Sheehan's syndrome pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==
===Background on [[pituitary gland]] [[blood]] supply===
===Background on pituitary gland blood supply===
*In order to understand the [[pathophysiology]] of Sheehan's syndrome, it is necessary to know the [[blood]] supply of the [[pituitary gland]], because Sheehan's syndrome occurs mainly by [[ischemia]] through different mechanisms such as compression or [[occlusion]] of blood supply to [[pituitary gland]].
*In order to understand the [[pathophysiology]] of Sheehan's syndrome, it is necessary to know the [[blood]] supply of the [[pituitary gland]], because Sheehan's syndrome occurs mainly by [[ischemia]] through different mechanisms such as compression or [[occlusion]] of blood supply to [[pituitary gland]].
*[[Pituitary gland]] is amongst the most vascularized [[tissues]] in the body that normally weighs about 0.5 g but gets doubled in size during pregnancy.<ref name="pmid8325288">{{cite journal |vauthors=Rolih CA, Ober KP |title=Pituitary apoplexy |journal=Endocrinol. Metab. Clin. North Am. |volume=22 |issue=2 |pages=291–302 |year=1993 |pmid=8325288 |doi= |url=}}</ref>  
*[[Pituitary gland]] is amongst the most vascularized [[tissues]] in the body that normally weighs about 0.5 g but gets doubled in size during pregnancy.<ref name="pmid8325288">{{cite journal |vauthors=Rolih CA, Ober KP |title=Pituitary apoplexy |journal=Endocrinol. Metab. Clin. North Am. |volume=22 |issue=2 |pages=291–302 |year=1993 |pmid=8325288 |doi= |url=}}</ref>  
*The [[pituitary gland]] is composed of two parts [[anterior]] ([[adenohypophysis]]) and [[posterior]] ([[neurohypophysis]]). Both parts are supplied by the [[carotid arteries]].
*The [[pituitary gland]] is composed of two parts [[anterior]] ([[adenohypophysis]]) and [[posterior]] ([[neurohypophysis]]). Both parts are supplied by the [[carotid arteries]].
[[Image: Gray1180.png|500 px|thumb|center|A pituitary gland anatomy By Henry Vandyke Carte - Via: Wikimedia.org<ref> Henry Gray (1918) Anatomy of the Human Body, Bartleby.com: Gray's Anatomy, Plate 721, Public Domain, <https://commons.wikimedia.org/w/index.php?curid=541543></ref>]]


=== [[Anterior pituitary gland|Anterior pituitary]] ([[Adenohypophysis]]) ===
=== Anterior pituitary (Adenohypophysis) ===
*[[Anterior pituitary gland|Anterior pituitary]] does not have a direct [[blood]] supply and is supplied by the [[hypophyseal portal system]].
*[[Anterior pituitary gland|Anterior pituitary]] does not have a direct [[blood]] supply and is supplied by the [[hypophyseal portal system]].
*The [[hypophyseal portal system]] is a [[Fenestration|fenestrated]] set of [[capillaries]] that allows rapid exchange of [[hormones]] between the [[hypothalamus]] and [[anterior pituitary]].
*The [[hypophyseal portal system]] is a [[Fenestration|fenestrated]] set of [[capillaries]] that allows rapid exchange of [[hormones]] between the [[hypothalamus]] and [[anterior pituitary]].
*Occlusion of the [[blood]] supply and other [[vascular]] abnormalities of the [[hypophyseal portal system]] may also cause [[complications]] with the exchange of [[hormones]] between the [[hypothalamus]] and the [[pituitary gland]] leading to [[hypopituitarism]].
*Occlusion of the [[blood]] supply and other [[vascular]] abnormalities of the [[hypophyseal portal system]] may also cause [[complications]] with the exchange of [[hormones]] between the [[hypothalamus]] and the [[pituitary gland]] leading to [[hypopituitarism]].


