Precocious Puberty
By Dr. Usama Ragab Youssif
Precocious puberty (PP) is defined as the development of pubertal changes (2ry sexual characters), at an age younger than the accepted lower limits for age of onset of puberty.
This document discusses precocious puberty, including its definition, types, epidemiology, evaluation, and treatment. Precocious puberty is defined as the onset of puberty before age 8 in girls and age 9 in boys. It can be central, originating from the brain, or peripheral, originating from the gonads or adrenal glands. Evaluation involves medical history, physical exam, labs, imaging, and bone age assessment. Treatment is aimed at delaying further pubertal progression using GnRH analogs.
Additional important history:
- Family history of precocious or early puberty
- Developmental milestones
- Medications/supplements
Examination:
- Bone age X-ray
- Pelvic/abdominal ultrasound
- MRI brain
Differential diagnosis:
- Central precocious puberty
- Peripheral precocious puberty (e.g. McCune-Albright syndrome)
- Pseudoprecocious puberty
Investigations:
- LH, FSH, estradiol
- Chromosome analysis
- MRI to rule out CNS pathology
Final diagnosis: Central precocious puberty likely due to early activation of hyp
Precocious puberty can be caused by central or peripheral conditions. Central precocious puberty is gonadotropin dependent and caused by organic brain lesions or idiopathically. Peripheral precocious puberty is gonadotropin independent and caused by conditions like McCune-Albright syndrome or adrenal tumors. Hypothyroidism can also cause precocious puberty by elevating TSH levels and interacting with FSH receptors. Evaluation involves assessing pubertal progression, growth, hormonal levels, and imaging. Treatment depends on the underlying cause, and may involve surgery, medication like GnRH agonists, or treating the primary condition in cases of hypothyroidism.
precocious puberty is one of the grey areas for pediatricians and gyenecologists. this is an attempt to answer some of the questions the content is references taken from authorative textbooks
This document discusses precocious puberty, including central precocious puberty and peripheral precocious puberty. Central precocious puberty is the early activation of the hypothalamic-pituitary-gonadal axis, leading to the onset of secondary sexual characteristics before age 8 in girls and 9 in boys. Peripheral precocious puberty is caused by external sex hormones and may be isosexual or heterosexual. McCune-Albright syndrome is a rare cause of peripheral precocious puberty associated with patchy skin pigmentation and fibrous dysplasia. Treatment for central precocious puberty involves suppressing puberty with GnRH agonists to help increase adult height potential.
A 15-year-old male presents with concerns of short stature and delayed puberty. Differential diagnoses include gonadotrophin deficiency, gonadal failure, and constitutional delay of growth and puberty. Physical exam and bone age assessment support a diagnosis of constitutional delay of growth and puberty, which is a condition of temporary short stature and delayed puberty but normal expected progression and attainment of full adult height. Reassurance and monitoring are the typical management approach.
Recent Trends in Pubertal Timing and Current Management of Precocious Puberty...Apollo Hospitals
Precocious puberty is defined as the development of pubertal signs at a younger age than the accepted lower limits for the onset of puberty. In girls, breast development before the age of 8 years, appearance of sexual pubic hair before the age of 8 years or beginning menses before the age of 9.5 years is traditionally considered as precocious puberty. This is accompanied by rapid growth rate, advanced skeletal maturation and increased levels of gonadotropins and/or sex steroids.
This newsletter article discusses predicting a woman's age at menopause. It explains that predicting age at menopause can help women plan their families and target health interventions. While difficult, several markers can be used including estradiol, FSH, inhibin, and AMH levels. AMH in particular decreases steadily with age and can provide insights into ovarian reserve years before menopause. The article provides ranges for these markers in the reproductive, early transition, late transition, and post-menopausal stages. References are also included to support the discussion.
This document discusses precocious puberty, including its definition, types, epidemiology, evaluation, and treatment. Precocious puberty is defined as the onset of puberty before age 8 in girls and age 9 in boys. It can be central, originating from the brain, or peripheral, originating from the gonads or adrenal glands. Evaluation involves medical history, physical exam, labs, imaging, and bone age assessment. Treatment is aimed at delaying further pubertal progression using GnRH analogs.
Additional important history:
- Family history of precocious or early puberty
- Developmental milestones
- Medications/supplements
Examination:
- Bone age X-ray
- Pelvic/abdominal ultrasound
- MRI brain
Differential diagnosis:
- Central precocious puberty
- Peripheral precocious puberty (e.g. McCune-Albright syndrome)
- Pseudoprecocious puberty
Investigations:
- LH, FSH, estradiol
- Chromosome analysis
- MRI to rule out CNS pathology
Final diagnosis: Central precocious puberty likely due to early activation of hyp
Precocious puberty can be caused by central or peripheral conditions. Central precocious puberty is gonadotropin dependent and caused by organic brain lesions or idiopathically. Peripheral precocious puberty is gonadotropin independent and caused by conditions like McCune-Albright syndrome or adrenal tumors. Hypothyroidism can also cause precocious puberty by elevating TSH levels and interacting with FSH receptors. Evaluation involves assessing pubertal progression, growth, hormonal levels, and imaging. Treatment depends on the underlying cause, and may involve surgery, medication like GnRH agonists, or treating the primary condition in cases of hypothyroidism.
precocious puberty is one of the grey areas for pediatricians and gyenecologists. this is an attempt to answer some of the questions the content is references taken from authorative textbooks
This document discusses precocious puberty, including central precocious puberty and peripheral precocious puberty. Central precocious puberty is the early activation of the hypothalamic-pituitary-gonadal axis, leading to the onset of secondary sexual characteristics before age 8 in girls and 9 in boys. Peripheral precocious puberty is caused by external sex hormones and may be isosexual or heterosexual. McCune-Albright syndrome is a rare cause of peripheral precocious puberty associated with patchy skin pigmentation and fibrous dysplasia. Treatment for central precocious puberty involves suppressing puberty with GnRH agonists to help increase adult height potential.
A 15-year-old male presents with concerns of short stature and delayed puberty. Differential diagnoses include gonadotrophin deficiency, gonadal failure, and constitutional delay of growth and puberty. Physical exam and bone age assessment support a diagnosis of constitutional delay of growth and puberty, which is a condition of temporary short stature and delayed puberty but normal expected progression and attainment of full adult height. Reassurance and monitoring are the typical management approach.
Recent Trends in Pubertal Timing and Current Management of Precocious Puberty...Apollo Hospitals
Precocious puberty is defined as the development of pubertal signs at a younger age than the accepted lower limits for the onset of puberty. In girls, breast development before the age of 8 years, appearance of sexual pubic hair before the age of 8 years or beginning menses before the age of 9.5 years is traditionally considered as precocious puberty. This is accompanied by rapid growth rate, advanced skeletal maturation and increased levels of gonadotropins and/or sex steroids.
This newsletter article discusses predicting a woman's age at menopause. It explains that predicting age at menopause can help women plan their families and target health interventions. While difficult, several markers can be used including estradiol, FSH, inhibin, and AMH levels. AMH in particular decreases steadily with age and can provide insights into ovarian reserve years before menopause. The article provides ranges for these markers in the reproductive, early transition, late transition, and post-menopausal stages. References are also included to support the discussion.
Research Article SummaryArticle’s Title Higher TSH Levels W.docxaudeleypearl
Research Article Summary
Article’s Title: Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility
Studies showed that ~10%-30% of couples that have unprotected intercourse over one year and do not succeed to conceive have unexplained or idiopathic interfertility. Hyperprolactinemia and thyroid dysfunction or thyrotropin are the known causes of infertility. Both of them are associated with irregular menstrual in women, but sometimes the normal levels of them associated with unexplained infertility, which the reasons are unknown. The main aim of this study is to compare the level of prolactin and TSH in women with normal fertility and women with unexplained infertility and with the exception of those women who have an oligospermic male partner. The treatment infertility is so expensive for couples.
