C31 Endocrine Disorders

Hyperandrogenism

Hirsutism

Hypertrichosis and Virilization

Role of Androgens

Laboratory Assessment of Hyperandrogenemia

The relative androgenicity of androgens is as follows:
DHT = 300 Testosterone = 100 Androstenedione = 10 DHEAS = 5.

Laboratory Evaluation

  • Ovarian source
    • eg, Sertoli-Leydig cell tumor
    • ?Testosterone(>150ng/dL), normal DHEAS
  • Adrenal source
    • eg, adrenal tumors
    • ?DHEAS (>700mcg/dL), normal testosterone

Polycystic Ovary Syndrome

Diagnostic Criteria

# 3 ? 2
Oligoovulation or Anovulation
Hyperandrogenism (clinical or biochemical)
Polycystic ovaries, r/o other etiologies

Pathology

Pathophysiology and Laboratory Findings

  • ?Adipose tissue
    • ?Insulin resistance and hyperglycemia ? ?production of SHBG ? ?free androgen.
    • ?peripheral conversion of androgens to estrone ? chronically elevated estrone levels ? high-frequency, short-interval GnRH pulses ? preferentially produce LH ? LH/FSH imbalance ? lack of LH surge ? failure of follicle maturation and oocyte release
  • LH ???? androgen? ??
    • d/t overexpression of 17?-hydroxylase, 17,20 lyase, 3?-hydroxysteroid dehydrogenase
    • POF? ??? ??. Hypergonadotropic hypogonadism
    • IGT ? DM. insulin ??? androgen ?
  • Excess androgen prevents development of a monthly dominant follicle ? anovulatory cycles.
    • Menstrual irregularity results in decreased progesterone secretion
    • Unopposed E ? ? Endometrial / Breast / Ovary ca ?

LH/FSH >2, FSH? E2? ?? ??
Androgen(DHEA), E1 ?, 17-OHPG? ??
???? ????: Testosterone>ADD

Insulin Resistance

Long-Term Risks and Interventions

Treatment of Hyperandrogenism and PCOS

Ovulation induction therapy

  1. ????, Metformin (insulin sensitizer)
  2. Inhibition of negative feedback of estrogen
    • Letrozole (aromatase inhibitor ? ?estradiol)
    • Clomiphene citrate (GnRH ?? ??. HPO axis? intact ? ? ??)
  3. Menotropin(hMG) – short course
    • Mimics FSH, triggers formation of dominant ovarian follicle. HPO axis? ??? ???? ??.
    • ?? ???? E2, TVUSG f/u ???? ??? ?? ????? ?????.
    • Cx: OHSS – GnRH agonist ?? ??
  4. FSG
  5. hCG – single injection
    • Alpha-subunit? LH? ?? ? mimics LH surge 

Weight Reduction

Oral Contraceptives

Hirsuitism, ?? ???? ?? progesteron or E+P
unopposed E ?? ??. P ??? hirsuitism? ??? ??.

Medroxyprogesterone Acetate

Cyclic progesterone for endometrial protection against uncontrolled endometrial proliferation.

Gonadotropin-Releasing Hormone Agonists

Glucocorticoids

Ketoconazole

Spironolactone

Antianrogen.

Cyproterone Acetate

= clomiphen citrate (?)

Estrogen? hypothalamus? ?? negative feedback ?? -> GnRH ?? ??.

Flutamide

Finasteride

Ovarian Wedge Resection

Laparoscopic Electrocautery

????? ovarian diathermy (drilling by cautery)

Physical Methods of Hair Removal

  • Hormonal suppression
    • Oral contraceptives, medroxyprogesterone, glucocorticoids, GnRH analogs
  • Anti-androgens: spironolactone

Insulin Sensitizers

Metformin, piglitazone

Cushing Syndrome

Causes

Treatment of ACTH-independent Forms of Cushing Syndrome

Treatment of Cushing Disease

Congenital Adrenal Hyperplasia

21-Hydroxylase De?ciency

11 ? -Hydroxylase De?ciency

3 ? -Hydroxysteroid Dehydrogenase De?ciency

Treatment of Adult-Onset Congenital Adrenal Hyperplasia

Androgen-Secreting Ovarian and Adrenal Tumors

Androgen-Producing Ovarian Neoplasms

Steroid Cell Tumors

Nonfunctioning Ovarian Tumors

Stromal Hyperplasia and Stromal Hyperthecosis

Virilization During Pregnancy

DiagnosisOvarian massMaternal virilization riskFetal virilization riskAfter delivery
Placental aromatase deficiencyNoneHighHighResolution of maternal symptoms.
LuteomaSolid, unilateral/bilateral massModerateHighSpontaneous regression of masses
Theca lutein cystCystic, bilateral massModerateLowSpontaneous regression of masses
Sertoli-leydig tumorSolid unilateral, complex massHighHighSurgery required (2nd trimester or postpartum)

Elevated ?-hCG levels stimulate the luteoma/theca lutein cysts to release androgens.
Management of bilateral, benign ovarian masses is observation and expectant management, as the masses and symptoms resolve spontaneously after delivery d/t falling ?-hCG levels.

Surgery is indicated if a malignant ovarian tumors is suspected.

Virilizing Adrenal Neoplasms

Prolactin Disorders

Prolactin Secretion

Hyperprolactinemia

Thyroid Disorders

Thyroid Hormones

Evaluation

Autoimmune Thyroid Disease

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