Hyperthyroidism in Pregnancy

Hyperthyroidism is a clinical syndrome characterized by an increase of thyroid hormones production. As much of the thyroid disease hyperthyroidism occurs more frequently in women with an estimated incidence of 3.9%.

Most frequent causes

Uncommon causes

  • Graves’ Disease
  • Toxic Multinodular Goiter
  • toxic adenoma (Plummer’s disease)
  • Thyroiditis

 

  • assumption of thyroid extracts in diet
  • exogenous administration of thyroid hormones
  • Trophoblastic tumors
  • TSH-secreting pituitary tumor
  • Thyroid Carcinoma
  • Struma Ovarii

 

Graves’ Disease is the most frequent cause and frequently affects under 45 women, then during reproductive age. despite being one of the causes of infertility is not uncommon its appearance during pregnancy .

The Toxic Multinodular Goiter is the second among the most frequent causes but usually affects over 50 women and generally appears in patients who already carrier a Non-Toxic Multinodular Goiter.

One of the possible consequences of Graves’ disease and hyperthyroidism is the infiltrative orbitopathy with a bulging of the eye anteriorly out of the orbit (exophthalmos also called proptosis), a particularly serious ocular complication.

Hyperthyroidism symptoms vary according to the disease seriousness and typically consist of an increase in heart rate (tachycardia) often greater than 100 beats per minute, weight loss (slimming), fatigue, irritability, anxiety, insomnia, vomiting (hyperemesis) and some typical symptoms of pregnancy can be accentuated as the tendency to tiredness, heat intolerance and perspiration. Sometimes it is very obvious a diffuse enlargement of the thyroid gland (located in the anterior region of the neck). Patients with hyperthyroidism often have eye problems (even asymmetric) ranging from eyelid retraction to Exophthalmos (protrusion of the eyeball) typical of Graves’ disease, are also frequent: nail brittleness, increased hair loss, thickening of the pretibial tissues (myxedema).

We must remember, however, that an easier tendency to fatigue, nausea especially in the morning and gagging, irritability and anxiety and some mild tachycardia may be present in many perfectly normal pregnant women so it will always very important to conduct a differential diagnosis. In initial conditions of poor pregnancy weight gain or slimming with excessive vomiting (hyperemesis) always require a thyroid evaluation.

In the family history of these women is frequently present other cases of thyroid disease. Histocompatibility complex studies (for example, those that run on the occasion of organ transplants) have also shown an association with groups HLA-B8 and HLA-DR3.

Hyperthyroidism diagnosis is based on the clinical picture and on laboratory hormonal investigations. It is in fact necessary to the blood levels determination of FT4, FT3 (free fractions of thyroid hormones circulating in the body) and TSH (small protein hormone produced by the pituitary gland). Typically, in Hyperthyroidism FT3 and FT4 will be higher than normal (in some cases may increase only the FT3) and TSH will be very low or undetectable. TSH in normal conditions has a role in thyroid stimulating but when it works too and in an uncontrolled way as occurs in hyperthyroidism its production is lowered as a result of a strong signal (feedback) negative at the pituitary level which is increased by levels of FT3 and FT4.

Gland direct palpation is a critical clinical moment because it provides information on the size, volume, achiness and surface appearance. It also is very important neck lymph nodes, lateral cervical and supraclavicular palpation.

to a number of instrumental and immunological analysis contributing significally to Hyperthyroidism identification in pregnancy:

–      Thyroid ultrasound

–      Thyroid color-doppler ultrasound

–      Searching for thyroglobulin antibodies (Tg), anti-thyroid peroxidase (TPO) and anti-TSH receptor antibodies (TRAb)

Since in most cases it is an autoimmune disease (ie triggered and maintained by a self-aggression of their own immune defense system), antibodies dosage is important not only for diagnosis but also for disease monitoring. The research of TRAb is particularly important during pregnancy because high levels may give rise to the suspicion that there is an involvement of the fetal thyroid with the consequent risk of fetal hyperthyroidism and possible future neonatal thyrotoxicosis. In some patients it is useful dosing iodine urinary excretion to exclude its excessive dieatry introduction and in other cases (subacute thyroiditis and fictitious) may be useful a dosage of serum thyroglobulin.

