History

Fact Explanation
At Birth abnormal genitalia[1][2] Females pseudohermaphroditism-Ambiguous genitalia may present due severe congenital adrenal hyperplasia with deficiencies of 21-hydroxylase, 11-beta-hydroxylase, or 3-beta-hydroxysteroid dehydrogenase. Males with 17-hydroxylase deficiency or pseudohermaphroditism-3-beta-hydroxysteroid dehydrogenase deficiency have ambiguous or female genitalia
In childhood- precocious pubic hair growth and/or clitoromegaly, or both, often accompanied by accelerated growth and skeletal maturation[3] (simple virilizing adrenal hyperplasia) This presentation seen in females with mild 21-hydroxylase deficiency. These presentation is often associated with accelerated growth. This condition is known as simple virilizing adrenal hyperplasia.
Adolescence with oligomenorrhea and hirsutism[3] This presentation commom in mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase enzymes.
Primary subfertility[1][3] Females- This presentation also common in milder deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase enzymes. Male pseudohermaphroditism- They live as females in society and present with subfertility.
Lack of secondary sexual characteristics such as lack of breast development, primary amenorrhoes[3] In 17-hydroxylase deficiency females are born with female external genitalia but in puberty they do not develop breasts or menstruation. This is an adolescent presentation. In males with 3-beta-hydroxysteroid dehydrogenase deficiency, or 17-hydroxylase deficiency born with ambiguous or female genitalia. These children may be raised as girls in the society and seek medical attention later in life because of lack of breast development and/ or primary amenorrhoea.
History of weight loss, Malaise, Weakness, Anorexia, Nausea, Vomiting, Diarrhoea/ Constipation, Postural dizziness, These symptoms can be present due to associated glucocorticoid insufficiency[3].
Generalized body weakness, palpitations, dizziness/ lightheadedness (when standing from seating position) fatigue, a craving for salt, frequent urination, sweating, feeling of thirst. Hyperkalaemia, Hyponatraemia, Hypotension and shock may be the presentation due to mineralocorticoid insufficiency, [3] associated with congenital adrenal hyperplasia.
Hyperpigmentation Pigmentations in sun exposed areas, pressure areas( elbows, knees, palmar creases), mucous membranes, conjunctiva and recent scars can occur due to ACTH excess .
Family history of babies born with ambiguous genitalia There can be a genetic association[3]
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. NEWNS GH. Congenital adrenal hyperplasia. Arch Dis Child [online] 1974 Jan, 49(1):1-3 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648855
  3. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155

Examination

Fact Explanation
Ambiguous genitalia[1][2] During neonatal examination, just after birth can be identified. the genital abnormalities can be seen are: partial/ complete fusion of the labioscrotal folds, phallic urethra, clitoromegaly. In females with pseudohermaphroditism, ambiguous genitalia may present due severe congenital adrenal hyperplasia with deficiencies of 21-hydroxylase, 11-beta-hydroxylase, or 3-beta-hydroxysteroid dehydrogenase. Males with 17-hydroxylase deficiency or pseudohermaphroditism-3-beta-hydroxysteroid dehydrogenase deficiency have ambiguous or female genitalia. [1,2]
Precocious pubic hair growth and/or clitoromegaly with accelerated growth[3] This findings can be seen in simple virilizing adrenal hyperplasia
Hirtusism[3] This presentation is common in mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase enzymes. Usually this is a adolescent presentation.
Poor breast development In 17-hydroxylase deficiency females born with normal female external genitalia in puberty may not develop breasts or menstruation[3].
Wasting, weakness, ill health These features are present in glucocorticoid insufficiency. [3]
Blood pressure measurement Postural hypotension can be detected in glucocorticoid insufficiency. Features are hypotension, low blood volume/ a high pulse in mineralocorticoid insufficiency. [3]
Generalized body weakness, unconsciousness Due to electrolyte imbalances in mineralocorticoid insufficiency. [3]
Hyperpigmentation in sun exposed areas, pressure areas, mucous membranes, conjunctivae and recent scars Increased secretion of ACTH due to congenital adrenal hyperplasia.
Vaginal examination[1] In vaginal examination some associated abnormalities can be identified such as a blind ended vagina.
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. NEWNS GH. Congenital adrenal hyperplasia. Arch Dis Child [online] 1974 Jan, 49(1):1-3 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1648855
  3. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155

