What is Peripheral Precocious Puberty?
Precocious puberty is when a child starts developing the physical traits of adults (called secondary sexual characteristics) earlier than expected – before age 8 in girls and age 9 in boys. This early puberty can be either ‘central’ or ‘peripheral’. Central precocious puberty happens when the brain signals the sex organs to work too early. Meanwhile, peripheral precocious puberty happens due to too much production of sex hormones either from the sex organs, glands near the kidneys (called the adrenal glands), or other sources.
The early signs of puberty are said to be ‘isosexual’ if they match the child’s gender; they are considered ‘contrasexual’ if they do not. If peripheral precocious puberty is not treated, it can cause the child to end up shorter as an adult than they might have otherwise been. It can also impact the child’s emotional wellbeing. Thus, spotting and treating this condition early is crucial to prevent these problems.
What Causes Peripheral Precocious Puberty?
In girls, ovarian cysts that function by releasing estrogen can cause early onset puberty, resulting in the premature development of breasts and even vaginal bleeding. Certain ovarian tumors, including granulosa cell tumors, Sertoli/Leydig cell tumors, Leydig cell tumors, and gonadoblastoma, can also lead to early puberty by producing excess amounts of hormones.
Boys can experience early onset puberty through Leydig cell tumors. These tumors often cause an increase in testosterone production, resulting in early puberty and asymmetrical testicle growth. Another cause in boys could be tumors that secrete human chorionic gonadotropin (hCG), a hormone that can stimulate early puberty.
Additionally, some boys might start puberty too early due to a rare condition known as familial male-limited precocious puberty. This condition can lead to early puberty and is usually evident in boys with family histories of early puberty.
Both boys and girls can experience early onset puberty due to primary hypothyroidism, a condition where the thyroid doesn’t produce enough hormones. Girls with this condition might develop breasts early and experience vaginal bleeding, while boys might experience premature testicle growth.
McCune Albright Syndrome is another condition that can cause early onset puberty in girls, with symptoms like breast development, vaginal bleeding, and rapid bone growth. This condition can also cause thyroid problems, Cushing syndrome, gigantism, or acromegaly.
Adrenal conditions like congenital adrenal hyperplasia or adrenal tumors can lead to hormone overproduction, causing early puberty. This can be attributed to a deficiency in enzymes leading to excess androgen production.
Finally, exposure to external sources of hormones or hormone-disrupting chemicals can lead to early puberty in both boys and girls. This can happen from prescribed creams or pills, certain food sources, or even environmental factors like pesticides and plasticizers.
Risk Factors and Frequency for Peripheral Precocious Puberty
Precocious puberty, or early-onset puberty, is generally seen in about 1 in 5,000 to 1 in 10,000 individuals. There are two types of precocious puberty: peripheral and central, with peripheral being less common, accounting for about 23.3% of cases. The prevalence of each type varies depending on the underlying condition. For instance, a rare condition, non-classic congenital adrenal hyperplasia, affects about 0.1% of the global population and is particularly prevalent among Hispanics, Mediterranean people, Eastern European Jews, and Yugoslavs. Another rare condition, McCune Albright syndrome, affects 1 in 100,000 to 1 in 1,000,000 people and is more common in females, while familial male precocious puberty, which only affects males, is also very rare.
Precocious puberty is overall 10 times more prevalent in females than in males. Some specific conditions that cause precocious puberty tend to affect one sex more than the other. McCune Albright syndrome, for instance, is mostly seen in females, while familial male precocious puberty is exclusive to males.
- The traditional age at which puberty is considered “early” is 8 years for girls and 9 years for boys.
- There has been a documented trend, however, indicating that puberty starts earlier in recent times due to various factors such as genetics, obesity, and exposure to certain chemicals.
- Factors like high body mass index, low birth weight, and early-onset puberty in the mother can influence a girl’s onset of puberty.
- There are noticeable race-based variations with African American girls typically hitting puberty earlier than Hispanic and Caucasian girls, in that order.
