Thyroid and parathyroid surgery in pregnancy

The consideration of surgery during pregnancy requires weighing the benefit of urgent surgery against the risk to mother and fetus. Surgery during pregnancy involves an increase in both maternal and fetal risks. Thyroid and parathyroid surgery involves physiological risks to both mother and fetus specific to the disease and function of these endocrine glands. Evaluation of a thyroid mass is similar in pregnant patients with ultrasound and fine-needle aspiration biopsy providing the most important information, while the use of radiographic imaging is severely constrained except when specifically required. In general, thyroid surgery can be delayed until after delivery except in cases of airway compromise or aggressive cancer. In contrast, parathyroid surgery is recommended during pregnancy to avoid adverse effects to the neonate.

Introduction

Although surgery of any kind involves a balance of risks and benefits, during pregnancy the risks of surgery and anesthesia involve both the fetus and the mother. Because the pregnant patient is in an altered physiologic state, additional factors must be considered regarding preparation for and techniques used during surgery. Diseases and surgery of the thyroid and parathyroid glands impose specific risks to both mother and fetus. The following review was derived from a total of 72 articles.

General considerations for surgery during pregnancy

Complications of surgery during pregnancy include miscarriage, possible teratogenesis from anesthetic agents, intrauterine fetal asphyxia, hemorrhage, infection, and preterm labor and delivery, in addition to the risks and complications associated with specific surgical procedures.

Miscarriage and birth defects

The baseline rate of miscarriage is approximately 8–16% of clinically recognized pregnancies under 13 weeks of gestation, and 2–4% of pregnancies between 13 and 20 weeks of gestation. In a recent literature review of 54 articles on pregnancy outcomes after non-obstetric surgical interventions, Cohen-Kerem et al. found a reported miscarriage rate of 10.5% for patients who underwent surgery during the first trimester. The data suggest that elective surgery be deferred during early pregnancy to minimize potential fetal loss. It is the general consensus that surgery should be performed during the second trimester if possible, to reduce the risks of premature labor and miscarriage. Surgery performed in the first trimester was associated with major birth defects in 3.9% of cases. Premature labor, preterm delivery and the delivery of an infant weighing less than 1,500 g are the most significant risks of surgery during pregnancy.

Anesthesia

The choice of anesthesia should be based on maternal factors, the site and nature of surgery, and the anesthesiologist’s experience. Regional anesthesia has a better safety profile for a pregnant woman compared to general anesthesia. A major complication of regional anesthesia is the development of maternal hypotension secondary to local anesthetic-induced sympathetic blockade, which may reduce placental perfusion. Maternal hypotension must be treated immediately with the administration of crystalloids or by using an agent with predominantly beta adrenergic effects, such as ephedrine. The use of local and regional anesthesia for surgical procedures is becoming more wide spread, particularly for thyroid and parathyroid surgery, and is a viable option for many pregnant patients. Administration of general anesthesia must be preceded by careful evaluation of the airway and preinduction denitrogenation. Precautions against aspiration should be taken from as early as the 12th week of gestation by administration of a clear non-particulate oral antacid, H2 receptor blocker and metoclopramide. Rapid sequence intubation with the application of cricoid pressure is recommended. Edema, weight gain and increase in breast size may make intubation of the trachea technically difficult. An array of laryngoscope blades and handles, and other emergency airway management equipment should be available. Capillary engorgement of the mucosal lining of the upper airway accompanies pregnancy and may be exacerbated by an upper respiratory infection. This condition mandates extreme care during manipulation of the airway and the use of a smaller-than-normal endotracheal tube. Nasotracheal intubation and the use of a nasal airway should be avoided. The maintenance of normal adequate O2 and CO2 levels is crucial to maintaining normal fetal physiology. The fetal heart rate should be documented pre and postoperatively at all gestational ages.

Fetal monitoring

Using a Doppler apparatus, fetal heart rate monitoring becomes feasible after the 16th week of pregnancy, which may be technically difficult to use during an intra-abdominal procedure, but is eminently feasible for thyroid and parathyroid surgery. Also, there must be a plan on how to proceed in the event of fetal distress. Prior to 23 or 24 weeks of gestation, when the fetus is not viable, optimization of the maternal condition by increasing the blood pressure or increasing the inspired O2 concentration may improve the fetal condition.

Ethical considerations

Clearly, there are ethical dilemmas facing the clinician and the patient when dealing with the question of surgery during pregnancy. The first consideration is to weigh the risks of the disease to the mother and the possibility of postponement of treatment against the risk of surgery to the fetus. Risk to the fetus includes the possibility of teratogenesis (though the material reviewed in this paper indicates this is a minimal risk, particularly if surgery is done after the first trimester), as well as the possibility of fetal loss. These issues should be identified and discussed with the patient, so that she is able to carefully consider the ramifications of surgery versus postponement.