Differential Diagnoses

Fact Explanation
5-alpha-reductase deficiency[1] This is an autosomal recessive sex-limited condition. There is inability to convert to testosterone dihydrotestosterone which is the more physiologically active form. Genetic males with ambiguous genitalia are born in this condition as the hormone is required for external genitalia masculinisation during intrauterine life.
Androgen insensitivity syndrome[2] In partial androgen insensitivity syndrome there will be mildly virilized female external genitalia (eg; clitorimegaly) or mildly undervirilized male external genitalia (eg; hypospadias and/or diminished penile size). In complete androgen insensitivity genetic males (46 XY) develop female external genitalia.
Genital anomalies[3] In a case of ambiguous genitalia this is one differential diagnosis. Maldevelopment during the embryological period can cause this.
Denys-Drash syndrome[4] This is a rare condition and it clinically manifests as an early onset nephrotic syndrome, gonadal dysgenesis with male pseudohermaphroditism.
Gonadoblastoma[5] This is a rare benign tumor and it is associated with maldevelopment of sexual organs.
Hypogonadism[6] This condition also presents with abnormal development of the genital organs
Gender identity disorders[7] Here person identifies him/her self as belonging to the opposite sex, so their behaviour reflects that of the opposite gender outwardly.
Precocious puberty[8] In precocious puberty, pubertal changes occur at an earlier age than is considered normal.
Menstrual disorders[9] Several menstrual disorders can be seen in adolescent period.
References
  1. GREENE SA, SYMES E, BROOK CG. 5-alpha-Reductase deficiency causing male pseudohermaphroditism. Arch Dis Child [online] 1978 Sep, 53(9):751-753 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1545103
  2. WILLIAMS DM, PATTERSON MN, HUGHES IA. Androgen insensitivity syndrome. Arch Dis Child [online] 1993 Mar, 68(3):343-344 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793874
  3. LIN PC, BHATNAGAR KP, NETTLETON GS, NAKAJIMA ST. Female genital anomalies affecting reproduction. Fertil Steril [online] 2002 Nov, 78(5):899-915 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12413972
  4. KUCINSKAS L, RUDAITIS S, PUNDZIENE B, JUST W. Denys-Drash syndrome. Medicina (Kaunas) [online] 2005, 41(2):132-4 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15758579
  5. GIBBONS B, TAN SY, YU CC, CHEAH E, TAN HL. Risk of gonadoblastoma in female patients with Y chromosome abnormalities and dysgenetic gonads. J Paediatr Child Health [online] 1999 Apr, 35(2):210-3 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10365364
  6. BHASIN S, BASARIA S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab [online] 2011 Apr, 25(2):251-70 [viewed 25 July 2014] Available from: doi:10.1016/j.beem.2010.12.002
  7. DE GASCUN C, KELLY J, SALTER N, LUCEY J, O'SHEA D. Gender identity disorder. Ir Med J [online] 2006 May, 99(5):146-8 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16892921
  8. PARTSCH CJ, SIPPELL WG. Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update [online] 2001 May-Jun, 7(3):292-302 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11392376
  9. WONG MS, LAM ST. Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong Kong: retrospective study. Hong Kong Med J [online] 2005 Aug, 11(4):267-72 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16085943

