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Precocious Puberty

AEXS


Presentation

Among girls: The first sign is the enlargement of breasts, which may be unilateral initially. Pubic hair, axillary hair and axillary odor also start appearing at the same time. Menarche is the latest event and occurs mostly 2-3 years after the onset of breast enlargement.

Among boys: The first signs of precocious puberty among boys are the testicular enlargement. After a year of testicular enlargement, there is the growth of the penis and scrotum. Pubertal growth spurt or accelerated linear growth is seen in the course of male puberty [6] [7].

Precocious Puberty
  • In most cases, the cause of central precocious puberty is unknown (called “true” central precocious puberty). Fortunately, today’s medicines, called GnRH agonists, can stop the progression of early puberty associated with central precocious puberty.[web.archive.org]
  • The 2 forms of precocious puberty are central (gonadotropin-dependent precocious puberty) and peripheral (gonadotropin-independent precocious puberty).[ncbi.nlm.nih.gov]
  • And for about 5% of boys, precocious puberty is inherited . (Less than 1% of girls with precocious puberty have inherited the condition.)[kidshealth.org]
  • We enrolled 17 patients with central precocious puberty aged 7 years (range: 2-8 years) and breast development onset RESULTS: No MKRN3 mutation was found among central precocious puberty patients.[ncbi.nlm.nih.gov]
  • : Precocious puberty girls had an association with increased MEP concentration.[ncbi.nlm.nih.gov]
Accelerated Growth
  • Abstract A 7-year-old Indian girl presented with symptoms of excessive development of breasts, early menarche, growth of pubic hairs, accelerated growth and abdominal distension.[ncbi.nlm.nih.gov]
  • Early puberty accelerates growth. These children may initially be considerably taller than their peers. Because bone maturation is also accelerated, growth may be completed at an unusually early age, resulting in short stature .[emedicine.com]
  • […] of 9: Penile enlargement Testicular development Increased muscle development Voice change Growth of body hair Accelerated growth There are two types of precocious puberty: Central precocious puberty (CPP).[rileychildrens.org]
  • Precocious puberty Puberty is a complex biological process involving sexual maturation and accelerated growth. These processes normally initiate when pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus begins.[imprinting-disorders.eu]
Turkish
  • The detected incidence of MKRN3 variants in our case series was much lower than reported elsewhere which suggests a need for further studies in Turkish iCPP patients.[ncbi.nlm.nih.gov]
Failure to Thrive
  • Abstract Marshall-Smith Syndrome (MRSHSS) is a very rare genetic disorder characterized by failure to thrive and characteristic dysmorphic features associated with accelerated osseous maturation.[ncbi.nlm.nih.gov]
Loss of Pubic Hair
  • The volume of the testicles has decreased to 7 ml and a slight loss of pubic hair was noted. In addition, his mother and his grandfather exhibited dermal masses, and focal cutaneous and subcutaneous growths.[ncbi.nlm.nih.gov]
Subcutaneous Nodule
  • Multiple cafe au lait spots well above 5 mm were noticeable on his skin, as well as hard subcutaneous nodules, mostly on his trunk. His intelligence and hearing are normal. He has no history of seizures.[ncbi.nlm.nih.gov]
Macrocephaly
  • CONCLUSIONS: Close attention must be paid in terms of PTEN mutations in cases of macrocephaly and accompanying neurological and dermatological findings.[ncbi.nlm.nih.gov]

Workup

Levels of sex-steroids: The measurement of serum testosterone is beneficial to diagnose precocious puberty. It must be noted that the early morning levels of testosterone in boys is higher than the afternoon levels.

The levels of testosterone in different stages of puberty changes:

  • Testosterone levels less than 30 ng/dL is considered prepubertal
  • Testosterone levels of 30-100 ng/dL is early pubertal
  • Testosterone levels of 100-300 ng/dL is mid- to late-pubertal

For girls, the estradiol level measurement is not a reliable method. Determining the levels of adrenal androgens such as dehydroepiandrosterone (DHEA), or dehydroepiandrosterone sulfate (DHEA-S) is a good indicator. In premature pubarche, the levels of these hormones are elevated. Thus, DHEA-S which is the storage form of DHEA is the preferred steroid as its levels are usually high in such patients, thus, helping in correct assessment of the condition.

