Primary hyperparathyroidism

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Primary hyperparathyroidism
Classification and external resources
Illu thyroid parathyroid.jpg
Thyroid and parathyroid.
ICD-10E21.0
ICD-9252.01
DiseasesDB6283
MedlinePlus000384
eMedicineradio/355
MeSHD049950
 
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Primary hyperparathyroidism
Classification and external resources
Illu thyroid parathyroid.jpg
Thyroid and parathyroid.
ICD-10E21.0
ICD-9252.01
DiseasesDB6283
MedlinePlus000384
eMedicineradio/355
MeSHD049950

Primary hyperparathyroidism causes hypercalcemia (elevated blood calcium levels) through the excessive secretion of parathyroid hormone (PTH), usually by an adenoma (benign tumors) of the parathyroid glands.

Epidemiology[edit]

The incidence of primary hyperparathyroidism is approximately 1 per 1,000 people (0.1%),[1] while there are 25-30 new cases per 100,000 people per year in the United States.[2] The prevalence of primary hyperparathyroidism has been estimated to be 3 in 1000 in the general population and as high as 21 in 1000 in postmenopausal women.[3] It is almost exactly three times as common in women as men.

Signs and Symptoms[edit]

The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by the mnemonic "stones, bones, abdominal groans and psychiatric moans".

The German description of the same symptoms is "Stein-, Bein- und Magenpein", literally "stone, bone, and stomach-pain".

Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.

When subjected to formal research, symptoms of depression, pain, and gastric dysfunction seem to correlate with mild cases of hypercalcemia.[7]

Diagnosis[edit]

The diagnosis of primary hyperparathyroidism is made by blood tests.

Serum calcium levels are elevated, and the parathyroid hormone level is abnormally high compared with an expected low level in response to the high calcium. A relatively elevated parathyroid hormone has been estimated to have a sensitivity of 60%-80% and a specificity of approximately 90% for primary hyperparathyroidism.[8]

A more powerful variant of comparing the balance between calcium and parathyroid hormone is to perform a 3 hour calcium infusion. After infusion, a parathyroid hormone level above a cutoff of 14 ng/l has a sensitivity of 100% and a specificity of 93% in detecting primary hyperparathyroidism, with a confidence interval of 80% to 100%.[9]

The serum chloride/phosphate ratio is 33 or more in most patients with primary hyperparathyroidism. However, usage of thiazide medications have been reported to causes ratios above 33.[10] Studies without any usage of thiazide diuretics have estimated a serum chloride/phosphate ratio to have a sensitivity of 94%[11] or 95%[12][13] and a specificity of 96%[11] or 100%.[12]

Urinary cAMP is occasionally measured; this is generally elevated.

Parathyroid hormone activity[edit]

Intact PTH levels are also elevated.

Causes[edit]

The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma[14] resulting from a clonal mutation (~97%). Less common are parathyroid hyperplasia[14] (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%).

Primary hyperparathyroidism is also a feature of several familial endocrine disorders: Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.

Genetic associations include:

OMIMNameGene
145000HRPT1MEN1, HRPT2
145001HRPT2HRPT2
610071HRPT3unknown at 2p13.3-14[15]

In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppressor genes (Menin gene in MEN1), or involve gain of function mutations (RET proto-oncogene MEN 2a).

Recently, it was demonstrated that liquidators of the Chernobyl power plant are faced with a substantial risk of primary hyperparathyroidism, possibly caused by radioactive strontium isotopes.[16]

Primary hyperparathyroidism can also result from pregnancy. It is apparently very rare, with only about 110 cases have so far been reported in world literature, but this is probably a considerable underestimate of its actual prevalence in pregnant women.[17]

Complications[edit]

The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

Treatment[edit]

Treatment is usually surgical removal of the gland(s) containing adenomas.

