Hypothalamic prepubertal hypogonadism: causes, symptoms, diagnosis, treatment

Hypothalamic prepubertal hypogonadism may be observed in the absence of organic changes in the hypothalamic region. In this case, a congenital, possibly hereditary nature of the pathology is assumed. It is also observed in structural lesions of the hypothalamus and pituitary stalk in craniopharyngiomas, internal hydrocephalus, neoplastic processes of various types, including leukemia, granuloma (eosinophilic granuloma, histiocytosis-X, sarcoidosis, tuberculosis), encephalitis, microcephaly, Friedreich's ataxia, demyelinating diseases.

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Causes hypothalamic prepubertal hypogonadism.

This condition can be caused by a variety of reasons, including:

1. Genetic factors: Certain genetic mutations or syndromes can result in underdevelopment of the hypothalamus or pituitary gland, which can cause hypogonadotropic hypogonadism.
2. Trauma and surgery: Trauma or surgery to the head, including brain trauma, can damage the hypothalamus or pituitary gland, which can affect the regulation of gonadal function.
3. Obesity: Obesity can decrease the sensitivity of the hypothalamus to gonadotropic hormones, which can lead to hypogonadotropic hypogonadism.
4. Chronic diseases: Certain chronic diseases, such as celiac disease and polycystic ovary syndrome in women, can affect gonadal function and cause hypogonadotropic hypogonadism.
5. Emotional stress: Severe emotional stress or depression can affect the functioning of the hypothalamus and pituitary gland, which can lead to hypogonadotropic hypogonadism.
6. Drug treatment: Some drugs, such as opioids or some antidepressants, can affect the function of the hypothalamus and pituitary gland and cause hypogonadotropic hypogonadism.
7. Other factors: Age, hormonal changes, autoimmune disorders, and other factors may also play a role in the development of hypothalamic prepubertal hypogonadism.

Pathogenesis

There is a dysfunction of the pituitary gland and sex glands due to insufficiency or impaired secretion of the LH-releasing factor.

Symptoms hypothalamic prepubertal hypogonadism.

Pathology is not observed until the age of 5-6 years. By the age of 6-7 years, boys are found to have small scrotum and testicles, penis. Cryptorchidism is often detected. Attention is drawn to the "eunuchoid tall stature", muscle weakness, asthenic physique, specific changes in the teeth (large medial incisors of a spatulate shape, lateral incisors are poorly developed, canines are short and blunt). Dry soft skin with pale pigmentation is noted. Acne is never observed in adolescents. Very lush hair on the head is combined with the absence of hairiness of the skin. Gynecomastia develops later. Boys are usually withdrawn, easily hurt, and behavior typical of girls is often observed.

Prepubertal hypothalamic hypogonadism in girls is manifested by the absence of normal sexual maturation, primary amenorrhea. Eunuchoid body proportions, skin with many acne, absence of skin hair with lush hair on the head, often vitiligo, underdevelopment of the external genitalia, mammary glands, infantile proportions of the uterus are noted. Mental development is within normal limits. Girls are distinguished by a feeling of inferiority, shyness, compliant character, easy touchiness, tearfulness.

Diagnostics hypothalamic prepubertal hypogonadism.

Diagnosing hypothalamic prepubertal hypogonadism can be challenging and requires a multidisciplinary approach. Here are some of the main methods and steps used to diagnose this condition:

1. Clinical assessment and history taking:

   • The doctor conducts a conversation with the patient and his parents (in the case of children and adolescents) to identify symptoms associated with delayed puberty.
   • Information is collected about growth, development of secondary sexual characteristics (such as breast development in girls or scrotal enlargement in boys), and other signs.

2. Exclusion of other causes:

   • Additional tests and examinations may be performed to rule out other medical conditions that may cause similar symptoms.

3. Measuring hormone levels:

   • Blood tests for levels of hormones such as gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and testosterone may be done to assess gonadal function.

4. Brain image:

   • Magnetic resonance imaging (MRI) of the brain may be performed to rule out abnormalities or tumors in the hypothalamus and pituitary gland.

5. Gonadotropic stimulation:

   • Gonadotropic stimulation tests are sometimes used to assess the response of the gonads to hormonal stimulation.

6. Genetic testing:

   • In some cases, genetic testing may be needed to identify genetic disorders that may be associated with hypothalamic prepubertal hypogonadism.

Differential diagnosis

Hypothalamic hypogonadism in the prepubertal period should be differentiated from Babinski-Frohlich disease, pituitary dwarfism in the context of Lauren-Lewy infantilism, from forms of hypothalamic obesity with hypogonadism, Laurence-Moon-Bardet-Biedl, Prader-Willi syndromes, primary hypopituitarism, from forms with primary testicular damage in boys, Turner syndrome in girls. Obesity, short stature, congenital defects, retinitis pigmentosa, mental retardation allow us to exclude the diagnosis of prepubertal hypogonadism.

The gonadotropin response to a single injection of LH-releasing factor (LH-RF) is markedly impaired or absent, indicating insufficient previous (endogenous) stimulation by LH-RF. If repeated administration of LH-RF causes a "release" of gonadotropins and a normal or even excessive response is observed, the diagnosis of primary hypopituitarism is excluded and, conversely, the diagnosis of prepubertal hypogonadism is confirmed. In boys, a differential diagnosis should also be made with Kallmann syndrome (olfactory-genital dysplasia), in which the symptoms of prepubertal hypothalamic hypogonadism are combined with ano- or hyposmia, color blindness, and deafness.

Treatment hypothalamic prepubertal hypogonadism.

Sex steroids are used to ensure the development and maintenance of secondary sexual characteristics. A treatment method using LH-releasing factor analogues is currently under development.