Materiały źródłowe

• #1 Timing of puberty: why is it changing and why does it matter? | Society for Endocrinology

  https://www.endocrinology.org/endocrinologist/134-winter19/features/timing-of-puberty-why-is-it-changing-and-why-does-it-matter/

  Puberty is the key developmental stage of transition from childhood to adult life, with the achievement of adult height and body proportions, the development of external sexual characteristics and the capacity to reproduce. […] In some children, puberty may take place prematurely to produce precocious puberty, whilst, in others, it fails to be switched on at the appropriate time, leading to delayed puberty. The mechanisms behind these pubertal timing abnormalities are varied, and many remain incompletely understood. […] Central to the process of puberty, and heralding its onset, is upregulation of pulsatile gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus. […] The hypothalamic-pituitary-gonadal (HPG) axis is active at three main developmental stages. […] However, the timing of puberty in most countries in the developed world exhibited a shift to earlier onset in the first half of the 20th century, most notably in girls.

• #1 Physiology, Puberty – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534827/

  Puberty is the process of physical maturation where an adolescent reaches sexual maturity and becomes capable of reproduction. […] However, due to differences in each individual, including environment and genetics, puberty may proceed in a less-than-predictable way. […] Gonadotropin-releasing hormone (GnRH) neurons of the hypothalamus control the initiation of puberty. The pulsatile secretion of GnRH by these neurons brings about the physiologic changes associated with puberty. […] The hypothalamus releases GnRH in a pulsatile manner, which then stimulates the release of FSH and LH from the anterior pituitary gland. […] Delayed puberty is the lack of physical evidence of puberty by 2 to 2.5 standard deviations above the mean age for the initiation of puberty. […] The pathophysiology of puberty can be broken down into three main categories: premature (precocious) puberty, delayed puberty, and contrasexual development.

• #1 Precocious Puberty: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/924002-overview

  High-amplitude pulses of GnRH from the hypothalamus at the onset of puberty cause pulsatile increases in the pituitary gonadotropins LH and follicle-stimulating hormone (FSH). Increased LH levels stimulate production of sex steroids by testicular Leydig cells or ovarian granulosa cells. Pubertal levels of androgens or estrogens cause the physical changes of puberty, including penile enlargement and sexual hair in boys and breast development in girls. These levels also mediate the pubertal growth spurt. Increased FSH levels cause enlargement of the gonads in both sexes and eventually promote follicular maturation in girls and spermatogenesis in boys. Research has implicated a family of peptides called kisspeptins, produced in the central nervous system (CNS), in the regulation of GnRH secretion.

• #1 Physiology, Puberty – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534827/

  Precocious puberty, or early development of secondary sexual characteristics, is defined as the appearance of secondary sexual characteristics prior to the age of eight in girls or before the age of nine in boys. […] Delayed puberty in girls is considered the absence of breast growth by 13 years of age or more than four years between thelarche and menarche. […] The causes of delayed puberty include hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, hypopituitarism, chromosomal abnormalities, and hypothalamic dysfunction due to secondary causes.

• #1 Disorders of Puberty: An Approach to Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1101/p590.html

  Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. […] Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. […] Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. […] Abnormal pubertal timing can adversely affect a child’s physical and psychosocial well-being and may be caused by a range of generally benign or pathologic etiologies.

• #1 Puberty – TeachMePaediatrics

  https://teachmepaediatrics.com/endocrinology/adrenal-glands/puberty/

  The mechanism behind the onset of puberty is via the HPA axis. Gonadotrophin-releasing hormone (GnRH) is released from the hypothalamus, stimulating the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These in turn stimulate the gonads to produce oestrogen or testosterone. […] Early-Onset (Precocious) Puberty is usually idiopathic and familial. In boys, you should have a high suspicion for underlying pathology such as a tumour or trauma. Precocious puberty may be classed as either true or false: True precocious puberty- due to early activation of the Hypothalamic-Pituitary axis. False precocious puberty- gonadotrophin independent. Usually presents with the isolated development of one pubertal characteristic. […] Causes of true gonadotrophin dependent precocious puberty include central malformation or damage e.g. hydrocephalus, neurofibromatosis, acquired- post-sepsis, surgery, radiotherapy, trauma, birth anoxia, and brain tumours.

• #1 Precocious Puberty: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/924002-overview

  The hypothesized mechanisms that suppress the onset of puberty in early childhood include (1) the HPG axis, which is highly sensitive to feedback inhibition by small amounts of sex steroids, and (2) central neural pathways that suppress the release of GnRH pulses. […] Most patients, particularly girls suspected of having CPP, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve. CNS imaging studies of these girls aged 6-8 years usually reveal no structural abnormalities. While older studies reported a significant proportion of abnormal findings such as tumors, subsequent reports have found an incidence of clinically significant brain imaging findings of less than 1%, even in girls below age 6 years. […] Abnormal computed tomography (CT) or MRI scans are more frequent among boys with CPP than among girls. However, a nationwide, retrospective Italian study by Cassio et al of 193 boys with CPP who were otherwise normal and healthy reported that CNS abnormalities were responsible for the condition in 5.7% of cases, while a Korean study of 138 boys with CPP and a mean age of 9.5 years found no pathologic findings; this suggests that the incidence of CNS lesions causing CPP in boys is much lower than past studies had found.

