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Thyroid and parathyroid.
Classification and external resources
Specialty Endocrinology
ICD-10 E21
ICD-9-CM 252.0
DiseasesDB 20710
MedlinePlus 001215
eMedicine emerg/265 med/3200
MeSH D006961

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 hypercalcemia (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 1
    • Primary 1.1
    • Secondary 1.2
    • Tertiary 1.3
    • Quaternary and Quintary 1.4
  • Signs and symptoms 2
  • Diagnosis 3
    • Intact PTH 3.1
    • Calcium levels 3.2
    • Serum phosphate 3.3
    • Alkaline phosphatase 3.4
    • Technetium sestamibi 3.5
  • Treatment 4
    • Calcimimetics 4.1
  • History 5
  • See also 6
  • References 7
  • External links 8



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.[2][3]

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.[4][5]

Patients with bipolar disorder who are receiving long-term lithium treatment are at increased risk for hyperparathyroidism.[6] 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.[6]


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[7] (caused by lack of sunlight, diet or malabsorption) and chronic kidney failure.

Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcemia and increased parathyroid hormone secretion. This increases bone resorption. In chronic kidney 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 kidney damage that now again causes a form of secondary (quaternary) hyperparathyroidism that may itself result in autonomy (quintary) hyperparathyroidism.[8] Additionally, quaternary hyperparathyroidism may ensue from hungry bone syndrome after parathyroidectomy.[9]

Signs and symptoms

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 hypercalcemia are relatively rare, being more common in patients with malignant hypercalcemia. If present, common manifestations of hypercalcemia 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.[10] A history of acquired racquet nails (trachyonychia) may be indicative of bone resorption.[11] 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 high primary hyperparathyroidism
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.

Intact PTH

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.

Calcium levels

In cases of primary hyperparathyroidism or tertiary hyperparathyroidism heightened PTH leads to increased serum calcium (hypercalcemia) due to:

  1. increased bone resorption, allowing flow of calcium from bone to blood
  2. reduced kidney clearance of calcium
  3. increased intestinal calcium absorption

Serum phosphate

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

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.

Technetium sestamibi

A sestamibi scan is a procedure in nuclear medicine which is performed to identify hyperparathyroidism (or parathyroid adenoma).[12] It is used by surgeons to locate ectopic parathyroid adenomas, most commonly found in the anterior mediastinum.


Treatment depends entirely on the type of hyperparathyroidism encountered. People with primary hyperparathyroidism who are symptomatic benefit from surgery to remove the parathyroid tumor (parathyroid adenoma). Indications for surgery are as follows:[13]

  • Symptomatic hyperparathyroidism
  • Asymptomatic hyperparathyroidism with any of the following:
    • 24-hour urinary calcium > 400 mg
    • serum calcium > 1 mg/dL above upper limit of normal
    • Creatinine clearance > 30% below normal for patient's age
    • Bone density > 2.5 standard deviations for below peak (i.e., T-score of -2.5)
    • Patient age < 50

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 kidney 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
  • Phosphorus


A calcimimetic (such as cinacalcet) is a potential therapy for some people with severe hypercalcemia and primary hyperparathyroidism who are unable to undergo parathyroidectomy and for secondary hyperparathyroidism on dialysis.[14][15]

In the treatment of secondary hyperparathyroidism due to chronic kidney disease on dialysis calcimimetics do not appear to affect the risk of early death.[16] They do decrease the need for a parathyroidectomy but cause more issues with low blood calcium levels and vomiting.[16]


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.[17]

See also


  1. ^ Fraser WD (July 2009). "Hyperparathyroidism". Lancet 374 (9684): 145–58.  
  2. ^ 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. 
  3. ^ McConnell, Thomas H. (2007). The Nature of Disease: Pathology for the Health Professions. Lippincott Williams & Wilkins. p. 466.  
  4. ^ Marx SJ. (2011) Hyperparathyroid Genes: Sequences Reveal Answers and Questions. Endocr. Pract.
  5. ^ Sulaiman L, Nilsson IL, Juhlin CC, Haglund F, Höög A, Larsson C, Hashemi J. (June 2012). "Genetic characterization of large parathyroid adenomas.". Endocr Relat Cancer 19 (3): 389–407.  
  6. ^ a b Pomerantz JM (2010). "Hyperparathyroidism Resulting From Lithium Treatment Remains Underrecognized". Drug Benefit Trends 22: 62–63. 
  7. ^ Zink AR, Panzer S, Fesq-Martin M, Burger-Heinrich E, Wahl J, Nerlich AG (2001). "Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications.". Endocr Rev. 22 (4): 477–501.  
  8. ^ Kaiser, W.; Schmidt G. A.; Gerlach H.. (June 1976). "Quintärer Hyperparathyreoidismus [Quintary hyperparathyroidism]". Z Gesamte Inn Med 31 (11): 358–64.  
  9. ^ Oltmann, Sarah C.; Maalouf, N. M.; Holt, S. (March 2011). "Significance of Elevated Parathyroid Hormone after Parathyroidectomy for Primary Hyperparathyroidism". Endocrine Practice 17 (S1): 57–73.  
  10. ^ Hyperparathyroidism. National Endocrine and Metabolic Diseases Information Service. May 2006.
  11. ^ 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. 
  12. ^ "Parathyroid Adenoma". 
  13. ^ Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med. 2004 Apr 22;350(17):1746-51
  14. ^
  15. ^ Ott, SM (April 1998). "Calcimimetics–new drugs with the potential to control hyperparathyroidism". J. Clin. Endocrinol. Metab. 83 (4): 1080–2.  
  16. ^ a b Ballinger, AE; Palmer, SC; Nistor, I; Craig, JC; Strippoli, GF (9 December 2014). "Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients.". The Cochrane database of systematic reviews 12: CD006254.  
  17. ^ Zink AR, Panzer S, Fesq-Martin M, Burger-Heinrich E, Wahl J, Nerlich AG (2005). "Evidence for a 7000-year-old case of primary hyperparathyroidism". JAMA 293 (1): 40–2.  

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