The researchers hypothesized that unexplained infertility in women caused by a higher level of prolactin and TSH compare to a controlled group of women who have normal fertility, but their partners are severely oligospermic. Understanding the mechanisms that underlie unexplained infertility will help couples to have less costly treatment.
The cross-sectional studies were used to obtain the data. Researchers studied a total of 239 female patients. The female patients were between the age of eighteen and thirty-nine that were diagnosed with infertility and without any irregular menstruation. They included 187 women in this study who did not conceive over one year of unprotected intercourse (unexplained infertility group), and 52 women that their husband had oligospermia. They exclude women who had hypothyroidism and hyperthyroidism.
Even though the researchers supported their findings from previous studies, but their research was different from those earlier studies. The other studies included various factors that cause the level of TSH to be high or elevate and leads to infertility. These researchers used a strict method to ensure their findings, and the purpose of their method was to show that even a mild difference in thyroid function can cause infertility or unexplained infertility.
Thus, about 75% of the patients’ prolactin and TSH levels were measured in the laboratory of Partners HealthCare, and the rest were measured in an outside laboratory. They included only the patients that had TSH ≤5 mIU/L. These two groups of women were studied within the 13-year study period, and their characteristics were compared. The unexplained infertility group was older than the other group that their husbands had male factor problems.
The results show that the unexplained infertility group had a higher TSH level than the severe male factor even the researchers excluded the UI (unexplained infertility) group that their partners had low morphology still the results were the same. About 27% of UI group women had ≥2.5 mIU/L TSH, which twice the percentage of the severe male factor group (13% mIU/L). The data showed that the pro ...
This document provides an overview of menstrual physiology and the normal menstrual cycle. It describes:
- Puberty and the events leading to menarche in the hypothalamus, pituitary, ovaries and uterus.
- What is considered normal for menarche, menstrual frequency, duration, volume and menopause based on evidence and large studies.
- The stages of reproductive aging in women from the reproductive years to menopause based on a 10 stage classification system.
This document provides an overview of menstrual physiology and the normal menstrual cycle. It describes:
- Puberty and the events leading to menarche in the hypothalamus, pituitary, and ovaries.
- What is considered normal for menarche, menstrual cycle length and regularity, blood loss, and menopause based on evidence and large studies.
- The stages of reproductive aging in women from the reproductive years to menopause based on a 10 stage classification system.
This document provides information on delayed puberty, including its definition, causes, evaluation, and treatment. Delayed puberty can be functional, due to hypogonadotropic hypogonadism, or hypergonadotropic hypogonadism. The most common cause is constitutional delay of growth and puberty. Evaluation involves medical history, physical exam, lab tests like LH, FSH and bone age. Treatment depends on the underlying cause, but aims to induce normal pubertal development and growth. For constitutional delay, watchful waiting is often recommended, while permanent hypogonadism requires hormone therapy like testosterone to initiate puberty.
Já acompanhamos alguns casos, mas há poucos publicações nessa área. A Lactação Adotiva é um fenômeno bem descrito e logramos sucesso em muitos casos.
Comprometo-me a reunir mais estudos sobre esses temas.
The document discusses various topics related to female reproductive health including:
1. It defines amenorrhea as the absence of menstruation and describes its different types and causes. Diagnosis involves taking a history, doing an examination, and running investigations.
2. Oligomenorrhea is defined as infrequent or light menstruation. It has various causes including stress, chronic illness, and eating disorders.
3. Dysmenorrhea is defined as painful menstruation. It can be primary or secondary and has various causes and treatments.
4. Menorrhagia is defined as blood loss greater than 80ml per period. It has various causes like fibroids and treatments including
This document discusses infertility, its causes and treatments including assisted reproductive technologies. It notes that infertility has risen 50% in India over recent decades with 46% of Indians aged 31-40 requiring medical help to conceive. Both male and female factors contribute nearly equally to infertility. After evaluating causes for each couple, treatments may include ovulation induction, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection or use of donor gametes. New assisted reproduction techniques have increased options but the best treatment depends on the individual infertility factors involved.
This is the presentation of my systems theory of autistogenesis made at the Western Psychological Association, the Autism Society, and the American Psychological Association. Since that time, new information has continued to support this theoretical perspective and I am now moving into experimental studies to confirm.
1. Pubertal induction in adolescent males can be achieved using testosterone injections or gonadotropins depending on the etiology and goals of treatment.
2. Gonadotropins such as follicle stimulating hormone and human chorionic gonadotropin are preferred for hypogonadotropic hypogonadism as they stimulate testicular growth and potential fertility.
3. Treatment protocols typically involve initial FSH priming followed by FSH and hCG to mimic the normal pubertal process, though protocols vary between studies and clinicians.
A thorough history and physical examination as well as laboratory testing can help narrow the differential diagnosis of amenorrhea. In patients with primary amenorrhea, the presence or absence of sexual development should direct the evaluation. Constitutional delay of growth and puberty commonly causes primary amenorrhea in patients with no sexual development. If the patient has normal pubertal development and a uterus, the most common etiology is congenital outflow tract obstruction with a transverse vaginal septum or imperforate hymen. If laboratory tests are normal, challenge tests can help determine if the cause is an outflow tract abnormality or inadequate estrogenization. The treatment of primary and secondary amenorrhea is based on the causative factor and aims to
A thorough history and physical examination as well as laboratory testing can help narrow the differential diagnosis of amenorrhea. In patients with primary amenorrhea, the presence or absence of sexual development should direct the evaluation. Constitutional delay of growth and puberty commonly causes primary amenorrhea in patients with no sexual development. If the patient has normal pubertal development and a uterus, the most common etiology is congenital outflow tract obstruction with a transverse vaginal septum or imperforate hymen. If laboratory tests are normal, challenge tests can help determine if the cause is an outflow tract abnormality or inadequate estrogenization. The treatment of primary and secondary amenorrhea is based on the causative factor and aims to
Delayed Puberty Topics in Adolescent Gynecology Delayed Puberty Topics in A...MedicineAndHealth14
This document discusses delayed puberty in adolescent girls. It begins by outlining normal pubertal development and defining delayed puberty. Delayed puberty is then classified into three categories: hypergonadotropic hypogonadism (43%), hypogonadotropic hypogonadism (31%), and eugonadism (26%). For evaluation and management, the document recommends obtaining a history, physical exam, initial labs (TSH, prolactin), and a progestational challenge to determine gonadotropin levels and identify underlying causes. Treatment strategies aim to correct the underlying pathology, prevent disease complications, and provide sex steroids.
The Hypothalamus involvement in the sexual dimorphismMaria Hajje
The hypothalamus plays an important role in sexual dimorphism and differentiation. It regulates the secretion of reproductive hormones from the testes and ovaries that direct embryonic development and the formation of primary and secondary sex characteristics. In particular, the hypothalamus influences the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA), which is larger in males compared to females. Studies in rats show that exposure to testosterone or estradiol in the neonatal period masculinizes and feminizes the SDN-POA, respectively. The size of the SDN-POA decreases with age in both sexes due to cell death.
