Hyperparathyroidism

Hyperparathyroidism is an increased parathyroid hormone (PTH)

Hyperparathyroidism
levels in the blood.[4] This occurs either from the parathyroid glands
inappropriately making too much PTH (primary hyperparathyroidism) or
other events triggering increased production by the parathyroid glands
(secondary hyperparathyroidism).[1] Most people with primary disease
have no symptoms at the time of diagnosis.[3] In those with symptoms
the most common is kidney stones with other potential symptoms
including weakness, depression, bone pains, confusion, and increased
urination.[1][2] Both types increase the risk ofweak bones.[2][3]

Primary hyperparathyroidism in 80% of cases is due to a single benign

tumor known as a parathyroid adenoma with most of the rest of the cases
due to a multiple benign tumors.[1][2] Rarely it may be due toparathyroid
Thyroid and parathyroid
cancer.[2] Secondary hyperparathyroidism typically occurs due to
vitamin D deficiency, chronic kidney disease, or other causes of low Specialty Endocrinology
blood calcium.[1] Diagnosis of primary disease is by finding ahigh blood Symptoms None, kidney stones,
calcium and high PTH levels.[2] weakness, depression, bone
pains, confusion, increased
Primary hyperparathyroidism may be cured by removing the adenoma or urination[1][2][3]
overactive parathyroid glands.[1][2] In those without symptoms, mildly
Complications Osteoporosis[2][3]
increased blood calcium levels, normal kidneys, and normalbone density
monitoring may be all that is required.[2] The medication cinacalcet may Usual onset 50 to 60[2]
also be used to decrease PTH levels.[2] In those with very high blood Types Primary, secondary
calcium levels treatment may include large amounts of intravenous Causes Primary: parathyroid
normal saline.[1] Low vitamin D levels should be corrected.[2] adenoma, multiple benign
tumors, parathyroid
Primary hyperparathyroidism is the most common form.[1] In the
cancer[1][2]
developed world between one and four per thousand people are
Secondary: vitamin D
affected.[3] It occurs three times more often in women than men and is
deficiency, chronic kidney
typically diagnosed between the ages of 50 and 60.[2] The disease was
disease, low blood calcium[1]
first described in the 1700s and in the late 1800s was determined to be
related to the parathyroid.[5] Surgery as a treatment was first carried out Diagnostic High blood calcium and high
in 1925.[5] method PTH levels[2]
Treatment Monitoring, surgery,
intravenous normal saline,
cinacalcet[1][2]
Contents
Frequency ~2 per 1,000[3]
Signs and symptoms
Cause
Mechanism
Diagnosis
Differential diagnosis
Blood tests
Nuclear medicine
Classification
Treatment
 Primary
Secondary
Calcimimetics
History
Notes
References
External links

Signs and symptoms

Symptoms depend on whether the hyperparathyroidism is the result of parathyroid overactivity or secondary
.

In primary hyperparathyroidism about 75% of people have no symptoms.[1] The problem is often picked up during blood work for
other reasons via a raised calcium.[3] Many other people 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 (See Foot Note[nb 1]) and
osteoporosis.[9] A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption.[10] Parathyroid adenomas
are very rarely detectable on clinical examination. Sur
gical removal of a parathyroid tumor eliminates 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 asrickets, osteomalacia and renal osteodystrophy.

Cause
Radiation exposure increases the risk of primary hyperparathyroidism.[1] A number of genetic conditions including multiple
endocrine neoplasia syndromesalso increase the risk.[1]

Mechanism
Normal parathyroid glands measure the ionized calcium (Ca2+) concentration in the blood and secrete parathyroid hormone
accordingly: if the ionized calcium rises above normal the secretion of PTH is decreased, whereas when the Ca2+ level falls,
parathyroid hormone secretion is increased.[6]

Secondary hyperparathyroidism occurs if the calcium level is abnormally low. The normal glands respond by secreting parathyroid
hormone at a persistently high rate. This typically occurs when the 1,25 dihydroxyvitamin D3 levels in the blood are low and there is
hypocalcemia. A lack of 1,25 dihydroxyvitamin D3 can result from a deficient dietary intake ofvitamin D, or from a lack of exposure
of the skin to sunlight, so the body cannot make its own vitamin D from cholesterol.[11] The resulting hypovitaminosis D is usually
due to a partial combination of both factors.Vitamin D3 (or cholecalciferol) is converted to 25-hydroxyvitamin D (orcalcidiol) by the
liver, from where it is transported via the circulation to the kidneys where it is converted into the active hormone, 1,25
dihydroxyvitamin D3.[6][11] Thus a third cause of secondary hyperparathyroidism is chronic kidney disease. Here the ability to
manufacture 1,25 dihydroxyvitamin D3 is compromised, resulting in hypocalcemia.

