium in the body. Mineralocorticoids are important in the excretion of the potassium and magnesium in the urine. Therefore in CAH there is elevation of serum levels of these electrolytes. [1]
Ultrasound scan Evaluation of the abnormal genitalia present at birth, may need USS. This will demonstrate the normal uterus in females with ambiguous genitalia. [3]
Xray for the bone age assessment Increased androgens will induce the rapid skeletal growth. [2]
References
  1. KOBAYASHI A, IGARASHI Y. Serum magnesium level in the salt-losing type of congenital adrenal hyperplasia. Arch Dis Child [online] 1968 Apr, 43(228):223-228 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2019827
  2. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  3. QAZI QH, THOMPSON MW. Incidence of salt-losing form of congenital virilizing adrenal hyperplasia. Arch Dis Child [online] 1972 Apr, 47(252):302-304 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648069
  4. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193

Management - General Measures

Fact Explanation
Management of fluid balance Initially patient should be hydrated with 0.9% sodium chloride. [2] Intravenous bolus of isotonic 0.9% sodium chloride (20 mL/kg) over the first hour, and then as required to normalize the blood volume. Amount of the required fluid will be based on the degree of sodium deficit and dehydration. [1]
Management of electrolyte imbalances Low sodium and high potassium is found in salt losing adrenal hyperplasia. [2] Sodium will be corrected according to the degree of deficit by using 0.9% normal saline. [1] Hyperkalaemia is treated with insulin only if severe.
Management of hypoglycaemia Dextrose is given in hypoglycemia, and in rehydration fluid to prevent hypoglycemia. [3]
Supplementation with oral salt Supplementation with 2-3g of sodium chloride [2] daily is occasionally done with oral feeds. [1]
Monitoring Blood pressure, pulse rate and urine out put need to be monitored during the acute episodes of salt losing crisis. Long-term monitoring during the treatment is done with growth velocity, bone age, menstrual pattern, signs of hypercortisoliam (striae, weight gain). [1]
Patient and parent education It is important to educate them on the disease, complications and early recognition of the symptoms of adrenal crisis, complications of the treatment, and particularly about the normal internal genital development in the female, thus the reassurance. [1]
References
  1. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  2. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193
  3. HINDE FR, JOHNSTON DI. Hypoglycaemia during illness in children with congenital adrenal hyperplasia. Br Med J (Clin Res Ed) [online] 1984 Dec 8, 289(6458):1603-1604 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1443900

Management - Specific Treatments

Fact Explanation
Glucocorticoids and aldosterone replacement This is done after initial stabilization of the patient. Long-term glucocorticoid or aldosterone replacement [2] may be indicated depending on the affected enzyme. Glucorticoid is able to suppress the raised 17-OH progesterone levels. It is given in s dose of 20mg/m2/day in divided doses at8 hour intervals. [1] Hydrocortisone is preffered as an initial treatment. 9-alfafludrocortisone is an mineralocorticoid is done once the person is stabilized.
Surgical management Surgery is needed for reduce the size of the enlarged clitoris and separate the fused labia. Only the clitoroplasty is done during the infancy and vaginoplasty is usually delayed till puberty unless there is infections due to the fused labia. [1]
Long term management Regular replacement of glucocorticoids is needed in these patients. [1] Dexamethasone is given in a dose of 12-15mg/m2/day in 2-3 divided doses till the satural growth is complete and then tailed off accordingly. Dexamethasone can be continued even after satural growth is complete, as it is important for the menstrual regulation and ovulation in postmenarchal females. [1]
References
  1. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 29 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  2. HASHEMIPOUR M, GHASEMI M, HOVSEPIAN S. A Case of Congenital Lipoid Adrenal Hyperplasia Int J Prev Med [online] 2012 Jul, 3(7):510-514 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415193