Puberty tumour by nikeborome

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									        Puberty

And the problems which arise
      around this time
   Normal genital development
• The mammalian fetus has an inherent tendency
  to develop into a female.
• The primitive human gonad starts to develop
  between the 4th and 6th week of fetal life deriving
  from cells of endodermal origin that migrate from
  the yolk sac to the genital ridge.
• The gonad is initially bipotential and develops
  into a testis or ovary depending upon karyotype.
Male genital development
               Y-Chromosome


           Testicular differentiation



Leydig cells                       Sertoli cells


Testosterone                Anti-Mullerian hormone
                                     Testosterone




     dihydrotestosterone                              Anti-mullerian hormone




Virilization of external genitalia                  Inhibition of mullerian ducts




       Wolfian ducts
    Male internal genitalia
    Male genital development
• Presence of Y chromosome
• Testicular hormone production
• Normal responsiveness of androgen-
  dependant tissues
   Female genital development
• Spontaneous process independent of hormonal
  influences.
• Without Y chromosome the primitive gonads
  develop into ovaries.
• Mullerian ducts develop into female internal
  genitalia
• Lower end of vagina forms from the urogenital
  sinus
• External genitalia similarly develop
  spontaneously.
   Categories of ambiguous genitalia


                                Ambiguous genitalia




Female pseudohermaphrodite   Male pseudohermaphrodite   Abnormal gonadal differentiation
 Female pseudohermaphrodite
• XX                   • Congenital adrenal
• No gonads palpable     hyperplasia
   Male pseudohermaphrodite
• XY                • Incomplete
• Two symmetrical     feminisation
  gonads              syndrome
                    • 5-alpha reductase
                      deficiency
                    • Inborn error of
                      testosterone
                      synthesis
  Abnormal gonadal differentiation
• One or asymmetrical   • True hermaphrodite
  gonads                (usually XX)
                        • Mixed gonadal
                          dysgenesis (XO / XY)
   Mangement of baby born with
      ambiguous genitalia
1. Delay registration of birth
2. Karyotype
3. Tests for congenital adrenal hyperplasia
  Mangagement of a baby born with
       ambiguous genitalia
                        Karyotype




