Please read the previous two entries before reading this one.
Case History Two
You are a busy pediatrician. You are seeing Nancy, a 7-year-old girl who has been followed by you since her birth. She has been generally quite health, with normal growth and development. The clinic visit was prompted by the parents having noticed that their daughter had recently developed breast buds. What should you do?
Just as in case history one I would start out by getting a complete medical history and performing a physical examination. Let’s assume there is no family history of precocious puberty, other than the patient’s mother, and a maternal aunt, who both had their had their first menstrual periods at about age 10 years. Let’s also assume that the physical examination shows bilateral breast buds (Tanner stage 2), pink and dull appearing vaginal mucosa, and scant pubic and axillary hair. Review of her growth chart shows that her height and weight have increased from the 60th percentile a year earlier, to the 80th percentile at the current clinic visit.
So, does this patient have precocious puberty? The answer is yes; remember that by definition, any pubertal changes before age 8 years of age in girls and 9 years of age in boys should be considered precocious puberty, until proven otherwise. We also know that this patient likely has central precocious puberty (CPP), that is, gonadotropin-dependent gonadarche, and in addition, adrenarche. Given the family history, it seems likely that the child has CPP on a genetic basis, but we cannot be certain of that without more information. What should you do? I would probably get a bone age, which I would expect to be somewhat advanced. I would also do a pelvic ultrasound examination. If this is CPP, we would expect to find bilateral ovarian enlargement, and probably both ovaries would contain numerous small cysts. Also, the uterus would be enlarged, i.e., pubertal in size. I would also order some blood work: serum LH and FSH, and serum estradiol. I would expect to find that the LH, FSH, and estradiol levels are in the pubertal range. Those results would confirm that the patient has central precocious puberty. Sometimes, the serum gonadotropins are not in the pubertal range, but you still think the patient might have CPP. In that situation, you would need to do a gonadotropin-releasing hormone stimulation test; at that point, you would probably refer the patient to a pediatric endocrinologist. But, for this discussion, let’s say that the serum LH is clearly in the pubertal range. You still do not know if the CPP is idiopathic/genetic or the result of some central nervous system abnormality, such as a development defect, prior head trauma, or a brain tumor. Prior cranial radiation can also cause CPP, but in this patient, there is no history of such prior treatment
The great majority of children with CPP are female, and most cases are idiopathic or genetic, which would include children with racial or ethnic factors that are associated with early-onset puberty. In addition, CPP is more common in overweight children than in children who are not overweight.
Let us assume that all the laboratory and radiologic studies are consistent with CPP. The next question is what to do about it? If the bone age is advanced several years, you would probably want to consider treating the patient with a gonadotropin-releasing hormone analogue (GnRha), such as leuprolide. The purpose of using a GnRha would be to improve the patient’s adult height potential. Several studies have shown that treating girls with a GnRha after age 8 years does not improve adult height potential (I do not know of similar data in boys). Regardless, in my opinion, before considering treating any child with a GnRha for precocious puberty, I would obtain a head MRI to help rule out a brain tumor or other central nervous system problem as the etiology of the precocious puberty. Where it gets tricky is in a 6 or 7 year old with CPP that does not seem to be progressing (not a rare occurrence), and who has a normal bone age, I might just “sit on my hands” and see where it is going.
I want to mention several other clinical entities you should know about, and which are not classified as CPP, but rather, as gonadotropin-independent precocious puberty. The first is called premature thelarche, and means premature breast development that is not caused by CPP. Typically, this situation is seen in 2-3 year old girls. They show no evidence of adrenarche or growth acceleration, they have normal bone ages, and normal LH, FSH, and estradiol levels. In most instances, the breast enlargement regresses over 6-12 months. I have always thought the condition was probably caused by a small ovarian cyst that produced estrogen for a while, and then popped (a large solitary ovarian cyst would show up on an ultrasound). But, who knows?
The second clinical entity is precocious puberty caused by autonomous ovarian activation. This rare, but frequently talked about entity, is called polyostotic fibrous dysplasia or McCune-Albright syndrome. It is caused by a G-protein abnormality that results in autonomous endocrine gland activation. The condition is not inherited, and can result in hyperthyroidism, excessive growth hormone production, hyperparathyroidism, and precocious puberty. By far the most common presentation is precocious puberty in girls (very rare in boys) which typically presents when the child is age 2-3 years. Children with this condition also have bone cysts and large cafe-au-lait skin lesions. A similar disorder called “testotoxicosis” occurs only in boys, affects only the testes, and like McCune-Albright syndrome, typically presents at age 2-3 years.
The third clinicalentity is exposure to estrogens in creams, ointments, medicinal oils (lavender oil), and by eating products laced with estrogen (back a few years ago, an “epidemic” of breast enlargement in boys and girls was caused by some chicken feeds that contained estrogens).
The fourth clinical entity is a group of tumors, which include Leydig-cell tumors and HCG-secreting germ cell tumors in boys; ovarian cysts and ovarian tumors in girls; and feminizing or virilizing adrenal tumors in girls and boys.
The fifth clinical entity is primary hypothyroidism. One clue to this disorder is that the patient presents with precocious puberty, but no growth spurt.
Last, but not least, is late-onset congenital adrenal hyperplasia, which can masquerade as premature adrenarche.
The question of whether a child has precocious puberty comes up frequently in the primary care setting. Despite some controversy among pediatric endocrinologists on how to define precocious puberty, it is my opinion that we should stick with the conventional definition- under age 8 years in girls, and under age 9-9.5 years in boys.
In most instances, children with precocious puberty will have benign variants of normal, which can be easily investigated by primary care providers. Of course, sometimes it can be something more serious or be a puzzling clinical presentation. That is when we pediatric endocrinologists can help sort things out (at least we hope we can). Usually a bit of detective work will sort things out in short order. If you have questions about the opinions I expressed in this or either of the previous two entries, let me know.