Van Wyke-Grumbach syndrome and pituitary hyperplasia in a six-year-old girlApollo Hospitals
Hypothyroidism is usually associated with delayed puberty and occasionally may present with isosexual precocious puberty. In girls, this may present with breast development, multicystic ovaries and vaginal bleeding. This entity characterized by ovarian hyper stimulation leading to early puberty secondary to hypothyroidism is known as Van Wyke Grumbach syndrome. In contrast to the early puberty caused by other causes, precocious puberty of hypothyroidism is characterized by short stature and delayed bone age. Awareness about this condition and the treatment of this condition with levothyroxine will lead to avoidance of surgery and unnecessary intervention. We present the case of a six-year-old girl who presented with precocious puberty and pituitary hyperplasia. This case highlights the need for the professionals to familiarize themselves about uncommon complications of untreated hypothyroidism.
L6-8.Disorders of the reproductive system.pptxDr Bilal Natiq
In the male, the testis serves two principal functions: synthesis of testosterone by the interstitial Leydig cells under the control of luteinising hormone (LH), and spermatogenesis by Sertoli cells under the control of follicle-stimulating hormone (FSH) (but also requiring adequate testosterone).
Key developments in the research on reproductive endocrinologyEFSA EU
This document summarizes key developments in research on reproductive endocrinology. It discusses how reproductive hormones regulate development and influence health risks. Males and females have different fat deposition and disease risks due to evolutionary reproductive roles. Disorders like cryptorchidism and low sperm counts are surprisingly common. Evidence suggests fetal exposure to hormones and nutrition can impact adult health and even grandchildren's health via epigenetic changes. Reproduction allows offspring to potentially adapt to environments, though current Western diets may impair this process.
The document discusses various topics related to puberty, including definitions of key terms, the normal sequence and timing of pubertal changes, causes and treatment of precocious and delayed puberty, and case studies. Precocious puberty can be true/idiopathic, due to tumors or other medical issues, or pseudopuberty caused by medication or conditions like premature adrenarche. Delayed puberty may be due to constitutional delay, medical issues impairing the HPA axis, or prior treatments like radiation therapy. Evaluation and management depends on the underlying cause and aim to initiate puberty normally or replace missing hormones.
Evaluation of Some Prominent Biochemical Agents in Menstrual Phases of Womeniosrjce
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
OVARIAN RESERVE DIAGNOSIS & MANAGEMENT DR Sharda Jain Lifecare Centre
Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of remaining eggs. It can be caused by factors like advanced age, chemotherapy, genetics, and lifestyle. Ovarian reserve tests assess markers like antral follicle count, anti-Mullerian hormone, and follicle-stimulating hormone to predict ovarian response. A combination of biochemical tests is effective for predicting diminished ovarian reserve. When test results indicate poor ovarian reserve, treatment options include protocols using gonadotropins, letrozole, or dehydroepiandrosterone to potentially increase live birth rates from in vitro fertilization.
Diabetic Peripheral Neuropathy and Vitamin B12 IssueUsama Ragab
Diabetic Peripheral Neuropathy and Vitamin B12 Issue
By Dr. Usama Ragab Youssif
Diabetic neuropathies are the most prevalent chronic complications of diabetes
Algorithms for Diabetes Management for StudentsUsama Ragab
This document discusses type 2 diabetes and cardiovascular disease. It provides the following key points:
1. Type 2 diabetes significantly increases the risk of cardiovascular disease, which is the leading cause of death in people with type 2 diabetes. Even modest reductions in blood sugar levels through treatment can substantially reduce cardiovascular risks.
2. Multiple modifiable risk factors like hypertension, dyslipidemia, and smoking are common in people with type 2 diabetes and contribute to increased cardiovascular risk. A multifactorial treatment approach targeting these risk factors alongside blood sugar control is recommended to reduce complications.
3. Incretin-based therapies that target the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide pathways
Más contenido relacionado
Similar a Central and Peripheral Precocious Puberty
Research Article SummaryArticle’s Title Higher TSH Levels W.docxaudeleypearl
Research Article Summary
Article’s Title: Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility
Studies showed that ~10%-30% of couples that have unprotected intercourse over one year and do not succeed to conceive have unexplained or idiopathic interfertility. Hyperprolactinemia and thyroid dysfunction or thyrotropin are the known causes of infertility. Both of them are associated with irregular menstrual in women, but sometimes the normal levels of them associated with unexplained infertility, which the reasons are unknown. The main aim of this study is to compare the level of prolactin and TSH in women with normal fertility and women with unexplained infertility and with the exception of those women who have an oligospermic male partner. The treatment infertility is so expensive for couples.
The researchers hypothesized that unexplained infertility in women caused by a higher level of prolactin and TSH compare to a controlled group of women who have normal fertility, but their partners are severely oligospermic. Understanding the mechanisms that underlie unexplained infertility will help couples to have less costly treatment.
The cross-sectional studies were used to obtain the data. Researchers studied a total of 239 female patients. The female patients were between the age of eighteen and thirty-nine that were diagnosed with infertility and without any irregular menstruation. They included 187 women in this study who did not conceive over one year of unprotected intercourse (unexplained infertility group), and 52 women that their husband had oligospermia. They exclude women who had hypothyroidism and hyperthyroidism.
Even though the researchers supported their findings from previous studies, but their research was different from those earlier studies. The other studies included various factors that cause the level of TSH to be high or elevate and leads to infertility. These researchers used a strict method to ensure their findings, and the purpose of their method was to show that even a mild difference in thyroid function can cause infertility or unexplained infertility.
Thus, about 75% of the patients’ prolactin and TSH levels were measured in the laboratory of Partners HealthCare, and the rest were measured in an outside laboratory. They included only the patients that had TSH ≤5 mIU/L. These two groups of women were studied within the 13-year study period, and their characteristics were compared. The unexplained infertility group was older than the other group that their husbands had male factor problems.
The results show that the unexplained infertility group had a higher TSH level than the severe male factor even the researchers excluded the UI (unexplained infertility) group that their partners had low morphology still the results were the same. About 27% of UI group women had ≥2.5 mIU/L TSH, which twice the percentage of the severe male factor group (13% mIU/L). The data showed that the pro ...
This document provides an overview of menstrual physiology and the normal menstrual cycle. It describes:
- Puberty and the events leading to menarche in the hypothalamus, pituitary, ovaries and uterus.
- What is considered normal for menarche, menstrual frequency, duration, volume and menopause based on evidence and large studies.
- The stages of reproductive aging in women from the reproductive years to menopause based on a 10 stage classification system.
This document provides an overview of menstrual physiology and the normal menstrual cycle. It describes:
- Puberty and the events leading to menarche in the hypothalamus, pituitary, and ovaries.
- What is considered normal for menarche, menstrual cycle length and regularity, blood loss, and menopause based on evidence and large studies.
- The stages of reproductive aging in women from the reproductive years to menopause based on a 10 stage classification system.
This document provides information on delayed puberty, including its definition, causes, evaluation, and treatment. Delayed puberty can be functional, due to hypogonadotropic hypogonadism, or hypergonadotropic hypogonadism. The most common cause is constitutional delay of growth and puberty. Evaluation involves medical history, physical exam, lab tests like LH, FSH and bone age. Treatment depends on the underlying cause, but aims to induce normal pubertal development and growth. For constitutional delay, watchful waiting is often recommended, while permanent hypogonadism requires hormone therapy like testosterone to initiate puberty.
Já acompanhamos alguns casos, mas há poucos publicações nessa área. A Lactação Adotiva é um fenômeno bem descrito e logramos sucesso em muitos casos.
Comprometo-me a reunir mais estudos sobre esses temas.