Thyroid is important for the entire body but hyperfunction (hyperthyroidism) in pregnancy has a lot of possible negative effects. In women whit hyperthyroid are more prevalent: Hypertension, Anemia, Heart disease, Pre-Eclampsia, Placental abruption, Miscarriage, premature birth, fetal malformations, intrauterine fetal death, low weight of babies at birth. Newborns of these patients may have altered thyroid function and also have higher incidence of pre-natal mortality. Of course everything is always related to the illness severity and duration.

Therapy in pregnancy is basically medical, surgical option is rare.

Medicines used are anti-thyroid, that is molecules that reduce the function of the gland and then the levels of its circulating hormones: Methimazole, Propylthiouracil and Carbimazole are the most commonly used molecules and belong to the group of “Thionamides.”

Therapy, when necessary, should be undertaken as early as possible and aims to Euthyroidism (normal serum levels of thyroid hormones) in the quickest time possible, however, that ranges between 2 and 6 weeks (the drugs do not affect thyroid hormones already produced and stored in the gland).

Methimazole (MMI) is the most widely used drug in Europe while Propylthiouracil (PTU) is the drug of choice in the United States. The latter also is not available in Italy, but can still be obtained with a “Galenic” prescription  in some pharmacies. Although it has been suggested that the PTU is preferable in pregnancy, many believe MMI equally safe and effective. Data that demonstrate a link between the administration of MMI with Aplasia Cutis and other infant malformations seem controversial and inconclusive. Choice of a molecule respect to another is then determined from experience, from scientific beliefs of the doctor and from availability of the drug. The “attack doses” in Hyperthyroidism are generally 20-30 mg of MMI and 200-400 mg of PTU divided into two (MMI) or three (PTU) daily doses. Then (if the clinical condition improves) we tend to always achieve the lowest effective dose that is around 5-10 mg MMI or 50-100 mg of PTU.

Medical therapy, whatever is the molecule chosen, it is very important: not only decreases the incidence of fetal malformations related to the disease but overall has a very positive influence on the  pregnancy course favoring reproductive success. 5% of women taking Thionamides have side effects such as rashes, itching, Agranulocytosis (decrease in white blood cell) which, however, does not necessarily require interruption of treatment. More rarely may occur liver changes (hepatotoxicity) and joint disorders.

The benefit / risk balance is greatly in favor of medical therapy with Thionamides.

Sometimes to control maternal heart rate symptomatology (tachycardia) and hypertension may be indispensable using beta-blockers. Propranolol is widely used, but also Atenolol is an excellent drug. These molecules are not contraindicated in pregnancy and also allow to monitor and heal tremors and anxiety often present in situations of high heart rate (eg Thyroid Storm).

Clinical monitoring of these patients and their fetus is another crucial moment. The clinical monitoring of these patients and fetus is another crucial moment. Are recommended, in addition to the common controls provided in pregnancy, frequent checks of pressure, Thyroid volume, maternal and fetal weight and heart rate. Monthly, it is also good to check blood counts and dosage of TSH, FT3, FT4. The FT4 dosage has a particular importance and the objective is to keep it within medium-high limits. Because of fetuses of hyperthyroid patients have increased risk of malformations and growth abnormalities, in addition to routine ultrasound scans it is strongly indicated a II level morphological ultrasound with Doppler flow  at the 20th week, and this will also allow to observe the fetal Thyroid.

The search for maternal anti receptor antibodies TSH (TRAb) is recommended at the 20th and at the 30th week to identify fetuses at increased risk and to adopt more stringent measures if necessary. Postnatal and breastfeeding periods require particular attention both to the mother and neonate. Mom and baby should be carefully monitored clinically and in laboratory. It is also important to look for TRAb in newborn. Usually pregnancy has a favorable effect on  Graves’ Disease and it is not uncommon to attend a clinical improvement, but in the postnatal period clinical picture may change again.

Thionamides treatment is not a contraindication to breastfeeding but the decision to keep it still requires more prudential attitudes (minimal doses of drugs, more frequent baby checks).

In women affect by Hyperthiroidism who wish to become pregnant it is advisable to first get a good control of the disease until arriving to take low doses of anti-thyroid drugs, at which point it is possible to try. After a treatment with radioactive iodine, it is advisable to wait at least a year. In these cases, there have not been reported adverse effects on newborns.

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Filiberto Di Prospero
Medical Doctor, Consultant in Gynecology and Obstetrics, Endocrinology and Metabolism. Director of Gynecologic Endocrinology Unit at Civitanova Marche General Hospital (Italy). Private clinics in Civitanova Marche, Rome and Milan.

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