=== [[Posterior pituitary gland|Posterior pituitary]] ([[Neurohypophysis]]) ===
=== Posterior pituitary (Neurohypophysis) ===
*[[Posterior pituitary]] has its own [[blood]] supply via [[inferior hypophyseal artery]] and is less commonly affected as compared to [[anterior pituitary]].
*[[Posterior pituitary]] has its own [[blood]] supply via [[inferior hypophyseal artery]] and is less commonly affected as compared to [[anterior pituitary]].
*If [[posterior pituitary]] is affected, it can result in [[Neurohypophysis|neurohypophseal]] dysfunction and [[ischemic necrosis]] of [[thirst]] center leading to increased [[osmotic]] threshold for thirst onset.<ref name="pmid17468192">{{cite journal |vauthors=Atmaca H, Tanriverdi F, Gokce C, Unluhizarci K, Kelestimur F |title=Posterior pituitary function in Sheehan's syndrome |journal=Eur. J. Endocrinol. |volume=156 |issue=5 |pages=563–7 |year=2007 |pmid=17468192 |doi=10.1530/EJE-06-0727 |url=}}</ref>
*If [[posterior pituitary]] is affected, it can result in [[Neurohypophysis|neurohypophseal]] dysfunction and [[ischemic necrosis]] of [[thirst]] center leading to increased [[osmotic]] threshold for thirst onset.<ref name="pmid17468192">{{cite journal |vauthors=Atmaca H, Tanriverdi F, Gokce C, Unluhizarci K, Kelestimur F |title=Posterior pituitary function in Sheehan's syndrome |journal=Eur. J. Endocrinol. |volume=156 |issue=5 |pages=563–7 |year=2007 |pmid=17468192 |doi=10.1530/EJE-06-0727 |url=}}</ref>


