Click here for Frequently Asked Questions on Parathyroids.
The parathyroid glands are located anatomically within the thyroid gland. There are usually 4 parathyroid glands, 2 in the left lobe of the thyroid and 2 in the right lobe. Occasionally, there are fewer than 4 or some individuals may rarely have more than 4. Similarly, occasionally one or more parathyroid glands may be located outside the thyroid, either in the neck, mediastinum (under the breast bone), or lungs, but these situations are uncommon. When the parathyroid glands function normally, blood calcium is controlled within a narrow physiological range. Inappropriate secretion of parathyroid hormone from one or more parathyroid glands may lead to an increase in blood calcium, and the condition known as hyperparathyroidism. Alternatively, damage to the parathyroid glands, if extensive, may lead to defective parathyroid hormone secretion, a low blood calcium, and the condition known as hypoparathyroidism. For an overview of parathyroid gland function, and the control of blood calcium in normal and disease states, see the review article Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000 Dec 21;343(25):1863-75. Review.
The normal role of the parathyroid glands is to control the blood calcium by secreting parathyroid hormone (PTH). The levels of blood calcium are constantly monitored by a protein expressed by parathyroid cells, designated the calcium sensing receptor. Persistent excess production of PTH by one or more parathyroid glands may lead to the development of a high level of blood calcium, referred to as Hyperparathyroidism. This disease may be associated, often over a period of many years, with the development of osteoporosis, kidney stones, impaired kidney function, increased thirst or increased frequency of urination and sometimes, stomach upset and ulcers. Evidence for Hyperparathyroidism is frequently detected incidentally, when blood tests reveal the presence of an elevated blood calcium (hypercalcemia). If no evidence for end-organ damage (normal bones, kidney function etc) is present, many patients with Hyperparathyroidism may simply be monitored. At present, several clinical trials are ongoing to determine the need for and optimal timing of therapy in patients with mild asymptomatic Hyperparathyroidism (see FAQs below).
The most common initial presentation of Hyperparathyroidism, or overactive parathyroid gland function, is the detection of a slightly increased calcium on routine blood testing. Alternatively, patients may present with osteoporosis or kidney stones. The majority of patients with Hyperparathyroidism. and elevated levels of blood calcium do not have symptoms, unless the levels of calcium become significantly elevated. On careful assessment, some patients may have mild symptoms that include weakness, decrease in energy, and occasional changes in mood. Accordingly, in the absence of symptoms, many patients are unaware that their calcium is abnormal, and are often understandably mystified about the diagnosis and potential need for treatment, as they feel fine. The vast majority of patients have benign disease involving one gland in about 90% of cases, whereas two or more glands (hyperplasia) may be abnormal in 10% of cases. Parathyroid cancer as a cause of hyperparathyroidism is extremely rare, and comprises less than 1% of all cases of hyperparathyroidism.
There are currently no medications available that can "cure" hyperparathyroidism.
Treatment of Hyperparathyroidism usually involves surgical identification of whether one (single adenoma) or several (multiple adenomas or more commonly, hyperplasia) parathyroid glands are hyperfunctioning, following which they the malfunctioning gland (s) are removed. At present, there are no approved medications available that have been shown to control or correct Hyperparathyroidism over the long term, although these type of medicines are under clinical development.
Impaired function or removal of significant amounts of parathyroid tissue may result in Hypoparathyroidism and a low blood calcium (hypocalcemia). If this happens rapidly, hypocalcemia may lead to numbness, tingling, and sometimes muscle cramps or spasm of muscles and vocal cords. In patients who have extensive thyroid surgery, removal of or damage to parathyroid gland tissue may be unavoidable and lead to the development of hypocalcemia. Treatment involves administration of calcium either orally or intravenously, and sometimes vitamin D, often in high doses not found in over the counter vitamin supplements. For more information, see Treatment of Hypocalcemia. In contrast, patients who have only half their thyroid glands removed are usually not at risk for development of hypocalcemia, as the remaining parathyroid glands will take over and usually secrete enough PTH to compensate. At the time of thyroid surgery, the thyroid surgeon will attempt to identify and preserve the parathyroid glands, however this may not always be possible, especially if the surgery is technically difficult or the cancer is extensive.
