{{Short description|Inflammation of the pituitary gland due to autoimmune dysfunction}} {{cs1 config |display-authors=6 |name-list-style=vanc}} {{Use dmy dates|date=September 2025}} {{Infobox medical condition (new) | name = Autoimmune hypophysitis | synonyms = '''Lymphocytic hypophysitis''' | image = | caption = | pronounce = | field = endocrinology | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }}
'''Autoimmune hypophysitis''' is defined as inflammation of the pituitary gland due to autoimmunity.
==Signs and symptoms== Autoimmune hypophysitis can lead to deficiencies in one or more pituitary hormones, causing central diabetes insipidus if the posterior pituitary gland is affected as well as central adrenal insufficiency and central hypothyroidism if the anterior pituitary gland is affected.<ref name="Lymphocytic Hypophysitis">{{cite web |last1=Naran |first1=Jaya |last2=Can |first2=Ahmet S. |date=8 August 2023 |title=Lymphocytic Hypophysitis |url=https://www.ncbi.nlm.nih.gov/books/NBK562255/ |access-date=29 June 2024 |publisher=StatPearls Publishing |pmid=32965926}}</ref> The symptoms depend on what part of the pituitary is affected. Lymphocytic adenohypophysitis (LAH) occurs when the anterior pituitary cells are affected by autoimmune inflammation resulting in either no symptoms, adrenal insufficiency (if the ACTH producing cells are affected), hypothyroidism (if the TSH producing cells are damaged), or hypogonadism (if the LH and/or FSH producing cells are involved). In some cases, the presence of inflammation within the pituitary gland leads to interruption of dopamine flow from the hypothalamus into the pituitary causing high levels of the hormone prolactin and, often as a consequence, milk production from the breasts (in older girls and women). Lymphocytic Infundibuloneurohypophysitis (LINH) occurs when the posterior pituitary is affected resulting in diabetes insipidus. Both LAH and LINH may also lead to symptoms of an intracranial mass such as headache or disturbance of vision, i.e. bitemporal hemianopia. The pituitary produces multiple hormones relating to various metabolic functions. Sufficiently low production of certain pituitary hormones can be fatal resulting in the failure of the thyroid or adrenal glands.{{citation needed|date=August 2020}} Common symptoms include nausea, vomiting, fatigue, loss of libido, amenorrhea, and dizziness.<ref name="Lymphocytic Hypophysitis"/> It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms.<ref name="pmid9691980">{{cite journal |vauthors=Strömberg S, Crock P, Lernmark A, Hulting AL |year=1998 |title=Pituitary autoantibodies in patients with hypopituitarism and their relatives |journal=J. Endocrinol. |volume=157 |issue=3 |pages=475–80 |doi=10.1677/joe.0.1570475 |pmid=9691980 |doi-access=free}}</ref> However, there have been cases of isolated attacks as a result of drug reactions (i.e., use of blocking antibody ipilimumab)<ref name="pmid12826605">{{cite journal |vauthors=Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA |year=2003 |title=Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue=14 |pages=8372–7 |bibcode=2003PNAS..100.8372P |doi=10.1073/pnas.1533209100 |pmc=166236 |pmid=12826605 |doi-access=free}}</ref><ref>{{multiref |1={{cite journal |journal=Hepatitis Weekly, Autoimmune Diseases |title=Cytotoxic Antigen Induces Hypophysitis in Cancer Patients |date=9 January 2006}}{{full citation needed|date=September 2025}} |2={{cite journal |vauthors=Weston SN, Weston CF |date=January 2000 |title=The mysterious case of the lost pituitary: amiodarone-induced hypothyroidism |journal=Hosp Med |volume=61 |issue=1 |pages=64–5 |doi=10.12968/hosp.2000.61.1.1869 |pmid=10735160}}}}</ref> or idiopathic events that have presented symptoms which may disappear after relatively short term treatment (i.e., 1 year on corticoids or other immune suppressants).<ref name="pmid16230817">{{cite journal |vauthors=Minakshi B, Alok S, Hillol KP |year=2005 |title=Lymphocytic hypophysitis presenting as pituitary apoplexy in a male |journal=Neurol India |volume=53 |issue=3 |pages=363–4 |doi=10.4103/0028-3886.16948 |pmid=16230817 |doi-access=free}}</ref> However, more rapid development of the disorder is the rule when it occurs during, or shortly after, pregnancy (even after miscarriage or abortion). Indeed, autoimmune hypophysitis occurs more commonly during and shortly after pregnancy than at any other time.<ref>{{cite journal |last=Foyouzi |first=N |date=February 2011 |title=Lymphocytic adenohypophysitis. |journal=Obstetrical & Gynecological Survey |volume=66 |issue=2 |pages=109–13 |doi=10.1097/ogx.0b013e31821d4047 |pmid=21592417 |s2cid=30199333}}</ref>
===Antibodies=== 80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones.<ref name="pmid9691980"/> Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies.<ref name="pmid17554056"/> It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis. Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.<ref name="pmid9691980"/>
==Cause== {{Empty section|date=October 2021}} Most cases are autoimmune, some related to thyroid autoimmunity.
