Endocrine Disorders - KMLE: 부인과 노박(Novak) 정리집

Chapter 25. Endocrine disorders

I. Hyperandrogenism

A. Hirsuitism

The presence of hair in androgen-dependent sites in which hair does not normally
appear in women
cf. Hypertrichosis
- Androgen-independent growth of hair that is prominent in nonsexual areas such as
  the trunk and extremities.
- ex) AD congenital disorder, metabolic disorder (Anorexia nervosa, hyperthyroidism,
  porphyria cutanea tarda), Medication (phenytoin, minoxidil, cyclosporine, diazoxide)
cf. Virilization
- Male-pattern baldness, coarsening of the voice, decreased in breast size, increase in
  muscle mass.
- Loss of female body contour (obesity, particularly of the upper segment,
  waist-to-hip ratio), enlargement of the clitoris.

1. Role of Androgens.

Figure 25-1
Testosterone : most important circulating androgen
- 50 % : peripheral conversion of secreted androstenedione
- 50 % : direct glandular secretion
- Circulating testosterone (85%) : bound to sex hormone-binding globuline (SHBG)
  
  ---> biologically inactive.
- SHBG
  
  ↑ : pregnancy, luteal phase, estrogen therapy, increased thyroid hormone level,
  liver cirrhosis
  
  ↓ : androgen, androgenic medication (Progestational agent, Danazol),
  androgenic disorder (PCOS, Cushing's syndrome), Glucocorticoid, Growth
  hormone, Prolactin, insulin, obesity.
- Relative androgenicity of androgen :
  Dihydrotestosterone, 300 , Testosterone, 100 , Androstenedione, 10 , DHEAS, 5

2. Laboratory evaluation.

Initial lab. testing for the assessment of hirsuitism

--> Total testosterone, DHEAS, 17-OH-progesterone
Table 25.1
Testosterone level in the male range ( > 200ng/dl )
-> marker of neoplasm (ovary, adrenal)
DHEAS ; moderate elevation - PCOS

> 700 ug/dl ( 20 nmol/L ) --> adrenal or ovarian tumor
17-HP : 200 ~ 800 ng/dl --> ACTH test

800 ng/dl ↑ --> 21-hydroxylase def.

B. Polycystic Ovarian Syndrome

Symptoms :
1. Oligomenorhea to Amenorrhea
2. Infertility
3. Hirsuitism
4. Obesity
5. Hyperandrogenism & chronic anovulation and exclude secondary causes such as
  neoplasm, hyperprolactinemia, and adult-onset congenital adrenal hyperplasia.

1. Pathology

Macroscopically, white thickened cortex with multiple cysts that are typically less
than 1cm in diameter.
Microscopically,
1. Superficial cortex is fibrotic & hypocellular and may contain prominent blood
  vessels
2. Increased number of follicles with luteinized interna.
3. Stroma : luteinized stromal cells.

2. Pathophysiology & Lab. findings

Dysregulation of the cytochrome P-450c17, the androgen-forming enzyme in both
the adrenals and the ovaries, may be the central pathogenetic mechanism underlying
hyperandrogenism in PCOS
Peripheral compartment : skin, adipose tissue
1. The presence of 5-a-reductase in the skin largely determines the presence or
  absence of hirsuitism
2. Aromatase and 17-b-HSD activities are increased in fat cells and peripheral
  aromatization is increased with body weight.
3. The metabolism of estrogens, by way of reduced 2-hydroxylation and
  17-a-oxidation, is decreased.
4. Whereas E2 is at a follicular phase level in PCOS patients, E1 levels are
  increased as a result of peripheral aromatization of androstenedione
5. Chronic hyperestrogenic state results with reversal of the E1:E2 ratio.
Hypothalamic - pituitary compartment
1. GnRH pulse frequency --> LH pulse frequency ↑
2. LH pulse frequency --> LH↑,LH/FSH ratio ↑
3. FSH : not increased with LH (because of the synergistic negative feedback of
  chronically elevated estrogen levels and normal follicular inhibin.)
4. Elevated prolactin level : abnormal estrogen feedback to the pituitary gland.

