eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Precocious Pseudopuberty: Treatment & Medication
Updated: Jun 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Available treatment options depend on the underlying etiology of the precocious pseudopuberty.
- The initial evaluation can usually be performed on an outpatient basis. However, inpatient studies and surgical treatment may be required.
- Medical and surgical therapies are directed at treatment of the underlying cause of precocious puberty. The therapies are designed to minimize both the short-term and the long-term morbidity and mortality of precocious puberty.
Surgical Care
- If the patient has a tumor that is causing the precocious puberty, consult the appropriate surgeon.
Consultations
- Pediatric endocrinologist: Pediatric endocrinologists may be invaluable in the diagnosis of precocious puberty, as well as in the treatment and follow-up care for the patient.
- Pediatric hematologist and oncologist (if supported by the diagnosis): In the case of malignancy leading to the sexual precocity, the oncologist needs to be involved for possible chemotherapy.
- Surgeon: In the case of malignancy, surgical subspecialists need to be consulted. Recommendation for clitoral reduction in virilized females is controversial at the present time.
- Pediatric urologist: A urologist may be needed for patients with testicular tumors.
Diet
- No special diet is required.
Activity
- No restrictions on activity are necessary.
Medication
The underlying pathophysiology of gonadotropin-independent precocious puberty is autonomous function of the gonadal axis; thus, the use of gonadotropin-releasing hormone (GnRH) analogs does not appear to be effective in the management of these disorders. No medications are routinely used in young children with a US Food and Drug Administration (FDA)-approved indication for the treatment of gonadotropin-independent precocious puberty. Therefore, a physician with expertise in the area should closely monitor the use of medications.
Steroid synthesis inhibitors
Ketoconazole blocks enzymes in the steroid biosynthetic pathway. It primarily inhibits C-17,29-desmolase, the enzyme responsible for androstenedione biosynthesis.
Ketoconazole (Nizoral)
More commonly used in treating fungal infections, but may be used in treating precocious pseudopuberty. It inhibits steroid synthesis at the level of 17 a -hydroxylase/17,20-lyase, a key enzyme in sex steroid production. It also inhibits testosterone binding to its binding globulin. In some cases, especially in those children with markedly advanced bone age, a rapid decrease in sex hormone levels may trigger true central puberty. In this event, add GnRH analogs to the treatment regimen.
Adult
Pediatric
Boys with testotoxicosis: 200 mg PO q8-12h
Strong inhibitor of CYP 3A4; isoniazid may decrease bioavailability of ketoconazole; coadministration decreases effects of either rifampin or ketoconazole; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hepatotoxicity may occur; may reversibly decrease cortisol serum levels (adverse effects are avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2-blockers at least 2 h after taking ketoconazole
Antiandrogens
These drugs block the effect of testosterone and dihydrotestosterone at the androgen receptor.
Spironolactone (Aldactone)
Mainly used as an antimineralocorticoid diuretic. It is also a weak competitive androgen antagonist. Other properties include inhibition of 17 a -hydroyxlase/17,20-lyase and interference with testosterone binding to sex hormone binding globulin. It is typically used to treat precocious pseudopuberty in conjunction with another drug (eg, an aromatase inhibitor). Specific nonsteroidal androgen antagonists (eg, flutamide) are more effective; however, they also carry greater toxicity. Therefore, the latter class of drug is used only in children in the context of clinical trials in the United States. As noted above, adjunctive use of GnRH analogs may be required if true central puberty occurs as a complication of treatment.
Adult
Pediatric
2-6 mg/kg/d PO divided bid; may be increased q2wk prn
May decrease effect of anticoagulants; potassium and potassium-sparing drugs (potassium-sparing diuretics, ACE inhibitors) may increase toxicity of spironolactone
Documented hypersensitivity; anuria; renal failure; hyperkalemia
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal and hepatic impairment
Aromatase inhibitors
This category of drugs is usually used in conjunction with an antiandrogen. Aromatase inhibitors prevent the conversion of androstenedione to estrone and testosterone to estrogen. Because estrogens play a major role in epiphyseal maturation (besides their obvious role in generating female secondary sexual effects), inhibiting estrogen production has salutary effects on slowing the progress of precocious pseudopuberty.
Testolactone (Teslac)
First-generation aromatase inhibitor used to prevent conversion of androstenedione to estrone and testosterone to estrogen in children. Newer preparations are now available, but no new agents have had published clinical trials. As noted above, adjunctive use of GnRH analogs may be required if true central puberty occurs as a complication of treatment.
Adult
Pediatric
20 mg/kg/d PO divided qid; increase over 4 wk to 40 mg/kg/d
May increase effect of warfarin, monitor INR and adjust dose accordingly
Documented hypersensitivity; males with breast cancer
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor liver function; edema may develop in patients with congestive heart failure, liver insufficiency, or renal insufficiency; may worsen hypertension; may exacerbate epilepsy and migraine
Antiestrogens
Estrogen receptor blockade (eg, with tamoxifen) may be an alternative to aromatase inhibitors and progestins in the treatment of MAS in girls. The predominant problem in childhood is precocious pseudopuberty associated with excess estrogen secretion from ovarian cysts.
Tamoxifen (Nolvadex)
Competitively binds to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. This drug is currently being tested in clinical trials. A single case report suggested a dose of 10-30 mg PO daily is effective in controlling estrogenic affects in MAS.
Adult
Pediatric
10-30 mg PO qd
May exacerbate hepatotoxic effects of allopurinol; may increase cyclosporine serum levels; increases anticoagulant effects of warfarin; aminoglutethimide reduces the serum concentration of tamoxifen; cyclophosphamide, methotrexate, and 5-FU increase thrombotic risk
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Exercise caution in leukopenia, thrombocytopenia, and hyperlipidemia; decreased visual acuity, corneal changes, and retinopathy may occur with >1 y of use
More on Precocious Pseudopuberty |
| Overview: Precocious Pseudopuberty |
| Differential Diagnoses & Workup: Precocious Pseudopuberty |
 Treatment & Medication: Precocious Pseudopuberty |
| Follow-up: Precocious Pseudopuberty |
| Multimedia: Precocious Pseudopuberty |
| References |
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References
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Further Reading
Keywords
precocious pseudopuberty, precocious puberty, gonadotropin-independent precocious pseudopuberty, gonadotropin-independent precocious puberty, gonadotropin-dependent precocious pseudopuberty, gonadotropin-dependent precocious puberty, incomplete precocious pseudopuberty, incomplete precocious puberty, peripheral precocious pseudopuberty, peripheral precocious puberty, secondary sexual characteristics, congenital adrenal hyperplasia, CAH, human chorionic gonadotropin, HCG, McCune-Albright syndrome, MAS, aromatase excess syndromes, Cushing syndrome, acromegaly, hyperprolactinemia, ovarian cysts, hyperparathyroidism, bone cysts, polyostotic fibrous dysplasia, hepatobiliary dysfunction, pancreatitis, gastrointestinal polyps, abnormal cardiac muscle cells, 21-hydroxylase deficiency, testotoxicosis, familial male precocious puberty, FMPP, polycystic ovarian disease, ambiguous genitalia, salt-wasting adrenal crisis, treatment, diagnosis