Medications[edit]

Medications include estrogen replacement therapy in postmenopausal women and bisphosphonates. Bisphosphonates may improve bone turnover.[18] Newer medications termed "calcimimetics" used in secondary hyperparathyroidism are now being used in Primary hyperparathyroidism. Calcimimetics reduce the amount of parathyroid hormone released by the parathyroid glands. They are recommended in patients in whom surgery is inappropriate.[19]

Surgery[edit]

The surgery on parathyroid is called "Parathyroidectomy"; it was first done in 1925.[20] The symptoms of the disease, listed above, are indications for surgery. Surgery reduces all cause mortality as well as resolving symptoms. However, cardiovascular mortality is not significantly reduced.[6]

A consensus statement in 2002 recommended the following indications for surgery in asymptomatic hyperparathyroidism:[21]

More recently, three randomized controlled trials have studied the role of surgery in patients with asymptomatic hyperparathyroidism. The largest study reported that surgery showed increase in bone mass, but no improvement in quality of life after one to two years among patients with:[22]

Two other trials reported improvements in bone density and some improvement in quality of life with surgery.[23][24]

Future therapies[edit]

Future developments such as calcimimetic agents (e.g. cinacalcet) which activate the parathyroid calcium-sensing receptor may offer a good alternative to surgery.

See also[edit]

References[edit]

