Materiały źródłowe

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Hypopituitarism-Pathophysiology.aspx

  Hypopituitarism is a health condition characterized by the reduced production of hormones from the pituitary gland. The pathophysiology of hypopituitarism usually involves damage to the pituitary gland, which renders it unable to produce one or more hormones in the normal manner. […] When the production of one or more pituitary hormones is impaired, the gland targeted by the tropic pituitary hormone will have a reduced secretory action, in its turn. […] However, in patients with hypopituitarism, the pituitary gland or some of its component secretory cells are unable to respond adequately to a reduction in the target hormone levels. […] There are many possible causes of hypopituitarism. The most common is a pituitary adenoma or other tumor of the pituitary tissue. Other causes of trauma to the head and brain may also cause damage to the pituitary gland and affect its ability to produce hormones.

• #2 Hypopituitarism (Panhypopituitarism): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/122287-overview

  Hypopituitarism is a clinical syndrome of deficiency in pituitary hormone production. This may result from disorders involving the pituitary gland, hypothalamus, or surrounding structures. Panhypopituitarism refers to the involvement of all pituitary hormones; however, if one or more, but not all, pituitary hormones are involved, this results in partial hypopituitarism. […] When pituitary hormone production is impaired, target gland hormone production is reduced because of a lack of trophic stimulus. Normally, subphysiologic target hormone levels stimulate the pituitary gland to increase trophic hormone production; however, in hypopituitarism, the pituitary gland response is absent, suboptimal, or inappropriate (with biologically inert hormone production). This results in progressive secondary failure of the target glands. Patients with hypopituitarism typically present with low target hormone levels accompanied by low or inappropriately normal levels of the corresponding trophic hormone.

• #3 Hypopituitarism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470414/

  Hypopituitarism is a medical condition characterized by insufficient hormone production in the pituitary gland. […] This activity provides a comprehensive review of the pathophysiological aspects of hypopituitarism, shedding light on its underlying mechanisms. […] Hypopituitarism can originate from 2 primary sources: pathology of the hypothalamus, which affects the production of tropic hormones that act on the pituitary, or direct pathology within the pituitary gland itself. […] The predominant cause of hypopituitarism is pituitary tumors, which account for 61% of cases. […] Inflammatory conditions that affect the pituitary gland may also contribute to the development of hypopituitarism. […] The latest immunotherapy category involving immune checkpoint inhibitors can cause hypophysitis.

• #4 Hypopituitarism | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23284

  Hypopituitarism can originate from 2 primary sourcespathology of the hypothalamus, which affects the production of tropic hormones that act on the pituitary, or direct pathology within the pituitary gland itself. […] The predominant cause of hypopituitarism is pituitary tumors, which account for 61% of cases. These tumors may cause overproduction of a single hormone, leading to a deficiency in other pituitary hormones. […] Inflammatory conditions that affect the pituitary gland may also contribute to the development of hypopituitarism. […] The latest immunotherapy category involving immune checkpoint inhibitors, including cytotoxic T-lymphocytes antigen-4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PDL-1), can cause hypophysitis. […] Infiltrative diseases such as hemochromatosis, sarcoidosis, and histiocytosis have been associated with hypopituitarism development.

• #5 Hypopituitarism (Panhypopituitarism): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/122287-overview

  Causes of hypopituitarism include pituitary adenomas or other intrasellar and parasellar tumors, inflammatory and infectious destruction, surgical removal, radiation-induced destruction of pituitary tissue, traumatic brain injury (TBI), subarachnoid hemorrhage, and postpartum pituitary infarction (Sheehan syndrome). […] Hypopituitarism resulting from pituitary adenomas is due to impaired blood flow to the normal tissue, compression of normal tissue, or interference with the delivery of hypothalamic hormones via the hypothalamus-hypophysial portal system. […] In primary pituitary destruction, the anterior pituitary is destroyed, causing a deficiency in some or all pituitary hormones, including prolactin. […] Hypothalamic disease involves destruction of the hypothalamus. This causes a deficiency or loss of hypothalamic regulatory hormone input to the pituitary, which leads to the loss of anterior pituitary hormone secretion, with an elevated serum prolactin level.

• #6 Hypopituitarism: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22102-hypopituitarism

  Hypopituitarism is a rare condition in which theres a deficiency of one, multiple or all of the hormones made by your pituitary gland. It happens when theres a disorder or damage to your pituitary gland or hypothalamus. […] Your pituitary gland doesnt act alone. It works together with your hypothalamus. This brain structure tells your pituitary gland to release certain hormones. It also regulates functions like blood pressure, heart rate, body temperature and digestion. If you have a disease or injury that affects your pituitary gland or hypothalamus, you may develop hypopituitarism. […] Many conditions and situations can cause hypopituitarism. In some cases, healthcare providers cant determine the cause. In general, these three main factors can cause the condition: Something is putting pressure on (compressing) your pituitary gland or hypothalamus. Theres damage to your pituitary gland or hypothalamus. You have a rare condition or a condition that causes hypopituitarism.

