Meeting Highlights

Early pubertal changes do not necessarily mean precocious puberty

Premature thelarche and premature adrenarche are frequently benign and may not lead to precocious puberty.

ORLANDO, Fla. - Children today are reaching developmental milestones earlier than before but early onset of breast development or early activation of the adrenal gland alone does not necessarily constitute a diagnosis of precocious puberty.

Since 1850, the typical age of onset of menarche in young girls has dropped from 16 to about 12.5 years of age. Several guidelines now set the onset of secondary sexual changes in girls at age 8 (with menarche as early as age 10) and the onset of secondary sexual changes in boys at age 9 years.

Changes prior to these ages, the guidelines say, should cause concern for precocious puberty. However, developmental changes occur across a spectrum and some changes that appear to be happening too early may be benign, according to Gary Francis, MD, PhD, professor and associate chair for research at the Uniformed Services University of the Health Sciences, Bethesda, Md.

Some girls will have breast development prior to age 8 (premature thelarche) that is distinctly different from precocious puberty. Whether or not these patients should cause immediate concern may depend on the age of onset and premature thelarche should not be the only reason for a diagnosis of precocious puberty, according to Francis.

Likewise, some children have early activation of the adrenal gland (premature adrenarche) that may cause early development of axillary hair, said Francis.

Premature development

Sex hormones are present and active at all stages of life, even in the first few years after birth. By about age 2 years until the onset of puberty, gonadotropic surges are actively suppressed by the brain.

At the onset of puberty, the hypothalamic-pituitary-gonadal axis reactivates, spurring production of gonadotropin-releasing hormone, which leads to the release of luteinizing hormones and follicle stimulating hormones.

However, in some children, incomplete inhibition of the hypothalamic-pituitary-gonadal axis leads to the release of hormones earlier than expected, possibly leading to premature thelarche.

“Why does this happen? Probably the hypothalamic-pituitary-axis is more responsive in some children in the first few months of life than it is others,” said Francis.

But premature thelarche may not be a cause for concern if it occurs before 2 years of age. Studies have shown approximately 4% of girls with premature thelarche develop precocious puberty, said Francis, and “96% have isolated breast development.”

“For those with breast development after age 2, it's not the same story. One-third of them will have real precocious puberty, and the first thing you see is the breast development,” said Francis.

Related to race?

Premature thelarche may also be related to race. A study looking at more than 17,000 children and age of pubertal changes found that breast development in black girls might be present as early as age 6 and in white girls as early as age 7. In such cases, if there are no other signs of pubertal development and there is no accelerated growth velocity or bone age, premature thelarche is an appropriate diagnosis, said Francis.

chart

Another finding of that same study was the development of pubic hair, an event related to the activation of the adrenal gland and the start of puberty, may also be related to race. Black children may develop pubic hair as early as age 6 while white children may develop pubic hair as early as age 7.

“Some children are very sensitive to the increase in androgen production and will develop pubic hair but nothing more than that,” said Francis.

Premature adrenarche is associated with modest acceleration in growth velocity or advanced bone age, axillary hair and mild acne, but has not been associated with increased muscle mass or clitoral or phallic enlargement.

A subset of girls with premature adrenarche have a condition known as non-classical congenital adrenal hyperplasia, which can lead to advanced bone age and clitoromegaly. The syndrome is a genetic disorder and predominates among Eskimo, black, Jewish and Hispanic children.

Premature adrenarche may also be related to intrauterine growth retardation, as hyperinsulinism is another cause of increased androgen production. Premature adrenarche is also a risk factor in developing polycystic ovarian syndrome, said Francis.

Precocious puberty

Established guidelines on precocious puberty state that any secondary sexual change in girls prior to age 8 (menarche prior to age 10) or onset of secondary sexual changes in boys prior to age 9 is precocious puberty. But those guidelines may be too restrictive as some developmental changes prior to the appropriate age turn out to be benign, according to Francis.

Instead, he said, the presence of more than one sign of puberty before the appropriate age is a cause for concern. What may look like precocious puberty may be McCune Albright syndrome, growth hormone deficiency, hyperthyroidism or hyperinsulinism.

Precocious puberty can be either gonadotropin dependent or gonadotropin independent. Gonadotropin dependent precocious puberty is frequently idiopathic, but not in boys. “Boys get precocious puberty, but it's almost never benign,” said Francis.

Central nervous system malformation is common and imaging is required if gonadotropin-dependent precocious puberty is suspected. Testing for gonadotropin levels and performing an ultrasound is also recommended, said Francis.

If, however, gonadotropin is suppressed, “you should look for bony abnormalities, café-au-lait spots, family history and look at the adrenals for tumors” if gonadotropin-independent precocious puberty is suspected, according to Francis. – by Bryan Bechtel

For more information:
  • Francis G. Precocious puberty: new guidelines in age and evaluation. Presented at the AAP CME Orlando. March 13-15, 2003. Orlando, Fla..

