Endocrine Pathology From Robbins/lecture Week 3

Front 1

Describe CAH due to 17a-hydroxylase deficiency:

Back 1

Mutations in the CYP17 gene prevent synthesis of any sex hormones.
Affected male patients have external female genitalia but have no mullerian structures due to secretion of AMH by the testes.
Affected female patients remain sexually infantile without hormone replacement.
These patients are able to synthesize corticosterone and aldosterone, so do not develop adrenal insufficiency.

Front 2

Describe CAH due to 21-hydroxylase deficiency:

Back 2

Most common cause of CAH.
In female patients, the high level of androgens prevents development of seperate vaginal and urethral canals, induce clitoral enlargment and fusion of the labial folds. Internal Mullerian structures are intact.
Boys will present with precocious puberty.
3/4 of patients will present early on with salt wasting due to insufficient aldosterone production.

Front 3

Describe CAH due to 11b-hydroxylase deficiency:

Back 3

Patients have elevated levels of aldosterone and cortisol precursors with an excess of androgens.
Virilization is seen without salt wasting. Hypertension is common.

Front 4

Describe aromatase deficiency:

Back 4

Mutations in CYP19 cause aromatase deficiency in both the fetus and placenta.
The placenta can convert DHEAS to androstenedione and testosterone but can't convert these further to estrone and estradiol.
These androgens virilize both the mother and the fetus, if female.
Affected female patients virilize further at puberty if left untreated.

Front 5

Describe Androgen Insensitivity syndrome:

Back 5

One of the more frequent forms of male psuedohermaphroditism.
Although genotypically male, these patients have female external genetalia with an absecence of the internal Mullerian duct structures.
Wolfian structures are also absent because thier development depends on androgens.
At puberty, testosterone produced by the testes is aromatized into estradiol by breast tissue.

Front 6

Describe hypogonadotrophic hypogonadism:

Back 6

*First trimester testosterone secretion is controlled by hCG
* Late testosterone secretion is controlled by LH

Defective FSH or LH secretions result from a failure of gonadotropin releasing cells to migrate into the hypothalamus (Kallmans), gene deletions/mutations associated with Prader-Willi syndrome, failure of the anterior pituitary, and PROP1/Pit-1 mutations leading to panhypopituitarism.

Male external genitalia is normal - micropenis develops from failure of late testosterone stimulation.

Front 7

Describe Turner's syndrome:

Back 7

Patients have normal external female genitalia with dysgenetic streak ovaries.
Classical karyotype is 45X.
Patients are short with lymphedema of the neck, webbed neck, shield chest, low set ears.

Front 8

Describe Klinefelter's syndrome:

Back 8

Male patients have normal development of the penis and scrotum, but the testes are small and firm.
Patients tend to be tall. Gynecomastia at puberty is frequent. Signs of testosterone deficiency are common and most have aspermia.
Usual karyotype is 47XXY

Front 9

What happens at weeks 7, 12 and 20 in a developing embryo?

Back 9

Week 7: The indifferent embryo begins sexual differentiation.

Week 12: Female or male characteristics of the external genitalia can be recognized.

Week 20: Phenotypic sexual differentiation is complete.

Front 10

What does the SRY gene on chromosome Y code for?

Back 10

Testes determining factor.

Front 11

What do the Leydig and Sertoli cells produce in the male fetal gonad?

Back 11

Leydig cells produce testosterone.
Sertoli cells produce Mullerian inhibiting factor.

Front 12

Define hypospadias:

Back 12

Hypospadias occur when the urethral folds fail to fuse completely, resulting in the external urethral orifice opening onto the ventral surface of the penis.

Front 13

Define Chordee:

Back 13

A poorly developed penis that curves ventrally; often associated with hypospadias.

Front 14

Define Epispadias:

Back 14

Epispadias occur when the external urethral orifice opens onto the dorsal surface of the penis. It is generally associated with exstrophy of the bladder.
(The penis may be "split in half")

Front 15

What male sexual properties is testosterone required for?

Back 15

- Development of internal male genital tract
- Muscle mass
- Pubertal growth spurt
- Penile growth
- Deepening of voice
- Spermatogenesis
- Libido

Front 16

What male sexual properties is Dihydrotestosterone responsible for?

Back 16

- Development of external male genitalia.
- Male hair pattern
- Baldness
- Sebaceous glands
- Prostate growth

Front 17

Outline of effect of XX or XY on genital development:

Back 17

Front 18

Ambiguous genitalia diagnosis chart:

Back 18

Front 19

Steroid hormone biosynthesis chart:

Back 19

Front 20

Define balanitis:

Back 20

Local inflammation of the glans penis.

