Physiology of the Pituitary Gland
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Abnormalities can occur in the HPA axis at several levels. Depression can cause chronic central stimulation of the HPA axis. ACTH-secreting adenomas, ectopic ACTH-secreting tumours and adrenal cortisol-secreting tumours lead to Cushing’s syndrome. Cushing’s syndrome is a hormone disorder that results from high levels of cortisol in the blood, while Cushing’s disease refers to one specific cause of Cushing’s syndrome, a corticotroph adenoma in the pituitary gland that produces large amounts of ACTH. POMC mutations lead to glucocorticoid deficiency together with altered skin colouring and obesity due to the lack of ACTH and alpha melanocyte-stimulating hormone. Damage to the adrenal gland (causes include autoimmune and infective, e.g. tuberculosis) results in Addison’s disease (primary adrenal insufficiency). Familial glucocorticoid deficiency arises secondary to mutations in the MC2R or its accessory protein MRAP (MC2R accessory protein), and further genes have been recently identified in the steroidogenic pathway. Abnormalities in the steroid synthesis pathway (as seen in congenital adrenal hyperplasia) may lead to glucocorticoid deficiency in some cases. Finally, abnormalities in the pre-receptor metabolism of cortisol or mutations in the glucocorticoid receptor itself will also lead to abnormalities in the HPA axis.
Endocrine system
Aida Lai in Essential Concepts in Anatomy and Pathology for Undergraduate Revision, 2018
Adrenal insufficiency Inadequate secretion of cortisol and aldosteroneCauses: primary (increased levels of ACTH): – autoimmune– TBsecondary (reduced levels of ACTH): – pituitary diseaseSymptoms: – fatigue– hypotension
Endocrine diseases and pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Treatment of adrenal insufficiency is straightforward and largely empiric. Primary adrenal insufficiency obligates hormone replacement for both cortisol and aldosterone, whereas secondary adrenal insufficiency obligates replacement only for cortisol (since the renin–angiotensin–aldosterone axis is preserved). For cortisol replacement, a physiologically sound surrogate regimen is hydrocortisone 20mg orally in the morning and 10mg orally in the late afternoon; a pharmacologically equivalent alternative glucocorticoid such as cortisone acetate or prednisone may be substituted. As aldosterone surrogate, the synthetic mineralocorticoid fludrocortisone (Florinef) is used in a dose averaging 0.1mg (range 0.05–0.2 mg) orally each morning (67). The dose of fludrocortisone can be adjusted to maintain blood pressure and plasma potassium within the normal range. During labor and delivery, surgery, or severe intercurrent illness, supplemental glucocorticoid in doses intended to mimic natural stress-stimulated hypercortisolemia is prescribed. A traditional “stress” regimen is hydrocortisone 50mg intravenously every 8hours (63). At this dosage, hydrocortisone exhibits sufficient mineralocorticoid agonism that fludrocortisones is unnecessary.
Sex differences in the hypothalamic-pituitary-adrenal axis response following a single or multiple days of sleep restriction
Published in Stress, 2020
Katelyn N. Buban, Elizabeth A. Shupe, Stephen W. Rothwell, T. John Wu
Relative expression of 11β-hydroxylase, which is an enzyme involved in the biosynthesis of CORT via the conversion of deoxycorticosterone to the active corticosterone (White, Pascoe, Curnow, Tannin, & Rösler, 1992), was measured in the adrenal glands to assess for adrenal insufficiency following PSD. Adrenal insufficiency is a form of adrenal fatigue or exhaustion believed to be caused by a period of overactivation of the adrenal glands, whereby the adrenals are unable to produce CORT due to either a change in local enzymatic activity, or due to a disruption in higher level systems involved in CORT release (Guilliams & Edwards, 2010). 11β-hydroxylase expression, was increased in males but not females following both one and three days of sleep deprivation. While, females showed greater 11β-hydroxylase expression overall compared to their male counterparts. These findings suggests that it is not adrenal insufficiency caused by changes in enzymes that is responsible for the dysregulation in HPA axis reactivity, and that there might be sex-specific differences in baseline enzymatic activity that might contribute to overall sex differences in the HPA axis reported in the literature (Rao & Androulakis, 2017). Therefore, the alterations seen at the level of the adrenal glands might be due to changes in higher-order systems such as the adrenal-sympathetic system or they might be sex-specific strategies employed by the adrenals to combat disruptions elsewhere in the HPA axis.
Management of immune-related adverse events resulting from immune checkpoint blockade
Published in Expert Review of Anticancer Therapy, 2019
Barouyr Baroudjian, Dimitri Arangalage, Stefania Cuzzubbo, Baptiste Hervier, Celeste Lebbé, Gwenael Lorillon, Abdellatif Tazi, Gerard Zalcman, Mohamed Bouattour, Frédéric Lioté, Jean-François Gautier, Solenn Brosseau, Nelson Lourenco, Julie Delyon
Hypophysitis occurs in 8% of patients treated with combination therapy and is classically associated with anti-CTLA4 rather than anti-PD1 (9% with ipilimumab 3 mg/kg vs. 0.5% with nivolumab 3 mg/kg), with a dose-dependent relationship for ipilimumab [54]. Patients with hypophysitis may present with fatigue and acute headache which may be associated with hypopituitarism, including gonadal, thyroid and adrenal deficiency. Initial symptoms may be nonspecific with complaints of fatigue, nausea, amenorrhea, erectile dysfunction, hypotension, hyponatremia, and hypoglycemia. Hypophysitis with adrenocorticotropic hormone (ACTH) release has been reported in a patient with an acute and transient Cushing’s syndrome that consecutively converted into secondary adrenal deficiency [55]. The most common signs of adrenal insufficiency are nausea, vomiting, weakness, fatigue, mild cognitive dysfunction, hypotension and fever, and are mostly related to primary adrenal insufficiency. Diagnosis is typically made by characteristic results of laboratory investigations (Table 3) and/or radiographic alterations, such as pituitary gland enlargement. ACTH stimulation tests can differentiate primary from secondary failure, although steroid replacement therapy might permanently be required in both cases.
Approaches for development of LAG-3 inhibitors and the promise they hold as anticancer agents
Published in Expert Opinion on Drug Discovery, 2022
Martin Perez-Santos, Maricruz Anaya-Ruiz, Luis Villafaña-Diaz, Gabriela Sánchez Esgua
Treatment-related adverse events observed in at least 10% of patients were pruritus, fatigue, rash, hypothyroidism, diarrhea, and vitiligo. Treatment with antibodies can lead to immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and myocarditis, among others. 3.7% of treated patients developed pneumonitis, which was resolved in 85% with corticosteroid treatment. Colitis occurred in 7% of treated patients and resolved in 83% with corticosteroid treatment. Hepatitis was found in 6% of the treated patients, which resulted in 70% after of corticosteroid treatment. Adrenal insufficiency occurred in 4% of patients, where 87% were treated with hormone replacement therapy and corticosteroids. Thyroiditis was present in 2.8% of treated patients, which resulted in 90% after corticosteroid treatment. Nephritis and renal dysfunction were observed in 2% of patients, which resolved in 71% with corticosteroid treatment. Dermatitis occurred in 9% of patients, resulting in 70% after corticosteroid treatment. Myocarditis was present in 1.7% of patients and was 100% resolved after treatment with corticosteroids.