Identifying the Signs of Cortisone Reductase Deficiency

Because Apparent Cortisone Reductase Deficiency (ACRD) is a condition of androgen excess, the signs and symptoms are physical changes driven by these hormones. These signs often appear differently depending on whether the person affected is a growing child or an adult woman ^[1].

Note: While typical symptoms of ACRD develop gradually, a very rapid onset of severe signs—such as a markedly deepening voice, clitoral enlargement, or extreme hair growth over just a few months—warrants immediate medical assessment to rule out androgen-secreting tumors or other urgent conditions ^[2].

Signs in Children

In children, the primary sign of ACRD is premature pubarche—the appearance of pubic or underarm hair before the age of 8 in girls or 9 in boys ^[3][4]. While this can sometimes happen normally (a common condition called premature adrenarche), in ACRD, it is often more pronounced and accompanied by other signs of “speeding up” the body’s development:

• Accelerated Growth: Children with ACRD often experience a rapid increase in height velocity, making them significantly taller than their peers for a period of time ^[5][6].
• Advanced Bone Age: This is a key clue for doctors. While the child is growing tall on the outside, their skeleton may be maturing even faster on the inside. If bone age is significantly advanced (e.g., more than two years ahead of their actual age), it is a sign that a more complex condition like ACRD, nonclassic CAH, or another disorder may be present and warrants further evaluation ^[3][5].
• Skin Changes: Early-onset acne and adult-like body odor may also occur well before the typical start of puberty ^[3][4].

Signs in Adult Females

For adult women, the symptoms of ACRD are often described as hyperandrogenism—physical changes caused by the overproduction of androgens from the adrenal glands ^[1]. These symptoms can vary widely in severity between individuals:

• Hirsutism: This is the growth of coarse, dark hair in areas such as the face (chin/upper lip), chest, or back ^[2][7].
• Menstrual Irregularity: Excess androgens can interfere with the normal cycle of ovulation, leading to oligomenorrhea (infrequent periods) or irregular cycles ^[6].
• Persistent Acne: Severe or cystic acne that continues well past the teenage years can be a sign of the underlying hormone imbalance in ACRD ^[1].
• Thinning Hair: Some women may experience androgenic alopecia, which is thinning of the hair on the scalp ^[7].

Presentations in boys (other than early pubarche), men, and people with atypical gender identities may differ and are less frequently detailed in the published case reports.

Overlooked Signs and Confusion

Because ACRD is so rare, its symptoms are frequently attributed to more common conditions. This can lead to a long journey before the correct diagnosis is found.

• The “PCOS Mimic”: In women, the combination of irregular periods and hair growth is almost always first suspected to be Polycystic Ovary Syndrome (PCOS) ^[2]. While ACRD is primarily an adrenal issue, it is important to know that PCOS can coexist with adrenal disorders. Having polycystic ovaries on an ultrasound does not definitively confirm PCOS or rule out ACRD ^[3].
• The “Premature Adrenarche” Delay: In children, early hair growth is often dismissed as a benign variation of normal development. However, if the bone age is significantly advanced or if growth is exceptionally rapid, it prompts evaluation for nonclassic CAH, exogenous androgen exposure, or rare conditions like ACRD ^[5][4].
• Subtle Clues: Doctors look for the combination of high 17-hydroxyprogesterone (17-OHP) levels and a very specific ratio of cortisol to cortisone metabolites in the urine to help distinguish ACRD from other causes ^[3][8].