According to a broad study carried out in San Francisco, New York, and Cincinnati, it was confirmed that indications of puberty like breast development were more common in African American girls (23%), followed by Hispanic girls (15%), and then White girls (10%) in the 7 to 8 age group. Similarly, testicular enlargement in boys occurred about a year earlier in African American boys compared to White and Hispanic boys. Because of these racial differences, the Lawson Wilkins Pediatric Endocrine Society (LWEPS) suggest an evaluation if signs of puberty appear in Caucasian girls before 7 years and in African American girls before 6 years of age.
Signs and Symptoms of Peripheral Precocious Puberty
Precocious puberty, or early puberty, is a medical condition investigated through a thorough history and physical examination. Doctors will first ask about when signs of sexual development began. Typically, testing for early puberty is recommended if puberty signs appear before the age of 8 in girls, or 9 in boys. Doctors will focus on a few things:
- Type of pubertal changes and their rate of progression – growth of pubic and underarm hair, acne, body odor similar to adults, and excessive hair growth might point towards adrenal disorders. Breast development and menstrual bleeding may suggest higher levels of estrogen in the body.
- The speed of puberty signs – rapid puberty progression could indicate a testicular, ovarian, or adrenal tumor.
- Sequence of pubertal changes – an abnormal sequence of puberty symptoms is often linked to peripheral precocious puberty, like McCune-Albright syndrome where menstrual bleeding may occur before breast development.
- Changes in height – patients with peripheral precocious puberty often experience a sudden height increase.
- Neurological symptoms, chronic diseases, and any damage to the central nervous system (through head trauma, asphyxia at birth, tumors, radiation therapy).
- Hormone intake or exposure to topical agents with estrogenic/androgenic/endocrine-disrupting activity.
- Family medical history – onset age of parents’ puberty, ambiguous genitalia in siblings suggesting possible congenital adrenal hyperplasia, and early puberty in male relatives.
The physical examination starts with vital sign measurement. High blood pressure could be a sign of congenital adrenal hyperplasia, while low heart rate might indicate hypothyroidism. Doctors also take a look at the growth parameters—height, weight, and head circumference—and calculate the growth speed.
In the general examination, doctors check for signs that could hint at specific conditions. They look for thyroid enlargement and café au lait spots, hyperpigmented areas of the skin. In McCune Albright syndrome, café-au-lait spots have a “Coast of Maine” appearance, characterized by irregular borders and a segmental distribution. Doctors also look for bony deformities, gait abnormalities, and bone pain that often signal polyostotic fibrous dysplasia. A neurological exam and visual field testing could reveal neurological complications due to an intracranial mass. Doctors may also check the abdomen for any detectable masses due to adrenal or ovarian tumors.
The key part of the exam is grading sexual maturity using the Tanner staging. Sexual maturity rating (SMR) helps assess pubic hair, breast, and genitalia development on a scale from 1 (representing prepuberty) to 5 (representing adult development). In girls, breast development must be carefully evaluated to distinguish normal breast tissue from other less firm tissue. In boys, the size of the testes, penis length, and testicular volume are measured accurately. When penile dimensions seem disproportionately large compared to testicular dimensions, it may indicate early puberty due to adrenal pathology. A moderate symmetric enlargement of testes can signal familial male limited precocious puberty or a tumor secreting human chorionic gonadotropin (HCG). Conversely, testicular enlargement on one side along with a palpable testicular mass might suggest a Leydig cell tumor.
Testing for Peripheral Precocious Puberty
If your doctor suspects that your child might be experiencing precocious puberty, which is the term for early onset puberty, they will order blood tests to measure certain hormone levels and an x-ray of the hand and wrist to examine bone maturity. They might also recommend an ultrasound or CT scan.
Blood tests might include tests for testosterone in boys and estradiol (a type of estrogen) in girls. If these hormone levels are high, but another type of hormone called gonadotropins are low, it can indicate that precocious puberty is not being caused by the brain or pituitary gland, but instead by an issue in the testes, ovaries or adrenal glands. It’s also useful to measure other hormones called luteinizing hormone, follicular stimulating hormone, human chorionic gonadotropin, and various adrenal steroids. These measurements can help to rule out other potential causes of early puberty, such as adrenal tumors or congenital adrenal hyperplasia.
