Familial Hyperparathyroidism

In patients with hyperparathyroidism, one or more parathyroid glands become enlarged and make too much parathyroid hormone. This causes the levels of calcium to rise in the blood. 

In familial hyperparathyroidism, the condition is inherited and passed down from generation to generation. There are three types of familial hyperparathyroidism. These include MEN 1 (multiple endocrine neoplasia, type 1), MEN 2A (multiple endocrine neoplasia, type 2), and familial hypocalciuric hypercalcaemia. 

MEN 1 is an inherited condition comprised of tumors in one or more of the following glands: 
  • Parathyroid 
  • Pancreas 
  • Pituitary gland 
  • Adrenals 
  • Thyroid gland 
MEN 2A is an inherited condition comprised of medullary thyroid cancer, pheochromocytoma (a tumor of the adrenal gland), and parathyroid hyperplasia (enlargement of all four parathyroid glands). 

Familial hypocalciuric hypercalcaemia is an inherited condition where the parathyroid perceives calcium levels to be too low, which causes the parathyroid to excrete higher levels of PTH. 

At Yale Endocrine Surgery, we offer surgical treatment and management options for familial hyperparathyroidism. In addition to being well-versed with the traditional or classic techniques and surgeries, many additional procedures offered by our innovative surgeons are at the leading edge of endocrine and minimally invasive surgery. 

Our multidisciplinary team, which includes internationally renowned surgeons, oncologists, and endocrinologists, works collectively to create personalized treatment plans that provide the best options for each patient, reflecting his or her specific condition and individual needs.

Causes of Familial Hyperparathyroidism

Most cases of familial hyperparathyroidism are caused by genetic mutations, or abnormalities, in a particular gene that is passed down from generation to generation. MEN 1 is caused by a genetic mutation in the menin gene. MEN 2A is associated with a genetic mutation in the RET proto-oncogene. Familial hypocalciuric hypercalcaemia is associated with loss-of-function mutations in the CASR gene. 

Some cases of familial hyperparathyroidism can be spontaneous and the first genetic mutation that causes the condition to occur in a family.

Risk Factors

A risk factor is anything that increases a person's chance of getting a disease. Different diseases have different risk factors. Some risk factors can be controlled with lifestyle changes. Other risk factors cannot be changed. 

A major risk factor for familial hyperparathyroidism is genetics. In most cases, a mutated gene causes MEN 1, MEN 2A, and familial hypocalciuric hypercalcaemia. This gene is autosomal dominant, which means that only one parent needs to have the mutation to pass it on to his or her children. There is a 50 percent chance of passing it on. If one or more close relatives have MEN 1, MEN 2A, or familial hypocalciuric hypercalcaemia, your risk of developing the condition is much greater.

Having a genetic risk factor does not mean that you will develop familial hyperparathyroidism. Understanding your risk factors will help you determine, what, if any, precautions and possible screening options you should consider.
If you have familial hyperparathyroidism, you may experience a range of symptoms from mild to non-specific, or you may experience severe symptoms. 

Some of the signs of hyperparathyroidism may include: 
  • Kidney stones 
  • Fragile bones that easily fracture (osteoporosis) 
  • Excessive urination 
  • Abdominal pain 
  • Tiring easily or weakness 
  • Depression or forgetfulness 
  • Bone and joint pain 
  • Frequent complaints of illness with no apparent cause
  • Nausea, vomiting, or loss of appetite
Symptoms of MEN 1 may include: 
  • Abdominal pain 
  • Burning, aching, or hunger discomfort in the upper abdomen or lower chest that is relieved by antacids, milk, or food 
  • Black, tarry stools 
  • Nausea and vomiting 
  • Bloated feeling after meals 
  • Weakness 
  • Headache 
  • Vision problems 
  • Loss of coordination 
  • Anxiety 
  • Mental changes or confusion 
  • Coma if hypoglycemia is untreated 
  • Loss of appetite 
  • Muscle pain 
  • Fatigue 
  • Sensitivity to the cold 
  • Unintentional weight loss 
  • Low blood pressure 
  • Loss of pubic hair 
  • In women, cessation of menses, infertility, or failure to lactate 
  • In men, decreased sexual interest, loss of body or facial hair 
Symptoms of familial hypocalciuric hypercalcaemia may include: 
  • Constipation 
  • Nausea 
  • Abdominal pain 
  • Poor appetite 
  • Vomiting 
  • Frequent thirst 
  • Frequent urination 
  • Muscle twitches 
  • Muscle weakness 
  • Dementia 
  • Depression 
  • Irritability 
  • Memory loss 
  • Bone pain 
  • Bowing of the shoulders 
  • Bone fractures 
  • Loss of height 
  • Curvature of the spine 
Having one or more of the above symptoms does not mean that you have familial hyperparathyroidism. If you think you have this condition, please call your doctor.


