Precocious Puberty

Tolle Causam
Tamara Cullen, ND

It’s not just your imagination; kids are growing up faster these days. From the clothing styles to the attitudes, kids sometimes seem like little adults at the youngest of ages. Yes, some of this has to do with a change in parenting styles and expectations of children, but how do we as physicians know when to further evaluate a child who is developing too quickly? We must not only know the normal course of development through puberty, with appropriate ages and tanner staging, but also how to differentiate a possible cause of early development. Finally, we need to know how to initiate treatment and when to refer to a pediatric endocrinologist.

How Do We Define Precocious Puberty?

The mean age of onset of secondary sexual characteristics is 10.5 years in girls and 11.5 years in boys.1 Menarche is girls typically begins 2 years after the onset of puberty. Precocious puberty is usually defined as the onset of secondary sexual development before the age of 8 years in girls and 9 years in boys. However, detailed evaluation is typically only pursued for Caucasian girls who have breast and/or pubic hair development before 7 years of age, and African-American girls before 6 years of age.2 That being said, girls between the ages of 7 and 8 years should be minimally evaluated with a comprehensive history and PE.

Classifications of Precocious Puberty

Precocious puberty may be caused by a process occurring either centrally (gonadotropin-dependent precocious puberty, or GDPP) or peripherally (gonadotropin-independent precocious puberty, or GIPP).

GDPP is idiopathic in 80% of cases, occurs 10 to 20 times more often in girls, and demonstrates isosexual characteristics.3 In addition, you will see accelerated linear growth for age, advanced bone ages, and pubertal levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Additionally, you will see pubertal levels of estradiol in girls and testosterone in boys.4

As GDPP may be caused by lesions of the central nervous system (CNS), a contrast-enhanced MRI must be performed, even in the absence of any neurologic abnormalities.5 Types of CNS lesions seen include: hamartomas, astrocytomas, ependymomas, pinealomas, and optic and hypothalamic gliomas, CNS irradiation associated with growth hormone deficiency, hydrocephalus, cysts, trauma, CNS inflammatory disease, and congenital mid-line defects, such as optic nerve hypoplasia.6

Non-CNS causes can include: genetics, previous excess steroid exposure, and primary hypothyroidism.

GIPP, sometimes called “pseudo-precocious puberty,” involves excess secretion of sex hormones (estrogens or androgens) derived either from the gonads or adrenal glands, exogenous sources of sex steroids, or ectopic production of gonadotropin from a germ cell tumor (eg, hCG). Clinically, you may see isosexual or contrasexual effects.

In girls, GIPP may be caused by ovarian cysts (large, functioning follicular cyst of the ovaries is the most common cause) or ovarian tumors (rare).

In boys with isosexual symptoms, GIPP may be caused by a Leydig cell tumor (should be considered in any boy with asymmetric testicular enlargement) or an HCG-secreting germ-cell tumor (results in increased testosterone secretion).

In both boys and girls there are various causes of GIPP, including: exposure to exogenous estrogens (creams, phthalates, food sources, lavender and tea tree oils),7 adrenal pathology (tumors and congenital adrenal hyperplasia), pituitary gonadotropin-secreting tumors (extremely rare, associated with elevated levels of FSH and/or LH), and McCune-Albright syndrome (a rare disorder defined as the triad of peripheral precocious puberty, café-au-lait skin pigmentation, and fibrous dysplasia of bone).

Incomplete precocious puberty (Incomplete PP) can be seen as either an isolated premature thelarche or premature adrenarche.

Most cases of premature thelarche are idiopathic and occur in two peaks: one during the first 2 years of life and the other at 6 to 8 years of age. Typically, they either remit spontaneously or progress very slowly, with no other signs of pubertal development and normal growth rate. Serum estradiol levels are typically in the prepubertal range. Cases can progress to true isosexual precocious puberty in 14 to 20% of cases.8

Premature adrenarche is characterized by the appearance of pubic and/or axillary hair prior to the age of 8 years in girls and 9 years in boys. It is more common in girls (especially African-American), and individuals with obesity and insulin resistance. It is considered a variant of normal development but is also a risk factor for polycystic ovarian syndrome (PCOS) in girls. You will see an elevated serum DHEA-sulfate, but 17-hydroxyprogesterone and testosterone are in their age-appropriate normal ranges. A bone age should be determined, and if this is normal or only slightly advanced, no other tests are usually required and you can monitor over time.

How Do We Begin to Determine Cause of Precocious Puberty?

1. Look at the sequence and pacing of the pubertal development.

GDPP follows normal pubertal development, but at an earlier age. By contrast, children with GIPP are more likely to display deviations from the normal sequence and pace of puberty.

As an example, a girl who progresses to menstrual bleeding within 1 year of the onset of breast development is more likely to have ovarian disease (a cause of GIPP) than GDPP.

2. How quickly is the puberty progressing?

A rapid rate of linear growth (over 6 cm per year over the usual growth) and skeletal maturation (measured as an increased bone age on a hand x-ray) suggests either GDPP or GIPP specifically due to ovarian or testicular disease with high concentrations of sex steroids.

Pubertal progression would be considered slow if there is no change in stage of breast, pubic hair, or genital development during 6 or more months of observation.

Example: A child with premature adrenarche or with GIPP and low concentrations of sex steroids will have little or no acceleration of growth or bone age.

3. Is the precocity because of excess estrogen or androgen? In other words, are the secondary sexual characteristics virilizing or feminizing?

In girls, isolated virilization excludes a central etiology.

In boys, feminization excludes both a central and most testicular etiologies.

When Do We Refer 
to an Endocrinologist?