===[[Hypothalamic]] and [[Pituitary gland|pituitary]] [[hormones]] with their action on the target [[glands]]===
===Hypothalamic and pituitary hormones with their action on the target glands===
{| class="wikitable"
{| class="wikitable"
!
!
![[Hypothalamic]] [[hormone]]
!Hypothalamic hormone
!Mode of action
!Mode of action
![[Pituitary gland|Pituitary]] hormone
!Pituitary hormone
or target [[Organ (anatomy)|organ]]
or target organ
!Action  
!Action  
|-
|-
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* [[Luteinizing hormone|Leutinizing hormone]]
* [[Luteinizing hormone|Leutinizing hormone]]
|
|
* Males: stimulates [[testosterone]] production and [[spermatogenesis]]
* Males: Stimulates [[testosterone]] production and [[spermatogenesis]]
* Female: stimulates [[estradiol]] and [[progesterone]] production, [[ovulation]] and [[folliculogenesis]]
* Female: Stimulates [[estradiol]] and [[progesterone]] production, [[ovulation]] and [[folliculogenesis]]
|-
|-
|[[Dopamine]]
|[[Dopamine]]
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|[[Vasopressin]]
|[[Vasopressin]]
|Stimulatory
|Stimulatory
|
|[[Kidney]]
|Stimulates free water reabsorption in the [[collecting ducts]]
|Stimulates free water reabsorption in the [[collecting ducts]]
|-
|-
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===Pathogenesis===
===Pathogenesis===
*Sheehan's syndrome occurs mainly due to [[ischemic necrosis]] of [[pituitary gland]] causing destruction of the [[pituitary gland]] cells that results in decreased production of one or more [[pituitary]] [[hormones]] depending upon the severity of damage.
*Sheehan's syndrome occurs mainly due to [[ischemic necrosis]] of [[pituitary gland]] causing destruction of the [[pituitary gland]] cells, that results in decreased production of one or more [[pituitary]] [[hormones]] depending upon the severity of damage.
*[[Sheehan's syndrome]] results in mild to severe pituitary dysfunction resulting in partial or [[panhypopituitarism]] such as [[Growth hormone|GH]], [[thyroid hormone]], [[glucocorticoid]], [[gonadotropins]] ([[LH]], [[FSH]]), and [[prolactin]] hormone deficiencies that manifest as a wide spectrum of presentation.<ref name="pmid8043090">{{cite journal |vauthors=Vance ML |title=Hypopituitarism |journal=N. Engl. J. Med. |volume=330 |issue=23 |pages=1651–62 |year=1994 |pmid=8043090 |doi=10.1056/NEJM199406093302306 |url=}}</ref>  
*Sheehan's syndrome results in mild to severe pituitary dysfunction which can lead to partial or [[panhypopituitarism]], such as [[Growth hormone|GH]], [[thyroid hormone]], [[glucocorticoid]], [[gonadotropins]] ([[LH]], [[FSH]]), and [[prolactin]] hormone deficiencies; that manifest as a wide spectrum of presentation.<ref name="pmid8043090">{{cite journal |vauthors=Vance ML |title=Hypopituitarism |journal=N. Engl. J. Med. |volume=330 |issue=23 |pages=1651–62 |year=1994 |pmid=8043090 |doi=10.1056/NEJM199406093302306 |url=}}</ref>  
*Usually, [[Growth hormone|GH]] levels decrease first before others.<ref name="pmid15237929">{{cite journal |vauthors=Keleştimur F |title=Sheehan's syndrome |journal=Pituitary |volume=6 |issue=4 |pages=181–8 |year=2003 |pmid=15237929 |doi= |url=}}</ref>
*Usually, [[Growth hormone|GH]] levels decreased first before others.<ref name="pmid15237929">{{cite journal |vauthors=Keleştimur F |title=Sheehan's syndrome |journal=Pituitary |volume=6 |issue=4 |pages=181–8 |year=2003 |pmid=15237929 |doi= |url=}}</ref>Amongst all [[pituitary]] [[hormones]], the first and the most common [[hormonal]] deficiency seen in [[hypopituitarism]] is growth hormone deficiency followed by deficiencies of [[gonadotropins]] ([[FSH]], [[LH]]), [[TSH]], [[ACTH]] and [[Prolactin|prolactin.]]<ref name="pmid7955461">{{cite journal |vauthors=Toogood AA, Beardwell CG, Shalet SM |title=The severity of growth hormone deficiency in adults with pituitary disease is related to the degree of hypopituitarism |journal=Clin. Endocrinol. (Oxf) |volume=41 |issue=4 |pages=511–6 |year=1994 |pmid=7955461 |doi= |url=}}</ref><ref name="pmid10770165">{{cite journal |vauthors=Benvenga S, Campenní A, Ruggeri RM, Trimarchi F |title=Clinical review 113: Hypopituitarism secondary to head trauma |journal=J. Clin. Endocrinol. Metab. |volume=85 |issue=4 |pages=1353–61 |year=2000 |pmid=10770165 |doi=10.1210/jcem.85.4.6506 |url=}}</ref><ref name="pmid11059653">{{cite journal |vauthors=Kelly DF, Gonzalo IT, Cohan P, Berman N, Swerdloff R, Wang C |title=Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report |journal=J. Neurosurg. |volume=93 |issue=5 |pages=743–52 |year=2000 |pmid=11059653 |doi=10.3171/jns.2000.93.5.0743 |url=}}</ref>
====Compression of the [[blood vessels]]:====
====Compression of the blood vessels====
<br><br>
'''(a)  Pituitary gland enlargement'''
{{familytree/start}}
*[[Pituitary gland]] enlargement due to [[hypertrophy]] and [[hyperplasia]] of [[Lactotrophs|lactotrophic cells]] in [[anterior pituitary]] results in [[superior hypophyseal artery]] compression, which is complicated by decreased portal pressure and [[vasospasm]] during delivery, playing an important role in the [[pathogenesis]] of Sheehan's syndrome.<ref name="pmid2159093">{{cite journal |vauthors=Scheithauer BW, Sano T, Kovacs KT, Young WF, Ryan N, Randall RV |title=The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases |journal=Mayo Clin. Proc. |volume=65 |issue=4 |pages=461–74 |year=1990 |pmid=2159093 |doi= |url=}}</ref>
*[[Pituitary gland]] enlargement results in increasing its [[blood]] and [[oxygen]] demand, thus making it more susceptible to [[ischemia]] in a setting of massive [[hemorrhage]] during or after [[parturition]].
'''(b) Smaller size of sella'''
* Smaller and rigid [[sella]] may also be associated with compression of [[blood vessels]] supplying the [[pituitary]] resulting in compromised [[blood]] supply.
 