Medical (non-surgical) options for patients with hyperparathyroidism
Many patients with the diagnosis of Hyperparathyroidism are asymptomatic, feel well, and are not keen on undergoing surgery. Patients who have co-existing osteoporosis are often treated with medications such as estrogen, raloxifene (Evista) or bisphosphonates (etidronate, Didrocal, Fosamax (alendronate) etc). These medications are used in the treatment of osteoporosis in patients without Hyperparathyroidism, and it seems reasonable to try and combat bone loss in the same way in Hyperparathyroid patients, although definitive long term data on how effective the medications are in the presence of Hyperparathyroidism is not yet available. Postmenopausal women with Hyperparathyroidism treated with estrogen for 2 years did show significant improvement in bone mineral density, in one short term study, which is relatively encouraging. See Effects of Hormone Replacement Therapy on Bone Mineral Density in Postmenopausal Women With Primary Hyperparathyroidism: Four-Year Follow-up and Comparison With Healthy Postmenopausal Women. Arch Intern Med. 2000 Jul 24;160(14):2161-2166 and Effect of hormone replacement therapy on bone mineral density in postmenopausal women with mild primary hyperparathyroidism. A randomized, controlled trial. Ann Intern Med. 1996 Sep 1;125(5):360-8.
A new class of medications that function by regulating activity of the calcium sensing receptor is also under active clinical investigation for the treatment for patients with Hyperparathyroidism. The medications are still investigational however, and have not been approved for release by US or Canadian Regulatory agencies. For more information on these agents, see NPS Pharmaceuticals.
What are the long term consequences of not treating hyperparathyroidism?
The majority of patients with slightly elevated levels of blood calcium feel fine and are mystified and often alarmed at the suggestion that they should consider surgery to correct the problem of Hyperparathyroidism. Data from A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med. 1999 Oct 21;341(17):1249-55. presents long term follow-up information on 121 patients with Hyperparathyroidism. who had no symptoms at the time of diagnosis. Bone density (osteoporosis) improved in the patients who had surgery, but not in the control group. Similarly, recurrent kidney stones were much more common in the patients who did not have surgery, and mild evidence for disease progression became evident in 27% of patients who declined surgery. This type of data is useful for patients and physicians contemplating the merits of surgical correction of Hyperparathyroidism. At present, it seems reasonable to carefully consider medical vs surgical options in each patient individually, as every patient will present with a unique set of clinical circumstances. For an overview, see Asymptomatic primary hyperparathyroidism: new issues and new questions--bridging the past with the future. J Bone Miner Res. 2002 Nov;17 Suppl 2:N57-67. Review.
Is surgery the only treatment option for hyperparathyroidism?
At present, surgical correction of the Hyperparathyroidism. is the only proven definitively effective modality for treatment and "cure" of this disease. Options such as "injection of an abnormal parathyroid" with alcohol, laser ablation, or medications, have not yet been proven effective. Several clinical trials are underway to determine whether a new class of drugs known as calcimimetics can block secretion of parathyroid hormone and reduce the consequences of Hyperparathyroidism.. At present, we do not have access to this experimental treatment, nor do we know whether it will prove to be safe and effective. For an overview of these options, see Nonoperative management of hyperparathyroidism: present and future. Curr Opin Oncol. 2001 Jan;13(1):33-38.
Can my parathyroid glands be removed by laser or laparoscopy?
Given the tremendous advances in non-invasive surgery and laparoscopic-guided surgical procedures, patients are often frustrated to learn that non-invasive surgery has not yet found wide acceptance in the parathyroid field however the experience with this technique is increasing rapidly. Localization of one or more parathyroid adenomas requires considerable skill and current experience suggests that only a subset of patients with localized parathyroid disease will have successful minimally invasive parathyroid surgery. Furthermore, the success rate and complication rate of minimally invasive parathyroid exploration may not always be as good as with traditional parathyroid surgery, however this is a rapidly evolving area and it may turn out that with proper patient selection, the results will improve considerable. For representative reports, see Minimally invasive parathyroid surgery Surg Endosc. 2000 Nov;14(11):987-90 and Br J Surg 1999 Dec;86(12):1563-1566 Endoscopically assisted, minimally invasive parathyroidectomy, and Minimally invasive video-assisted parathyroidectomy: lesson learned from 137 cases. J Am Coll Surg. 2000 Dec;191(6):613-8, and Surgery 1999 Dec;126(6):1004-9; Unilateral neck exploration under local anesthesia: the approach of choice for asymptomatic primary hyperparathyroidism and Surgery 1999 Dec;126(6):1011-4; Bilateral neck exploration for parathyroidectomy under local anesthesia: a viable technique for patients with coexisting thyroid disease with or without sestamibi scanning.
How useful and accurate are current localization techniques for identification of parathyroid adenomas in patients with hyperparathyroidism (HPT)? The answer depend on the clinical setting and context. The aim of the decision making process is to provide guidance to the surgeon in deciding whether a focal approach to surgery on one side of the neck is appropriate, or whether both sides of the neck need to be explored to find the abnormal parathyroid gland(s). An experienced group of surgeons report that a minimal approach can be considered in a select group of patients that does not have familial primary HPT, secondary or tertiary disease, coexisting thyroid pathology, or an equivocal sestamibi scan preoperatively. Only patients with a positive single hot spot on sestamibi scan can be considered candidates for the minimal approach. Using this criteria only 64% of all patients with hyperparathyroidism are candidates for a minimally invasive approach. See Parathyroid Surgery: Separating Promise from Reality. J Clin Endocrinol Metab. 2002 Mar 1;87(3):1024-1029.