3. Insulin Resistance

Most common cause of insulin resistance & compensatory hyperinsulinemia
: obesity
Acanthosis nigricans
- Marker for insulin resistance in hirsute women
- Thickened, pigmented, velvety skin lesion -- vulva, axilla, nape of the neck, below
  the breast, inner thigh
Hair-AN syndrome
- Hyperandrogenism, insulin resistance, acanthosis nigricans
- High testosterone level ( > 1.5ng/ml )
- Fasting insulin level (> 25 ug/ml), maximal serum insulin responses to glucose load
  
  (> 300ug/ml)

4. Radiologic studies

USG -- Ovarian size is increased. Bilaterally increased number of microcysts
measuring 0.5 ~ 0.8 cm with generally more than five microcysts in each ovary

5. Long-term risks

Coronary artery disease.
Persistently elevated estrogen levels, uninterrupted by progesterone --> increased the
risk of endometrial cancer.
Breast cancer.

C. Treatment of Hyperandrogenism & PCOS

Treatment depends on a patient's goals.
1st line of treatment : Weight loss
Table 25.2

1. Oral Contraceptives

Benefits
- Progestine components suppresses LH. --> ovarian androgen production↓
- Estrogen -> SHBG production↑ -> free testosterone concentration↓
- Circulating androgen level↓
- Decrease conversion of testosterone to dihydrotestosterone in the skin
  by inhibition of 5-a-reductase.
- Adrenal androgen secretion is reduced.

2. Medroxyprogesterone acetate : directly affects the hypothalamic pituitary axis.

Side effects : amenorrhea, headache, fluid retention, weight gain, hepatic dysfunction,
depression.

3. GnRH agonists

Leuprolide acetate IM (every 28days)
Suppress ovarian steroids to castrate levels in patient with PCOS

4. Glucocorticoids

Dexamethasone 0.25mg nightly or every other night --> suppress DHEAS
concentrations to < 400 ng/ml

5. Ketoconazole

Inhibit the key steroidogenic cytochromes

6. Spironolactone

Mechanism of action
- Competitive inhibition at the intracellular receptor level for dihydrotestosterone
  (DHT)
- Suppression of testosterone biosynthesis by a decrease in the P-450 system
- Increase in androgen catabolism (with increased peripheral conversion of
  testosterone to E2)
- Inhibition of skin 5-a-reductase activity
Side effect : menstrual irregularity (metrorrhagia), urticaria, mastodynia, scalp hair
loss, nausea, fatigue
Contra Indication : renal insufficiency, hyperkalemia

7. Cyproterone acetate

Synthetic progestin derived from 17-HP with potent antiandrogenic properties.
Competitive inhibition of testosterone and dihydrotestosterone at the level of
androgen receptors.
Induce hepatic enzyme --> increase the metabolic clearance rate of plasma
androgens
Side effects : fatigue, weight gain, decreased libido, irregular bleeding, nausea,
headaches.

8. Flutamide

Nonsteroidal antiandrogen, weak inhibitor of testosterone biosynthesis
Side effects : dry skin, hot flashes, increased appetite, headache, fatigue, nausea,
dizziness, decreased libido, breast tenderness

9. Cimetidine : weak antiandrogenic effect.

10. Finasteride : specific inhibitor of 5-a-reductase enzyme activity

11. Ovarian wedge resection (bilateral)

Transient reduction in androstenedione levels & prolonged minimal decrease in
plasma testosterone

12. Laparoscopic electrocautery

Five to eight points in each ovary were cauterized for 5 ~ 6 sec. with 300 - 400 W.