• #1 Precocious Puberty: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/924002-overview

  CNS abnormalities associated with precocious puberty include the following: Tumors (eg, astrocytomas, gliomas, germ cell tumors secreting human chorionic gonadotropin [HCG]), Hypothalamic hamartomas, Acquired CNS injury caused by inflammation, surgery, trauma, radiation therapy, or abscess, Congenital anomalies (eg, hydrocephalus, arachnoid cysts, suprasellar cysts).

• #1 Precocious puberty – Wikipedia

  https://en.wikipedia.org/wiki/Precocious_puberty

  Central precocious puberty can also be caused by brain tumors, infection (most commonly tuberculous meningitis, especially in developing countries), trauma, hydrocephalus, and Angelman syndrome. […] Precocious puberty is associated with advancement in bone age, which leads to early fusion of epiphyses, thus resulting in reduced final height and short stature. […] The gene MKRN3, which is a maternally imprinted gene, was first cloned by Jong et al. in 1999. MKRN3 was originally named Zinc finger protein 127. It is located on human chromosome 15 on the long arm in the Prader-Willi syndrome critical region2, and has since been identified as a cause of premature sexual development or CPP. […] The identification of mutations in MKRN3 leading to sporadic cases of CPP has been a significant contribution to better understanding the mechanism of puberty. […] MKRN3 appears to act as a „brake” on the central hypothalamic-pituitary access. Thus, loss of function mutations of the protein allow early activation of the GnRH pathway and cause phenotypic CPP.

• #1 Timing of puberty: why is it changing and why does it matter? | Society for Endocrinology

  https://www.endocrinology.org/endocrinologist/134-winter19/features/timing-of-puberty-why-is-it-changing-and-why-does-it-matter/

  The effect of possible endocrine-disrupting chemicals (EDCs) on the timing of puberty has also been an ongoing concern. […] Despite the importance of environmental factors, a genetic influence on the timing of puberty is fundamental. […] Attempts to identify key genetic regulators have ranged from genome-wide association studies of age-at-menarche, examining pubertal timing in healthy women, to next generation sequencing approaches to identify causal mutations in disease cohorts with delayed, absent or precocious puberty. […] Mutations in the pubertal brake gene MKRN3, and more rarely in the kisspeptin gene KISS1 and DLK1, highlight the importance of upstream control of GnRH secretion in the pathogenesis of CPP. […] In delayed or absent puberty, more than 40 genes have been identified, mutation of which causes or contributes to the aetiology of these conditions.

• #1 Molecular link between body weight, early puberty identified | OHSU News

  https://news.ohsu.edu/2018/10/10/molecular-link-between-body-weight-early-puberty-identified

  Lomniczi and colleagues identified the enzyme SIRT1 in the hypothalamus as being a key player in transmitting body weight information to the brain. In overweight rats, there is less SIRT1 in the hypothalamus, allowing the Kiss1 gene to be expressed earlier, leading the rats to undergo puberty early. In lean rats, SIRT1 is higher for a prolonged period of time, taking longer for Kiss1 gene activation, which delayed puberty in those rats. […] Lomniczi continues to explore the causes of early-onset puberty through animal model studies.

• #1 Early Puberty and Hormone Disruptors | 2021, Volume 2 – Issue 2 | Journal of Experimental and Basic Medical Sciences

  https://jebms.org/full-text/64

  The key mechanism of BPA-induced precocious puberty is a positive feedback mechanism that activates the operation of the GnRH pulse generator, resulting in increased pituitary LH and FSH secretion. […] Early menarche was also documented by Vasiliu et al. after potential prenatal/early postnatal exposure to dichlorodiphenyldichloroethylene, a DDT metabolite. […] The causes of precocious puberty and their connection to multiple hormone disruptors have not been adequately elucidated in view of all of this information; the frequency and dosage of exposure, environmental consequences, hereditary and pathological disorders that impair puberty preclude a definite observation.

• #1 Delayed Puberty – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK544322/

  Delayed puberty not infrequently occurs in the pediatric population and a common reason for referral to a pediatric endocrinologist. […] This activity reviews the evaluation and management of pubertal delay and highlights the role of interprofessional team members in collaborating to provide well-coordinated care to patients with this condition. […] Identify the etiology of delayed puberty. […] Recall the history, physical, and evaluation of delayed puberty. […] List the treatment and management options available for delayed puberty. […] Review the importance of improving care coordination amongst interprofessional team members to improve outcomes for patients affected by delayed puberty. […] In females, delayed puberty is the lack of breast development by 13 years, a delay of over 4 years between thelarche and completion of puberty, or a lack of menarche by 16 years. In males, a pubertal delay is evident by a lack of testicular enlargement by 14 years or more than 5 years between testicular enlargement and completion of puberty.

