« Outline

1. Hyperandrogenism:

1). Polycystic ovarian syndrome

2). Cushing’s syndrome

3). Congenital adrenal hyperplasia

4). Androgen-secreting ovarian and adrenal tumors

5). Androgen-producing ovarian neoplasm

6). Stromal hyperplasia and stromal hyperthecosis

7). Virilization during pregnancy

8). Virilizing adrenal neoplasms

2. Hyperprolactinemia:
3. Thyroid Disorders:

1). Hashimoto’s thyroiditis

2). Graves’ disease

3). Postpartum thyroid dysfunction

　

　

1. Hyperandrogenism

Ÿ Hirsutism

? Definition: the presence of hair in androgen-dependent sites in which hair does not

normally appear in women. Ie. “midline hair”, eg. side burns, moustache, beard,

chest or intermammary hair, and inner thigh and midline lower back hair entering

the intergluteal area.

‚ Distinguished from:

• Hypertrichosis: hair in androgen-independent sites, eg. trunk and extremities
• Virilization: characteristics of male pattern, eg. coarsening of the voice, decrease in breast size, increase in muscle mass, loss of female body contour, and enlargement of the clitoris.

ƒ the most frequent manifestation of androgen excess in women.

Acne, chronic anovulation, virilization à hirsutism

„ Evaluation:

• History: age of onset, rate of progression, amenorrhea or oligomenorrhea, family history,

• Physical Examination: obesity, hypertension, galactorrhea, male pattern baldness, acne,

• Lab. Survey:

a). serum androgen: total testosterone, DHEAS, and 17-hydroxyprogesteron (p 836-7)

b). If oligomenorrhea (+), check LH, FSH, prolactin, and TSH.

c). If Cushing’s syndrome is suspected, check 24-hour urine cortisol (most sensive), or

overnight dexamethasone suppression test. (p836)

　

1). Polycystic ovarian syndrome

? Clinical Definition: oligomenorrhea/amenorrhea, infertility, hirsutism, and obesity.

‚ Diagnostic Criteria:

- hyperandrogenism, chronic anovulation, exclusion of secondary causes such as

neoplasm, hyperprolactinemia, and adult-onset congenital adrenal hyperplasia.

- An elevated LH/FSH ratio is often but not always present, and cystic ovarian

changes are usually present but not essential for diagnosis.

ƒ Sonographic Findings:

• bilaterally increased numbert of microcysts measuring 0.5-0.8 cm with

generally more than 5 microcysts in each ovary

„ Long-term Risks:

• CAD, hypertension
• Insulin resistance, acanthosis nigrcans (a marker of insuline resistance),

hair-AN syndrome (severe insulin resistance)

• Endometrial carcinoma

… Treatment: (depending on patient’s goals)

• Weight loss:
• Hormonal suppression:

· oral contraceptives:

· medroxyprogesterone: 20-40 mg daily in divided dosage, or 150 im. every 6ws to 3ms

· GnRH analogs: leuprolide acetate im. every 28ds

· glucocorticoids:

dexamethasome 0.25 mg nightly or every other nightly, monitoring of serum cortisol.

• Steroidogenic enzyme inhibitors: ketoconazole 200 mg qd
• 5a -reductase inhibitors: finasteride
• Antiandrogens:

· spironolactone: 25-100 mg bid

· cyproterone acetate:

cyproterone acetate 100 mg qd on D5-15, and

ethinyl estradiol 30-50 m g qd on D5-26

When a desired clinical response is achieved, the dose of may be tapered gradually at 3-6

month intervals

· flutamide:

• Mechanical:

· temporary: shaving, etc.

· permanent (electrolysis)

　

2). Cushing’s syndrome

? Causes:

‚ Clinical Manifestations:

• hyperfunction of three classes of steroid hormones in the adrenal cortex:

ƒ Diagnostic Work-up: (Figure 25.2, p846)

„ Treatment:

1. surgical removal of neoplasm
2. several months of glucocorticoid replacement
3. treatment of ectopic ACTH/CRH-producing neoplams:

3). Congenital adrenal hyperplasia (CAH)

? Genetics:

• an autosomal recessive disorder
• 21-hydroxylase gene: CYP21, CYP21P (the pseudogene)

‚ Pathogenesis:

• failure to synthesize the fully fully functional adrenocortical enzymes for cortisol biosynthesis (Several adrenocortical enzymes my be affected.)