--> 90% ovulation & 70% conception rate

13. Physical methods of Hair removal

D. Cushing's Syndrome

Three classes of steroid hormone

a. Glucocorticoids
b. Mineralocorticoid
c. Sex steroid ( androgen and estrogen precursors)
Laboratory findings : CBC - granulocytosis, lymphocyte↓, eosinophil↓

urine - calcium secretion↑

1. Causes

Table 25.3
Pituitary ACTH-secreting adenomas or Cushing's disease are the most common cause
of Cushing's syndrome.
Ectopic ACTH syndrome is most often caused by malignant tumors

ex) Small-cell carcinoma of the lung, bronchial & thymic carcinoma, Carcinoid tumor
of the pancreas, medullary carcinoma of the thyroid
The hallmark of ACTH-dependent forms of Cushing's syndrome

; presence of normal or high plasma ACTH concentrations with increased cortisol
levels.

; adrenal glands -- hyperplastic bilaterally
The most common cause of ACTH-independent Cushing's syndrome is exogenous or
iatrogenic (superphysiologic therapy with cortical steroids) or factitious (self-induced)
Figure 25.2
Table 25.4

2. Treatment of Cushing syndrome : surgical removal of a neoplasm

3. Treatment of Ectopic ACTH/CRH-producing neoplasm

Adrenal enzyme inhibitors : mitotane, aminoglutethimide, metyrapone, trilostane,
etomidate.
Ketoconazole : inhibit adrenal steroid biosynthesis at the side arm cleavage &
11-β-hydroxylation steps.

◎ Nelson's SD.

an ACTH-secreting pituitary adenoma (macroadenoma) that develops after bilateral
adrenalectomy for Cushings disease.
Symptoms ; sellar pressure symptom. of headaches, visual-field disturbances,
ophalmoplegia, severe hyperpigmentation (melanocyte stimulating hormone activity)
Treatment ; surgical removal or radiation

E. Congenital Adrenal hyperplasia

AR.
Definition of 21-hydroxylase : 90 ~ 95 % of all cases of CAH

1. Laboratory testing

Basal follicular 17-HP, 200 ng/ml --> excludes the disorder
Basal 17-HP > 500 ng/ml --> establishes the diagnosis
200 < 17-HP < 500 : requires ACTH stimulating testing
In the ACTH stimulation test, plasma levels of 17-HP are checked 1 hour following
intravenous administration of a bolus of 0.25mg ACTH 1-24
17-HP levels after ACTH stimulation in adult-onset adrenal hyperplasia are
generally > 1000 ng/dl.

2. Clinical Presentation

PCOS (39%)
Hirsuitism alone without amenorrhea (39%)
Cryptic(22%) -- Hyperandrogenism but no hyperandrogenic symptom

3. Genetics

21-hydroxylase gene is located on the short arm of chromosome 6 in the midst of
the HLA region
21-hydroxylase gene is now termed CYP 21,
Its homologue is the pseudogene cyp21p
The CYP21 gene & the CYP21p pseudogene alternate with two genes called C4b &
C4a, both of which code for the fourth component(C4) of serum complement

4. 11-β hydroxylase def.

11-deoxycortisol levels are higher than 25ng/ml 60min. after ACTH 1-24 stimulation
Classic pattern

a. Diagnosed at a younger age.

b. Virilization, hypertension with related cardiomyopathy

c. Retinopathy.

5. 3-β hydroxysteroid dehydrogenase def.

6. Treatment of adult-onset adrenal hyperplasia

Dexamethasone - evening administration is more effective with a dosage of
0.25 - 0.5mg.

F. Androgen-secreting Ovarian & Adrenal Tumors

In prepubertal girls, virilizing tumors may cause signs of heterosexual precocious
puberty in addition to hirsuitism, acne, and virilization
Markedly elevated testosterone level (2.5times the upper normal range or over
200ug/dl) : typical of an ovarian tumor
DHEAS level > 8ug/ml --> typical of an adrenal tumor
Evaluation ; Vaginal & abdominal ultrasound, CT scanning. MRI, Selective venous
catheterization, nuclear medicine scanning of the abdomen and pelvis after injection
with Np-59

G. Androgen-Producing Ovarian Neoplasm

1. Granulosa cell tumor

Associated with estrogen production
Most common functioning tumors in children & lead to isosexual precocious

2. Thecoma

Rarely malignant, rarely bilateral

3. Sclerosing stromal tumor ; 30 yrs old↓

4. Sertoli-leydig cell tumor

Most common virilizing tumors in women of reproductive age.

