Thyroid disease COPY Flashcards
Physiology of thyroid gland
TRH produced by hypothalamus
TSH produced by anterior pituitary
Thyroid gland produces all T4 and 20% T3
The majority T3 is converted peripherally from T4
Only free T3 and T4 are able to have to have effect on tissues
The rest of T3/T4 is bound to thyroid-binding globulins produced by the liver
Free T3/T4 have negative feedback effect on the pituitary gland
Changes to thyroid gland in pregnancy
The thyroid increases in size by 10-20% due to HCG stimulation and relative iodine deficiency during pregnancy.
HCG alpha-subunit is structurally similar to TSH.
As HCG peaks between 9-12 weeks, it stimulates thyroid and causes increased total T3/T4, with a drop in TSH.
Total T3 and T4 levels increase in response to HCG, but
Thyroid-binding globulin levels increase two-fold through pregnancy, so total T4 levels are not representative of metabolically active free T4 levels.
This plateaus around 20 weeks and through the rest of pregnancy the TSH and free T4 returns to relatively normal levels. Hence TSH is the most accurate hormone to assess hypothyroidism, and free T4 the best to asses hyperthyroidism
What is the prevalence of thyroid disease?
2-3% pregnant women
Majority is hypothyroidism
Only 0.2% pregnant women have hyperthyroidism
How do thyroid hormones affect the developing fetus?
TSh does not cross placenta.
Maternal T3 and T4 cross the placenta and are important for development in the first trimester.
After 12week the fetus starts producing its own T3/T4.
Prevalence and causes of hyperthyroidism in pregnancy?
Hyperthyroidism occurs in 0.2% of pregnant women and most are diagnosed before pregnancy or in the first trimester.
Overt hyperthyroidism is defined as a serum TSH below the trimester specific level, with an elevated T3 or T4.
Causes of maternal hyperthyroidism include:
- Graves disease (90% of cases)
- toxic nodule
- toxic multinodular goitre
- iodine, Amiodarone, lithium therapy
- gestational hyperthyroidism (due to high HCG levels)
- hydatiform mole
- hyperemesis gravidarum (45% risk hyperthyroidism)
- multiple pregnancy- -> worse in 1st trimester then generally self resolves during 2nd trimester. No need for medication.
What are the specific neonatal concerns with Graves disease?
TRAb (TSH receptor stimulating antibodies) cross the placenta and can cause:
- fetal thyrotoxicosis (thyroid enlargement, growth restriction, hydrops, presence of goitre, advanced bone age, tachycardia, cardiac failure)
- miscarriage
- stillbirth
- neonatal thyrotoxicosis (incidence 1–5%; mortality rate as high as 12–20%).
Neonatal hypothyroidism; due to transplacental crossing of anti-thyroid medications
What are the obstetric and maternal concerns with Graves Disease?
Risk increases with poor thyroid control
- Pre-eclampsia
- thyroid storm and thyrotoxic heart failure – both are an acute and life-threatening conditions in pregnancy caused by an excess of thyroid hormone; clinical features are fever, tachycardia, cardiac dysrhythmia and central nervous system dysfunction.; treatment should be carried out in a critical care setting with antithyroid medications, steroids, β-blockers and supportive measures such as temperature control
- fetal growth restriction
- prematurity
- miscarriage/stillbirths
- fetal thyrotoxicosis / neonatal thyrotoxicosis
- Neonatal hypothyroidism
What drugs are available for anti-thyroid treatment?
What are the risks of each?
What is the general consensus on thyroid management in pregnancy?
carbimazole (CBZ), methiamazole (MMI, the active part of CBZ) or propylthiouracil (PTU), which block thyroid hormone synthesis and reduce the titre of TSH receptor antibodies. All of these cross the placenta, but PTU less so than CBZ and MMI.
There is a possible rare risk of fetal aplasia cutis (reversible) or an embryopathy (choanal atresia, trachea-oesophagael fistula, facial dymorphism and cognitive development delay) with CBZ or MMI.