• #7 Hypopituitarism: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22102-hypopituitarism

  Conditions that can cause pressure on these areas of your brain, possibly leading to hypopituitarism, include: Pituitary adenomas: A benign tumor on your pituitary gland that can change the way it releases hormones. Brain tumors: A brain tumor near your hypothalamus and/or pituitary gland can affect hormone production. Lymphocytic hypophysitis (LH): This is a rare condition where lymphocytes invade your pituitary gland. Pituitary or hypothalamus sarcoidosis: Sarcoidosis is a disease that causes inflammation. […] Examples of situations that can cause pituitary or hypothalamus damage include: Surgery: Complications from brain surgery (especially surgery to remove a pituitary adenoma). Radiation therapy: Prior cancer radiation therapy or radiation used to treat a pituitary adenoma. Traumatic brain injury: Situations like a vehicle accident, a fall or contact sports. Pituitary apoplexy: Sudden destruction of pituitary gland tissue.

• #8 Hypopituitarism: Causes, Symptoms, and Treatment

  https://patient.info/doctor/hypopituitarism-pro

  Hypopituitarism is the inability of the pituitary gland to provide sufficient hormones, either due to an inability of the gland to produce hormones or due to an insufficient supply of hypothalamic-releasing hormones. […] The most common cause of hypopituitarism is anterior pituitary tumours. The causes of hypopituitarism include: Pituitary tumours: for example, adenomas. Non-pituitary tumours: craniopharyngiomas, meningiomas, gliomas, chordomas, ependymomas, metastases. Infiltrative processes: sarcoidosis, histiocytosis X, haemochromatosis. Infections: cerebral abscess, meningitis, encephalitis, tuberculosis, syphilis. Ischaemia and infarction: subarachnoid haemorrhage, ischaemic stroke, Sheehan’s syndrome (postpartum haemorrhage with anterior pituitary infarction), pituitary apoplexy (caused by an acute infarction of a pituitary adenoma). Empty sella syndrome: radiological diagnosis of absence of normal pituitary within the sella turcica. Usually benign and asymptomatic but may develop headaches and hypopituitarism. Iatrogenic: irradiation, neurosurgery, withholding previous chronic glucocorticoid replacement. Head injury (may have occurred up to several years before). Congenital: Kallmann’s syndrome (congenital hypogonadotropic hypogonadism with midline defects such as anosmia). Autoimmune: lymphocytic hypophysitis. Pituitary hypoplasia or aplasia. Genetic causes – eg, PIT1, PROP1 gene mutations, septo-optic dysplasia. Idiopathic causes. […] If hypopituitarism has been caused by a tumour, pituitary function may be restored after successful surgical or medical removal of the lesion.

• #9 Hypopituitarism | Lima Memorial Health System

  https://www.limamemorial.org/m/health-library/HIE%20Multimedia-TextOnly/1/000343

  Hypopituitarism is a condition in which the pituitary gland does not produce normal amounts of some or all of its hormones. […] In hypopituitarism, there is a lack of one or more pituitary hormones. Lack of a hormone leads to loss of function in the gland or organ the hormone controls. For example, lack of TSH leads to loss of normal function of the thyroid gland. […] Hypopituitarism may be caused by: Brain surgery, Brain tumor, Head trauma (traumatic brain injury), Infections or inflammation of the brain and the tissues that support the brain, Death of an area of tissue in the pituitary gland (pituitary apoplexy), Radiation therapy to the brain, Stroke (rare), Subarachnoid hemorrhage (from a burst aneurysm), Tumors of the pituitary gland or hypothalamus. […] Sometimes, hypopituitarism is due to uncommon immune system or metabolic diseases, such as: Too much iron in the body (hemochromatosis), Abnormal increase in immune cells called histiocytes (histiocytoses), Autoimmune condition that causes inflammation of the pituitary (lymphocytic hypophysitis), Sarcoidosis, a condition that causes inflammation of various tissues and organs, Infections of the pituitary, such as primary pituitary tuberculosis.

• #10 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Hypopituitarism-Pathophysiology.aspx

  Damage to the pituitary gland due to a tumor may occur either because of impaired blood flow to the gland or compression of the pituitary tissue caused by the tumor growth, or by related inflammation. […] Many other circumstances may cause damage to the pituitary gland in a similar manner and cause hypopituitarism.

