Editing Hyperparathyroidism (section)

=== Regulation of PTH ===
Rapid PTH regulation is controlled by the parathyroid [[G protein-coupled receptor|G-protein coupled]], [[Calcium-sensing receptor|calcium sensing receptors]] which responds to fluctuations in serum calcium levels.<ref>{{cite journal |last1=Brown |first1=Edward M. |last2=MacLeod |first2=R. John |title=Extracellular Calcium Sensing and Extracellular Calcium Signaling |journal=Physiological Reviews |date=2001 |volume=81 |issue=1 |pages=239–297 |doi=10.1152/physrev.2001.81.1.239 |pmid=11152759 }}</ref> Alternatively, prolonged changes in serum calcium influences mRNA-binding proteins altering the encoding of PTH mRNA.<ref name=":0">{{Cite journal |last1=Kumar |first1=Rajiv |last2=Thompson |first2=James R. |date=February 2011 |title=The Regulation of Parathyroid Hormone Secretion and Synthesis |journal=Journal of the American Society of Nephrology |language=en |volume=22 |issue=2 |pages=216–224 |doi=10.1681/ASN.2010020186 |pmid=21164021 |pmc=5546216 }}</ref> There are also calcium independent mechanisms which include repression of PTH transcription through [[1,25-dihydroxyvitamin D|1α,25-dihydroxyvitamin D]] binding with the [[vitamin D receptor]].<ref name=":0" /> Furthermore, 1α,25-dihydroxyvitamin D also has an impact on the expression of calcium-sensing receptors, indirectly affecting PTH secretion.<ref name=":0" />

'''Effects of PTH on the Bones'''

PTH stimulates the bones to release calcium through multiple mechanisms. 1) PTH stimulates [[osteoblast]]s which increase expression of [[RANKL]] which causes differentiation of the osteoblasts into [[osteocyte]]s.<ref name=":1">{{Cite journal |last1=Silva |first1=Barbara C |last2=Bilezikian |first2=John P |date=June 2015 |title=Parathyroid hormone: anabolic and catabolic actions on the skeleton |journal=Current Opinion in Pharmacology |language=en |volume=22 |pages=41–50 |doi=10.1016/j.coph.2015.03.005|pmid=25854704 |pmc=5407089 }}</ref> 2) PTH inhibits secretion of [[osteoprotegerin]]a to allow for [[osteoclast]] differentiation.<ref name=":1" /> 3) PTH will also directly activate osteoclasts to cause bone resorption through degradation of [[hydroxyapatite]] and organic material.<ref name=":1" /> This then causes bone to release calcium into the blood.
[[File:Michelle Karam Parathyroid (2).svg|thumb|Effects of PTH bone resorption]]
'''Effects of PTH on the Kidneys'''

Calcium reabsorption in the nephron occurs in [[proximal convoluted tubule]] and at the [[Ascending limb of loop of Henle|ascending Loop of Henle]].<ref name=":3">{{Cite journal |last1=Arnaud |first1=C D |last2=Tenenhouse |first2=A M |last3=Rasmussen |first3=H |date=March 1967 |title=Parathyroid Hormone |journal=Annual Review of Physiology |volume=29 |issue=1 |pages=349–372 |doi=10.1146/annurev.ph.29.030167.002025 |pmid=5335437 }}</ref> PTH acts on the [[distal convoluted tubule]] and [[Collecting duct system|collecting duct]] to increase calcium reabsorption in the [[nephron]].<ref name=":3"/> PTH also acts on the proximal convoluted tubule to decrease [[phosphate]] reabsorption to lower the serum phosphate.<ref name=":3"/> This decreases formation of insoluble calcium phosphate salts leading to an increase in serum ionized calcium.

'''Effects of PTH on the Small Intestines'''

PTH stimulates the production of [[1-alpha-hydroxylase]] in the proximal convoluted tubule.<ref name=":3"/> This enzyme activation hydroxylates inactive [[25-hydroxycholecalciferol]] to active vitamin D [[125-Dihydroxycholecalciferol|(1, 25 dihydroxycholecalciferol]]).<ref name=":3" /> Active vitamin D allows for calcium absorption through [[Transcellular transport|transcellular]] and [[Paracellular transport|paracellular]] pathways.<ref name=":3" />

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 [[Calcitriol|1,25 dihydroxyvitamin D<sub>3</sub>]] levels in the blood are low and [[hypocalcemia]] is present. A lack of 1,25 dihydroxyvitamin D<sub>3</sub> can result from a deficient dietary intake of [[vitamin D]], or from a lack of exposure of the skin to sunlight, so the body cannot make its own vitamin D from cholesterol.<ref name="Stryer-1995">{{cite book | vauthors = Stryer L | title= Biochemistry. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |page= 707|isbn= 0-7167-2009-4 }}</ref> The resulting [[hypovitaminosis D]] is usually due to a partial combination of both factors. Vitamin D<sub>3</sub> (or [[cholecalciferol]]) is converted to 25-hydroxyvitamin D (or [[calcidiol]]) by the liver, from where it is transported via the circulation to the kidneys, and it is converted into the active hormone, 1,25 dihydroxyvitamin D<sub>3</sub>.<ref name="Blaine-2015" /><ref name="Stryer-1995" /> Thus, a third cause of secondary hyperparathyroidism is [[chronic kidney disease]]. Here the ability to manufacture 1,25 dihydroxyvitamin D<sub>3</sub> is compromised, resulting in hypocalcemia.{{citation needed|date=August 2020}}