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Autoimmune hypophysitis
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DiseasesDB 34426

Autoimmune hypophysitis is defined as below normal production of one or more hormones by the pituitary gland due to autoimmunity.



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.

It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms.[1] However, there have been cases of isolated attacks as a result of drug reactions (i.e., use of blocking antibody ipilimumab) [2][3] 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). [4]


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.[5] As Magnetic Resonance Imaging became more available diagnosis increased dramatically.[6] At this time it is believed that the disease is far more prevalent than is diagnosed.[7] Nevertheless, autoimmune hypophysitis is frequently referred to as a rare disease and estimates as to its prevalence vary.[1]


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.


Biopsy is the only means of accurate diagnosis as no autoantigen has been discovered.[7][8] Biopsy of the pituitary gland is not easily performed with safety as it sits under the brain.[1] However, a test does exist to detect antibodies to the pituitary without biopsy.[1] 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.[9]


80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones.[1] Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies.[7] 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 pan-autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.[1]


  1. ^ a b c d e f Strömberg S, Crock P, Lernmark A, Hulting AL (1998). "Pituitary autoantibodies in patients with hypopituitarism and their relatives". J. Endocrinol. 157 (3): 475–80. doi:10.1677/joe.0.1570475. PMID 9691980.  
  2. ^ Phan GQ, Yang JC, Sherry RM, et al. (2003). "Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma". Proc. Natl. Acad. Sci. U.S.A. 100 (14): 8372–7. doi:10.1073/pnas.1533209100. PMID 12826605.  
  3. ^ HEPATITIS WEEKLY, Autoimmune Diseases, "Cytotoxic Antigen Induces Hypophysitis in Cancer Patients," January 9, 2006; see also, Case Report: "The mysterious case of the lost pituitary: amiodarone-induced hypothyroidism," by SN Weston, CFM Weston, Hospital Medicine, January 2000, Vol 61, No 1
  4. ^ Minakshi B, Alok S, Hillol KP (2005). "Lymphocytic hypophysitis presenting as pituitary apoplexy in a male". Neurol India 53 (3): 363–4. PMID 16230817.;year=2005;volume=53;issue=3;spage=363;epage=364;aulast=Minakshi.  
  5. ^ THE AUTOIMMUNE DISEASES, by Noel R. Rose and Ian R. Mack; Chapter 40, "Hypophysitis," by Patrizio Caturegli and Shey-Cherng Tzou, at pg. 548.e
  6. ^ Id.
  7. ^ a b c Caturegli P (2007). "Autoimmune hypophysitis: an underestimated disease in search of its autoantigen(s)". J. Clin. Endocrinol. Metab. 92 (6): 2038–40. doi:10.1210/jc.2007-0808. PMID 17554056.  
  8. ^ See "Pituitary autoantibodies." By Crock, Patricia A., et al. ,Neuroendocrinology, Current Opinion in Endocrinology & Diabetes. 13(4):344-350, August 2006.
  9. ^ See, i.e., "Failure of the short ACTH test to unequivocally diagnose long-standing symptomatic secondary hypoadrenalism," Note, by Steven G. Soule, Michael Fahie-Wilson & Sophie Tomlinson, Division of Reproductive Medicien, Dept. of Medicine, UCL Medical School, Cobbold Laboratories, The Middlesex Hospital, London, UK, Depts. Of medicine and Biochemistry, Southend General Hospital, Pittwell Chase, Westcliff-on-Sea, Essex SSO ORY, UK; "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," M. Maghnie, et al., pub.: European Journal of Endocrinology, Vol. 152, Issue 5, 735-741; EVALUATION OF PATIENTS WITH PITUITARY/ HYPOTHALAMIC SPACE OCCUPYING LESIONS, Chapter 11b. "Pituitary-Hypothalamic Tumor Syndromes: Adults," Klaus von Werder, MD, FRCP, and Richard Clayton, MD, FRCP, Updated: August 10, 2006; "Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement," Mohamad Maghnie, et al., European Journal of Endocrinology, Vol 152, Issue 4, 589-596; "Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency," Doc. No. 295237, by Biller BM, Samuels MH, Zagar A., Cook DM, Arafah BM, Journal of Clinical Endocrinology and Metabolism, 2002 May;87(5):2067-2079; see also, "Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH," NIH, Endocrine and Metabolic Diseases Information Service,

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