Persistent adrenarche syndrome

Overview

Persistent adrenarche syndrome is a clinical condition characterized by the prolonged presence of signs of adrenarche—such as body odor, acne, oily skin, and pubic or axillary hair—without progression to true central puberty. Adrenarche is a normal developmental phase that typically begins between ages 6 and 8 in girls and slightly later in boys, involving the maturation of the adrenal glands and increased production of adrenal androgens, particularly dehydroepiandrosterone sulfate (DHEAS). In some children, these signs persist beyond the expected age range without the emergence of puberty-related changes like breast development or testicular enlargement. Persistent adrenarche may raise concerns about underlying endocrine disorders, future metabolic risks, or psychosocial impact, and often requires clinical evaluation to differentiate it from other conditions like premature adrenarche, precocious puberty, or androgen-secreting tumors.

Causes

Persistent adrenarche syndrome results from continued adrenal androgen production beyond the expected timeframe, typically without central (hypothalamic-pituitary-gonadal axis) activation. The exact cause is not fully understood, but several factors may contribute:

• Constitutional variation: Some children naturally have a prolonged adrenarche phase without progression to puberty

• Increased adrenal sensitivity: Overactivity or hypersensitivity of the adrenal zona reticularis

• Genetic predisposition: Familial patterns are often observed

• Low birth weight or intrauterine growth restriction (IUGR): Associated with early and possibly persistent adrenarche

• Obesity and insulin resistance: May enhance adrenal androgen production and prolong symptoms

In some cases, persistent adrenarche may be a benign variant, but in others, it could indicate an early marker of metabolic syndrome or polycystic ovary syndrome (PCOS) in girls, particularly when accompanied by features like insulin resistance or menstrual irregularity during adolescence.

Symptoms

The clinical features of persistent adrenarche overlap with those of early or premature adrenarche but are noted for their persistence over several years without the onset of central puberty. Common symptoms include:

• Pubic hair (pubarche) and/or axillary hair (axillarche): Present without other pubertal signs

• Body odor: Due to apocrine gland activation

• Oily skin and mild acne: Particularly on the face and back

• Mild hirsutism: In girls, excessive or male-pattern hair growth may occur

• Normal or delayed growth acceleration: Unlike central puberty, no significant height velocity increase

Importantly, there are no signs of gonadal or central pubertal activation, such as breast development in girls (thelarche) or testicular enlargement in boys (gonadarche).

Diagnosis

The diagnosis of persistent adrenarche syndrome is based on clinical evaluation, hormonal profiling, and imaging to exclude other conditions. A detailed history and physical examination are essential to distinguish this condition from other causes of early androgenization.

Diagnostic Steps:

• Clinical assessment: Evaluation of pubertal staging using Tanner scale

• Hormonal testing:

  • Elevated DHEAS levels (marker of adrenal androgen activity)

  • Normal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol/testosterone levels (indicating absence of central puberty)

• Bone age assessment: X-ray of the left hand and wrist may show slight advancement, but usually less than seen in true precocious puberty

• GnRH stimulation test: Helps differentiate between central precocious puberty and isolated adrenarche by assessing LH/FSH response

• Pelvic ultrasound (in girls): Used to assess ovarian and uterine development if puberty is suspected

Additional testing may be needed to rule out conditions like non-classic congenital adrenal hyperplasia (NCCAH) or androgen-secreting tumors if symptoms are severe or rapidly progressive.

Treatment

There is no specific treatment required for benign persistent adrenarche, especially if the child is otherwise healthy and developing normally. However, management focuses on monitoring growth, pubertal progression, and addressing any metabolic concerns or psychosocial issues.

Monitoring and Supportive Measures:

• Regular follow-up: Every 6–12 months to monitor for onset of puberty and changes in symptoms

• Skin care: Over-the-counter acne treatments or dermatologist referral for persistent acne

• Weight management: Nutritional counseling and physical activity for overweight children

• Psychological support: For body image or social anxiety related to early physical changes

When Medical Treatment Is Considered:

• If symptoms are severe or progressive

• If there are features suggestive of metabolic syndrome (e.g., insulin resistance, obesity)

• In adolescent girls with features of PCOS, where hormonal therapy may be required

Hormonal therapy, such as low-dose antiandrogens or oral contraceptives, may be considered in older adolescents with persistent symptoms and risk of PCOS under specialist care.

Prognosis

The prognosis for children with persistent adrenarche syndrome is generally good, especially when no underlying endocrine disorder is present. Most children will eventually enter normal puberty, and the androgenic symptoms often stabilize or resolve as hormonal regulation matures. However, persistent adrenarche may be an early risk factor for developing metabolic syndrome or PCOS later in life, particularly in girls with obesity or a family history of endocrine disorders.

With careful monitoring and supportive care, long-term health outcomes are usually favorable. Early identification and management of associated metabolic risks can further improve prognosis and quality of life for affected individuals.