Thyroid and parathyroid surgery in pregnancy: overview

In 2009, Kuy et al. reviewed 201 pregnant women compared with 31,155 age-matched non-pregnant controls who underwent thyroid or parathyroid surgery. The authors found that pregnant women had significantly longer hospital stays (2 vs. 1 day), higher inpatient costs ($6873 vs. $5963) and higher rates of complications. Maternal complications were described as either endocrine (maternal hypoparathyroidism, hypocalcemia, tetany and recurrent nerve injury) or general surgical (cardiovascular, gastrointestinal, hematologic/vascular, urologic, pulmonary, infectious/wound and other) complications. Rates of both categories of complications combined were significantly higher in the population of pregnant women who underwent thyroid or parathyroid surgery compared to the controls (23.9 vs. 10.4%). Other variables that significantly increased the likelihood of complications included the presence of additional maternal comorbidities, the diagnosis of thyroid cancer, non-white ethnicity, and performance of surgery by someone other than a high-volume surgeon. Fetal complications occurred in 5.5% of pregnancies and included induced, spontaneous or missed abortion (fetal death without abortion), early or threatened labor, fetal distress, intrauterine death, stillbirth, neonatal hypocalcemic tetany and neonatal hypoparathyroidism. Maternal complications including hysterectomy, cesarean section, and dilatation and curettage occurred in 4.5% of cases. No breakdown was given regarding the incidence of each of these complications. Parathyroid surgery has evolved significantly over the last decade so that many cases are performed through very small incisions under local anesthesia, in as little as 20 min. the risks and morbidity of parathyroid surgery may be substantially less than for thyroid surgery. The authors concluded that: (a) thyroid and parathyroid surgery during pregnancy should be approached with caution and careful deliberation regarding risks and benefits (b) parathyroid surgery during pregnancy is usually indicated for protection of the fetus and prevention of neonatal hypoparathyroidism and tetany (c) thyroid surgery is not usually indicated unless airway compromise is imminent or an advanced thyroid cancer is present; and (d) high-volume endocrine surgeons achieve better outcomes than less experienced surgeons. Highest-volume surgeons had the shortest length of stay and the lowest complication rate.

Benign thyroid disease in pregnancy

Airway and esophageal obstruction

During pregnancy, the thyroid gland becomes enlarged from a generalized increase in vascularity, and also from the thyroid-stimulating hormone-like effects of human chorionic gonadotropin. In most patients, these changes do not significantly affect the patient’s ability to breathe and swallow. The airway is of particular concern with thyroid masses, since anesthesia may be needed at the time of delivery. Often, a goiter affecting the airway is apparent on physical examination from the size of the thyroid gland, the presence of tracheal deviation and whether the patient is able to breathe comfortably and silently at rest. Non-radiographic studies to examine the airway include fiberoptic laryngoscopy, esophagoscopy, ultrasound and magnetic resonance imaging (MRI). There are several reported cases of urgent thyroid surgery in the pregnant patient to alleviate impending airway obstruction.
In general, a goiter that is compressing the esophagus will not require treatment until the physiologic state of pregnancy is completely resolved long after delivery. Most patients can tolerate a soft or liquid diet even with the largest of goiters. Rarely, an aggressive thyroid cancer may invade the esophagus and cause complete obstruction, necessitating immediate treatment.
A hyper functional goiter (nodular or diffuse) can be successfully treated with anti-thyroid medications (propylthiouracil and methimazole), although there is some concern of adverse effects on the fetus. If these medications are used by the mother during pregnancy, the fetus should be monitored for the development of goiter. After delivery, thyroid function tests of the newborn should be followed to detect hypothyroidism.

Thyroid cancer

Davies and Welch reported an increased incidence of thyroid cancer in the USA, thought to be due to increased detection of papillary thyroid cancers (PTCs) less than 2 cm in size. The incidence has increased from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002, which is a 2.4-fold increase. Thyroid cancer occurs more commonly in women; often of child-bearing age. With the increasing age at which women are becoming pregnant, the incidence of cancer during pregnancy is likely to rise.
In 1970, Cunningham and Slaughter reported on 71 patients with thyroid disease detected in pregnancy, 8 of which were PTCs, and concluded that “pregnancy had no adverse influence on the course of thyroid cancer”.
In 1976, Asteris and DeGroot commented that “the numerous stimuli to thyroid gland documented urge caution, and … pregnancy is best avoided by women with known residual cancer. With regard to operating during pregnancy or waiting until after delivery, they stated that “although thyroid neoplasms are slow-growing and generally carry a good prognosis, we prefer not to temporize unnecessarily and are still concerned that pregnancy may accelerate tumor growth. In fact, the authors recommended near total thyroidectomy for any pregnant patient with any new thyroid nodule.