Front 21

Define balanoposthitis:

Back 21

Local inflammation of the glans penis and overlying prepuce.

Front 22

Define phimosis and paraphimosis:

Back 22

A condition in which the prepuce cannot be retracted easily over the glans penis.
Paraphimosis is when the retracted prepuce is stiff and compromises circulation to the glans

Front 23

Clinical findings of genital candidiasis in males:

Back 23

Common in patients with diabetes.
Presents as an erosive, painful, intensely pruritic lesion involving the glans penis, scrotum and adjacent areas.
Scrapings reveal budding yeast forms and psuedohyphae.

Front 24

Most penile neoplasms originate from what type of cell?

Back 24

Squamous epithelium

Front 25

Appearance of squamous cell carcinoma of the penis:

Back 25

Gray, crusted, papular lesion, most commonly on the glans penis or prepuce. In many cases there is an indurated, ulcerated lesion with irregular margins.

Front 26

Overall 5 year survival rate for patients with squamous cell carcinoma of the penis?

Back 26

70%

Front 27

Bowen disease:

Back 27

Occurs in older uncircumcised males and appears as a solitary plaquelike lesion on the shaft of the penis.
33% of cases will progress to carcinoma.

Front 28

Bowenoid Papulosis:

Back 28

Occurs in young sexually active males and presents with multiple reddish brown papules on the glands. It is most often transient with only rare progression to carcinoma in immunocompromised patients.

Front 29

What type of penile lesions are associated with HPV?

Back 29

Squamous cell carcinoma and its precursor lesions are the most important. All are associated with HPV infection.

Front 30

What is "erythroplasia of Queyrat"?

Back 30

When Bowden disease presents as an erythematous patch on the glans penis.

Front 31

What 3 forms does carcinoma in situ of the penis occur in?

Back 31

1. Bowen disease
2. Bowenoid papulosis
3. erythroplasia of Queyrat

Front 32

What is cryptorchidism?

Back 32

A failure of testicular descent into the scrotum.
- Associated with a 3-5 fold increased risk of testicular malignancy. Surgical placement of the testes into the scrotum before puberty decreases, but does not eliminate, the likelihood of cancer and infertility.

Front 33

In adults 95% of testicular tumors are ________?

Back 33

Malignant; derived from germ cells.
Tumors derived from Sertoli or Leydig cells are benign.

Front 34

What are the two broad catagories of testicular neoplasms defined by the WHO?

Back 34

1. Seminoma
2. Nonseminomatous germ cell tumor.

Front 35

What 4 types of tumor can a nonseminomatous germ cell neoplasm turn into?

Back 35

1. Embryonal carcinoma
2. Yolk sac tumor
3. Choriocarcinoma
4. Teratoma

Front 36

What are some tumor markers for testicular tumors?

Back 36

hCG - elevated in choriocarcinoma, in 10-25% of seminomas.
AFP - elevated in nonseminomatous tumors & hepatocellular carcinomas

Front 37

Seminomas are responsive to what type of cancer therapy?

Back 37

Radiation and chemotherapy

Front 38

Nonseminomatous germ cell tumors are sensitive to what type of therapy?

Back 38

Platinum based chemotherapy agents.

Front 39

What is the most common cause of painless testicular enlargement?

Back 39

Testicular tumors

Front 40

Which type of testicular cancer remains confined to the testes for a long time and spread mainly to para-aortic nodes?

Back 40

Seminomas

Front 41

Which type of testicular tumor tends to spread early on by both lymphatics and blood vessels?

Back 41

Nonseminomatous tumors.

Front 42

Prostatitis:

Back 42

1. Acute prostatitis
- caused by common UTI bacteria
2. Chronic prostatitis
- May be bacterial or non-bacterial (non-bacterial caused by C. trachomatis and U. urealyticum)
3. Granulomatous prostatits

* Prostatits is characterized by dysuria, urinary frequency, lower back pain, poorly localized suprapubic or pelvic pain.

Front 43

The prostate gland is divided into what 4 sections?

Back 43

1. Peripheral zone
2. Central zone
3. Transitional zone
4. Periurethral zone

Front 44

Most hyperplastic lesions of the prostate arise in which zone?

Back 44

The inner transitional and central zones.

Front 45

Most carcinomas of the prostate arise in which zone?

Back 45

The peripheral zone

Front 46

What hormone is the main stimulus for hyperplasia of the prostate?

Back 46

Dihydrotestosterone and it's metabolite, 3a-androstenediol

Front 47

Nodular hyperplasia arises most commonly from what areas of the prostate?

Back 47

The inner, periurethral glands. The nodularity is most pronounced in the inner (central and transitional) region.

Front 48

Histology of prostatic hyperplasia can show what type of secretions?