• #11 Diagnosis and Treatment of Hypopituitarism

  https://www.e-enm.org/journal/view.php?doi=10.3803/enm.2015.30.4.443

  Hypopituitarism is defined as the total or partial loss of anterior and posterior pituitary gland function that is caused by pituitary or hypothalamic disorders. […] The most common causes of primary hypopituitarism are pituitary adenoma and complications from surgery or radiation therapy for the treatment of pituitary adenoma. […] Several putative mechanisms of hormone deficiency include the application of direct pressure onto or damage to the normal tissues surrounding the tumor, mechanical compression of the portal veins by the pituitary stalk, raised intrasellar pressure, and focal necrosis due to the prolonged portal vein interruption. […] Damage to the pituitary stalk often occurs after the head and/or neck injury accompanying a fracture of the bones surrounding the sella turcica.

• #12 Hypopituitarism pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypopituitarism_pathophysiology

  Hypopituitarism occurrs secondarly to ischemia of the pituitary gland. This ischemia can be due to hemorrhage, tumors, or brain injury. Compression of the blood vessels is one of the mechanisms that cause ischemia to the pituitary gland and leads to hypopituitarism. Pituitary adenomas cause compression of the hypophyseal vessels leading to interruption in the blood supply of the pituitary gland. Traumatic brain injury either primary or secondary also leads to pituitary gland dysfunction. […] Hypopituitarism occurrs mainly due to the destruction of the pituitary gland cells via ischemia, inflammation or infiltration. However, ischemia is believed to be the cornerstone of the pathogenesis of hypopituitarism. […] Pituitary adenoma (secretory or non-secretory) is one of the common causes of compression of the hypophyseal vessels resulting in ischemia.

• #13 Hypopituitarism pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypopituitarism_pathophysiology

  The tumor growth in the pituitary gland participates in increasing the intrasellar pressure, which causes a decrease in the hypophyseal blood flow leading to a decrease of hormonal delivery from the hypothalamus to the pituitary gland. […] Pituitary gland enlargement due to hypertrophy and hyperplasia of lactotrophic cells in anterior pituitary result in superior hypophyseal artery compression, which may be complicated by decreased portal pressure and vasospasm during delivery, playing an important role in the pathogenesis of Sheehan’s syndrome leading to hypopituitarism. […] The anatomical sitting of the pituitary gland increases its susceptibility to getting injured from trauma. […] It is believed that tissue necrosis results in the release of sequestered antigens, precipitating autoimmunity of the pituitary gland and hypopituitarism in Sheehan’s syndrome.

• #14 Diagnosis and Treatment of Hypopituitarism

  https://www.e-enm.org/journal/view.php?doi=10.3803/enm.2015.30.4.443

  Additionally, tumors near the sella turcica may press against the stalk and damage it. […] The stalk is often accidentally severed during surgery on a sellar or parasellar mass. […] Depending on the anatomical location of the lesion, patients may manifest symptoms consistent with a single hormone deficiency, panhypopituitarism, or a posterior pituitary failure (diabetes insipidus). […] The influence of stress seems to manifest via inflammatory cytokines such as interleukin 1 (IL-1) and IL-6, which have severely suppressive effects on thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) levels while at the same time stimulating the secretion of corticotropin releasing hormone (CRH). […] In rare cases, genetic conditions such as Kallmann syndrome or neurohypophyseal diabetes insipidus may contribute to reduced pituitary function.

• #15 Hypopituitarism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470414/

  Infiltrative diseases such as hemochromatosis, sarcoidosis, and histiocytosis have been associated with hypopituitarism development. […] Hypopituitarism induced by traumatic brain injury is one of the more recently recognized mechanisms that can result in isolated or global pituitary deficits. […] Pituitary apoplexy is a medical emergency that arises from acute ischemic infarction or hemorrhage within the pituitary gland. […] Congenital absence of the pituitary gland is related to midline craniofacial defects. […] Empty Sella syndrome is a rare disorder characterized by the enlargement or malformation of the sella turcica, resulting in a herniation of the arachnoid membrane into the pituitary fossa. […] Kallmann syndrome is another rare genetic condition characterized by an inability to detect odor and hypogonadotropic hypogonadism. […] The primary objective and management strategies for hypopituitarism are customized to address the condition’s underlying cause. […] Many patients may require hormone replacement therapy to restore hormonal balance and alleviate associated symptoms.

• #16 Hypopituitarism (Panhypopituitarism): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/122287-overview

  Longstanding target gland hyposecretion may result in hyperplasia of the relevant pituitary cell secreting the trophic hormone, the level of which would be elevated. […] Another common intracranial tumor is craniopharyngioma, a squamous cell tumor that arises from remnants of the Rathke pouch. […] Sheehan syndrome occurs with a large volume of postpartum hemorrhage. […] Pituitary apoplexy denotes the sudden destruction of the pituitary tissue resulting from infarction or hemorrhage into the pituitary. […] Head trauma from a motor vehicle accident, a fall, or a projectile can cause hypopituitarism by direct damage to the pituitary or by injuring the pituitary stalk or the hypothalamus. […] Physiologic states can influence the hypothalamus by impairing synthesis and secretion of regulating hormones.