  1. ^ Deshmukh, R. G.; Alsagoff, S. A. L.; Krishnan, S.; Dhillon, K. S.; Khir, A. S. M. (1998). "Primary hyperparathyroidism presenting with pathological fracture". Journal of the Royal College of Surgeons of Edinburgh 43 (6): 424–427. PMID 9990797. 
  2. ^ Bilezikian, John P.; Silverberg, Shonni J. (2002). "Primary hyperparathyroidism: Epidemiology and clinical consequences". Clinical Reviews in Bone and Mineral Metabolism 1 (1): 25–34. doi:10.1385/BMM:1:1:25. 
  3. ^ Bolland, M. J.; Grey, A. B.; Gamble, G. D.; Reid, I. R. (2004). "Association between Primary Hyperparathyroidism and Increased Body Weight: A Meta-Analysis". Journal of Clinical Endocrinology & Metabolism 90 (3): 1525. doi:10.1210/jc.2004-1891.  edit
  4. ^ Barreras, R. F.; Donaldson, R. M. (1967). "Role of Calcium in Gastric Hypersecretion, Parathyroid Adenoma and Peptic Ulcer". New England Journal of Medicine 276 (20): 1122–1124. doi:10.1056/NEJM196705182762005. PMID 6024167.  edit
  5. ^ Stefenelli T, Abela C, Frank H, et al. (1997). "Cardiac abnormalities in patients with primary hyperparathyroidism: implications for follow-up". J. Clin. Endocrinol. Metab. 82 (1): 106–12. doi:10.1210/jc.82.1.106. PMID 8989242. 
  6. ^ a b Vestergaard, P.; Mosekilde, L. (2003). "Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism". BMJ 327 (7414): 530–534. doi:10.1136/bmj.327.7414.530. PMC 192894. PMID 12958111. 
  7. ^ Bargren AE, Repplinger D, Chen H, Sippel RS (2011). "Can biochemical abnormalities predict symptomatology in patients with primary hyperparathyroidism?". J Am Coll Surg 213 (3): 410–4. doi:10.1016/j.jamcollsurg.2011.06.401. PMID 21723154. 
  8. ^ [1] Lepage, R.; d'Amour, P.; Boucher, A.; Hamel, L.; Demontigny, C.; Labelle, F. (1988). "Clinical performance of a parathyrin immunoassay with dynamically determined reference values". Clinical chemistry 34 (12): 2439–2443. PMID 3058363.  edit
  9. ^ Titon, I.; Cailleux-Bounacer, A.; Basuyau, J. P.; Lefebvre, H.; Savoure, A.; Kuhn, J. M. (2007). "Evaluation of a standardized short-time calcium suppression test in healthy subjects: Interest for the diagnosis of primary hyperparathyroidism". European Journal of Endocrinology 157 (3): 351–357. doi:10.1530/EJE-07-0132. PMID 17766719.  edit
  10. ^ Lawler FH, Janssen HP (1983). "Chloride:phosphate ratio with hypercalcemia secondary to thiazide administration". The Journal of family practice 16 (1): 153–4. PMID 6848626. 
  11. ^ a b Reeves CD, Palmer F, Bacchus H, Longerbeam JK (1975). "Differential diagnosis of hypercalcemia by the chloride/phosphate ratio". Am. J. Surg. 130 (2): 166–71. doi:10.1016/0002-9610(75)90365-7. PMID 1155729. 
  12. ^ a b Palmer FJ, Nelson JC, Bacchus H (1974). "The chloride-phosphate ratio in hypercalcemia". Ann. Intern. Med. 80 (2): 200–4. PMID 4405880. 
  13. ^ Broulík PD, Pacovský V (1979). "The chloride phosphate ratio as the screening test for primary hyperparathyroidism". Horm. Metab. Res. 11 (10): 577–9. doi:10.1055/s-0028-1092784. PMID 521012. 
  14. ^ a b "Endocrine Pathology". Retrieved 2009-05-08. 
  15. ^ Warner JV, Nyholt DR, Busfield F, et al. (March 2006). "Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3–14". J. Med. Genet. 43 (3): e12. doi:10.1136/jmg.2005.035766. PMC 2563254. PMID 16525030. 
  16. ^ Boehm, Bernhard O.; Rosinger, Silke, Belyi, David, Dietrich, Johannes W. (August 2011). "The Parathyroid as a Target for Radiation Damage". New England Journal of Medicine 365 (7): 676–678. doi:10.1056/NEJMc1104982. PMID 21848480. Retrieved 19 August 2011. 
  17. ^ Primary Hyperparathyroidism in Pregnancy - a review at obgyn.net. By Sushanta Bhadra and John Fairbank. Retrieved April 2011
  18. ^ Khan AA, Bilezikian JP, Kung AW, et al. (2004). "Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial". J. Clin. Endocrinol. Metab. 89 (7): 3319–25. doi:10.1210/jc.2003-030908. PMID 15240609. 
  19. ^ http://pi.amgen.com/united_states/sensipar/sensipar_pi_hcp_english.pdf
  20. ^ Weber T, Eberle J, Messelhäuser U,and et al. (2013). "Parathyroidectomy, elevated depression scores, and suicidal ideation in patients with primary hyperparathyroidism: results of a prospective multicenter study". JAMA Surg. 148 (2): 109–115. doi:10.1001/2013.jamasurg.316. 
  21. ^ Bilezikian JP, Potts JT, Fuleihan Gel-H, et al. (2002). "Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century". J. Clin. Endocrinol. Metab. 87 (12): 5353–61. doi:10.1210/jc.2002-021370. PMID 12466320. 
  22. ^ Bollerslev J, Jansson S, Mollerup CL, et al. (2007). "Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial". J. Clin. Endocrinol. Metab. 92 (5): 1687–92. doi:10.1210/jc.2006-1836. PMID 17284629. 
  23. ^ Ambrogini E, Cetani F, Cianferotti L, et al. (2007). "Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial". J. Clin. Endocrinol. Metab. 92 (8): 3114–21. doi:10.1210/jc.2007-0219. PMID 17535997. 
  24. ^ Rao DS, Phillips ER, Divine GW, Talpos GB (2004). "Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism". J. Clin. Endocrinol. Metab. 89 (11): 5415–22. doi:10.1210/jc.2004-0028. PMID 15531491. 

Weber T, Eberle J, Messelhäuser U and et al.Parathyroidectomy, elevated depression scores, and suicidal ideation in patients with primary hyperparathyroidism: results of a prospective multicenter study. JAMA Surg. 2013 Feb;148(2):109-15.

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