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At the beginning of June, we addressed a very frequent topic capable of generating doubts even among specialists, which is the management of thyroid changes in gestation. In the previous publication, we covered the importance and minutiae in the care of hypothyroidism and subclinical hypothyroidism. Today, we will focus on care when diagnosing hyperthyroidism, the management of thyroid nodules and cancer in general lines during pregnancy and also on how to diagnose postpartum thyroiditis. The basis of the text was the review published in January 2022 in Nature Endocrine Reviews regarding the topic.
The two leading causes of hyperthyroidism in pregnancy are Graves’ disease (prevalence estimated at 0.05%) and transient thyrotoxicosis of pregnancy (TTG) (prevalence estimated at 2 to 11%). It is critical to distinguish between conditions.
GTT is caused by high levels of bHCG, especially in early pregnancy and is commonly associated with hyperemesis. Both will present with a suppressed TSH profile (don’t forget that physiological TSH reduction is very common, but in these cases there is no elevation of free T4, nor are there any symptoms!) and elevated T4l. An early clue may be a T3/T4 ratio > 20:1 in Graves’ disease, due to the preferential production of T3 in this condition, and < 20:1 in GTT, where T3 levels do not usually rise as much. In addition, symptoms in Graves can start before pregnancy and it is possible for the patient to notice this.
But the main clues remain the main criteria for diagnosing Graves: TRAb positive and ophthalmopathy.
GTT is a benign condition, which tends to be self-limiting and resolves by the end of the first trimester, not being associated with worse pregnancy outcomes. Treatment must be symptomatic.
Also listen: ENDO 2022 Highlights [podcast]
Hyperthyroidism caused by Graves’ disease should be treated, as it can have consequences for pregnancy, such as pre-eclampsia, increased risk of miscarriage, maternal heart failure, preterm labor, low birth weight and fetal hyperthyroidism.
It is worth remembering that subclinical hyperthyroidism no is associated with proven adverse outcomes.
The prevalence of thyroid nodules in pregnancy varies between 3 and 29%. Older age, insufficient or excessive iodine intake, and greater parity may increase the risk. During pregnancy, the nodules can grow, especially when stimulated by hCG (this phenomenon can also lead to a slight hyperplasia of the gland with an increase in volume). The exam of choice remains ultrasound, with the same criteria for defining the need for FNAB, which is a safe procedure during pregnancy. Benign nodules should have the same management as outside of pregnancy, while BETHESDA III nodules should have the FNA repeated. In cases of TSH suppressed beyond the 16th week associated with a nodule, a toxic adenoma is suspected. In this case, due to the high probability of benignity, FNA can be postponed until after delivery, when it is possible to perform scintigraphy to clarify whether it is indeed a hot nodule.
Considering the high stress associated with a possible cancer diagnosis and the good overall prognosis, in some cases it is possible to postpone FNA until after pregnancy, if the patient prefers, with data from studies showing that this practice does not have a worse impact on outcomes such as overall survival, changes in tumor volume, or development of lymph node metastases.
The incidence of thyroid cancer is increasing in young women. Data from the USA (between 1991 and 1999) show that thyroid cancer was the second most diagnosed in the perinatal period, totaling an incidence between 1 year before and 1 year after delivery, approximately 17 cases per 100,000 women.
More importantly, follow-up of the same cohort showed that there was no worsening of maternal or neonatal outcomes in women diagnosed with cancer during this period, nor was there an impact on survival.
The ATA considers that most women with well-differentiated thyroid cancer (DTC) can maintain active surveillance with serial US. If tumor growth or metastases are observed, surgical treatment should be considered in mid-pregnancy (2nd trimester), when it is safer. The other subtypes (medullary and anaplastic) should be submitted to surgical treatment, considering their more aggressive nature.
If radioiodine therapy (RIT) is indicated, it should be postponed until postpartum. The mammary gland also expresses NIS, which symports sodium and iodine and therefore accumulates radioactive iodine. In such cases, it is important to stop breastfeeding at least 6 weeks to 3 months before iodine treatment.
The history of a DTC does not contraindicate pregnancy in a global way. Data from a Korean cohort from 2006 to 2014 suggested no worse outcomes in pregnancy. A North American study, in turn, showed that pregnant women who had an excellent or indeterminate response had no negative impact on cancer control. Among the patients with incomplete structural response, 29% had disease progression. So, in this case, you need to be careful. The recommendation is for usual follow-up in case of excellent or indeterminate response, more frequent reassessment if biochemical response is incomplete. Cases of incomplete structural response should be individualized and explained to the patient.
Know more: ENDO 2022: Treating hypothyroidism with levothyroxine is enough
As for TSH targets, as it has been well demonstrated that subclinical hyperthyroidism has no consequences for pregnancy, there are no problems in maintaining suppressive therapy with levothyroxine.
Postpartum thyroiditis can occur in up to 8% of women within 1 year of pregnancy. It is a destructive thyroiditis, which usually occurs 4 to 8 weeks after delivery. It can affect even after an abortion and can also affect those who already have hashimoto and use levothyroxine. It is more common in those who are anti-TPO positive.
Like other thyroiditis, there are different phases. The first phase presents as thyrotoxicosis, resulting from thyroid inflammation and release of hormone stores. This phase lasts about 1 to 2 months and treatment is supportive. Afterwards, a phase of transient hypothyroidism may occur, and up to 50% may develop permanent hypothyroidism, with a higher risk in patients with positive anti-TPO. In 70% of the time there is recurrence in subsequent pregnancies.
Thyroid diseases during pregnancy are a separate chapter due to the various hormonal changes typical of the period, especially the increase in estrogen and hCG. Such patients should be followed up by an endocrinologist when there is any doubt, in order to avoid unnecessary treatments that may have undesirable consequences.
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