• #17 Hypopituitarism | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23284

  Hypopituitarism induced by traumatic brain injury is one of the more recently recognized mechanisms that can result in isolated or global pituitary deficits. […] Pituitary apoplexy is a medical emergency that arises from acute ischemic infarction or hemorrhage within the pituitary gland. […] Congenital absence of the pituitary gland is related to midline craniofacial defects. […] Empty Sella syndrome is a rare disorder characterized by the enlargement or malformation of the sella turcica, resulting in a herniation of the arachnoid membrane into the pituitary fossa. […] Kallmann syndrome is another rare genetic condition characterized by an inability to detect odor, also referred to as hyposmia or anosmia, and hypogonadotropic hypogonadism, marked by decreased FSH, LH, testosterone, or estradiol levels.

• #18 Hypopituitarism | Lima Memorial Health System

  https://www.limamemorial.org/m/health-library/HIE%20Multimedia-TextOnly/1/000343

  Hypopituitarism is also a rare complication caused by severe bleeding during pregnancy. The loss of blood leads to tissue death in the pituitary gland. This condition is called Sheehan syndrome. […] Certain medicines can also suppress pituitary function. The most common medicines are glucocorticoids (such as prednisone and dexamethasone), which are taken for inflammatory and immune conditions. Medicines used to treat prostate cancer can also lead to low pituitary function.

• #19 Pituitary Insufficiency and Pathology – 2023-2024 M26 Endocrine System Syllabus

  https://tuftsmedicine.pressbooks.pub/endocrine/chapter/pituitary-insufficiency/

  The majority of cases of hypopituitarism occurring on a vascular basis result from obstetric shock related to postpartum hemorrhage, or Sheehans Syndrome. The pathogenesis of this condition is not established, but Sheehan proposed that it results from arteriolar spasm in the vessels supplying the pituitary portal venous system. […] The adenohypophysis is more selectively affected by bleeding in pituitary tumors. An extreme form of the latter is pituitary apoplexy in which bleeding in a tumor may produce signs of acute expansion, followed by destruction of tumor and adjacent tissue and onset of hypopituitarism.

• #20

  https://link.springer.com/article/10.1007/s11102-008-0130-6

  The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. […] It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. […] In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. […] Chronic anterior hypopituitarism, although reversible in some patients, persists in 25-40% of moderate and severe TBI survivors and likely contributes to long-term neurobehavioral and quality of life impairment. […] While the rates and risk factors of acute and chronic pituitary dysfunction have been documented for moderate and severe TBI victims in numerous recent studies, the pathophysiology remains ill-defined.

• #21 (PDF) Pathophysiology of hypopituitarism in the setting of brain injury

  https://www.academia.edu/57289667/Pathophysiology_of_hypopituitarism_in_the_setting_of_brain_injury

  The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. […] It has been hypothesized that, apart from the primary mechanical event, secondary insults such as hypotension, hypoxia, increased intracranial pressure, as well as changes in cerebral flow and metabolism may contribute to hypothalamic-pituitary damage. […] While the precise pathophysiology of post traumatic hypopituitarism has not yet been elucidated, it has been hypothesized that, apart from the primary mechanical event, secondary insults such as hypotension, hypoxia, increased intracranial pressure, as well as changes in cerebral flow and metabolism may contribute to hypothalamic-pituitary damage.

• #22

  https://link.springer.com/article/10.1007/s11102-008-0130-6

  Herein we discuss the hypotheses and available data concerning hypothalamic-pituitary vulnerability in the setting of head injury. […] Four possible pathophysiological mechanisms are considered: (1) the primary brain injury event, (2) secondary brain insults, (3) the stress of critical illness and (4) medication effects. […] Although each of these factors appears to be important in determining which hormonal axes are affected, the severity of dysfunction, their time course and possible reversibility, this process remains incompletely understood.

• #23 PATHOGENESIS OF HYPOPITUITARISM | Oncohema Key

  https://oncohemakey.com/pathogenesis-of-hypopituitarism/

  PATHOGENESIS OF HYPOPITUITARISM Part of CHAPTER 17 HYPOPITUITARISM Table 17-1 lists many of the causes of hypopituitarism. There are no reliable statistics for the percentage of patients in each subgroup, but pituitary tumors represent the largest single category, and a pituitary adenoma (see Chap. 11) is the most common single cause of hypopituitarism in adults. […] The mechanisms by which pituitary tumors cause hypopituitarism include mechanical compression of normal pituitary tissue and interference with delivery of hypothalamic hormones to the pituitary via the hypothalamic-hypophysial portal system. […] Hypopituitarism caused by a pituitary tumor may be reversible; surgical removal of the tumor or shrinkage via medical therapy is often accompanied by return of normal pituitary function. However, treatment of pituitary tumors with surgery or radiotherapy may worsen or cause hypopituitarism.

