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{{SK}}Autoimmune hypophysitis, lymphocytic hypophysitis


==Overview==
'''Hypophysitis''' is the inflammation of the [[pituitary gland]] that typically results in some degree of pituitary dysfunction, ranging from under secretion of some pituitary hormones to complete [[panhypopituitarism]] requiring lifelong hormone supplementation. While hypophysitis by itself is seldom life-threatening, the sequelae of pituitary inflammation, particularly [[adrenal insufficiency]] and [[severe hypothyroidism]], may be fatal if unrecognized and left untreated. There are several recognized causes of hypophysitis, including lymphocytic infiltration, granulomatous infiltration (e.g. in the setting of a systemic granulomatous disease such as [[sarcoidosis]] or [[granulomatosis with polyangiitis]]), and cell-mediated autoimmune reactivity in the setting of treatment of certain solid tumors with immunomodulatory [[checkpoint inhibitors]] (i.e. [[CTLA-4 inhibitors]] and [[PD-1 inhibitors]]). Although there are several different subtypes of hypophysitis, there are many commonalities in the diagnostic evaluation and treatment of this rare endocrinopathy.
==Historical Perspective==
The first documented case of hypophysitis occurred in a 22-year-old woman who died of circulatory collapse within 8 hours of appendectomy for gangrenous appendicitis in 1962. Autopsy was notable for an enlarged thyroid, grossly normal pituitary, and absent adrenal glands. Histologic examination of the thyroid was consistent with Hashimoto's thyroiditis, and microscopic examination of the pituitary revealed extensive lymphocytic infiltration of the anterior lobe. The authors of the case report posited an autoimmune etiology to the patient's apparent thyroid and pituitary dysfunction.<ref name="pmid13900798">{{cite journal| author=GOUDIE RB, PINKERTON PH| title=Anterior hypophysitis and Hashimoto's disease in a young woman. | journal=J Pathol Bacteriol | year= 1962 | volume= 83 | issue=  | pages= 584-5 | pmid=13900798 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13900798  }} </ref>
==Classification==
== Pathophysiology==
=== Genetics ===
=== Associated Conditions===
===Gross Pathology===
===Microscopic Pathology===
==Causes==
===Life Threatening Causes===
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
===Common Causes===
===Causes by Organ System===
{| style="width:80%; height:100px" border="1"
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" | '''Cardiovascular'''
| style="width:75%" bgcolor="Beige" ; border="1" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Opthalmologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| bgcolor="Beige" | No underlying causes
|-
|}
===Causes in Alphabetical Order===
*A...
*Z...
Make sure that each diagnosis is linked to a page.
==Differentiating Hypophysitis From Other Diseases==
[[Hypophysitis]] should be differentiated from other [[diseases]] causing severe [[headache]] for example: <ref>{{Cite journal
| author = [[Endrit Ziu]] & [[Fassil Mesfin]]
| title = Subarachnoid Hemorrhage
| year = 2017
| pmid = 28722987
}}</ref><ref>{{Cite journal
| author = [[Benedikt Schwermer]], [[Daniel Eschle]] & [[Constantine Bloch-Infanger]]
| title = &#91;Fever and Headache after a Vacation in Thailand&#93;
| journal = [[Deutsche medizinische Wochenschrift (1946)]]
| volume = 142
| issue = 14
| pages = 1063–1066
| year = 2017
| doi = 10.1055/s-0043-106282
| pmid = 28728201
}}</ref><ref>{{Cite journal
| author = [[Otto Rapalino]] & [[Mark E. Mullins]]
| title = Intracranial Infectious and Inflammatory Diseases Presenting as Neurosurgical Pathologies
| journal = [[Neurosurgery]]
| year = 2017
| doi = 10.1093/neuros/nyx201
| pmid = 28575459
}}</ref><ref>{{Cite journal
| author = [[I. B. Komarova]], [[V. P. Zykov]], [[L. V. Ushakova]], [[E. K. Nazarova]], [[E. B. Novikova]], [[O. V. Shuleshko]] & [[M. G. Samigulina]]
| title = &#91;Clinical and neuroimaging signs of cardioembolic stroke laboratory in children&#93;
| journal = [[Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova]]
| volume = 117
| issue = 3. Vyp. 2
| pages = 11–19
| year = 2017
| doi = 10.17116/jnevro20171173211-19
| pmid = 28665364
}}</ref><ref>{{Cite journal
| author = [[Sanjay Konakondla]], [[Clemens M. Schirmer]], [[Fengwu Li]], [[Xiaogun Geng]] & [[Yuchuan Ding]]
| title = New Developments in the Pathophysiology, Workup, and Diagnosis of Dural Venous Sinus Thrombosis (DVST) and a Systematic Review of Endovascular Treatments
| journal = [[Aging and disease]]
| volume = 8
| issue = 2
