(PROF.) DR. SRIMANTA KUMAR PAL (SENIOR GYNECOLOGIST): Q. 1. What is precocious puberty ? Q.2. What are tye classifications ? Q. 3. What are the pathophysiology? Precocious Puberty

Precocious Puberty

precocious Puberty

• What is the prevalence? Precocious puberty occurs in only 1 of 10,000 girls and is defined as the presence of secondary sexual characteristics at an age >2.5 standard deviations below the mean (i.e., 6 years old in African Americans and 7 years old in Caucasians).

• What are the side effects if P.Puberty ensues? Accelerated growth velocity and rapid bone growth can result in short adult

stature.

• Classifications:-Causes are divided into gonadotropin-dependent and gonadotropin-independent

disorders.

Type 1:-Gonadotropin-Dependent Disorders—Central Precocious Puberty

• Related to premature development of the hypothalamic-pituitary axis

• A condition results in pulsatile secretion of GnRH from the hypothalamus, resulting in release of FSH and LH, which stimulate ovarian function.

• Most commonly idiopathic; secondary sexual characteristics progress in normal sequence but more rapidly than in normal puberty and may fluctuate between progression and regression.

• Characteristic signs and symptoms include breast development without pubic hair development, an increase in height, acne, oily skin or hair, and emotional

Changes.

• May be transmitted in an autosomal recessive fashion

• Often, ovarian follicular cysts are present due to elevated levels of LH and FSH.

• Other causes involve central nervous system disease, particularly mass effects near the hypothalamus. The most common neoplasm is a hamartoma in the posterior hypothalamus.

• Disease often involves areas surrounding the hypothalamus; mass effect, radiation, or ectopic GnRH-secreting cells are thought to cause premature activation of pulsatile secretion of GnRH from the hypothalamus.

• Diagnosis is by CT or MRI of the head; history may be significant for headache, mental status changes, mental retardation, dysmorphic syndromes, along with the premature development of secondary sexual characteristics.

• Treatment should be directed at the underlying cause; the location of many of such tumors makes resection difficult, and, as a result, chemotherapy or radiation may be indicated.

• Treatment with a GnRH agonist can result in a short burst of gonadotropin release, followed by downregulation and a decrease in the level of circulating gonadotropins. Follow estradiol levels to make appropriate dose adjustments.

Type II P Puberty:

Gonadotropin-Independent Disorders—Pseudoprecocious Puberty

• Exogenous hormones causing early puberty result from a peripheral source.

’ development of pubertal characteristics may be more rapid than with central causes flue to a faster initial rate of hormone production.

differential diagnosis includes estrogen-secreting tumors, benign follicular ovarian eysts, McCune-Albright syndrome, Peutz-Jeghers syndrome, adrenal disorders, and primary hypothyroidism. ^ts,rogen-Secreting Ovarian Tumors '

Benign Ovarian Cysts

• Most common form of estrogen-secreting masses in children

• May require a diagnostic laparoscopy or possibly exploratory laparotomy to differentiate from a malignant tumor. Removal of the cyst may be therapeutic.

What is McCune-Albright Syndrome

• Triad: ca(6 au lait spots in skin, polyostotic fibrous dysplasia (bone changes) , and cysts of skull and long bones; precocious puberty is present in 40% of cases

• Associated with rapid breast development and early occurrence of menarche

• Sexual precocity results from recurrent follicular cysts. Removal of cyst is not helpful.

• Aromatase inhibitors may help control symptoms.

• Evaluate with serial pelvic sonograms to detect the presence of gonadal tumors.

Peutz-Jeghers Syndrome

• Commonly characterized by mucocutaneous pigmentation and gastrointestinal polyposis.

• Also associated with rare sex cord tumors, including epithelial tumors of the ovary, dysgerminomas, or Sertoli-Leydig cell tumors, whose estrogen secretion may result in feminization and incomplete sexual precocity.