5. Pure sertoli cell tumor

6. Gynandroblastoma

7. Sex cord tumors with annular tubulesSCTAT)

Associated with Peutz-Jeghers syndrome (GI polyposis, mucocutaneous melanin
pigmentation)
SCTAT with P-J SD ; bilateral, benign
SCTAT without P-j SD : unilateral ,malignant

H. Stromal hyperplasia & Stromal HyperThecosis

1. Stromal hyperplasia

Nonneoplastic proliferation of ovarian stromal cells.
60 ~ 80 years of age.
Hyperandrogenism, endometrial cancer, obesity, hypertension, glucose intolerance

2. Stromal hyperthecosis

Presence of luteinized stromal cells at a distance from the follicle
Virilization, obesity, hypertension, hyperinsulinemia, glucose intolerance
Treatment - Wedge resection, bilateral oophorectomy, GnRH agonist

I. Virilization during pregnancy

Luteomas of pregnancy - associated with maternal & fetal masculinization

Krukenberg tumor.

Mucinous cystic tumor

Brenner tumor

Serous cystadenoma

Endodermal sinus tumor

Dermoid cyst

II. Prolactin Disorders

Product of anterior pituitary
Primary function - initiation & maintenance of lactation
Significant role within & beyond the reproductive system

A. Prolactin secretion

199 amino acids. MW 23,000 daltons
3 forms i) " little "; monomer

ii) " big " ; dimer

iii) " big-big"; multimer

: proportion vary with physiologic, pathologic, hormonal situation
"little" prolactin ; 50%↑
Bioactivity & immunoreactivity - influenced by glycosylation

glycosylated form - predominant

most potent biologic form ; 23000 dalton MW nonglycosylated form
Secretion is primarily under inhibitory control by dopamine

c.f.) metoclopramide ; dopamine antagonists --> abolishes the pulsatility of prolactin
release and increase serum prolactin level.
Table 25.5

B. Hyperprolactinemia

1. Evaluation

Normal range ; 5-27 ng/ml during menstrual cycle

(sample should not be drawn soon after the patient awakes or after procedure)
Secreted in pulsatile fashion

* frequency ; 14 pulse/ 24 hrs - late follicular phase

9 pulse/ 24 hrs - late luteal phase
Diurnal variation

; lowest level- midmorning after the patient awakes

; levels rise 1 hr after the onset of sleep

; peak- between 5^7 AM
Elevated level should always be rechecked !

; at midmorning, not after stress, venipuncture, breast stimulation, physical exam

-> increase PRL levels
Physical signs
- Amenorrhea without galactorrhea ; a/w hyperprolactinemia in 15 %
- Elevated prolactin related to the following gonadal & hypothalamic-pituitary effects
  
  i) Reduction in granulosa cell number and FSH binding
  
  ii) Inhibition of granulosa cell 17 β estradiol production by interfering with
  FSH action
  
  iii) Inadequate luteinization and reduced progesterone
  
  iv) Suppression of prolactin on GnRH pulsatile release
- Isolated galactorrhea ; prolactin levels are within normal range in 50%
  
  (earlier transient episode of hyperprolactinemia --> triggering persistent
  galactorrhea)
- 1/3 of galactorrhea have normal menses.
- Hyperprolactinemia (66%) occurs in the absence of galactorrhea - may result
  from inadequate estrogenic or progestational priming of the breast
- In patient with both galactorrhea & amenorrhea
  
  . 2/3 : hyperprolactinemia
  
  . 1/3 : pituitary adenoma.
Imaging Technique.
- Prolactin level with adenoma : usually 100ng/ml ↑
- Drug-induced or physiologic etiology : scanning may not be necessary.
- Cone-down view : screening technique.
- CT / MRI
- For patient who desire fertility, MRI is indicated to differentiate microadenoma
  from macroadenoma.

