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Diagnosis & therapy options

Diagnosis & therapy options

Diagnosis and appropriate treatment are of paramount importance to ensure normal physical and psychological development of children with suspected precocious puberty.[1]

Assessment may include the following:

History

Areas of inquiry can include clinical, family, and social aspects of the child, such as:[1]

  • Age of onset, sequence, and progression of pubertal changes
  • Family history: timing of onset of puberty in mother and siblings
  • Neurological symptoms
  • Exogenous sex steroid exposure from plant estrogens (e.g., lavender oil, tea tree oil),
  • Drugs, or cosmetics (e.g., steroid creams, estrogen, anabolic steroids)
  • Social history: history of adoption or abuse

Clinical examination[1]

Height and weight measurements plotted using age-specific growth charts (Figure 1):

  • Body mass index
  • Pubertal Tanner staging
  • Neurological examination
  • Examination of eyes including visual fields and fundoscopy
  • Skin lesions (e.g., cafe au lait spots)
  • Abdominal examination
  • Examination of external genitalia
  • Signs of virilization: enlarged clitoris, deepening of voice, hirsutism
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Laboratory assessments

The GnRH stimulation test is the gold standard test for diagnosing CPP.[2]

It is performed by measuring FSH and LH levels 30 to 60 minutes after administering a GnRH agonist bolus and measuring hormone levels 24 hours after the injection.[3]

In CPP, GnRH-induced stimulation results in LH often above 8 mIU/mL and an LH:FSH ratio >1 (Figure 2).[1][4]

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Various biochevmical/laboratory assessments are used to rule out other endocrine gland conditions. Not all children require all of these tests to be performed:

  • Serum LH and FSH levels (baseline)
  • GnRH stimulation test (LH and FSH)
  • Gonadal steroids: Estradiol/testosterone levels
  • Thyroid assessment: Free thyroxine and thyroid-stimulating hormone
  • Serum prolactin levels (may be increased in chronic hypothyroidism or prolactinomas)
  • Adrenal assessment:
    • Urinary steroid profile (to identify and quantify excess adrenal androgens)
    • Adrenal steroids (which are increased incongenital adrenal hyperplasia and with adrenal tumors)
    • Adrenocorticotrophic hormone (ACTH) stimulation test (to identify steroid synthesis defects)

Imaging

Evaluation using various imaging technologies. [1]

Not all children require all of these tests:

  • Left wrist X-ray for bone age
  • Cranial MRI/CT to exclude a CNS lesion (e.g., a tumor).
  • CT adrenals (adrenal masses)
  • Pelvic ultrasound (size, shape of uterus, endometrial thickness and ovarian morphology)
  • Skeletal survey/bone scan (other syndromes that affect bone)

Treatment goals

Include arresting physical maturation, preventing early menarche in girls, bringing predicted adult height closer to genetic expectations, and allowing normal psychosocial development. [5]

References
  1. Tirumuru SS, Arya P, Latthe P, Kirk J. Understanding precocious puberty in girls. Obstet Gynaecol. 2012;14(2):121-129. Doi: 10.1111/j.1744-4667.2012.00094.x.
  2. Partsch C-J. Sippell WG. Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reproduct. 2001;7(3):292-302. AND Tirumuru SS, Arya P, Latthe P, Kirk J. Understanding precocious puberty in girls. Obstet Gynaecol. 2012;14(2):121-129. Doi: 10.1111/j.1744-4667.2012.00094.x.
  3. Krishna KB, Fuqua JS, Rogol AD, et al. Use of gonadotropin- releasing hormone analogs in children: Update by an international consortium. Horm Res Paediatr 2019;91:357–372. AND Kaplowitz PB, Precocious puberty. https://emedicine.medscape.com/article/924002-overview. Updated March 11, 2020. Accessed March 20, 2020.
  4. Effects of exogenous oestrogens. Hum Reproduct. 2001;7(3):292-302.
  5. National Organization for Rare Disorders (NORD). Precocious Puberty. https://rarediseases.org/rare-diseases/precocious-puberty/. Accessed October 3, 2019.

IMPORTANT SAFETY INFORMATION

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FENSOLVI (leuprolide acetate) for injectable suspension is a gonadotropin releasing hormone (GnRH) agonist used to treat patients 2 years of age and older with central precocious puberty (CPP). CPP may be diagnosed when signs of sexual maturity begin to develop in girls under the age of 8 or in boys under the age of 9.

FENSOLVI is contraindicated in individuals with hypersensitivity to any drug that is in the same class as FENSOLVI, in individuals who are allergic to any of the ingredients in FENSOLVI, or in individuals who are pregnant. FENSOLVI may cause fetal harm when administered to a pregnant patient.

During the first few weeks of treatment, increases in gonadotropins and sex steroids above baseline may result in an increase in signs and symptoms of puberty including vaginal bleeding in girls.

Psychiatric events have been reported in patients taking GnRH agonists. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Patients should be monitored for development or worsening of psychiatric symptoms.

Convulsions have been observed in patients treated with GnRH agonists with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs.

Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) has been reported in pediatric patients treated with GnRH agonists.  Patients should be monitored for headache, papilledema and blurred vision.

The most common adverse events seen with FENSOLVI were: injection site pain, nasopharyngitis, pyrexia, headache, cough, abdominal pain, injection site erythema, nausea, constipation, vomiting, upper respiratory tract infection, bronchospasm, productive cough and hot flush. 

Please see Full Prescribing Information for FENSOLVI for additional important safety information. 

To report suspected adverse reactions contact Tolmar at 1-844-4TOLMAR (486-5627) or the FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.