The only treatment for a hyperparathyroidism and tumors of the parathyroid glands is surgery to remove the affected glands. This surgery is referred to as a parathyroidectomy. Once the affected glands are removed, symptoms of hyperparathyroidism resolve. 

Parathyroid Procedures: At Yale Endocrine Surgery, we understand that you probably have many questions and concerns regarding the surgical treatment of your condition. We want you to feel completely comfortable with what to expect before, during, and after the surgical process, which is why our surgeons take the time to review your surgical plan in detail and provide in-depth answers to all your questions. 

While the type of surgical treatment you receive depends on your unique situation and condition, our emphasis is always on providing the best solution with the least pain, trauma, scarring, and recovery time. Our surgical team is second to none, providing compassionate care and the most advanced techniques available. 

  • Parathyroid Localization: For certain parathyroid conditions, having radiographic images, which document the location of the enlarged and hyperfunctioning parathyroid glands, are necessary. These may include parathyroid ultrasound, SESTAMIBI scan with SPECT, special CT scans, etc. Your surgeon will determine the best parathyroid localization imaging that you should undergo. Appropriate localization is necessary for Minimally Invasive Parathyroidectomy (MIP), and reoperative surgery for all parathyroid conditions.

  • Traditional (Bilateral) Parathyroidectomy: This approach involves exploring both sides (bilateral) of the neck in order to identify and remove the affected parathyroid glands. This method is usually done under general anesthesia using open surgery.

    Bilateral surgery is necessary when it appears that both sides of the neck contain affected parathyroid glands, or if nodules need to be removed from the thyroid gland as well.

  • Focused or Directed (Unilateral): This approach involves exploration of only one side (unilateral) of the neck using a small incision and specialized minimally invasive instruments.

    Preoperative imaging is necessary to determine which side has the diseased parathyroid glands. If one side cannot be determined through imaging, unilateral surgery is not possible. 

    Surgeons must make sure that the condition is resolved before the end of the surgery. To do this, an intraoperative PTH assay is used to confirm that PTH (parathyroid hormone) blood levels decrease within a certain range after the affected parathyroid glands are removed. If not, it may indicate that other parathyroid glands are affected and bilateral exploration may be necessary.

    Both traditional and focused parathyroid procedures may require preoperative imaging depending on the approached being used and the condition being treated.

    Some imaging tests include a parathyroid scan, a neck ultrasound, a CT scan, and an MRI.

    Intraoperative adjuncts may also be necessary before the surgery is completed. These may include PTH (parathyroid hormone) monitoring, PTH assay to be certain the hormone levels are corrected after the parathyroid glands have been removed, a frozen section to confirm parathyroid hyperplasia, and cryopreservation of parathyroid tissue in order to freeze and store some tissue in case it is needed for the patient at a later date.

  • Minimally Invasive Parathyroid Surgery: This surgery is performed under local analgesia with sedation, with a small incision to remove the enlarged parathyroid gland(s). While removing the gland(s), the surgeon talks with the patient to ensure that the recurrent laryngeal nerve is not affected by the surgery. After removal of the affected gland(s), and while the patient is still under sedation, the surgeon performs a blood test to check the patient's parathyroid hormone level in the operating room. This blood test will allow the surgeon to confirm that all enlarged parathyroid glands have been removed before the patient leaves the operating room. Patients will recover in the hospital for 24 to 72 hours so that blood calcium levels can continue to be monitored.

  • Reoperative Parathyroid Surgery: After a parathyroidectomy, the calcium levels and parathyroid hormone levels (PTH) are checked using blood tests to be certain that they return to normal. Tests are repeated again in about six months. If levels remain elevated, reoperative parathyroid surgery may be necessary.

    The number of patients who need reoperative parathyroid surgery is only between 2 and 5 percent. Reoperative parathyroid surgery is extremely specialized because it involves more risk than the initial parathyroid procedure, making the surgery more complex. Our expert surgeons are highly experienced in performing reoperative parathyroid surgery and have a high success rate. 
There are two types of disease that may require reoperative parathyroid surgery: persistent primary hyperparathyroidism and recurrent primary hyperparathyroidism. 
  • Persistent primary hyperparathyroidism occurs when the calcium and PTH levels do not return to normal levels following the removal of affected parathyroid glands. This form of hyperparathyroidism usually occurs if not all diseased parathyroid tissue is removed. Tissue may be missed for several reasons, including a surgeon’s inexperience, ectopic glands in a difficult-to-find location, or multiple diseased glands. 
  • Recurrent primary hyperparathyroidism occurs when calcium and PTH levels are normal following surgery but then once again become elevated high six months after the initial surgery. Recurrent hyperparathyroidism usually occurs when one or more of the remaining glands become hyperactive. 
At Yale Endocrine Surgery, we use the most advanced preoperative testing methods to localize the remaining parathyroid glands. We also employ necessary intraoperative tools, such as PTH monitoring, to assure that the surgery is successful.

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Yale Endocrine/General Surgery
Multispecialty Clinic 4th Floor
New Haven, CT 06510

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