Evaluation of thyroid nodules during pregnancy

Guidelines by Abalovich et al. for thyroid dysfunction during and after pregnancy help to clarify the management of such nodules. They suggest that diagnostic evaluation can be carried out as if the patient were not pregnant, except that radioactive iodine scanning is contraindicate. In our opinion, the use of calcitonin screening seems appropriate in the pregnant patient, as a diagnosis of medullary cancer would likely change the management to a more proactive surgical approach. Ultrasound is useful for detection of the number, size and characteristics of the nodules. FNAB is the critical test for diagnosis whether or not the patient is pregnant and is generally highly accurate.
FNAB interpreted as “follicular neoplasm” indicates a tumor that is most likely benign. Most pregnant patients are among the younger age group in which pure follicular cancers are rare. In pregnancy, malignant follicular neoplasms are generally the follicular variant of PTCs, which are typically non-aggressive. Some authors feel that biopsy results suggestive of Hürthle cell carcinomas warrant more aggressive treatment, although the opinion that these tumors are more aggressive than non-Hürthle cell follicular carcinomas is controversial. If the result of the FNAB is suspicious or definitive for PTC, then the pros and cons of surgery during pregnancy versus delay until after delivery must be considered. These considerations will depend on the features of the tumor, as well as on the stage of pregnancy.

Indications for surgery of thyroid cancer during pregnancy

It is generally accepted that almost any cancer discovered in the third trimester may be observed until after delivery. Second trimester surgical intervention may be considered for aggressive variants of cancer and, in particular, for medullary cancer. Many reviews of thyroid cancer in pregnancy generally advise postponing surgery for well-differentiated thyroid cancer, but suggest that a more aggressive surgical approach may be warranted when medullary cancer is diagnosed.
Even though patients with thyroid nodules and proven medullary carcinoma can be observed, the general tendency is to consider surgical intervention unless the tumor is very small and the calcitonin level is quite low, as cure is dependent on surgical treatment and delay could decrease the chance of cure.
Appropriate surgery would include total thyroidectomy, central compartment dissection and ipsilateral neck dissection if necessary. Calcitonin is a good tumor marker and should be followed throughout the pregnancy and postpartum period. Carcinoembryonic antigen (CEA) is also an important tumor marker, as there are occasional medullary cancers that do not produce calcitonin but do produce CEA.
There are several series in literature that discuss important aspects of the management of pregnant patients with thyroid nodules. Moosa and Mazzaferri retrospectively compared 61 pregnant women diagnosed with thyroid cancer with 528 age-matched, non-pregnant women with a similar array of tumor types (approximately 80% papillary). The median follow-up time for the 2 groups was 22.4 and 19.5 years, respectively. Of the pregnant subjects, 77% underwent thyroidectomy after delivery, while 20% underwent surgery during the second trimester. Near total thyroidectomy was the procedure of choice for 73% of the pregnant subjects. Of the pregnant subjects, 30% were treated with radioactive iodine postoperatively after delivery. No significant differences between pregnant and non-pregnant subjects were detected with respect to cancer recurrence, distant recurrence and cancer deaths. Recurrence rate was 15% in pregnant women and 23% in non-pregnant women. Among the women who were pregnant, recurrence rate was 14% in those who underwent surgery during their pregnancy and 15% in women who had surgery after delivery, with an average time to recurrence of 16 months after diagnosis. None of the pregnant women and 1.2% of the non-pregnant women suffered cancer deaths. The authors concluded that surgery for thyroid cancer could be delayed until after delivery in most cases.
These articles generally demonstrate the lack of urgency in treating pregnant women who have apparently non-aggressive well-differentiated thyroid cancer, and that FNABs are often reliable in guiding therapy. They also recognize that surgery can be performed very safely during pregnancy and may serve to relieve the mother’s anxiety while offering an earlier cure for the neoplastic condition. In most cases of thyroid cancer without evidence of aggressive disease, it is quite reasonable to delay surgery until after delivery. If there are factors such as a large tumor, rapid growth or concern in the mind of the patient, then surgery should be undertaken electively during the second trimester, when the risk of maternal or fetal complications is generally low. However, one needs to keep in mind that occasionally certain complications of thyroid surgery may be detrimental to the fetus, such as unexpected severe maternal hypotension, postoperative hematoma or severe maternal hypoparathyroidism. Therefore, the decision of whether to operate must be made with full understanding, cooperation and agreement between the patient, family, surgeon, obstetrician and endocrinologist.

