Adrenal hyperplasia is a genetic condition affecting the adrenal glands, small organs located above the kidneys. These glands produce important hormones like cortisol (which manages the body’s stress response) and androgens (sex hormones). In individuals with adrenal hyperplasia, a genetic change causes an enzyme deficiency, leading to a hormone imbalance where some hormones are underproduced and others are overproduced. While often diagnosed in infancy, milder forms can appear in adulthood.
Understanding Adrenal Hyperplasia in Adults
Adrenal hyperplasia is an autosomal recessive disorder, meaning a person inherits a mutated gene from each parent. The most common form, 21-hydroxylase deficiency (21-OHD), accounts for about 95% of cases and arises from mutations in the CYP21A2 gene.
The CYP21A2 gene instructs the production of the 21-hydroxylase enzyme, essential for converting 17-hydroxyprogesterone (17-OHP) into cortisol and aldosterone. When this enzyme is deficient, the body cannot produce enough cortisol. This triggers the pituitary gland to release more adrenocorticotropic hormone (ACTH), attempting to stimulate cortisol production.
Elevated ACTH levels cause the adrenal glands to enlarge. Because the 21-hydroxylase enzyme remains deficient, cortisol precursors accumulate and divert into alternative pathways, often resulting in androgen overproduction. While severe forms are identified early, a milder type, Non-Classical Congenital Adrenal Hyperplasia (NCCAH), is often diagnosed in late childhood or adulthood due to less pronounced symptoms at birth.
Recognizing Signs and Effects
Adults with adrenal hyperplasia, particularly NCCAH, often experience symptoms from excess androgen production. In women, these include hirsutism (excessive facial or body hair growth) and acne. Menstrual irregularities, like absent or infrequent periods, are also common, along with fertility difficulties.
Some women with NCCAH may develop features similar to polycystic ovary syndrome (PCOS), which also involves hormone imbalances and can lead to irregular periods and fertility issues. While cortisol deficiency can cause fatigue and low blood pressure in severe cases, these symptoms are typically less pronounced or absent in adults with NCCAH.
In men, androgen excess signs include early balding or low sperm count. If left undiagnosed or untreated, long-term effects for both men and women can include metabolic issues and reduced bone density. Chronic hormone imbalance can also contribute to shorter adult stature due to accelerated bone maturation during childhood.
Diagnosis and Treatment
Diagnosing adrenal hyperplasia in adults typically begins with blood tests measuring specific hormone levels. A high level of 17-hydroxyprogesterone (17-OHP) is a primary indicator of 21-hydroxylase deficiency, the most common form of the condition. Basal 17-OHP levels in unaffected adults are usually below 6 nmol/L.
An ACTH stimulation test often confirms the diagnosis and assesses enzyme deficiency severity. During this test, a blood sample is taken, synthetic ACTH is administered, and then further samples are taken at intervals (typically 30 and 60 minutes) to measure 17-OHP level changes. A stimulated 17-OHP level of 30 nmol/L or higher is consistent with an adrenal hyperplasia diagnosis. Genetic testing can also be used to identify mutations in the CYP21A2 gene, providing definitive diagnosis confirmation.
Treatment for adrenal hyperplasia primarily involves hormone replacement therapy with glucocorticoids like hydrocortisone or prednisone. These medications replace deficient cortisol and suppress excessive androgen production by reducing ACTH levels. While hydrocortisone is often given in divided doses, prednisone or prednisolone may be administered once or twice daily. Treatment goals are to manage symptoms, prevent complications, and improve quality of life, necessitating regular monitoring of hormone levels and clinical presentation.