ƒ Clinical Presentation of Adult-onset CAH:

• three phenotypic varieties:

„ Lab. Testing:

… Treatment: dexamethasone

• 0.25-0.5 mg
• evening administration
• periodic evaluation of serum cortisol (³ 2 m g/dl is favorable)

6). Stromal hyperplasia and stromal hyperthecosis

• Stromal Hyperplasia: a nonneoplastic proliferation of ovarian stromal cells
• Stromal Hyperthecosis: presence of luteinized stromal cells at a distance from the follecles

1. Hyperprolactinemia

? Workup for Hyperprolactinemia: (Figure 25.4, p858)

‚ Causes of Hyperprolactinema: (Table 25.5, p856)

• Inhibitory factors: dopamine, etc.
• Stimulatory factors: GnRH, histamine, TRH, etc.
• Physiologic conditions: anesthesia, empty sella syndrome, idiopathic, intercourse, major surgery and disorders of chest wall, newborns, nipple stimulation, pregnancy, postpartum, sleep, stress.
• Hypothalamic conditions: craniopharyngioma, etc.
• Pituitary conditions: acromegaly, Addison’s disease, Cushing’s syndrome, hypothyroidisim, pituitary adenoma (microadenoma, or macroadenoma), etc.
• Metabolic dysfunction: ectopic production, hepatic cirrhosis, renal failure, starvation refeeding.
• Drug conditions: cimetidine, estrogen therapy, antidepressants, opiates, etc.

1. Thyroid Disorders

¤ Evaluations:

• Thyroid Function:

total serum T4, TSH, T3 (in pregnancy, oral contraceptive, estron replacement hepatitis,

and genetic abnormalities of TBG)

• Immunologic Survey:

Antithyroglobulin antibodies, antimicrosomal antibodies, antibodies to T3 and T4, thyoid-stimulating antibodies (TSAb) or thyroid stimulating immunoglobulin (TSI), TSH-binding inhibitor immunoglobulin (TBII), thyroid growth-promoting immunoglobulin (TGI)

　

1).Hypothyroidism

　

? Causes: (Table25.9, p868)

• Primary:

Congenital absence of thyroid gland, external thyroid gland radiation, familial disorders and thyroxine synthesis, Hasnimoto’s thyroiditis, ¹³¹Iablation for Graves’ disease, ingestion of antithyroid drugs, iodine deficiency, idiopathic myxedema, surgical removal of thyroid gland

‚ Reproductive Effects of Hypothyroidism:

decreased fertility from ovulatory difficulties, menstrual disturbance, luteal phase defect, and

ƒ Hashimoto’s Thyroiditis:

1. Clinical Characteristics and Diagnosis:

• mostly, relatively asymptomatic with painless goiter and hypothyroidism
• symptoms of hypothyroidism:

2).Hyperthyroidism

? Causes:

• factitious hyperthyroidism
• Graves’ disease
• Metastatic follicular cancer
• Pituitary hyperthyroidism
• Postpartum thyroiditis
• Silent hyperthyroidism (low radioiodine uptake)
• Struma ovarii
• Subacute thyroiditis
• Toxic multinodular goiter
• Toxic nodule
• Tumors secreting HCG (molar pregnancy, choriocarcinoma)

‚ Reproductive Effects of Hyperthyroidism:

ƒ Graves’ Disease:

1. Clinical Characteristics and Diagnosis:

• classical triad: exophthalmos, goiter, and hyperthyroidism
• symptoms of hyperthyroidism: frequent bowel movement, heat intolerance, irritability, nervousness, palpitations or tachycardia, tremor, weight loss, and lower extremitiy swelling
• physical examination: lid lag, nontender thyroid enlargement, onycholysis, palmar erythema, proptosis, staring gaze, and thick skin.
• Lab. Data: elevated T3, normal T4, normal TSH, antimicrosomal antibodies, TSAb (useful in evaluating medical treatment, prognosis, and potential fetal complications)

• 131I Ablation:

w most commonly utilized definitive treatment in nonpregnant women

w single dose

w Any woman of childbearing age should be tested for pregnancy before use of ¹³¹I