• Girls with Peutz-Jeghers syndrome should be screened with serial pelvic sonograms.

Adrenal Disorders

• Some adrenal adenomas secrete estrogen and may result in sexual precocity.

Primary Hypothyroidism

• Characterized by premature breast development and galactorrhea without an associated growth spurt. See Chapter 13.

Key Points in Evaluation and Management of Precocious Puberty

• Perform a detailed evaluation with Tanner staging.

• Laboratory data should include LH, FSH, prolactin, estradiol, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, TSH, T4, human chorionic gonadotropin.

• A GnRH stimulation test can definitively diagnose central precocious puberty.

• Obtain an x-ray to determine bone age. Head CT or MR1 can rule out an intracranial mass. Abdominal/pelvic ultrasound can be used to evaluate the ovaries.

• Goals for management include maximizing adult height and delaying maturation. Treat the intracranial, ovarian, or adrenal pathology if present and attempt to reduce associated emotional problems.

Premature Thelarche

• Premature Thelarche is defined as bilateral breast development without other signs of sexual maturation in girls before age 8 years.

• Commonly occurs by age 2 years and is rare after age 4 years.

• The etiology is unclear, but exogenous estrogen must be excluded.

• Precocious puberty must be ruled out.

• Document the appearance of the vaginal mucosa, breast size, and presence or absence of a pelvic mass.

• Obtain bone age. It is within normal range in premature thelarche.

• Perform pelvic ultrasonography, which should exclude ovarian pathology.

• Obtain plasma estrogen levels. They may be mildly elevated; significant elevations suggest another etiology.

. In idiopathic cases, regression often occurs after a few months but may persist for several years.

Which subspecialty is most competent to investigate cases of Precocious Puberty (PP) cases? N precocious puberty how should be given Inj. Leuprolide and what investigation should done in follow up.?

· .

11.75mg i. M 3 monthly

Do MRI rule out Central cause of precocious puberty .

The dose of GnRH agonist depends on age and weight . at present i am having a patient who is on 9 months on LH ,this time i gave het 22.5 depends on lH

Which subspecialty is most competent to investigate cases of Precocious Puberty (PP) cases?
Should we, the gynecologists at all investigate & treat PP cases? -In my opinion Neurologists and or Endocrinologists are the appropriate persons to streamline .

Can the parents produce the municipality/Corporation issued birth certificates? Can we be satisfied with are age? Or we have to bank upon the determination of bony age cfor which we have to rely on the X-ray of hand & wrist.

How to examine her? 1) Measure height, Wt, serial recording of growth velocity per 6 months ,Fundoscopy, Skin for spots as stated above, Tanner staging every 6 monthly, Then come radiological & Endocrine evaluation-as I have warned that to find out the cause of Pre.Puberty is a mammoth task, & Exact final diag is possible by exclusion only.

What is her medical history? If a gynecologist intend to keep the case of Precocious Puberty under his/her care then detail medical history elicitation in of utmost importance. A) Childhood diseases e.g. any neurological disease/ Trauma or fall over head/meningitis/Koch’s meningitis /Encephalitis /seizure disorder. Any visual disorders have to be enquired. Any skin spots of McCune Albright Syndrome-( café-U-LAIT SPOTS))have to observed. Any drug intake, cosmetics with oestrogen, Ingestions of xenoestrogens? Chronological apearnce of symptoms –monthwiese-thelarche, Puvberache and menarche –documentation. Is she taking Thyroid replacing agents-because sever Pr. Hypothyroid cases can present with Pre.Puberty(PP) simply because high serum TSH level can activate FSH receptors and stimulate E2 secretion for m ovaries as there is structural similarity with TSH & FSH.

