Term
| Development of Internal Genitalia From Common Genital Structures |
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Definition
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Term
• A10yearoldgirlpresentsfora well child check-up.
• Shehasabreastbudnoted upon palpation of the left breast
• Momisconcernedthatsheis growing up too quickly and notes that she has been outgrowing clothing and shoes rapidly
• Sheworriesthat“periods”will be right around the corner
How would you counsel this mother and her daughter? |
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Definition
| She is developing normally and would not expect periods for another 2 years or so |
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Term
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Definition
• Cognitive, psychosocial and biologic maturation – 4 – 4.5 years
• Consists of series of predictable events
• Tanner stages – sequence, timing and tempo of pubertal maturation:
• pubic hair • breasts
• genitalia |
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Term
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Definition
| Activation of the hypothalamic-pituitary- gonadal (HPG) axis with production of sex steroids and germ cell maturation (Central Puberty or True Puberty) |
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Term
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Definition
| Onset of breast development |
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Term
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Definition
| Onset of menstrual cycles |
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Term
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Definition
| Maturation of the adrenals with production of weak androgens |
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Term
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Definition
| Acne, adult body odor, pubic hair, axillary hair |
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Term
| Tanner Staging: Breast Development |
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Definition
Stage I: prepubertal
Stage II: breast bud w elevation of breast and papilla; enlargement of areaola
Stage III: further enlargement of breast and areola; no separation of contour
Stage IV: areola and papilla form secondary mound above level of breast
Stage V: mature stage; projection of papilla only, related to recession of areola |
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Term
| Tanner stages of femal pubic hair development |
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Definition
stage 1: no pubic hair
stage 2: straight hair is extending along labia
stage 3: pubic hair has increased in quantiity, is darker and is present in typical femal triangle, but in smaller quantity than in later stages
stage 4: pubic hair is more dense, curled, and adult in distribution, but less abundant than in adults
stage 5: abundant, adult-type pattern; hair may extend onto the medial aspect of the thighs |
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Term
| Normal Pubertal Timing: Girls |
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Definition
Tanner 2 Breast avg 10.2 years
Tanner 3 PH avg 11.6 years
Menarche avg 12.6 years |
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Term
A15yearoldgirlcomes in with complaint of not starting puberty/ menses
What questions to you want to ask?
What do you want to look for on physical exam? What labs or studies do you want to get?
• She has always been small for her age. She has a history of ear infections but has otherwise been healthy. Her parents are average height. There is no family history of delayed puberty. ROS is unremarkable.
• Exam is normal except she is Tanner I for breast development and Tanner III for pubic hair and is much shorter than one would expect for her parents’ heights (5th percentile)
• Studies: Bone age x-ray is delayed at 10 years
• Labs:
• LH, FSH, estradiol, prolactin,
• Short stature labs: TSH, Free T4, IGF-1, IGFBP3, CMP, CBC, UA, Sed Rate, Celiac screening
• Karyotype |
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Definition
Turner Syndrome
• Karyotype returned Turner syndrome
• Labs showed elevated LH, FSH with low
estradiol
• Patient was started on estrogen replacement ‘cyclic progesterone was added later; she was also started on growth hormone therapy with improvement of linear growth
• She was sent for cardiac exam, lipid panel, and renal ultrasound
• She was referred to Turner syndrome support group |
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Term
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Definition
- Primary:
• no menses by age 13 with no sexual characteristics
• no menses by age 15 with sexual characteristics
- Secondary:
• no period for 3 months
- Oligomenorrhea: • < 9 cycles/year |
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Term
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Definition
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Term
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Definition
| genetic condition where a female is missing an x chromosome. patients have short and webbed neck, low-set ears and short stature and shielf-shaped throax and widely spaced nipples and no menstruation. the avg height in the absence of hormone treatment is 4ft 7in. 17-45% of pts have cardiac defects. most common heart condition in turner syndrome is bicuspid aortic valve. 10% have narrowing of the aorta. 99% of turner syndrome conceptions end in spontaneous abortion. may be diagnosed by amniocentesis or chorionic villus sampling during pregnancy |
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Term
| Diagnostic Categories of Turner syndrome |
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Definition
• Breasts absent, uterus present
• Breasts absent, uterus absent
• Breasts present, uterus absent
• Breasts present, uterus present |
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Term
| Breasts absent (no E) Uterus present (XX)* -> |
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Definition
FSH low- hypogonadotrophic hypogonadism
FSH high- gonadal disorders |
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Term
| Hypogonadotropic Hypogonadism |
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Definition
- Pituitary:
• Tumors, infection, trauma, RT, infiltration • Hemochromatosis
• Idiopathic hypopituitarism
- Hypothalamic:
• Dysfunctional (exercise, nutrition, stress) • Idiopathic HH (Kallmann’s, Prader Willi) • Infection, tumors, trauma
• Chronic disease |
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Term
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Definition
• Gonadal Dysgenesis (Turners, X
mosaic) – 30-40%
• Gonadal Agenesis – normal karyotype
(XX) - ? viral/metabolic damage in utero
• Enzyme deficiency – 17OH, 17, 20-lyase, aromatase
• FSH, LH receptor mutations
• Galactosemia – toxic effect of galactose metabolism |
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Term
| Breasts present (+E) Uterus absent -> |
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Definition
Testosterone low- mullerian agenesis
Testosterone high - androgen insensitivity |
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Term
| Breasts present (+E) Uterus present |
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Definition
pregnancy test, TSH, prolactin, cortisol
Prolactinoma, Hypothyroidism, Cushing's, or Progesterone (E status) |
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Term