| pages = 136–148
| year = 2017
| doi = 10.14336/AD.2016.0915
| pmid = 28400981
}}</ref><ref>{{Cite journal
| author = [[Priyanka Yadav]], [[Alec L. Bradley]] & [[Jonathan H. Smith]]
| title = Recognition of Chronic Migraine by Medicine Trainees: A Cross-Sectional Survey
| journal = [[Headache]]
| year = 2017
| doi = 10.1111/head.13133
| pmid = 28653369
}}</ref><ref>{{Cite journal
| author = [[S. Wulffeld]], [[L. S. Rasmussen]], [[B. Hojlund Bech]] & [[J. Steinmetz]]
| title = The effect of CT scanners in the trauma room - an observational study
| journal = [[Acta anaesthesiologica Scandinavica]]
| volume = 61
| issue = 7
| pages = 832–840
| year = 2017
| doi = 10.1111/aas.12927
| pmid = 28635146
}}</ref><ref>{{cite journal |vauthors=Johnston PC, Chew LS, Hamrahian AH, Kennedy L |title=Lymphocytic infundibulo-neurohypophysitis: a clinical overview |journal=Endocrine |volume=50 |issue=3 |pages=531–6 |year=2015 |pmid=26219407 |doi=10.1007/s12020-015-0707-6 |url=}}</ref><ref>{{cite journal |vauthors=Makale MT, McDonald CR, Hattangadi-Gluth JA, Kesari S |title=Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours |journal=Nat Rev Neurol |volume=13 |issue=1 |pages=52–64 |year=2017 |pmid=27982041 |doi=10.1038/nrneurol.2016.185 |url=}}</ref><ref name="pmid9541295">{{cite journal| author=Sato N, Sze G, Endo K| title=Hypophysitis: endocrinologic and dynamic MR findings. | journal=AJNR Am J Neuroradiol | year= 1998 | volume= 19 | issue= 3 | pages= 439-44 | pmid=9541295 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9541295  }} </ref>
{| class="wikitable"
! rowspan="3" |Disease
! colspan="3" |Symptoms
! rowspan="3" |Gold Standard
! rowspan="3" |CT/MRI
! rowspan="3" |Other Investigation Findings
|-
! colspan="2" |'''Headache'''
! rowspan="2" |Other features
|-
!Onset
!Characterstics
|-
|[[Subarachnoid hemorrhage]]
|Sudden
|
* [[Headache|Severe headache]]
* <nowiki/>[[Thunderclap headache|Thunderclap]]
* Described as the worst headache of life
|
* [[Double vision]]
* [[Nausea]] and [[vomiting]]
* Symptoms of [[meningeal irritation]]
* Sudden [[Loss of consciousness|decreased level of consciousness]]
|[[Digital subtraction angiography]]
|
* The modality of choice for diagnosis of [[subarachnoid hemorrhage]] is noncontrast head [[Computed tomography|computed tomography (CT)]], with or without [[lumbar puncture]].<sup>[[Subarachnoid hemorrhage CT#cite note-pmid7897421-1|[1]]]</sup>
* [[Computed tomography|CT]] shows hyperattenuating material filling the subarachnoid space.
|
* [[Lumbar puncture|Lumbar puncture (LP)]] is necessary when there is a strong suspicion of [[subarachnoid hemorrhage]]. LP will show:
** Elevated opening pressure
** Elevated [[Red blood cell|red blood cell (RBC)]]
** [[Xanthochromic|Xanthochromia]]
|-
|[[Meningitis]]
|Sudden
|[[Headache]] is associated with:
* [[Fever]]
* [[Neck stiffness]]
|
* [[Photophobia]]   
* [[Phonophobia]] 
* [[Irritability]]
* [[Altered mental status]]
|[[Lumbar puncture]] for [[CSF]]
|
* [[CT]] scan of the head may be performed before [[Lumbar puncture|LP]] to determine the risk of [[herniation]].
|
* Diagnosis is based on clinical presentation in combination with [[CSF]] analysis.
* [[CSF]] analysis is the investigation of choice.
* For more information on [[CSF]] analysis in meningitis please [[Meningitis#Diagnosis|click here.]]
|-
|[[Intracranial mass]]
|Gradual
|[[Morning headache]]
|
* [[Nausea]]
* [[Vomiting]]
* [[Change in mental status]]
* [[Seizures]]
* Focal neurological deficits
|[[MRI]]
|
* [[CT]] or [[MRI]] is the initial test to detect intracranial lesions (ring enhancing lesions).
* These imaging tests determine the location of [[intracranial mass]] lesion(s) and help in guiding [[therapy]].
|
* [[Biopsy]] of the lesion may be done to identify the nature of the lesion such as:
** [[Tumor]]
** [[Abscess]]
* X- ray of the skull is a non specific test, but useful if any of the lesions are [[Calcified lesion|calcified]].
|-
|[[Cerebral hemorrhage]]
|Sudden
|Rapidly progressing headache
|
* Symptoms of [[increased intracranial pressure]] (ICP)
* Focal neurological deficits
|[[CT]] without [[Contrast medium|contrast]]
(differentiate [[ischemic stroke]] from [[hemorrhagic stroke|hemorrhagic stroke.]])
|
* [[CT]] is very sensitive for identifying acute [[hemorrhage]] which appears as hyperattenuating clot.
* Gradient echo and T2 susceptibility-weighted [[MRI]] are as sensitive as [[CT]] for detection of acute hemorrhage and are more sensitive for identification of prior hemorrhage.
|
* [[PT]]/ [[INR]] and [[aPTT]] should be checked to rule out [[coagulopathy]].
