Hyperparathyroidism is defined as an elevated total or ionized calcium level in the blood in combination with an elevation of the parathyroid hormone (PTH) level. Parathyroid hormone is secreted from the four parathyroid glands located immediately adjacent to the thyroid in the central area of the neck. Prior to the widespread testing of routine laboratory values, most patients with primary hyperparathyroidism were diagnosed only when they manifested symptoms of this disease. More often than not, patients in the contemporary era of medicine are asymptomatic and diagnosed only as a result of an abnormal calcium level detected on routine laboratory screening.
There is normally an inverse relationship between the levels of calcium and parathyroid hormone. An elevated level of calcium is usually associated with a low level of parathyroid hormone. Conversely a low level of calcium normally leads to an increase in the secretion of parathyroid hormone. When both calcium and parathyroid hormone are elevated, then this represents an abnormal state, and is diagnostic for the condition known as primary hyperparathyroidism.
Symptoms associated with hyperparathyroidism include the development of kidney stones; an abnormal demineralization of the bones leading to increased risk of fractures; an actual history of abnormal fractures; and the development of gastric ulcers and pancreatitis. In severe forms of hypercalcemia, there may be a disturbance in the normal cardiac rhythm leading to life-threatening arrhythmias. There is a variety of other symptoms that have been attributed to primary hyperparathyroidism, including memory loss, hypertension, emotional lability, muscle and joint pain and impaired cognition. While the treatment of hyperparathyroidism will most often lead to a correction in the calcium level, prevent the development of future kidney stones and often lead to a correction in the bone density, the “softer signs” of this disease, such as memory loss and hypertension may not necessarily be resolved. It is difficult to predict whether treatment of primary hyperparathyroidism will be effective since many of these very common problems may result from a host of other health conditions.
Not all patients with primary hyperparathyroidism require treatment. Since most patients are now detected as a result of an abnormality of their blood chemistries, and without the presence of symptoms, guidelines have been established to help determine which patients require therapy and which patients can be observed and monitored.
The indications for treatment of primary hyperparathyroidism include a history or the presence of kidney stones, an impairment of kidney function, excess secretion of calcium in the urine, deterioration in bone density studies that reflect significant demineralization, and calcium levels that are more than one unit above the upper limits of normal for the particular laboratory in which the determination was made. In addition patients younger than 50 years of age are considered candidates for treatment, primarily because of the increased likelihood that they will manifest signs and symptoms due to the long time horizon for that to happen.
In 90 percent of patients with primary hyperparathyroidism, only one of the four glands is abnormal and responsible for the excess secretion of parathyroid hormone. Nine percent of patients with this condition will have two, three or all four parathyroid glands involved in the excess secretion leading to the abnormal levels of parathyroid hormone in the blood. Less than one percent of the patients who are diagnosed with hyperparathyroidism will have the malignant condition known as parathyroid cancer. The latter patients usually present with very elevated levels of calcium (in the 14 and 15 range) and extremely high levels of parathyroid hormone.
The treatment for primary hyperparathyroidism is surgery for those patients who meet the criteria for therapeutic management of the disease. Surgery involves the removal of the diseased gland or glands that are responsible for the excess secretion of parathyroid hormone. As noted above, the majority of patients with primary hyperparathyroidism have a single gland that is responsible for the excess levels of parathyroid hormone. In the early era of surgical management of this condition, surgeons usually performed an exploration of all four parathyroid glands to determine which gland or glands was responsible for the excess secretion of parathyroid hormone based on a visual determination of which glands appeared to be abnormal in size and contour. Several advances in the surgical management of this condition have led to what is known as a “directed surgical approach,” whereby the diseased glands are identified prior to surgery through one or a series of localization studies, and during the operation the level of parathyroid hormone is measured as a gauge of the success of the procedure. The latter advance, known as intraoperative parathyroid hormone assessment, is a major advance made possible by the rapid turnover of parathyroid hormone in the body, known as the half-life of PTH, which is in the range of between three and a half to four minutes. The implication of this rapid metabolism of PTH is this: if the cause of the excess production is eliminated through removal of the abnormal parathyroid gland, then the levels of PTH should return to normal in a very short period of time — on the order of minutes — which can be readily measured during the surgical procedure through a variety of assays performed in the operating room or a nearby laboratory.