==Diagnosis== Lymphocytic hypophysitis continues to be a diagnosis of exclusion, and histopathology with tissue biopsy is needed for a definitive diagnosis.{{cn|date=September 2025}} However, clinical, laboratory data, and imaging can all help with the diagnosis.{{cn|date=September 2025}} First and foremost, patients present with symptoms of hypopituitarism and must undergo pituitary hormone function evaluation.<ref name="Lymphocytic Hypophysitis"/> Biopsy is the only means of accurate diagnosis as no autoantigen has been discovered.<ref name="pmid17554056"/><ref>{{cite journal |title=Pituitary autoantibodies |journal=Neuroendocrinology, Current Opinion in Endocrinology & Diabetes |volume=13 |issue=4 |pages=344–350 |date=August 2006 |doi=10.1097/01.med.0000235324.46788.47 | vauthors = Crock PA, Bensing S, Smith CJ, Burns C, Robinson PJ }}</ref> Biopsy of the pituitary gland is not easily performed with safety as it sits under the brain, however, a test does exist to detect antibodies to the pituitary without biopsy: autoantibodies to M(r) 49,000 pituitary cytosolic protein may represent markers for an immunological process affecting the pituitary gland.<ref name="pmid9691980"/> Tests for normal pituitary gland hormone production tend to be expensive and in some cases difficult to administer. In addition, certain hormone levels vary largely throughout the day and in response to metabolic factors, making abnormal levels difficult to calibrate—further hampering diagnosis.<ref>{{cite journal |vauthors=Soule SG, Fahie-Wilson M, Tomlinson S |date=February 1996 |title=Failure of the short ACTH test to unequivocally diagnose long-standing symptomatic secondary hypoadrenalism |journal=Clin. Endocrinol. |volume=44 |issue=2 |pages=137–40 |doi=10.1046/j.1365-2265.1996.540363.x |pmid=8849565 |s2cid=37708979}}</ref><ref>{{cite journal |vauthors=Maghnie M, Uga E, Temporini F, Di Iorgi N, Secco A, Tinelli C, Papalia A, Casini MR, Loche S |date=May 2005 |title=Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests |url=http://eje-online.org/cgi/pmidlookup?view=long&pmid=15879359 |journal=Eur. J. Endocrinol. |volume=152 |issue=5 |pages=735–741 |doi=10.1530/eje.1.01911 |pmid=15879359 |url-access=subscription |doi-access=free}}</ref><ref>{{cite web |last=Clayton |first=Richard |title=Evaluation of Patients With Pituitary/Hypothalamic Space Occupying Lesions |url=http://www.endotext.org/neuroendo/neuroendo11b/index.html |url-status=dead |archive-url=https://web.archive.org/web/20130225040342/http://www.endotext.org/neuroendo/neuroendo11b/index.html |archive-date=25 February 2013 |access-date=2 January 2013 |work=endotext.org}}</ref><ref>{{cite journal |vauthors=Maghnie M, Aimaretti G, Bellone S, Bona G, Bellone J, Baldelli R, de Sanctis C, Gargantini L, Gastaldi R, Ghizzoni L, Secco A, Tinelli C, Ghigo E |date=April 2005 |title=Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement |url=http://eje-online.org/cgi/pmidlookup?view=long&pmid=15817915 |journal=Eur. J. Endocrinol. |volume=152 |issue=4 |pages=589–96 |doi=10.1530/eje.1.01873 |pmid=15817915 |url-access=subscription |doi-access=free}} </ref><ref>{{cite journal |vauthors=Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou S, Kleinberg DL, Chipman JJ, Hartman ML |date=May 2002 |title=Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=5 |pages=2067–2079 |doi=10.1210/jcem.87.5.8509 |pmid=11994342 |doi-access=free}}</ref><ref>{{cite web |title=Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated With hGH |url=http://endocrine.niddk.nih.gov/pubs/creutz/alert.aspx |url-status=dead |archive-url=https://web.archive.org/web/20130127132216/http://endocrine.niddk.nih.gov/pubs/creutz/alert.aspx |archive-date=27 January 2013 |access-date=2 January 2013 |work=National Endocrine and Metabolic Diseases Information Service}}</ref> Assessment for other autoimmune and inflammatory diseases should also be performed by obtaining complete blood count, complete metabolic panel, c-reactive protein, erythrocyte sedimentation rate, antinuclear antibody, and lupus antibodies at the very least. Gadolinium-enhanced MRI of the pituitary is the imaging of choice as well, and it is important to distinguish lymphocytic hypophysitis from a pituitary adenoma.<ref name="Lymphocytic Hypophysitis"/>