|-
|[[Intracranial venous thrombosis]]
|Gradual
|
* Diffuse [[headache]]
* [[Headache]] can be the only symptom of [[Cerebral venous sinus thrombosis|cerebral venous thrombosis]]
|
* Focal neurological deficits
* [[Seizure|Seizures]]
* [[Coma|Depressed level of consciousness]] 
|[[Digital subtraction angiography]]
|
* The classic finding of sinus thrombosis on unenhanced [[CT]] images is a hyperattenuating thrombus in the occluded sinus.
* [[CT]] and [[MRI]] may identify [[Cerebral edema]] and venous [[infarction]] may be apparent.
|
* CT [[venography]] detects the [[thrombus]], [[computed tomography]] with [[radiocontrast]] in the venous phase (CT venography or CTV) has a detection rate that in some regards exceeds that of [[MRI]].
* [[Cerebral angiography]] may demonstrate smaller clots, and obstructed veins may give the "corkscrew appearance".
|-
|[[Migraine]]
|Sudden
|
* Severe to moderate [[headache]]
* One-sided
* Pulsating
* Lasts between several hours to three days.
|
* [[Nausea and vomiting]]
* Preceding [[Aura (symptom)|aura]]
* [[Photophobia]]
* [[Phonophobia]]
|'''---'''
|
* [[CT]] and [[MRI]] may be needed to rule out other suspected possible causes of [[headache]].
|[[Migraine]] is a clinical [[diagnosis]] that does not require any laboratory tests. Laboratory tests can be ordered to rule out any suspected coexistent metabolic problems or to determine the baseline status of the patient before initiation of [[migraine]] therapy.
|-
|[[Head injury]]
|Sudden
|
* Dull
* Throbbing
* One sided or all around
|
* [[Confusion]]
* [[Drowsiness]]
* Personality change
* [[Seizure|Seizures]]
* [[Nausea]] and [[vomiting]]
* [[Headache|Loss of consciousness]]
* [[Lucid interval]]
|[[CT]] scan without contrast
|
* [[CT]] scan is the first test performed and identifies [[cerebral hemorrhage]] (appears as hyperattenuating clot) following head injury.
* [[MRI]] is more sensitive, takes more time and is done in patients with symptoms unexplained by [[Computed tomography|CT]] scan.
|
* The [[Glasgow Coma Scale]] is a tool for measuring degree of unconsciousness and is a useful tool for determining severity of injury.
* The [[Pediatric Glasgow Coma Scale]] is used in young children.
|-
|[[Lymphocytic hypophysitis]]
|Sudden
|
* Generalized
* Retro-orbital or Bitemporal
|
* Most often seen in late pregnancy or the [[postpartum]] period
* Mass lesion effect such as [[Visual field defect|visual field defects]]
* [[Hypopituitarism]]
|Pituitary biopsy
|
* [[CT]] & [[MRI]] typically reveal features of a pituitary mass.
|
* The most accurate test is pituitary [[biopsy]] which will show [[lymphocytic]] [[Infiltration (medical)|infiltration]].
|}
[[Hypophysitis]] should be differentiated from other [[diseases]] causing [[hypopituitarism]].<ref name="pmid9541295">{{cite journal |vauthors=Sato N, Sze G, Endo K |title=Hypophysitis: endocrinologic and dynamic MR findings |journal=AJNR Am J Neuroradiol |volume=19 |issue=3 |pages=439–44 |year=1998 |pmid=9541295 |doi= |url=}}</ref><ref name="pmid7758238">{{cite journal |vauthors=Powrie JK, Powell M, Ayers AB, Lowy C, Sönksen PH |title=Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature |journal=Clin. Endocrinol. (Oxf) |volume=42 |issue=3 |pages=315–22 |year=1995 |pmid=7758238 |doi= |url=}}</ref><ref name="pmid26262437">{{cite journal |vauthors=Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, Strasburger C, Störmann S, Küppers A, Streetz-van der Werf C, Deutschbein T, Stieg M, Rotermund R, Milian M, Petersenn S |title=Diagnosis of Primary Hypophysitis in Germany |journal=J. Clin. Endocrinol. Metab. |volume=100 |issue=10 |pages=3841–9 |year=2015 |pmid=26262437 |doi=10.1210/jc.2015-2152 |url=}}</ref><ref name="pmid7629223">{{cite journal |vauthors=Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S |title=Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue=8 |pages=2302–11 |year=1995 |pmid=7629223 |doi=10.1210/jcem.80.8.7629223 |url=}}</ref><ref name="pmid8345854">{{cite journal |vauthors=Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H |title=Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus |journal=N. Engl. J. Med. |volume=329 |issue=10 |pages=683–9 |year=1993 |pmid=8345854 |doi=10.1056/NEJM199309023291002 |url=}}</ref><ref name="pmid21668725">{{cite journal |vauthors=Hsieh CY, Liu BY, Yang YN, Yin WH, Young MS |title=Massive pericardial effusion with diastolic right ventricular compression secondary to hypothyroidism in a 73-year-old woman |journal=Emerg Med Australas |volume=23 |issue=3 |pages=372–5 |year=2011 |pmid=21668725 |doi=10.1111/j.1742-6723.2011.01425.x |url=}}</ref><ref name="pmid9747750">{{cite journal |vauthors=Dejager S, Gerber S, Foubert L, Turpin G |title=Sheehan's syndrome: differential diagnosis in the acute phase |journal=J. Intern. Med. |volume=244 |issue=3 |pages=261–6 |year=1998 |pmid=9747750 |doi= |url=}}</ref>