Back 48

Pink proteinaceous secretory material, called corpora amylacea

Front 49

Clinical features of prostatic hyperplasia?

Back 49

Lower urinary tract obstruction; difficulty starting stream, interruption of the stream, complete obstruction - can lead to hydronephrosis.
Urinary urgency, frequency, nocturia, and increased UTI's

Front 50

Characteristics of prostate cancers:

Back 50

1. Most arise in the outer glands.
2. Palpable as hard irregular nodules on rectal digital examination
3. Less likely to cause urethral obstruction than hyperplasia.

Front 51

Demographics of prostate cancer:

Back 51

Carcinoma of the prostate is a common cancer of older men between 65-75. It is more common in American blacks than in Caucasian.

Front 52

PSA levels:

Back 52

PSA levels under 4 ng/mL are considered normal, and values over 10 ng/mL are suggestive of prostate cancer.
PSA levels may be elevated above 4 ng/mL in hyperplasia and prostatitis.

Front 53

A 16 year old woman who is visiting her OB/GYN has an ultrasound and is found to have a double uterus; failure of what process is responsible?

Back 53

Fusion of the inferior portion of the paramesonephric ducts.

Front 54

In a fetus with XX chromosomes and an absence of androgen secretion by the gonad will see differentiation and development of what system?

Back 54

The Mullerian duct system

Front 55

In an XX fetus whose mother is taking an adronergic medication, what would you see?

Back 55

Hypertrophy of the clitoris

Front 56

Primordial germ cell migration from the yolk sac to the genital ridge is necessary for gonad development:

Back 56

Front 57

The mesoneprhic duct system is also called what?

Back 57

The Wolffian system

Front 58

The paramesonephric duct system is also called what?

Back 58

The Mullerian system

Front 59

Undifferentiated gonads in 8 week old embryo:

Back 59

Front 60

Development of uterus and vagina from urogential sinus and paramesonephric ducts:

Back 60

Front 61

From what embryonic structure does the prostate develop from?

Back 61

The urogenital sinus

Front 62

Normal male/female sex differentiation:

Back 62

Front 63

From what embryonic structure does the prostate develop from?

Back 63

The urogenital sinus

Front 64

Timeline for fetal sex differentiation:

Back 64

Front 65

Flowchart of female genital development:

Back 65

Front 66

Flowchart of male genital development:

Back 66

Front 67

Name 3 causes of male pseudohermaphroditism:

Back 67

1. XY with feminization
2. Androgen insensitivity syndromes
3. 5 alpha reductase deficiency

Front 68

Name 2 causes of female pseudohermaphroditism:

Back 68

1. XX with masculinization
2. Androgen excess from
- Fetal congenital adrenal hyperplasia
- Maternal androgen intake

Front 69

What kind of gonads do true hermaphrodites have?

Back 69

Both male and female gonads; externally could appear either male of female.

Front 70

Diagram of normal male and female sex differentiation:

Back 70

Front 71

Characteristics of a 46XX with CAH:

Back 71

- 95% of congenital adrenal hyperplasia is due to 21-hydroxylase deficiency
- Autosomal recessive inheritance
- Classic CAH presence in the newborn period and is associated with low aldosterone and salt wasting in 75%
- Hyperpigmentation of areola and scrotum
- Cervix on rectal exam
- Shock after 7-10 days if missed

Front 72

What would you expect to see on lab tests for a newborn female with CAH?

Back 72

- Increased 17 hydroxyprogesterone
- Increased DHEA
- Increased androstenedione
- Increased plasma renin activity(PRA): Most sensitive measure of aldosterone activity
Renin is elevated in infants with CAH. Renin is secreted from the kidney in response to decreased renal perfusion pressure. Remember renin circulates in the blood and cleaves angiotensinogen into angiotensin I. Angiotensin I us cleaved in the lungs by angiotensin converting enzyme to make angiotensin II, a potent vasoconstrictor that also stimulates release of aldosterone from the adrenal glands.
- XX karyotype

Front 73

What would the medical and surgical treatment be for a be for a female with CAH be?

Back 73

Medication: Hydrocortisone and fludrocortisone with NaCl supplements if needed.

Surgery: Reduce size of clitoris and reduce/feminize labioscrotal folds

Front 74

Micropenis is the result of what?

Back 74

Testicular dysgenesis or dysfunction between 8 and 20 weeks.

