Multiple endocrine neoplasia: Clinical sciences

Multiple endocrine neoplasia, or MEN, is a group of rare inherited conditions where tumors develop in multiple endocrine glands. These conditions can be associated with serious complications caused by excess hormone production. Based on the affected endocrine glands, MEN can be further subdivided into MEN1, MEN2A, and MEN2B.

Now, if your patient presents with chief concerns suggesting MEN, you should first perform an ABCDE assessment to determine if they are unstable or stable. If the patient is unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen.

Now, let’s go back to the ABCDE assessment and discuss stable patients. In this case, you should first perform a focused history and physical exam.

Alright, let’s start with MEN1! These individuals typically report a personal or family history of parathyroid, pituitary and gastro-entero-pancreatic tumors. Parathyroid tumors can cause hypercalcemia, so your patient might report symptoms, such as bone or abdominal pain, as well as a history of kidney stones or low-impact fractures. On the other hand, pituitary tumors can cause vision changes and headaches, while gastroenteropancreatic tumors can cause gastric ulcers, diarrhea, as well as hyper- or hypoglycemia.

Here’s a clinical pearl! Gastro-entero-pancreatic tumors arise from neuroendocrine cells of the pancreas and small intestine, and can cause various manifestations, depending on the hormone secreted.

For example, gastrinomas can arise either in the small intestine or the pancreas, and they secrete excess gastrin, which stimulates gastric acid production. This causes Zollinger-Ellison syndrome, a condition characterized by recurrent peptic ulcers.

On the other hand, insulinomas secrete insulin, which can lead to hypoglycemia; while glucagonomas secrete glucagon, causing hyperglycemia.

There are also VIPomas, which secrete vasoactive intestinal peptide, or VIP, causing watery diarrhea. Finally, there can be carcinoid tumors, which can arise anywhere in the digestive tract, but can also develop in the lungs. These tumors secrete serotonin, leading to carcinoid syndrome, which can manifest as flushing, diarrhea, and wheezing.

Here’s a high-yield fact! Serotonin-secreting neuroendocrine tumors can sometimes cause a carcinoid crisis, which is when carcinoid syndrome is associated with sudden onset hemodynamic instability. This happens when a lot of serotonin is released at once, often in the context of surgical tumor removal. To prevent or reverse a carcinoid crisis, intravenous Octreotide infusions can be helpful.

The physical exam can reveal different findings depending on the tumor. With a parathyroid tumor, there could be muscle weakness or, if a kidney stone is present, flank pain. With a pituitary tumor, there’s decreased visual acuity and signs of excess hormone production, like features of Cushing syndrome, acromegaly, or hyperprolactinemia. There could also be signs of hormone deficiencies, since a large pituitary tumor can compress healthy pituitary cells, halting their production. Finally, a patient with a gastro-entero-pancreatic tumor may have abdominal tenderness on exam. Based on these findings, you should suspect MEN1, so your next step is to assess for each endocrine tumor.

Let’s start by assessing for parathyroid tumors. You’ll need to order labs, including parathyroid hormone, or PTH; calcium and phosphorus levels; as well as imaging methods such as a neck ultrasound and Technetium 99m scan to identify the tumor; and a DXA scan to assess bone mineral density at the lumbar spine, hip and forearm levels.

With a parathyroid tumor, there’s high PTH and calcium; and low phosphorus. The neck ultrasound can show a parathyroid mass; while the Technetium 99m scan confirms its presence. Finally, the DXA scan can reveal secondary osteoporosis, often at the level of the forearm.

Next, assess for pituitary tumors. Order labs, including prolactin, ACTH and cortisol; GH and IGF1; TSH and FT4; as well as FSH and LH levels. Additionally, order a head MRI to identify the tumor.

Now, these labs can show signs of pituitary hormone excess, most commonly either high prolactin; high ACTH and cortisol; or high GH and IGF1. Alternatively, one or more pituitary hormones could be deficient; or all pituitary hormone levels can be normal. Finally, the head MRI can identify a pituitary tumor and assess its extension.

Finally, assess for gastro-entero-pancreatic tumors. Order labs like chromogranin A, which is a nonspecific marker for neuroendocrine tumors; and also insulin, glucagon, gastrin, VIP, and finally, serotonin and its main metabolite urine 5-hydroxyindoleacetic acid. Next, order imaging studies, such as an abdominal CT or MRI, or an Octreotide scan.

With all gastroenteropancreatic tumors, chromogranin A levels are usually high; and depending on the type of tumor, insulin, glucagon, gastrin, VIP, serotonin and urine 5-hydroxyindoleacetic acid can be elevated or normal. The abdominal CT or MRI usually identifies the tumor, whereas the Octreotide scan can find even smaller tumors that escape detection with a CT or MRI.