Should we, the gynecologists at all investigate & treat PP cases? -In my opinion Neurologists and or Endocrinologists are the appropriate persons to streamline the investigations cases of PP and to find out the exact etiology, if there be any. Otherwise if such a case is left to gynecologists then there will be many unnecessary investigations because basically there are many causes of PP and exact diagnosis is only possible by a method of exclusion. Such costly investigation is MRI Brain, Other radiological/ CT investigations of abdomen many costly hormone assays etc . Neurlogists, can hopefully streamline the investigations and make out the exact diagnosis.

What are the different types of Precocious Puberty? There are broadly two types of PP i.e. Gonadotrophin-dependent Isosexual PP (Precocious Puberty) & another is Gonadotrophin-independent Isosexual PP (Precocious Puberty). In the former group ,once substantiated by diff lab tests , then Depot agonists drugs will work though there are other pharmacological agents lkie Inj Depot Progesterone.

What is the uncommon but third type of PP? Additionally there is another large group of cases where there is only either premature adrenarche or only P. Thealrche. But fortunately most of such girls with singular expression are found to be variant normal puberty on follow up. They need follow up only, once diag is confirmed by multiple tests as quoted above.

Why Adrenarche does occur? Its Dynamics?:- In cases of isolated pubarche unassociated with thealrche, the symptom of premature excessive growth of sex hairs are due to premature activation of adrenal glands(most possibly P-H are not involved in these disorder) à Raised serum DHEASO4—a serum level in P. Adrenarche will be somewhere 40 mcg/dL.

Is premature adrenarche is a forerunner of PCOS/DM in Male children too? The cause as it why premature activation of adrenal occurs is unclear but researches have observed that most of such girls eventually develop PCOS as they grow up à by late teens they develop Androgen excess disorders. Maternal hyperinsulinaemia may have some impact in the genesis of decreased growth in foetal life, -> later appearance of Pre. Pubarcheà Early appearance of hyperandrogenism in the childhoodàlater by mid-thirties appearance of CVS diseases & T2D.

What is meant by Gonadotrophin-dependent Isosexual PP (Precocious Puberty)? This is mostly idiopathic as why in few girls there is activation of HPO axis occurs and why some active neuropeptide like Kisxpeptin –which is an excitatory neuroregulator of GnRH secretion.) get prematurely activated is still not known to the investigators involved-except possible ) are largely unknown.

Characteristics of Gonadotrophin-dependent PP (which is also sometimes termed as central PP/ True PP):-- The diag is only made after –exclusion of abut other 10 common causes of PP. Such investigations, as I have said early are quite costly. Detailed history taking backed up by neurologist/Endocrinologist colleague will quickly help gynecologists at a rational diagnosis with minimal expenses .In Central PP -both breast and P hair dev occurs simultaneously in an orderly way but too early before the age of 8 yrs... This premature growth of sex characteristics are as per gender of child. If there is confirmed due to early maturation of H-P axis if there is confirmed due to early maturation of H-P axis after

On most cases the serum gonadotrophin will be at pubertal level and cause is mostly idiopathic and why so early maturation of H-P-Gonadal axis matures us as yet elusive to researches. But, then again diagnosis has to be made by a process of exclusion . For exclusion of other causes one has to perform at least MRI of Brain to exclude cranial tumours, cysts, mild hydrocephalus-? Koch’s etiology, midline Septal defects .Additionally one should refer to neurologist for any neurodeficits. In addition to CNS abnormalities mentioned above, the following diseases can yield to G-dependent PP. Such disease s are CAH, Virilizing tumours Mc Cune- Albright Syndrome often favour early mat. Of HPO axis.

What is the role played by kisxpeptin gene receptors ?? Researchers have claimed that abnormalities of kisxpeptin gene receptors can also cause such abnormality. Because Kisxpeptin is an excitatory neuroregulator of GnRH secretion.

Defined as dev. Of S Sex characters before the age of 8 yrs. Some countries have lowered the age upto 6 yrs as normal in black girls.

Type 1. What is meant by Gonadotrophin-independent Isosexual PP (Precocious Puberty)?