Front 75

Characteristics of 5-alpha-reductase deficiency:

Back 75

- Autosomal recessive disorder
- Low dihydrotestosterone levels
- Undervirilized external genitalia at birth
- Clitoris-like microphallus
- Bifid scrotum
- Hypospadias
- Urogenital sinus that opens at perineum
- Normal Wolffian structures
- No Mullerian structures
- Masculinize at puberty due to higher testosterone levels ( "penis at 12", testes descend, scrotum enlarges, phallus lengthens)

Front 76

Characteristics of androgen insensitivity:

Back 76

- Binding of testosterone and dihydro-testosterone is impaired due to a receptor defect
- No Mullerian structures because anti-Mullerian hormone present (produced by Sertoli cells)
- No Wolffian structures develop because the receptors do not respond to testosterone
- Intra-abdominal testes, blind vaginal pouch
- At puberty breasts develop due to peripheral conversion of testosterone to estrogen
- After puberty remove intra-abdominal testes to prevent cancer
- X-linked recessive inheritance as androgen receptor coding is on the short arm of chromosome X

Front 77

After a gonadectomy, a patient with androgen insensitivity is at increased risk of?

Back 77

Osteoporosis

Front 78

Characteristics of a true hermaphrodite:

Back 78

- Has both testicular and ovarian tissue
- One ovary and one testes or ovotestes or combination.
- Over half are 46XX
How can a 46XX have a testes?
They acquire an SRY gene during meiosis I
- A rudimentary uterus is found in 90%
Differentiates on the side with no testicular tissue
- Wolffian ducts develop on the side with testicular tissue

If sufficient amount of testicular tissue will look phenotypically male and be raised as males

Front 79

Characteristics of pure ovarian dysgenesis:

Back 79

- Phenotypic females
- Present at adolescence with delayed puberty
- Usually have streak gonads with ovarian stroma and fibrous tissue but no primordial follicles
- Cannot get pregnant on thier own, but can carry a pregnancy.

Front 80

Workup for ambiguous genitalia:

Back 80

- Physical exam
- General exam to look for other malformations
- Palpate for gonads
If present below inguinal ligament, almost always testes
If unilateral testis and asymmetric labioscrotal fold, probable true hermaphrodite
- Measure phallus, look for labioscrotal fold and hyperpigmentation
Labs:
- Electrolytes
- 17-OH-P, plasma renin, DHEA, DHT, testosterone, FSH
- Chromosomal analysis
- Imaging to define internal structures
Ultrasound
Retrograde genitogram (dye inserted through genital orifice) or voiding cystourethrogram (dye inserted though bladder)

Front 81

Name 4 determinants of growth:

Back 81

1. Hormonal factors
2. Genetic potential
3. Nutritional
4. Environmental
- Emotional factors
- Cellular environment conducive for growth

Front 82

Name 4 hormonal influences on growth:

Back 82

1. Growth Hormone (GH)
- Insulin like growth factor I (IGF 1)
2. Insulin
3. Thyroid Hormone (TH)
4. Sex steroids
- Estrogen
- Testosterone

Front 83

Characteristics of growth hormone:

Back 83

- Most abundant anterior pituitary hormone
- Production begins early in fetal life and peaks in adolescence then decrease by 50% every 7 years

Front 84

Effects of thyroid hormone on growth:

Back 84

- Modulates energy metabolism independently of growth effects
- Effects on growth mediated through growth factors
Somatamedins
Erythropoietin
Nerve growth factor
Epidermal growth factor
- TH binding to nuclear receptors stimulates growth hormone (GH) synthesis
- TH potentiates GH stimulation of IGF production
- TH regulates IGF I receptors

Front 85

Sex steroid effect on growth:

Back 85

- Act centrally by modifying GH secretion
- Act centrally and peripherally by modulating IGF-1
- Act peripherally by modifying GH responsiveness especially to metabolic effects

Front 86

Growth during fetal period:

Back 86

Depends on:
Maternal uterine size and function, maternal nutrition and maternal/fetal/placental/ insulin and non-GH dependant IGF's
* Not dependant on GH or thyroid hormone
* Genetics plays no role
* Most rapid growth velocity

Front 87

Growth during infancy and childhood:

Back 87

- Genetically determined potential PLUS
- GH and TH dependant growth
- Nutrition plays a role
- Rapid linear decline in growth velocity

Front 88

Growth and puberty graph:

Back 88

Front 89

Growth during infancy and childhood:

Back 89

- Genetically determined potential PLUS
- GH and TH dependant growth
- Nutrition plays a role
- Rapid linear decline in growth velocity

Front 90

Phases of growth during childhood:

Back 90

Front 91

Markers of a growth problem:

Back 91

- Absolute height significantly below norms >3 S.D.
- Abnormal height velocity after 3 years of age
- Absolute height markedly different than expected genetic height
- Delayed puberty
- Failure of small for gestational age/intrauterine growth restriction(SGA/IUGR) infant to have appropriate catch up growth by 2 years of age

Front 92

Classification of short stature:

