What Are the Symptoms of Multiple Endocrine Neoplasia?

The major endocrine glands that may be affected by multiple endocrine neoplasia syndromes include thyroid, parathyroid, pituitary, adrenal, and pancreas.

Multiple endocrine neoplasia (MEN) syndromes are rare endocrine system disorders that cause tumors in the endocrine glands. Most of the time the tumors are benign (not cancerous). 

The major endocrine glands that may be affected by multiple endocrine neoplasia syndromes include:

• Thyroid
• Parathyroid
• Pituitary
• Adrenal
• Pancreas

There are several different types of multiple endocrine neoplasias: 

• Multiple endocrine neoplasia type 1 (MEN1) (also called multiple endocrine adenomatoses or Wermer's syndrome)
  • Tumors usually are benign but can cause problems by releasing too much hormone or growing against other parts of the body
  • About half of people with MEN1 eventually develop cancer
• Multiple endocrine neoplasia type 2 (MEN2)
  • MEN2 is divided into three types:
    • Multiple Endocrine Neoplasia Type 2A (MEN2A)
    • Multiple Endocrine Neoplasia Type 2B (MEN2B)
    • Familial Medullary Thyroid Carcinoma (FMTC)
• Pheochromocytomas in multiple endocrine neoplasia type 2

Symptoms of multiple endocrine neoplasia vary depending on whether it is type 1 or type 2. 

Symptoms of multiple endocrine neoplasia type 1 include: 

• Hyperparathyroidism (parathyroid gland produces excess hormone)
  • Tiredness
  • Weakness
  • Muscle or bone pain
  • Constipation
  • Kidney stones 
  • Bone thinning 
• High levels of gastrin
  • Ulcers
  • Inflammation of the esophagus
  • Diarrhea
  • Abdominal pain
• Headaches 
• Vision changes
• Problems with sexual function and fertility
• Enlargement of bones (acromegaly)
• Cushing’s syndrome
• Excess production of breast milk

Symptoms of multiple endocrine neoplasia type 2B include: 

Growths around nerves (neuromas) of mucous membranes, such as the lips and tongue

Thickening of eyelids and lips

Abnormalities of the bones of the feet and thighs

Spinal curvature

Long limbs and loose joints

Physical characteristics, including being tall and slender

Enlarged and irritated large intestine

Multiple endocrine neoplasia is caused by genetic mutations passed down in families.

• MEN1 is caused by gene mutations in the MEN1 gene
• MEN2 is caused by gene mutations in the RET gene

Children of parents who have MEN syndrome have a 50% chance of developing the disease.

Multiple endocrine neoplasia (MEN) is diagnosed with a physical exam and patient history, and tests such as: 

• Blood tests
  • Gastrin stimulation test 
  • C-peptide levels
  • Proinsulin levels 
  • Serum glucagon levels 
  • Chromogranin A
  • Calcitonin
  • Corticotropin
  • Urinary 5-hydroxyindoleacetic acid (5-HIAA)
  • Growth hormone levels 
  • Parathyroid hormone level 
  • Calcium levels
  • Urine tests
• Imaging tests
  • Computerized tomography (CT) or computed axial tomography (CAT) scans
  • Magnetic resonance imaging (MRI) scan
  • Endoscopic ultrasounds (EUS) of stomach and abdomen 
• Genetic testing, if family members have or had MEN 

Treatment for multiple endocrine neoplasia (MEN) may include one or more of the following: 

• Surgery
  • Removal of the affected gland 
  • Hyperparathyroidism caused by MEN1 is usually treated with surgical removal of three-and-a-half of the four parathyroid glands (though sometimes all four glands are removed) with a portion of the parathyroid gland inserted into the forearm
• Medications to help balance hormone levels or treat symptoms
  • Somatostatin analogues
    • Octreotide (Sandostatin)
  • Proton pump inhibitors
    • Omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), and rabeprazole sodium (AcipHex)
  • Histamine receptor antagonists
    • Cimetidine (Tagamet), ranitidine (Zantac), and famotidine (Pepcid)
  • Dopamine agonists
    • Bromocriptine (Parlodel) and cabergoline (Dostinex)
  • Antihypoglycemic agents
    • Diazoxide (Hyperstat, Proglycem)
• Radiation therapy
• Active surveillance (“watch and wait”)
  • Doctors monitor MEN to see if it progresses or can be managed with medication