Summary about Disease
17-alpha-hydroxylase deficiency is a rare genetic disorder affecting the adrenal glands and gonads. It disrupts the production of several crucial steroid hormones, including cortisol and sex hormones (androgens and estrogens). This leads to a buildup of mineralocorticoids (like aldosterone) and a deficiency in sex hormones and cortisol. There are two forms of the condition, classic and non-classic.
Symptoms
Females (46,XX):
Lack of puberty
Primary amenorrhea (failure to start menstruation)
Absent or underdeveloped secondary sexual characteristics
High blood pressure (hypertension)
Low potassium levels (hypokalemia)
Fluid retention
Males (46,XY):
Ambiguous genitalia at birth or female external genitalia.
Undescended testes
Lack of puberty
High blood pressure (hypertension)
Low potassium levels (hypokalemia)
Fluid retention
Causes
The disease is caused by mutations in the CYP17A1 gene. This gene provides instructions for making the 17-alpha-hydroxylase enzyme, which is essential for the production of cortisol and sex hormones in the adrenal glands and gonads. The gene is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Glucocorticoid Replacement: Hydrocortisone or prednisone is used to replace the deficient cortisol and suppress excess ACTH production.
Mineralocorticoid Antagonists: Spironolactone or eplerenone is used to block the effects of excess mineralocorticoids, managing hypertension and hypokalemia.
Sex Hormone Replacement: Estrogen and progesterone replacement therapy may be used in females to induce puberty and menstruation and maintain bone density. Testosterone replacement therapy may be necessary for males after gonadectomy (removal of the gonads).
Is Communicable
No. 17-alpha-hydroxylase deficiency is a genetic disorder and is not contagious or communicable.
Precautions
Genetic Counseling: For families with a history of the disorder, genetic counseling is important to assess the risk of having an affected child.
Monitoring: Regular monitoring of blood pressure, potassium levels, and hormone levels is necessary to adjust medication dosages.
Adrenal Crisis Prevention: Patients need to be educated about the signs and symptoms of adrenal crisis (caused by cortisol deficiency) and how to manage it, especially during times of stress, illness, or surgery.
Medical Alert: Individuals with this deficiency should wear a medical alert bracelet or carry identification indicating their condition and the need for glucocorticoid replacement in emergencies.
How long does an outbreak last?
This is not an outbreak type of illness. It is a chronic condition. The symptoms, without treatment, will persist indefinitely.
How is it diagnosed?
Hormone Testing: Blood tests to measure levels of cortisol, ACTH, aldosterone, renin, and sex hormones (androgens, estrogens). Characteristic findings include low cortisol and sex hormone levels, high aldosterone and renin levels.
Genetic Testing: Sequencing of the CYP17A1 gene to identify mutations.
Karyotype: Chromosomal analysis to confirm the sex chromosomes (46,XX or 46,XY).
Imaging Studies: Pelvic ultrasound in females to evaluate the presence of a uterus and ovaries.
Timeline of Symptoms
Prenatal/Infancy (Males): Ambiguous genitalia may be apparent at birth.
Childhood: Hypertension and hypokalemia may develop.
Adolescence: Failure to undergo puberty is a key feature. Females will not menstruate, and both sexes will lack development of secondary sexual characteristics without treatment.
Important Considerations
Gender Assignment: In males with ambiguous genitalia, gender assignment decisions require careful consideration and discussion with a multidisciplinary team (endocrinologists, surgeons, geneticists, psychologists).
Gonadectomy: Due to the risk of gonadal tumors, gonadectomy (removal of the gonads) may be recommended for males, typically after puberty if male gender is assigned, or earlier if female gender is assigned.
Psychological Support: The challenges of ambiguous genitalia, delayed puberty, and chronic medical management can have significant psychological impact. Counseling and support groups are beneficial.
Long-term Management: Lifelong hormone replacement therapy and monitoring are essential.
Fertility: Affected individuals are typically infertile.