Autoimmune hypophysitis

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Autoimmune hypophysitis
Other namesLymphocytic hypophysitis
Specialty Endocrinology

Autoimmune hypophysitis is defined as inflammation of the pituitary gland due to autoimmunity.

Contents

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. [1] 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 ] Common symptoms include nausea, vomiting, fatigue, loss of libido, amenorrhea, and dizziness. [1] It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms. [2] However, there have been cases of isolated attacks as a result of drug reactions (i.e., use of blocking antibody ipilimumab) [3] [4] 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). [5] 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. [6]

Antibodies

80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. [2] 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 autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid. [2]

Cause

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.[3] However, clinical, laboratory data, and imaging can all help with the diagnosis.[8] First and foremost, patients present with symptoms of hypopituitarism and must undergo pituitary hormone function evaluation. [1] 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, 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. [2] 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] [10] [11] [12] [13] [14] 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. [1]

Treatment

Inflammation resolves usually after several months of glucocorticoid treatment[ citation needed ] For those that show no improvement with corticosteroids or have relapsed after treatment with corticosteroids, immunosuppressive medications such as methotrexate, azathioprine, and cyclosporine can be used as well. In particular, azathioprine plus glucocorticoids has been discovered to successfully treat recurrent hypophysitis. [15] There have also been some cases where dopamine agonists such as cabergoline/bromocriptine have also been successfully used in those with hyperprolactinemia due to pituitary inflammation. Surgery is only an option for those suffering from visual problems/ophthalmoplegia, have a mass like an effect from compression of nearby structures, or for those that require histology for diagnosis. [1]

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 ] 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. [1] 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. [1]

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. [16] As magnetic resonance imaging became more available diagnosis increased dramatically. [16] 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 the most recent estimates as to its prevalence give it a value of around 5 per million. [17]

See also

Related Research Articles

<span class="mw-page-title-main">Hyperthyroidism</span> Clinical syndrome caused by excessive thyroid hormone

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon but life-threatening complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature; this often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Graves' disease</span> Autoimmune endocrine disease

Graves disease, also known as toxic diffuse goiter or Basedow’s disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems.

<span class="mw-page-title-main">Hypothyroidism</span> Endocrine disease

Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as poor ability to tolerate cold, extreme fatigue, muscle aches, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goitre. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

<span class="mw-page-title-main">Addison's disease</span> Endocrine disorder

Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal glands, causing adrenal insufficiency. Symptoms generally come on slowly and insidiously and may include abdominal pain and gastrointestinal abnormalities, weakness, and weight loss. Darkening of the skin in certain areas may also occur. Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness. Mood changes may also occur. Rapid onset of symptoms indicates acute adrenal failure, which is a clinical emergency. An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.

<span class="mw-page-title-main">Adrenal insufficiency</span> Medical condition

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.

<span class="mw-page-title-main">Hashimoto's thyroiditis</span> Autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. A slightly broader term is autoimmune thyroiditis, identical other than that it is also used to describe a similar condition without a goiter.

<span class="mw-page-title-main">Hypopituitarism</span> Medical condition

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used.

<span class="mw-page-title-main">Sheehan's syndrome</span> Medical condition

Sheehan's syndrome, also known as postpartum pituitary gland necrosis, occurs when the pituitary gland is damaged due to significant blood loss and hypovolemic shock usually during or after childbirth leading to decreased functioning of the pituitary gland (hypopituitarism). The pituitary gland is an endocrine organ, meaning it produces certain hormones and is involved in the regulation of various other hormones. This gland is located in the brain and sits in a pocket of the sphenoid bone known as the sella turcica. The pituitary gland works in conjunction with the hypothalamus, and other endocrine organs to modulate numerous bodily functions including growth, metabolism, menstruation, lactation, and even the "fight-or-flight" response. These endocrine organs release hormones in very specific pathways, known as hormonal axes. For example, the release of a hormone in the hypothalamus will target the pituitary to trigger the release of a subsequent hormone, and the pituitary's released hormone will target the next organ in the pathway. Hence, damage to the pituitary gland can have downstream effects on any of the aforementioned bodily functions.

An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are associated with such antibodies.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

<span class="mw-page-title-main">Thyroiditis</span> Medical condition

Thyroiditis is the inflammation of the thyroid gland. The thyroid gland is located on the front of the neck below the laryngeal prominence, and makes hormones that control metabolism.

<span class="mw-page-title-main">Adrenocorticotropic hormone deficiency</span> Medical condition

Adrenocorticotropic hormone deficiency is a rare disorder characterized by secondary adrenal insufficiency with minimal or no cortisol production and normal pituitary hormone secretion apart from ACTH. ACTH deficiency may be congenital or acquired, and its symptoms are clinically similar to those of glucocorticoid deficiency. Symptoms consist of weight loss, diminished appetite, muscle weakness, nausea, vomiting, and hypotension. Low blood sugar and hyponatremia are possible; however, blood potassium levels typically remain normal because affected patients are deficient in glucocorticoids rather than mineralocorticoids because of their intact renin-angiotensin-aldosterone system. ACTH may be undetectable in blood tests, and cortisol is abnormally low. Glucocorticoid replacement therapy is required. With the exception of stressful situations, some patients with mild or nearly asymptomatic disease may not require glucocorticoid replacement therapy. As of 2008 about two hundred cases have been described in the literature.

Pituitary apoplexy is bleeding into or impaired blood supply of the pituitary gland. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously. The most common initial symptom is a sudden headache, often associated with a rapidly worsening visual field defect or double vision caused by compression of nerves surrounding the gland. This is often followed by acute symptoms caused by lack of secretion of essential hormones, predominantly adrenal insufficiency.