Random LH level determination is now considered as the best screening test for the diagnosis of central precocious puberty (CPP). The definitive test for the diagnosis of CPP is measurement of LH and FSH levels 30-60 minutes after the stimulation by GnRH.

Radiography: The radiography of hand and wrist can help to ascertain the bone age and estimate the likelihood and speed of CPP [8].

Hypsarrhythmia
  • Abstract The authors present 2 girls with progressive encephalopathy, hypsarrhythmia, and optic atrophy syndrome. They describe a novel finding, precocious puberty, a feature not previously reported in this syndrome.[ncbi.nlm.nih.gov]
Multilocular Cyst
  • We report a case of sex cord tumor with annular tubules featuring a giant multilocular cyst, grossly similar to cystadenoma, in the ovary of an 8.5 year old girl.[ncbi.nlm.nih.gov]
Liver Biopsy
  • The diagnosis of hepatoblastoma was made by liver biopsy. Chemotherapy was administered, and the patient was referred to surgery. Ten months later, testis volumes were below 4 ml bilaterally, and penile length was 5.5 cm.[ncbi.nlm.nih.gov]

Treatment

Continuous administration of LHRH and GnRH agonists cause a decrease in the levels of LH and FSH 2 to 4 weeks after the initiation of the treatment through a negative feedback mechanism [9].

Leuprolide acetate: Leuprolide helps to suppress the ovarian and testicular steroidogenesis. It helps to decrease the levels of LH and FSH in the body [10].

Histrelin: This drug is an LHRH agonist and is a potent inhibitor of the gonatotrophin secretion. It helps to desensitize the responsiveness of pituitary gonatotrophin. Long term administration of this drug causes the levels of FSH and LH to decrease. Histrelin implants can provide a continuous release of the drug [11].

Prognosis

The prognosis of the disease depends on the underlying cause. However, without treatment, most girls who have onset of puberty between ages 6 and 8 years, achieves the adult height in the normal range. Boys with precocious puberty, on the other hand, do not achieve average height [5].

Complications

Some of the possible complications of precocious puberty are as follows:

  • Short height: Though children with precocious puberty may be tall at first (due to their quick growth and early maturation of their bones), they stop growing earlier than usual which make them shorter than the average as adults. If early diagnosis and treatment of the condition is done, then it can help them grow taller. 
  • Social and emotional problems: If the child has earlier puberty than the peers, it can make them extremely self-conscious about their body and may impact their self-esteem with increased chances of depression among them.

Etiology

Genetics plays a crucial role in the etiology of the precocious puberty. An increase in the body mass index (BMI) is often associated with precocious puberty in girls, though; its impact on boys is still debated.

Thus, body weight and fat mass are two important factors that can influence the onset of puberty among girls. In one study, it was found that the increased BMI at an age 3 and rate of increase of BMI in ages between 3 and 6 years is positively correlated to the early onset of puberty [2].

Epidemiology

In a recent report from Denmark, it was found that over the 15-years of the study, the mean age at which the appearance of the breast tissues in girls was visible decreased to 9.86 years from 10.88 years, while the age of the menarche declined slightly from 13.42 to 13.13 years.

In the Chinese study, the mean age of development of breast was 9.2 years while the mean age at menarche was 12.27 years. Thus, from different studies across the world, there was seen a decline in the age of breast development and menarche in girls. The exposure to different chemicals from the environment has been one of the causes of this change [4].

Sex distribution
Age distribution

Pathophysiology

Most of the patients with precocious puberty (especially the girls who are suspected to have central precocious puberty), are healthy. The early CNS imaging studies of these 6-year old and 8-years old girls show no structural abnormalities.

The onset of puberty is a result of the secretion of the hormone gonatotrophin-releasing hormone (GnRH) by the hypothalamus. Some of the mechanisms that suppress the onset of the puberty are:

  • HPG axis: Highly sensitive to feedback inhibition by even small quantities of sex steroids.
  • Central neural pathways: Suppresses the release of the GnRH pulses.

When there are high-amplitude pulses or release of the GnRH, it causes the pulsatile increase in the levels of the pituitary gonadotropin-luteinizing hormone or LH and follicle-stimulating hormone (FSH).

