Thyroid Disease In Pregnancy

It is usual for the thyroid gland to hypertrophy in normal pregnancies. There is also an increase in thyroid-binding globulin and albumin due to increased hepatic synthesis.¹

• An increased rate of pregnancy failure
• An increased incidence of gestational thyroid dysfunction
• A predisposition to postpartum thyroiditis

Thyroid function should be measured in women with severe hyperemesis gravidarum but not in every patient with nausea and vomiting during pregnancy.

Epidemiology

Hypothyroidism (including subclinical hypothyroidism) occurs in 2.5% of pregnant women.³
Aetiology:

• Autoimmune thyroiditis, e.g. Hashimoto's thyroiditis
• Radiotherapy or surgery
• Congenital
• Drugs, e.g. lithium, amiodarone
• Iodine deficiency
• Infiltrative diseases
• Pituitary or hypothalamic disease

Presentation

Dry skin with yellowing especially around eyes.
Weakness, tiredness, hoarseness, hair loss, intolerance to cold, constipation, sleep disturbance.
Goitre, delayed relaxation of deep tendon reflexes.

• Anaemia, low T4, raised TSH.
• In sub-clinical form TSH raised, but free T4 and T3 normal. Antibodies to thyroid peroxidase, TSH receptor or thyroglobulin.

Management

• Thyroxine at increasing dosages until TSH brought to normal-low range.⁴
• Hypothyroidism in pregnancy is treated with a larger dose of thyroxine than in the nonpregnant state.
• Dose will need to be reduced as necessary after delivery, but postpartum thyroid dysfunction (PPTD) occurs in 50% of women found to have thyroid peroxidase antibodies in early pregnancy. The hypothyroid phase of PPTD is symptomatic and requires thyroxine therapy.
• A high incidence (25-30%) of permanent hypothyroidism has been noted in these women.² Women having transient PPTD with hypothyroidism should be monitored frequently, as there is a 50% chance of these patients developing hypothyroidism during the next 7 years.

Complications

Congestive heart failure most significant potential problem.
Women may also develop megacolon, adrenal crisis, organic psychosis, myxoedema coma, hyponatraemia (due to syndrome of inappropriate secretion of antidiuretic hormone).

Prognosis

• Prognosis for mother and fetus is excellent with appropriate treatment.
• However there is a small increase in stillbirth rate, and fetal assessment in third trimester is necessary.
• Recent research has suggested increased risk of lower IQ of children of women with hypothyroidism, even with euthyroid fetus as maternal thyroid hormone needed for neuronal development until 12-13 weeks.⁵

Epidemiology

Seen in 0.2% of pregnant women.³Aetiology:

• Graves disease; commonly found in 3rd and 4th decades of life. An autoimmune condition with highly variable episodes of worsening of condition (precipitated by stress) mixed with periods of remission.
• Toxic nodular goitre; uncommon result of long-standing simple goitre usually in women over 40 years or age.
• Toxic adenomas; greatly vary in size, histology and function independently of TSH. Usually present as solitary nodule with function increasing with time. This causes subsequent atrophy of remaining gland, with frank thyrotoxicosis usually developing.

Presentation

Restlessness, tiredness, weakness, weight loss, diarrhoea, intolerance to heat. Tachycardia, tremor, goitre, muscle weakness, lid retraction or lag.

• TSH is usually reduced
• Free T4 raised

With Graves disease there may be antibodies to thyroid peroxidase or TSH receptor.
Thyroid-stimulating hormone-receptor antibody measurements at 36 weeks' gestation are predictive of transient neonatal hyperthyroidism, and should be checked even in previously treated patients receiving thyroxine.

Management

• Graves hyperthyroidism during pregnancy is best managed with propylthiouracil administered throughout gestation.
• Where ineffective, subtotal thyroidectomy, often performed in second trimester. Radioiodine therapy in pregnancy is absolutely contraindicated.
• Postpartum exacerbation of hyperthyroidism is common, and women with Graves disease not on treatment should be monitored.

Complications

• Severe exophthalmos, cardiac disturbances, increased rate of stillbirth.
• Rarely fetal goitre may cause extension of head at delivery, requiring operative delivery and/or obstruction of airway.
• Passage of TSH receptor antibodies across placenta can cause fetal and neonatal hyperthyroidism. This is suggested by:
  • History of stillbirth
  • Fetal heart rate >160bpm after 22 weeks gestation with raised level of antibody early in pregnancy. Untreated can cause fetal growth restriction, craniocynostosis and death.
  • Symptoms may continue for up to 10 months after birth.

Aetiology

• Acute; usually caused by infection of piriform sinus in younger patients
• Sub-acute thyroiditis; de Quervain's or granulomatous thyroiditis and includes postpartum thyroiditis and infection with bacteria or mycobacteria
• Chronic thyroiditis; 3 types are autoimmune thyroiditis e.g. Hashimoto's thyroiditis, Riedel's thyroiditis (occurs in middle-aged pregnant women) and parasitic thyroiditis.

Presentation

• Sub-acute thyroiditis; tender thyroid enlarged on one side and may have pain in throat or otalgia. May have history of earlier malaise and upper respiratory tract infection. Patients may show signs of thyrotoxicosis due to release of hormones from follicular destruction.
  At this point
  • TSH low with free T4 elevated
  • This is followed by raised TSH and low free T4
• Postpartum thyroiditis; silent thyroiditis often presents 3-6 months postpartum and is usually painless with positive test for thyroid peroxidase antibodies and normal ESR.
• Chronic thyroiditis; Hashimoto's disease is characterised by antibodies to several components of thyroid tissue and uniform goitre eventually developing into hypothyroidism. Riedel's thyroiditis presents as a hard, asymmetrical fixed thyroid gland, may cause symptoms by compressing the oesophagus or trachea.
  • Thyroid function test normal
  • ESR raised
  • Leucocytosis

Associations

Hashimoto's disease may be associated with other autoimmune diseases e.g. Addison's, pernicious anaemia also shows increased incidence of mitral valve prolapse. Rarely, autoantibodies cross placenta to cause thyroiditis in the fetus.

Management

• Sub-acute thyroiditis; usually resolves spontaneously. Patients may need treatment if prolonged hypothyroidism.
• Postpartum thyroiditis; does not usually require treatment, may benefit from yearly reassessment.
• Chronic thyroiditis; Hashimoto's may cause hypothyroidism requiring treatment with thyroxine. Reidel's thyroiditis may require rescue surgery for severe compression symptoms on trachea or oesophagus.⁶

Complications

Hashimoto's thyroiditis is associated with an increased risk of miscarriage. The patient may be left hypothyroid in the longterm.