Investigations - for Diagnosis

Fact Explanation
Karyotyping [2] This is help to identify the genetic origin of a patient with ambiguous genitalia as it is difficult to differentiate the real sex of the patient. (Male-46 XY/Female- 46 XX) Used to assess the genetic predisposition, for example congenital adrenal hyperplasia is a autosomal recessive condition. [1][3] in which DNA CYP21A2 mutations[8] have been observed. In addition cortisol biosynthesis is HLA-linked and 21-hydroxylase deficiency is associated with HLA-DR7. [5]
Endocrine screening[7] which includes: ACTH stimulation test[9], androgen levels, serum/ Urine cortisol levels[10], 17-OH Progesterone levels, Modified LC-MS/MS protocol, Aldosterone levels[12]and Renin levels. Congenital adrenal hyperplasia is a genetic disease that increases the levels of androgen production by the adrenal gland.In this condition there is a lack of an enzyme which is needed in the production of cortisol and aldosterone. So the pathway of adrenal androgen production is stimulated resulting in over production. Stimulation testing with a pharmacological dose of 0.125–0.25 mg cosyntropin (ACTH 1–24) is useful to assess serum ACTH levels. Serum cortisol should be measured before and 60 minutes after the ACTH injection. ACTH levels are high in this condition[8]. Along with the blood tests, patient may also have a urinary free cortisol test/ urinary 17-ketosteroids test, urine should be collected for a 24 hour period. Androgen levels[1] are helpful in arriving at a diagnosis. Adrenal androgen concentrations should measure in the morning, before medication as other times of the day and following medication levels will be lower the levels. Androgen levels will be high in this condition[8] ( low levels of serum cortisol/ aldosterone gives rise to a lack of feedback inhibition in hypothalamus and will increase ACTH levels). -Serum cortisol level- Cortisol level rises and falls throughout the day, the test may need to be done three or more separate times to get a more accurate picture of average cortisol production. In these patients cortisol levels are found to be low. For Urine cortisol level- 24-hour urine sample is needed. 17- OH progesterone level[2] is increased in this condition. 17-OH progesterone levels are normally high at birth and decrease rapidly during the first few postnatal days. In contrast, 17-OH Progesterone levels increase with time in infants affected with CAH. In modified LC-MS/MS protocol, sum of 17-OH Progesterone and 21-deoxycortisol levels are divided by the cortisol level. This has a positive predictive value of 100%. [3] Aldosterone is measured in the blood/24-hour urine sample, (measures the amount of aldosterone removed from urine in 24 hrs). If the test is positive, aldosterone production should be further evaluated with stimulation and suppression testing. Renin levels are high in congenital adrenal hyperplasia.[12]
Serum electrolytes[2][7] including serum sodium, serum calcium and serum potassium Due to glucocorticoid insufficiency, hyperkalaemia, hyponatraemia(dilutional) and hypercalcaemia [13] can occur. Due to mineralocorticoid insufficiency[3] hyponatraemia (depletional) can occur.
Casual venous plasma glucose/ capillary blood sugar Hypoglycaemia[1] occurs in glucocorticoid insufficiency. As cortisol is a stress hormone and it helps to balance the effects of insulin in breaking down sugar for energy. So in patients with congenital adrenal hyperplasia insulin-induced hypoglycaemia can occur.
Insulin-induced hypoglycemia test This tests the hypothalamo- pituitary- adrenal axis[14]. First blood is taken for glucose and cortisol levels and then fast-acting insulin is injected. Again at 30, 45, and 90 minutes after the insulin injection blood glucose and cortisol levels are measured . The normal response is for blood glucose levels to fall and cortisol levels to rise.