2. Hypothalamic disorder.

Dopamine - produced in the arcuate nucleus

- inhibit prolactin release
Lesions that disrupt dopamine release -> result in hyperprolactinemia
Lesion that disrupt dopamine release : suprasellar area, pituitary gland, infundibular
stalk, adjacent bone, brain, cranial nerve, dura, leptomeninges, nasopharynx, vessels

3. Pituitary Disorders.

Microadenoma
- < 1cm, benign
- Over 1/3 of hyperprolactinemia : radiologic abnormality consistent with adenoma
  remainder : simple hyperplasia.
- Hypothesis for the formation of adenoma :
  reduction in dopamine concentration in hypophyseal portal system
  vascular isolation of tumor
- Microadenoma rarely progress to macroadenoma.
- Should be advised to notify of chronic headache, visual disturbance, extraocular
  muscle palsy.
- Formal visual field testing : unnecessary.
- Treatment
  1. Expectant Mx : if do not desire fertility
  - Hyperprolactinemia induced estrogen deficiency --> osteopenia.
    estrogen replacement or OC are indicated to amenorrhea or irregular menses.
  - Drug-induced hyperprolactinemia : expectantly with attention to the risk of
    osteoporosis
  - Repeat imaging in 6 ~ 12 months that there has been no further growth
    (5% of tumors show on increase in size.)
  1. Medical Tx.
  - Ergot alkaloid ; mainstay of therapy ' bromocriptine' - increase dopamine level
  - Excretion ; biliary tree (caution to liver disease)
  - Adverse effect ; nausea, headache, hypotension, dizziness, fatigue, drowsiness,
    nasal congestion, constipation
  - Oral or vag. Bromocriptine, pergolide, cabergoline, methergoline, CV205-502
  - Repeat MRI at 6^12 months after prolactin levels are normal.
    : Normal prolactin levels and resumption of menses should not be considered
    proof of tumor response to treatment.
  - Discontinuation of bromocriptine therapy after 2 to 3 yrs - because some
    adenomas undergo hemorrhagic necrosis & cease to function
  - Further MRI ; only to evaluate new symptoms.
Macroadenoma
- Symptoms ; severe headache, visual change, Diabetes Insipidus, blindness
- Follow Up ; after prolactin level has reached normal range, MRI within 6 months,
  then yearly for several years, (prolactin ; 6 months)
- Medical treatment
  - Bromocriptine : best initial & long-term treatment option.
    
    1/2 : 50% reduction in size. after 6months of Tx.
    
    1/4 : 33% reduction
  - Tumor regrowth occurs in over 60% after discontinuation
    
    ∴ long-term treatment is the rule
- Surgical treatment
  - Indication Unresponsive to bromocriptine
    
    Persistent visual field loss
- Recurrence of hyperprolactinemia & tumor growth - not uncommon
- Recurrent hyperprolactinemia - periodic MRI scan

4. Use of Estrogen in Hyperprolactinemia

In rodent, rapid prolactinoma occurs with high dose estrogen
In human, estrogen administration : no evidence of growth of pituitary adenoma
or progression of idiopathic hyperprolactinemia to adenoma

5. Pituitary adenoma in Pregnancy

Microadenoma : rarely create complication during pregnancy
Monitoring : serial gross visual field exam, fundoscopic exam, if symptom (+), MRI

* prolactin level : no value.
Macroadenoma : monitoring as microadenoma with monthly Goldman perimetry visual
field testing.
Bromocriptine : to resolve symptom & visual field deficiency temporarily to allow
completion of pregnancy before definitive therapy
Breast feeding : is not contraindication in the presence of prolactinoma.

III. Thyroid disorder.

10 times more common in women than men
1% of females : overt hypothyroidsm.