Back 92

Front 93

Endocrine PICNICS:

Back 93

Front 94

FDA approved uses of GH:

Back 94

- Growth Hormone deficiency/insufficiency
- Chronic Renal Insufficiency (pre transplantation)
- Turner Syndrome
- Adults with GH deficiency
- Adults with AIDS Wasting
- Short stature secondary to Prader Willi Syndrome
- Children with IUGR who have not reached a normal height by 2 years
- Children with idiopathic short stature who are >2.25 SD in height

Front 95

Hormonal changes in puberty:

Back 95

- Hypothalamic-pituitary-gonadal axis functional by 20 weeks’ gestation into infancy (runs due to maternal estrogens)
- Infantile central activity reduces to near pre-pubertal levels by about 3 to 6 months of age in males and until 18 months of age in females (maternal steroid withdrawal)
- The exact trigger for puberty is unknown
- In simplified model, changes in balance of gammaaminobutyric acid (GABA) and glutamatergic neurotransmission stimulates GnRH production

Front 96

Hormonal changes in puberty:

Back 96

- Hypothalamic-pituitary-gonadal axis functional by 20 weeks’ gestation into infancy (runs due to maternal estrogens)
- Infantile central activity reduces to near pre-pubertal levels by about 3 to 6 months of age in males and until 18 months of age in females (maternal steroid withdrawal)
- The exact trigger for puberty is unknown
- In simplified model, changes in balance of gammaaminobutyric acid (GABA) and glutamatergic neurotransmission stimulates GnRH production

Front 97

Puberty is associated with what 3 hypothalamic-pituitary changes?

Back 97

- Pulsatile release of GnRH leads to nocturnal sleep-related augmentation of pulsatile LH secretion
- Sensitivity of hypothalamus and pituitary to estradiol and testosterone decreases, causing LH and FSH to increase
- In females, critical levels of estrogen trigger GnRH, stimulating LH to initiate ovulation

Front 98

What does LH and FSH stimulate in females?

Back 98

- LH enhances thecal cell production of androgens and granulosa cell production of progesterone.
- FSH stimulates granulosa cell production of estrogen

Front 99

What does LH and FSH stimulate in males?

Back 99

- LH stimulation of Leydig cells causes testosterone production
- FSH stimulation of Sertoli cells vital for germ cell development

Front 100

Characteristics of adrenarche:

Back 100

- Secretion of adrenal androgens DHEA and DHEAS and androstenedione, associated with regrowth of zona reticularis
- Local conversion of DHEA-S to testosterone then DHT is responsible for hair growth in androgen-dependent areas
- Axillary and pubic hair areas are most sensitive to androgens
- Local conversion of DHEA-S within apocrine glands of the axilla causes body odor
- Responsible for pubarche and acne.
- Can begin by age 6-8, and continues to age 13-15.
- Is independent of HPG axis
- Adrenal androgens are not necessary for pubertal development or growth spurt

Front 101

Functions of sex steroids:

Back 101

Front 102

Characteristics of male sexual maturation:

Back 102

- First sign in males is testicular enlargement to >2.5cm in length/4ml in volume at mean of 11.5 years (9-14 years)
- Testicular enlargement > Phallic enlargement > Pubic and axillary hair > PHV
Completed in 3.5 yrs (range 2-4.5 yrs)
- Spermarche occurs at SMR 2.5 and ejaculation at SMR 3 (13.5 yrs old)
- Fertility usually occurs at SMR 4

Front 103

Tanner stages:

Back 103

Front 104

Pubic Hair tanner staging:

Back 104

Front 105

Mean ages of female pubarche/menarche and thelarche

Back 105

Front 106

Why does it take longer to start menarche than to start breast development?

Back 106

Because the uterus is immature and has to grow an endometrium before menarche starts.

Front 107

Signs of precocious puberty:

Back 107

Definition in girls:
Girls with progression to Tanner III breast development under the age of 8
Girls with both breasts and pubic hair under the age of 8
Girls who are short with puberty under the age of 8
Girls with bone age advanced more than 2 years

Definition in boys:
Onset of puberty before age 9
10x more common in girls than boys

Front 108

Characteristics of central isosexual precocious puberty in girls:

Back 108

- Early maturation of hypothalamic secretion of GNRH
- Most common (90%) is “idiopathic” (i.e. no underlying cause found)
- Other CNS disorders: tumors, trauma, post-infectious, hydrocephalus
- Pattern and timing of progression of development are preserved

Front 109

Why is primary hypothyroidism associated with precocious puberty?