Both GDPP and GIPP warrant referral to an endocrinologist, whereas Incomplete PP requires only sympathetic reassurance and monitoring over time.

With Incomplete PP, if you begin to notice progressive secondary sexual development, increasing growth velocity or accelerated bone maturation, then referral is warranted at that time.5

What Can We Use for Naturopathic Treatment?

Many of our therapeutic options are theoretical or based on clinical observance rather than evidence-based. All can be applied to cases of Incomplete PP, and some may be applied to GDPP or GIPP, along with conventional medical treatments.

Lifestyle counseling: Eliminate exogenous estrogens (plastics, food additives, and pesticides) and other endocrine disruptors (eg, phthlates in beauty products). Lavender oil and tea tree oil have been associated with thelarche, especially with gynecomastia in boys.7

Nutritional: Eliminate dairy, eggs, and meats with added hormones. Consider eliminating soy, flax, and sesame, as they are phytoestrogens and young tissue may be ultrasensitive to them. Soy-based infant formulas have been implicated in premature thelarche, although the evidence is weak.9

Fiber to decrease excess hormone effect. Acacia fiber is great for kids—no taste or grit: 1 tsp – 1 Tbsp QD in 8 oz water

Liver detoxification support to decrease exogenous hormone effect. Foods: Dark leafy greens, broccoli, beets, artichoke, turmeric, lemon, etc. Botanicals: Taraxacum root – 100-300 mg QD; or Silybum – 50-100 mg QD. Nutrients: Choline and inositol –100-300 mg QD; DIM – 120-240 mg QD; calcium-d-glucarate – 100-300 mg QD

Botanicals to support hormone regulation: Vitex for estrogen – 100-300 mg QD; Serenoa for testosterone – 300 mg QD

Botanicals to decrease adrenal hormone output: Eleutherococcus – 100-200 mg QD; Withania – 200 mg QD; Rhodiola – 100-300 mg QD

Case study

A 6-year-old girl presents with her mother with symptoms of breast development and recent onset of pubic hair growth. There has been no galactorrhea or menstrual bleeding noted. The young girl is unaware of these bodily changes.

ROS: All negative

Family Hx: Mother started to have puberty changes at age 9-10. Older sister started developing at age 10. Father’s onset of puberty is unknown.

Personal Hx: Growth has been of normal velocity, at the 75th percentile for both height and weight. There has been no major past medical hx.

Diet: Has always been of good quality, according to mother, following the standard food pyramid guidelines. She loves milk.

PE: She is at a Tanner stage 2. Vitals are normal. Neuro exam is normal. Skin exam 
is normal.

Should this girl be evaluated for precocious puberty? Yes, evaluation should be done for Caucasian girls who have breast 
and/or pubic hair development before 
7 years of age.

Would you order labs at this point? Yes, FSH, LH, and estradiol are warranted.

Would you order imaging? Yes, a hand x-ray for bone age is warranted. Depending on results, consider a brain MRI.

Would you refer to an endocrinologist? Whether you discover GDPP or GIPP, a 
referral to endocrinology is warranted. If all levels are normal, a watch-and-wait approach is appropriate.

What can you do for initial naturopathic treatment? Switch to organic, hormone-free, cow’s milk dairy, as well as organic eggs and meat. Eliminate plastics, food additives, pesticides an phthalates. Consider eliminating or limiting dietary soy. Support liver detoxification through foods and botanicals. Consider acacia fiber: 1 tsp – 1 Tbsp QD in 8 oz water.

Tamara Cullen, ND is a 1999 graduate of Bastyr University and is currently practicing primary care medicine in Seattle, Washington. Dr Cullen has always had a special love for working in pediatrics. She believes that teaching our children the philosophy and principles of naturopathic medicine will cause the greatest healthcare change in this world. It is because of this belief that she enjoys educating other providers on practicing pediatric medicine. She currently serves as the Advanced Pediatrics professor at Bastyr University and she sits on the American Board of Naturopathic Pediatrics, an organization dedicated to the creation of a Naturopathic Pediatrics Board Certification exam. Additionally, she was a founding board member of the PedANP and co-author of The Baby Cuisine Cookbook. To date, her greatest accomplishment is raising her 15-year-old son, Max.

 References

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2. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics. 1999;104(4 Pt 1):936-941.
3. Bridges NA, Christopher JA, Hindmarsh PC, Brook CG. Sexual precocity: sex incidence and aetiology. Arch Dis Child. 1994;70(2):116-118.
4. Chemaitilly W, Trivin C, Adan L, et al. Central precocious puberty: clinical and laboratory features. Clin Endocrinol (Oxf). 2001;54(3):289-294.
5. Ng SM, Kumar Y, Cody D, et al. Cranial MRI scans are indicated in all girls with central precocious puberty. Arch Dis Child. 2003;88(5):414-418.
6. Jung H, Carmel P, Schwartz MS, et al. Some hypothalamic hamartomas contain transforming growth factor alpha, a puberty-inducing growth, but not luteinizing hormone-releasing hormone neurons. J Clin Endocrinol Metab. 1999;84(12):4695-4701.
7. Henley DV, Lipson N, Korach KS, Bloch CA. Prepubertal gynecomastia linked to lavender and tea tree oils. N Engl J Med. 2007;356(5):479-485.
8. Hoffman P, Pescovitz OH. Premature thelarch. In: Findberg L, Kleinman RE, eds. Saunders Manual of Pediatric Practice. Philadelphia, PA: WB Saunders; 2002:745.
9. Zung A, Glaser T, Kerem Z, Zadik Z. Breast development in the first 2 years of life: an association with soy-based infant formulas. J Pediatr Gastroenterol Nutr. 2008;46(2):191-195.