3.6 Thyroid Disorders & Anemia in Pregnancy

Thyroid Disorders in Pregnancy

Gestational Thyroid Physiology

Maternal thyroid hormone production increases by 30% to 50% during pregnancy to meet maternal and embryonic metabolic demands. Two key mechanisms drive this adaptation:

1. Human Chorionic Gonadotropin (hCG): Shares structural homology (alpha subunit) with TSH. High first-trimester hCG levels weakly stimulate the TSH receptor, resulting in a physiologic surge in free thyroxine (FT4) and a transient physiologic suppression of serum TSH (nadir at 10–12 weeks).
2. Estrogen-Induced Thyroxine-Binding Globulin (TBG): Estrogen stimulates hepatic TBG synthesis and impairs TBG clearance, doubling total circulating TBG levels. Consequently, total T4 and total T3 concentrations increase by 50%, while free T4 (FT4) remains the active, physiologically regulated fraction.

Overt Hypothyroidism

Defined as an elevated serum TSH with a decreased FT4 concentration, or a serum TSH >10 mIU/L regardless of FT4 level.

• Maternal-Fetal Consequences: Untreated overt hypothyroidism is linked to increased rates of early spontaneous abortion, preeclampsia, gestational hypertension, placental abruption, low birth weight, and irreversible deficits in fetal neuropsychological and cognitive development.
• Pharmacotherapy: Levothyroxine (T4) is the drug of choice (starting dose 1.6 mcg/kg/day for overt disease). In individuals with pre-existing hypothyroidism, pregnancy increases levothyroxine requirements by 20% to 30% as early as the fifth week of gestation. Patients should be counseled to preemptively increase their dosage (e.g., taking two additional tablets per week, or increasing the daily dose by 25%–30%) upon a positive pregnancy test and immediately contact their provider.
• Target TSH Thresholds:
  • First trimester: <2.5 mIU/L (or lower reference limit of population normal, ~0.1–2.5 mIU/L)
  • Second and third trimesters: <3.0 mIU/L (or 0.2–3.0 mIU/L)
• Surveillance: Monitor serum TSH every 4 to 6 weeks during the first half of pregnancy until stable, and at least once per trimester thereafter.

Hyperthyroidism

Overt hyperthyroidism (suppressed TSH with elevated FT4 or FT3) occurs in 0.2% of pregnancies, most commonly caused by Graves' disease (autoimmune stimulation of TSH receptors by thyroid-stimulating immunoglobulin [TSI]).

• Risks: Thyroid storm, heart failure, preeclampsia, fetal hydrops, intrauterine growth restriction, and neonatal Graves' disease (due to transplacental crossing of TSI).
• Pharmacotherapy Protocol:
  • First Trimester: Propylthiouracil (PTU) is the preferred thioamide (dose: 50–150 mg PO three times daily). Methimazole is avoided during organogenesis because of associated teratogenic embryopathy (aplasia cutis, choanal atresia, and esophageal atresia).
  • Second and Third Trimesters: Switch from PTU to Methimazole (dose: 5–20 mg PO daily) starting at the beginning of the second trimester to avoid PTU-induced severe maternal fulminant hepatic necrosis.
  • Target Range: Titrate thioamides to maintain maternal free T4 at or slightly above the upper limit of the normal non-pregnant range using the lowest effective dose, thereby preventing fetal drug exposure and fetal goitrous hypothyroidism.

Anemia in Pregnancy: Hemodilution vs. Iron Deficiency

Physiologic Hemodilution ("Physiologic Anemia")

During normal pregnancy, maternal intravascular plasma volume expands by 45% to 50%, whereas erythrocyte mass expands by only 20% to 30% in response to erythropoietin. This disproportionate fluid expansion results in physiologic hemodilution, characterized by decreased blood viscosity, enhanced uteroplacental perfusion, and a physiologic drop in hemoglobin and hematocrit that nadirs in the late second trimester (24–28 weeks).

Diagnostic Criteria for Anemia (CDC & ACOG Standards)

• First Trimester: Hemoglobin <11.0 g/dL (Hematocrit <33%)
• Second Trimester: Hemoglobin <10.5 g/dL (Hematocrit <32%)
• Third Trimester: Hemoglobin <11.0 g/dL (Hematocrit <33%)
• Postpartum: Hemoglobin <10.0 g/dL (Hematocrit <30%)

Iron Deficiency Anemia (IDA)

Iron deficiency accounts for over 75% of non-physiologic anemias in pregnancy. Fetal iron demands take precedence across the placental transfer gradient; maternal iron stores deplete first.

• Diagnostic Biomarkers:
  • Serum Ferritin: The single most sensitive and specific test for total body iron depletion in pregnancy. A serum ferritin <30 ng/mL confirms iron deficiency anemia even before red blood cell indices change.
  • Complete Blood Count Indices: Low mean corpuscular volume (MCV <80 fL, microcytosis), low mean corpuscular hemoglobin concentration (MCHC, hypochromia), and elevated red blood cell distribution width (RDW >14.5%).
• Oral Iron Therapy:
  • Dose: 60 to 120 mg of elemental iron daily (e.g., ferrous sulfate 325 mg tablet provides 65 mg elemental iron; ferrous fumarate 325 mg provides 106 mg elemental iron; ferrous gluconate 325 mg provides 36 mg elemental iron).
  • Patient Education: Take on an empty stomach with a source of vitamin C (ascorbic acid, e.g., orange juice) to enhance enteric iron absorption. Avoid concurrent ingestion with calcium supplements, antacids, dairy, tea, or coffee, which bind iron and block absorption.
  • Alternate-Day Dosing: Recent clinical trials demonstrate that alternate-day iron dosing (e.g., 60–100 mg elemental iron every other morning) induces lower hepcidin peaks, improves fractional iron absorption, and substantially mitigates gastrointestinal side effects (nausea, constipation, abdominal cramping).
• Intravenous Iron Therapy:
  • Indications: Severe intolerance or non-adherence to oral iron, severe malabsorption syndromes (e.g., post-Roux-en-Y gastric bypass, celiac disease, inflammatory bowel disease), or severe late-gestation anemia (Hb <8.0–9.0 g/dL at >34 weeks) where rapid repletion prior to delivery is imperative.
  • Agents: Intravenous iron sucrose, ferric carboxymaltose, or ferumoxytol provide complete store replenishment within 1 to 2 infusions with low risk of anaphylactoid reactions.