Back 109

Because an increase in TSH can trigger FSH receptors due to similar structures

Front 110

Characteristics of peripheral isosexual precocious puberty in girls:

Back 110

- Exogenous estrogen exposure
- Estrogen secreting tumors (adrenal or ovary)
- Ovarian cysts
- McCune Albright syndrome:
Sporadic post-zygotic somatic mutation in G protein
Recurrent follicular cysts secrete estrodiol
Polyostotic fibrous dysplasia
Large irregular café au lait spots

Front 111

What is the difference between central and peripheral causes of precocious puberty?

Back 111

Central comes from activation of the HPG axis.
Peripheral comes from exogenous or gonadal source of androgens/estrogens.

Front 112

Characteristics of peripheral isosexual precocious puberty in boys:

Back 112

- Exogenous androgen exposure
- Adrenal androgen exposure
- Congenital adrenal hyperplasia
- Adrenal tumors
- Testicular androgen secretion
- Tumors
- Familial Leydig Cell hyperplasia (Familial Testotoxicosis)
Autosomal dominant affecting males
Premature Leydig cell maturation even with prepubertal LH levels
Spermatogenesis occurs-fertile!
- McCune Albright (rare in boys)

Front 113

In idiopathic central precocious puberty, which lab values would you expect to find?

Back 113

Increased FSH/LH, an increased Estrogen/Testosterone and a pubertal response GnRH response

Front 114

In peripheral isosexual precocious puberty, which lab values would you expect to find?

Back 114

Decreased FSH/LH, increased E/T and a flat GnRH response.

Front 115

GnRH agonists are indicated to treat central precocious puberty. Why?

Back 115

To prevent short stature.

Front 116

Evaluation of delayed puberty:

Back 116

Evaluation indicated if no pubertal development:
In girls by age 13
In boys by age 14
Evaluate if puberty starts then stops
Measurement of gondatotropins (FSH/LH)
If high, reflects gonadal (ovaries or testes) failure
If low, reflects CNS (hypothalamic) problem or chronic illness

Front 117

Delayed puberty with high gonadotropins:

Back 117

Gonadal failure
Autoimmune, chemotherapy, radiation
Pure gonadal dysgenesis
Complete androgen insensitivity
X-linked recessive
Androgen receptor absent or non-functional
(breasts develop but no menses…why?)
Chromosomal abnormalities
Turners Syndrome
Kleinfelters Syndrome
P450c17 deficiency/17-hydroxylase deficiency: Very rare, complete absence of sex steroid production in adrenals, ovaries, and testes (What would females look like? What would males look like?)

Front 118

Delayed puberty with low gonadotropins:

Back 118

Constitutional delay (most common; genetic predisposition)
Hypopituitarism
Kallmann’s Syndrome
LH/FSH deficiency associated with anosmia
Chronic disease
Hypothalamic hypogonadism
Also calorie restriction or athletics

Front 119

- A 16 years old girl with Turner’s syndrome gets labs, what would you expect?

Back 119

Elevated FSH and low estradiol.

Front 120

17 year old boy with delayed puberty from Somalia; short with SMR of 3. What lab values would you expect?

Back 120

Low LH and low testosterone (due to hypothalamic hypogonadism)

Front 121

16 year old girl treated with whole pelvis radiation has delayed puberty, what is her medical management?

Back 121

Hormone replacement.

Front 122

Describe the differentiation of spermatogonium to sperm:

Back 122

1. 2N spermatogonium undergo mitosis without dividing to give a 4N primary spermatocyte.
2. 4N primary spermatocytes undergo Meiosis I to give 2N secondary spermatocytes.
3. 2N secondary spermatocytes undergo Meiosis II to give 1N spermatid
4. 1N spermatid undergo maturation to produce spermatozoan

* Gonium is going to be a sperm; Zoan is zooming out of the cell.

Front 123

Describe the maturation and differentiation of an ovum:

Back 123

1. 2N oogonium undergo mitosis without dividing to give 4N primary oocytes.
2. 4N primary oocytes begin Meiosis I and are arrested in prophase until ovulation.
3. At ovulation, 1 2N secondary oocyte survives, the other turns into a polar body.
4. The surviving 2N secondary oocyte undergoes Meiosis II and is arrested in metaphase II until fertilization.
5. One 1N ovum and one polar body are formed when fertilization occurs.

* An egg MET a sperm

Front 124

What type of mutation is common in testicular germ cell tumors?

Back 124

p53

Front 125

Name 2 genetic syndromes which predispose toward testicular cancer?