• #24 Hypopituitarism | 5-Minute Pediatric Consult

  https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/618208/all/Hypopituitarism

  Hypopituitarism refers to deficiencies of one or more pituitary hormones. […] There is increasing understanding of the genetic etiology of familial and/or congenital forms of hypopituitarism. Patterns of inheritance include autosomal recessive, autosomal dominant, X-linked, and digenic forms; can occur in the setting of other complex medical syndromes. […] Pathology is based on specific deficiency or deficiencies. […] Genetic disorders due to mutations in genes important for CNS development, including transcription factors can be associated with de novo or familial forms (POUF1, HESX1, LHX3, LHX4, OTX2, SOX2, SOX3, PTX2, PROP1, etc.). […] Antenatal exposures/insults may precipitate. […] Mechanical causes include birth trauma or perinatal insult, surgical resection of the gland or damage to the stalk, and traumatic brain injury.

• #25 Hypopituitarism – Wikipedia

  https://en.wikipedia.org/wiki/Hypopituitarism

  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. […] The pituitary develops in the third week of embryogenesis from interactions between the diencephalon part of the brain and the nasal cavity. […] The cells then differentiate further into the various hormone-producing cells of the pituitary. This requires particular transcription factors that induce the expression of particular genes. […] Some of these transcription factors have been found to be deficient in some forms of rare combined pituitary hormone deficiencies (CPHD) in childhood. […] Each transcription factor acts in particular groups of cells. Therefore, various genetic mutations are associated with specific hormone deficiencies.

• #26 Hypopituitarism – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK278989/

  Hypopituitarism refers to complete or partial failure of secretion of anterior and/or posterior pituitary hormones. […] It may arise as a result of congenital defects in the development of individual anterior pituitary cell types or hypothalamic function, acquired disease of the pituitary or hypothalamus, or from infundibular lesions which interfere with the hypothalamic control of the pituitary. […] The underlying mechanism for this condition, once thought to be a consequence of birth trauma, remains undetermined but a congenital molecular defect is likely. […] Mutations of the HESX1 gene in humans are associated with septo-optic dysplasia and evolving hypopituitarism. […] The PROP1 gene encodes a transcription factor with a single paired-like DNA-binding domain. […] Autosomal recessive defects of PIT1 are associated with combined deficiencies of growth hormone (GH), prolactin, and thyrotropin stimulating hormone (TSH).

• #27 Hypopituitarism – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK278989/

  SOX2 belongs to the SRY-related HMG box (SOX) family of transcription factors which are expressed in various stages of embryonic development and cell differentiation, and play critical roles from the earliest stages of development, in particular expression of anterior neuroectoderm. […] SOX3 also belongs to the SRY-related HMG box (SOX) family of transcription factors. […] OTX2 belongs to the orthodenticle homeobox (OTX) and plays an essential role in brain, eyes, and pituitary development. […] Mutations in DAX1, which is another X chromosome gene, cause hypogonadotropic hypogonadism in association with congenital adrenal hypoplasia in males. […] Isolated gonadotropin deficiency with hyposmia (Kallmann syndrome) may be inherited as an autosomal X-linked disorder or occur sporadically.

• #28

  https://discovery.ucl.ac.uk/id/eprint/10123537/

  PATHOGENESIS: Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8. Over the last 5 years, several novel genes have been identified in association with CH, but it is likely that many genes remain to be identified, as the majority of patients with CH do not have an identified mutation. […] The majority of CH cases are sporadic; however, a small number of familial cases have been identified. In the latter, a molecular basis has frequently been identified. Between 8090% of CH cases remain unsolved in terms of molecular genetics.

• #29 A Novel Mechanism of Hypopituitarism: Defective Interaction of Pit-1 with CBP | Pediatric Research

  https://www.nature.com/articles/pr1999630

  Naturally occurring mutants of the pituitary transcription factor Pit-1 cause combined pituitary hormone deficiency (CPHD) of growth hormone (GH), prolactin, and thyrotropin. […] In sporadic and autosomal dominant forms of this disorder, however, Pit-1 mutations found on only one allele cause CPHD through dominant negative inhibition of wild type Pit-1 function. […] Interestingly, however, this sporadic mutation does not decrease basal activation of human (h) GH gene expression. […] Pit-1 also interacts with two specific regions of the cAMP response element binding protein, CBP. […] However, the K216E mutant Pit-1 has decreased synergism with CBP of PKA-dependent activation of the hGH promoter. […] Thus, our data indicate that a mechanism of hypopituitarism may be through impaired interaction between mutant Pit-1 and CBP.

