Brytsev syndrome

Place of the syndrome in the classification of precocious puberty

Precocious puberty (PP) is characterized by an abnormally early start of sex hormone secretion. To understand the nature of Brytsev syndrome, one must review the basic classification of this pathology according to the source of hormonal activity:

1. Gonadotropin-dependent (true) precocious puberty. Occurs due to premature activation of the pituitary gland and release of gonadotropic hormones. This mechanism is identical to normal puberty but is triggered ahead of time. The causes often remain unknown (idiopathic), but neoplastic processes in the hypothalamo-pituitary region must always be ruled out.
2. Gonadotropin-independent precocious puberty. Hormones are secreted by the gonads themselves in an absolutely autonomous manner, without command signals from the pituitary gland. Congenital genetic anomalies, such as testotoxicosis and McCune–Albright–Brytsev syndrome, belong to this group. A similar picture is also observed in tumor lesions of the brain or the gonads themselves.
3. Pseudoprecocious puberty. A condition in which excess sex hormones are provided by adrenal activity or hormone-producing neoplasms. In clinical practice, Brytsev syndrome is also frequently classified as a variant of ovarian-origin pseudoprecocious puberty, since the hypothalamic-pituitary system remains physiologically immature in this condition.

Classical triad and forms of the disease

McCune–Albright–Brytsev syndrome is a rare pathology, the diagnosis of which largely relies on identifying a specific symptom complex. The classical clinical triad includes:

• Pseudoprecocious puberty (autonomous estrogen production).
• Fibrous dysplasia of long bones (the etiology of this component of the disease remains a subject of debate).
• Asymmetric skin pigmentation (characteristic spots).

Depending on the severity of symptoms, two main clinical forms of the syndrome are distinguished:

• Incomplete form. Characterized by accelerated physical development of the patient. However, since the linear growth rate of long bones and the rate of epiphyseal ossification completely match, visually such girls do not differ in height and general body proportions from their healthy peers.
• Complete form. Characterized by a significant acceleration of puberty rates. The leading clinical sign is regular acyclic uterine bleeding occurring against the background of autonomous estrogen stimulation.

Differential diagnosis with other forms of ovarian precocious puberty

Brytsev syndrome must be differentiated from other conditions causing ovarian-origin pseudoprecocious puberty, primarily follicular cysts and hormone-producing tumors (e.g., teratoblastomas).

In ovarian follicular cysts (usually small, about 3–4 cm), the child's somatic development is not accelerated. Symptoms are limited to scanty serosanguineous discharge (menstruation-like) and mild breast enlargement. These manifestations are transient and disappear as the cyst spontaneously regresses within 2–3 months. Surgical intervention is not recommended in such cases.

In hormone-producing tumors, neurological symptoms are absent, and secondary sexual characteristics are poorly developed. A specific differential sign of a tumor process is a gross disruption of the physiological sequence of puberty: spotting or bleeding manifests first, outpacing the development of other sexual characteristics. Unlike cysts, tumors require mandatory surgical removal with histological examination, after which the signs of precocious puberty regress in 1.5–2 months.

Diagnostic Principles

Diagnosing Brytsev syndrome and other forms of precocious puberty requires a comprehensive approach. The diagnosis is formed based on the medical history, evaluation of physical and sexual maturation dynamics, and the results of a gynecological examination.

The mandatory diagnostic minimum includes:

• Pelvic ultrasound (US).
• Determination of basal serum estrogen and gonadotropin levels.

Additional methods (prescribed for strict indications):

• Determination of bone age (biological age based on ossification centers). This is a crucial criterion for assessing final height prognosis.
• Neurophysiological studies: electroencephalography (EEG) and rheoencephalography (REG).
• Brain magnetic resonance imaging (MRI) — critically important when pituitary or hypothalamic space-occupying lesions are suspected.
• Laparoscopy.

Management of patients with suspected Brytsev syndrome necessarily requires interdisciplinary collaboration: an endocrinologist, neurologist, and ophthalmologist are involved in the process. Subsequent therapeutic tactics depend on the identified form of pathology and aim to inhibit excessive puberty.

Class and exam questions

What else to study on this topic

• Gonadotropin-dependent (true) precocious puberty and pituitary tumors
• Ovarian-origin precocious puberty: tumors and cysts
• Heterosexual type of precocious puberty and congenital adrenal hyperplasia (CAH)
• Adrenogenital syndrome (AGS): simple virilizing form
• Constitutional form of precocious puberty and early menarche
• Medical suppression of puberty: use of GnRH analogues

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