Elevated or low levels of prolactin have been reported , and hypogonadotropic hypogonadism and low levels of insulinClike growth factor 1 (IGF1) can also be present 
June 28, 2022
Elevated or low levels of prolactin have been reported , and hypogonadotropic hypogonadism and low levels of insulinClike growth factor 1 (IGF1) can also be present . chance of irAEs. Symptoms and clinical signs vary depending on the target organ. IrAEs are usually managed by an oncological therapist, but in more challenging circumstances (i.e., for new onset insulinCdependent diabetes, hypoadrenalism, gonadal hormones dysfunctions, or durable hypophysitis) an endocrinologist is needed. = 0.005) and concluded that male gender and older age can be considered to be risk factors . Clinical Manifestations of HypophysitisThe autoimmune inflammation of the hypophysis generally induces structural changes and the enlargement of the glands leading to a headache, which is one of the first symptoms, and hormonal disturbance [76,77]. The measured change in pituitary size is about of 5 mm . Symptoms such as anorexia, fatigue, diarrhoea, weakness, and nausea are unspecific and could be associated with pituitary dysfunction or nonendocrineCrelated adverse events, while visual symptoms are rare . Other symptoms have been described as confusion, loss of libido, hallucination, polyuria, polydipsia, memory loss, erectile dysfunction, cold intolerance, insomnia, and dizziness [43,66,77,78]. The presence of unspecific symptoms, in particular hyponatremia, hypotension, or hypoglycaemia, points to the necessity of additional endocrine evaluations. Owing to the possible fatal nature of untreated hypoadrenalism, these patients should be immediately evaluated. The time to onset of endocrine adverse events is approximately LDV FITC 9 weeks (with a range of 5C36 weeks) after the beginning of the therapy [68,69]. A case of hypophysitis occurring 19 months after the first ipilimumab infusion has also been described . Therefore, longer term monitoring should be evaluated. Adrenocorticotropic hormone (ACTH) and/or thyroidCstimulating hormone (TSH) deficiencies are the most common manifestations, and anterior hypopituitarism is more prevalent than diabetes insipidus [49,51,79]. Elevated or low levels of prolactin have been reported , and hypogonadotropic hypogonadism and low levels of insulinClike growth factor 1 (IGF1) can also be present . A male gender and older age are considered risk factors for ICIsCrelated hypophysitis . It is important to cautiously evaluate the basal hormonal assessment at the beginning of immunotherapy and to carry out a questionnaire regarding suspicious symptoms for hypophysitis (hypoglycemia, headache, weakness, nausea, fatigue, hypotension) and measurements of glucose (before each cycle), TSH, free thyroxine (FT4), electrolytes, and morning cortisol (9 am), as hypopituitarism and cancer can have common LDV FITC symptoms and laboratory results. Pituitary magnetic resonance imaging (MRI) and a complete endocrine workCup (follicleCstimulating hormone/luteinizing hormone, estradiol/testosterone, IGFC1, prolactin, LDV FITC TSH, FT4, cortisol (9am), ACTH) should be carried out in case of compression symptoms (visual defects, headache) and/or clinically suspicious hypophysitis. When morning cortisol is 250 nmol/L or random cortisol is 150 nmol/L with clinically suspicious adrenal insufficiency, a dynamic ACTH testing should be performed and replacement therapy with glucocorticoids should be administered. An MRI is necessary to exclude the new occurrence of brain metastases and to assess the pituitary status, as pituitary morphology can vary during the course of the disease, from mild to moderate diffuse enlargement with homogenous or heterogeneous enhancement after contrast administration with stalk thickening at disease onset, to a subsequent atrophy of the gland and empty sella. A normal MRI does not exclude hypophysitis, and management should be done according to the clinical presentation and hormonal evaluation. The pituitary morphology sometimes changes before function or LDV FITC biochemical disturbances, and this could be resolved after 1C8 weeks of glucocorticoid treatment . Hypophysitis can be managed especially by HRT and evaluation of ICIs discontinuation and/or highCdose (immunosuppressive) steroid therapy. Generally, immunotherapy may be continued in patients with grade 1 (mild) hypophysitis, while for the other grades of toxicities, the therapy should be stopped and highCdose systemic steroids (0.5C2 mg/kg/day of prednisolone or equivalent) should be administered, finally moving to a physiological replacement dose of hydrocortisone or prednisolone . Once clinical improvement has been reached and toxicity is grade 1 or less, immunotherapy can resume, and appropriate HRT should be added. The Itga1 European Society of Medical Oncology (ESMO) has recently published the regarding guidelines . The thyrotroph axis and gonadotroph function may be regained, but it is uncommon for corticotroph function to be restored. Low levels of prolactin lead to a supposed lack of recovery function, with a positive predictive value of 85.7%, a negative predictive value of 57.1%, a specificity of 88.9%, sensitivity of 50%, and accuracy of 66.7% . 4.2. Thyroid Disorders and Their Management Thyroid diseases and alterations (such as hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm ) are reported in 1C6% of patients treated with antiCCTLAC4Cantibodies , representing the second most frequent kind of irAEs [11,49]. Primary hypothyroidism is established biochemically with high TSH associated to low FT4 or.