A. Thyroids Hormones

Iodide : actively transported into the thyroid follicular cell

--> Thyroid peroxide TPO) oxidizes iodide near the cell-colloid surface &
incorporates it into tyrosyl residues within the thyroglobulin molecule

--> result in the formation of monoiodotyrosine (MIT) & diiodotyrosine (DIT)

--> Triiodothyronine (T3) & Thyroxine (T4) formed by secondary coupling of MIT & DIT catalyzed by TPO
TPO : membrane-bound, heme-containing oligomer, localized in rER, Golgi vesicle &
follicular cell surface
Thyroid antimicrosomal antibodies found in patients with autoimmune thyroid disease
are directed against the TPO enzyme
Thyroid-stimulating hormone (TSH)

: regulates thyroidal iodine metabolism by activation of adenylate cyclase

--> facilitates endocytosis, digestion of thyroglobulin-containing colloid & release
of thyroid hormones T4, T3, rT3
Thyroid hormones - effects on cells include increased oxygen consumption, heat
production, increased metabolism of fat, proteins & carbohydrate

1. Iodide Metabolism

Daily allowance : 150 ~ 300 g/day
Sufficiency of iodine : a/w development of autoimmune thyroid disorder.

2. Factors affecting Thyroid function

Iodide
Pollutants (plasticizers, polychlorinated bipheols & coal processing pollutants)
Ab to Yersinia enterocolitica.
Female hormonal milieu & its potential effects on immune surveillance

B. Evaluation

1. Thyroid Function.

↑TBG conditions : pregnancy, oral pill, ERT, hepatitis, genetic abnormality of TBG,
--> require measuring T3RU for clarification.
FTI ( Free T4 Index ) : % free T4 ( T3RU ) × T4 total
TSH measurement : best single screen for thyroid dysfunction.

2. Immunologic Abnormalities

Antithyroglobuliin Ab.

: noncomplement-fixing IgG polyclonal antibodies, (+) in Hashimoto's thyroiditis, Graves' Dz, acute thyroiditis, nontoxic goiter, thyroid cancer, normal women.
Antimicrosomal antibody-direct against TPO

: (+) in Hashimoto's thyroiditis, Graves' disease & postpartum thyroiditis
,cytotoxic, complement fixing Ig G Ab
Atibody to T3 & T4.

: (+) in Hashimoto's thyroiditis & Graves' Dz. who have antithyroglobulin Antibody
Antibody to TSH receptor

TSAb. (Thyroid-stimulating Ab) or PSI (Thyroid stimulating Ig)

: monoclonal or limited polyclonal --> mimic TSH action
TBII (TSH-binding Inhibitor Ig)

block TSH binding

block both pre-& postreceptor process

TGI (Thyroid Growth-promoting Ig)

: stimulate growth, but not hormone release.

c.f antagonist : TGI-blocking Ab. - inhibiting TSH-mediated growth response

C. Autoimmune Thyroid Disease.

Hypothyroidism > hyperthyroidism
F>M
Other autoimmune conditions a/w Graves' Dz.

: Hashimoto's thyroiditis, Addison's Dz, ovarian failure, RA, Sjoren's SD, IDDM,
vitiligo, pernicious anemia, MG, ITP...

1. Hashimoto's thyroiditis

Chronic lymphocytic thyroiditis
Present as hyperthyroidism, hypothyroidism, euthyroid goiter, or diffuse goiter.
High levels of anti-microsomal & antithyroglobulin Ab (+)
The composition of various Ab (TBII, TGI etc.) result in varied physical finding
Autoantibody
- TBII : causing the atophic form & congenital hypothyroidism in some neonates.
- TGI : causing the goitrous variety
3 Classic types of autoimmune injury
- complement-mediated cytotoxicity
- stimulation or blockade of hormone receptor

1) Clinical Characteristics & Dx.

Mostly, relatively asymptomatic with painless goiter & hypothyroidism
Symptom : Cold intolerance, constipation, carotene deposition in the periorbital
region, carpal tunnel syndrome, dry skin, fatigue, hair loss, lethargy, wt.gain.
c.f Hashitoxicosis (<-- represent a variant of Graves' Dz.) - in 4~8%
Diagnosis

↑ TSH level during routine screening

↑ serum antithyroglobulin & antimicrosomal Ab

↑ ESR

2) Treatment

Symptomatic hypothyroidism --> T4 replacement
Pregnant women with↑ TSH level --> L-thyroxine.