        XX               XO/XY           XY




     Not CAH            Pelvic US      HCG test
     ?XX male          Urethrogram      DHT
?True hermaphrodite   Gonadal biopsy   LH/FSH
           Physiology of growth
• Short stature is defined as height below the 3rd centile for
  age. Since the centile charts are based on normal
  children this definition will include 3% of normal children.
• These normal children either have “constitutional” short
  stature (delayed normal growth) in which bone age is
  delayed consistently with height age , where normal
  adult height will be achieved late
• or “familial” short stature in which bone age is consistent
  with chronological age, where the family is short and the
  child’s final height will be short.
Commonest causes of short stature
• Constitutional short stature
• Genetic short stature
• The 3rd centile is 2 standard deviations
  below the mean for age. Children initially
  on a high centile may fail to grow for
  several months and remain above the 3rd
  centile thus the height velocity is important
  when predicting short stature.
 Important causes of short stature
1. Inadequate calorie     5. Neuroendocrine
   intake                     disorders
2. Deficient digestion    6. End-organ
3. Deficient absorption       hyporesponsiveness
4. Chronic disorders      7. Genetic factors
                          8. Short stature after
                              early growth spurt
       Familial short stature
• Child’s corrected height is above 3rd
  centile
• Bone age is normal for chronological age
• History and examination are normal
• See child after a period of 6 months to
  measure height velocity.
   Constitutional short stature
• Child looks normal
• Bone age is delayed consistent with height
  age
• Height velocity over 6 – 12 months is
  normal
  Investigations of short stature
1.    Bone age (x-ray left wrist and hand)
2.    Imaging of pituitary fossa
3.    Urinalysis for protein and sugar
4.    Serum thyroxine and TSH
5.    Karyotype (in girls)
6.    Serum creatinine
7.    Serum calcium, Phosphate and alkaline phosphatase
8.    Small bowel endoscopy
9.    Sweat test
10.   Growth Hormone stimulation test
                 Tall stature
1.   CNS
2.   Hormonal
3.   Metabolic
4.   Genetic
              Normal Puberty
• Complex interactions of    • Before puberty circulating
  hypothalmo-pituitary-        levels of gonadotrophins
  gonadal axis                 are extremely low due
• Hypothalmus stimulates       mainly to negative
  GnRH.                        feedback of gonadal sex
• GnRH stimulates              hormones on
  secretion of both LH and     hypothalmus and a
  FSH from the anterior        degree of pituitary hypo
  pituaitry.                   responsiveness.
• LH and FSH in turn         • Before puberty FSH is the
  stimulate sex hormone        principal pituitary
  secretion by the gonads.     hormone secreted but in
                               adults LH is the principal
                               hormone.
            Normal Puberty
• The hypothalamus       • Pituitary
  becomes much less        gonadotrophins
  sensitive to the         stimulate gonadal sex
  negative feedback of     hormones and as the
  gonadal sex              levels of these
  hormones.                hormones rise the
• GnRH is secreted in      hypothalamus is
  pulses for a few         “reset” at a higher
  minutes per hour.        threshold of
                           sensitivity.
    Normal pubertal gonadotrophin
              function
• FSH is first hormone secreted      • FSH promotes development of
  by both sexes at puberty             seminiferous tubules in boys
• LH is then secreted in pulses        and consequent testicular
  probably in response to              enlargement which is the first
  pulsatile GnRH secretion             clinical sign of male pubertal
• Initially LH secretion occurs        development.
  mainly during sleep but later in   • LH secretion then stimulates
  puberty occurs throughout the        Leydig cells to produce
  day.                                 testosterone, which is
                                       responsible for many of the
                                       male secondary sexual
                                       characteristics.
   Normal pubertal gonadotrophin
             function
• In girls FSH stimulates     • In both sexes, androgen
  oestrogen production by       secretion from the
  the ovarian follicles.        adrenal glands increases
• At puberty, there is a        markedly at or just before
  change form negative to       puberty. Androgens
  positive feedback of          causes the development
  oestrogen on the              of sexual hair, particularly
  production of pre-            in girls.
  ovulatory LH and, to a
  lesser extent FSH, and
  this permits the LH surge
  that precedes ovulation.
         Precocious puberty
• Age of onset 8-13 yrs girls, 10-15 yrs boys
• Pubertal changes before or after these
  ages may be considered abnormal
• Considerable variation in the normal age
  of onset
• Most cases of apparently delayed puberty
  in both sexes are due to constitutional
  delay in growth and puberty.
          Sexual precocity
• True precocious puberty
• Pseudo-precocious puberty
• Dissociated or incomplete precocious
  puberty.
     True precocious puberty
• This is said to occur when there is adult
  type puberty occurring before 8 years in
  girls and 10 years in boys with activation
  of the hypothalamo-pituitary-gonadal axis.
   Pseudo-precocious puberty
• In contrast, this results from sex steroid
  stimulation independent of the axis, and is
  usually distinguishable clinically from true
  precocious puberty because pubertal
  changes are not complete.
      Dissociated or incomplete
         precocious puberty
• In this 3rd category, pubertal changes are
  again incomplete but the category is
  considered separately because the
  prognosis for these children is generally
  benign.
     Some causes of true precocious
                 puberty
1.   Idiopathic
2.   CNS lesions (e.g. trauma, tumours)
3.   Neurofibromatosis
4.   McCune-Albright syndrome (mainly girls)
5.   Hypothyroidism
6.   Gonadotrophin-producing tumours
7.   Miscellaneous
      Some causes of Pseudo-
        precocious puberty
1. Congenital adrenal hyperplasia
2. Virilizing adrenal tumours
3. Ovarian or testicular tumours
4. Non-endocrine gonadotrophin-producing
   tumours
5. Iatrogenic
    Categories of Dissociated or
  incomplete precocious puberty
• Premature thelarche
• Premature adrenarche (pubarche)
• Premature menarche
  Commonest causes of true and
   pseudo-precocious puberty
                            Boys




                                            CNS tumour
 True precocious puberty
                                                 or
       Large testes
                                             idiopathic




Pseudo-precocious puberty          Congenital adrenal hyperplasia
      Small testes                   Virilizing adrenal tumour
      Commonest causes of true and
       pseudo-precocious puberty
                                      Girls




     True precocious puberty                           Idiopathic
  Oestrogenization and virilization                   CNS tumour




                                              Congenital adrenal hyperlasia
PSEUDO-PRECOCIOUS PUBERTY
                                                            Or
 Androgenised with clitoromegaly
                                                Virilizing adrenal tumour
         Physical findings in
       True precocious puberty
• Boys            • Girls
1. Testicular     1. Breast development
   enlargment     2. Other signs of
2. Rapid growth      oestrogenisation
   velocity          (vaginal mucosa)
                  3. Virilization
                  4. Rapid growth
            Investigations in
        True precocious puberty
•   Bone age / skeletal survey
•   GnRH test (measure LH / FSH)
•   Serum androgens (basal and after HCG)
•   Serum oestrogens
•   Serum alpha-fetoprotein
•   Thyroid function
•   Abdominal US or CT scan
•   Cranial CT scan
        Physical findings in
     pseudo precocious puberty
• Boys            •    Girls
1. Small testes   1.   Androgenised
                  2.   Cliteromegaly
                  3.   No signs of
                       Oestrogenisation
                       (breasts /vagina)
           Investigations of
       pseudo-precocious puberty
•    Pubarche / adrenarche or excessive virilization
Test
1. Bone age
2. Plasma 17 OH –progesterone
   11-deoxycortisol
    DHEA-sulphate
     Androstenedione
(basal and after synachten)
3. Urinary steroids
4. Dexamethasone suppresion test
5. Ultrasound or CT of abdomen

								
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