==== Vascular abnormalities causing vascular occlusion<ref name="pmid15237929">{{cite journal |vauthors=Keleştimur F |title=Sheehan's syndrome |journal=Pituitary |volume=6 |issue=4 |pages=181–8 |year=2003 |pmid=15237929 |doi= |url=}}</ref><ref name="McKayMerrill1953">{{cite journal|last1=McKay|first1=Donald G.|last2=Merrill|first2=Samuel J.|last3=Weiner|first3=Albert E.|last4=Hertig|first4=Arthur T.|last5=Reid|first5=Duncan E.|title=The pathologic anatomy of eclampsia, bilateral renal cortical necrosis, pituitary necrosis, and other acute fatal complications of pregnancy, and its possible relationship to the generalized Shwartzman phenomenon|journal=American Journal of Obstetrics and Gynecology|volume=66|issue=3|year=1953|pages=507–539|issn=00029378|doi=10.1016/0002-9378(53)90068-4}}</ref><ref>{{cite journal |last=Apitz |first=Kurt |date=September 1, 1935 |title=A Study of the Generalized Shwartzman Phenomenon|url=http://www.jimmunol.org/content/29/3/255.short|journal=The Journal of Immunology |volume=29 |issue=3 |pages=255-266}}</ref> ====
 
'''(a) Vasospasm'''
*[[Vasospasm]] due to severe [[Postpartum hemorrhage|postpartum hemorrhage (PPH)]] (loss of > 500 ml of blood during the first 24 hr), leading to [[hypotension]] and [[ischemic necrosis]] of [[pituitary gland]], is the most common cause of Sheehan's syndrome.<ref name="pmid15237929">{{cite journal |vauthors=Keleştimur F, Chow YW, Pietranico R, Mukerji A, Wiesmann UN, DiDonato S, Herschkowitz NN, Voigt WG, Johnson CR, Moroi K, Sato T, Keleştimur F, Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N, Wrightstone RN, Smith LL, Wilson JB, Vella F, Huisman TH, Marniemi J, Parkki MG, Ward CW, Stellwagen E, Babul J, Pogodina VV, Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N, Schmoldt A, Benthe HF, Haberland G, Lyons HA, Thomas JS, Heurich AE, Shepherd DA, Wetmore SD, Mekler LB, Sealey JE, White RP, Laragh JH, Rubin AL, Makar AB, McMartin KE, Palese M, Tephly TR, Frankle RT, Makar AB, McMartin KE, Palese M, Tephly TR, Makar AB, McMartin KE, Palese M, Tephly TR, Makar AB, McMartin KE, Palese M, Tephly TR, Makar AB, McMartin KE, Palese M, Tephly TR, Frankle RT, Thornton JA, Harrison MJ, Stellwagen E, Babul J, Leroy M, Loas G, Perez-Diaz F, Schmoldt A, Benthe HF, Haberland G, Coller BS, Franza BR, Gralnick HR |title=Sheehan's syndrome |journal=Pituitary |volume=6 |issue=4 |pages=181–8 |year=2003 |pmid=15237929 |doi=10.1210/jc.2001-020242 |url=}}</ref>
'''(b) Disseminated intravascular coagulation (DIC)'''
* [[Disseminated intravascular coagulation|DIC]] results in [[intravascular]] [[fibrin]] deposition leading to [[occlusion]] in [[hypophyseal portal system]], thus contributing to the [[ischemia]] of [[pituitary gland]] [[cells]].
* The pathophysiologic mechanism behind [[intravascular]] [[fibrin]] deposition is found to be similar to that of [[Shwartzman phenomenon|generalized Shwartzman reaction]].
 
