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List of terms related to Hypophysitis

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

Synonyms and keywords:Autoimmune hypophysitis, lymphocytic hypophysitis


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]




Associated Conditions

Gross Pathology

Microscopic Pathology


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
  • 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


  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.

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Epidemiology and Demographics




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Risk Factors


Natural History, Complications and Prognosis


Diagnostic Criteria

If available, the diagnostic criteria are provided here.


A directed history should be obtained to ascertain


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

"Type non specific symptoms" may be present.

Past Medical History

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Social History



The frequency and amount of alcohol consumption should be characterized.

Drug Use



Physical Examination

Appearance of the Patient

Vital Signs















Laboratory Findings

Electrolyte and Biomarker Studies


Chest X Ray



Echocardiography or Ultrasound

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