• #1 A Current Perspective on Delayed Puberty and Its Management – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/a-current-perspective-on-delayed-puberty-and-its-management/doi/jcrpe.galenos.2024.2024-2-7

  Delayed puberty is defined as the lack of development of secondary sex characteristics in childhood. Based on a review of the literature, delayed puberty can be divided into three main categories: (i) hypergonadotropic hypogonadism (congenital and acquired); (ii) permanent hypogonadotropic hypogonadism (congenital and acquired); and (iii) transient hypogonadotropic hypogonadism [constitutional delay of growth and puberty (CDGP) and functional hypogonadotropic hypogonadism]. CDGP is the most common cause of hypogonadism in both males and females, accounting for 60% and 30% respectively. Testosterone is the primary treatment for male hypogonadism, while estrogen and progesterone are used for female hypogonadism. However, in recent years, physiological induction therapy protocols such as human chorionic gonadotropin (hCG) monotherapy, hCG + follicle-stimulating hormone combined therapy, and gonadotropin-releasing hormone infusion have been recommended for the treatment of hypogonadotropic hypogonadism to increase long-term fertility success. There is no clear consensus on treatment protocols for physiological induction treatment and its effect on fertility. This review will discuss the clinical approach to hypogonadism, as well as traditional and physiological induction protocols.

• #1 Revista Española Endocrinología Pediátrica – Molecular advances in the diagnosis of delayed puberty

  https://www.endocrinologiapediatrica.org/modules.php?name=articulos&idarticulo=433&idlangart=EN&preproduccion=&in_window=1

  The majority of families display an autosomal dominant pattern of inheritance (with or without complete penetrance). 50 to 75% of subjects with self-limited DP have a family history of delayed pubertal onset. […] More recently, whole exome and targeted resequencing methods have implicated two pathogenic mutations in IGSF10 as the causal factor for late puberty in six unrelated families from a large Finnish cohort with familial DP. Mutations in IGSF10 appear to cause a dysregulation of GnRH neuronal migration during embryonic development. […] Pathogenic IGSF10 mutations leading to disrupted IGSF10 signalling potentially result in reduced numbers or mis-timed arrival of GnRH neurons at the hypothalamus; producing a functional defect in the GnRH neuroendocrine network. With this impaired GnRH system there would follow an increased threshold for the onset of puberty, with an ensuing delay in pubertal timing.

• #1 Constitutional Growth Delay: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/919677-overview

  Children with constitutional growth delay (CGD), the most common cause of short stature and pubertal delay, typically have retarded linear growth within the first 3 years of life. […] At the expected time of puberty, the height of children with constitutional growth delay begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt. […] Constitutional growth delay is a global delay in development that affects every organ system. Delays in growth and sexual development are quantified by skeletal age, which is determined from bone age radiographic studies of the left hand and wrist. Growth and development are appropriate for an individual’s biologic age (skeletal age) rather than for their chronologic age. Timing and tempo of growth and development are delayed in accordance with the biologic state of maturity.

• #1 Current clinical management of constitutional delay of growth and puberty | Italian Journal of Pediatrics | Full Text

  https://ijponline.biomedcentral.com/articles/10.1186/s13052-022-01242-5

  In hypo- or hyper-gonadotropic hypogonadism long-term hormone substitutive therapy is advised. Girls usually start on a low dose of estrogen administered orally with tablets (5-10g/Kg per day) or through transdermal patches every 3-4days per week, for cycles of 6months until breast development reaches Tanner III stage. […] In conclusions, the ability to make a correct and prompt diagnosis has clinical implications. CDGP subjects have a late but normal puberty, which starts spontaneously. On the contrary, hypogonadic patients do not initiate spontaneous pubertal development.

• #1 A Current Perspective on Delayed Puberty and Its Management – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/a-current-perspective-on-delayed-puberty-and-its-management/doi/jcrpe.galenos.2024.2024-2-7

  Hypogonadotropic hypogonadism, characterized by low gonadotropins, can be caused by either a permanent (isolated or in combination with other pituitary hormone deficiencies) or a transient deficiency caused by either a primary delay in HPG axis maturation (known as CDGP) or a secondary delay in HPG maturation (known as FHH). […] CDGP is the most common cause of delayed puberty in both sexes. It accounts for 65-73% of boys and 30-43% of girls. It is self-limited and has classically been described as representing late variants of the normal spectrum of pubertal timing. […] The diagnosis of CHH is the most difficult clinical situation, especially when the clinical presentation overlaps with CDGP and gives no diagnostic signs. The gold standard for distinguishing between these two conditions is clinical monitoring until the age of 18 years for signs of endogenous activation of the HPG axis (progressive testicular enlargement or breast development).

• #1 Delayed puberty – Wikipedia

  https://en.wikipedia.org/wiki/Delayed_puberty

  Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormonal signs that puberty has begun. […] Delay of puberty may also occur due to various causes such as malnutrition, various systemic diseases, or defects of the reproductive system (hypogonadism) or the body’s responsiveness to sex hormones. […] Primary failure of the ovaries or testes (gonads) will cause delayed puberty due to the lack of hormonal response by the final receptors of the HPG axis. In this scenario, the brain sends a lot of hormonal signals (high gonadotropin), but the gonads are unable to respond to said signals causing hypergonadotropic hypogonadism. […] The hypothalamic-pituitary-gonadal axis can also be affected at the level of the brain. The brain does not send its hormonal signals to the gonads (low gonadotropins), causing the gonads to never be activated in the first place, resulting in hypogonadotropic hypogonadism.