• #30 New research from Raetzman lab, led by undergraduate, investigates the mechanism behind genetic cause of congenital hypopituitarism  | School of Molecular & Cellular Biology | Illinois

  https://mcb.illinois.edu/news/2023-10-24/new-research-raetzman-lab-led-undergraduate-investigates-mechanism-behind-genetic

  Hypopituitarism occurs when the pituitary gland, a small, pea-sized gland at the base of the brain, does not make enough hormones that are essential for growth, metabolism, and reproduction. […] In recent years, she and members of her lab have been working to identify the genetic causes of hypopituitarism, leading her to study the growth hormone-releasing hormone receptor (GHRHR) gene. Mutations in this gene cause hypopituitarism in humans. […] Researchers have known that a loss-of-function mutation in the growth hormone-releasing hormone receptor gene would cause hypopituitarism. However, it was unclear how the mutation caused the disease to occur. To investigate the mechanism, researchers used mouse models with a loss-of-function mutation in GHRHR. […] To the surprise of researchers, in mice lacking GHRHR, this precursor cell population failed to expand properly, unlike the stem cells. […] Through single-cell RNA sequencing of mouse models with and without functional GHRHR, Dr. Raetzman’s lab identified a unique proliferating precursor cell population critical for proper pituitary development.

• #31 Diagnosis and Treatment of Hypopituitarism

  https://www.e-enm.org/journal/view.php?doi=10.3803/enm.2015.30.4.443

  The underlying pathology, speed of onset and the severity of hypopituitarism have a significant impact on the clinical features. […] The clinical expression of severe panhypopituitarism, which typically occurs immediately after hypopituitary patients discontinue hormone replacement or following the pituitary apoplexy or hypophysectomy, may be evident within several hours or a few days. […] GH-secreting cells (somatotrophs) are particularly vulnerable to pressure, which is why GH deficiency occurs first and most frequently among all pituitary hormones, followed by deficiencies of gonadotropin (luteinizing hormone [LH] and follicle stimulating hormone [FSH]), TSH and ACTH (or ACTH and TSH), and prolactin. […] The diagnosis of hypopituitarism is made by measuring basal hormone levels in the morning fasting status or performing stimulation tests if necessary.

• #32 Hypopituitarism – Hypothalamus and Pituitary Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.8.3.

  Hypopituitarism refers to a syndrome caused by deficiency of 1 pituitary hormone, which can result from pituitary or hypothalamic disease (deficiency of pituitary hormonereleasing hormones). […] The resulting changes in hormonal levels and in the choice of diagnostic tests are related to the presence of several short and long feedback loops among different parts of the hypothalamic-pituitary-peripheral gland system. […] In general, the acquired loss of pituitary function follows the sequence of growth hormone (GH), luteinizing hormone (LH)/follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and prolactin with tumors and radiation, but the sequence may vary with other etiologies. […] Diagnosis entails a clinical examination looking for clinical manifestations of hormone deficiency and requires the documentation of subnormal secretion of pituitary hormones in basal and/or stimulated tests exploring stimulation and feedback loops in the endocrine system.

• #33 Hypopituitarism – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/hypopituitarism/

  Hypopituitarism refers to the inadequate production of one or more anterior pituitary hormones as a result of damage to the pituitary gland and/or hypothalamus. […] The most common cause of hypopituitarism is compression of the pituitary gland by a nonsecretory pituitary macroadenoma. […] Hypopituitarism becomes symptomatic when more than 80% of pituitary cells are damaged. […] In most cases, hypopituitarism develops slowly (e.g., adenomas, postirradiation). […] Certain cases of hypopituitarism develop rapidly (e.g., pituitary apoplexy). […] Hypopituitarism refers to deficiency of one or more anterior pituitary hormones. […] In addition to the aforementioned hormone deficiencies, patients with severe pituitary damage (panhypopituitarism) also present with deficiencies of posterior pituitary hormones.

• #34 Anterior Pituitary (Its Hormones, Functions, & More)

  https://www.rupahealth.com/post/hormones-by-anterior-pituitary

  Hypopituitarism conditions are associated with decreased secretion of pituitary hormones, which may originate from the hypothalamus or the pituitary gland. Hypofunction of the anterior pituitary occurs when approximately 75% of the parenchyma is lost or absent. […] Some common causes of anterior pituitary hypofunction include the following: […] Pituitary Tumors and Mass Lesions: tumors may compress and exert pressure on the pituitary gland, thus impairing its function. […] Traumatic Brain Injury and Subarachnoid Hemorrhage: damage to or disruption of the blood supply to the anterior pituitary may result in hypopituitarism. […] Pituitary Surgery or Radiation: surgical removal of a pituitary adenoma or radiation therapy to the brain can damage the pituitary gland and impair hormone secretion.

