What is the likely diagnosis and treatment for a 6-year-old with precocious puberty, low Luteinizing Hormone (LH) (<0.1), but normal Follicle-Stimulating Hormone (FSH), estradiol, and prolactin levels?

Peripheral Precocious Puberty (Gonadotropin-Independent)

This 6-year-old has peripheral (gonadotropin-independent) precocious puberty, not central precocious puberty, as evidenced by the suppressed LH (<0.1) with normal FSH and estradiol—indicating sex steroid production independent of hypothalamic-pituitary-gonadal axis activation. 1

Understanding the Hormonal Pattern

The key diagnostic feature here is the dissociation between LH and FSH:

• **LH <0.1 IU/L is profoundly suppressed**, ruling out central precocious puberty where you would expect LH >5-10 IU/L after GnRH stimulation 2, 3
• Normal FSH and estradiol indicate autonomous sex steroid production that is suppressing the hypothalamic-pituitary axis through negative feedback 4
• This pattern is pathognomonic for peripheral precocious puberty (PPP), where sex steroids are produced independently of gonadotropin stimulation 5, 6

Critical distinction: In central precocious puberty, you see LH-predominant activation (LH/FSH ratio >1) with both gonadotropins elevated. Here, the suppressed LH with normal FSH creates the opposite pattern, confirming a peripheral source 1, 2

Differential Diagnosis for Peripheral Precocious Puberty

The most likely etiologies in a 6-year-old girl include:

Primary Considerations:

• McCune-Albright Syndrome (MAS): Activating GNAS1 mutation causing autonomous ovarian cyst formation with estrogen hypersecretion 5, 4
• Autonomous ovarian cysts: Isolated follicular cysts producing estrogen without underlying syndrome 6
• Ovarian tumors: Granulosa cell tumors or other estrogen-secreting neoplasms 4, 7

Less Common:

• Exogenous estrogen exposure: Topical preparations, supplements, or environmental sources 1, 7
• Adrenal pathology: Feminizing adrenal tumors (rare in girls) 4

Essential Diagnostic Workup

Immediate Next Steps:

Imaging studies (highest priority):

• Pelvic ultrasound to evaluate for ovarian cysts, masses, or asymmetric ovarian enlargement 1, 7
• Bone age X-ray to assess skeletal advancement and predict impact on final adult height 1, 7

Additional laboratory testing:

• DHEAS and androstenedione to exclude adrenal sources of sex steroids 8
• Thyroid function (TSH, free T4) as hypothyroidism can rarely cause precocious puberty 7
• Beta-hCG if any concern for germ cell tumor 7

Clinical assessment:

• Document Tanner staging precisely—look for breast development (thelarche), pubic hair, and growth velocity 1, 7
• Examine for café-au-lait spots (McCune-Albright), skeletal abnormalities, or signs of virilization 5, 4
• Obtain detailed exposure history to exogenous estrogens (creams, supplements, herbal products) 7

Brain MRI is NOT indicated

Unlike central precocious puberty where brain MRI is mandatory (especially <6 years), peripheral precocious puberty does not require routine brain imaging unless neurological symptoms are present 1, 7

Treatment Approach

Treatment depends entirely on the underlying etiology identified through the workup above:

For McCune-Albright Syndrome:

• Aromatase inhibitors (letrozole, anastrozole) are first-line to block peripheral estrogen synthesis 5
• Tamoxifen (selective estrogen receptor modulator) has shown variable success 5
• GnRH analogs are ineffective because the HPG axis is already suppressed 5, 4

For Autonomous Ovarian Cysts:

• Observation if small and asymptomatic, as many resolve spontaneously 6
• Surgical intervention if large, persistent, or causing symptoms 6

For Ovarian Tumors:

• Surgical resection is definitive treatment 4, 6

For Exogenous Estrogen Exposure:

• Eliminate the source and monitor for resolution of symptoms 7

Critical Pitfalls to Avoid

• Do NOT start GnRH analog therapy without confirming central precocious puberty via GnRH stimulation test—it will be completely ineffective in peripheral precocious puberty and delay appropriate treatment 5, 4
• Do NOT assume idiopathic central precocious puberty in a 6-year-old girl without proper hormonal evaluation—while most girls with central precocious puberty have idiopathic disease, this patient's suppressed LH excludes that diagnosis 7
• Do NOT skip pelvic imaging—ovarian pathology must be ruled out given the age and hormonal pattern 1, 7
• Ensure hormone levels were drawn correctly: fasting morning sample, not during stress, and document menstrual timing if applicable 8

Referral and Follow-up

Immediate referral to pediatric endocrinology is mandatory for:

• Confirmation of peripheral precocious puberty diagnosis 7
• Coordination of imaging and specialized testing 1
• Management decisions based on final etiology 6

Monitor closely for:

• Progression of secondary sexual characteristics 1
• Growth velocity and bone age advancement 1, 7
• Psychosocial impact and need for counseling 5