PTU does not cause fetal anomaly but is a rare, proven cause of maternal liver damage that has resulted in many worldwide cases of death or liver transplant requirements. There is a small chance of maternal agranulocytosis with both PTU and CBZ.
There is indecision across the literature as to the best drug to use for hyperthyroidism in pregnancy. The current general consensus, however, is to use PTU in the first trimester and then change to CBZ or MMI for the second and third trimesters. In effect, the decision is between a small risk of fetal abnormality and a similarly small but real risk of life-threatening maternal liver failure. It therefore may also be appropriate to leave well-controlled women on CBZ or MMI in the first trimester of pregnancy.
In terms of breastfeeding, PTU is preferred if treatment is required because negligible amounts are secreted in breast milk.
Block and replace regimens should not be used because higher doses of antithyroid drugs are required and, as there is minimal transplacental transfer of T4, there is a higher risk of fetal hypothyroidism and goitre.
What treatment options are available for Graves disease / hyperthyroidism in pregnancy?
Medication: PTU/CBZ/MMI
Thyroid function tests should be monitored every 4–6 weeks and free T4 should be kept at, or moderately above, the normal reference range.
Surgery is rarely performed in pregnancy but it is a possibility if there is drug resistance or serious side effects with antithyroid drugs, e.g. agranulocytosis.
Radioactive iodine treatment is contraindicated during pregnancy and pregnancy should be avoided for at least 6 months after treatment.
Ideally, women should be treated with surgery or radioactive iodine prior to next pregnancy.
Define overt and subclinical hypothyroidism.
Overt hypothyroidism (OH)
- elevated TSH (using pregnancy-specific ranges for each trimester) AND decreased free T4 concentration
- Women with TSH levels >/= 10.0 mIU/l irrespective of their free T4 levels
Subclinical hypothyroidism
- elevated serum TSH of 2.5–10.0 mIU/l BUT a normal free T4 concentration.
What causes hypothyroidism in pregnancy?
OH complicates 2–10 per 1000 pregnancies and is commonly due to:
Hashimoto's thyroiditis previous radioiodine therapy/thyroid surgery previous postpartum thyroiditis hypopituitarism iodine deficiency.
What are the obstetric risks of overt hypothyroidism?
- miscarriage,
- pre-eclampsia,
- pregnancy-induced hypertension,
- postpartum haemorrhage
- low birth weight,
- slight reduction in IQ in the fetus
- NO increased risk of congenital malformations.
The fetus is dependent on maternal thyroid hormones until 12 weeks of gestation when autonomous fetal thyroid function begins; therefore, adequate thyroxine replacement early in pregnancy is essential.
What is the effect and concerns for TPO (thyroid peroxidase) antibodies in pregnancy?
The presence of thyroid peroxidase (TPO) antibodies is strongly associated with:
- postpartum thyroiditis
- risk of developing OH
Several meta-analyses have shown TPO antibodies are associated with miscarriage, preterm birth and infertility, even in euthyroid women, but controversy remains.
There is no evidence that thyroxine replacement in these women improves outcomes (TABLET trial 2017).
Thus RANZCOG does not endorse testing TPO antibodies.
How it hypothyroidism managed through pregnancy?
Subclinical hypothyroidism - no management
Overt hypothyroidism:
- Ideally obtain stable thyroid function prior to conception
- If new diagnosis, commence thyroxine at 100-125mcg daily
- Up titrate by 25-50mcg until good control obtained
TSH monitoring:
- Aim to keep TSH in the lower half of reference range for pregnancy
- If new Dx or poorly controlled thyroid disease: 4-6 weekly
- If stable disease once every trimester
What are the obstetric benefits of using thyroxine to treat hypothyroidism in pregnancy?
Treatment seems to reduce the incidence of miscarriage and preterm birth, and improve fetal intellectual development; however, it has little impact on hypertensive disorders and placental abruption.
There is insufficient evidence to support levothyroxine replacement therapy in preventing adverse outcomes related to subclinical hypothyroidism. However, the most recent the Endocrine Society guideline recommendation is to treat pregnant women with subclinical hypothyroidism (evidence categorised as fair or poor).