The document discusses various topics related to female reproductive health including:
1. It defines amenorrhea as the absence of menstruation and describes its different types and causes. Diagnosis involves taking a history, doing an examination, and running investigations.
2. Oligomenorrhea is defined as infrequent or light menstruation. It has various causes including stress, chronic illness, and eating disorders.
3. Dysmenorrhea is defined as painful menstruation. It can be primary or secondary and has various causes and treatments.
4. Menorrhagia is defined as blood loss greater than 80ml per period. It has various causes like fibroids and treatments including
This document discusses infertility, its causes and treatments including assisted reproductive technologies. It notes that infertility has risen 50% in India over recent decades with 46% of Indians aged 31-40 requiring medical help to conceive. Both male and female factors contribute nearly equally to infertility. After evaluating causes for each couple, treatments may include ovulation induction, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection or use of donor gametes. New assisted reproduction techniques have increased options but the best treatment depends on the individual infertility factors involved.
This is the presentation of my systems theory of autistogenesis made at the Western Psychological Association, the Autism Society, and the American Psychological Association. Since that time, new information has continued to support this theoretical perspective and I am now moving into experimental studies to confirm.
1. Pubertal induction in adolescent males can be achieved using testosterone injections or gonadotropins depending on the etiology and goals of treatment.
2. Gonadotropins such as follicle stimulating hormone and human chorionic gonadotropin are preferred for hypogonadotropic hypogonadism as they stimulate testicular growth and potential fertility.
3. Treatment protocols typically involve initial FSH priming followed by FSH and hCG to mimic the normal pubertal process, though protocols vary between studies and clinicians.
A thorough history and physical examination as well as laboratory testing can help narrow the differential diagnosis of amenorrhea. In patients with primary amenorrhea, the presence or absence of sexual development should direct the evaluation. Constitutional delay of growth and puberty commonly causes primary amenorrhea in patients with no sexual development. If the patient has normal pubertal development and a uterus, the most common etiology is congenital outflow tract obstruction with a transverse vaginal septum or imperforate hymen. If laboratory tests are normal, challenge tests can help determine if the cause is an outflow tract abnormality or inadequate estrogenization. The treatment of primary and secondary amenorrhea is based on the causative factor and aims to
A thorough history and physical examination as well as laboratory testing can help narrow the differential diagnosis of amenorrhea. In patients with primary amenorrhea, the presence or absence of sexual development should direct the evaluation. Constitutional delay of growth and puberty commonly causes primary amenorrhea in patients with no sexual development. If the patient has normal pubertal development and a uterus, the most common etiology is congenital outflow tract obstruction with a transverse vaginal septum or imperforate hymen. If laboratory tests are normal, challenge tests can help determine if the cause is an outflow tract abnormality or inadequate estrogenization. The treatment of primary and secondary amenorrhea is based on the causative factor and aims to
Delayed Puberty Topics in Adolescent Gynecology Delayed Puberty Topics in A...MedicineAndHealth14
This document discusses delayed puberty in adolescent girls. It begins by outlining normal pubertal development and defining delayed puberty. Delayed puberty is then classified into three categories: hypergonadotropic hypogonadism (43%), hypogonadotropic hypogonadism (31%), and eugonadism (26%). For evaluation and management, the document recommends obtaining a history, physical exam, initial labs (TSH, prolactin), and a progestational challenge to determine gonadotropin levels and identify underlying causes. Treatment strategies aim to correct the underlying pathology, prevent disease complications, and provide sex steroids.
The Hypothalamus involvement in the sexual dimorphismMaria Hajje
The hypothalamus plays an important role in sexual dimorphism and differentiation. It regulates the secretion of reproductive hormones from the testes and ovaries that direct embryonic development and the formation of primary and secondary sex characteristics. In particular, the hypothalamus influences the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA), which is larger in males compared to females. Studies in rats show that exposure to testosterone or estradiol in the neonatal period masculinizes and feminizes the SDN-POA, respectively. The size of the SDN-POA decreases with age in both sexes due to cell death.
Van Wyke-Grumbach syndrome and pituitary hyperplasia in a six-year-old girlApollo Hospitals
Hypothyroidism is usually associated with delayed puberty and occasionally may present with isosexual precocious puberty. In girls, this may present with breast development, multicystic ovaries and vaginal bleeding. This entity characterized by ovarian hyper stimulation leading to early puberty secondary to hypothyroidism is known as Van Wyke Grumbach syndrome. In contrast to the early puberty caused by other causes, precocious puberty of hypothyroidism is characterized by short stature and delayed bone age. Awareness about this condition and the treatment of this condition with levothyroxine will lead to avoidance of surgery and unnecessary intervention. We present the case of a six-year-old girl who presented with precocious puberty and pituitary hyperplasia. This case highlights the need for the professionals to familiarize themselves about uncommon complications of untreated hypothyroidism.
L6-8.Disorders of the reproductive system.pptxDr Bilal Natiq
In the male, the testis serves two principal functions: synthesis of testosterone by the interstitial Leydig cells under the control of luteinising hormone (LH), and spermatogenesis by Sertoli cells under the control of follicle-stimulating hormone (FSH) (but also requiring adequate testosterone).
Key developments in the research on reproductive endocrinologyEFSA EU
This document summarizes key developments in research on reproductive endocrinology. It discusses how reproductive hormones regulate development and influence health risks. Males and females have different fat deposition and disease risks due to evolutionary reproductive roles. Disorders like cryptorchidism and low sperm counts are surprisingly common. Evidence suggests fetal exposure to hormones and nutrition can impact adult health and even grandchildren's health via epigenetic changes. Reproduction allows offspring to potentially adapt to environments, though current Western diets may impair this process.
The document discusses various topics related to puberty, including definitions of key terms, the normal sequence and timing of pubertal changes, causes and treatment of precocious and delayed puberty, and case studies. Precocious puberty can be true/idiopathic, due to tumors or other medical issues, or pseudopuberty caused by medication or conditions like premature adrenarche. Delayed puberty may be due to constitutional delay, medical issues impairing the HPA axis, or prior treatments like radiation therapy. Evaluation and management depends on the underlying cause and aim to initiate puberty normally or replace missing hormones.
Evaluation of Some Prominent Biochemical Agents in Menstrual Phases of Womeniosrjce
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
OVARIAN RESERVE DIAGNOSIS & MANAGEMENT DR Sharda Jain Lifecare Centre
Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of remaining eggs. It can be caused by factors like advanced age, chemotherapy, genetics, and lifestyle. Ovarian reserve tests assess markers like antral follicle count, anti-Mullerian hormone, and follicle-stimulating hormone to predict ovarian response. A combination of biochemical tests is effective for predicting diminished ovarian reserve. When test results indicate poor ovarian reserve, treatment options include protocols using gonadotropins, letrozole, or dehydroepiandrosterone to potentially increase live birth rates from in vitro fertilization.
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Diabetic Peripheral Neuropathy and Vitamin B12 IssueUsama Ragab
Diabetic Peripheral Neuropathy and Vitamin B12 Issue
By Dr. Usama Ragab Youssif
Diabetic neuropathies are the most prevalent chronic complications of diabetes
Algorithms for Diabetes Management for StudentsUsama Ragab
This document discusses type 2 diabetes and cardiovascular disease. It provides the following key points:
1. Type 2 diabetes significantly increases the risk of cardiovascular disease, which is the leading cause of death in people with type 2 diabetes. Even modest reductions in blood sugar levels through treatment can substantially reduce cardiovascular risks.
2. Multiple modifiable risk factors like hypertension, dyslipidemia, and smoking are common in people with type 2 diabetes and contribute to increased cardiovascular risk. A multifactorial treatment approach targeting these risk factors alongside blood sugar control is recommended to reduce complications.