• #1 Disorders of Puberty: An Approach to Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1101/p590.html

  In patients with precocious puberty, brain magnetic resonance imaging should be performed in girls younger than six years, all boys, and children with neurologic symptoms to evaluate for a central nervous system lesion. […] Boys older than 14 years and girls older than 13 years with possible constitutional delay of growth and puberty may benefit from a short course of sex steroids to jump-start puberty. […] Delayed puberty is the absence of breast development by 13 years of age in girls or the absence of testicular growth to at least 4 mL in volume or 2.5 cm in length by 14 years of age in boys. […] Constitutional delay of growth and puberty is the most common cause of delayed puberty in boys (60%) and girls (30%). […] Other etiologies of delayed puberty are categorized based on gonadotropin levels. In hypergonadotropic hypogonadism, gonadal insufficiency delays puberty and results in elevated levels of FSH and LH. […] Persistent hypogonadotropic hypogonadism is caused by a congenital abnormality in the HPG axis or an acquired etiology such as a central nervous system tumor, trauma, surgery, or radiation.

• #1 Delayed Puberty – Boys – Pediatric Endocrine Society

  https://pedsendo.org/patient-resource/delayed-puberty-boys/

  Boys can start puberty at a wide range of ages, with 95% starting between the ages of 9 and 14, so we consider puberty delayed when it has not started by age 14. The earliest sign of puberty in boys is enlargement of the testicles, followed by growth of the penis and pubic hair. Puberty happens when the pituitary starts making more of two hormones, luteinizing hormone (called LH) and follicle-stimulating hormone (called FSH), which cause the testicles to grow and produce the male hormone testosterone. […] By far, the most common cause is constitutional delayed puberty. These boys are generally healthy and will eventually go through puberty if given enough time. In about two thirds of cases, it is inherited from one or both parents. […] A smaller number of boys with delayed puberty have a life-long deficiency of the puberty hormones LH and FSH, a problem we call isolated gonadotropin deficiency (IGD). This is usually a condition present from birth, and many boys with IGD are born with a penis that is smaller than it should be.

• #1 Delayed Puberty – Zero To Finals

  https://zerotofinals.com/paediatrics/development/delayedpuberty/

  Hypogonadism refers to a lack of the sex hormones, oestrogen and testosterone, that normally rise prior to and during puberty. A lack of these hormones causes a delay in puberty. This is fundamentally due to one of two reasons: […] Hypogonadotropic hypogonadism is where there is a deficiency of LH and FSH, leading to a deficiency of the sex hormones testosterone and oestrogen. […] A deficiency of LH and FSH is the result of abnormal functioning of the hypothalamus or pituitary gland. […] Hypergonadotropic hypogonadism is where the gonads fail to respond to stimulation from the gonadotrophins (LH and FSH). There is no negative feedback from the sex hormones (testosterone and oestrogen), therefore the anterior pituitary produces increasing amounts of LH and FSH to try harder to stimulate the gonads. […] Hypergonadotropic hypogonadism is the result of abnormal functioning of the gonads. […] Kallman syndrome is a genetic condition causing hypogonadotrophic hypogonadism, resulting in failure to start puberty.

• #1 Delayed Puberty – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK544322/

  Common causes of delayed puberty for both males and females can be from functional hypogonadotropic hypogonadism – this is normally a temporary clinical state brought on by different stresses to the body, including chronic illnesses such as severe persistent asthma, sickle cell anemia, cystic fibrosis, or ulcerative colitis. […] Hypogonadotropic hypogonadism occurs when there is a permanent delay in the maturation of the HPG axis. […] Hypogonadotropic hypogonadism may be idiopathic or congenital. […] In males, the most common congenital form of primary gonadal insufficiency is Klinefelter syndrome. […] In females, hypergonadotropic hypogonadism results from primary ovarian failure and is either acquired or congenital. […] The prognosis of delayed puberty depends on the underlying condition.

• #1 Copy number variation (CNV) in self-limited delayed puberty (SLDP) | SFEBES2023 | Society for Endocrinology BES 2023 | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0094/ea0094p358

  Self-limited delayed puberty (SLDP) is characterized by an onset of puberty that is more than 2-2.5 standard deviations later than the population mean age and is often familial with strong genetic determinants. […] Disruption in GnRH neuron development or hypothalamic function can lead to delayed puberty (DP). […] Consequently, there has been extensive research to investigate genes affecting the hypothalamic-pituitary-gonadal (HPG) axis that might be implicated in the pathogenesis of DP by our group and others which has identified sequence variation contributing to the aetiology of SLDP. […] However, factors beyond nucleotide variations, such as epigenetic changes and CNVs can also lead to pubertal timing disorders. […] This study highlights the role of CNVs in SLDP and expands our understanding of the biological processes involved in this condition, shedding light on the complex mechanisms underlying DP.