The localization studies noted above attempt to identify the diseased parathyroid glands prior to surgery through the use of a variety of imaging techniques including nuclear scans (most commonly using an agent known as technetium sestamibi), ultrasound, CT and MRI. In some patients where the diseased gland or glands can’t be clearly localized before surgery, an exploration of the central compartment of the neck is required to determine which of the glands is enlarged and which are abnormal and require removal. Failure to localize the diseased gland or glands does not mean that the diagnosis is not correct, since the diagnosis of primary hyperparathyroidism is based on the laboratory determination of an abnormal level of parathyroid hormone in combination with an elevated level of calcium. The process of preoperative localization is performed to hasten and reduce the extent of the surgical procedure.
In preparation for surgery for hyperparathyroidism, it is important to rule out the presence of a coexisting thyroid gland abnormality, which if diagnosed (most often by ultrasound), may require simultaneous surgical removal. A history of radiation exposure and a family history of thyroid or parathyroid pathology should be elicited from the patient as part of the preoperative evaluation, and may raise the awareness of the possibility of coexisting thyroid disease.
The surgical management of primary hyperparathyroidism involves the removal of the abnormal parathyroid gland(s) that are determined by the experienced surgeon to be enlarged and/or abnormal in contour. This is performed in conjunction with the measurement of intraoperative PTH in order to determine the biochemical success of the parathyroidectomy. When removal of a single enlarged parathyroid gland produces a threshold drop in the levels of PTH, then the surgeon can comfortably terminate the procedure without having to expose and identify the other parathyroid glands. Alternatively, if the PTH levels do not drop, then the surgeon must search for other enlarged glands in order to achieve a biochemical cure. In most individuals, only one parathyroid gland removal is required for normal levels of PTH to return in the blood. This measurement should reveal a significant drop in parathyroid hormone levels, indicating that the hyperparathyroid state has been successfully treated. If the parathyroid level fails to drop, an exploration of the remaining parathyroid glands is required and may lead to the removal of one, two or all three of the remaining parathyroid glands. However, if all four parathyroid glands are diseased and require removal, then one of two options remain: either to remove three and one-half of the glands leaving a portion of an abnormal gland in the neck, or to perform a parathyroid autotransplantation of a portion of one diseased gland to a muscle in the forearm. The latter technique permits the diseased gland to be relocated out of the head and neck in order to permit ease of removal should there be a recurrence of the hyperparathyroid state at a later point. Such patients with recurrent elevation of PTH and calcium following the initial surgery can be treated by removing a portion of the transplanted parathyroid gland in the forearm, without having to re-enter the previously operated thyroid bed, putting the nerves to the vocal cords at increased risk due to the scarring resulting from the prior surgery.
In a very small group of patients — roughly one or two percent — the parathyroid glands are located in abnormal positions. Due to embryologic development of the parathyroid gland, these diseased glands may be located higher in the neck or much lower, in the central portion of the chest.
Parathyroid surgery is usually performed through a short horizontal incision in the lower central portion of the front of the neck. Minimally invasive surgery can be performed when the location of the diseased gland is definitively determined prior to the procedure. In this procedure a smaller incision is required in the neck and a directed approach to the localized gland is performed. This may be performed in conjunction with special scopes that help to magnify and enhance the visualization of structures in the neck, thereby facilitating the surgery. Newer techniques have been developed using robots to help to perform the procedure. There is a host of surgical approaches that have been reported using robotic-assisted surgery. However, to date, the true merits of using the robot to perform this surgery have not been proven.
When either a conventional or a minimally invasive procedure is performed, patients who recover quickly and well from the procedure can often return home the same day. Usually a period of observation is required following surgery in order to ensure that patients are able to swallow comfortably and that their pain is well controlled. Occasionally patients with long-standing hyperparathyroidism may develop a significant drop in calcium after surgery (a condition known as “hungry bone syndrome”) that requires treatment with either oral calcium, or occasionally, intravenous calcium. Usually patients who are predisposed to postoperative hypocalcemia can be identified by a preoperative elevation in their alkaline phosphatase level in the blood.
Patients in whom the location of the diseased parathyroid gland is clear and the contour of the neck is favorable may choose to undergo a parathyroidectomy under local anesthesia, thereby reducing the side effects associated with the drugs used for a general anesthetic and speeding the postoperative recovery.
Recovery from parathyroid surgery is usually very rapid. Most patients recover within 48 hours with a postoperative sore throat being the only lingering symptom. Many patients will notice a dramatic improvement in some of their related symptoms such as bone pain, impaired cognitive abilities and impaired memory. As noted above, in rare instances, patients with long-standing hyperparathyroidism may require treatment with calcium and vitamin D due to a rapid drop in calcium levels that may require a prolonged stay in the hospital.