==== Autoimmunity ====
*It is believed that [[Necrosis|tissue necrosis]] results in the release of sequestered [[antigens]], precipitating [[autoimmunity]] of the [[pituitary gland]] and [[hypopituitarism]] in [[Sheehan's syndrome]].<ref name="pmid12213861">{{cite journal |vauthors=Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N |title=Pituitary autoimmunity in patients with Sheehan's syndrome |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=9 |pages=4137–41 |year=2002 |pmid=12213861 |doi=10.1210/jc.2001-020242 |url=}}</ref><ref name="urlAUTOANTIBODIES IN SHEEHANS SYNDROME - ScienceDirect">{{cite web |url=http://www.sciencedirect.com/science/article/pii/S0140673665913619?via%3Dihub |title=AUTOANTIBODIES IN SHEEHAN'S SYNDROME - ScienceDirect |format= |work= |accessdate=}}</ref><ref name="pmid24434361">{{cite journal |vauthors=Falorni A, Minarelli V, Bartoloni E, Alunno A, Gerli R |title=Diagnosis and classification of autoimmune hypophysitis |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=412–6 |year=2014 |pmid=24434361 |doi=10.1016/j.autrev.2014.01.021 |url=}}</ref>
 
<br>{{familytree/start}}
{{familytree | | A01 | | | A02 | | | A03 | | | A04 | | | A05 | |A01=[[DIC]]<sup>‡</sup>|A02=Severe [[PPH]]<sup>†</sup>|A03=[[Glandular]] [[hypertrophy]] and [[hyperplasia]]|A04=Small [[sella]] size|A05=[[Autoimmunity]]}}
{{familytree | | A01 | | | A02 | | | A03 | | | A04 | | | A05 | |A01=[[DIC]]<sup>‡</sup>|A02=Severe [[PPH]]<sup>†</sup>|A03=[[Glandular]] [[hypertrophy]] and [[hyperplasia]]|A04=Small [[sella]] size|A05=[[Autoimmunity]]}}
{{familytree | | |!| | | | |!| | | | |!| | | | |!| | | | |!| | }}
{{familytree | | |!| | | | |!| | | | |!| | | | |!| | | | |!| | }}
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<br>
<br>
†[[Postpartum Hemorrhage|Postpartum hemorrhage (PPH)]] i.e., >500 ml after [[Vaginal|vaginal delivery]] or 1000 ml after [[C-section]].
†[[Postpartum Hemorrhage|Postpartum hemorrhage (PPH)]] i.e., >500 ml after [[Vaginal|vaginal delivery]] or 1000 ml after [[C-section]].
<br> </small></small>
<br></small></small>
*[[Pituitary gland]] enlargement due to [[hypertrophy]] and [[hyperplasia]] of [[Lactotrophs|lactotrophic cells]] in [[anterior pituitary]] result in [[superior hypophyseal artery]] compression which is complicated by decreased portal pressure and [[vasospasm]] during delivery, playing an important role in the [[pathogenesis]] of [[Sheehan syndrome|Sheehan's syndrome]].<ref name="pmid2159093">{{cite journal |vauthors=Scheithauer BW, Sano T, Kovacs KT, Young WF, Ryan N, Randall RV |title=The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases |journal=Mayo Clin. Proc. |volume=65 |issue=4 |pages=461–74 |year=1990 |pmid=2159093 |doi= |url=}}</ref>
*Apart from pituitary gland enlargement during and before [[parturition]], [[vasospasm]], [[Schwartzman reaction|generalized Schwartzman phenomenon]], [[thrombosis]] and compression of the hypophyseal arteries, [[autoimmunity]], [[DIC]], and smaller size of [[sella]] are understood to play a role in the [[pathogenesis]] of [[Sheehan syndrome|Sheehan's syndrome]].<ref name="pmid15237929">{{cite journal |vauthors=Keleştimur F |title=Sheehan's syndrome |journal=Pituitary |volume=6 |issue=4 |pages=181–8 |year=2003 |pmid=15237929 |doi= |url=}}</ref><ref name="McKayMerrill1953">{{cite journal|last1=McKay|first1=Donald G.