Back 125

1. Li-Fraumeni syndrome
2. Isochromsome 12p

Front 126

Embryonic cell precursors for testicular tumors:

Back 126

Front 127

Classification of germ cell tumors:

Back 127

Front 128

Characteristics of Intratubular Germ Cell Neoplasm:

Back 128

Front 129

Histology of ITGCN:

Back 129

- Large cells, clear cytoplasm, hyperchromatic nuclei, prominent nucleoli, frequent mitoses
- Resemble seminoma cells
- Present along thickened/hyalinized tubular basement membrane, displacing Sertoli cells toward the lumen
- Spermatogenesis absent in involved tubules

Front 130

Characteristics of Seminomas:

Back 130

Front 131

Gross appearance of a seminoma vs. a mixed germ cell tumor:

Back 131

Gross: bulky, homogenous gray-white, lobulated, bulging cut surface, usually well demarcated
Absence of extensive necrosis or hemorrhage
Grossly similar to lymphoma

Front 132

Histology of testicular seminoma:

Back 132

Micro: sheets of relatively uniform tumor cells divided into poorly demarcated lobules by delicate fibrous septa infused with T-lymphocytes

Front 133

Characteristics of non-seminomatous and mixed germ cell tumors:

Back 133

Front 134

Treatment of nonseminomatous and germ cell tumors:

Back 134

Front 135

Gross appearance of non-seminomatous and mixed germ cell tumors:

Back 135

Gross: heterogeneous and often variegated gross appearance
Usually a mixture of different components; hemorrhage, necrosis, cyst formation, and scarring are typical

Front 136

Characteristics and histology of embryonal carcinoma:

Back 136

- Pure tumors are rare
- Seen in ages 20-30
- Most anaplastic looking of all germ cell tumors

Front 137

Characteristics of a yolk sac tumor:

Back 137

- Unilaterally developed teratoma mimicking embryonal yolk sac tissue
- >95% of individuals with tumors containing yolk sac elements have elevated serum α-fetoprotein (AFP)
- Most common testicular tumor of children age 3 or less
Good prognosis at this age (80%+ are stage I)
In adults, usually part of a mixed germ cell tumor
- Histological appearance of fibrous cores of tissue or hepatoid pattern.

Front 138

Characteristics of a choriocarcinoma:

Back 138

Front 139

Histology of choriocarcinoma:

Back 139

Gross: small, may be replaced by fibrous scar with hemosiderin as it outgrows blood supply
Micro:
Hemorrhage and necrosis
Cells intermingled in biphasic plexiform pattern
- Cytotrophoblast
- Syncytiotrophoblast

Front 140

Teratoma in children:

Back 140

Front 141

Teratoma in adults:

Back 141

Front 142

Characteristics of a teratoma:

Back 142

Front 143

A normal adult prostate weighs how much?

Back 143

About 20 grams

Front 144

Anatomy of the prostate:

Back 144

Front 145

AUA assessment of BPH symptoms:

Back 145

Front 146

Treatment options for nodular hyperplasia:

Back 146

- Transurethral resection
- Suprapubic prostatectomy
- Medicaments
Androgen antagonists
Smooth muscle relaxers
5-α-reductase inhibitors

Front 147

Pathology of nodular hyperplasia:

Back 147

Gross:
Large, discrete, periurethral nodules.
Occurs in transition zone.
Microscopic:
Hyperplasia of glandular and stromal tissue .

Front 148

Prostatic intraepithelial neoplasia (PIN); a precancerous condition:

Back 148

- Cancer nuclei
- Benign pattern
- Basal cells present
- Present in about 15-25% of patients
- Indicates increased risk of carcinoma
- Does not cause elevated PSA
- If found on TURP specimen, examine all submitted tissue for carcinoma

Front 149

Atypical small acinar proliferation (ASAP); a risk factor for prostatic cancer:

Back 149

- Diagnosed in 5% of biopsies
- 50-60% have adenocarcinoma with additional sampling, suggesting need for additional biopsies
- Represents either or any combination of
Precursor lesion
Budding HPIN
Poorly sampled well differentiated cancer

Front 150

Characteristics of prostate carcinoma:

Back 150

- Comprises 25% of cancer diagnoses among men
- 1 in 6 American men are diagnosed with prostate cancer during their lifetimes
- 1 in 33 (3%) of these die of prostate cancer
- Most men with clinical disease are age >50 years
- Prostate surgery carries a large risk of incontinence.
- Blacks > Whites > Asians

Front 151

At what age is prostate screening recommended?

Back 151

Over 50, or at 40 years of age in high risk males.

Front 152

Gleason grading of prostate cancer:

Back 152

Grade is 1 to 5, based on glandular differentiation at low power
Score is 2 to 10, based on Gleason grade for first and second most predominant patterns:
Score 2-4 almost never develop aggressive disease
Score 8-10 may die of disease
Clinically important distinctions are Gleason scores
2-6, may watch and wait
7, intervention required
8, 9-10, poor prognosis

Front 153

Gleason grading numerical values:

Back 153

1. Glands small, well-formed, closely packed
2. Glands larger, more tissue between them
3. Recognizable glands, some cells have left glands and are invade surrounding tissue, sometimes between normal glands
4. Few recognizable glands, many cells invading surrounding tissue
5. Rare to no recognizable glands, often just sheets of cells throughout surrounding tissue

Front 154

The higher the Gleason score for prostate cancer, the higher the __________ ?