• #1 Revista Española Endocrinología Pediátrica – Molecular advances in the diagnosis of delayed puberty

  https://www.endocrinologiapediatrica.org/modules.php?name=articulos&idarticulo=433&idlangart=EN&preproduccion=&in_window=1

  A wide variety of genetic and epigenetic defects affecting different aspects of the HPG axis at different time periods in fetal and postnatal life may result in delayed and disordered puberty. Although our understanding of the highly complex underlying biological network remains imperfect, results to date demonstrate the importance of defects in GnRH neuronal development and function, GnRH receptor and LH/FSH abnormalities, transcriptional regulation of the HPG axis and metabolic and energy homeostasis derangements in the control of pubertal timing.

• #1 Delayed Puberty Associated with Inflammatory Bowel Disease | Pediatric Research

  https://www.nature.com/articles/pr2003210

  Delayed puberty frequently complicates the clinical course of young patients with inflammatory bowel disease, more often in Crohn’s disease than ulcerative colitis. […] However, puberty may be delayed despite a normal nutritional status. […] Observations in patients with inflammatory bowel disease and in rats with experimental colitis suggest that inflammatory mediators may have a direct adverse influence, independent of undernutrition, on the onset and progression of puberty. […] Management of delayed puberty involves calorie supplements to correct undernutrition and treatment of inflammation. […] Observations in boys with delayed puberty and controlled studies in experimental models of intestinal inflammation suggest that testosterone therapy can accelerate puberty. […] The nutritional deficit results primarily from inadequate intake rather than from increased needs or losses.

• #1 Precocious Puberty: An Unusual Presentation of Hypothyroidism

  https://jpp.mums.ac.ir/article_2165.html

  Hypothyroidism is usually associated with delayed pubertal development but in rare occasions precocious puberty may ensue which is seen in cases of prolonged and untreated hypothyroidism. This is also called the Van Wyk Grumbach syndrome. […] Delayed puberty is a common manifest- tation in hypothyroid patients but rarely can it present as precocious puberty. The onset is usually with breast enlargement and vaginal bleeding in girls and testicular enlargement without virilization in boys. This presentation is also called as Van Wyk Grumbach syndrome. […] Hypothyroidism associated precocious puberty is also called Van Wyk Grumbach syndrome. It was first described in 1960 by Van Wyk and Grumbach. In girls the onset of symptoms is with thelarche followed by menarche and charactaristicly there is no development of pubic or axillary hair and opposite the patients with true precocious puberty these patients have a decreased linear growth.

• #1 Precocious Puberty: An Unusual Presentation of Hypothyroidism

  https://jpp.mums.ac.ir/article_2165.html

  The exact hormonal mechanism of hypothyroidism associated precocious puberty is not understood. Wyk and Grumbach explained that in response to thyroid hormone deficiency overproduction of gonadotropins as well as thyrotropin (which both share common subunit) occurs. But these elevated gonadotropins have been shown to be bioinactive in earlier studies and also absence of characteristics of gonadotropin excess such as advanced bone age in these cases makes the gonadotropin excess as the underlying mechanism unlikely. […] Another theory is that interaction of TSH with human FSH receptor is the possible mechanism of this syndrome. Elevated levels of TSH produce FSH like effects on the gonads in the absence of LH effects. This seems to be the most likely mechanism of this syndrome.

• #1 Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status | Scientific Reports

  https://www.nature.com/articles/s41598-017-01183-8

  Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. […] The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. […] Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity. […] Remarkably, knockout of GnIH prevented the effect of hypothyroidism to delay the pubertal onset, resulting in indistinguishable pubertal timing in GnIH-knockout female mice between control and hypothyroidism-induced group, indicating that increased GnIH expression induced by hypothyroidism may lead to delayed puberty.

• #1 Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status | Scientific Reports

  https://www.nature.com/articles/s41598-017-01183-8

  These findings indicate a novel function of GnIH to mediate HPT-HPG interactions that contribute to proper pubertal development. […] We hypothesized that the reason why pubertal onset is delayed by hypothyroidism is that the inhibitory factor GnIH is not decreased during this period. […] Importantly, hypothyroidism-induced delayed puberty as observed in WT was blocked in PTU-administered GnIH-KO female mice, leading to an equivalent pubertal onset to control GnIH-KO mice. […] These results indicate that the negative effect of hypothyroidism on pubertal development is alleviated by knockout of GnIH in support of our hypothesis of which increased GnIH levels may contribute to delay pubertal onset in hypothyroidism state. […] Our data showed that GnIH mRNA expression is changed by the thyroid status, which is increased by hypothyroidism and decreased by hyperthyroidism. […] Together, these results indicate that thyroid status alters GnIH expression by epigenetic modification of the GnIH promoter region. […] This is the first evidence showing the involvement of GnIH in pubertal disorders induced by abnormal thyroid status.

