COMMENTS
MEN 2 is an autosomal dominant disorder with an estimated prevalence of 2.5 per 100,000.[8] Activating germline mutations of the RET proto-oncogene are present in 98% of the families of MEN-2 patients. There is a strong genotype- phenotype correlation between a specific RET mutation and its clinical course, with some genotypes being associated with aggressive disease. The overall rarity of this syndrome along with scant literature available on its management in pregnancy posed significant challenges for the treating team. This was further compounded by the COVID-19 pandemic and diversion of healthcare resources for managing those afflicted which made it very difficult to provide individualized care, which is mandated in such cases. To the best of our knowledge, ours is the first case of pregnancy in a patient with MEN-2A syndrome to be successfully managed and reported.
The primary step is management of pheochromocytoma, which, if left untreated, may have devastating consequences and is associated with high maternal and fetal morbidity and mortality. As it presents with hypertension, it is often misdiagnosed as pre-eclampsia in the earlier stages of pregnancy[9] Most cases of MEN 2A in pregnancy reported till date presented with PCC crisis mandating the need to undergo adrenalectomy. Our patient was fortunately diagnosed prior to conception and underwent adrenalectomy prior to an unplanned conception. These patients need glucocorticoid and mineralocorticoid replacement therapy as received by our patient postoperatively.
MTC is the next challenge to tackle owing to the aggressive and malignant nature of the disease. The impact of newly diagnosed MTC in pregnancy is unknown and no major guidelines are available to guide management of the same in pregnancy.[10] Our patient conceived spontaneously while awaiting surgery for MTC, which forced us to delay our surgical intervention till the second trimester. During this time, we followed up out patient with serial serum calcitonin levels which is generally used in postoperative follow up as recommended by ATA.[11] However, it is important to highlight that a rise in calcitonin or even its doubling time must be interpreted with caution in pregnant females due to physiological increase in calcitonin during pregnancy.[12] Delays in management of MTC are known to be associated with poorer outcomes. This, along with the difficulty in monitoring pre-operatively with serum calcitonin values, led us to pursue the surgery in the second trimester.[10] Planning an elective surgery during the ongoing pandemic where the entire healthcare infrastructure was restructured for COVID management posed several logistic issues which were dealt with successfully by the treating team and administration services of our centre.
Tewari et al (2001) described a case report of a 22-year-old primigravida who was diagnosed with MEN 2A in her first trimester and underwent adrenalectomy followed by thyroidectomy during her second trimester and had successful maternal and fetal outcome at term.[13]Sarathi et al in 2011 described a 21-year-old primigravida presenting with PCC crisis at 12 week’s gestation and was diagnosed with MEN 2A and RET mutation (C634W).[14] She successfully underwent bilateral adrenalectomy followed by thyroidectomy during her second trimester with calcitonin levels 713 pg/ml preoperatively and 32.6 pg/ml postoperatively. A larger case series of ten patients with pheochromocytoma in pregnancy was described by Donatini et al in 2018, out of which three patients had MEN 2A. Two of them had undergone thyroidectomy for MTC prior to pregnancy and one patient had PCC crisis at 27 weeks POG, for which she underwent unilateral adrenalectomy along with total thyroidectomy and central neck dissection at 28 week’s gestation. Her Ctn levels before and after surgery were 311 pg/ml and 95.7 pg/ml respectively.[15]
A majority of the cases of MEN 2A in pregnancy reported so far where surgery for MTC had to be undertaken during pregnancy were either diagnosed for first time during pregnancy or presented with PCC crisis leading to a diagnosis of MEN 2 and mandating the need for simultaneous adrenalectomy and thyroidectomy. This case merits special attention not only for highlighting the rarity of this syndrome during pregnancy but also for the numerous challenges in management that were overcome to deliver a successful outcome, which included a pandemic, an unplanned pregnancy, second trimester surgery in a high-risk pregnancy, uneventful COVID, pre-eclampsia at term culminating in an emergency cesarean section!
This case posed a multitude of challenges in management which were overcome by a well-coordinated multidisciplinary teamwork and the effective utilization of teleconsultation services which proved to be crucial in providing antenatal and postoperative services during such testing times. It would be amiss to not recognize the courage of our patient and the support provided by her family who braved such a difficult pandemic to continuously remain in touch with us and also for actively assisting us in decision making at several points of her tumultuous course in hospital.