Back 154

Mortality rate

Front 155

Treatment options for prostate cancer:

Back 155

- Radical prostatectomy (generally not warranted if pelvic lymph nodes are positive; proviso, Gleason score 7)
- Radiation therapy
- Brachytherapy (radioactive seeds)
- External beam radiation therapy
- Cryotherapy or microwave irradiation
- Watchful waiting (for low grade tumors, localized tumor or limited life expectancy)
- Chemotherapy or hormonal therapy (LHRH analogs, antiandrogens, orchiectomy) for metastatic disease

Front 156

Prostate cancer staging:

Back 156

- T1, clinically unapparent tumor
No pathologic T1
- pT2, organ confined tumor
- pT3, extraprostatic tumoral extension
- pT4, invasion of bladder or rectum by prostate cancer

Front 157

Distant metastasis of prostate cancer:

Back 157

- 35% incidence
- Most common sites are bone (90%), lung (46%), liver (25%), pleura (21%), adrenals (13%)
- Spine involvement common even in small tumors
- Upward spread from lumbar to cervical level (Batson plexus)
- Bony metastases: multiple, usually osteoblastic, may radiographically simulate Paget disease or osteosarcoma

Front 158

75% of hypospadias are either ________ or _________?

Back 158

Glandular or coronal

Front 159

Peyronie's Disease:

Back 159

Front 160

Priapism:

Back 160

- Definition: The erect penis does not return to its flaccid state, despite the absence of stimulation for 4 hours
Risk factors:
Sickle cell disease
Spinal cord injury
Medications:
Antipsychotics
Trazodone
Intracavitary papaverine
Complications: Ischemia and thrombosis
Untreated=>gangrene
Treatment:
Oral pseudophedrine, intracavitary aspiration, intracavitary phenylephrine injection

Front 161

How do phenylephrine and pseudophedrine cause arrest of priapism?

Back 161

Alpha stimulation of the penile arterial supply

Front 162

Layers of testes from skin inwards:

Back 162

Skin
Dartos
Ext. sp. fascia
Cremaster
Int. sp. Fascia
Tunica vaginalis
Testis

* Some Damn Englishman Called It The Testes

Front 163

Epididymitis:

Back 163

Front 164

Varicocele:

Back 164

Front 165

Hydrocele:

Back 165

Front 166

A patient describes a fluid accumulation in the R hemi-scrotum which “fills” during the day and is empty in the a.m. Diagnosis?

Back 166

Hernia
Non-communicating hydrocele
**Patent processus vaginalis
He wants attention

Front 167

Sensitivity vs specificity:

Back 167

Sensitivity: Positive in disease
Specificity: Negative without disease

*Use a specific test to rule something in
*Use a sensitive test to rule something out

Front 168

Sensitivity and specificity calculations:

Back 168

Front 169

2 x 2 table for calculations:

Back 169

Front 170

STD screening guidelines from CDC:

Back 170

Front 171

STI screening in MSM

Back 171

Front 172

Treatment of Chlamydia:

Back 172

Front 173

Lymphogranuloma venereum:

Back 173

Front 174

Treatment of gonorrhoeae:

Back 174

Front 175

Outpatient treatment of PID:

Back 175

Front 176

Inpatient therapy for PID or Abscess:

Back 176

Front 177

What 2 HPV types are associated with genital warts?

Back 177

11 and 6

Front 178

What type of shell and DNA does HPV have?

Back 178

Non-enveloped dsDNA

Front 179

Treatment algorithm of genital warts:

Back 179

Front 180

Imiquimod cream:

Back 180

Front 181

Antibodies to which HPV capsid protein are formed after infection or vaccination?

Back 181

L1

Front 182

Podophyllum resin treatment for genital warts:

Back 182

Front 183

HSV antiviral therapy:

Back 183

Front 184

Clinical diagnosis of bacterial vaginosis:

Back 184

Front 185

Common questions about BV drugs:

Back 185

Front 186

Diagnosis of Trich Vag:

Back 186

Front 187

Presentation of Vulvovaginal Candidiasis:

Back 187

Front 188

Diagnosis of VVC:

Back 188

Front 189

Recommended therapy for VVC:

Back 189

One vaginal dose of miconazole
OR
One oral dose of fluconazole

Front 190

Treatment for complicated VVC:

Back 190