<small>
{| class="wikitable"
! rowspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diseases}}
! rowspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Onset}}
! colspan="5" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Manifestations}}
! colspan="4" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnosis}}
|-
! colspan="4" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|History and Symptoms}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Physical examination}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Laboratory findings}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Gold standard}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Imaging}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Other investigation findings}}
|-
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Trumatic delivery}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Lactation failure}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Menstrual irregularities}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Other features}}
|-
![[Sheehan's syndrome]]
|Acute
|<nowiki>++</nowiki>
| ++
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|Symptoms of:
* [[Adrenal insufficiency]]
* [[Hypothyroidism]]
|
* [[Breast tissue]] [[atrophy]]
* Decreased [[axillary]] and [[pubic]] hair growth
|
* [[Pancytopenia]]
* [[Eosinophilia]]
* [[Hyponatremia]]
* Low [[fasting plasma glucose]]
* Decreased levels of [[anterior pituitary]] [[hormones]] in blood
|
* Clinical diagnosis 
* Most senitive test: Low baseline [[prolactin]] levels w/o response to [[Thyrotropin-releasing hormone|TRH]]
|CT/MRI:
* Sequential changes of pituitary enlargement followed by:
* Shrinkage and [[necrosis]] leading to decreased sellar volume or [[empty sella]]
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
![[Lymphocytic hypophysitis]]
|Acute
|<nowiki>+/-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* Associated with [[autoimmune]] conditions
* Generalized [[headache]]
* Retro-orbital or Bitemporal [[pain]]
* Mass lesion effect such as [[Visual field defect|visual field defects]]
|
* [[Diabetes insipidus|DI]]
* [[Autoimmune]] [[thyroiditis]]
|
* Decreased pituitary hormones([[Gonadotropins]] most common)
* [[Hyperprolactinemia]](40%)
* [[Growth hormone|GH]] excess
|
* [[Pituitary gland|Pituitary]] [[biopsy]]: [[lymphocytic]] [[Infiltration (medical)|infiltration]]
|
* [[CT]] & [[MRI]]: Features of a [[Pituitary gland|pituitary]] [[mass]]
* Diffuse and homogeneous contrast enhancement
|[[Assay|Assays]] for:
* Anti-TPO 
* Anti-Tg Ab
|-
![[Pituitary apoplexy]]
|Acute
|<nowiki>+/-</nowiki>
|<nowiki>++</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|Severe [[headache]]
* [[Nausea and vomiting]]
* Paralysis of eye muscles ([[diplopia]])
* Changes in vision
|
* [[Visual acuity]] defects
* [[Cranial nerve palsies|CN palsies]] (nerves III, IV, V , and VI)
|
* Decreased levels of [[anterior]] pituitary hormones in blood.
|
* [[Magnetic resonance imaging|MRI]]
|
* [[CT]] scan without [[Contrast medium|contrast]]: Hemorrhag<nowiki/>e on [[CT]] presents as a hyperdense lesion
* [[MRI]]: If inconclusive [[CT]]
|
[[Blood tests]] may be done to check:
* [[PT]]/[[INR]] and [[aPTT]]
* [[Pituitary gland|Pituitary]] [[hormonal]] assay
|-
![[Empty sella syndrome]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Erectile dysfunction]]
* [[Headache]]
* Low [[libido]]
|
* Signs of raised [[intracranial pressure]] may be present
* [[Nipple discharge|Nipple]] discharge
|
* Decreased levels of  pituitary hormones in blood.
|
* [[MRI]]
|
* [[Empty sella]] containing [[Cerebrospinal fluid|CSF]]
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
![[Simmond's Disease|Simmonds' disease]]/[[Pituitary]] [[cachexia]]
|Chronic
|<nowiki>+/-</nowiki>
| +
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Cachexia]]
* [[Premature aging|Premature]] aging
|
* Progressive [[emaciation]]
* Loss of body hair
|
* Decreased levels of anterior pituitary hormones in blood.
|
* [[Magnetic resonance imaging|MRI]]
|
* Done to rule out any pituitary cause
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
! [[Primary hypothyroidism|Hypothyroidism]]
|Chronic
|<nowiki>+/-</nowiki>
|<nowiki>-</nowiki>
|[[Oligomenorrhea]]/[[menorrhagia]]
|
* Cold intolerance
* [[Constipation]]