| Premature Ovarian failure |
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Definition
• 1–5%ofwomen<40y/o
• Intermittent ovarian function
• Iatrogenic causes (chemo, RT)
• Infection
• Associated with autoimmunity
• Accelerated atresia due to genetic disorders (fragile X, mixed gonadal dysgenesis) |
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Term
| Most Common Causes of 1° Amenorrhea |
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Definition
• Gonadal dysgenesis
• Mullerian agenesis
• Androgen insensitivity syndrome |
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Term
| Most Common Causes of 2° Amenorrhea |
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Definition
• Pregnancy
• PCOS
• Functional hypothalamic amenorrhea
• Hyperprolactinemia
• Ovarian failure |
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Term
• A 12 year old boy is seen for growth concerns. He has a twin sister who has surpassed him in height
• Dad is concerned he may have growth hormone deficiency
• His pubertal exam shows Tanner II pubic hair and testicular length of 3 cm
How would you counsel this boy and his father? |
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Definition
| He is developing and growing normally |
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Term
| Normal Pubertal Timing: Boys |
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Definition
• Firstsignofcentral puberty: testicular enlargement (3cc to 4cc)
• Range of normal onset of puberty 9- 13.5
• Average age of onset is 11-11.5 years |
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Term
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Definition
stage I: prepubertal; testicular size less than 4 cc in volume and 2.5 cm in longest dimension
stage II: enlargement of scrotum and testes; scrotal skin reddens and changes in texture; growth of testes to 4 cc or greater in volume
stage III: enlargement of penis (length at first); further growth of testes
stage IV: increased size of penis with growth in breadth and development of glans; testes and scrotum larger, scrotal skin darker
stage V: adult genitalia |
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Term
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Definition
• Occursin approximately 2/3 of boys during puberty
• Onsetusuallyaround ages 13-14
• Persists18-24 months, resolves typically by age 16 |
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Term
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Definition
| So going on to testicular anatomy, there are two main cells in the testes. The one is called the Leydig cells. They are responsible for the production of the testosterone. They are controlled by the LH-- luteinizing hormone-- from the pituitary gland. And then, you have the seminiferous tubules, which have the Sertoli cells and that's where the sperm production happens. |
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Term
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Definition
(7000 mcg/day) converted to: DHT (350 mcg/day) by 5α-reductase in genital tissues, accessory sex organs, hair follicles, brain and bone
• 60% SHBG bound
• 40% bioavailable – free + albumin bound |
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Term
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Definition
| (10 mcg/day) – about 25% of total, the rest comes from aromatization of T in peripheral tissues |
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Term
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Definition
Decrease:
• Obesity
• Malnutrition
• Nephrotic syndrome
• Androgens
• Drugs (GC, opioids, ketoconazole)
• Hypothyroidism
Increase:
• Age
• Cirrhosis
• Estrogen
• Hyperthyroidism
• Drugs (Dilantin)
• Hypogonadism |
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Term
| Clinical Action of Androgens |
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Definition
• Sexual maturation
• Muscular mass and strength
• Mood and cognitive function
• Cancellous bone formation |
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Term
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Definition
| in a man refers to a decrease in one or both of the two major functions of the testes: sperm production and testosterone production |
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Term
| Clinical Presentation of Congenital Hypogonadism in males |
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Definition
first trimester: incomplete virilization- ambiguous genitalia
third trimester: micropenis, criptorchidism |
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Term
| Clinical Presentation of Hypogonadism After Birth in males |
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Definition
Post puberty:
• More specific:
• Decreased libido
• Gynecomastia
• Loss of body hair, less shaving
• Decreased testicular size
• Infertility, low/no sperm counts
• Low bone mass
• Hot flashes, sweats
• Less specific:
• Low energy, motivation, memory
• Depressed mood
• Sleeping issues
• Reduced muscle mass, weight gain
Pre puberty:
• Scant or absent pubic, axillary and facial hair
• Small testes, prostate and phallus
• Eunuchoidal proportions
• Decreased musculature
• High pitched voice
• Gynecomastia |
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Term
| Causes of Male Hypogonadism |
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Definition
• Hypothalamic pituitary disease (1-2%)
↓ or nomal FSH, LH
gynecomastia is less common
• Testicular disease (10-13%) – damage to seminiferous tubules > damage to Leygic cells
↑ in FSH and LH
gynecomastia is more common
• Idiopathic (45-60%) – mostly presents as central
HH |
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Term
| Hypothalamic pituitary disorders |
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Definition
• Genetic
• Structural
• Functional |
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Term
| Hypothalamic Pituitary Disorders/Genetic |
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Definition
Isolated hypogonadotrophic hypogonadism
GnRH
FSH and LH subunit
GnRH receptor
GPR54 Kisspeptin receptor
Kallmann syndrome (IHH with anosmia)
GnRH neuronal migration
Congenital panhypopituitarism
PROP 1
Congenital Adrenal Hypoplasia
X-linked DAX-1 |
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Term
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Definition
| rare genetic disorder characterized by delayed or absent puberty, affects males 4x more frequently than females, caused by inability to produce hormones for sexual maturation, symptoms are impaired smell small penis and undescended testis, secondary sexual characteristics are delayed in both males and females, cleft lip cleft palate hearing loss tooth loss and kidney issues are common, diagnosed by genetic karyotyping, treated by hormone replacement therapy |
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Term
| Hypothalamic Pituitary Disorders |
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Definition
• Hypothalamic/pituitary tumors
• Trauma
• Vascular lesions
• CNS radiation
• Infiltrative disorders (hemochromatosis, sarcoidosis, infection, metastases)
• Hemochromatosis |
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Term
| Hypothalamic Pituitary Disorders/Functional |
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Definition
• Hyperprolactinemia
• Androgen, estrogen or cortisol excess
• Excessiveexercise
• Systemic illness (DM, COPD, sleep apnea, ESRD, cirrhosis, HIV, osteoporosis, acute illness...)