Type 2; - Gonadotrophin-independent PP: - also called peripheral/ Pseudo-PP: - the symptoms of breast dev (P. thealrche) or * hair dev (P. adrenarche/peerage) is independent of endogenous gonadotrophin levels. Causes of such G-independent are diseases, usually tumours of Gonads, Adrenaks, Environmental disorders, and rarely die to ingestion of sex steroids. This Type 2 may of two types e.g. a) is sexual b) contra-sexual-uncommon indeed e.g. virilization in girls and Feminization our boys.

There is another term called “Incomplete PP: - which means that there is either isolated thealrche or adrenarche, Puberache). These are mostly variants of normal pubertal development. Though few will eventually yield to full-fledged complete PP in few months.

Investigations-Endocrine evaluations.

Estimate Bone age.

Imaging of brain, Pelvic USG

How is the abnormal function & early acquisition of the GnRH secreting neurons bring early puberty in girls?

What normally happens at the beginning of Puberty? We are aware of the fact that pubertal developmental changes ( i.e. thealrche, menarche, wt gain, height spurt & appearance of puberache) all are controlled by maturity of neuroendocrine signalling . But what cause or initiate signalling in a positive way or beneficial way but few year ahead is still unknown. But if for some reason or other neurones get activated then P P will bound to followed by to sexual maturity is not yet fully known. But it is presumed that if there is disruption of cerebral cortical functions then can occasionally initiation of P puberache .These factors change

Can maternal obesity and or Gestational diabetes be linked to early puberty in daughters.I leave this Q to be answered by members who have enough time to read at library.

A new study published online in American Journal of Epidemiology investigated the hypothesis than in utero exposure to obesity and hyperglycemia leads to early puberty.

http://obgynupdated.blogspot.com/…/maternal-obesity-and-ges…

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Firstly :Do not blame the parents ,mother in particular whenever a precocious pubertal case is brought to your clinic or OPD. Firstly, whenever clinicians face a case of Pre Puberty he/ she should not consider all such symptoms are related to maternal environment in utero. Because nothing could be done once the neonate is born and it is no poin tin blaming the mother who carried the foetus in her womb.

Causes of early pubertal changes are varying and mandate detailed neuro-endocrine evaluation. Not all Pre Puberty/ Adrenarche/Thelarche are due to maternal GDM /Obesity.

Point to remember 1A. Point to recollect when you were at canteen taking half cigarette sharing rest half of cigarette with your boy friend ( your classmates) : You and your boyfriend now hubby came out of Lecture theatre as soon Attendance( roll call ) was over!! This still happens??: Did you attended Physiology classes regularly or sent time at College canteen when Gonadotrophins were taught?? When and how puberty occurs: Dynamics of hormonal interplay!! Ans:-The onset of puberty is caused by the secretion of high-amplitude pulses of gonadotropin-releasing hormone (GnRH) by the hypothalamus. The hypothesize HPG axis, which is highly sensitive to feedback inhibition by 1) small amounts of sex steroids, and (2) central neural pathways that suppress the release of GnRH pulses. Then after a few months

high-amplitude pulses of GnRH cause-à pulsatile increases in the pituitary gonadotropin A) -luteinizing hormone (LH) and B) later follicle-stimulating hormone (FSH).

Point to remember 1 B. What does LH does at this time .You are still unmarried?? Increased LH levels stimulate production of sex steroids from A) in boys by testicular Leydig cells or b) in girls :-ovarian granulosa cells.

What causes physical changes at puberty?? It is not LH. It is pubertal levels of androgens or estrogens cause the physical changes of puberty, including d mechanisms that suppress onset of puberty include (1) the gonadotropin-releasing hormone (GnRH) by the hypothalamus ,It is hypothesize 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.

