Precocious Pseudopuberty Workup

Updated: Oct 18, 2017
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Robert P Hoffman, MD  more...
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Workup

Approach Considerations

Once precocious puberty is established clinically, the next step is determining whether the process is GnRH-dependent (CPP) or GnRH-independent (PPP). The gold-standard biochemical diagnosis is based on the assessment of gonadotropins, mainly LH, after stimulation with exogenous GnRH or GnRH agonists. Biochemical diagnostic criteria for CPP include a serum LH concentration greater than 5 U/L after GnRH or leuprolide administration. [6]

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Laboratory Studies

The following laboratory studies may be peformed:

  • Sex steroids: The common laboratory finding for all causes of precocious pseudopuberty consists of pubertal levels of sex steroids (ie, substances with either androgenic or estrogenic effects in the presence of low-basal luteinizing hormone [LH] and follicle-stimulating hormone [FSH] with the lack of a pubertal increase in LH and FSH concentrations in response to exogenous gonadotropin-releasing hormone [GnRH] stimulation).

  • LH and FSH levels: LH and FSH levels are in the prepubertal range. LH and FSH levels are not increased in response to exogenous gonadotropin-releasing hormone.

  • Adrenal steroid precursors: Enzyme deficiencies in the pathway for cortisol synthesis lead to elevated cortisol precursors. The exact elevated precursor depends on the enzymatic deficiency. 17α-Hydroxyprogesterone is elevated in 21-hydroxylase deficiency and also in 11β-hydroxylase deficiency (see 17-Hydroxyprogesterone, Serum and 17-Hydroxyprogesterone, Urine). 11-Deoxycortisol and deoxycorticosterone are elevated in 11β-hydroxylase deficiency but should be either low or low-normal in patients with 21-hydroxylase deficiency. Androstenedione is more stable and is not an acute phase reactant. Therefore, androstenedione may provide a more reliable marker of 21-hydroxylase deficiency than does the 17α-hydroxyprogesterone. An elevated androstenedione is not a specific cause of precocious puberty because androstenedione may be elevated in individuals with tumors and CAH.

  • Human chorionic gonadotropin (HCG): This is elevated in patients with HCG-secreting tumors.

  • Urinary 17-ketosteroids: The level of 17-ketosteroids in a 24-hour urine collection provides a means of quantifying the amount of adrenal androgens being produced. 17-Ketosteroids tend to be markedly elevated in patients with tumors of the adrenal glands. Dehydroepiandrosterone (DHEA) and DHEA-sulfate and metabolites (eg, androstenedione) are the major constituents of this assay. Testosterone and dihydrotestosterone contribute less than 1% of total urinary 17-ketosteroids.

  • Estradiol: A random measurement of estradiol may not be elevated because secretion may be cyclic in individuals with McCune-Albright syndrome (MAS).

  • Testosterone: In FMPP, the levels of testosterone are pubertal with low-basal LH and FSH.

  • Thyroid function test: Serum thyroid-stimulating hormone (TSH) should be elevated markedly, and the serum free thyroxine (T4) should be markedly decreased if the patient's sexual precocity is secondary to severe primary hypothyroidism.

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Imaging Studies

The number of imaging studies that a clinician should obtain depends on the suspected diagnosis.

Ultrasonography is a sensitive test that aids in the evaluation of the ovaries, testes, and adrenal glands.

  • Ultrasonography of the ovaries and uterus can aid in determining the etiology of PPP. The uterus is sensitive to estrogen and is a good bioassay to determine the length of time and magnitude of estrogen exposure. In girls with MAS, the ovaries are frequently asymmetric secondary to the presence of large unilateral cysts. Ovarian tumors are also visible using ovarian ultrasonography.  
  • Testicular ultrasonography may detect Leydig cell tumors that are not palpable on testicular examination.

  • Ultrasonography of the adrenal glands may help establish the diagnosis of an adrenal tumor; however, abdominal CT scanning and MRI are more sensitive techniques for imaging the adrenal gland.

Many clinicians perform bone scanning in young girls suspected of having MAS. Areas of fibrous dysplasia are positive on bone scan. A skeletal survey may identify the presence of polyostotic fibrous dysplasia, which is observed in patients with MAS.

Brain MRI to detect small lesions in the pineal or hypothalamic-optic regionis is indicated in children younger than 6 years with sexual precocity or in any child with neurologic signs or symptoms. [3] Routine screening of girls with precocious puberty older than 6 years is controversial and may not be necessary. [15]

Pelvic MRI can be useful in the diagnosis and evaluation of females with precocious puberty. Uterine volume and evaluation of the different uterine layers can be well visualized on MRI. In premenarchal girls, the uterine corpus is small, and the cervical length is greater than that of the uterine body until about 13 years of age. The ovarian tumors have characteristic MRI findings and may assist in the diagnosis of ovarian neoplasms.

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Other Tests

 Other tests that may be useful in the assessment of PPP include the following:

  • Bone age: Perform a bone age assessment for any patient who presents with clinical signs of early puberty. Bone age is advanced (>2 standard deviations above the mean for age) in children who have had significant sex steroid exposure over an extended time, regardless of etiology. However, the absence of advanced bone age is not a reason to discontinue follow-up assessment when increased growth velocity and other clinical symptoms of progressive puberty are present. [11]

  • Genetic testing: Genetic testing can be used to confirm the diagnosis and provide genetic counseling for different types of CAH (including the most common form, 21-hydroxylase deficiency), gain-of-function mutations in the GNAS gene for MAS, and gain-of-function mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR) for FMPP.

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