Ultrasonography[1] Ultrasound scan of the abdomen and pelvis; to see adrenal glands( may be enlarged in congenital adrenal insufficiency, but can not exclude if the gland appears normal), to look for internal genitalia, cystic ovaries, similar to polycystic ovary syndrome.
Magnetic Resonance Imaging[1]/ Computed tomography These imaging studies may helpful to identify structural anomalies.
Biopsy and histological examination This is helpful in differentiating between gonadal tissues. [4]
Chorionic villus sampling/ amniocentesis [2][6] For prenatal diagnosis,fetal genomic DNA obtained using amniocentesis or chorionic villus sampling[ can be used. [6] This used for early diagnosis in baby of a mother with positive family history.
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  3. SPEISER PW, AZZIZ R, BASKIN LS, GHIZZONI L, HENSLE TW, MERKE DP, MEYER-BAHLBURG HF, MILLER WL, MONTORI VM, OBERFIELD SE, RITZEN M, WHITE PC. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab [online] 2010 Sep, 95(9):4133-4160 [viewed 25 July 2014] Available from: doi:10.1210/jc.2009-2631
  4. ELZANATY S. Varicocele repair in non-obstructive azoospermic men: diagnostic value of testicular biopsy - A meta-analysis. Scand J Urol [online] 2014 Jul 8:1-5 [viewed 26 July 2014] Available from: doi:10.3109/21681805.2014.932839
  5. WHITE PC, NEW MI, DUPONT B. HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation. Proc Natl Acad Sci U S A [online] 1984 Dec, 81(23):7505-7509 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC392175
  6. MA D, GE H, LI X, JIANG T, CHEN F, ZHANG Y, HU P, CHEN S, ZHANG J, JI X, XU X, JIANG H, CHEN M, WANG W, XU Z. Haplotype-based approach for noninvasive prenatal diagnosis of congenital adrenal hyperplasia by maternal plasma DNA sequencing. Gene [online] 2014 Jul 10, 544(2):252-8 [viewed 26 July 2014] Available from: doi:10.1016/j.gene.2014.04.055
  7. RAFF H, SHARMA ST, NIEMAN LK. Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia. Compr Physiol [online] 2014 Apr, 4(2):739-69 [viewed 26 July 2014] Available from: doi:10.1002/cphy.c130035
  8. ALMEIDA MQ, KAUPERT LC, BRITO LP, LERARIO AM, MARIANI BM, RIBEIRO M, MONTE O, DENES FT, MENDONCA BB, BACHEGA TA. Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia. BMC Endocr Disord [online] 2014 May 12:42 [viewed 26 July 2014] Available from: doi:10.1186/1472-6823-14-42
  9. GANDHI PG, SHAH NS, KHANDELWAL AG, CHAUHAN P, MENON PS. Evaluation of low dose ACTH stimulation test in suspected secondary adrenocortical insufficiency. J Postgrad Med [online] 2002 Oct-Dec, 48(4):280-2 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12571383
  10. SAM S, CORBRIDGE TC, MOKHLESI B, COMELLAS AP, MOLITCH ME. Cortisol levels and mortality in severe sepsis. Clin Endocrinol (Oxf) [online] 2004 Jan, 60(1):29-35 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/14678284
  11. ROOT AW. Disorders of aldosterone synthesis, secretion, and cellular function. Curr Opin Pediatr [online] 2014 Aug, 26(4):480-6 [viewed 27 July 2014] Available from: doi:10.1097/MOP.0000000000000104
  12. Primary excess and deficiency or renin. Br Med J [online] 1973 Mar 17, 1(5854):627-628 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1588596
  13. SAKAO Y, SUGIURA T, TSUJI T, OHASHI N, YASUDA H, FUJIGAKI Y, KATO A. Clinical Manifestation of Hypercalcemia Caused by Adrenal Insufficiency in Hemodialysis Patients: A Case-series Study. Intern Med [online] 2014, 53(14):1485-90 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25030558
  14. NYE EJ, GRICE JE, HOCKINGS GI, STRAKOSCH CR, CROSBIE GV, WALTERS MM, TORPY DJ, JACKSON RV. The insulin hypoglycemia test: hypoglycemic criteria and reproducibility. J Neuroendocrinol [online] 2001 Jun, 13(6):524-30 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11412339
  15. CROWN A, LIGHTMAN S. Why is the management of glucocorticoid deficiency still controversial: a review of the literature. Clin Endocrinol (Oxf) [online] 2005 Nov, 63(5):483-92 [viewed 27 July 2014] Available from: doi:10.1111/j.1365-2265.2005.02320.x