Diagnosis
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:
 Serum
Phosphate ALP PTH Likely type
calcium
Primary
↑ ↓ ↑ ↑
hyperparathyroidism[12]
Secondary
↓ ↑ ↑ ↑
hyperparathyroidism[12]

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.

Differential diagnosis
Familial benign hypocalciuric hypercalcaemia can present with similarly lab
changes.[1] In this condition the calcium creatinine clearance ratio; however, is Calcification in the brain due to
typically under 0.01.[1] hyperparathyroidism

Blood tests

Intact PTH
In primary hyperparathyroidism, parathyroid hormone (PTH) levels are 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 detects only relatively intact and biologically active
Pepper & Salt, classical X-Ray
PTH molecules. Older tests often detected other, inactive fragments. Even "Intact appearance of hyperparathyroidisim
PTH" may be inaccurate in patients with kidney 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 reabsorption of phosphate in the
kidney tubules. 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 kidney disease.

Alkaline phosphatase
Alkaline phosphatase levels are usually elevated in hyperparathyroidism. In primary hyperparathyroidism, levels may remain within
the normal range, however this is 'inappropriately normal' given the increased levels of plasma calcium.

Nuclear medicine
A technetium sestamibi scan is a procedure in nuclear medicine that identifies hyperparathyroidism (or parathyroid adenoma).[13] It
is used by surgeons to locate ectopic parathyroid adenomas, most commonly found in the anterior mediastinum.

Classification

Primary
Primary hyperparathyroidismresults 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 psychiatric overtones
referring to the presence of kidney stones, hypercalcemia, constipation and peptic
ulcers, as well as depression, respectively.[14][15]

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 geneMEN1) or type 2a (caused
by a mutation in the gene RET). Other mutations that have been linked to
parathyroid neoplasia include mutations in the genesHRPT2, and CASR.[16][17]

Patients with bipolar disorder who are receiving long-term lithium treatment are at
increased risk for hyperparathyroidism.[18] 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 Parathyroid adenoma.
clinical symptoms of hyperparathyroidism. Lithium-associated hyperparathyroidism
[18]
is usually caused by a single parathyroid adenoma.

Secondary
Secondary hyperparathyroidismis 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[19] (caused by
lack of sunlight, diet or malabsorption) andchronic 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 kidney failure is termed renal
osteodystrophy.

Tertiary
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
end-stage kidney disease and is an autonomous activity
.

Treatment
Treatment depends entirely on the type of hyperparathyroidism encountered.

Primary
People with primary hyperparathyroidism who are symptomatic benefit from surgery to remove the parathyroid tumor (parathyroid
adenoma). Indications for surgery are as follows:[20]
 Symptomatic hyperparathyroidism
Asymptomatic hyperparathyroidism with any of the following:

24-hour urinary calcium > 400 mg (seeFoot Note, below)

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)
People age < 50

Surgery can rarely result inhypoparathyroidism.

Secondary
In people 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)

Calcimimetics
A calcimimetic (such as cinacalcet) is a potential therapy for some people with severe hypercalcemia and primary
[21][22]
hyperparathyroidism who are unable to undergo parathyroidectomy and for secondary hyperparathyroidism on dialysis.

In the treatment of secondary hyperparathyroidism due to chronic kidney disease on dialysis calcimimetics do not appear to affect the
risk of early death.[23] They do decrease the need for a parathyroidectomy but cause more issues with low blood calcium levels and
vomiting.[23]

History
The oldest known case was found in a cadaver from an EarlyNeolithic cemetery in southwest Germany.[24]

Notes
1. Although parathyroid hormone (PTH) promotes the re-absorption of calcium from the kidneys' tubular fluid, thus
decreasing the rate of urinary calcium excretion, its effect is only noticeable at anygiven plasma ionized calcium
concentration. The primary determinant of the amount of calcium excreted into the urine per day is the plasma
ionized calcium concentration. Thus, in primary hyperparathyroidism the quantity of calcium excreted in the urine per
day is increased despite the high levels of PTH in the blood. This is because hyperparathyroidism results in
hypercalcemia, which increases the urinary calcium concentration hypercalcuria).
( Kidney stones are therefore often
a first indication of hyperparathyroidism, especially since the hypercalcuria is accompanied by an increase in urinary
phosphate excretion (a direct result of the high plasma PTH levels). ogether
T the calcium and phosphate tend to
precipitate out as water-insoluble salts, which readily form solid “stones”.[6][7][8]

