|Classification and external resources|
Thyroid and parathyroid.
Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels. Excessive PTH secretion may be due to problems in the glands themselves, in which case it is referred to as primary hyperparathyroidism and which leads to hypercalcaemia (raised calcium levels). It may also occur in response to low calcium levels, as encountered in various situations such as vitamin D deficiency or chronic kidney disease; this is referred to as secondary hyperparathyroidism. In all cases, the raised PTH levels are harmful to bone, and treatment is often needed.
- 1 Classification
- 2 Symptoms and signs
- 3 Diagnosis
- 4 Treatment and monitoring
- 5 History
- 6 See also
- 7 References
- 8 External links
Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands themselves. There is oversecretion of PTH due to a parathyroid adenoma, parathyroid hyperplasia or, rarely, a parathyroid carcinoma. This disease is often characterized by the quartet stones, bones, groans, and psychic overtones referring to the presence of kidney stones, hypercalcemia, constipation and peptic ulcers, as well as depression, respectively.
In a minority of cases this occurs as part of a multiple endocrine neoplasia (MEN) syndrome, either type 1 (caused by a mutation in the gene MEN1) or type 2a (caused by a mutation in the gene RET). Other mutations that have been linked to parathyroid neoplasia include mutations in the genes HRPT2, and CASR.
Patients with bipolar disorder who are receiving long-term lithium treatment are at increased risk for hyperparathyroidism. Elevated calcium levels are found in 15% to 20% of patients who have been taking lithium long-term. However, only a few of these patients have significantly elevated levels of parathyroid hormone and clinical symptoms of hyperparathyroidism. Lithium-associated hyperparathyroidism is usually caused by a single parathyroid adenoma.
Secondary hyperparathyroidism is due to physiological (i.e. appropriate) secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels). The most common causes are vitamin D deficiency (caused by lack of sunlight, diet or malabsorption) and chronic renal failure.
Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcaemia and increased parathyroid hormone secretion. This increases bone resorption. In chronic renal failure the problem is more specifically failure to convert vitamin D to its active form in the kidney. The bone disease in secondary hyperparathyroidism caused by renal failure is termed renal osteodystrophy.
Tertiary hyperparathyroidism is seen in patients with long-term secondary hyperparathyroidism which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with chronic renal failure and is an autonomous activity.
Quaternary and Quintary
Quaternary and quintary are rare conditions that may be observed after surgical removal of primary hyperparathyroidism, when it has led to renal damage that now again causes a form of secondary (quaternary) hyperparathyroidism that may itself result in autonomy (quintary) hyperparathyroidism. Additionally, quaternary hyperparathyroidism may ensue from hungry bone syndrome after parathyroidectomy.
Symptoms and signs
These depend entirely on whether the hyperparathyroidism is primary or secondary.
In primary hyperparathyroidism about 50% of patients have no symptoms and the problem is picked up as an incidental finding (via a raised calcium or characteristic X-ray appearances). Many other patients only have non-specific symptoms. Symptoms directly due to hypercalcaemia are relatively rare, being more common in patients with malignant hypercalcaemia. If present, common manifestations of hypercalcaemia include weakness and fatigue, depression, bone pain, muscle soreness (myalgias), decreased appetite, feelings of nausea and vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones and osteoporosis. A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption. Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor will eliminate the symptoms in most patients.
In secondary hyperparathyroidism the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal osteodystrophy.
The gold standard of diagnosis is the Parathyroid immunoassay. Once an elevated Parathyroid hormone has been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level:
|PTH||serum calcium||likely type|
|high||low or normal||secondary hyperparathyroidism|
Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.
In primary hyperparathyroidism, parathyroid hormone (PTH) levels will be either elevated or "inappropriately normal" in the presence of elevated calcium. Typically PTH levels vary greatly over time in the affected patient and (as with Ca and Ca++ levels) must be retested several times to see the pattern. The currently accepted test for PTH is "Intact PTH" which is intended to detect only relatively intact and biologically active PTH molecules. Older tests often detected other, inactive fragments. Even "Intact PTH" may be inaccurate in patients with renal dysfunction.