Stress hormones are secreted by endocrine glands to modify one's internal environment during the times of stress. By performing various functions such as mobilizing energy sources, increasing heart rate, and downregulating metabolic processes which are not immediately necessary, stress hormones promote the survival of the organism. The secretions of some hormones are also downplayed during stress. Stress hormones include, but are not limited to:

<span class="mw-page-title-main">Subacute thyroiditis</span> Medical condition

Subacute thyroiditis refers to a temporal classification of the different forms of thyroiditis based on onset of symptoms. The temporal classification of thyroiditis includes presentation of symptoms in an acute, subacute, or chronic manner. There are also other classification systems for thyroiditis based on factors such as clinical symptoms and underlying etiology.

<span class="mw-page-title-main">Hypothalamic–pituitary–thyroid axis</span> Part of the neuroendocrine system

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

<span class="mw-page-title-main">Hashimoto's encephalopathy</span> Human disease (neurological condition)

Hashimoto's encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological condition characterized by encephalopathy, thyroid autoimmunity, and good clinical response to corticosteroids. It is associated with Hashimoto's thyroiditis, and was first described in 1966. It is sometimes referred to as a neuroendocrine disorder, although the condition's relationship to the endocrine system is widely disputed. It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.

<span class="mw-page-title-main">Pituitary disease</span> Medical condition

A pituitary disease is a disorder primarily affecting the pituitary gland.

<span class="mw-page-title-main">Autoimmune disease</span> Disorders of adaptive immune system

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.

<span class="mw-page-title-main">Hypophysitis</span> Medical condition

Hypophysitis refers to an inflammation of the pituitary gland. Hypophysitis is rare and not fully understood.

References

  1. 1 2 3 4 5 6 7 Naran, Jaya; Can, Ahmet S. (2023-08-08). "Lymphocytic Hypophysitis". StatPearls Publishing. PMID   32965926 . Retrieved 2024-06-29.
  2. 1 2 3 4 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.
  3. 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 (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. Bibcode:2003PNAS..100.8372P. doi: 10.1073/pnas.1533209100 . PMC   166236 . PMID   12826605.
  4. Hepatitis Weekly, Autoimmune Diseases, "Cytotoxic Antigen Induces Hypophysitis in Cancer Patients," 2006-1-9;
    see also, Weston SN, Weston CF (January 2000). "The mysterious case of the lost pituitary: amiodarone-induced hypothyroidism". Hosp Med. 61 (1): 64–5. doi:10.12968/hosp.2000.61.1.1869. PMID   10735160.
  5. Minakshi B, Alok S, Hillol KP (2005). "Lymphocytic hypophysitis presenting as pituitary apoplexy in a male". Neurol India. 53 (3): 363–4. doi: 10.4103/0028-3886.16948 . PMID   16230817.
  6. Foyouzi, N (February 2011). "Lymphocytic adenohypophysitis". Obstetrical & Gynecological Survey. 66 (2): 109–13. doi:10.1097/ogx.0b013e31821d4047. PMID   21592417. S2CID   30199333.
  7. 1 2 3 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. Crock, Patricia A., et al., Pituitary autoantibodies, Neuroendocrinology, Current Opinion in Endocrinology & Diabetes, 13(4):344-350, August 2006.
  9. Soule SG, Fahie-Wilson M, Tomlinson S (February 1996). "Failure of the short ACTH test to unequivocally diagnose long-standing symptomatic secondary hypoadrenalism". Clin. Endocrinol. 44 (2): 137–40. doi:10.1046/j.1365-2265.1996.540363.x. PMID   8849565. S2CID   37708979.
  10. Maghnie M, Uga E, Temporini F, Di Iorgi N, Secco A, Tinelli C, Papalia A, Casini MR, Loche S (May 2005). "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". Eur. J. Endocrinol. 152 (5): 735–41. doi: 10.1530/eje.1.01911 . PMID   15879359.
  11. Clayton, Richard. "EVALUATION OF PATIENTS WITH PITUITARY/ HYPOTHALAMIC SPACE OCCUPYING LESIONS". endotext.org. Archived from the original on 25 February 2013. Retrieved 2 January 2013.
  12. 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 (April 2005). "Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement". Eur. J. Endocrinol. 152 (4): 589–96. doi: 10.1530/eje.1.01873 . PMID   15817915.
  13. Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou S, Kleinberg DL, Chipman JJ, Hartman ML (May 2002). "Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency". J. Clin. Endocrinol. Metab. 87 (5): 2067–79. doi: 10.1210/jcem.87.5.8509 . PMID   11994342.
  14. "Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated With hGH". National Endocrine and Metabolic Diseases Information Service. Archived from the original on 27 January 2013. Retrieved 2 January 2013.
  15. "Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases Guo-Qing Yang 1 , Zhao-Hui Lu, Wei-Jun Gu, Jin Du, Qing-Hua Guo, Xian-Ling Wang, Jian-Ming Ba, Jing-Tao Dou, Yi-Ming Mu, Ju-Ming Lu".
  16. 1 2 Caturegli, Patrizio, and Tzou, Shey-Cherng, Hypophysitis, in Rose, Noel R., and Mack, Ian R., The Autoimmune diseases, chap. 40, at pg. 548.
  17. Howlett T.A.; Levy M.J.; Robertson I.J. (2010). "How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy". Clinical Endocrinology. 73 (1): 18–21. doi: 10.1111/j.1365-2265.2009.03765.x . PMID   20039888. S2CID   12311424.