|last2=Merrill|first2=Samuel J.|last3=Weiner|first3=Albert E.|last4=Hertig|first4=Arthur T.|last5=Reid|first5=Duncan E.|title=The pathologic anatomy of eclampsia, bilateral renal cortical necrosis, pituitary necrosis, and other acute fatal complications of pregnancy, and its possible relationship to the generalized Shwartzman phenomenon|journal=American Journal of Obstetrics and Gynecology|volume=66|issue=3|year=1953|pages=507–539|issn=00029378|doi=10.1016/0002-9378(53)90068-4}}</ref><ref>{{cite journal |last=Apitz |first=Kurt |date=September 1, 1935 |title=A Study of the Generalized Shwartzman Phenomenon|url=http://www.jimmunol.org/content/29/3/255.short|journal=The Journal of Immunology |volume=29 |issue=3 |pages=255-266}}</ref>
*It is believed that [[Necrosis|tissue necrosis]] results in release of sequestered [[antigens]], precipitating [[autoimmunity]] of the pituitary gland and [[hypopituitarism]] in [[Sheehan's syndrome]].<ref name="pmid12213861">{{cite journal |vauthors=Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N |title=Pituitary autoimmunity in patients with Sheehan's syndrome |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=9 |pages=4137–41 |year=2002 |pmid=12213861 |doi=10.1210/jc.2001-020242 |url=}}</ref><ref name="urlAUTOANTIBODIES IN SHEEHANS SYNDROME - ScienceDirect">{{cite web |url=http://www.sciencedirect.com/science/article/pii/S0140673665913619?via%3Dihub |title=AUTOANTIBODIES IN SHEEHAN'S SYNDROME - ScienceDirect |format= |work= |accessdate=}}</ref><ref name="pmid24434361">{{cite journal |vauthors=Falorni A, Minarelli V, Bartoloni E, Alunno A, Gerli R |title=Diagnosis and classification of autoimmune hypophysitis |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=412–6 |year=2014 |pmid=24434361 |doi=10.1016/j.autrev.2014.01.021 |url=}}</ref>
*Severe [[Postpartum hemorrhage|PPH]] (loss of >500ml of blood during the first 24hr) leading to [[hypotension]] and [[ischemic necrosis]] of [[pituitary gland]] is the most common cause of [[Sheehan's syndrome]].<ref name="pmid15237929">{{cite journal |vauthors=Keleştimur F, Chow YW, Pietranico R, Mukerji A, Wiesmann UN, DiDonato S, Herschkowitz NN, Voigt WG, Johnson CR, Moroi K, Sato T, Keleştimur F, Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N, Wrightstone RN, Smith LL, Wilson JB, Vella F, Huisman TH, Marniemi J, Parkki MG, Ward CW, Stellwagen E, Babul J, Pogodina VV, Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N, Schmoldt A, Benthe HF, Haberland G, Lyons HA, Thomas JS, Heurich AE, Shepherd DA, Wetmore SD, Mekler LB, Sealey JE, White RP, Laragh JH, Rubin AL, Makar AB, McMartin KE, Palese M, Tephly TR, Frankle RT, Makar AB, McMartin KE, Palese M, Tephly TR, Makar AB, McMartin KE, Palese M, Tephly TR, Makar AB, McMartin KE, Palese M, Tephly TR, Makar AB, McMartin KE, Palese M, Tephly TR, Frankle RT, Thornton JA, Harrison MJ, Stellwagen E, Babul J, Leroy M, Loas G, Perez-Diaz F, Schmoldt A, Benthe HF, Haberland G, Coller BS, Franza BR, Gralnick HR |title=Sheehan's syndrome |journal=Pituitary |volume=6 |issue=4 |pages=181–8 |year=2003 |pmid=15237929 |doi=10.1210/jc.2001-020242 |url=}}</ref>


==Genetics==
==Genetics==
There is no genetic association found to be associated with Sheehan's syndrome.
There is no [[genetic]] association found to be associated with Sheehan's syndrome.


