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PPP
The treatment of PPP depends on its etiology. For example, PPP symptoms due to congenital adrenal hyperplasia can be suppressed with glucocorticoids. Surgery is the standard of care for sex steroid-secreting tumors; however, surgery may not be required for E2-producing follicular cysts as they may regress spontaneously.
The treatment of McCune-Albright syndrome (MAS) deserves special mention. MAS is characterized by precocious puberty, abnormal brous tissue in bones called polyostotic brous dysplasia, and light brown patches of skin called café-au- lait spots. MAS is caused by an activating mutation of the α-subunit of the G-protein. PPP in MAS is caused by E2 synthesized from autonomously functioning ovarian cysts. Young MAS girls with frequent menses, rapidly progressing puberty, and accelerated growth and bone age normally bene t from treatment. Due to their binding to the cytochrome P450 portion of aromatase, aromatase inhibitors inhibit the conversion of androgens to estrogens, thereby forming the mainstay of PPP treatment in girls with MAS. Oral letrozole 2.5 mg daily is considered rst-line for the management of PPP in MAS, whereas tamoxifen is used as second-line or for adjuvant therapy. Bisphosphonates can be used to treat persistent and/or moderate- to-severe bone pain. However, its impact on reducing the progression or size ofbrous dysplasia lesions is unknown.
It is important to note that CPP and PPP can occur concomitantly in children due to early activation of the HPO access. In such cases, additional GnRH-a treatment is indicated.
Discussion
Precocious puberty is a complex clinical entity, which can be distressing to young girls and their parents. Clinicians evaluating young girls with precocious puberty should aim to differentiate between isolated thelarche, isolated adrenarche, and precocious puberty. The former two are generally benign and self-limited, without onset of menses. Within the realm of precocious puberty, clinicians should focus their clinical history and investigation to distinguish between CPP and PPP. The majority of precocious puberty cases are CPP or GnRH-dependent, of which up to 90% of cases are idiopathic in nature. PPP or GnRH-dependent precocious puberty occurs when there is excessive secretion of sex steroids independent of the HPO axis. Administration of long-acting GnRH-agonist is the main therapeutic strategy in cases of CPP. In contrast, PPP requires suppression of sex steroids depending on its source.
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References
1.\ Cheuiche AV, da Silveira LG, de Paula LCP, Lucena IRS, Silveiro SP. Diagnosis and management of precocious sexual maturation: an updated review. Eur J Pediatr. 2021;180(10):3073–87.
2.\ Schoelwer M, Eugster EA. Treatment of peripheral precocious puberty. Endocr Dev. 2016;29:230–9.
3.\ Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62–89.
4.\ Cantas-Orsdemir S, Eugster EA. Update on central precocious puberty: from etiologies to outcomes. Expert Rev Endocrinol Metab. 2019;14(2):123–30.
5.\ Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertility. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
6.\ Strauss JF, Barbieri RL. Yen & Jaffe’s reproductive endocrinology, Chapter 18. 7th ed. Philadelphia, PA: Elsevier; 2014.
Chapter 3
Delayed Puberty
Nigel Pereira
Case
A 14-year-old young girl presents to the of ce with her mother for the evaluation of delayed puberty. Her past pediatric and medical history is unremarkable. Physical examination reveals height of 140 cm, Tanner stage I breast development and pubic hair development. A webbed-neck and broad chest is noted. How does a physician approach this clinical presentation?
Background
Puberty is characterized by rapid physical and psychological changes which result in reproductive competence and the ability to conceive. The pubertal transition requires an intact hypothalamic–pituitary–ovarian (HPO) axis and is marked by increased pulsatility of gonadotropin-releasing hormone (GnRH). This in turn results in increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, thereby stimulating sex-steroid production by the ovaries.
N. Pereira (*)
Reproductive Medicine and Ob/Gyn, The Ronald Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA e-mail: nip9060@med.cornell.edu
© Springer Nature Switzerland AG 2023 |
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P. H. Chung, Z. Rosenwaks (eds.), Problem-Focused Reproductive Endocrinology and Infertility, Contemporary Endocrinology, https://doi.org/10.1007/978-3-031-19443-6_3
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N. Pereira |
Defnition of Delayed Puberty
The stages of normal puberty have been discussed in the Precocious Puberty chapter. In general, delayed puberty is de ned as the absence of breast development in girls at an age that is 2–2.5 standard deviations later than the population mean. In the United States, this has been traditionally set at age 13 years for females. Population-based data have suggested a downward or earlier trend in female pubertal timing in the United States and some European countries. Therefore, some clinicians have proposed to revise the criteria with younger age cut-offs for certain countries, races, and/or ethnic groups. It is important to note that the development of pubic hair is not considered for the diagnosis of delayed puberty given that isolated pubarche can occur due to the adrenal glands, independent of the HPO axis.
As puberty involves estradiol (E2)-mediated increase in linear growth, delayed puberty can affect skeletal growth and bone mineralization. In fact, almost a third of total bone mineralization occurs within 4 years of puberty, and approximately 90% of peak skeletal bone mass is attained by age 18. Thus, delayed puberty causes inadequate circulating estradiol (E2), which can result in sub-optimal bone mineralization, and therefore, an increased risk of fracture. Although adult height can theoretically be compromised, most girls with delayed puberty have an adult height that is only slightly below their genetic potential. Delayed puberty may have a major impact on psychological health and has been shown to impact psychosocial outcomes for patients and their families. Some observational studies also suggest that delayed puberty can also hinder early academic success.
Differential Diagnosis of Delayed Puberty
A detailed discussion about the physiologic and genetic mechanisms underlying delayed puberty is beyond the scope of this chapter. However, it is important to note that delayed puberty may occur as an extreme variation of normal pubertal development. Such a developmental pattern is called constitutional delay of growth and puberty (CDGP). Current data suggest that up to 30–35% of girls with delayed puberty may have CDGP and therefore constitutes the most common form of delayed puberty. Although CDGP is common, it remains a diagnosis of exclusion, i.e., other forms of delayed puberty have to be ruled out. While the precise cause of CDGP remains unknown, it is thought to have a strong genetic predisposition, with the majority of patients reporting a family history of delayed puberty.
The other causes of delayed puberty can be classi ed into three different categories based on FSH and LH levels—hypergonadotropic hypogonadism, permanent hypogonadotropic hypogonadism, and transient hypogonadotropic hypogonadism. Hypergonadotropic hypogonadism is characterized by elevated FSH and LH levels due to gonadal dysfunction or failure. Primary ovarian insuf ciency due to Turner’s syndrome (45 X0) or XX gonadal dysgenesis is perhaps the most well-recognized