Gonadotropin - Dependent Precocious Puberty - Causes, Symptoms, and Treatment

What Is Precocious Puberty?

Puberty refers to the process of change that a body undergoes as it changes into that of an adult. Precocious puberty is when these changes appear far too early - that is, a child’s body begins to undergo pubertal changes while they are still too young. Precocious puberty is of two types:

1. Gonadotropin-releasing hormone (GnRH)–dependent precocious puberty or central precocious puberty.

2. GnRH-independent precocious puberty or peripheral sex hormone effects.

At What Age Is Pubertal Development Considered Precocious?

• Girls: Puberty that begins before the age of 8 years.

• Boys: Puberty that begins before the age of 9 years.

What Is Gonadotropin-Dependent Precocious Puberty?

Precocious puberty that occurs due to the early secretion of hormones called gonadotropins is considered gonadotropin-dependent precocious puberty. Gonadotropins are peptide hormones (hormones made of chains of amino acids, which are small molecules that combine to form proteins) requisites for normal growth and development - specifically sexual development. They are also essential for normal reproductive function. They are secreted by the gonadotropic cells of the anterior pituitary glands and are also made in the placenta. Human gonadotropins include,

1. Pituitary Gonadotropins:

• Follicle-stimulating hormone (FSH).

• Luteinizing hormone (LH).

2. Placental Gonadotropin:

• Human chorionic gonadotropin (hCG).

Who Is Affected by Gonadotropin-Dependent Precocious Puberty?

Both females and males are affected by gonadotropin-dependent precocious puberty. However, it is about 5-10 times more frequent in females than males. Most females and nearly half of the males with precocious puberty present with this type of precocious puberty.

How Does Gonadotropin-Dependent Precocious Puberty Occur?

Gonadotropin-dependent precocious puberty occurs due to the premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. The HPG axis is usually activated during puberty due to estrogen secretion by the ovaries and testosterone secretion by the testes. When the HPG axis is activated, it causes the gonadotropin (FSH and LH) and sex steroid (testosterone and estradiol) levels to increase. This helps regulate reproductive activity and results in physiological and psychological changes. Therefore, early activation of the HPG axis can lead to gonadotropin-dependent precocious puberty. The reasons for early activation of the HPG axis may be:

• Tumor in the hypothalamus.

• Tumor in the pituitary gland.

• Hydrocephalus.

The mechanisms by which the HPG axis may be activated are unclear and not fully understood.

What Are the Causes of Gonadotropin-Dependent Precocious Puberty?

Gonadotropin-dependent precocious puberty may be caused by,

1. Tumors of the Brain or Spinal Cord:

• Germinomas.

2. Non-Cancerous Brain Tumors:

• Hamartomas.

• Adenomas.

3. Illnesses:

• Hypothyroidism.

• Congenital adrenal hyperplasia.

• Neurofibromatosis.

• McCune-Albright syndrome.

4. Brain Defects:

• Hydrocephalus (buildup of excess fluid in the brain).

5. Iatrogenic Causes:

• Surgery.

• Chemotherapy for cancer.

• Radiation therapy of the brain or spinal cord.

6. Injury:

• Injury to the brain.

• Injury to the spinal cord.

What Are the Risk Factors for Gonadotropin-Dependent Precocious Puberty?

Risk factors may include:

• Family history of gonadotropin-dependent precocious puberty.

• Genetic mutations that may predispose to gonadotropin-dependent precocious puberty.

• Gender: Being a girl is a risk factor for precocious puberty.

• Race: African- Americans are most likely to be at risk.

• Obesity: Children who are obese are at greater risk of developing gonadotropin-dependent precocious puberty.

How Does Gonadotropin-Dependent Precocious Puberty Present?

The HPG axis is activated early and leads to:

• Enlargement of the gonads (reproductive organs - testes and ovaries in males and females, respectively).

• Early development of secondary sexual characteristics. Secondary sexual characteristics are sexual characteristics that are not immediately involved in reproduction and are not essential for reproduction. These may include the development of a beard in males and breasts in females, voice changes, changes in muscularity, and fat tissue distribution.

• Spermatogenesis (development, growth, and maturation of sperm cells in males with fertilizing ability).

• Oogenesis (development, growth, and maturation of primary eggs in females with fertilizing ability).

What Are the Signs and Symptoms of Gonadotropin-Dependent Precocious Puberty?

In Girls:

• Development of breasts.

• Development of pubic hair.

• Development of axillary hair.

• Early menstruation (periods).

• Vaginal discharge.

• Body odor.

• Behavioral changes.

• The appearance of acne.

In Boys:

• Growth of the penis.

• Testicular enlargement may occur.

• Development of pubic hair.

• Development of axillary hair.

• Development of facial hair.

• Body odor.

• Behavioral changes.

• The appearance of acne.

How Is Gonadotropin-Dependent Precocious Puberty Diagnosed?

1. Medical and Family History:

• Time of development of pubertal change.

• The extent of development of pubertal change.

• Symptoms such as vision loss and headaches.

2. Physical Examination:

• Development of breasts in girls.

• Enlargement of testicles in boys.

3. X-rays:

An x-ray of the hand and wrist (non-dominant hand) taken to show the bone age will show advanced skeletal maturation compared to the chronological age.

4. Other Tests:

- For Patients With Androgen Effects:

• Total testosterone.

• Luteinizing hormone (LH).

• Dehydroepiandrosterone sulfate.

• 17-hydroxyprogesterone.

- For Patients With Estrogen Effects:

Girls:

• Estradiol.

• Ultrasensitive LH and follicle-stimulating hormone (FSH).

Boys:

• Estradiol.

• FSH.

• LH.

• Beta-human chorionic gonadotropin.

5. Ultrasonography:

• Adrenal ultrasonography.

• Pelvic ultrasonography.

6. Brain MRI (Magnetic Resonance Imaging).

7. GnRH Stimulation Test.

How Is Gonadotropin-Dependent Precocious Puberty Treated?

Treatment is cause-specific. Identifying the cause for the development of gonadotropin-dependent precocious puberty would be essential for treatment. Following this, treatment may include:

• Treatment of underlying tumors.

• Excision of tumors if possible.

• GnRH agonist therapy.

• Hormonal therapy for skeletal maturation and height issues.

What Are the Possible Complications of Gonadotropin-Dependent Precocious Puberty?

1. Height: Initially, affected children may grow faster than their peers and display maturity quite early. They may be taller and more well-developed than others of their age. However, early skeletal maturation also means that they will quickly stop growing - they may be shorter than average as adults.

2. Psychological Issues: Early growth and maturation can be potentially awkward for children whose bodily changes set them apart from their peers. This may result in several psychologically-rooted issues, including:

• Issues of self-esteem.

• Body image issues.

• Anxiety.

• Depression.

Conclusion:

The formative years are the best years of life, but they can also be highly awkward for growing children and teenagers. When precocious puberty is added to the mix, things seem even more unbearable. However, early consultation with a physician and compliance with therapy can revert or avert many potentially embarrassing situations one may face with gonadotropin-dependent precocious puberty.