Serum calcium or Ionized Calcium (Ca++)
In cases of primary hyperparathyroidism or tertiary hyperparathyroidism heightened PTH leads to increased serum calcium (hypercalcemia) due to:
- increased bone resorption, allowing flow of calcium from bone to blood
- reduced renal clearance of calcium
- increased intestinal calcium absorption
In primary hyperparathyroidism, serum phosphate levels are abnormally low as a result of decreased renal tubular phosphate reabsorption. However, this is only present in about 50% of cases. This contrasts with secondary hyperparathyroidism, in which serum phosphate levels are generally elevated because of renal disease.
Alkaline phosphatase levels are usually elevated in hyperparathyroidism. In primary hyperthyroidism, levels may remain within the normal range, however this is 'inappropriately normal' given the increased levels of plasma calcium.
A sestamibi scan is a procedure in nuclear medicine which is performed to identify hyperparathyroidism (or parathyroid adenoma). It is used by surgeons to locate ectopic parathyroid adenomas, most commonly found in the anterior mediastinum.
Treatment and monitoring
Endocrinologists diagnose diseases affecting glands and should be consulted for hyperparathyroidism. Again, treatment depends entirely on the type of hyperparathyroidism encountered. Patients with primary hyperparathyroidism who are symptomatic benefit from surgery to remove the parathyroid tumor (parathyroid adenoma). Indications for surgery are as follows:
- Symptomatic hyperparathyroidism
- Asymptomatic hyperparathyroidism with any of the following:
In patients with secondary hyperparathyroidism, the high PTH levels are an appropriate response to low calcium and treatment must be directed at the underlying cause of this (usually vitamin D deficiency or chronic renal failure). If this is successful PTH levels should naturally return to normal levels unless PTH secretion has become autonomous (tertiary hyperparathyroidism)
Testing for hyperparathryroidism:
- Calcium level
- Bone density
- Vitamin D
A calcimimetic (cinacalcet) is a new type of drug to be considered as a potential therapy for some people with severe hypercalcemia and primary hyperparathyroidism who are unable to undergo parathyroidectomy and for secondary hyperparathyroidism on dialysis. It is recognised by the body as if it is calcium, in other words, it mimics the effect of calcium in your tissues. This tricks the body into thinking there is more calcium in the blood which reduces PTH release from parathyroid glands, leading to lower calcium and phosphorus levels in the blood. Calcimimetics control PTH release from parathyroid glands without increasing calcium and phosphorus levels. The most common side effects of calcimimetics are mild or moderate nausea and vomiting.
Hyperparathyroidism was first described and treated in the 1930s by Fuller Albright of Massachusetts General Hospital, working at the Mallinckrodt General Clinical Research Center. The oldest known case was found in a cadaver from an Early Neolithic cemetery in southwest Germany.
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- Carrol, Mary F.; David S. Schade (1 May 2003). "A Practical Approach to Hypercalcemia". American Family Physician 67 (9): 1959–1966. "his constellation of symptoms has led to the mnemonic “Stones, bones, abdominal moans, and psychic groans,” which is used to recall the signs and symptoms of hypercalcemia, particularly as a result of primary hyperparathyroidism."
- McConnell, Thomas H. (2007). The Nature of Disease: Pathology for the Health Professions. Lippincott Williams & Wilkins. p. 466. ISBN 9780781753173. ""Stones" refers to kidney stones, "bones" to associated destructive bone changes, "groans" to the pain of stomach and peptic ulcers that occur in some cases, and "moans" to the depression that frequently accompanies the disease and is often its first and most prominent manifestation."
- Marx SJ. (2011) Hyperparathyroid Genes: Sequences Reveal Answers and Questions. Endocr. Pract.
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- Baran, R.; Turkmani, M.G.; Mubki, T. "Acquired Racquet Nails: a Useful Sign of Hyperparathyroidism". Wiley Online Library. Journal of the European Academy of Dermatology and Venereology. Retrieved 27 June 2014.
- "Parathyroid Adenoma".
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- Section on parathyroid disease at endocrineweb.com
- Overview at Endocrine and Metabolic Diseases Information Service