Adrenal Hypoplasia Follow-up
- Author: Thomas A Wilson, MD; Chief Editor: Stephen Kemp, MD, PhD more...
Further Outpatient Care
See the list below:
- Patients with adrenal hypoplasia on chronic glucocorticoid therapy must be monitored for adequacy of dosing.
- Too little therapy results in symptoms of adrenal insufficiency (anorexia, nausea, vomiting, abdominal pain, asthenia).
- Too much therapy results in excess weight gain, cushingoid features, hypertension, hyperglycemia, cataracts, osteopenia, and growth failure.
- Growth failure is one of the more sensitive indicators of excess exposure in children.
- Blood pressure and plasma renin activity provides a guide for adequacy of mineralocorticoid therapy.
- If no signs of puberty are seen by age 14-15 years, suspect hypogonadotropic hypogonadism.
- This is associated with low serum concentrations of gonadotropins (eg, leuteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and low serum concentration of testosterone in the male.
- Patients with hypogonadotropic hypogonadism may be unresponsive to gonadotropin-releasing hormone (GnRH) analogues suggesting insufficiency of pituitary secretion of gonadotropins, as well as a deficiency of GnRH.
- The simplest treatment for hypogonadotropic hypogonadism in the male is testosterone enanthate or cypionate in oil initially at 75-100 mg intramuscularly every month and gradually increasing to full adult doses of 200-300 mg intramuscularly every 2 weeks.
- Testosterone also can be administered by cutaneous patch or gel; however, this makes adjustment of dose more difficult, and accurate dosing for adolescents has yet to be resolved.
- Oral preparations of androgen (oxandrolone, Halotestin) are more likely to cause hepatic dysfunction than injectable preparations or transdermal preparations. Transcutaneous preparations provide more stable serum concentrations.
See the list below:
- With proper identification of the genetic cause, prenatal diagnosis should be possible once an index case is identified in a family.
- Prenatal diagnosis is also possible by taking serial measurements of dehydroepiandrosterone sulfate (DHEAS) and estriol in maternal plasma during pregnancy, because these hormones are derived from the fetal adrenal cortex. These hormones are unusually low in cases of fetal adrenal hypoplasia; however, this test is nonspecific. Low levels of these hormones also are observed in panhypopituitarism, in steroid sulfatase deficiency, and in women treated with glucocorticoids during pregnancy.
See the list below:
- Main complications of adrenal hypoplasia include hypotension, electrolyte abnormalities, hypoglycemia, and death.
- Complications of excessive administration of glucocorticoids are growth failure, obesity, striae, hypertension, hyperglycemia, and cataracts.
- Excess mineralocorticoid administration can cause hypertension and hypokalemia.
- Patients with X-linked congenital adrenal hypoplasia and defects in SF1 develop hypogonadotropic hypogonadism. Watch for this and treat appropriately if puberty does not occur in a timely fashion. Curiously, the minipuberty that occurs in the newborn period appears to be preserved. Most of these patients also experience testicular atrophy and are infertile.
- Perform screening for hearing deficits since some patients with X-linked congenital adrenal hypoplasia have been described to have sensorineural (high-frequency) hearing deficits.
See the list below:
- Prognosis of untreated congenital adrenal hypoplasia is poor if the disorder is unrecognized or untreated, and death is a common outcome.
- With proper treatment and compliance, patients can live a normal life span without limitations.
- Hypogonadotropic hypogonadism is nearly certain to develop secondary to DAX1 mutations or deletions. Infertility is common.
- If the gene for muscle dystrophin is absent as a contiguous gene deletion, Duchenne muscular dystrophy (OMIM 310200) results, and the prognosis is poor.
See the list below:
- Patients should be advised to wear medical alert bracelets or anklets that alert medical personnel to the diagnosis of adrenal insufficiency and the need for glucocorticoid therapy in times of stress.
- Caretakers must be educated about the consequences and the potentiality of death if adequate replacement therapy is not provided.
- Teach patients and caretakers how to give supplemental glucocorticoid in times of illness or traumatic stress. Also, teach them how to give injectable glucocorticoid when the patient is vomiting or unable to take the stress doses orally. This information must be periodically reinforced because caretakers are often reluctant to give injectable medication.
- Advise family to seek medical help early if the patient becomes ill.
Fujieda K, Tajima T. Molecular basis of adrenal insufficiency. Pediatr Res. 2005 May. 57(5 Pt 2):62R-69R. [Medline].