Point to remember 2:--Do you know that it is the only condition where there is gonadotrophin secretion unassociated with LH secretion. It is characterized by FSH dominance and overnight gonadotrophin secretion, which is characterized by single FSH pulses The classical type, however commences during the first year of life and tends to resolve by the age of 2yrs. The second type of P thelarche where the age of onset is over 2 years of age and this tends to be more persistent and with a higher incidence of uterine bleeding is characterized by single FSH pulses!!!

Point to remember 3:- Is it a beningn self limiting diseases or a matter of concern?? How to diagnose it at clinic that it is Prem Thelarche?? Ans:-The breast appearance is typically with relatively immature nipple development and is never more than Tanner Breast Stage III.:- Point to remember 4:-Isolated Premature Thelarche, to me appears to mostly a benign, self-limiting condition which is characterized by breast development with no other signs of sexual maturation. There is no pubic or axillary hair development(adrenarche) , girls behavior at home(psychological maturity-Reasoning) and at school is normal, growth is normal (no growth spurt-Puberty) and the skeletal age is appropriate. The breast development has atypical appearance with relatively immature nipple development and is never more than Tanner Breast Stage III. Breast development is usually asymmetrical.

Point to remember 5: Treatment reqd? If Treat by what agent? Gonadotrophins to suppress FSH?? Treat Outcome: To Treat or not to treat?? Ans from Grand-pa: Don’t treat :-The condition tends to resolve after about 1–2 years and then the onset of normal puberty occurs at the appropriate age and in the normal way. Very occasionally, vaginal bleeding can occur.

Point to remember 6:- Any warning? Yes. There is a Caution: large follicular cysts may be visible at USG. There have been some reports of women who have had premature thelarche as a child developing large follicular cysts during their menstrual cycles and, thereby, having reduced fertility. However, this has not been substantiated and what limited follow-up has been achieved in further series suggests that there are no long-term sequelae. Isolated premature thelarche is a relatively common condition.

. Point to remember 7:-USG mandatory a noninvasive low cost tets to exclude Granulososa cell tumour?? Ans:-On ultrasound the ovaries are small, but often contain large follicular cysts, which increase and decrease in synchrony with the breast development.

Point to remember 8: Types of P T(Premature Thelarche) ?? Ans:-There may well be two types of premature thelarche. The classical type commences during the first year of life and tends to resolve by the age of 2.

There is a second form of premature thelarche, of which the age of onset is over 2 years of age and this tends to be more persistent and with a higher incidence of uterine bleeding. In this ‘non-classical’ form of premature thelarche, it may well be associated with progression to gonadotrophin-dependent precocious puberty. Isolated premature thelarche is a condition which is easy to diagnose clinically and requires no treatment.

Point to remember 9:-The other way of classification: Precocious Puberty (Complete, Partial)

Girls suspected of having central precocious puberty, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve.

Point to remember 10: Do members recommend CT brain? Ans;-No & No. Is the Pt a boy?? Yes. Then do CT because boys with central precocious puberty have more CNS disorders,. So far as girls with P T are concerned imaging studies of these otherwise healthy 6-year-old to 8-year-old girls usually reveal no structural abnormalities. A study of 200 girls in France identified abnormal brain imaging findings in 2% of girls whose onset of puberty was between age 6-8 years and in 20% of girls whose onset of puberty was before age 6 years.

A smaller study from the United Kingdom reported abnormal findings in 15% of 67 girls.Abnormal CT scan or MRI findings are more frequent among boys with central precocious puberty than among girls with central precocious puberty. Point to remember 12:-CNS abnormalities associated with precocious puberty include the following:

Tumors (egg, 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 (e,g, hydrocephalus, arachnoid cysts, suprasellar cysts)

Sent & sent

Point to remember 12: Did you attended Physiology classes regularly or sent time at College canteen when Gonadotrophins were taught?? Ans:-The onset of puberty is caused by the secretion of high-amplitude pulses of gonadotropin-releasing hormone (GnRH) by the hypothalamus. The hypothesize HPG axis, which is highly sensitive to feedback inhibition by 1) small amounts of sex steroids, and (2) central neural pathways that suppress the release of GnRH pulses.