|
* Dry skin
* [[Bradycardia]]
* Hair loss
* [[Myxedema]]
* Delayed relaxation phase of deep [[Tendon reflex|tendon reflexes]]
|
* Low [[T3]],[[T4]]
* Normal/ low [[Thyroid-stimulating hormone|TSH]]
* Rest of pituitary hormone levels WNL
|
* [[TSH]] levels
|
* Done to rule out any pituitary cause
|
*Assays for anti-TPO and anti-Tg Ab
*FNA biopsy
|-
![[Hypogonadotropic hypogonadism]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Hot flushes]]
* Energy and mood changes
* Decreased [[libido]]
|
* [[Breast tissue]] [[atrophy]]
* Decreased [[maturation]] of [[vaginal]] [[mucosa]]
|
* Low [[estrogen]], [[testosterone]]
* High [[FSH]]/[[Luteinizing hormone|LH]]
|
* [[FSH]]
* [[Luteinizing hormone|LH]]
|
* Done to rule out any pituitary cause
|
* Genetic tests  ([[karyotype]])
* Measurement of total and free [[testosterone]] and [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] concentrations
|-
!Hypoprolactinemia
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
* [[Infertility]]
* Subfertiliy
|
* Puerperal agalactogenesis
|
* No workup is necessary
|
* Decreased prolactin levels
|
* Done to rule out any pituitary cause
|
* [[Prolactin]] assay in [[3rd trimester]]
* [[Luteinizing hormone|LH]], [[Follicle-stimulating hormone|FSH]]
* [[Thyrotropin]] and free [[thyroxine]]
|-
![[Panhypopituitarism]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Polyuria]]
* [[Polydipsia]]
* Features of [[hypothyroidism]] and [[hypoadrenalism]]
|
* [[Growth failure]]
* B/L [[hemianopsia]]
* [[Papilledema]]
|
* All pituitary hormones decreased
|
* [[Magnetic resonance imaging|MRI]]
|
* Done to rule out any pituitary cause
|
* Left hand and wrist [[radiograph]] for [[bone age]]
|-
![[Primary adrenal insufficiency]]/[[Addison's disease]]
|Chronic
|<nowiki>-</nowiki>
| -
|<nowiki>-</nowiki>
|
* [[Hypoglycemia]]
* [[Hypotension]]
|
* [[Dehydration]]
* [[Hyperpigmentation]]
* loss of [[pubic]] and [[axillary]] hair
|
* [[Hyponatremia]] with/without [[hyperkalemia]]
* [[Plasma renin activity]] to [[Aldosterone|aldosterone ratio]]
|
* Abdominal [[Computed tomography|CT]]
|
* Abdominal [[Computed tomography|CT]]
|
* Serum [[cortisol]] testing
* Serum [[ACTH]] testing
* Anti-adrenal [[Antibody|Ab]] testing
|-
![[Menopause]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+/-</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Hot flashes]]
* [[Insomnia]]
* [[Weight gain]] and [[bloating]]
* Mood changes
|
* [[Vaginal atrophy]]
* Loss of pelvic [[muscle tone]]
|
* ↑ [[FSH]]
* ↓ [[Estradiol]] and [[inhibin]]
|
* [[FSH]] > [[LH]]
|Normal
|
* [[Endometrial biopsy]]
|}
<small>
==References==
{{Reflist|2}}
{{reflist|2}}
[[Category:Needs content]]
[[Category:Emergency medicine]]
[[Category:Endocrinology]]
[[Category:Neurology]]
[[Category:Obstetrics]]
[[Category:Disease]]
{{WH}}
{{WS}}
== Epidemiology and Demographics ==
===Age===
===Gender===
===Race===
===Developed Countries===
===Developing Countries===
== Risk Factors ==
== Screening ==
== Natural History, Complications and Prognosis==
== Diagnosis ==
===Diagnostic Criteria===
If available, the diagnostic criteria are provided here.
===History===
A directed history should be obtained to ascertain
=== Symptoms ===
"Type symptom here" is pathognomonic of the "type disease name here".
"Type non specific symptoms" may be present.
===Past Medical History===
===Family History===
===Social History===
====Occupational====
====Alcohol====
The frequency and amount of alcohol consumption should be characterized.
====Drug Use====
====Smoking====
===Allergies===
=== Physical Examination ===
==== Appearance of the Patient ====
====Vital Signs====
====Skin====
====Head====
==== Eyes ====
==== Ear ====
====Nose====
====Mouth====
====Throat ====
==== Heart ====
==== Lungs ====
==== Abdomen ====
==== Extremities ====
==== Neurologic ====
====Genitals====
==== Other ====
=== Laboratory Findings ===
==== Electrolyte and Biomarker Studies ====
==== Electrocardiogram ====
==== Chest X Ray ====
====CT ====
==== MRI ====
==== Echocardiography or Ultrasound ====
==== Other Imaging Findings ====
=== Other Diagnostic Studies ===
== Treatment ==
=== Pharmacotherapy ===
==== Acute Pharmacotherapies ====
==== Chronic Pharmacotherapies ====
=== Surgery and Device Based Therapy ===
==== Indications for Surgery ====
==== Pre-Operative Assessment ====
==== Post-Operative Management ====
==== Transplantation ====
=== Primary Prevention ===
=== Secondary Prevention ===
=== Cost-Effectiveness of Therapy ===
=== Future or Investigational Therapies ===
==References==
{{Reflist|2}}
[[Category:Disease]]