ORLANDO, Fla. - Children today are reaching developmental milestones earlier than before but early onset of breast development or early activation of the adrenal gland alone does not necessarily constitute a diagnosis of precocious puberty.

Since 1850, the typical age of onset of menarche in young girls has dropped from 16 to about 12.5 years of age. Several guidelines now set the onset of secondary sexual changes in girls at age 8 (with menarche as early as age 10) and the onset of secondary sexual changes in boys at age 9 years.

Changes prior to these ages, the guidelines say, should cause concern for precocious puberty. However, developmental changes occur across a spectrum and some changes that appear to be happening too early may be benign, according to Gary Francis, MD, PhD, professor and associate chair for research at the Uniformed Services University of the Health Sciences, Bethesda, Md.

Some girls will have breast development prior to age 8 (premature thelarche) that is distinctly different from precocious puberty. Whether or not these patients should cause immediate concern may depend on the age of onset and premature thelarche should not be the only reason for a diagnosis of precocious puberty, according to Francis.

Likewise, some children have early activation of the adrenal gland (premature adrenarche) that may cause early development of axillary hair, said Francis.

Premature development

Sex hormones are present and active at all stages of life, even in the first few years after birth. By about age 2 years until the onset of puberty, gonadotropic surges are actively suppressed by the brain.

At the onset of puberty, the hypothalamic-pituitary-gonadal axis reactivates, spurring production of gonadotropin-releasing hormone, which leads to the release of luteinizing hormones and follicle stimulating hormones.

However, in some children, incomplete inhibition of the hypothalamic-pituitary-gonadal axis leads to the release of hormones earlier than expected, possibly leading to premature thelarche.

“Why does this happen? Probably the hypothalamic-pituitary-axis is more responsive in some children in the first few months of life than it is others,” said Francis.

But premature thelarche may not be a cause for concern if it occurs before 2 years of age. Studies have shown approximately 4% of girls with premature thelarche develop precocious puberty, said Francis, and “96% have isolated breast development.”

“For those with breast development after age 2, it's not the same story. One-third of them will have real precocious puberty, and the first thing you see is the breast development,” said Francis.

Related to race?

Premature thelarche may also be related to race. A study looking at more than 17,000 children and age of pubertal changes found that breast development in black girls might be present as early as age 6 and in white girls as early as age 7. In such cases, if there are no other signs of pubertal development and there is no accelerated growth velocity or bone age, premature thelarche is an appropriate diagnosis, said Francis.

chart

Another finding of that same study was the development of pubic hair, an event related to the activation of the adrenal gland and the start of puberty, may also be related to race. Black children may develop pubic hair as early as age 6 while white children may develop pubic hair as early as age 7.

“Some children are very sensitive to the increase in androgen production and will develop pubic hair but nothing more than that,” said Francis.

Premature adrenarche is associated with modest acceleration in growth velocity or advanced bone age, axillary hair and mild acne, but has not been associated with increased muscle mass or clitoral or phallic enlargement.

A subset of girls with premature adrenarche have a condition known as non-classical congenital adrenal hyperplasia, which can lead to advanced bone age and clitoromegaly. The syndrome is a genetic disorder and predominates among Eskimo, black, Jewish and Hispanic children.

Premature adrenarche may also be related to intrauterine growth retardation, as hyperinsulinism is another cause of increased androgen production. Premature adrenarche is also a risk factor in developing polycystic ovarian syndrome, said Francis.

Precocious puberty

Established guidelines on precocious puberty state that any secondary sexual change in girls prior to age 8 (menarche prior to age 10) or onset of secondary sexual changes in boys prior to age 9 is precocious puberty. But those guidelines may be too restrictive as some developmental changes prior to the appropriate age turn out to be benign, according to Francis.

Instead, he said, the presence of more than one sign of puberty before the appropriate age is a cause for concern. What may look like precocious puberty may be McCune Albright syndrome, growth hormone deficiency, hyperthyroidism or hyperinsulinism.

Precocious puberty can be either gonadotropin dependent or gonadotropin independent. Gonadotropin dependent precocious puberty is frequently idiopathic, but not in boys. “Boys get precocious puberty, but it's almost never benign,” said Francis.

Central nervous system malformation is common and imaging is required if gonadotropin-dependent precocious puberty is suspected. Testing for gonadotropin levels and performing an ultrasound is also recommended, said Francis.

If, however, gonadotropin is suppressed, “you should look for bony abnormalities, café-au-lait spots, family history and look at the adrenals for tumors” if gonadotropin-independent precocious puberty is suspected, according to Francis. – by Bryan Bechtel

For more information:
  • Francis G. Precocious puberty: new guidelines in age and evaluation. Presented at the AAP CME Orlando. March 13-15, 2003. Orlando, Fla..