Managing MEN2—Multidisciplinary Approach to Hypoparathyroid Diseases

Written by Kathleen Doheny

Interviews with Naifa Busaidy, MD, David Terris, MD, and Swati Mehrotra, MD

It takes a pathologist, a surgeon, and an endocrinologist to manage the toughest cases of medullary thyroid cancer, or multiple endocrine neoplasia (MEN) syndrome,according to a panel of specialists presenting Multidisciplinary Approaches to Endocrine Diseases: MEN2a and hypoparathryoid disorders at the 26th Annual Scientific and Clinical Congress of the American Association of Clinical Endocrinologists (AACE).

Thyroid cancer, compared to other cancers, is uncommon in the U.S. In 2016, about 64,000 patients heard the diagnosis, about half the number who learned of a colon cancer diagnosis.2 It's also very treatable, with a generally optimistic prognosis.

However, managing patients with a suspected medullary thyroid cancer (MTC), which accounts for 1-2% of all thyroid cancers in the U.S., can be very challenging as the inherited forms can be linked with other endocrine tumors in syndromes, known as multiple endocrine neoplasias (MEN) 2a and MEN2b.2

Patients with MEN2a may have pheochromocytomas or parathyroid gland tumors; those with MEN2b have pheochromocytomas and neuromas in the GI tract or oral sites.1

Difficult to Treat Endocrine Diseases

In the AACE session, 3 experts offered recommendations on how to achieve the best management for MTC. On the panel:

Patients with MEN2a or 2b represent ''a syndrome where 100% have medullary thyroid cancer and other endocrine organs with tumors," Dr. Busaidy told Endocrine Web. Those tumors are mostly benign, but may be cancerous, she said, in which case the best outcome is arrived at with a multidisciplinary team approach.

Patient Case Study: 31-Year-Old Male 

The patient, a father of 4 children, age 31 years, was recently diagnosed with MTC after a finding on palpation of a lymph node on the left lateral neck. Upon questioning, he reported loose stools and some palpitations. He admitted he did not monitor his blood pressure.

On ultrasound of the neck, a 3.5-centimeter ovoid hypoechoic nodule was revealed in the left side of thyroid and a 1 cm nodule isoechoic on the right thyroid. In addition, multiple lymph nodes in the left and right neck were shown to be enlarged.

Other findings:

A fine needle aspiration of the lateral lymph node was performed, along with surgical and genetics counseling and RET testing.3 It’s worth noting that more than 25 mutations in the RET gene are now linked with MEN2.3

"We have to do RET gene testing to rule out any other disorders," Dr. Busaidy said. The 2 forms of MTC are hereditary, which make up 20% of cases,  and the other 80% are sporadic or non-inherited.

"The treatment is surgery, but before sending the patient to OR, there are certain things to look for," Dr. Busaidy told EndocrineWeb. Among them: a pheochromocytoma.  While awaiting RET test results, assessing for pheochromocytoma and hyperparathyroidism can be done.

In this patient, plasma metanephrines were 10 nmol/L; normetanephrines were 1 nmol/L. Ultrasound of the neck is recommended for all patients with MTC, the panel unanimously agreed.

Arriving at Diagnosis, Prognosis

The final diagnosis—a right-sided pheochromocytoma with a genetic test showing positive for RET 634.

Dr. Mehrotra reported on ancillary studies, including immunohistochemistry and molecular testing, performed on cell block material. The tumor cells were positive for calcitonin, chromogranin A, monoclonal carcinoembryonic antigen (mCEA), TTF1 and negative for thyroglobulin, she said.

Total thyroidectomy and lymph node dissection were done. No radioactive iodine was given; the patient’s TSH level remained normal. For the long-term, the plan was to monitor with follow-up blood testing of calcitonin, mCEA and imaging studies (ultrasound and CT) of the neck.

MTC prognosis is good for both localized (95.6% at 10 years) and regional (75.5% for 10 years) MTC. The 10-year survival for distant is 40%. Overall survival is better in hereditary MTC.

Dr. Terris presented 4 key considerations for endocrinologists to consider with regard to surgery for an MTC patient:

Remember that "this is a primarily surgical disease, primarily," Dr. Terris tells Endocrine Web. Surgery, he says, is the most common way to manage and the only way to cure it.

Arriving at a Diagnosis, Post-Op Plan

The surgical findings disclosed a 3.5 cm MTC of the left lobe, with extension into the isthmus as well as some extension into the perithyroid adipose tissue. In all, 22 of 33 lymph nodes were positive for metastatic cancer; the largest tumor was 4 cm with extracapsular extension.

At 6 months post-op, the patient was doing well, with no complaints of diarrhea and flushing and a serum calcitonin at 27pg/DL. The serum tumor secondary marker, mCEA was 1.3.

Form an Effective Multidisciplinary Team

To manage a patient who receives a diagnosis of MTC, this panel of experts recommends a multidisciplinary, patient-centric approach with a clinical team that includes:

Dr. Busaidy consults for Eisai. Dr. Terris directs thyroid courses for Genzyme and receives royalties from several endocrine books. Dr. Mehrotra reports no disclosures

Sources

American Thyroid Association.  Medullary Thyroid Cancer.  Available at:  http://www.thyroid.org/medullary-thyroid-cancer/. Accessed May 7, 2017.

Busaidy N, Terris D, Mehrotra S. Multidisciplinary approaches to endocrine disease: MEN2a and hypoparathryoid disorders. Presented at: 26th Annual Scientific and Clinical Congress of the American Association of Clinical Endocrinologists, May 7, 2017, Austin.

Genetics Home Reference. RET. Available at: ghr.nlm.nih.gov/gene/RET. Accessed May 7, 2017.