'''Hypophysitis''' is the inflammation of the [[pituitary gland]].


{{Symptoms and signs}}     
{{Symptoms and signs}}     
      
      
[[Category:Signs and symptoms]]




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Latest revision as of 18:33, 14 September 2017

Hypophysitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords:Autoimmune hypophysitis, lymphocytic hypophysitis

Overview

Hypophysitis is the inflammation of the pituitary gland that typically results in some degree of pituitary dysfunction, ranging from under secretion of some pituitary hormones to complete panhypopituitarism requiring lifelong hormone supplementation. While hypophysitis by itself is seldom life-threatening, the sequelae of pituitary inflammation, particularly adrenal insufficiency and severe hypothyroidism, may be fatal if unrecognized and left untreated. There are several recognized causes of hypophysitis, including lymphocytic infiltration, granulomatous infiltration (e.g. in the setting of a systemic granulomatous disease such as sarcoidosis or granulomatosis with polyangiitis), and cell-mediated autoimmune reactivity in the setting of treatment of certain solid tumors with immunomodulatory checkpoint inhibitors (i.e. CTLA-4 inhibitors and PD-1 inhibitors). Although there are several different subtypes of hypophysitis, there are many commonalities in the diagnostic evaluation and treatment of this rare endocrinopathy.

Historical Perspective

The first documented case of hypophysitis occurred in a 22-year-old woman who died of circulatory collapse within 8 hours of appendectomy for gangrenous appendicitis in 1962. Autopsy was notable for an enlarged thyroid, grossly normal pituitary, and absent adrenal glands. Histologic examination of the thyroid was consistent with Hashimoto's thyroiditis, and microscopic examination of the pituitary revealed extensive lymphocytic infiltration of the anterior lobe. The authors of the case report posited an autoimmune etiology to the patient's apparent thyroid and pituitary dysfunction.[1]

Classification

Pathophysiology

Genetics

Associated Conditions

Gross Pathology

Microscopic Pathology

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Causes by Organ System

Cardiovascular No underlying causes
Chemical / poisoning No underlying causes
Dermatologic No underlying causes
Drug Side Effect No underlying causes
Ear Nose Throat No underlying causes
Endocrine No underlying causes
Environmental No underlying causes
Gastroenterologic No underlying causes
Genetic No underlying causes
Hematologic No underlying causes
Iatrogenic No underlying causes
Infectious Disease No underlying causes
Musculoskeletal / Ortho No underlying causes
Neurologic No underlying causes
Nutritional / Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic No underlying causes
Opthalmologic No underlying causes
Overdose / Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal / Electrolyte No underlying causes
Rheum / Immune / Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Dental No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

  • A...
  • Z...

Make sure that each diagnosis is linked to a page.

Differentiating Hypophysitis From Other Diseases

Hypophysitis should be differentiated from other diseases causing severe headache for example: [2][3][4][5][6][7][8][9][10][11]

Disease Symptoms Gold Standard CT/MRI Other Investigation Findings
Headache Other features
Onset Characterstics
Subarachnoid hemorrhage Sudden Digital subtraction angiography
Meningitis Sudden Headache is associated with: Lumbar puncture for CSF
  • CT scan of the head may be performed before LP to determine the risk of herniation.
  • Diagnosis is based on clinical presentation in combination with CSF analysis.
  • CSF analysis is the investigation of choice.
  • For more information on CSF analysis in meningitis please click here.
Intracranial mass Gradual Morning headache MRI
  • CT or MRI is the initial test to detect intracranial lesions (ring enhancing lesions).
  • These imaging tests determine the location of intracranial mass lesion(s) and help in guiding therapy.
  • Biopsy of the lesion may be done to identify the nature of the lesion such as:
  • X- ray of the skull is a non specific test, but useful if any of the lesions are calcified.
Cerebral hemorrhage Sudden Rapidly progressing headache
  • Focal neurological deficits
 CT without contrast

(differentiate ischemic stroke from hemorrhagic stroke.)