As the level of LH is increased, it stimulates the production of the sex steroids by the leydig cells of testis in boys and ovarian granulose cells among girls. With these pubertal levels of androgens and estrogens, physical changes are seen in the children, including the enlargement of penis and breast development in girls. Also, the increased FSH levels cause the gonads to enlarge in both the genders, promoting follicular maturation and spermatogenesis in girls and boys respectively.

Some of the abnormalities associated with precocious puberty are as follows:

  • Germ cell tumors (such as those secreting human chorionic gonadotropin (HCG))
  • Acquired CNS injury which is caused by surgery, trauma, and radiation therapy.
  • Congenital abnormalities: Arachnoid cysts, hydrocephalous [5].

Prevention

Some preventive measures to reduce the chances of precocious puberty among children are as follows:

  • Avoiding the children from consumption of the external sources of estrogen and testosterone (steroids) such as dietary supplements, prescription medications for adults etc.
  • Encouraging the children to maintain a healthy body weight by exercising regularly.

Summary

When the signs of the pubertal development occur at an age earlier than which is considered normal, it is defined as precocious puberty. In girls, the development of these signs of early puberty at age 8 years or younger, and among boys the onset of puberty before 9 years is considered as precocious puberty. Early onset of puberty can cause several problems. Initial growth can make the child grow taller among peers, but this early bone maturation causes linear growth to stop early, eventually leading to short adult stature.

The early appearance of breasts or menses in girls and increased libido in boys can cause emotional distress in some children. From the history and the physical examination, if it is ascertained that the child exhibits precocious puberty, the clinician must differentiate between central precocious puberty (CPP) and precocious pseudopuberty.

While the CPP is gonadotrophin-dependent and causes the maturation of the entire hypothalamic-pituitary-gonadal (HPG) axis, the precocious pseudopuberty is a condition in which there is an increased production of sex-hormone and is gonadotropin-independent. Owing to such differences, the correct diagnosis of the condition becomes critical [1].

Patient Information

When the signs of the pubertal development occur at an age earlier than which is considered normal, it is called precocious puberty. Early symptoms of the precocious puberty must come as a warning signal to the patient and the parents. Thus, knowledge of the condition and the ensuing complication can be very helpful in managing the condition.

References

Article

  1. Stephen MD, Zage PE, Waguespack SG. Gonadotropin-dependent precocious puberty: neoplastic causes and endocrine considerations. Int J Pediatr Endocrinol. 2011; 2011;2011:184502. Published online Jan 27, 2011
  2. Ng SM, Kumar Y, Cody D, et al. Cranial MRI scans are indicated in all girls with central precocious puberty. Arch Dis Child. May 2003;88(5):414-8; discussion 414-8.
  3. Chalumeau M, Chemaitilly W, Trivin C, et al. Central precocious puberty in girls: an evidence-based diagnosis tree to predict central nervous system abnormalities. Pediatrics. Jan 2002;109(1):61-7.
  4. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. Jun 1969;44(235):291-303.
  5. Macedo DB, Cukier P, Mendonca BB, et al. Advances in the etiology, diagnosis and treatment of central precocious puberty. Arq Bras Endocrinol Metabol. 2014 Mar;58(2):108-17. 
  6. de Vries L, Kauschansky A, Shohat M, Phillip M. Familial central precocious puberty suggests autosomal dominant inheritance. J Clin Endocrinol Metab. Apr 2004;89(4):1794-800.
  7. Mamun AA, Hayatbakhsh MR, O'Callaghan M, Williams G, Najman J. Early overweight and pubertal maturation--pathways of association with young adults' overweight: a longitudinal study. Int J Obes (Lond). Jan 2009;33(1):14-20.
  8. Armengaud JB, Charkaluk ML, Trivin C, Tardy V, Bréart G, Brauner R. Precocious pubarche: distinguishing late-onset congenital adrenal hyperplasia from premature adrenarche. J Clin Endocrinol Metab. Aug 2009;94(8):2835-40.
  9. Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. Apr 2009;123(4):e752-62.
  10. Kim YJ, Lee HS, Lee YJ, et al. Multicenter clinical trial of leuprolide acetate depot (Luphere depot 3.75 mg) for efficacy and safety in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2013 Dec;18(4):173-8.
  11. Lewis KA, Goldyn AK, West KW, Eugster EA. A single histrelin implant is effective for 2 years for treatment of central precocious puberty. J Pediatr. 2013 Oct;163(4):1214-6.

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Last updated: 2018-06-22 05:54