• #35 Pituitary Insufficiency and Pathology – 2023-2024 M26 Endocrine System Syllabus

  https://tuftsmedicine.pressbooks.pub/endocrine/chapter/pituitary-insufficiency/

  Pituitary insufficiency (hypopituitarism) may arise from congenital defects or acquired disease of the pituitary or hypothalamus. […] There are many disorders that can cause hypopituitarism, either by affecting the hypothalamus or the pituitary gland. Congenital disorders are a cause for hypopituitarism presenting in children. Formation of the pituitary during embryonic development depends upon the juxtaposition of cells of neurectodermal origin, which form the posterior pituitary, and endodermal cells which form the anterior pituitary. Defects in the transcription factors HESX-1, PROP-1, and PIT-1 are known to result in various degrees of hypopituitarism. […] Pituitary adenomas are the most common cause for hypopituitarism in adults. […] The functional reserve of the adenohypophysis is sufficiently great that hypopituitarism will not become apparent until about 70% of its tissue is destroyed.

• #36 Panhypopituitarism: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/923789-overview

  Panhypopituitarism is a condition of inadequate or absent production of the anterior pituitary hormones. It is frequently the result of other problems that affect the pituitary gland and either reduce or destroy its function or interfere with hypothalamic secretion of the varying pituitary-releasing hormones. […] The effects of hypopituitarism in children depend on the affected hormones. GH deficiency can result in hypoglycemia and short stature. Gonadotropin deficiency leads to prenatal micropenis and delayed or interrupted puberty in older children. Corticotropin deficiency interferes with normal carbohydrate, protein, and lipid metabolism and may result in weight loss, hypoglycemia, fatigue, hypotension, and death. Thyrotropin deficiency leads to hypothyroidism.

• #37 Hypopituitarism: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22102-hypopituitarism

  Hormonal deficiencies that accompany hypopituitarism can lead to the development of other conditions. The exact effects vary depending on which hormone is lacking. Some examples are: GH deficiency can lead to obesity, high cholesterol and metabolic syndrome. Estrogen deficiency (from FSH deficiency) can lead to osteoporosis in females. ACTH deficiency can lead to an adrenal crisis.

• #38 The pathophysiological mechanism between hypopituitarism and nonalcoholic fatty liver disease

  https://www.sciopen.com/article/10.1016/j.iliver.2022.02.004

  Nonalcoholic fatty liver disease (NAFLD) is a common chronic metabolic liver disease worldwide. […] Current research shows that patients with hypopituitarism have a high risk of developing NAFLD. […] In this review, we analyzed the mechanisms related to NAFLD through thyroid secretion, growth hormone secretion, sex hormone, and prolactin axes in patients with hypopituitarism, which will provide information and a theoretical basis for clinical diagnosis and treatment. […] Hypothyroidism and nonalcoholic fatty liver disease – a chance association? […] The multiple-hit pathogenesis of nonalcoholic fatty liver disease (NAFLD). […] Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. […] Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy. […] Insulin-like growth factor (IGF) system in liver diseases. […] Prolactin improves hepatic steatosis via CD36 pathway.

• #39 Management of Hypopituitarism

  https://www.mdpi.com/2077-0383/8/12/2153

  Hypopituitarism includes all clinical conditions that result in partial or complete failure of the anterior and posterior lobe of the pituitary gland’s ability to secrete hormones. […] Hypopituitarism may be the result either of pituitary or hypothalamic dysfunction, the former interfering with pituitary hormone secretion (secondary dysfunction) and the latter with hypothalamic pituitary-releasing hormone secretion (tertiary dysfunction). […] A number of congenital or acquired, inherited or sporadic clinical entities may result in isolated deficiency (IHD) or multiple pituitary hormone deficiency (MPHD). […] Novel mutations are now recognised to be responsible for many patients with congenital hypopituitarism, although their presentation may be delayed. […] Hence, hypopituitarism includes central or secondary adrenal insufficiency (SAI) caused by adrenocorticotropic hormone (ACTH) deficiency, secondary hypothyroidism (SHT) caused by thyroid-stimulating hormone (TSH) deficiency, secondary hypogonadism (SHG) caused by deficiency of the gonadotroph hormones (Luteinising (LH) and Follicle Stimulating Hormones (FSH)), growth hormone deficiency (GHD), and central diabetes insipidus (CDI) caused by antidiuretic hormone (ADH or arginine vasopressin, AVP) deficiency.