  • CT is very sensitive for identifying acute hemorrhage which appears as hyperattenuating clot.
  • Gradient echo and T2 susceptibility-weighted MRI are as sensitive as CT for detection of acute hemorrhage and are more sensitive for identification of prior hemorrhage.
Intracranial venous thrombosis Gradual Digital subtraction angiography
  • The classic finding of sinus thrombosis on unenhanced CT images is a hyperattenuating thrombus in the occluded sinus.
  • Cerebral angiography may demonstrate smaller clots, and obstructed veins may give the "corkscrew appearance".
Migraine Sudden
  • Severe to moderate headache
  • One-sided
  • Pulsating
  • Lasts between several hours to three days.
 ---
  • CT and MRI may be needed to rule out other suspected possible causes of headache.
 Migraine is a clinical diagnosis that does not require any laboratory tests. Laboratory tests can be ordered to rule out any suspected coexistent metabolic problems or to determine the baseline status of the patient before initiation of migraine therapy.
Head injury Sudden
  • Dull
  • Throbbing
  • One sided or all around
 CT scan without contrast
  • CT scan is the first test performed and identifies cerebral hemorrhage (appears as hyperattenuating clot) following head injury.
  • MRI is more sensitive, takes more time and is done in patients with symptoms unexplained by CT scan.
Lymphocytic hypophysitis Sudden
  • Generalized
  • Retro-orbital or Bitemporal
  • Most often seen in late pregnancy or the postpartum period
 Pituitary biopsy
  • CT & MRI typically reveal features of a pituitary mass.

Hypophysitis should be differentiated from other diseases causing hypopituitarism.[11][12][13][14][15][16][17]

Diseases Onset Manifestations Diagnosis
History and Symptoms Physical examination Laboratory findings Gold standard Imaging Other investigation findings
Trumatic delivery Lactation failure Menstrual irregularities Other features
Sheehan's syndrome Acute ++ ++ Oligo/amenorrhea Symptoms of:
  • Clinical diagnosis
  • Most senitive test: Low baseline prolactin levels w/o response to TRH
 CT/MRI:
  • Sequential changes of pituitary enlargement followed by:
  • Shrinkage and necrosis leading to decreased sellar volume or empty sella
Lymphocytic hypophysitis Acute +/- + Oligo/amenorrhea
  • Retro-orbital or Bitemporal pain
  • Diffuse and homogeneous contrast enhancement
 Assays for:
  • Anti-TPO
  • Anti-Tg Ab
Pituitary apoplexy Acute +/- ++ Oligo/amenorrhea Severe headache
  • Decreased levels of anterior pituitary hormones in blood.
  • CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion

Blood tests may be done to check:

Empty sella syndrome Chronic - + Oligo/amenorrhea
  • Decreased levels of pituitary hormones in blood.
Simmonds' disease/Pituitary cachexia Chronic +/- + Oligo/amenorrhea
  • Loss of body hair
  • Decreased levels of anterior pituitary hormones in blood.
  • Done to rule out any pituitary cause
Hypothyroidism Chronic +/- - Oligomenorrhea/menorrhagia
  • Dry skin
  • Hair loss
  • Normal/ low TSH
  • Rest of pituitary hormone levels WNL
  • Done to rule out any pituitary cause
  • Assays for anti-TPO and anti-Tg Ab
  • FNA biopsy
Hypogonadotropic hypogonadism Chronic - - Oligo/amenorrhea
  • Energy and mood changes
  • Done to rule out any pituitary cause
Hypoprolactinemia Chronic - + -
  • Puerperal agalactogenesis
  • No workup is necessary
  • Decreased prolactin levels
  • Done to rule out any pituitary cause
Panhypopituitarism Chronic - + Oligo/amenorrhea
  • All pituitary hormones decreased
  • Done to rule out any pituitary cause
Primary adrenal insufficiency/Addison's disease Chronic - - -
  • Abdominal CT
  • Abdominal CT
  • Anti-adrenal Ab testing
Menopause Chronic - +/- Oligo/amenorrhea Normal

