Precocious Pseudopuberty Workup
- Author: Sunil Sinha, MD; Chief Editor: Stephen Kemp, MD, PhD more...
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- 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: This steroid precursor is elevated in 21-hydroxylase deficiency and also in 11β-hydroxylase deficiency (see 17-Hydroxyprogesterone, Serum and 17-Hydroxyprogesterone, Urine).
- 11-deoxycortisol and deoxycorticosterone: These steroid precursors are elevated in 11β-hydroxylase deficiency but should be either low or low-normal in patients with 21-hydroxylase deficiency.
- Androstenedione: This precursor of testosterone 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.
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- 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 precocity. 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 to 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 is indicated in males (and in select females at the discretion of the clinician) with sexual precocity and in any patient with neurologic signs or symptoms.
- 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 age 13 years. The ovarian tumors have characteristic MRI findings and may assist in the diagnosis of ovarian neoplasms.
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- GnRH stimulation test: Administer a standardized dose of GnRH (3.5 mcg/kg intravenously; not to exceed 100 mcg) after obtaining baseline LH/FSH levels. Then, obtain FSH and LH levels at 30, 60, and 90 minutes (or an abbreviated test may be performed with sampling at 30 min only). In the case of gonadotropin-independent precocious puberty, no increase over basal levels is observed. FSH and LH response is termed flat.
- Leuprolide acetate stimulation test: GnRH has been difficult to obtain; an alternative to the GnRH stimulation test is GnRH agonist Leuprolide acetate stimulation test. Administer leuprolide acetate [20 µg/kg2] Obtain a baseline LH, estradiol and testosterone are optional. Measure the LH level at 3 hours after injection. Measure estradiol or testosterone 24 hours after injection. An LH level of more than 8 IU/L is consistent with central precocious puberty (CPP). If the estradiol stimulates to 50 pg/mL or greater this is consistent with CPP. If the estradiol levels are 25-50 pg/mL this is consistent with early CPP. Sathasivam et al, however, demonstrate a baseline serum level of LH greater than or equal to 0.3 U/L and a stimulated (peak) LH level greater than or equal to 5 U/L with the leuprolide-stimulation test accurately predicting pubertal progression.
- 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.
- 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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