3. Incretin-based therapies that target the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide pathways
Gestational Diabetes mellitus (GDM) for StudentsUsama Ragab
Gestational diabetes is diabetes that develops during pregnancy. It is diagnosed either pre-existing type 1 or type 2 diabetes, or gestational diabetes diagnosed during pregnancy. Gestational diabetes screening involves a glucose challenge test between 24-28 weeks of pregnancy, or earlier for those at high risk. Treatment involves lifestyle changes like diet and exercise, and may require insulin if needed to control blood glucose levels. After delivery, women with gestational diabetes have increased risk of developing type 2 diabetes and should undergo testing to check for prediabetes or diabetes.
This document provides information about an upcoming event celebrating World Diabetes Day hosted by the Egyptian Society of Metabolic Syndrome. It includes contact information for Dr. Usama Ragab, who is a speaker at the event. The event will take place on November 16, 2023 at the Sharkia Medical Syndicate. The document also contains slides on topics related to diabetes classification, diagnosis, and epidemiology.
Renal System - History Taking
By Dr. Usama Ragab Youssif
Lecturer of Medicine, Zagazig University
Email: usamaragab@medicine.zu.edu.eg, usama.ragab.zu@gmail.com
SlideShare: https://www.slideshare.net/dr4spring/
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Clinical Endocrinology Round
By Dr. Usama Ragab Youssif
Lecturer of Medicine
Zagazig University
Acromegaly
Cushing
Diabetes
Thyroid
Addison
Techniques and clinical insights
This document provides an overview of peripheral neuropathy (PN), including:
- PN most commonly presents as a length-dependent, symmetric sensorimotor polyneuropathy affecting the distal portions of limbs more than proximal.
- The clinical exam evaluates superficial sensation, deep sensation, motor function, and autonomic involvement. Sensory testing assesses patterns, distributions, and cortical sensation when possible.
- Common causes of PN include diabetes, paraproteinemias, alcoholism, renal failure, vitamin deficiencies, and some infectious diseases. A thorough history helps determine the temporal pattern and potential etiologies.
This document provides information on functional bowel disorders and gastroparesis. It begins with an overview of functional bowel disorders, noting they refer to disorders of gut function without obvious structural abnormalities. It then discusses the Rome IV diagnostic criteria for functional gastrointestinal disorders, which categorizes them into several classes including esophageal, gastroduodenal, bowel, and anorectal disorders. Specific disorders like irritable bowel syndrome, functional dyspepsia, and rumination syndrome are defined. The document then focuses on gastroparesis, defining it as delayed gastric emptying without mechanical obstruction. It discusses the difference between functional dyspepsia and gastroparesis, classifications, epidemiology, etiology, predictive factors, typical presentation,
Heat, Cold and High Altitude Related illnessUsama Ragab
Heat, Cold and High Altitude Related illness
By Dr Usama Ragab
Lecturer of Medicine
Topics are heat and cold related illness and high altitude medical disorders
Sensory, coordination & gait Examination for UndergradUsama Ragab
The document provides information on examining the sensory system. It discusses the different types of sensation including somatic, visceral, and special senses. It then describes in detail how to examine superficial sensation, deep sensation including vibration, joint position, nerve, and muscle sensation. The document outlines examining dermatomal distribution and patterns of sensory loss. It also discusses examining cortical sensation including tactile localization, two-point discrimination, stereognosis, and other tests. Finally, it provides guidance on examining coordination and gait abnormalities.
Imeglimin is a novel, first-in-class antidiabetic drug that targets mitochondrial function. It was shown to improve both insulin resistance and insulin secretion based on animal and human studies. Imeglimin received its first approval in Japan in 2021 based on positive results from the Phase III TIMES clinical trials program demonstrating its efficacy in lowering blood glucose levels and its safety both as monotherapy and in combination with other oral antidiabetic drugs or insulin. Imeglimin may also provide cardiovascular benefits given its effects on improving mitochondrial function in multiple tissues beyond just glycemic control.
Diabetes and Gut interplay
By Dr. Usama Ragab Youssif
In Gastro Canal Association Annual Conference
Agenda
Diabetes as the main player
Gut as the main player
Diabetes and gut in a separate game
Gut as game changer
Tips and tricks: diabetes drugs
Guidelines in Obesity management
By Dr. Usama Ragab Youssif
Obesity-related counseling should be offered to those with BMI ≥25 kg/m2
A 3% to 5% weight loss can result in meaningful reductions in triglycerides, blood glucose, hemoglobin A1c, and the risk of developing type 2 diabetes
Set an initial weight loss goal of 5% to 10% of current body weight over 6 mo
After 6 mo, focus on weight maintenance before attempting further weight loss
Participating in a weight loss program long-term can help improve weight maintenance
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
Insulin Lispro Revisited
By Dr. Usama Ragab Youssif
The discovery of insulin was one of the most dramatic and important milestones in medicine - a Nobel Prize-winning moment in science.
No, the combination of an ACE inhibitor and an ARB is not generally recommended for patients with diabetes and CKD. Some key points:
- There is no evidence that combining an ACEi with an ARB provides additional renal protection compared to monotherapy in patients with diabetes and CKD.
- Combining the two classes of drugs increases the risk of hyperkalemia and acute kidney injury without proven additional benefit over monotherapy.
- Current guidelines recommend using either an ACEi or an ARB as first-line therapy for albuminuria, but do not recommend combining the two classes of drugs.
So in summary, while ACEis and ARBs are both reasonable first-line options, combining
This document summarizes key findings from the IDF Diabetes Atlas 2021:
1) An estimated 537 million adults aged 20-79 have diabetes globally in 2021, representing 1 in 10 adults. 6.7 million deaths are attributed to diabetes each year.
2) The top 10 countries for number of adults with diabetes are China, India, USA, Brazil, Pakistan, Indonesia, Mexico, Egypt, Italy, and Bangladesh. The top countries for diabetes healthcare expenditure are USA, China, Japan, Germany, and India.
3) Diabetes prevalence is increasing worldwide, with the majority (75%) of people with diabetes living in low and middle income countries. Cardiovascular disease is the leading cause of death for people
This document discusses vitamin D deficiency as a global health problem, definitions of vitamin D deficiency, sources and requirements of vitamin D, and consequences of vitamin D deficiency such as osteomalacia and rickets. It provides treatment recommendations for vitamin D deficiency in adults, including initiating treatment at vitamin D levels below 20 ng/mL, recommended dosages of 6000 IU/day, duration of treatment of 4-12 weeks, and follow-up maintenance dosages. Higher dosages may be needed for certain high-risk individuals. Oral cholecalciferol is the preferred route of treatment.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
2. Case
Dr. Usama Ragab Youssif
A 6-year-old girl presents with
advanced breast development. On
examination, some pubic hair is
also observed.
Parents mention that the breast
development started about 6 months
ago, but the pubic hair is recent.
She has been outgrowing clothes
rather rapidly this year.
Neurological examination is normal.
3. To
remember
puberty
terminol
ogy
Onset in girls= 8 – 13 years
Onset in boys= 9 – 14 years
Adrenarche= initiation of
adrenal androgen production
Gonadarche= initiation of
gonadal hormones production
Thelarche= onset of breast
development
Menarche= onset of menses
Dr. Usama Ragab Youssif
4. Definition
Precocious puberty (PP) is
defined as the development
of pubertal changes (2ry
sexual characters), at an
age younger than the
accepted lower limits for
age of onset of puberty.
