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.