Investigations - Fitness for Management

Fact Explanation
Serum electrolytes [2] Should be performed to detect hyponatraemia, hypercalcaemia and hyperkalaemia.
Casual venous plasma glucose Hypoglycaemia[1] can be present in glucocorticoid insufficiency.
Dual-energy x-ray absorptiometry (DEXA) scan[1] This useful in assessing the bone mineral density of the bones because these patients are at risk of developing osteoporosis.
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155

Investigations - Followup

Fact Explanation
Serum electrolytes[2][3] including serum sodium, serum potassium and serum calcium In the follow up of patients these investigations useful in both measuring both the disease condition as well as response to the treatment.[8]
Pictorial nomogram of 17-0H progesterone[2] To monitor the response for the treatment during follow up.
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  3. RAFF H, SHARMA ST, NIEMAN LK. Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia. Compr Physiol [online] 2014 Apr, 4(2):739-69 [viewed 26 July 2014] Available from: doi:10.1002/cphy.c130035
  4. SPEISER PW, AZZIZ R, BASKIN LS, GHIZZONI L, HENSLE TW, MERKE DP, MEYER-BAHLBURG HF, MILLER WL, MONTORI VM, OBERFIELD SE, RITZEN M, WHITE PC. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab [online] 2010 Sep, 95(9):4133-4160 [viewed 25 July 2014] Available from: doi:10.1210/jc.2009-2631
  5. SAKAO Y, SUGIURA T, TSUJI T, OHASHI N, YASUDA H, FUJIGAKI Y, KATO A. Clinical Manifestation of Hypercalcemia Caused by Adrenal Insufficiency in Hemodialysis Patients: A Case-series Study. Intern Med [online] 2014, 53(14):1485-90 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25030558
  6. ROOT AW. Disorders of aldosterone synthesis, secretion, and cellular function. Curr Opin Pediatr [online] 2014 Aug, 26(4):480-6 [viewed 27 July 2014] Available from: doi:10.1097/MOP.0000000000000104
  7. Primary excess and deficiency or renin. Br Med J [online] 1973 Mar 17, 1(5854):627-628 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1588596
  8. CROWN A, LIGHTMAN S. Why is the management of glucocorticoid deficiency still controversial: a review of the literature. Clin Endocrinol (Oxf) [online] 2005 Nov, 63(5):483-92 [viewed 27 July 2014] Available from: doi:10.1111/j.1365-2265.2005.02320.x
  9. AL-HUSSAINI A, ALMUTAIRI A, MURSI A, ALGHOFELY M, ASERY A. Isolated Cortisol Deficiency: A Rare Cause of Neonatal Cholestasis Saudi J Gastroenterol [online] 2012, 18(5):339-341 [viewed 27 July 2014] Available from: doi:10.4103/1319-3767.101137
  10. VENTURA A, BRUNETTI G, COLUCCI S, ORANGER A, LADISA F, CAVALLO L, GRANO M, FAIENZA MF. Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency Biomed Res Int [online] 2013:250462 [viewed 27 July 2014] Available from: doi:10.1155/2013/250462

Investigations - Screening/Staging

Fact Explanation
Genetic screening [1][2] To identify any genetic association, this helpful in screening family members. Congenital adrenal hyperplasia (CAH) is a common inherited autosomal recessive metabolic disorder. This is caused by the deficiency of one of four steroidogenic enzymes- steroid 21-hydroxylase (CYP21A2), 11beta-hydroxylase (CYP11B1), 17alpha-hydroxylase (CYP17A1) and 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency. Inactivating POR gene mutations cause CAH to manifest with apparent combined CYP17A1-CYP21A2 deficiency. [3]
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. SPEISER PW, AZZIZ R, BASKIN LS, GHIZZONI L, HENSLE TW, MERKE DP, MEYER-BAHLBURG HF, MILLER WL, MONTORI VM, OBERFIELD SE, RITZEN M, WHITE PC. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab [online] 2010 Sep, 95(9):4133-4160 [viewed 25 July 2014] Available from: doi:10.1210/jc.2009-2631
  3. KRONE N, ARLT W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab [online] 2009 Apr, 23(2):181-92 [viewed 27 July 2014] Available from: doi:10.1016/j.beem.2008.10.014