2. Reproductive effects of Hypothyroidism.

Hypothyroidism : a/w↓ fertility resulting from ovulatory difficulties and not
spontaneous abortion.
Menorrhagia, amenorrhea, anovulation, luteal phase defect
Replacement therapy - reverse the hyperprolactinemia & correct ovulatory defect

3. Graves' Disease

Heritable specific defect by suppressor T cell

--> development of helper T cell

--> react to thyroid antigen

--> induce B-cell mediated response
HLA class II antigen DR, DP, DQ, DS

1) Clinical Characteristics & Dx.

Classical triad : Exophthalmos, goiter, & hyperthyroidism
a/w symptom :↑bowel movement, heat intolerance, irritability, nervousness,
palpitation, tachycardia, tremor, wt.loss, lower external swelling.
P/E : lidlag, nontender thyroid enlargement, onycholysis, palmar erythema, proptosis,
staring gaze, thick skin...

if. severe cases : acropachy, chemosis, clubbing, dermopathy, exophalmus with
ophthalmoplegia, follicular conjunctivitis, pretibial myxedema, vision loss.
Diagnosis

T3 ↑, but T4 levels - mostly normal

TSH↓

Antimicrosomal Ab (+)

TSAb : useful in evaluating medical treatment, prognosis & potential fetal
complication..

2) Treatment

Medication --> potentially harmful effects on the fetus, special attention must be
given to the case of contraception & the potential for pregnancy.

(1) 131I Ablation

Effective care in about 80% of cases
Most commonly utilized definitive Tx. in nonpregnant women
Postablative hypothyroidism : 50% within 1st year.

(2) Antithyroid Drugs.

PTU & Methimazole
Low doses : block the secondary coupling Rx. that form T3 & T4 from DIT &
MIT.
Higher doses --> block iodination of tyrosyl residues in thyroglobulin.
30% --> remission.

PTU (100mg, every 8 ~ 24hr)

- block the intrathyroid synthesis of T3 & the pph conversion of T4 to T3.

- not cross placenta.

- drug of choice in pregnancy.
Methimazole (10mg, every 8 ~ 24hr)

- not drug of choice in pregnancy , d/t not block pph conversion & cross
placenta.
Iodide & Lithium.

- reduce thyroid hormone release & inhibit the organification of iodine.
(3) Surgery
- Subtotal thyroidectomy
- Ix.
  1. Medical Tx failed
  2. Hypersensitive to medical Tx.
- Risk
  1. Hypoparathyroidism
  2. Recurrent laryngeal n. paralysis
  3. Hypothyroidism.
(4) β-blocker.

4. Reproductive Effects of Hyperthyroidism
- Most women. : ovulatory & fertile
- Severe thyrotoxicosis : wt. loss, irregular mens, amenorrhea, ↑spontaneous abortion,
  ↑congenital anomalies.
5. Postpartum Thyroid Dysfunction.
- Often difficult to diagnose, Sx. appear 1 ~ 8 months postpartum.
- Incidence : 5 % -> 25% permanent hypothyroid
- Histo : lymphocytic infiltration & inflammation.
- Antimicrosomal Ab (+)
1) Clinical Characteristics & Dx.
- Symptom : Depression, fatigue, palpitation, at 6 ~ 12 wks. postpartum.
  
  c.f. postpartum thyroid dysfunction should be considered in all women with
  postpartum psychosis.
- Diagnosis
  
  (-) of thyroid tenderness, pain, fever, ↑ESR, leucocytosis
  
  TSH, T4, T, T3RU, antimicrosomal Ab titer.
2) Treatment
- mostly hypothyroid phase and require 6 ~ 12 months of T4 replacement if they are
  symptomatic.
  
  (c.f.. 10 ~ 30% --> permanent hypothyroidism)
- rarely hyperthyroid phase : not routinely use of anti-thyroid medication, but
  propranolol for symptomatic relief.