HYPOTHYROIDISM IN PREGNANCY

CASE PRESENTATION ANTENATAL WARD 30/3/11

Control of thyroid function

By a negative-feedback loop: The hypothalamus releases TRH TRH acts on the pituitary gland to release TSH TSH acts on the thyroid gland to release the thyroid hormones (T3 and T4) that regulate metabolism TRH and TSH concentrations are inversely related to T3 and T4 concentrations. 99% circulating T3 and T4 is bound to TBG. 1% circulate in the free form, and only the free forms are biologically active.

Physiological changes of thyroid during pregnancy 1. TBG Increase {hepatic synthesis is increased} 2. TT4 & TT3 increase to compensate for this rise 3. FT4 & FT3 decrease. FT4 are altered less by pregnancy, but do fall a little in the 2nd & 3rd trimesters. 4. TSH decrease in 1st trimester, between 8 & 14 wk {increase HCG, HCG has thyrotropin-like activity}, increase in 2nd & 3rd trimester {Increased TBG}

5. Pregnancy is associated with a state of

relative iodine deficiency
{a. increase maternal iodine requirement because of active transport to fetoplacental unit b. Increase iodine excretion in urine, 2 fold, because of increased GFR & decreased renal tubular reabsorption} The thyroid gland increases its uptake from the blood 3 fold {fall of plasma iodine}

If there is already dietary insufficiency of iodine, the thyroid gland hypertrophies in order to trap a sufficient amount of iodine

Phenomenon High thyroxine-binding globulin (TBG)

Explanation Increased serum estrogen

First trimester TSH suppression Slight increase in FT4 Goitre in iodine deficiency areas Goitre in iodine sufficient areas Increased T4 and T3 demand High total T4 and T3 Increased thyroglobulin

HCG HCG Increased iodide clearance Increased demand High type III deiodinases Increase in TBG Increased demand for thyroid hormones

Non-pregnant TSH mu/l 0-4

1st trimester 0-1.6 11-22 4-8

2nd trimester 0.1-1.8 11-19 4-7

3rd trimester 0.7-7.3 7-15 3-5

FT4 pmol/l 11-23 FT3 pmol/l 4-9

The shaded area represents the normal range in non pregnant

Thyroid physiology and the impact of pregnancy

Fetal thyroid function During early gestation: the fetus receives thyroid hormone from the mother. Maternal T4 crosses the placenta actively, the only hormone that does so. (T3, TSH) The fetus s need for thyroxine starts to increase as early as 5 wk of gestation. Fetal thyroid development does not begin until 10 to 12 wk, and then continues until term.

The fetus relies on maternal T4 exclusively before 12 wk & partially thereafter for normal fetal neurologic development. Maternal hypothyroidism could be detrimental to fetal development if not detected and corrected very early in gestation. Preconceptional optimization of T4 therapy is important

Incidence Much more common in women than men Common in those with family history Overt hypothyroidism: 0.3% - 2.5% of pregnancies
Thus, about 40 patients need to be screened to detect one case.

Subclinical disease: 2% to 3% of pregnancies

Causes

Iodine deficiency: Most common cause in most of the world Hashimoto s thyroiditis (chronic autoimmune thyroiditis): Most common cause in developed countries, where lack of iodine in the diet is not a problem characterized by: antithyroid antibodies (thyroid antimicrosomial and antithyroglobulin antibodies). Both iodine deficiency and Hashimoto s thyroiditis are associated with goiter.

Other causes: -Radioactive iodine therapy for Graves disease; -Thyroidectomy -Viral thyroiditis -Pituitary tumors -Sheehan s syndrome; -Medications
y

Thionamides Lithium Drugs that inhibit absorption of thyroid medication

( Ferrous sulfate, Sucralfate, Cholestyramine, Antacids (aluminum hydroxide)

Iodine and lithium inhibit thyroid function and, along with dopamine antagonists, increase TSH levels. Thioamides, glucocorticoids, dopamine agonists, and somatostatins decrease TSH levels. Ferrous sulfate, sucrafate, cholestyramine, and aluminum hydroxide antacids all inhibit GIT absorption of thyroid hormone and therefore should not be taken within 4 hrs of thyroid medication.