J Clin Res Pediatr Endocrinol. 2009;1(4):164-74.
Dr. Usama Ragab Youssif
5. We need
revisio
n
Historic. The mean age of menarche in
Europe has decreased from 17 years in
1900 to 12.8 years today, likely due to
improved childhood nutrition and growth.
Genetic. Age at onset of puberty is a
polygenic trait with estimated
heritability of about 50–60%.
Ethnicity. Afro-Caribbean and South
Asian girls tend to have earlier puberty
than Caucasians.
Weight gain is linked to earlier
puberty, while those who are thin and
engage in regular physical activity
often experience delayed puberty.
Dr. Usama Ragab Youssif
6. Epidemiology
0.2 % of females had some form of precocious
puberty (CPP, PPP or benign variants) while it
was less than 0.05% in males.
Female = benign
Male = tumor
Pediatrics. 2005 Dec;116(6):1323-8. Dr. Usama Ragab Youssif
7. Burden
• Psychosocial?
• Kids and their carer
• Initially taller than
their peers
• Finally shorter than
their peers
Dr. Usama Ragab Youssif
8. Rajendram, R., Preedy, V.R. and Martin, C.R. eds., 2022. Cellular, molecular, physiological, and behavioral aspects of
traumatic brain injury. Academic Press.
Dr. Usama Ragab Youssif
9. Santoro et al. International journal of molecular sciences. 2021 Jan 19;22(2):972 Bajpai & Menon. Indian journal of endocrinology and metabolism. 2011 Sep
1;15(Suppl3):S172-9.
KiSS1 R
(GPR54)
Dr. Usama Ragab Youssif
10. Classifications
and subtypes
• Central precocious puberty
(GnRH dependent) = true
• Peripheral precocious puberty
(GnRH independent) = false
• Isolated reversible
• Combined start as PPP then
proceed to CPP
• Isosexual “phenotypically
appropriate” or heterosexual
“phenotypically inappropriate”
Dr. Usama Ragab Youssif
11. The 2 main categories
• Activation of HPG axis
• Elevated “pubertal” LH & FSH
• Elevated T or E2
CPP
• No activation of HPG axis
• Non elevated “prepubertal” LH &
FSH
• Endogenous or exogenous T or E2
PPP
Dr. Usama Ragab Youssif
12. Precocious puberty requires differentiation from
the benign forms of puberty
Owen, K., Turner, H. and Wass, J. eds., 2022. Oxford handbook of endocrinology & diabetes. Oxford
University Press.
lease, follow up these cases as they may represent early phases of P
Dr. Usama Ragab Youssif
13. Obesity Related Precocious Puberty
Dr. Usama Ragab Youssif
Obesity increases leptin → leptin ↑ GnRH release → ↑ FSH/LH
Obesity induced IR → hyperinsulinemia
Excess insulin → ++ aromatase activity
Excess insulin → - - SHBG synthesis in liver → free sex hormones
More apparent in girls than boys
Calcaterra et al. Children. 2023 Jan 29;10(2):241.
15. PPP
Sex steroids from endogenous (gonadal or
extragonadal) or exogenous sources.
Without true HPG axis activation
It is less frequent compared to the CPP.
Prolonged exposure to sex hormones may also
trigger central precocious puberty
Dr. Usama Ragab Youssif
18. Male =
brain
lesion
Mostly hypothalamic hamartoma.
Ectopic neural cells = accessory
GnRH pulse generator.
CPP as early as 12 months of
age.
Gelastic seizures refractory to
ttt
Dr. Usama Ragab Youssif
25. Listen
Early = before the normal age of onset.
Sometimes not early but rapid tempo…
Headache, vomiting, blurring of vision, seizure = CPP
Head trauma, past infection = CPP
Abdominal pain or swelling = ovarian or adrenal
Abnormal diet
A complete family history of puberty onset is also important.
Drug history for kid and parents
Dr. Usama Ragab Youssif
26. Look
• Premature puberty i.e., T2
on SMR
• Linear growth acceleration:
height, weight, growth
velocity (cm/year) and BMI
• 1st = Breast development in
females
• 1st = Increased testicular
volume (greater than 4 ml)
in males.
• Others:
Taller than peers
Adult skin: acne, body
odor
Pubic and axillary hair
development.
Dr. Usama Ragab Youssif
27. Tanner staging
• Sexual maturity
rating (SMR)
• Challenging
• Need practicing
• Difficult e.g.,
breast assessment in
obese girl or penile
length assessment in
obese boy
Dr. Usama Ragab Youssif
28. Adolescent health care : a practical guide. Neinstein, Lawrence S., Neinstein, Lawrence S. (5th
ed.). Philadelphia: Lippincott Williams & Wilkins. 2008. ISBN 9780781792561. OCLC 148727849
Marshall, William A., and James M. Tanner. "Variations in the pattern of pubertal changes
in boys." Archives of disease in childhood 45, no. 239 (1970): 13-23.
Marshall, William A., and James M. Tanner. "Variations in pattern of pubertal changes in
girls." Archives of disease in childhood 44, no. 235 (1969): 291.
• 5 stages
• Based on 2ry sexual characters: genital
development in boys, breast in girls and
pubic hair in both
• Assessed independently i.e., breast,
genitalia, pubic hair
• Puberty means Tanner 2 before 95th of same
age kids
Dr. Usama Ragab Youssif
33. Clues for
the cause
Small testes in presence of
pubic, axillary and body odor
may denote PPP
Aggressive progressive course
= PPP mostly tumors
Unilateral testicular
enlargement = testicular
tumors.
Skin pigmentation = NF-1 or
Mc Cune
Dr. Usama Ragab Youssif
35. Easy
Confirm i.e., precocious T2
Height “+ plotting curves and calculate FH and
MPH”
Bone age
Dr. Usama Ragab Youssif
36. What are the tests should be
performed in PP?
Kim et al. Annals of Pediatric Endocrinology & Metabolism. 2023 Sep;28(3):168.
Dr. Usama Ragab Youssif
37. Measuremen
t of LH,
FSH and
sex
hormones
Kim et al. Annals of Pediatric Endocrinology & Metabolism. 2023 Sep;28(3):168.
Dr. Usama Ragab Youssif
38. LH measurement
3rd generation LH assays
detect levels as low as
0.1 IU/L, making random
LH a good screening test
for CPP, with levels of
0.3 IU/L or higher
considered diagnostic
Many children with CPP
have prepubertal basal
LH levels, but respond
to challenges with GnRH
with an increase to 5
IU/L or above,
indicating pubertal
status
Dr. Usama Ragab Youssif
39. When should a
brain MRI be
performed to
identify organic
causes in patients
with CPP?
Kim et al. Annals of Pediatric Endocrinology & Metabolism.
2023 Sep;28(3):168. Dr. Usama Ragab Youssif
45. CPP
Treatme
nt
Aim: psychosocial support, preserve adult
height
Concept: long-acting GnRH analogues to
suppress HPG axis “Pituitary LH and FSH
secretion is inhibited by continuous exposure
to GnrH analogues”
Goserelin 3.6mg SC monthly or 10.8mg SC 3-
monthly, or triptorelin 3.75mg monthly or
11.25mg 3-monthly SC or deep IM every 2 weeks
for the first three injections, then 3- to 4-
weekly thereafter. Leuprolide acetate.
Safety: safe, skin reaction, flushing
Dr. Usama Ragab Youssif
47. Monitoring
of
treatment –
Clinically
and Lab
• Clinically: pubertal progression, growth
velocity, and skeletal maturation
• Lab: ensuring that pre-dose LH, FSH, and sex
hormone levels remain at low prepubertal
levels.