• #40 Clinical manifestations of hypopituitarism – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-of-hypopituitarism

  The presentation of hypopituitarism can be considered as the presentation of deficiency of each anterior pituitary hormone. The presentations of patients with deficiencies of those hormones that control target glands are often similar to the presentations of patients with primary deficiencies of the target gland hormones they control, with some notable exceptions. […] Damage to the anterior pituitary can occur suddenly or slowly, can be mild or severe, and can affect the secretion of one, several, or all of its hormones. As a result, the clinical presentation of anterior pituitary hormone deficiencies varies, depending upon the following factors: […] The rapidity with which a disease affects anterior pituitary cells. Some diseases, such as pituitary apoplexy, develop rapidly, causing sudden impairment of corticotropin (ACTH) secretion and, consequently, sudden onset of symptoms of cortisol deficiency. Other insults, such as radiation therapy to the pituitary or hypothalamus, usually act slowly, causing symptoms many months or, more likely, years later. […] Complete ACTH and cortisol deficiency, as an example, can cause symptoms under basal circumstances, while partial ACTH deficiency may cause symptoms only during times of physical stress.

• #41 Hypopituitarism – Hypothalamus and Pituitary Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.8.3.

  Each pituitary hormone must be tested. […] Differential diagnosis depends on the signs and symptoms and will vary, depending on the pituitary deficiencies, but may include primary adrenal insufficiency, primary hypothyroidism, or primary hypogonadism. Nevertheless, measurements of biochemical hormone levels, basal and/or stimulated, will confirm a definite diagnosis.

• #42 Management of Hypopituitarism

  https://www.mdpi.com/2077-0383/8/12/2153

  The absent or insufficient replacement of pituitary hormones may not be compatible with life, particularly in the context of ACTH deficiency. […] Moreover, hypopituitarism per se has been associated with an increase in both morbidity and mortality. […] These risks have mandated the need for evidence-based guideline for hormonal replacement in hypopituitary adults, either of isolated or combined hormonal insufficiency, and Endocrine Society Clinical Practice Guidelines have been recently issued for the management of hypopituitarism but also for each target-hormone deficiency either at a primary or a secondary level of hypothalamo-pituitary target endocrine gland axis. […] Significantly, many novel research studies do not focus on the hormonal replacement per se, but on ways of administration and delivery of the drug in order to achieve a better compliance from the patients’ point of view, but also to most closely parallel the physiological circadian secretion of the deficient hormone, and thus to optimise quality of life (QoL).

• #43 Hypopituitarism: Causes, Symptoms, and Treatment

  https://patient.info/doctor/hypopituitarism-pro

  Hypopituitarism is the inability of the pituitary gland to provide sufficient hormones, either due to an inability of the gland to produce hormones or due to an insufficient supply of hypothalamic-releasing hormones. […] The most common cause of hypopituitarism is anterior pituitary tumours. The causes of hypopituitarism include: Pituitary tumours: for example, adenomas. Non-pituitary tumours: craniopharyngiomas, meningiomas, gliomas, chordomas, ependymomas, metastases. Infiltrative processes: sarcoidosis, histiocytosis X, haemochromatosis. Infections: cerebral abscess, meningitis, encephalitis, tuberculosis, syphilis. Ischaemia and infarction: subarachnoid haemorrhage, ischaemic stroke, Sheehan’s syndrome (postpartum haemorrhage with anterior pituitary infarction), pituitary apoplexy (caused by an acute infarction of a pituitary adenoma). Empty sella syndrome: radiological diagnosis of absence of normal pituitary within the sella turcica. Usually benign and asymptomatic but may develop headaches and hypopituitarism. Iatrogenic: irradiation, neurosurgery, withholding previous chronic glucocorticoid replacement. Head injury (may have occurred up to several years before). Congenital: Kallmann’s syndrome (congenital hypogonadotropic hypogonadism with midline defects such as anosmia). Autoimmune: lymphocytic hypophysitis. Pituitary hypoplasia or aplasia. Genetic causes – eg, PIT1, PROP1 gene mutations, septo-optic dysplasia. Idiopathic causes. […] If hypopituitarism has been caused by a tumour, pituitary function may be restored after successful surgical or medical removal of the lesion.

• #44 Diagnosis and Treatment of Hypopituitarism

  https://www.e-enm.org/journal/view.php?doi=10.3803/enm.2015.30.4.443

  The expected values and responses of the pituitary gland and target organ hormones under basal and stimulated states are provided in Table 4. […] The diagnosis of posterior pituitary hormone deficiency can be easily made through a review of clinical symptoms/signs and a water deprivation test. […] The pre- and postoperative incidence rates of hypopituitarism are similar because some hormone function can be recovered following the removal of a pituitary tumor. […] This is why it is necessary for physicians to inform their patients that they may require lifetime treatment unless there are special circumstances, such as the discontinuation of estrogen replacement after menopause. […] Given that there is a variety of causes underlying hypopituitarism as well as varying degrees of hormone deficiencies and types of deficient hormones, it is important to individualize hormone replacement therapy to the specific needs of a particular patient.

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