Ferraz-de-Souza B, Achermann JC. Disorders of adrenal development. Endocr Dev. 2008. 13:19-32. [Medline].
Kempná P, Flück CE. Adrenal gland development and defects. Best Pract Res Clin Endocrinol Metab. 2008 Feb. 22(1):77-93. [Medline].
NCBI. Online Mendelian Inheritance in Man, OMIM (TM). Available at http://www.ncbi.nlm.nih.gov/omim/.
Li N, Liu R, Zhang H, Yang J, Sun S, Zhang M, et al. Seven novel DAX1 mutations with loss of function identified in Chinese patients with congenital adrenal hypoplasia. J Clin Endocrinol Metab. 2010 Sep. 95(9):E104-11. [Medline].
Engiz O, Ozön A, Riepe F, Alikasifoglu A, Gönç N, Kandemir N. Growth hormone deficiency due to traumatic brain injury in a patient with X-linked congenital adrenal hypoplasia. Turk J Pediatr. 2010 May-Jun. 52(3):312-6. [Medline].
Habiby RL, Boepple P, Nachtigall L, et al. Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production. J Clin Invest. 1996 Aug 15. 98(4):1055-62. [Medline].
Achermann JC, Ito M, Ito M, et al. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet. 1999 Jun. 22(2):125-6. [Medline].
Bergada I, Del Rey G, Lapunzina P, et al. Familial occurrence of the IMAGe association: additional clinical variants and a proposed mode of inheritance. J Clin Endocrinol Metab. 2005 Jun. 90(6):3186-90. [Medline]. [Full Text].
McCabe ER. DAX1: Increasing complexity in the roles of this novel nuclear receptor. Mol Cell Endocrinol. 2007 Feb. 265-266:179-82. [Medline].
Lin L, Gu WX, Ozisik G, et al. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) in children and adults with primary adrenal failure: ten years'' experience. J Clin Endocrinol Metab. 2006 May 9. [Medline]. [Full Text].
Manna PR, Dyson MT, Jo Y, Stocco DM. Role of dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1 in protein kinase A- and protein kinase C-mediated regulation of the steroidogenic acute regulatory protein expression in mouse Leydig tumor cells: mechanism of action. Endocrinology. 2009 Jan. 150(1):187-99. [Medline].
Merke DP, Tajima T, Baron J, Cutler GB Jr. Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene. N Engl J Med. 1999 Apr 22. 340(16):1248-52. [Medline].
Peter M, Viemann M, Partsch CJ, Sippell WG. Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. J Clin Endocrinol Metab. 1998 Aug. 83(8):2666-74. [Medline].
Schwarz K, Thwaites R, Minford A, et al. Congenital adrenal hypoplasia presenting as a chronic respiratory condition. Arch Dis Child. 2003 Mar. 88(3):261-2. [Medline].
Reutens AT, Achermann JC, Ito M, et al. Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita. J Clin Endocrinol Metab. 1999 Feb. 84(2):504-11. [Medline].
Kaiserman KB, Nakamoto JM, Geffner ME, McCabe ER. Minipuberty of infancy and adolescent pubertal function in adrenal hypoplasia congenita. J Pediatr. 1998 Aug. 133(2):300-2. [Medline].
Parker KL, Schimmer BP. Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev. 1997 Jun. 18(3):361-77. [Medline].
Lashansky G, Saenger P, Fishman K, et al. Normative data for adrenal steroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropin stimulation. J Clin Endocrinol Metab. 1991 Sep. 73(3):674-86. [Medline].
Heckmann M, Hartmann MF, Kampschulte B, et al. Cortisol production rates in preterm infants in relation to growth and illness: a noninvasive prospective study using gas chromatography-mass spectrometry. J Clin Endocrinol Metab. 2005 Oct. 90(10):5737-42. [Medline].
Kazlauskaite R, Evans AT, Villabona CV, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab. 2008 Nov. 93(11):4245-53. [Medline].
Schurmeyer TH, Avgerinos PC, Gold PW, et al. Human corticotropin-releasing factor in man: pharmacokinetic properties and dose-response of plasma adrenocorticotropin and cortisol secretion. J Clin Endocrinol Metab. 1984 Dec. 59(6):1103-8. [Medline].
Peter M, Partsch CJ, Dorr HG, Sippell WG. Prenatal diagnosis of congenital adrenal hypoplasia. Horm Res. 1996 Jul. 46(1):41-5. [Medline].