• The dosing intervals may need to be reduced
if there is evidence of inadequate
suppression of pubertal development.
Dr. Usama Ragab Youssif
50. Is the treatment with a GnRH agonist
associated with an increased risk of other
diseases in the long term?
Dr. Usama Ragab Youssif
51. PPP
Treatme
nt
Concept: Eliminating the source of sex steroids.
Gonadal and adrenal tumors: Surgery
Classic CAH is treated with dexamethasone.
McCune-Albright syndrome: block estrogen
synthesis by aromatase inhibitors (anastrozole,
letrozole) and selective estrogen selective
receptor modulator (tamoxifen).
Familial male-limited precocious puberty is not
well established, but the preferred treatment is
a combination of an androgen antagonist
(spironolactone) and an aromatase inhibitor
Dr. Usama Ragab Youssif
52. Recap
PP = early puberty i.e., <8 and <9
• Identified by Tanner
Causes
• CPP often idiopathic mostly in females or have a cause often
in males
• PPP: excess sex steroids or hCG or hypersensitive LH receptors
Dr. Usama Ragab Youssif
53. Diagnosis
Bone age: advanced
Sex hormones & Gonadotrophin levels:
dependent or independent
Imaging: Brain or gonads or elswhere
Dr. Usama Ragab Youssif
55. Thank
You
Dr. Usama Ragab Youssif
Email: usamaragab@medicine.zu.edu.eg, usama.ragab.zu@gmail.com
SlideShare: https://www.slideshare.net/dr4spring/
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Notas del editor
The traditional definition of precocious puberty is the development of secondary sexual characteristics before 8 years of age in girls and 9 years in boys.
--------------------------
This is due to premature activation of pulsatile GnrH secretion from the hypothalamus.
The normal progression in physical changes (‘consonance’) is maintained but may be accelerated. As precocious puberty is defined as age at onset 2 SD before the average age, with ongoing secular trends to earlier puberty, this may be physiological in an increasing number of children, especially in girls with a family history of early puberty.
By contrast, boys with precocious puberty have a greater risk of intracranial or other pathology.
This is due to premature activation of pulsatile GnrH secretion from the hypothalamus.
The normal progression in physical changes (‘consonance’) is maintained but may be accelerated. As precocious puberty is defined as age at onset 2 SD before the average age, with ongoing secular trends to earlier puberty, this may be physiological in an increasing number of children, especially in girls with a family history of early puberty.
By contrast, boys with precocious puberty have a greater risk of intracranial or other pathology.
The first epidemiologic study from a Danish national registry estimated that 0.2 % of females had some form of precocious puberty (CPP, PPP or benign variants) while it was less than 0.05% in males.
----------------------
This is due to premature activation of pulsatile GnrH secretion from the hypothalamus.
The normal progression in physical changes (‘consonance’) is maintained but may be accelerated. As precocious puberty is defined as age at onset 2 SD before the average age, with ongoing secular trends to earlier puberty, this may be physiological in an increasing number of children, especially in girls with a family history of early puberty.
By contrast, boys with precocious puberty have a greater risk of intracranial or other pathology.
Precocious puberty can lead to short stature, emotional and behavioral issues, substance abuse, conduct issues, social isolation, truancy, multiple sexual partners, peer pressure, and self-image concerns, often resolved by early adulthood.
Precocious puberty can lead to short stature, emotional and behavioral issues, substance abuse, conduct issues, social isolation, truancy, multiple sexual partners, peer pressure, and self-image concerns, often resolved by early adulthood.
Leydig cell produces testosterone
Why I have mentioned KISS here?
Because: one of the causes of CPP may be genetics –gain of function mutation encoding the kisspeptin (KISS1) and its receptor (KISSR) genes
This type of precocious puberty represents true pubertal development due to the earlier maturation and activation of the HPG axis.
Most of the time, the common cause in females is idiopathic, and in males, there is usually an underlying pathology.
This type of precocious puberty represents true pubertal development due to the earlier maturation and activation of the HPG axis.
Most of the time, the common cause in females is idiopathic, and in males, there is usually an underlying pathology.
-------------------------
This is due to premature activation of pulsatile GnrH secretion from the hypothalamus.
The normal progression in physical changes (‘consonance’) is maintained but may be accelerated. As precocious puberty is defined as age at onset 2 SD before the average age, with ongoing secular trends to earlier puberty, this may be physiological in an increasing number of children, especially in girls with a family history of early puberty.
By contrast, boys with precocious puberty have a greater risk of intracranial or other pathology.
--------------------------------
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.
Precocious development of secondary sexual characteristics independent of the GnRH pulsatile secretion constitutes PPP
This is due to the production of sex steroids from endogenous or exogenous sources.
It is less frequent compared to the CPP.
The most common brain lesion causing CPP is hypothalamic hamartoma.
The ectopic neural cells in the lesion serve as an accessory GnRH pulse generator.
It presents with precocious puberty in infancy as early as 12 months of age.
The most characteristic association is gelastic seizures, which are usually refractory to medications.
Treatment is with androgen receptor-blocking agents (CPA or flutamide) and aromatase inhibitors.
Early = before the normal age of onset.
Sometimes not early but rapid tempo…
Rapid progression of puberty, even at a normal age, is abnormal.
Symptoms include neurological issues like headaches, seizures, and visual and cognitive changes may suggest central pathology.
Ovarian pathology may also present with abdominal pain.
A history of head trauma, brain infections, or unusual diets should be explored.
A complete family history of puberty onset is also important.
---------------------------
Age when 2° sexual features first noted.
What features are present and in what order did they appear? For example, virilization (pubic, axillary, or facial hair; acne; body odour), genital or breast enlargement, galactorrhoea (very rare), menarche, or cyclical mood changes?
recent growth acceleration?
Family history of early puberty?
Past history of rapid early life weight gain, adoption or migration from a poorer social setting, or prior CNS abnormality or insult (e.g. irradiation)?
The presentation is usually consistent with premature development of pubertal signs.
The initial clinical signs are breast development in females and increased testicular volume (greater than 4 ml) in males.
The other signs and symptoms include increased linear growth, acne, muscular changes, body odor, and pubic and axillary hair development.
-------------------------------
Breast or genital and testicular size; degree of virilization (clitoromegaly in girls indicates abnormal androgen levels).
Neurological examination, including visual fields and fundoscopy.
Abdominal or testicular masses?
Unusual skin pigmentation? (café-au-lait patches—McCune–Albright (see E McCune–Albright syndrome, pp. 654–5) or NF type 1 (NF-1) (see E Neurofibromatosis, pp. 658–60)).
Assess height and BMI, and height velocity over 4–6 months.
In females, accurate Tanner staging of the breast should take place, which is particularly challenging in obese or overweight girls to differentiate between adipose tissue and the glandular breast tissue.
------------------------
The 1st indication of puberty is breast development in girls and an increase in testicular size in boys.
Puberty then progresses in an orderly or ‘consonant’ manner through distinct stages (see Table 7.2). Puberty rating by an experienced observer involves identification of the pubertal stage—particularly, breast development in girls and testicular volume (using an orchidometer) in boys.
Genitals (male)[edit]
Photos of the Tanner scale for males.