• #1 Timing of puberty: why is it changing and why does it matter? | Society for Endocrinology

  https://www.endocrinology.org/endocrinologist/134-winter19/features/timing-of-puberty-why-is-it-changing-and-why-does-it-matter/

  Disturbances of puberty encompass an important group of pathologies within the field of paediatric endocrinology, affecting over 4% of adolescents. […] Early puberty, in particular, is associated with adverse health outcomes, including breast and endometrial cancer, obesity, type 2 diabetes, cardiovascular disease, short stature and even increased mortality. […] The considerable progress in understanding the mechanisms which control puberty over the last 10 years has been a success story for basic research in neuroendocrinology, but has also been translated into clinical practice to allow a better understanding of the mechanisms of disordered pubertal development and, in some cases, to enable diagnostic genetic testing and counselling.

• #1

  https://www.healio.com/news/hematology-oncology/20201021/longitudinal-study-reveals-mechanism-of-early-puberty-as-a-driver-of-breast-cancer-risk

  Early-onset of puberty and other pubertal parameters have been linked to a significantly increased risk for developing breast cancer later in life. […] The mechanism of this association was the focus of a longitudinal study conducted by researchers at Cincinnati Childrens Hospital Medical Center and University of Cincinnati. The results, published in Journal of Adolescent Health, identified higher insulin-like growth factor-1 (IGF-1) levels, greater lifelong estrogen exposure and longer pubertal growth period as factors driving this correlation. […] Studies have demonstrated that for every year that menarche is delayed, the risk for premenopausal breast cancer decreases by 9% and the risk for postmenopausal breast cancer decreases by 4%. […] Environmental factors slightly influenced the age of onset of some of these pubertal parameters.

• #1 Normal and Delayed Puberty | Oncohema Key

  https://oncohemakey.com/normal-and-delayed-puberty/

  The timing of sexual maturation is highly correlated within families and in twin studies, suggesting strong genetic determinants. […] Despite this strong heritability, however, little is known about the genetic control of human puberty either in the normal population or in cases of disturbed pubertal timing. […] A lack of clear understanding of the genetic factors that control and trigger the onset of puberty is an important barrier to deciphering the mystery of EDC and other environment/external cues to understand the secular trend toward earlier puberty. […] Disturbances of puberty encompass an important group of pathologies within the field of pediatric endocrinology. […] However, persons with delayed puberty are also at risk of short adult height, decreased bone mineral density, and psychological sequelae.

• #1 Normal and Delayed Puberty | Oncohema Key

  https://oncohemakey.com/normal-and-delayed-puberty/

  Self-limited delayed puberty (DP), also known as constitutional delay of growth and puberty (CDGP), represents the most common cause of delayed puberty in both sexes. […] Patients with self-limited DP represent the extreme tail of normal puberty, defined as the markers of the onset of puberty occurring two or more standard deviation (SD) later than the population mean age for gender. […] In DP, probably because of a low estrogen concentration for chronological age (but not for bone age), growth hormone (GH) secretion is functionally and temporally reduced for age, and when this functional GH deficiency is prolonged, it may also impact adult height. […] The presence or absence of red flag features remains the strongest discriminator between self-limited DP and IHH.

• #1 Puberty Disorders Causes, Symptoms, and Treatments

  https://www.upmc.com/services/womens-health/conditions/puberty-disorders

  Whether puberty arrives too early or late, a complication can be psychological and social problems. […] For girls, delayed puberty complications relate to treating it with hormones, which may cause infertility, early menopause, and osteoporosis many years down the line. […] Delayed puberty complications for boys are due to having a low level of sex hormones. This may cause erection issues (impotence), male infertility, weakness, and Osteoporosis. […] In general, girls who show signs of pubertal development before the age of 8 and boys with pubertal development before the age of 9 should be evaluated for precocious puberty. […] Treatment for delayed puberty will depend on the underlying reasons for the delayed puberty. In certain situations, hormone therapy can start puberty.

• #1 Delayed puberty | Endocrine Conditions

  https://www.yourhormones.info/endocrine-conditions/delayed-puberty/

  Disorders of the testes or ovaries can cause hypergonadotrophic delayed puberty. In this case, levels of gonadotrophins are high, but the ability of the testes or ovaries to detect this is impaired and therefore they cannot respond to the gonadotrophins by producing testosterone and oestrogens, respectively. […] The defining signs of delayed puberty are no breast development in girls by 13 years and small testes of less than 4 ml in volume in boys by 14 years. […] Diagnosing delayed puberty is relatively straightforward because a physical examination will reveal whether puberty is occurring or not. […] The exact cause of the delayed puberty is more difficult to diagnose. […] Hormonal treatment is usually reserved for true cases of gonadotrophin deficiency (hypogonadotrophic hypogonadism) and failure of the testes or ovaries such as in Klinefelters syndrome, Turner syndrome or any permanent damage to the testes or ovaries. […] Constitutional delayed growth and puberty does not normally cause any long-term consequences but other causes such as gonadal failure can cause reduced fertility or complete infertility.

• #1 Precocious Early Puberty | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/precocious-early-puberty

  The goal of treatment for precocious puberty is to stop, and possibly reverse, the onset of puberty. Treatment will also depend on the type of precocious puberty your child has and the underlying cause, if known. […] New developments in treatments for precocious puberty have led to the successful use of synthetic luteinizing-releasing hormone (LHRH). This hormone appears to stop sexual maturation brought on by the disorder by stopping the pituitary gland from releasing gonadotropin. […] Early puberty will cause your child’s body to change much sooner than his peers. This sense of being different, coupled with the hormonal change-induced emotional mood swings, may make him feel self-conscious. Your child may feel uncomfortable about his sexual changes, as well. […] Understanding kisspeptin and the search for other factors that control the onset of puberty will allow doctors to answer basic questions about the control of puberty as well as develop better methods of diagnosis and treatment.