High-amplitude pulses of GnRH cause pulsatile increases in the pituitary gonadotropin-luteinizing hormone (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 d mechanisms that suppress onset of puberty include (1) the gonadotropin-releasing hormone (GnRH) by the hypothalamus. The hypothesize 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.

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)

Sent already:_High-amplitude pulses of GnRH cause pulsatile increases in the pituitary gonadotropin-luteinizing hormone (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 d mechanisms that suppress onset of puberty include (1) theCNS 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)

Q.1. What are the cahnges at puberty in females?? Ans: The time spell when a carefree child becomes responsible adult -Puberty is the first phase of adolescence and is the transition from childhood to maturity. During puberty as many as sevencahnges are noticed by parents & relatives. These are A) physiological changes leading to adult reproductive capacity including B) maturation of hypothalamic pituitary gonadal axis takes place. The remainder of adolescence is concerned with C) mental and emotional adaptation to sex function and development of one’s maturity D) Psychological social and cognitive changes leading to the E) development of an adult identity individualization and maturation of cognitive reasoning skills leading to F) personal independence takes place during adolescence and carefree child becomes responsible adult. Words puberty and adolescence are derived from Latin words pubertas and adolescere which mean adulthood and to grow respectively As both proceed at the same time these are assumed to be identical This period extends from 10-19 years of age.

Timing of puberty

When does puberty occous? One million dolar Question to parents> They)(parents need to be educated. A) Geographic location exposure to light B) general health nutrition C) psychological factors and D) genetic factors influence puberty .

What about urban boys & girls? What do we mean by mesomorphs & n ectomorphs :-- Children 1) closer to equator 2) at lower altitudes 3) in urban areas obese and 4) with family history of early onset menstruation start puberty earlier. Earlier the onset longer is the duration of puberty mesomorphs begins to develop earlier and more rapidly than ectomorphs

Q.4;What is critical body weight theory? According to Rose Frisch critical body weight must be reached to achieved menarche Certain level of body fat is required to menstruate and higher level to ovulate. The theory is teleologically appealing and explains the association between the body weight and menarche and loss of menstrual function with weight loss However current data does not support it the evidence that other factors are involved is indicated by the fact that delayed menarche is experienced of normal weight.

Blind girls experience earlier menarche. All studies have not found relationship between onset of puberty and either body weight mass or body fat distribution to have some role in reproductive physiology Leptin acts as messenger to central nervous system neurons and regulates eating behavior and energy balance Leptin levels increase during childhood until the onset of puberty and suggest that threshold level of leptin is required for puberty to begin. Puberty is considered precocious if it occurs before the girl is 8 years old and delayed if development has not begun by the time she is 14 years.

Pubertal changes

Following changes take place during the puberty and adolescence

Endocrinal

Physical

Psychological

Endocrinal

IN prepubertal phase the activity of hypothalamic pituitary gonadal axis is dormant due to neuronal restraint pathway and by small amount of circulating gonadal steroids.

Adrenarche antedates the onset of gonadal activity by a few years the two processes are not interrelated as these are dissociated in conditions such as central precocious puberty and adrenicirtical failure. Factors governing adrenarche remain obscure.

It is not under control of ACTH propiomelanocortin peptides and melatonin secretion Puberty is associated with prominence of zona reticularis that is relatively deficient in 3 beta hydroxysteroid dehydrogenase activity The preeminence of zona reticularis leads to increased secretion of DHA and DHAS another hypothesis is that serine phosphorylation of P450c 17 enzyme is necessary for 17,20 lease activity and this phosphorylation stimulated by unknown mechanism is responsible for initiation of adrenarche.