Tanner I: testicular volume less than 1.5 ml; small penis (prepubertal)
Tanner II: testicular volume between 1.6 and 6 ml; skin on scrotum thins, reddens and enlarges; penis length unchanged
Tanner III: testicular volume between 6 and 12 ml; scrotum enlarges further; penis begins to lengthen
Tanner IV: testicular volume between 12 and 20 ml; scrotum enlarges further and darkens; penis further increases in length and starts to increase in breadth
Tanner V: testicular volume greater than or equal to 20 ml; adult scrotum and penis
---------------------
Breasts (female)
Photos of the Tanner scale for females
Tanner I: no glandular tissue: areola follows the skin contours of the chest (prepubertal)
Tanner II: breast bud forms, with small area of surrounding glandular tissue; areola begins to widen
Tanner III: breast begins to become more elevated, and extends beyond the borders of the areola, which continues to widen but remains in contour with surrounding breast
Tanner IV: increased breast sizing and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast
Tanner V: breast reaches final adult size; areola returns to contour of the surrounding breast, with a projecting central papilla
---------------------
Pubic hair (both male and female)
Tanner I: no pubic hair at all (prepubertal)
Tanner II: small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females)
Tanner III: hair becomes more coarse and curly, and begins to extend laterally\
Tanner IV: adult-like hair quality, extending across pubis but sparing medial thighs
Tanner V: hair extends to medial surface of the thighs
12 balls
First 3 balls are prepubertal stages
Adult is final 2 balls i.e., 20 and 25
An orchidometer is a tool used to assess testicular size, consisting of a series of beads or ellipsoids of increasing volume, typically ranging from 2 mL to 24 mL. The most common type of orchidometer is the Prader orchidometer, which is a chain of 12 solid wooden ellipsoids with volumes ranging from 1 mL to 25 mL. Testicular size is measured by visually comparing the size of each testis to the corresponding bead or ellipsoid on the orchidometer.
In males, an orchidometer should be used to determine the testicular volume. Volumes of more than 4 ml confirm pubertal development.
In males and females with pubic hair and body odor, the absence of increased testicular volume and breast development should prompt investigation of peripheral causes.
Unilateral testicular enlargement is likely due to testicular tumors.
Bone age is an initial screening test. If the bone age is advanced (greater than two standard deviations) than the chronologic age, further testing should follow.
Hormonal testing differentiates peripheral and central causes.
A baseline prepubertal LH level of greater than 0.3 IU/L is suggestive of CPP. Levels under 0.3 are indicative of peripheral causes or benign variants.
If there is a high suspicion for central causes, a GnRH stimulation test, which is considered to be the gold standard, should be done. This test is not available in the United States so that the GnRH agonist is an alternative.
FSH levels are of limited utility.
Very high levels of estradiol in females or testosterone in males associated with suppressed LH and FSH are indicative of peripheral precocity.
Measurement of adrenal androgens such as dehydroepiandrosterone sulfate (DHEA S) differentiates between testicular and adrenal sources of androgens.
Many children with CPP have prepubertal basal LH levels, but respond to challenges with GnRH with an increase to 5 IU/L or above, indicating pubertal status.
Because of the development of more sensitive third-generation assays for luteinizing hormone (LH), which can detect levels as low as 0.1 IU/L or lower, random LH is now considered a good screening test for CPP, with levels of 0.3 IU/L or above considered diagnostic. However, many children with CPP have prepubertal basal LH levels but will respond to a challenge with gonadotropin-releasing hormone (GnRH) with an increase to 5 IU/L or above, which is considered pubertal.
Bone age is an initial screening test. If the bone age is advanced (greater than two standard deviations) than the chronologic age, further testing should follow.
Hormonal testing differentiates peripheral and central causes.
A baseline prepubertal LH level of greater than 0.3 IU/L is suggestive of CPP. Levels under 0.3 are indicative of peripheral causes or benign variants.
If there is a high suspicion for central causes, a GnRH stimulation test, which is considered to be the gold standard, should be done. This test is not available in the United States so that the GnRH agonist is an alternative.
FSH levels are of limited utility.
Very high levels of estradiol in females or testosterone in males associated with suppressed LH and FSH are indicative of peripheral precocity.
Measurement of adrenal androgens such as dehydroepiandrosterone sulfate (DHEA S) differentiates between testicular and adrenal sources of androgens.
Magnetic resonance imaging is to be performed in all cases of CPP, especially in males, to rule out a hypothalamic lesion. It is also to be considered in females who present with early pubertal changes (less than 6 years of age).
The decision to treat depends on the age of the child and the progression of puberty. If the child has rapidly progressing symptoms or if bone age is significantly advanced, consider treatment. The main goals of treatment are to preserve the adult height and to alleviate the associated psychosocial stress. GnRH agonists are the standard of care.[6] Many different formulations (intranasal, intramuscular and subcutaneous) of long and short-acting GnRH agonists exist. The choice of the formulation depends on the patient and clinician preference. In the United States, leuprolide acetate is the most common. It is a depot injection administered every 3 months.
GnRH agonist therapy is generally considered safe, with no reported significant adverse events. The most common adverse events include local skin reactions (intramuscular pain, sterile abscesses) and post-menopausal symptoms (hot flushes).
While on treatment, periodic monitoring of pubertal progression, growth velocity, and skeletal maturation are necessary.
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Aims of treatment are:
• To avoid psychological distress for the child.
• To avoid reduced final height due to premature bone maturation and
early epiphyseal fusion. A final height prediction is often helpful when
considering treatment. Significant improvement in adult height is only
likely to be achieved if treatment is started ≤6 years of age.
ombination of GH and GnRH analog: GH has been used to counter growth suppression induced by GnRH analog.[41] While the role in children with underlying GH deficiency is clear, the effect on GH sufficient children is modest.
Patients on GnRH analogs should be followed up 3-monthly for pubertal status and growth parameters. Treatment is expected to result in cessation of pubertal development, but may not cause regression of all features. GnRH analog treatment has no effect on pubic hair development as it is controlled by adrenal androgens. Initial flare-up following GnRH analog may result in advancement of pubertal changes and rarely withdrawal of vaginal bleeding. Cyproterone acetate or medroxyprogesterone acetate may be combined with GnRH analog during the first 3 months of treatment to avoid the flare-up response. Good compliance to GnRH analog is mandatory as delay in treatment may result in resensitization of gonadotropes to GnRH and may cause flare-up response with the next dose.
Adequacy of treatment is assessed by demonstration of pre-pubertal LH levels in response to GnRH stimulation test performed 6-monthly (peak LH less than 2 IU/L).[33] Given the difficulties in procuring native GnRH and the need for separate intravenous injection, measurement of LH levels after GnRH agonist injection has been evaluated. LH levels below 6 IU/L, 2 hours after longacting GnRH agonist, indicates adequate gonadal suppression.[34] Children with inadequate gonadal suppression on 3-monthly injections should be shifted to monthly injection. If the suppression still remains inadequate, the frequency of injections should be increased. Bone age should be obtained annually and used for prediction of final height.
GnRH analog should be continued till the age of 10 years in girls and 12 years in boys (or GnRHa was discontinued when BA reached 12 years.)
Discontinuation of treatment results in gradual reappearance of secondary sexual characters.
Menarche is usually attained around 12–18 months following discontinuation of treatment
Treatment is directed towards eliminating the source of sex steroids. Surgery is indicated in gonadal and adrenal tumors. If exogenous sources of sex steroids are identified, they should be eliminated. Classic congenital CAH is treated with glucocorticoids. In McCune-Albright syndrome, some benefit occurs with blocking the estrogen synthesis using aromatase inhibitors (anastrozole, letrozole) and selective estrogen selective receptor modulator (tamoxifen). The optimal treatment for familial male-limited precocious puberty is not well established, but the preferred treatment is a combination of an androgen antagonist (spironolactone) and an aromatase inhibitor (anastrozole, testolactone).[7]