Management - General Measures

Fact Explanation
Multidisciplinary team approach [1][4] This approach is helpful to manage the patients physical as well as psychological condition. Paediatrician, obstetrician/ gynaecologist, endocrinologist, specialist in genetics, psychiatrist/ psychologist[1], surgeon/urologist, [3], sexual specialist and social worker should included in this team. In addition family support is also very important. Paediatrician and gynaecologist's role[3] starts from the prenatal period including prenatal screening of at risk babies, treatment to minimize virilization of the foetus, early diagnosis after birth, education of the parents about the condition and future management plan and follow up the patient. Endocrinologist's should investigate, diagnose and start hormonal treatment. Specialist in genetics[3]will screen and diagnose the associated genetic factors. Psychiatrist/ psychologist role[1] is a very sensitive subject depending on patient's social, cultural, spiritual background and the approach should be to have normal self-esteem and a satisfying social life. Family members also need help to cope with the situation. Surgeon/ urologist role[2] includes correction of ambiguous genitalia in early life of the baby after confirming the sex/ later according to the patient's preference and to improve the quality of life( eg; Surgical correction of vagina to help sexual intercourse) Sexual specialist's role deals with sexual problems are common among girls/ women with congenital adrenal hyperplasia. They will be embarrassed about the appearance of external genitals, there will be problems regarding intercourse(whether it is possible or not), complaints about pain and bleeding during intercourse and confiding in a new partner about the disease.
Long term care[2] Care plan should ensure patients normal growth and development [2] this will include monitoring of height, weight, and physical examination; annual bone age assessment. [3] Asses and intervene to achieve puberty at appropriate ages. [2] Improve adults fertility potentials. [2] Monitor and manage side effects of treatments. [2]
Prevent/ minimise complications Prevent osteoporosis[1] by improving physical activity and supplying calcium and vitamin D from a young age.
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
  2. HUGHES IA. Management of congenital adrenal hyperplasia. Arch Dis Child [online] 1988 Nov, 63(11):1399-1404 [viewed 25 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779155
  3. SPEISER PW, AZZIZ R, BASKIN LS, GHIZZONI L, HENSLE TW, MERKE DP, MEYER-BAHLBURG HF, MILLER WL, MONTORI VM, OBERFIELD SE, RITZEN M, WHITE PC. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab [online] 2010 Sep, 95(9):4133-4160 [viewed 25 July 2014] Available from: doi:10.1210/jc.2009-2631
  4. GERBER K. Surviving sepsis: a trust-wide approach. A multi-disciplinary team approach to implementing evidence-based guidelines. Nurs Crit Care [online] 2010 May-Jun, 15(3):141-51 [viewed 27 July 2014] Available from: doi:10.1111/j.1478-5153.2009.00378.x

Management - Specific Treatments

Fact Explanation
Glucocorticoid replacement[1][3][4] Maintenance therapy for this condition is usually achieved with hydrocortisone (6 to 25 mg/ m2/ per day- in two to three divided doses). As Hydrocortisone is a short acting drug it better than other glucocorticoids and it can be given in pulses which mimics natural cortisol secretion. Hydrocortisone has reduced side effects( eg; growth suppression in children) because it is more similar to cortisol. Prednisone/dexamethasone can also be used. In a stressful situation( eg; severe illness, surgery) patients may require three to ten times a higher dose than maintenance therapy. The doses are sufficient to suppress adrenal androgen secretion without total suppression of the hypothalamic-pituitary-adrenal axis. Administration should be done very carefully as over dose can induce Cushingoid features while lower doses may leave the effects of excess androgen production.
Minaralocorticoid replacement[1][3][4] Fludrocortisone(0.05 to 0.2 mg per day) can be used for mineralocorticoid replacement. This is an aldosterone analogue which helps to maintain normal electrolyte and plasma renin activity.
Emergency management[2][3] in adrenal crisis[5][6] This is a emergency encountered in these patients. Here the patient develops severe dehydration and circulatory collapse within few hours of onset of the symptoms (common in early life). Emergency management involves the following; take blood for cortisol and ACTH, hydrocortisone 100mg IV stat, intra venous infusion of plasma expanders/ 0.9% saline, monitor blood glucose for hypoglycaemia, blood, urine, sputum for culture, give antibiotics( eg; cefuroxime) There are several precipitating factors such as surgery, anesthesia (eg, etomidate), volume loss, trauma, asthma (steroid withdrawal), hypothermia, alcohol, myocardial infarction, fever/infection, hypoglycemia, pain, psychosis or depression and exogenous steroid withdrawal. So patients and family members must be educated regarding this condition, precipitating causes and how to prevent it.
Surgical treatment[3] For virilized female, feminizing genitoplasty, vaginoplasty and clitoroplasty can be performed. For undervirilized males, hypospadias surgical correction can be performed.
Androgen inhibition Flutamide[8] is an androgen inhibitor which helps to block the androgen effect. It also permits hydrocortisone to be given at lower dosages. Aromatase inhibitors[9] (40 mg/kg /day) prevent conversion of androgens to estrogen which help children with mild congenital adrenal hyperplasia to achieve their height potential.
Genetic counselling As congenital adrenal hyperplasia is an autosomal recessive condition, genetic counselling is very important. [1]
Prenatal treatment[3] Maternal dexamethasone is used and it helps to reduce female virilization but can not completely stop its occurrence. [3]
References
  1. MERKE DP. Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J Clin Endocrinol Metab [online] 2008 Mar, 93(3):653-660 [viewed 25 July 2014] Available from: doi:10.1210/jc.2007-2417
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