References
1. Fraser WD (July 2009). "Hyperparathyroidism".Lancet. 374 (9684): 145–58. doi:10.1016/S0140-6736(09)60507-9(h
ttps://doi.org/10.1016%2FS0140-6736%2809%2960507-9) . PMID 19595349 (https://www.ncbi.nlm.nih.gov/pubmed/
19595349).
2. "Primary Hyperparathyroidism"(https://www.niddk.nih.gov/health-information/health-topics/endocrine/primary-hyperp
arathyroidism/Pages/fact-sheet.aspx). NIDDK. August 2012. Archived (https://web.archive.org/web/2016100422390
9/https://www.niddk.nih.gov/health-information/health-topics/endocrine/primary-hyperparathyroidism/Pages/fact-shee
t.aspx) from the original on 4 October 2016. Retrieved 27 September 2016.
3. Michels, TC; Kelly, KM (15 August 2013). "Parathyroid disorders". American Family Physician. 88 (4): 249–57.
PMID 23944728 (https://www.ncbi.nlm.nih.gov/pubmed/23944728).
 4. Allerheiligen, DA; Schoeber, J; Houston, RE; Mohl, VK; Wildman, KM (15 April 1998). "Hyperparathyroidism".
American Family Physician. 57 (8): 1795–802, 1807–8.PMID 9575320 (https://www.ncbi.nlm.nih.gov/pubmed/95753
20).
5. Gasparri, Guido; Camandona, Michele; Palestini, Nicola (2015).Primary, Secondary and Tertiary
Hyperparathyroidism: Diagnostic and Therapeutic Updates(https://books.google.ca/books?id=T8MDCwAAQBAJ&pg
=PA2). Springer. ISBN 9788847057586. Archived (https://web.archive.org/web/20170908183155/https://books.googl
e.ca/books?id=T8MDCwAAQBAJ&pg=P A2) from the original on 2017-09-08.
6. Blaine J, Chonchol M, Levi M (2015). "Renal control of calcium, phosphate, and magnesium homeostasis".Clinical
Journal of the American Society of Nephrology
. 10 (7): 1257–72. doi:10.2215/CJN.09750913(https://doi.org/10.221
5%2FCJN.09750913). PMID 25287933 (https://www.ncbi.nlm.nih.gov/pubmed/25287933).
7. Harrison, T.R.; Adams, R.D.; Bennett Jnr., I.L.; Resnick, W.H.; Thorn, G.W.; Wintrobe, M.M. (1958). "Metabolic and
Endocrine Disorders.".In: Principles of Internal Medicine(Third ed.). New York: McGraw-Hill Book Company.
pp. 575–578.
8. "Symptoms of Hyperparathyroidism and Symptoms of Parathyroid Disease" (http://www.parathyroid.com/parathyroid
-symptoms.htm). Parathyroid.com. Norman Parathyroid Center. Archived (https://web.archive.org/web/20151124004
812/http://parathyroid.com/parathyroid-symptoms.htm)from the original on 2015-11-24. Retrieved 2015-12-30.
9. Hyperparathyroidism (http://www.endocrine.niddk.nih.gov/pubs/hyper/hyper.htm#symptoms) Archived (https://web.ar
chive.org/web/20110524101254/http://www .endocrine.niddk.nih.gov/pubs/hyper/hyper
.htm) 2011-05-24 at the
Wayback Machine.. National Endocrine and Metabolic Diseases Information Service. May 2006.
10. Baran, R.; Turkmani, M.G.; Mubki, T. "Acquired Racquet Nails: a Useful Sign of Hyperparathyroidism"(http://onlinelib
rary.wiley.com/doi/10.1111/jdv.12187/full). Wiley Online Library. Journal of the European Academy of Dermatology
and Venereology. 28: 257–259. doi:10.1111/jdv.12187 (https://doi.org/10.1111%2Fjdv.12187). Archived (https://web.
archive.org/web/20150718084347/http://onlinelibrary .wiley.com/doi/10.1111/jdv.12187/full) from the original on 18
July 2015. Retrieved 27 June 2014.
11. Stryer, Lubert (1995). In: Biochemistry (Fourth ed.). New York: W.H. Freeman and Company. p. 707. ISBN 0 7167
2009 4.
12. Le, T.; Bhushan, V.; Sochat, M.; Kallianos, K.; Chavda, Y
.; Zureick, A. H.; Kalani, M. (2017). First aid for the USMLE
step 1 2017. New York: Mcgraw-Hill Education.ISBN 978-1259837630.