What are the risk factors for developing a low calcium after parathyroid surgery?
In some studies, the extent of the operation, previous thyroid or neck surgery, the number of parathyroid glands removed, and the level of parathyroid hormone before the operation are predictive of hypocalcemia after surgery. See Risk factors for severe postoperative hypocalcaemia after operations for primary hyperparathyroidism. Eur J Surg. 2002;168(10):552-6.
Will my osteoporosis get better after surgical correction of my hyperparathyroidism?
The available evidence from follow-up studies suggests that the majority of patients will have a significant improvement in bone mass at multiple sites following correction of hyperparathyroidism. Remember that it takes years, often decades, for osteoporosis to develop, hence it is unreasonable to expect a return of bone mass to normal within a year of surgical correction of the hyperparathyroidism.
Can I take drugs instead of having an operation on my parathyroid glands?
There have been few randomized trials designed to assess whether currently available osteoporosis therapies can arrest progression of osteoporosis in the presence of Hyperparathyroidism.. There are also trials of new medications designed to treat this problem, but the results of most of these trials, and the medications, are not yet available. Estrogen treatment of postmenopausal women with Hyperparathyroidism seems to confer some benefit for patients with osteoporosis, as reviewed above. Furthermore, preliminary data from some trials of using medications such as alendronate (Fosamax) for the treatment of osteoporosis in women with mild hyperparathyroidism appear to show some benefit in terms of reducing bone loss in the group treated with alendronate. See Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. J Bone Miner Res. 2001 Jan;16(1):113-9.
Am I at risk for the development of other diseases if I have been diagnosed with hyperparathyroidism?
The majority of patients, about 90% of individuals, will present with sporadic hyperparathyroidism. The remaining 10% may develop hyperparathyroidism as a result of a genetic predisposition, either due to familial hyperparathyroidism, or as part of a multiple endocrine neoplasia syndrome (MEN). Patients with MEN-1 may exhibit hyperparathyroidism in association with pituitary or pancreatic endocrine tumors, whereas patients with MEN-2 may also present with cancer of the thyroid or adrenal tumors that produce epinephrine, known as pheochromocytomas.
My levels of parathyroid hormone (PTH) are elevated by my calcium is normal. Do I have hyperparathyroidism?
Some patients with hyperparathyroidism will have normal levels of ionized calcium, often at the upper limit of normal and slightly increased levels of circulating PTH. Other patients with this biochemical picture will not have hyperparathyroidism, yet may have mild vitamin D deficiency, a condition that may also produce elevated levels of circulating PTH. Measurement of the levels of vitamin D, and often a trial of vitamin D supplementation, may be helpful in arriving at an explanation for the abnormal blood chemistry. To review the normal ranges of vitamin D levels in older populations, see Vitamin D status and redefining serum parathyroid hormone reference range in the elderly. J Clin Endocrinol Metab. 2001 Jul;86(7):3086-90. For an overview of mild vitamin D deficiency, see Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001 Aug;22(4):477-501.
I had surgery for hyperparathyroidism, and although my calcium is normal, my PTH level is still elevated? Was the surgery a success?
This scenario may be observed in about 20% of patients. Explanations may include a lag time in the normalization of PTH function, secondary vitamin D deficiency, or possibly, the presence of hyperparathyroidism despite apparent surgical correction of the problem. Observation and repeat testing over time will usually sort out the reason for this biochemical picture. See Normocalcemia with elevated parathyroid hormone levels after surgical treatment of primary hyperparathyroidism. Am J Surg. 2001 Jul;182(1):15-9.
How do I decide if I should have surgery on my parathyroid glands, or simply watch and wait?
The answer to this question will be different for each patient. In some instances, surgery will more likely be indicated ( progressive bone disease/reduced bone density, rapid steady decline in kidney function, kidney stones, very high levels of blood calcium). In other instances, the decision as to proceed with surgery or careful observation may be more complex. To review recent consensus guidelines on this topic from the Third International Workshop on Hyperparathyroidism, held in May 2008, see Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop J Clin Endocrinol Metab. 2009 Feb;94(2):335-9 Medical management of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop J Clin Endocrinol Metab. 2009 Feb;94(2):373-81. and Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop J Clin Endocrinol Metab. 2009 Feb;94(2):366-72 and Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop J Clin Endocrinol Metab. 2009 Feb;94(2):351-65. and Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop J Clin Endocrinol Metab. 2009 Feb;94(2):340-50