==Associated Conditions==
==Associated Conditions==
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*[[Scarring]] of [[Paraventricular nucleus of hypothalamus|paraventricular]] and [[Supraoptic nucleus|supraoptic nuclei]]
*[[Scarring]] of [[Paraventricular nucleus of hypothalamus|paraventricular]] and [[Supraoptic nucleus|supraoptic nuclei]]


== Videos ==
{{#ev:https://youtube/_LGayYwSj50}}


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
 
​
{{WH}}
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[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Emergency medicine]]
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

It is thought that Sheehan's syndrome is the result of ischemic necrosis of pituitary gland, due to pituitary gland enlargement during parturition; precipitated by hypotension due to massive hemorrhage. Apart from pituitary gland enlargement during and before parturition, vasospasm, generalized Schwartzman phenomenon, thrombosis and compression of the hypophyseal arteries, autoimmunity, DIC, and smaller size of sella play a contributing role in pathogenesis of Sheehan syndrome. Occlusion and other vascular anomalies of the hypophyseal portal system can also complicate the exchange of hormones between the hypothalamus and the pituitary gland, leading to hypopituitarism. Sheehan's syndrome may result in mild to severe pituitary dysfunction (partial or panhypopituitarism), which is identified with growth hormone (GH), thyroid hormone, glucocorticoid, gonadotropins, and prolactin hormone deficiencies; manifests as a wide spectrum of presentation. Usually, GH deficiency is the earliest one to develop.

Pathophysiology

Background on pituitary gland blood supply

A pituitary gland anatomy By Henry Vandyke Carte - Via: Wikimedia.org[2]

Anterior pituitary (Adenohypophysis)

Posterior pituitary (Neurohypophysis)

Hypothalamic and pituitary hormones with their action on the target glands

Hypothalamic hormone Mode of action Pituitary hormone

or target organ

Action
Anterior pituitary hormones Thyrotropin-releasing hormone Stimulatory Thyrotropin Stimulates triiodothyronine and thyroxine production
Corticotropin-releasing hormone Stimulatory Corticotropin Stimulates production of cortisol and adrenal androgens
Stimulatory Prolactin Stimulates milk production from breasts in females
Gonadotropin-releasing hormone Stimulatory
Dopamine Inhibitory Prolactin _
Growth hormone-releasing hormone Stimulatory Growth hormone Stimulates insulin-like growth factor 1 production
Somatostatin Inhibitory Growth hormone _
Posterior pituitary hormones Vasopressin Stimulatory Kidney Stimulates free water reabsorption in the collecting ducts
Oxytocin Stimulatory Breast, uterus Stimulates milk ejection and uterine contraction

Pathogenesis

Compression of the blood vessels

(a) Pituitary gland enlargement

(b) Smaller size of sella

Vascular abnormalities causing vascular occlusion[5][10][11]

(a) Vasospasm

(b) Disseminated intravascular coagulation (DIC)

Autoimmunity


 
DIC‡
 
 
Severe PPH†
 
 
Glandular hypertrophy and hyperplasia
 
 
Small sella size
 
 
Autoimmunity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypotension/Shock
 
 
Pituitary enlargement
 
 
Pituitary compression
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood supply compression
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ischemic necrosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypopituitarism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amenorrhea
 
 
Agalactorrhea
 
 
 
Secondary adrenal insufficiency
 
 
Hypothyroidism
 


‡Disseminated intravascular coagulation (DIC) due to Amniotic fluid embolism or HELLP Syndrome.
†Postpartum hemorrhage (PPH) i.e., >500 ml after vaginal delivery or 1000 ml after C-section.