13. "Parathyroid Adenoma"(https://web.archive.org/web/20110716192203/http://brighamrad.harvard.edu/Cases/bwh/hc
ache/17/full.html). Archived from the original (http://brighamrad.harvard.edu/Cases/bwh/hcache/17/full.html)on
2011-07-16.
14. Carrol, Mary F.; David S. Schade (1 May 2003). "A Practical Approach to Hypercalcemia"(http://www.aafp.org/afp/20
03/0501/p1959.html). American Family Physician. 67 (9): 1959–1966. Archived (https://web.archive.org/web/201408
21185906/http://www.aafp.org/afp/2003/0501/p1959.html) from the original on 21 August 2014."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.
"
15. 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.
"
16. Marx SJ. (2011) Hyperparathyroid Genes: Sequences Reveal Answers and Questions. Endocr
. Pract.
17. Sulaiman L, Nilsson IL, Juhlin CC, Haglund F, Höög A, Larsson C, Hashemi J (June 2012)."Genetic characterization
of large parathyroid adenomas"(http://erc.endocrinology-journals.org/content/19/3/389.long)
. Endocr Relat Cancer.
19 (3): 389–407. doi:10.1530/ERC-11-0140(https://doi.org/10.1530%2FERC-11-0140). PMC 3359501 (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC3359501) . PMID 22454399 (https://www.ncbi.nlm.nih.gov/pubmed/22454399).
Archived (https://web.archive.org/web/20170908183155/http://erc.endocrinology-journals.org/content/19/3/389.long)
from the original on 2017-09-08.
18. Pomerantz JM (2010)."Hyperparathyroidism Resulting From Lithium T reatment Remains Underrecognized"(http://d
bt.consultantlive.com/display/article/1145628/1544855)
. Drug Benefit Trends. 22: 62–63. Archived (https://web.archiv
e.org/web/20100701080610/http://dbt.consultantlive.com/display/article/1145628/1544855) from the original on
2010-07-01.
19. Zink AR, Panzer S, Fesq-Martin M, Burger-Heinrich E, W ahl 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. doi:10.1210/er.22.4.477 (https://doi.org/10.1210%2Fer.22.4.477).
PMID 11493580 (https://www.ncbi.nlm.nih.gov/pubmed/11493580).
20. Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med. 2004 Apr
22;350(17):1746-51
21. "Archived copy" (http://pi.amgen.com/united_states/sensipar/sensipar_pi_hcp_english.pdf)
(PDF). Archived (https://
web.archive.org/web/20141005071147/http://pi.amgen.com/united_states/sensipar/sensipar_pi_hcp_english.pdf)
(PDF) from the original on 2014-10-05. Retrieved 2014-10-29.
22. Ott, SM (April 1998). "Calcimimetics–new drugs with the potential to control hyperparathyroidism" (http://jcem.endojo
urnals.org/cgi/content/full/83/4/1080). J. Clin. Endocrinol. Metab. 83 (4): 1080–2. doi:10.1210/jc.83.4.1080 (https://do
i.org/10.1210%2Fjc.83.4.1080). PMID 9543121 (https://www.ncbi.nlm.nih.gov/pubmed/9543121).
23. 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. doi:10.1002/14651858.CD006254.pub2(https://doi.org/10.1002%2F14651858.CD006254.pub2) .
PMID 25490118 (https://www.ncbi.nlm.nih.gov/pubmed/25490118).
24. 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. doi:10.1001/jama.293.1.40-c(https://doi.org/10.1001%2
Fjama.293.1.40-c). PMID 15632333 (https://www.ncbi.nlm.nih.gov/pubmed/15632333).

External links
Classification ICD-10: E21 · V · T · D
ICD-9-CM: 252.0 ·
Hyperparathyroidism at Curlie (based on DMOZ)
Overview at Endocrine and Metabolic Diseases Information Service
MeSH: D006961 ·
DiseasesDB: 20710
External MedlinePlus:
resources 001215 · eMedicine:
emerg/265
med/3200 · Patient
UK:
Hyperparathyroidism

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