The x-ray of your child’s hand and wrist helps the doctor to see how quickly their bones are maturing. If the bones are more mature than usual for their age, it could suggest that puberty is happening too soon. If the bones are not as mature, it could suggest that the early pubertal signs might be due to something else, like premature adrenarche (the early development of pubic hair).
Ultrasounds or CT scans may be ordered to see if there are any abnormal growths in the ovaries, testes or adrenal glands which might be causing the early puberty. These types of imaging can also provide insight into the amount of estrogen your child has been exposed to, which can also affect how early they begin puberty.
In some specific cases, other tests may be ordered. If your child is having problems with their vision or unusual urinary symptoms, they might need a brain MRI, in order to rule out any issues located there. They might also need tests to look for a condition called fibrous dysplasia, which is related to a syndrome that can cause early puberty. Genetic testing can also be useful in some cases to confirm certain diagnoses that can cause early puberty.
Treatment Options for Peripheral Precocious Puberty
If a child shows signs of developing too early (a condition known as peripheral precocious puberty), it’s essential to see a hormone specialist to avoid potential complications. The treatment aims to address the root cause and control the excessive sex hormones being produced in the child’s body. However, the specific course of treatment will depend on the cause:
– If the early puberty is caused by tumors in the ovary, testis, or adrenal glands, surgery may be needed to remove them. Some tumors may also need additional treatments, like chemotherapy or radiation therapy.
– If a child has functional follicular ovarian cysts (a condition where the ovaries develop cysts leading to early puberty), surgery is rarely required. These cysts tend to disappear on their own over time.
– Primary hypothyroidism (a condition where the thyroid gland doesn’t produce enough hormones) is usually managed with medicine to supplement the missing thyroid hormone.
For children with a condition known as McCune-Albright syndrome, which can cause early puberty, the most researched medications are aromatase inhibitors. These drugs are designed to reduce the production of estrogen, the hormone responsible for maturation during puberty. This could potentially slow down the maturation process, stop menstruation, and decrease the size of the ovaries.
However, different medicines within this group have varied results. For example, letrozole was found to be effective in slowing growth and stopping bone age advancement. On the other hand, medicines such as testolactone, fadrozole, and anastrozole had mixed results. Additionally, the long-term safety of letrozole use is still under investigation.
Certain patients with McCune-Albright syndrome may develop another form of early puberty known as central precocious puberty. In such cases, treatment may include using gonadotropin agonists, medicines that help to control the release of sex hormones.
In male children, a disorder called familial male-limited precocious puberty can trigger early puberty. The standard treatment includes medications to slow bone maturation and delay the onset of puberty. Additionally, a gonadotropin-releasing hormone analog may be prescribed if central precocious puberty occurs. Other drugs used to manage this condition include ketoconazole, bicalutamide, and letrozole.
What else can Peripheral Precocious Puberty be?
Benign pubertal variants are situations of early sexual development during puberty that don’t progress further or cause other problems. Generally, these situations have normal growth rates and aren’t due to any underlying health issues. Often, the only thing needed is reassurance and close monitoring to make sure that sexual development, growth rate, and bone age remain normal.
Common types of benign pubertal variants include:
- Premature thelarche: This is when young girls develop breasts early, usually before 6 to 8 years old, without any other signs of sexual development. The breasts typically don’t grow past a certain point. This differs from peripheral precocious puberty, which involves more signs of sexual development and abnormal growth and bone age.
- Premature pubarche: This situation involves the early growth of pubic and underarm hair before the age of 8 in girls and 9 in boys. This could be accompanied by a slight increase in a hormone called dehydroepiandrosterone sulfate and slightly advanced bone age. This condition needs to be monitored because it could be the first sign of peripheral precocious puberty. If there are signs of masculinization, faster growth, and significantly advanced bone age, doctors should check for more serious conditions like congenital adrenal hyperplasia or virilizing adrenal tumors.
