Primary hyperparathyroidism or thyroid disease often remain undiagnosed in pregnant women. The incidence of most parathyroid and thyroid problems is on the rise, and women of childbearing age comprise a large proportion of affected patients. The management of endocrine disease in this group is challenging, as the physiology and symptoms attributed to pregnancy can mask the diagnosis. In addition, the indications for emergency surgery in pregnancy are often controversial and daunting to consider given that the health of both mother and fetus is at stake. Prior studies which have examined the maternal and fetal risks of endocrine surgery have been limited to small series and case reports. Kuy et al.now report the findings of a large, population-based investigation of pregnant women who underwent parathyroidectomy or thyroidectomy.1 The researchers found that pregnancy is an independently predictive risk factor for surgical complications, prolonged hospitalization and higher hospital costs compared with nonpregnant women after parathyroidectomy or thyroidectomy.
In a retrospective cross-sectional study, the investigators assessed hospital discharge data from the Health Care Utilization Project Nationwide Inpatient Sample database to determine clinical and economic outcomes of parathyroid or thyroid procedures in 201 pregnant women compared with 31,155 age-matched, nonpregnant women.
Before surgical intervention is pursued, surgeons must consider the benefits of a procedure in the context of potential risks. For the pregnant patient, this decision also includes consideration of the optimal timing of surgery owing to the possibility to postpone surgery until after delivery. This calculation is contingent upon the week of gestation, the severity of disease, maternal and fetal health and multiple other factors. Parathyroid and thyroid surgeries in the nonpregnant patient are considered low-risk in the hands of an experienced endocrine surgeon. The study by Kuy and colleagues underlines the importance of referring the case to an experienced surgeon, particularly for pregnant women who are at a distinctly higher risk of complications during endocrine surgery than non-pregnant patients.
Primary hyperparathyroidism leads to maternal hypercalcemia, which suppresses fetal parathyroid function. If inadequately treated, primary hyperparathyroidism will result in fetal complications, such as low birth weight and fetal demise, in up to 53% of treated mothers and 80% of untreated mothers.2, 3 The diagnosis of primary hyperparathyroidism in pregnant women can be challenging, as maternal parathyroid hormone levels are naturally higher than before pregnancy and the nonspecific symptoms associated with primary hyperparathyroidism, for example fatigue, depression and musculoskeletal pain, are often attributed to the pregnancy. Maternal hypercalcemia is mitigated to a degree by the hypoalbuminemia and hypercalciuria that occur during pregnancy and the placental delivery of calcium to the fetus. This amelioration of hypercalcemia is lost in the hours after delivery, which puts the mother at risk for the critical condition of hypercalcemic crisis. Most cases are diagnosed postpartum when the neonate suffers from tetany. The decision of whether or not to operate might, therefore, seem less important than the need to improve diagnosis of primary hyperparathyroidism in pregnant women.
![Thyroid glandPregnancy|[mdash]|a risk factor for thyroid surgery complications](/nrendo/journal/v5/n11/images/nrendo.2009.211-i1.jpg)
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The management of primary hyperparathyroidism in pregnant women is controversial, as, in the absence of consensus guidelines, some clinicians have argued for parathyroidectomy, whereas others have proposed nonoperative treatment for all but the most severe cases.4 Given the risks of conservative intervention, such as neonatal morbidity, parathyroid carcinoma and the maternal risk of postpartum hypercalcemic crisis, some researchers have proposed parathyroidectomy for all pregnant women with primary hyperparathyroidism.Many surgeons have described successful outcomes after parathyroidectomy in this population, albeit mostly in the form of small series and case reports.5, 6, 7, 8 The study by Kuy and colleagues reinforces the notion that surgery should be carefully considered, and lends support to those who believe that parathyroidectomy should be delayed until after delivery, if nonoperative control is established in addition to careful newborn monitoring and supplementation for hypocalcemia.
Kuy et al. do not elaborate on the indications for thyroidectomy in their cohort; however most patients undergo thyroid surgery after diagnosis of confirmed or possible thyroid cancer and/or to alleviate the symptoms of goiter. As surgical thyroidectomy for Graves disease can lead to isolated fetal hyperthyroidism, most pregnant women with toxic goiters are treated effectively with antithyroid drugs. Definitive surgical management of both benign and most malignant thyroid disorders can usually be delayed safely until after delivery. The majority of thyroid cancers are well-differentiated and exhibit indolent tumor biology. In one prospective study of nonpregnant patients with small papillary thyroid cancers, over 70% of patients had no growth of the tumor without surgical intervention at a follow-up after 5 years.9 Given the potential risks of surgery, including vocal cord paralysis and hypocalcemia, it seems reasonable to carefully monitor pregnant women diagnosed with small, well-differentiated thyroid cancers by serial ultrasonography. With regards to patients with symptomatic goiters, although thyroid enlargement is common during pregnancy, acute airway obstruction that requires urgent thyroidectomy is very rare.10
The study by Kuy et al. has several weaknesses, many of which are unavoidable when administrative databases are used to perform observational research. Incomplete information in the database resulted in analysis of only a subgroup of patients studied. The investigators do not detail the actual number of pregnant women included in the multivariate analysis, in which pregnancy was not an independently predictive factor for complications specific to parathyroid and thyroid surgery, such as recurrent laryngeal nerve injury and hypoparathyroidism; however, pregnancy was predictive of complications not specific to thyroid or parathyroid surgery, such as deep venous thrombosis. Although the unique strength of this study is its sample size, deficiencies in patient detail from the use of an administrative database also prevented the investigators to adjust data for stage of thyroid cancer, which is an important determinant of outcome. Furthermore, without important details such as tumor size and metastasis available for analysis, the use of a comparable control group is unclear. With regards to primary hyperparathyroidism, several important factors that affect surgical outcomes were not considered in this study, including preoperative tumor localization, severity of hyperparathyroidism and extent of surgery.
Does the delay of surgery for thyroid cancer until after delivery affect prognosis?
Despite their anatomic proximity and the similarity in surgical technique used to gain access, parathyroid and thyroid diseases have unique pathophysiologic distinctions and should be considered separately. With regards to gestational primary hyperparathyroidism, the devastating and immediate effects of neonatal tetany and maternal hypercalcemic crisis are the essential outcome measures and were adequately addressed by this study. Fetal complication rates are extraordinarily high for women with poorly controlled hyperparathyroidism. A comparison of medical management versus parathyroidectomy, however, was not addressed; however, the results support the necessity for future projects to prospectively compare immediate surgical intervention versus optimal medical management and delayed parathyroidectomy.
Particular to thyroid disease, long-term outcomes, such as recurrence and survival, are important. Does the delay of surgery for thyroid cancer until after delivery affect prognosis? Several of my pregnant patients have asked this question, and it remains unanswered by the current study. As most thyroidectomies are performed for pathology that can wait several months with no likely adverse consequences, it seems reasonable to postpone curative resection until after delivery. Overall, this retrospective observational study does not clarify practice guidelines for pregnant women with parathyroid or thyroid disease. Future prospective, multicenter studies should investigate the determined factors that influence surgical outcomes for pregnant women with parathyroid and thyroid disease. In the end, the report by Kuy et al. supports what many surgeons already accept: pregnant women with thyroid and parathyroid disease require careful clinical management, and their definitive surgical care should be delayed until after delivery, whenever possible.
