Endocrinology Flashcards
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.
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.
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.
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.
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)
Normal thyroid weight
25 grams
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
T4 half-life
1 week, check q 5-6 weeks
T3 half-life
1 day, check q 2 weeks
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
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
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%
What is the function of placental type II deiodinase?
Converts T4 to T3
What is the function of type III deiodinase?
Converts T4 to reverse T3, which is metabolically inactive
Fetal hormone concentrations at 12w
TT4 - 2 ug/dLFT4 - 0.1 ng/dLFT3 - 6 ng/dLTSH - 4 mU/L
Fetal hormone concentrations at term
TT4 - 10 ug/dLFT4 - 1.5 ng/dLFT3 - 45 ng/dLTSH - 8 mU/L
Definition of subclinical hyperthyroidism
TSH <0.1 mU/L with normal FT4 and free triiodo- thyronine (FT3), in the absence of nonthyroidal illness.
MCC of hypothyroidism
Hashimoto thyroiditis (goiter + antithyroglobulin ab + antithyroid peroxidase ab
Complications of untreated hypothyroidism
SABGHTNPreeclampsiaAbruptionLBWPrematurityStillbirth
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)
Dosing - hypothyroidism
100 - 150 mcg of T4, adjusted q 4w. If already dx’d prepregnancy, may need increase at 5w
FeSO4 and T4
FeSO4 interferes with thyroxine absorption
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
Complications of untreated hyperthyroidism
SABPTBPreeclampsiaFetal deathAbruptionFGRNeonatal Gravesäó»Maternal CHFThyroid storm
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.
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
PTU side-effects
Rash (5%)PruritisDrug-related feverHepatitisLupus-like syndromeAgranulocytosis (0.1%)
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.
Placental transfer of thyroid hormone
Maternal FT3 and FT4 cross starting early in gestation, TSH does not cross the placenta
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.
Manifestations of fetal hyperthyroidism
Fetal tachycardia, fetal goiter, advanced bone age, poor growth, craniosynostosis. Cardiac failure and hydrops with severe disease
When to FNA thyroid nodules
-Sono features of malignancy (microcalcifications, hypoechoic patterns, irregular margins, elongated nodules, intranodular vascularity -High or normal serum TSH-Solid thyroid nodules larger than 1 cm, complex nodules 1.5 to 2 cm-Nodules 5 mm to 1 cm if high-risk famhx (MEN 2, familial papillary thyroid carcinoma, familial polyposis, familial medullary carcinoma)-High-risk personal hix (rapid onset or growth of nodule, hx of head and neck irradiation during childhood, hoarseness, persistent cough)-Nodules discovered in the last month of pregnancy could reasonably have FNA delayed until after delivery
What to do about a thyroid nodule + suppressed TSH
??
Thyroid nodules - risk of malignancy
-Differentiated thyroid cancer has been found in 5% to 40% of biopsies.
Most common malignancy in thyroid nodules
Papillary thyroid carcinoma.
Treatment of thyroid storm in pregnant women
-PTU 600äóñ800 mg orally, immediately, even before labs are back; then 150äóñ200 mg PO q 4äóñ6 hrs. If not takin PO, use MMI PR.-Starting 1äóñ2 hr after PTU, saturated solution of potassium iodide (SSKI), 2äóñ5 drops PO q 8 hrs; or sodium iodide, 0.5äóñ1.0 g IV q 8 hrs; or Lugoläó»s solution, 8 drops q 6 hrs; or Lithium carbonate, 300 mg PO q 6 hr.-Dexamethasone, 2 mg IV or IM q 6 hr x 4 doses. -Propranolol, 20äóñ80 mg PO q 4-6 hrs, or 1-2 mg IV q 5 min for total of 6 mg, then 1-10 mg IV q 4 hrs. -If history of severe bronchospasm:Reserpine, 1äóñ5 mg IM q 4äóñ6 hrs. Guanethidine, 1mg/kg PO q 12 hrs.Diltiazem, 60 mg PO q 6äóñ8 hrs.-Phenobarbital, 30äóñ60 mg PO q 6äóñ8 hrs prn extreme restlessness.
nl FT4 range
0.89 - 1.76 ng/dL (UCH)
nl TT3 range
60 - 181 ng/dL (UCH)
nl TT4 range
4 - 11 ug/dL (UCH). Per Creasy, the nl reference range for TT4 should be adjusted by a factor of 1.5 in pregnant patients (bc of increased TBG).
Why do we follow FT4, but total T3?
I think bc T4 is more tightly bound to TBG, so TT4 is high in pregnancy, and FT4 is more accurate, whereas T3 is less tightly bound.
Novolog - onset, peak, duration
Generic = AspartRapid-actingOnset 1-15 minPeak 1-2 hrsDuration 4-5 hrs
Humalog - onset, peak, duration
Generic = LisproRapid-actingOnset 1-15 minPeak 1-2 hrsDuration 4-5 hrs
NPH - onset, peak, duration
Onset 1-3 hrsIntermediate-actingPeak 5-6 hrsDuration 13-18 hrs
Regular - onset, peak, duration
Onset 30-60 minPeak 2-4 hrsDuration 6-8 hrs
Detemir - onset, peak, duration
Generic = LevemirOnset 1-2 hrsPeak 6-8 hrsDuration Up to 24 hrs
Lantus - onset, peak, duration
Generic = GlargineOnset 1 hrPeak noneDuration 24 hrs
HbA1c <7% - risk of congenital malformations
No increased risk
HbA1c 7-10% - risk of congenital malformations
3-7%
HbA1c 10-11% - risk of congenital malformations
10.00%
HbA1c >/=11% - risk of congenital malformations
10-20% or more