==Treatment== Inflammation typically resolves after several months of glucocorticoid treatment{{citation needed|date=August 2020}} In patients unresponsive to, or have relapsing symptoms after corticosteroid treatment, immunosuppressive medications such as methotrexate, azathioprine, and cyclosporine are often prescribed. In particular, combined azathioprine/glucocorticoid therapy has been shown to successfully treat recurrent hypophysitis.<ref>{{cite journal |last1=Yang |first1=Guo-Qing |last2=Lu |first2=Zhao-Hui |last3=Gu |first3=Wei-Jun |last4=Du |first4=Jin |last5=Guo |first5=Qing-Hua |last6=Wang |first6=Xian-Ling |last7=Ba |first7=Jian-Ming |last8=Dou |first8=Jing-Tao |last9=Mu |first9=Yi-Ming |last10=Lu |first10=Ju-Ming |date=2011 |title=Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases |journal=Endocrine Journal |volume=58 |issue=8 |pages=675–683 |doi=10.1507/endocrj.k10e-334 |pmid=21666339}}</ref> Some cases of hyperprolactinemia due to pituitary inflammation have been treated with combined dopamine agonists - such as cabergoline/bromocriptine.
Surgery is only an option for those suffering from visual problems/ophthalmoplegia, are suffering a mass-like effect from compression of nearby brain structures, or for the purposes of diagnostic histology.<ref name="Lymphocytic Hypophysitis"/>
==Epidemiology== A large scale study on cadavers done in Sweden, performed biopsies on hundreds of pituitary glands. The study indicated that perhaps as much as 5% of the population experiences some amount of autoimmune pituitary destruction. It is further hypothesized that perhaps half that many show, or may experience, clinical manifestations.{{citation needed|date=August 2020}} The prevalence of all the types of hypophysitis is low, with an incidence of approximately 1 in 9 million. However, it is thought that this may be an underestimate, especially due to the recent use of immune checkpoint inhibitors for cancer treatments, which have endocrine side effects affecting the pituitary gland.<ref name="Lymphocytic Hypophysitis"/> Although cases have been reported in children and the elderly, the mean age of diagnosis for men is 44.7 years, and the mean age of diagnosis for women is 34 years.<ref name="Lymphocytic Hypophysitis"/>
==History== Autoimmune attack of the pituitary gland resulting in reduced hormone production was first discovered as a result of an autopsy in 1962. The autopsy described destruction of the pituitary and thyroid consistent with autoimmune attack and included atrophy of the adrenal glands.<ref name="Caturegli">{{cite book |last1=Caturegli |first1=Patrizio |last2=Tzou |first2=Shey-Cherng |chapter=Hypophysitis |editor-last1=Rose |editor-first1=Noel R. |editor-last2=Mack |editor-first2=Ian R. |title=The Autoimmune diseases |page=548}}</ref> As magnetic resonance imaging became more available diagnosis increased dramatically.<ref name="Caturegli" /> At this time it is believed that the disease is far more prevalent than is diagnosed.<ref name="pmid17554056">{{cite journal |last=Caturegli |first=P |year=2007 |title=Autoimmune hypophysitis: an underestimated disease in search of its autoantigen(s) |url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=17554056 |journal=J. Clin. Endocrinol. Metab. |volume=92 |issue=6 |pages=2038–40 |doi=10.1210/jc.2007-0808 |pmid=17554056 |doi-access=free}}</ref> Nevertheless, autoimmune hypophysitis is frequently referred to as a rare disease and the most recent estimates as to its prevalence give it a value of around 5 per million.<ref name="pmid20039888">{{cite journal |last1=Howlett |first1=T. A. |last2=Levy |first2=M. J. |last3=Robertson |first3=I. J. |year=2010 |title=How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy |journal=Clinical Endocrinology |volume=73 |issue=1 |pages=18–21 |doi=10.1111/j.1365-2265.2009.03765.x |pmid=20039888 |s2cid=12311424 |doi-access=free}}</ref>
==See also== * Hypophysitis * Hypopituitarism * Pituitary disease
== References == {{reflist}}
== External links == {{Medical resources | DiseasesDB = 34426 | ICD10 = E23.6 | ICD9 = | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = | Orphanet = 95506 | SNOMED CT = 237706000 }} {{Pituitary disease}} {{Hypersensitivity and autoimmune diseases}}
Category:Pituitary disorders Category:Autoimmune diseases Category:IgG4-related disease