Screening Routine screening has been recommended: Infertility, menstrual disorders, Repeated pregnancy loss,Type 1 DM, Pregnant women who have S&S of deficient thyroid function.

In recent years, some authors have recommended screening all pregnant women for thyroid dysfunction, but such recommendations remain controversial.
Routine screening is not endorsed by the ACOG

Clinical pictures Similar to physiologic conditions seen in most pregnancies. cold intolerance, muscle cramps, intellectual slowness, depression, insomnia, periorbital edema, myxedema, and myxedema coma
SYMPTOM Fatigue Constipation Hair loss Dry skin Brittle nails Weight gain Fluid retention Bradycardia Goiter Carpal tunnel syndrome o o o o o o o o o o o o HYPOTHYROIDISM PREGNANCY o o

o
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laboratory tests Because screening is controversial and symptomatology does not reliably distinguish hypothyroidism from normal pregnancy, laboratory tests are the standard for diagnosis. Overt hypothyroidism: symptomatic patient elevated TSH level low levels of FT4 and FT3. Subclinical hypothyroidism: asymptomatic patient. elevated TSH normal FT4 and FT3

Effects of hypothyroidism on pregnancy The impact of maternal hypothyroidism on the fetus depends on the severity of the condition. A. Uncontrolled hypothyroidism. Miscarriage Anaemia Intrauterine fetal demise and stillbirth preterm delivery, low birth weight, preeclampsia, developmental anomalies including reduced IQ.

A. Maternal and congenital hypothyroidism resulting from severe iodine deficiency: profound neurologic impairment & mental retardation. If the condition is left untreated. Congenital cretinism: Growth failure, mental retardation, and other neuropsychologic deficits including deaf-mutism. If cretinism is identified & treated in the first 3 months of life: near-normal growth and intelligence can be expected. For this reason, newborn screening for congenital hypothyroidism.

B. Asymptomatic overt hypothyroidism. Women who had previously been diagnosed with hypothyroidism, (abnormal TSH and FT4 levels), but who do not have symptoms. 1. Impaired psychomotor development at 10
months in infants born to mothers who had low T4 during the first 12 ws of
gestation

2. low IQ scores in the offspring at 7 to 9 yrs of age was

correlated with elevated maternal TSH levels at less than 17 weeks gestation

C. Subclinical hypothyroidism. Low IQs of the children whose mothers were not treated (Mitchell and Klein, 2004). Undiagnosed subclinical hypothyroidism were more likely to be complicated by placental abruption, preterm birth (Casey, 2005).

Maternal and Neonatal Complications of Hypothyroidism in Pregnancy

Overt Hypothyroidism 60 (%) 13 (21) 3 (5) 4 (6.6) 4 (6.6) 2 (3.3) 10 (16.6) Subclinical Hypothyroidism 57 (%) 9 (15) 0 2 (3.5) 1 (1.7) 0 5 (8.7)

No. of Patients* PIH Placental abruption PPH Stillbirths Congenital malformations LBW

Treatment The treatment of choice is synthetic T4, or levothyroxine. Non pregnant: 1.7 g/kg/day or 12.5 to 25 g/day adjusted by 25 g/day every 2 to 4 ws until euthyroid state is achieved.

Pregnant: Safe in pregnancy and lactation. {Very little thyroxin crosses the placenta and the fetus is not at risk of thyrotoxicosis} Patients who were on thyroxine therapy before pregnancy should increase the dose by 30% once pregnancy is confirmed. TSH should be monitored /4 wk k to maintain a TSH level between 1 and 2 mU/L and FT4 in upper third of normal. Once euthyroid state has been achieved, TSH should be monitored /trimester until delivery.

During pregnancy, thyroid function merits regular monitoring, finetuning of treatment