Hyperparathyroidism in pregnancy

Primary hyperparathyroidism is of critical concern in the pregnant patient. Secondary and tertiary hyperparathyroidism in pregnancy is extremely unlikely as the most common cause of these conditions, end-stage renal failure, generally precludes pregnancy. Primary maternal hyperparathyroidism is rare. While numbers vary, the incidence is estimated to be approximately 8/100,000 per year. Most patients are asymptomatic, but can be screened with a serum calcium and, if indicated, PTH level. The diagnosis of hyperparathyroidism in the pregnant patient can be challenging due to the fact that maternal PTH levels may vary, and calcium levels may be falsely depressed due to hypercalciuria of pregnancy and placental transfer of calcium. Asymptomatic mothers are often diagnosed only when the infant becomes symptomatic. Complications occurred either during pregnancy or in the postnatal period, and include spontaneous abortions, stillbirths, intrauterine growth retardation, preterm labor, neonatal hypocalcemia and permanent neonatal hypoparathyroidism. This adds support to the argument that parathyroid surgery should not be delayed until after delivery, and that it should not be delayed within the pregnancy.

Neonatal hypocalcemia

Transient hypocalcemia in the newborn is common, particularly in sick or low birth weight infants. Causes of hypocalcemia are varied and include: maternal factors such as vitamin D deficiency, diabetes and hyperparathyroidism infant factors such as sepsis, prematurity, birth asphyxia, hypomagnesemia and hyperbilirubinemia; and external factors such as the administration of citrated blood products and lipid infusions. Most infants with hypocalcemia are asymptomatic. Among infants who are symptomatic, tetany is seen most commonly. Significant hypocalcemia with tetany has been reported in 20–50% of infants born to mothers with untreated hyperparathyroidism. Infants who have symptoms should be treated promptly with intravenous calcium gluconate (10%).

Treatment of maternal hyperparathyroidism

Parathyroidectomy is the only definitive treatment for hyperparathyroidism. A review of all cases reported in the literature of parathyroidectomy performed in the third trimester of pregnancy revealed a low rate of surgical complications (5.9% fetuses, 0% mothers). Postoperative hypocalcemia was detected in 63% of mothers and 18% of newborns, but was easily replaced with calcium supplementation. Therefore, the authors recommended surgery to prevent the known complications to mother and fetus of untreated hyperparathyroidism. It should be noted that hypercalcemia in pregnancy can also be caused by PTH-related protein produced by malignant tumors of various kinds, or by the placenta. Therefore, care must be taken to distinguish this condition from true hyperparathyroidism by directly measuring the PTH. The authors concluded that hyperparathyroidism in pregnancy should be treated surgically unless it is an asymptomatic case of mild hyperparathyroidism in the third trimester in which case surgery can be postponed until after delivery.

Parathyroid surgery in pregnancy

As hyperparathyroidism is potentially harmful to both mother and fetus, parathyroid surgery is generally recommended for pregnant patients with hyperparathyroidism except in very mild cases, particularly those diagnosed in the third trimester. If possible, surgery should be done under local anesthesia with a focused exploration and intraoperative PTH assay for confirmation of cure. A major problem in this respect is the inability to employ (99m) technetium sestamibi scintigraphy, which is the most reliable and most commonly used study for preoperative parathyroid localization. High-resolution ultra sound and occasionally MRI may be employed for parathyroid localization without subjecting the fetus to ionizing radiation. If preoperative localization cannot be accomplished, the patient should be explored using general anesthesia and a conventional, usually small, transverse cervical incision.

Conclusions

Surgery of any sort during pregnancy must be carefully considered, as there are potential risks and benefits to both mother and fetus. Regional anesthesia is preferable to general anesthesia if it can be safely employed. The main risk of surgery during pregnancy is the increased risk of miscarriage, particularly in the first trimester. The risk of teratogenicity has not been substantiated. Pregnant patients undergoing surgery have longer and more expensive hospital stays than comparable non-pregnant patients. Surgical complications are increased in pregnant patients. Therefore, surgery is generally undertaken only when the risks of surgery are significantly outweighed by the benefits of proceeding with the operation. Generally, thyroid surgery can be postponed until after delivery, whereas parathyroid surgery should not be delayed. Exceptions include thyroid pathology causing air way compromise, or aggressive thyroid cancers (Table1). In these situations, surgery during pregnancy must be strongly considered. Parathyroid surgery should only be delayed when hyperparathyroidism is mild and/or when it is detected in the third trimester. The best time for elective thyroid and parathyroid surgery during pregnancy is the second trimester. Better outcomes have been reported by experienced endocrine surgeons than by those less familiar with surgery in this region. Most of the literature reviewed indicates no increased risk of mortality or cancer recurrence even with substantial delay of surgery for well-differentiated papillary or follicular cancers of the thyroid gland. Thus, in both thyroid and parathyroid surgery, the risks and benefits of surgery versus observation in the pregnant patient must be carefully considered and the treatment plan tailored to the individual patient’s needs and expectations.