• #1 Puberty: Early and Delayed | PEMC of Florida

  https://www.toplinemd.com/pemc-florida/puberty-early-and-delayed/

  Additionally, underweight children or those with chronic illnesses may experience delayed puberty due to poor nutrition or other underlying health issues. […] Psychologically, delayed puberty can be a difficult and stressful experience for children and adolescents. […] Furthermore, delayed puberty can also have an impact on future fertility. […] It is important to note that while delayed puberty can have negative consequences, it is not always a permanent condition.

• #1 Delayed Puberty – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK544322/

  The more complicated causes of pubertal delay may require additional specialists for support and care. […] Delayed puberty has repercussions beyond just the secondary sexual characteristics. […] Thus, the condition is best managed by an interprofessional team that deals with not only growth but the psychosocial aspect of the disorder.

• #1 Revista Española Endocrinología Pediátrica – Molecular advances in the diagnosis of delayed puberty

  https://www.endocrinologiapediatrica.org/modules.php?name=articulos&idarticulo=433&idlangart=EN&preproduccion=&in_window=1

  The pathogenesis of delayed puberty (DP) encompasses several conditions including functional hypogonadism, most commonly due to self-limited (also known as constitutional) DP, GnRH deficiency leading to hypogonadotropic hypogonadism, and disorders causing primary hypogonadism. […] Self-limited DP is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Some insights into the genetic mutations that lead to familial DP have come from sequencing genes known to cause GnRH deficiency, most recently via next generation sequencing, and others from large-scale genome wide association studies in the general population. Results of these studies suggest that a variety of different pathogenic mechanisms affecting the release of the puberty brake can lead to self-limited DP. These include abnormalities of GnRH neuronal development and function, GnRH receptor and LH/FSH abnormalities, metabolic and energy homeostasis derangements and transcriptional regulation of the HPG axis. Thus, genetic causes of DP may have effects as early as in fetal life, throughout early childhood and on into adolescence.

• #2 Disorders of Puberty: An Approach to Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1101/p590.html

  Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. […] Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. […] Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. […] Abnormal pubertal timing can adversely affect a child’s physical and psychosocial well-being and may be caused by a range of generally benign or pathologic etiologies.

• #2 Precocious puberty – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/precocious-puberty/symptoms-causes/syc-20351811

  Precocious puberty is when children’s bodies begin to change into adult bodies too soon. This change is known as puberty. Most of the time, puberty occurs after age 8 in girls and after age 9 in boys. However, Black, Hispanic, and Native American children might naturally reach puberty earlier. Precocious puberty is when puberty begins too early for the child who’s going through it. […] The cause of precocious puberty often can’t be found. Rarely, certain conditions, such as infections, hormone issues, tumors, brain issues or injuries, may cause precocious puberty. Treatment for precocious puberty usually includes medicines to delay puberty. […] To understand the causes of precocious puberty in some children, it’s helpful to know what happens at puberty. The brain starts the process by making a hormone called gonadotropin-releasing hormone (GnRH).

• #2 Timing of puberty: why is it changing and why does it matter? | Society for Endocrinology

  https://www.endocrinology.org/endocrinologist/134-winter19/features/timing-of-puberty-why-is-it-changing-and-why-does-it-matter/

  The effect of possible endocrine-disrupting chemicals (EDCs) on the timing of puberty has also been an ongoing concern. […] Despite the importance of environmental factors, a genetic influence on the timing of puberty is fundamental. […] Attempts to identify key genetic regulators have ranged from genome-wide association studies of age-at-menarche, examining pubertal timing in healthy women, to next generation sequencing approaches to identify causal mutations in disease cohorts with delayed, absent or precocious puberty. […] Mutations in the pubertal brake gene MKRN3, and more rarely in the kisspeptin gene KISS1 and DLK1, highlight the importance of upstream control of GnRH secretion in the pathogenesis of CPP. […] In delayed or absent puberty, more than 40 genes have been identified, mutation of which causes or contributes to the aetiology of these conditions.

• #2 Early Puberty and Hormone Disruptors | 2021, Volume 2 – Issue 2 | Journal of Experimental and Basic Medical Sciences

  https://jebms.org/full-text/64

  Adolescence is a dynamic mechanism influenced by a variety of factors like race, gender, and environmental forces as well as physical and psychological processes. […] While not all causes of early puberty have been identified, the most frequent one is early activation of the hypothalamic-pituitary-gonadal (HPG) axis, which can be caused by a variety of hormone disruptors. […] Precocious puberty is most often caused by the early initiation of pulsatile GnRH secretion, also known as gonadotropin-dependent precocious puberty. […] Endocrine-disrupting chemicals in the brain begin their function by stimulating estrogen-sensitive nuclei, such as hypothalamic neurons, allowing kisspeptin to be released and the hypothalamus to grow, leading puberty to begin earlier and possibly prematurely. […] Early life exposure to endocrine disruptors may play a role in pubertal timing, with children moving to Belgium for foreign adoption having an 80-fold higher risk of sexual early development than Belgian native children.