Genetics

There is no genetic association found to be associated with Sheehan's syndrome.

Associated Conditions

Sheehan's syndrome is associated with:[15]

Gross Pathology

Microscopic Pathology

On microscopy, the following findings may be observed:


References

  1. ↑ Rolih CA, Ober KP (1993). "Pituitary apoplexy". Endocrinol. Metab. Clin. North Am. 22 (2): 291–302. PMID 8325288.
  2. ↑ Henry Gray (1918) Anatomy of the Human Body, Bartleby.com: Gray's Anatomy, Plate 721, Public Domain, <https://commons.wikimedia.org/w/index.php?curid=541543>
  3. ↑ Atmaca H, Tanriverdi F, Gokce C, Unluhizarci K, Kelestimur F (2007). "Posterior pituitary function in Sheehan's syndrome". Eur. J. Endocrinol. 156 (5): 563–7. doi:10.1530/EJE-06-0727. PMID 17468192.
  4. ↑ Vance ML (1994). "Hypopituitarism". N. Engl. J. Med. 330 (23): 1651–62. doi:10.1056/NEJM199406093302306. PMID 8043090.
  5. ↑ 5.0 5.1 5.2 Keleştimur F (2003). "Sheehan's syndrome". Pituitary. 6 (4): 181–8. PMID 15237929.
  6. ↑ Toogood AA, Beardwell CG, Shalet SM (1994). "The severity of growth hormone deficiency in adults with pituitary disease is related to the degree of hypopituitarism". Clin. Endocrinol. (Oxf). 41 (4): 511–6. PMID 7955461.
  7. ↑ Benvenga S, Campenní A, Ruggeri RM, Trimarchi F (2000). "Clinical review 113: Hypopituitarism secondary to head trauma". J. Clin. Endocrinol. Metab. 85 (4): 1353–61. doi:10.1210/jcem.85.4.6506. PMID 10770165.
  8. ↑ Kelly DF, Gonzalo IT, Cohan P, Berman N, Swerdloff R, Wang C (2000). "Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report". J. Neurosurg. 93 (5): 743–52. doi:10.3171/jns.2000.93.5.0743. PMID 11059653.
  9. ↑ Scheithauer BW, Sano T, Kovacs KT, Young WF, Ryan N, Randall RV (1990). "The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases". Mayo Clin. Proc. 65 (4): 461–74. PMID 2159093.
  10. ↑ McKay, Donald G.; Merrill, Samuel J.; Weiner, Albert E.; Hertig, Arthur T.; Reid, Duncan E. (1953). "The pathologic anatomy of eclampsia, bilateral renal cortical necrosis, pituitary necrosis, and other acute fatal complications of pregnancy, and its possible relationship to the generalized Shwartzman phenomenon". American Journal of Obstetrics and Gynecology. 66 (3): 507–539. doi:10.1016/0002-9378(53)90068-4. ISSN 0002-9378.
  11. ↑ Apitz, Kurt (September 1, 1935). "A Study of the Generalized Shwartzman Phenomenon". The Journal of Immunology. 29 (3): 255–266.
  12. ↑ Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N (2002). "Pituitary autoimmunity in patients with Sheehan's syndrome". J. Clin. Endocrinol. Metab. 87 (9): 4137–41. doi:10.1210/jc.2001-020242. PMID 12213861.
  13. ↑ "AUTOANTIBODIES IN SHEEHAN'S SYNDROME - ScienceDirect".
  14. ↑ Falorni A, Minarelli V, Bartoloni E, Alunno A, Gerli R (2014). "Diagnosis and classification of autoimmune hypophysitis". Autoimmun Rev. 13 (4–5): 412–6. doi:10.1016/j.autrev.2014.01.021. PMID 24434361.
  15. ↑ Abourawi, F (2006). "Diabetes Mellitus and Pregnancy". Libyan Journal of Medicine. 1 (1): 28–41. doi:10.4176/060617. ISSN 1993-2820.

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