Estimated reading time: 7 minutes
Medically reviewed and verified by Kate Burke, MD, MHA
When it comes to genetic disorders, you can run across a number of complicated terms. Understanding how these conditions affect the body is important, but you can't do that without first understanding the forces at play behind the disease. For those living with congenital adrenal hyperplasia (CAH), you may have heard the term "17-Hydroxylase deficiency" before. This is a rare genetic condition that can lead to a form of CAH. First, we will need to break down a few key terms: "congenital adrenal hyperplasia," "17-hydroxylase (17-OHP)," and "hormone production." PatientsLikeMe will guide you through the basics, explaining how it impacts the body, how it leads to CAH, and what that means for those affected.
The Basics
What Is CAH?
Congenital adrenal hyperplasia is a group of genetic conditions that affect the adrenal glands, small organs located above the kidneys. These glands produce hormones like cortisol, aldosterone, and androgens. In CAH, there is a deficiency in one of the enzymes required to make these hormones. CAH is an autosomal recessive disorder, meaning that a person needs to inherit two copies of the gene, one from each parent, for the condition to show up. The most common form of CAH is due to a deficiency in the 21-hydroxylase (21-OH) enzyme, but 17-OHP deficiency, while much rarer, also leads to CAH.
17-Hydroxylase and Hormone Production
17-Hydroxylase is an enzyme involved in making several hormones. It helps convert precursor molecules into cortisol and sex hormones like testosterone and estrogen. This enzyme is also tied to 17,20-lyase activity, which helps produce these hormones. When 17-hydroxylase or 17,20-lyase1 is missing or non-functional because of mutations in the CYP17A1 gene, the body cannot make enough cortisol or sex hormones. This imbalance causes problems with normal body functions, including blood pressure regulation and sexual development.
17-Hydroxylase Deficiency
In the case of 17-hydroxylase deficiency2, the body is unable to properly make cortisol and sex hormones. However, it overproduces other hormones like aldosterone. This affects the balance of salt and water in the body. Over time this can lead to several major issues.
- Cortisol Deficiency: Cortisol is the "stress hormone" that helps regulate metabolism, blood sugar, and your immune response. In CAH, your body cannot produce3 cortisol naturally. It sends signals to your adrenal glands trying to stimulate their production, but this results in a blockage of the normal steroid production.
- Excess Aldosterone: Aldosterone is a hormone that helps control blood pressure by regulating salt and water levels in the body. When, it causes high blood pressure (hypertension) and low potassium levels (hypokalemia).
- Sex Hormones: In CAH, the body produces too many androgens. As a result, sexual development is heavily affected4. It can lead to delayed puberty or ambiguous genitalia, especially in those with XY chromosomes.
Acne? CAH Symptom. Gaining weight? Side effect. It can be tough to tell apart symptoms of congenital adrenal hyperplasia (CAH) and treatment side effects of steroids apart.
Watch now: Is it a symptom or a side effect?
Your body may feel out of whack when living with CAH. Too little cortisol can make you feel tired or unwell and high androgen levels can cause early puberty, premature growth, and more. Treating CAH with high-dose steroids can cause side effects like weight gain, diabetes, and bone density issues. See why it’s important to talk to your doctor about what you’re experiencing and your treatment plan.
Questions about CAH symptoms and/or side effects from high-dose steroids? Visit: WhatTheCAH to learn more.
Sponsored by Neurocrine Biosciences, Inc.
How Does 17-Hydroxylase Deficiency Lead to CAH?
The connection between 17-hydroxylase deficiency and CAH is in how the adrenal glands react when they can’t make enough cortisol. Normally, the pituitary gland5 releases ACTH to signal the adrenal glands to produce cortisol. However, when the adrenal glands cannot do so because of a 17-hydroxylase deficiency, the pituitary gland continues making androgens. Over time this leads to an overgrowth (or hyperplasia) of the adrenal tissue. This overgrowth is what gives CAH its name: congenital adrenal hyperplasia.
Signs and Symptoms
The symptoms of 17-hydroxylase deficiency change depending on each person's sex chromosomes and the severity of the enzyme deficiency. Here are the most common ways it presents.
In Genetic Females
Females with 17-hydroxylase deficiency often experience delayed puberty6. This might mean an absence of menstruation and a lack of secondary sexual characteristics like breast development and pubic hair. High blood pressure and low potassium levels are also common. Girls can develop ambiguous genitalia, and their internal reproductive organs may be underdeveloped.
In Genetic Males
Like females, males will have delayed puberty and may not develop typical male secondary sexual characteristics like facial hair or a deeper voice. As with females, high blood pressure7 and low potassium levels are common.
Diagnosis and Treatment
Doctors diagnose 17-hydroxylase deficiency with blood tests for hormone levels. A key sign of this deficiency is a low level of cortisol and sex hormones, along with elevated ACTH and aldosterone levels. Genetic testing for mutations in the CYP17A1 gene can confirm the diagnosis. Fortunately, with proper treatment, people with 17-hydroxylase deficiency can lead normal lives. Treatment8 typically involves hormone replacement therapies to correct the deficiencies and manage symptoms.
- Glucocorticoid Therapy: Medications like hydrocortisone or dexamethasone are used to replace cortisol and suppress the excess ACTH and androgen production.
- Sex Hormone Replacement: People may need estrogen or testosterone therapy to promote secondary sexual characteristics and normal puberty.
- Blood Pressure Management: For those with hypertension because of too much aldosterone, medications like spironolactone may be prescribed to help manage blood pressure and potassium levels.
- Surgical Intervention: In some cases, surgery may be needed to correct ambiguous genitalia or remove undescended testes.
With consistent hormone replacement and management, most people with 17-hydroxylase deficiency can live healthy lives. However, many people struggle with fertility issues. Due to the lack of normal sex hormone production, fertility may be a concern, particularly in genetic males who often lack functional testes. People with ambiguous genitalia or delayed puberty may face psychological or social challenges. Counseling and support can help!
17-Hydroxylase deficiency is a rare but manageable cause of CAH. By understanding the hormone imbalances it causes, we can see how this enzyme deficiency affects everything from blood pressure regulation to sexual development. With proper diagnosis and treatment, people with this condition can manage their symptoms effectively and improve their quality of life. With ongoing medical advances and supportive care, people with 17-hydroxylase deficiency can get a better understanding of their health and well-being.
PatientsLikeMe puts you in control of your health, providing you the tools and community support you need to manage your wellness journey effectively. Join others who share their experiences and insights, offering you invaluable advice and encouragement. Track your symptoms, treatments, and outcomes with ease, enabling you to make informed decisions about your health and communicate better with your healthcare team. Moreover, evaluate the effectiveness of treatments based on comprehensive patient data, helping you choose the best options for your health. Embrace a proactive approach to your well-being with PatientsLikeMe.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4976049/
- https://www.ncbi.nlm.nih.gov/books/NBK546644/
- https://www.yourhormones.info/endocrine-conditions/congenital-adrenal-hyperplasia/
- https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.770782/full
- https://my.clevelandclinic.org/health/articles/23151-adrenocorticotropic-hormone-acth
- https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-019-2166-9
- https://medlineplus.gov/genetics/condition/17-alpha-hydroxylase-17-20-lyase-deficiency/#:~:text=Hormone%20imbalances%20lead%20to%20the,severity%20of%20the%20features%20varies.
- https://pubmed.ncbi.nlm.nih.gov/8481334/