• #2 Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition in: Journal of Endocrinology Volume 242 Issue 2 (2019)

  https://joe.bioscientifica.com/view/journals/joe/242/2/JOE-19-0223.xml

  In addition to AMPK and mTOR, sirtuins have emerged in the last decades as pleiotropic metabolic modulators. […] A potential role of SIRT1 in reproductive physiology was initially suspected based on the defective reproductive phenotype observed in Sirt1-null mice. […] Our findings demonstrated that the hypothalamic content of SIRT1 declines during postnatal/pubertal maturation, which is coincident with the well-characterized increase of Kiss1 expression during this developmental period. In addition, by using suitable preclinical models of pubertal alteration due to nutritional/metabolic manipulations, our data have shown that hypothalamic SIRT1 content is modulated by the nutritional status, as suggested by previous data in adult mice and is negatively correlated to Kiss1 expression. Thus, in a rat model of precocious puberty induced by early-onset obesity, we have documented a reduction in the hypothalamic levels of SIRT1 and a concomitant increase of Kiss1 expression, whereas a model of chronic peripubertal undernutrition, which delayed puberty onset, presented an elevation of SIRT1 protein and reduced expression of Kiss1 at the hypothalamic level.

• #2 A Current Perspective on Delayed Puberty and Its Management – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/a-current-perspective-on-delayed-puberty-and-its-management/doi/jcrpe.galenos.2024.2024-2-7

  Delayed puberty is defined as lack of the initial signs of sexual maturation by an age that is more than 2-2.5 standard deviation above the mean for the population. Delayed pubertal onset is considered in the absence of testicular enlargement (testicular volumes 4 mL) by the age of 14 years in boys and breast development (absence of glandular breast tissue) by the age of 13 years in girls. […] There is no clear consensus in the literature on the classification of delayed puberty. Based on a review of the literature and text books, delayed puberty can be divided into three main categories: (i) hypergonadotropic hypogonadism (congenital and acquired); (ii) permanent hypogonadotropic hypogonadism (congenital and acquired); and (iii) Transient hypogonadotropic hypogonadism [constitutional delay of growth and puberty (CDGP) and functional hypogonadotropic hypogonadism (FHH)].

• #2 Disorders of Puberty: An Approach to Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1101/p590.html

  In patients with precocious puberty, brain magnetic resonance imaging should be performed in girls younger than six years, all boys, and children with neurologic symptoms to evaluate for a central nervous system lesion. […] Boys older than 14 years and girls older than 13 years with possible constitutional delay of growth and puberty may benefit from a short course of sex steroids to jump-start puberty. […] Delayed puberty is the absence of breast development by 13 years of age in girls or the absence of testicular growth to at least 4 mL in volume or 2.5 cm in length by 14 years of age in boys. […] Constitutional delay of growth and puberty is the most common cause of delayed puberty in boys (60%) and girls (30%). […] Other etiologies of delayed puberty are categorized based on gonadotropin levels. In hypergonadotropic hypogonadism, gonadal insufficiency delays puberty and results in elevated levels of FSH and LH. […] Persistent hypogonadotropic hypogonadism is caused by a congenital abnormality in the HPG axis or an acquired etiology such as a central nervous system tumor, trauma, surgery, or radiation.

• #2 Precocious Puberty: An Unusual Presentation of Hypothyroidism

  https://jpp.mums.ac.ir/article_2165.html

  The exact hormonal mechanism of hypothyroidism associated precocious puberty is not understood. Wyk and Grumbach explained that in response to thyroid hormone deficiency overproduction of gonadotropins as well as thyrotropin (which both share common subunit) occurs. But these elevated gonadotropins have been shown to be bioinactive in earlier studies and also absence of characteristics of gonadotropin excess such as advanced bone age in these cases makes the gonadotropin excess as the underlying mechanism unlikely. […] Another theory is that interaction of TSH with human FSH receptor is the possible mechanism of this syndrome. Elevated levels of TSH produce FSH like effects on the gonads in the absence of LH effects. This seems to be the most likely mechanism of this syndrome.

• #2 Puberty Disorders Causes, Symptoms, and Treatments

  https://www.upmc.com/services/womens-health/conditions/puberty-disorders

  Whether puberty arrives too early or late, a complication can be psychological and social problems. […] For girls, delayed puberty complications relate to treating it with hormones, which may cause infertility, early menopause, and osteoporosis many years down the line. […] Delayed puberty complications for boys are due to having a low level of sex hormones. This may cause erection issues (impotence), male infertility, weakness, and Osteoporosis. […] In general, girls who show signs of pubertal development before the age of 8 and boys with pubertal development before the age of 9 should be evaluated for precocious puberty. […] Treatment for delayed puberty will depend on the underlying reasons for the delayed puberty. In certain situations, hormone therapy can start puberty.

Zobacz więcej