Increased adrenal cortical function results in rise in circulating dehydroepiandrosterone sulphate and androstenedione associated with increased adrenal 17b alpha hydroxylase and 17,20 lease activity from age 6-7 years to adolescence . it causes sebum formation growth of pubic and axillary hair change in voice and erectility of clitoris

Gonadarche One to three years before puberty low serum levels of LH during sleep become demonstrable and there is reawakening of hypothalamic pituitary gonadal axis. There is nocturnal release of luteinising hormone releasing factor from hypothalamus leading to secretion of FSH and LH from pituitary gland. GnRH acts as self primer on the gonadotropic cells of the anterior pituitary by inducing cell surface receptors specific for GnRh . Thus synthesis and secretion of gonadotrophins results in ovarian follicle steroid synthesis stimulation . Nocturnal LH pulses increase in amplitude as clinical puberty reaches By mid puberty LH pulse becomes evident during daytime also at 90-120 minutes interval . Hypothalamus receives stimuli from CNS and from other endocrine glands like adrenals and thyroid Genetic nutritional and psychological factors also influence it.

The notion that the negative feedback system of childhood becomes less sensitive as puberty approaches is doubtful. The system is controlled by central mechanism and ultimately positive feedback mechanism needing pulsatile secretion develops. At midpuberty oestrogen enhances LH secretory response to GnRH while combining with inhibin maintains relative inhibition of FSH . Levels in inhibin B are undetectable in pre pubertal girls increase sharply through pubertal stage II to peak in stage III . these reflect increasing ovarian stimulation resulting in increased ovarian follicles . and follicles reaching later stage of development before undergoing atresia. Inhibin B decreases through puberty stage IV and V Inhibin A levels are undetectable or very low in early puberty increasing gradually through pubertal stages to reach their highest values in adult women . Levels of inhibin A > 90 pg / ml are seen only in postmenarcheal girls and in adult women as inhibin A is primarily produced by corpus luteum. Finally regular Lc surges and ovulation takes place The factors regulating the hypothalamic neurons responsible for GnRH secretion are unknown and understanding of these is complex due to following reasons.

Pituitary gonadotrophins are heterogeneous and more active isoforms of LH may be present during puberty

LH immunoreactivity is variable in different immunoassays and results are different from different labs.

Gonadotrophins are secreted in pulsed fashion and single measurement can give wrong conclusion

There is combined reduction in intrinsic suppression of GnRH and decreased sensitivity of negative feedback of oestrogen and this results in reactivation of gonadotrophin secretion in pituitary ad oestrogen production in ovaries in females . FSH rises initially and plateaus in mid puberty while LH tends to rise more slowly and reaches adult levels in late puberty

Reduction of melatonin secretion by pineal gland perhaps is not important in physiological onset of puberty The role of thyroid is also ill defined . Increased thyroid enlargement and skin pigmentation is noted during puberty Prolactin levels rise in parallel with the serum oestrogen levels. With a significant increase in late puberty Although generally more emphasis is placed on the pattern LH secretion than on FSH secretion as the earliest reliable indicator of activities of hypothalamus pituitary axis . emergence of FSH pulses as indicated by a FSH dominant response to GnRH stimulation test has the greatest clinical use.

The increase in gonadotropin production and steroids results in development of secondary sex characteristics and eventual adult function consisting of menarche and ovulation in females.

To summaries there is adrenarche suppression of inhibition of GnRH production by hypothalamus production of FSH and LH pulses by pituitary initially at night and then during day time also oestrogen production by ovaries development of positive feedback mechanism for LH and relative negative feedback of FSH in combination with inhibin.

Important sex differences exist in the maturation of hypothalamus and pituitary gland and serum LH concentration rise earlier in boys than in girls during puberty

(PROF.) DR. SRIMANTA KUMAR PAL (SENIOR GYNECOLOGIST)

Wednesday, 22 May 2019

Q. 1. What is precocious puberty ? Q.2. What are tye classifications ? Q. 3. What are the pathophysiology? Precocious Puberty

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