Multiple endocrine neoplasia: Clinical sciences

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Introduction0:00–0:33

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.

Unstable patient0:33–1:01

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!

Stable patient1:01–1:14

MEN1 H&P1:14–4:20

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.

Assess for parathyroid tumors 4:20–5:07

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.

Assess for pituitary tumors 5:07–5:54

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.

Assess for GEP tumors 5:54–7:11

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.
Finally, if one or more MEN1-associated tumors is identified, make sure to send blood for genetic testing, to look for the MEN 1 mutation.
If the mutation comes back positive, that confirms MEN 1. Once you diagnose MEN1, proceed with the necessary treatment, The first-line management includes tumor resection, so make sure to consult your surgery team!

MEN1 Treatment7:11–8:19

Medical management can also be needed sometimes. For example, in patients with hyperparathyroidism, calcimimetics can lower calcium levels, and bisphosphonates can improve bone mineral density.
For pituitary tumors, consider Cabergoline for prolactinomas, or Octreotide for GH-secreting tumors, as well as hormone replacement therapy if there are any deficiencies.
Finally, in individuals with gastro-entero-pancreatic tumors, you can use proton pump inhibitors or H2-blockers to reduce gastric acid secretion.
Targeted therapy with Octreotide can also be helpful if surgical removal isn’t possible. Next, encourage genetic counseling to at-risk family members, and provide surveillance, including annual hormone levels and imaging studies, depending on your patient's history and symptoms.Alright, let’s move on to MEN2.
This comes in two flavors: MEN2A and MEN2B. With both subtypes, patients have a personal or family history of medullary thyroid carcinoma, as well as pheochromocytoma.

MEN2A8:19–9:59

Additionally, patients with MEN2A could have a personal or family history of parathyroid adenoma; while those with MEN2B could report mucosal neuromas, which are benign tumors of the peripheral nerves that often occur on the tongue and oral mucosa.Patients with medullary thyroid carcinoma can report neck swelling, voice changes, and dysphagia; while those with pheochromocytoma typically report paroxysmal hypertension associated with headache, pallor, palpitations and sweating.
Finally, individuals with MEN2A can report bone or abdominal pain and a history of kidney stones or low impact fractures.
The physical exam might reveal a palpable thyroid nodule, a palpable abdominal mass, or hypertension; as well as scaly reddish-brown papules suggesting cutaneous lichen amyloidosis in individuals with MEN2A; and a mouth exam could reveal lip or tongue nodules suggestive of mucosal neuromas in MEN2B.
Based on these findings, you should suspect MEN2, so your next step is to assess for associated endocrine tumors! Let’s start with medullary thyroid carcinoma.

Assess for medullary thyroid carcinoma9:59–10:19

You should order a calcitonin level, which is a serum biomarker for this tumor; as well as imaging studies, such as a neck ultrasound.
Typically, calcitonin levels are elevated, and the neck ultrasound shows a thyroid nodule. Next, investigate a potential pheochromocytoma.

Assess for pheochromocytoma10:19–10:44

Order urine catecholamines, as well as an abdominal CT, MRI or a meta-iodo-benzyl-guanidine scintigraphy, which we can fortunately call a MIBG scan for short.
Results typically show elevated urine metanephrines, while imaging studies can identify the tumor. Finally, assess for a parathyroid tumor.

Assess for parathyroid tumor10:44–11:50

Order PTH, calcium and phosphorus levels; and imaging studies, including a neck ultrasound, a Technetium 99m scan and a DXA scan.
Labs typically show high PTH and calcium levels associated with low phosphorus, and imaging studies can identify the tumor or diagnose secondary osteoporosis.Finally, if one or more MEN2-associated tumors is identified, make sure to send blood for genetic testing, to look for the RET mutation.
If the mutation comes back positive, that confirms MEN2.Ok, now, the common features of MEN2 syndromes are medullary thyroid carcinoma and pheochromocytoma.
If these two are identified alongside parathyroid tumors, diagnose MEN2A. On the other hand, if mucosal neuromas are present, diagnose MEN2B.Once you diagnose MEN2, proceed with the pertinent treatment.
The first-line management includes tumor resection, so, again, make sure to consult your surgery team! Consider treating medullary thyroid carcinoma with a RET inhibitor, like Vandetanib; and treating hyperparathyroidism with calcimimetics and bisphosphonates.

MEN2 Treatment11:50–12:58

Encourage genetic counseling to at-risk family members, and provide surveillance, including annual hormone levels, as well as imaging studies, depending on your patient's history and symptoms.One last clinical pearl!
Patients with pheochromocytoma can develop life-threatening hypertensive crises, which can often be precipitated by surgery.
So preoperative management of hypertension is super important. Typically, patients are started on alpha-1 adrenergic blockers first, and only after, on beta-blockers.
That’s because giving beta-blockers without blocking the alpha receptors first can cause vasoconstriction and precipitate a hypertensive crisis!
Alright, as a quick recap... MEN1 causes parathyroid, pituitary, and gastro-entero-pancreatic tumors.
Both MEN2A and MEN2B present with medullary thyroid carcinoma and pheochromocytoma. Additionally, MEN2A can present with parathyroid adenomas, while MEN2B may cause mucosal neuromas.

Review12:58–13:30

Once you diagnose MEN, consult your surgery team; initiate medical management, if needed; encourage genetic counseling; and finally, perform regular surveillance.
may cause mucosal neuromas Once you diagnose men consult your surgery team initiate medical management if needed
Multiple endocrine neoplasia: Clinical Sciences | Osmosis