- Benign prepubertal vaginal bleeding: This is when young girls experience vaginal bleeding that stops on its own. The cause of the bleeding needs to be determined and could be sexual abuse, a foreign object, or local trauma. If there are no other signs of sexual development, normal pelvic ultrasound and normal prepubertal hormone levels, this situation differs from precocious puberty, which involves more signs of sexual development.
Central precocious puberty happens when the parts of the brain that regulate sexual development start working too soon. This can be for no known reason, because of genetic factors, or because of lesions in the central nervous system. Unlike peripheral precocious puberty, these patients typically experience the normal sequence of sexual development. They might also experience neurological signs or vision changes. This condition involves increased levels of hormones called follicular stimulating hormone (FSH) and luteinizing hormone (LH). It can be confirmed by a certain LH level in the blood or an increase in LH in response to a GnRH stimulation test.
What to expect with Peripheral Precocious Puberty
The outlook for people with McCune-Albright syndrome can vary greatly. This is based on how severely their bones are affected and how many endocrine system issues they have, such as problems with hormone production. If a person has non-classical congenital adrenal hyperplasia, which is a group of disorders that affect the adrenal glands, their outlook is generally good if treated early with medication that helps control hormone levels (glucocorticoids). However, despite this treatment, many patients may still end up being shorter in height as adults.
The outlook for ovarian granulosa cell tumors, a type of ovarian cancer, depends on how advanced the disease is and whether any of it is still present after treatment. Leydig tumors, which are a rare type of testicular cancer, generally have a good outlook and high rates of being disease-free if the condition hasn’t spread.
However, if the disease has spread beyond the testicles (metastatic disease), the outcome can be poor. Cases of early puberty caused by exposure to hormones outside the body or chemicals that disrupt hormones (endocrine-disrupting chemicals) usually get better on their own once the exposure stops.
Possible Complications When Diagnosed with Peripheral Precocious Puberty
People with early onset puberty, also known as precocious puberty, may face a variety of complications depending on their specific situation:
- In some cases, while children might experience a growth spurt during their early years, the bones may mature and stop growing prematurely, leading to shorter height in adulthood.
- In girls, early growth of breasts, and for boys, an increased sexual drive, may cause emotional distress.
- The hormonal changes that come with early puberty can lead to long term stress, behavioral issues, and mental health problems, including depression.
- In girls, an overproduction of male hormones, causing characteristics like an enlarged clitoris, may require surgery to correct the male-like physical traits.
For patients with McCune Albright syndrome, which is a genetic disease that affects the bones and skin, they may face complications such as:
- Bone issues like pain, deformities, fractures and walking abnormalities
- Overgrowth of certain body parts, overactive thyroid, and Cushing syndrome – a condition caused by an overproduction of a hormone called cortisol
- Other risks include irregular heart rhythms, intestinal growths, and cancer
People with a condition named congenital adrenal hyperplasia may experience fertility issues and complications related to long-term treatment with a medication called glucocorticoids, like:
- Developing features similar to Cushing syndrome
- Slowed growth, fragile bones, secondary diabetes, and suppressed adrenal glands, which produce hormones
- Women with this condition may require a cesarean delivery due to a mismatch between the size of the fetus and the mother’s pelvis
Preventing Peripheral Precocious Puberty
If a child is going through early puberty, which is also known as peripheral precocious puberty, it’s important for them to have emotional and psychological support. This is because the physical changes that come with puberty can sometimes cause emotional upset. Another challenge is that society sometimes treats these children based on their physical maturity rather than their actual age. This can create unrealistic expectations, which can be difficult for them to meet.
As a result, it’s crucial to remind parents and teachers to keep their expectations in line with the child’s actual age, rather than their physical appearance. Additionally, some children who go through early puberty may start participating in risky behaviors, such as using drugs or alcohol, or becoming sexually active, at an earlier age. So, it’s also necessary to provide them with age-appropriate sex education to help them understand the implications of these behaviors.