• Malnutrition
• Drugs(opioids,steroids,CNSactivatingdrugs, GnRH analogues)
• Obesity |
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Term
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Definition
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Term
| Testicular Disorders/Congenital |
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Definition
• Klinefelter’s syndrome
• Anorchia(vanishedtestessyndrome)
• Cryptorchidism
• Defective androgen response or synthesis
• Disorders of the androgen receptor or gene
• Disorders of the estrogen receptor or synthesis (↓ sperm motility)
• Ychromosomedefects:about10–18%of infertile men have microdeletions of the Y chromosome |
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Term
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Definition
47 XXY
• Most common 1:500 phenotypic males
• Hypogonadism (damage to Leygic cells)
• Infertility (damage to Sertoli calls)
• Tall stature – failure to close epiphyseal plates
• Cognitive and behavioral difficulties
• Predisposition to chronic bronchitis, bronchiectasis, emphysema germ cell tumors, breast cancer, non-Hodgkin lymphoma,varicose veins and DM2 |
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Term
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Definition
• Failureofdescentofthetestesintothescrotum during fetal development
• Both unilateral and bilateral cryptorchidism is associated with impaired spermatogenesis
• Spermatogenesis defect is most likely due to developmental defects
• Increasedriskfortesticulartumors
• MedicalRx(HCGorGnRH)at4–6moofage -> surgery for non-responders |
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Term
| Testicular Disorders/Acquired |
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Definition
• Orchitis(viral,TB,leprosy,chlamydia)
• Torsion
• Varicocele
• Trauma
• Radiation
• Drugs (alkylating agents, antiandrogens, ketoconazole, cimetidine)
• Smoking, ETOH
• Systemic disorders (ESRD, cirrhosis, celiac)
• Immunological infertility (4 -6 %) |
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Term
| Testicular Disorders/Acquired Evaluation |
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Definition
- Ageofthepatient
- History(payattentiontomorespecificsigns)
- PE:
• general – eunuchoid proportions
• (armspan>heightby2cm
• heel-to pubis > pubis-to-crown by 2 cm)
• skin – loss of hair, fine wrinkles
• genitalia – Prader orchiometer (N: >15 ml) • Breasts – r/o gynecomastia
- Endocrine tests:
• Total and free testosterone (morning), repeat to confirm
• LH, FSH with the second sample
• Prolactin
• Other, if history indicates
- Semen analysis:
• The concentration - 15 million per ml
• The total volume – 1.5 ml
• The total number of spermatozoa in the ejaculate – 39 million
• 58% of the spermatozoa should be alive
• 4% of the spermatozoa should be of normal shape and form
• 32% of the spermatozoa should be swimming with rapid forward movement
• 40% of the spermatozoa should be mobile
- Needtoberepeated2–3x2–3monthsapart.
- Imaging studies (pituitary MRI, testicular US)
- Genetictesting-karyotypeoftheperipheral leukocytes
- Specialized semen analysis:
• Antibodies
• Semen culture
• Sperm-cervical mucus interaction
• Sperm function tests
- Testicular biopsy |
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Term
| Treatment Goals are to Eliminate Androgen Deficiency and Restore Fertility |
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Definition
• Treat the underlying cause (infection, varicocele, high prolactin...)
• Treat with T to prevent consequences of androgen deficiency
• Fertility focused therapy |
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Term
| Testosterone Preparations |
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Definition
IM Injections
Enanthate/ Cypionate
Undecanoate
Transdermal
Patch, Lotion, Gel
Implants
Pellets |
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Term
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Definition
• Target mid normal range 400 – 700 ng/mL (age dependent)
• Transient gynecomastia
• Aggressive behavior
• Prostate enlargement
• Increase in Hb
• Sleep apnea
• Infertility
• Contraindicated in:
- Prostate, breast cancer patients
- Ht>50%
- Untreated sleep apnea |
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