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Flashcards in Endocrinology Deck (50)
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1

What are the effects of placental sulfatase deficiency?

X-linked recessive deficiency
Leads to an estrogen deficiency w/ susubsequent prolongation of pregnancy and difficulties in induction and cervical ripening.
Also associated with the formation of ichthyosis later in life.

2

What are the effects of aromatase deficiency?

Androstenedione can_Ñét be converted to estradiol-17 beta.
The excess androstenedione is secreted in to the maternal and fetal circulations causing maternal and female fetus virulization.
Male fetuses are largely unaffected, but have a delayed puberty and tall stature.

3

How does pregnancy affect aldosterone, renin and angiotensin?

Marked increases in all component of this system.
Renin activity is 5-10 times that of non-pregnant values.
Renin substrate, angiotensinogen are increased 4 to 5 fold and lead to elevated aldosterone.
In the third TM, aldosterone levels are 2 times higher than non-pregnant state -> likely a key factor in sodium resorption along with estrogen and deoxycortisone.

4

What is phenylketonuria?

Autosomal recessive deficiency of phenylalanine hydroxylase activity, homozygotes are unable to metabolize phenylalanine to tyrosine. If diet unrestricted, incomplete protein metabolism leads to abnormally high phenylalanine levels that cause neuro damage and MR. Also causes hypopigmented hair, eyes, skin b/c phenylalanine competitively inhibits tyrosine hydrolase, which is essential for melanin production.

5

Maternal PKU is associated with fetal:

a. epiphyseal abnl
b. abnormal eyebrows? (hypopigmented)
c. others (also assoc w/ MR, microcephaly, low birth wt, congenital heart defects)

6

Normal thyroid weight

25 grams

7

Production of T4 and T3

T4 is produced completely by the thyroid20% of T3 is produced by the thyroid, the rest is made by peripheral conversion

8

T4 half-life

1 week, check q 5-6 weeks

9

T3 half-life

1 day, check q 2 weeks

10

TSH range by trimester

1st trim - 0.1 - 2.5 mlU/L2nd trim - 0.2 - 3.0 mlU/L3rd trim - 0.3 - 3.0 mlU/L

11

1st trimester TSH changes

high hCG levels may stim thyroid T4 to suppress the serum TSH to 0.03 to 0.5 mU/L in up to 15% of women

12

Pregnancy changes - TBG and TT4/TT3

Increased due to increasing estrogen, basal levels increase 2-3 fold. As a result, TT4 & TT3 levels increase by 50%

13

What is the function of placental type II deiodinase?

Converts T4 to T3

14

What is the function of type III deiodinase?

Converts T4 to reverse T3, which is metabolically inactive

15

Fetal hormone concentrations at 12w

TT4 - 2 ug/dLFT4 - 0.1 ng/dLFT3 - 6 ng/dLTSH - 4 mU/L

16

Fetal hormone concentrations at term

TT4 - 10 ug/dLFT4 - 1.5 ng/dLFT3 - 45 ng/dLTSH - 8 mU/L

17

Definition of subclinical hyperthyroidism

TSH <0.1 mU/L with normal FT4 and free triiodo- thyronine (FT3), in the absence of nonthyroidal illness.

18

MCC of hypothyroidism

Hashimoto thyroiditis (goiter + antithyroglobulin ab + antithyroid peroxidase ab

19

Complications of untreated hypothyroidism

SABGHTNPreeclampsiaAbruptionLBWPrematurityStillbirth

20

Goal of treatment - hypothroidism

TSH 0.5 - 2 mU/mL, FT4 in upper third of nl range (nl range 0.89 - 1.76 ng/dL @ UCH)

21

Dosing - hypothyroidism

100 - 150 mcg of T4, adjusted q 4w. If already dx'd prepregnancy, may need increase at 5w

22

FeSO4 and T4

FeSO4 interferes with thyroxine absorption

23

Ddx of goiter in pregnancy

Iodine deficiency (WHO recs 150 ug/d adults, 250 ug/d pregnant)Graves (95% of hyperthyroidism in pregnancy)Hashimoto thyroiditisExcessive iodine intakeLymphocytic thyroiditisThyroid cancerLymphomaLithium or thionamide therapy

24

Complications of untreated hyperthyroidism

SABPTBPreeclampsiaFetal deathAbruptionFGRNeonatal Gravesäó»Maternal CHFThyroid storm

25

Goals of treatment - hyperthyroidism

Maintain maternal free T4 in the high-normal range (nl range 0.89 - 1.76 ng/dL @ UCH), TSH less than 0.5 mU/mL. In many pts, MMI can be d/c'd by 32-36w, bc remission of Graves during pregnancy is common, often w/ relapse after delivery.

26

Dosing - hyperthyroidism

-Initial doses: MMI 5-15 mg/d, PTU 50-300 mg/d in divided doses (Barbour äóñ mild 150 mg/d, mod 300 mg/d, severe 600)-After pt is euthyroid, the dose of PTU should be tapered/halved, with further reduction as pregnancy progresses-Equivalent doses of PTU to MMI are 10:1 to 15:1 (100 mg PTU = 7.5 to 10 mg MMI)-MMI, PTU cross the placenta; both safe for breastfeeding

27

PTU side-effects

Rash (5%)PruritisDrug-related feverHepatitisLupus-like syndromeAgranulocytosis (0.1%)

28

B-blockers in hyperthyroidism

Treat hyperadrenergic sx only until euthyroid, bc long-term tx has been assoc with FGR. Metoprolol or propranolol usu favored over atenolol.

29

Placental transfer of thyroid hormone

Maternal FT3 and FT4 cross starting early in gestation, TSH does not cross the placenta

30

TSI & TRAB, and the fetus

-Immunoglobulin G (IgG) TSH receptor-stimulating antibodies (thyroid-stimulating immunoglobulins [TSI] and TSH receptor antibodies [TRAB]) cross placenta as early as 18 to 20w when levels are at least 2.5-fold elevated. -TRAb present in over 95% of pts with active Graves, if > 3x nl then close follow up of fetus. -Some recommend testing in 1st trimester, then repeat at 22-26w, others prefer one test at 24-28 bc of the normal decline in ab concentration, which starts at approx 20w.