References

  1. ↑ GOUDIE RB, PINKERTON PH (1962). "Anterior hypophysitis and Hashimoto's disease in a young woman". J Pathol Bacteriol. 83: 584–5. PMID 13900798.
  2. ↑ Endrit Ziu & Fassil Mesfin (2017). "Subarachnoid Hemorrhage". PMID 28722987.
  3. ↑ Benedikt Schwermer, Daniel Eschle & Constantine Bloch-Infanger (2017). "[Fever and Headache after a Vacation in Thailand]". Deutsche medizinische Wochenschrift (1946). 142 (14): 1063–1066. doi:10.1055/s-0043-106282. PMID 28728201.
  4. ↑ Otto Rapalino & Mark E. Mullins (2017). "Intracranial Infectious and Inflammatory Diseases Presenting as Neurosurgical Pathologies". Neurosurgery. doi:10.1093/neuros/nyx201. PMID 28575459.
  5. ↑ I. B. Komarova, V. P. Zykov, L. V. Ushakova, E. K. Nazarova, E. B. Novikova, O. V. Shuleshko & M. G. Samigulina (2017). "[Clinical and neuroimaging signs of cardioembolic stroke laboratory in children]". Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 117 (3. Vyp. 2): 11–19. doi:10.17116/jnevro20171173211-19. PMID 28665364.
  6. ↑ Sanjay Konakondla, Clemens M. Schirmer, Fengwu Li, Xiaogun Geng & Yuchuan Ding (2017). "New Developments in the Pathophysiology, Workup, and Diagnosis of Dural Venous Sinus Thrombosis (DVST) and a Systematic Review of Endovascular Treatments". Aging and disease. 8 (2): 136–148. doi:10.14336/AD.2016.0915. PMID 28400981.
  7. ↑ Priyanka Yadav, Alec L. Bradley & Jonathan H. Smith (2017). "Recognition of Chronic Migraine by Medicine Trainees: A Cross-Sectional Survey". Headache. doi:10.1111/head.13133. PMID 28653369.
  8. ↑ S. Wulffeld, L. S. Rasmussen, B. Hojlund Bech & J. Steinmetz (2017). "The effect of CT scanners in the trauma room - an observational study". Acta anaesthesiologica Scandinavica. 61 (7): 832–840. doi:10.1111/aas.12927. PMID 28635146.
  9. ↑ Johnston PC, Chew LS, Hamrahian AH, Kennedy L (2015). "Lymphocytic infundibulo-neurohypophysitis: a clinical overview". Endocrine. 50 (3): 531–6. doi:10.1007/s12020-015-0707-6. PMID 26219407.
  10. ↑ Makale MT, McDonald CR, Hattangadi-Gluth JA, Kesari S (2017). "Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours". Nat Rev Neurol. 13 (1): 52–64. doi:10.1038/nrneurol.2016.185. PMID 27982041.
  11. ↑ 11.0 11.1 Sato N, Sze G, Endo K (1998). "Hypophysitis: endocrinologic and dynamic MR findings". AJNR Am J Neuroradiol. 19 (3): 439–44. PMID 9541295.
  12. ↑ Powrie JK, Powell M, Ayers AB, Lowy C, Sönksen PH (1995). "Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature". Clin. Endocrinol. (Oxf). 42 (3): 315–22. PMID 7758238.
  13. ↑ Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, Strasburger C, Störmann S, Küppers A, Streetz-van der Werf C, Deutschbein T, Stieg M, Rotermund R, Milian M, Petersenn S (2015). "Diagnosis of Primary Hypophysitis in Germany". J. Clin. Endocrinol. Metab. 100 (10): 3841–9. doi:10.1210/jc.2015-2152. PMID 26262437.
  14. ↑ Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S (1995). "Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings". J. Clin. Endocrinol. Metab. 80 (8): 2302–11. doi:10.1210/jcem.80.8.7629223. PMID 7629223.
  15. ↑ Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H (1993). "Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus". N. Engl. J. Med. 329 (10): 683–9. doi:10.1056/NEJM199309023291002. PMID 8345854.
  16. ↑ Hsieh CY, Liu BY, Yang YN, Yin WH, Young MS (2011). "Massive pericardial effusion with diastolic right ventricular compression secondary to hypothyroidism in a 73-year-old woman". Emerg Med Australas. 23 (3): 372–5. doi:10.1111/j.1742-6723.2011.01425.x. PMID 21668725.
  17. ↑ Dejager S, Gerber S, Foubert L, Turpin G (1998). "Sheehan's syndrome: differential diagnosis in the acute phase". J. Intern. Med. 244 (3): 261–6. PMID 9747750.

Template:WH Template:WS

Epidemiology and Demographics

Age

Gender

Race

Developed Countries

Developing Countries

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

If available, the diagnostic criteria are provided here.

History

A directed history should be obtained to ascertain

Symptoms

"Type symptom here" is pathognomonic of the "type disease name here".

"Type non specific symptoms" may be present.

Past Medical History

Family History

Social History

Occupational

Alcohol

The frequency and amount of alcohol consumption should be characterized.

Drug Use

Smoking

Allergies

Physical Examination

Appearance of the Patient

Vital Signs

Skin

Head

Eyes

Ear

Nose

Mouth

Throat

Heart

Lungs

Abdomen

Extremities

Neurologic

Genitals

Other

Laboratory Findings

Electrolyte and Biomarker Studies

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Pharmacotherapy

Acute Pharmacotherapies

Chronic Pharmacotherapies

Surgery and Device Based Therapy

Indications for Surgery

Pre-Operative Assessment

Post-Operative Management

Transplantation

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

References


Template:Skin and subcutaneous tissue symptoms and signs Template:Nervous and musculoskeletal system symptoms and signs Template:Urinary system symptoms and signs Template:Cognition, perception, emotional state and behaviour symptoms and signs Template:Speech and voice symptoms and signs Template:General symptoms and signs



Template:WikiDoc Sources

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