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Oncological effects on the central nervous system
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Hypophysitis is an inflammatory process of the pituitary gland which manifests with headache, fatigue, dizziness, and memory impairment. Most patients also have deficiency of several anterior pituitary hormones, usually adrenocorticotropic hormone (ACTH) or thyroid stimulating hormone (TSH). Conversely, posterior pituitary function is usually preserved, as central diabetes insipidus is only infrequently reported. This compares to pituitary metastatic disease in which central diabetes insipidus is a common feature. Hypophysitis is more prevalent in association with the anti-CTLA4 drugs (e.g. ipilimumab), where it occurs in 9%–10% of patients, compared to other ICI drug groups (anti-PD1 or anti-PDL1 monoclonal antibodies such as pembrolizumab), where it occurs in <1% of patients (29). Hypophysitis tends to present 6–12 weeks after the initiation of anti-CTLA4 therapy and is more frequent in patients treated with higher doses; it affects men and women equally (30).
Endocrinology and diabetes
Published in Shibley Rahman, Avinash Sharma, A Complete MRCP(UK) Parts 1 and 2 Written Examination Revision Guide, 2018
Shibley Rahman, Avinash Sharma
In true central diabetes insipidus, patients are unable to concentrate their urine to greater than plasma osmolality but after administration of vasopressin the urine osmolality increases by >50%. Patients with nephrogenic diabetes insipidus are unable to concentrate their urine and they show no response to vasopressin.
Surgical Endocrine Emergencies
Published in Stephen M. Cohn, Matthew O. Dolich, Kenji Inaba, Acute Care Surgery and Trauma, 2016
Sara B. Edwards, Steven Brower, Jennifer L. Marti
Central diabetes insipidus (CDI) results from inadequate secretion of the hypothalamic polypeptide antidiuretic hormone (ADH). ADH originates in the supraoptic and paraventricular nuclei of the hypothalamus and is excreted by the posterior pituitary gland [1]. Hypovolemia or increased serum osmolality stimulates ADH secretion, which increases renal water reabsorption. Insufficient ADH secretion results in polyuria that can lead to severe hypovolemia, hypotension, and hypernatremia if unrecognized.
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
The small intestine is another major part of the human digestive system and further processes macromolecules into tri-, di-, and mono-peptides [38]. In small intestinal fluids, proteins showed greater stability than peptides. The reason might be that proteins have more complex secondary and tertiary structures, leading to less easily accessible peptide bonds [40]. Therefore, peptides were more often evaluated in small intestinal fluids than proteins were. Oxytocin and vasopressin are pituitary neuropeptides, functioning as an integrated, adaptive system, allowing the mammalian body to survive, maintain homeostasis, and reproduce [41]. The two molecules are potential drugs to treat social deficits in neurodevelopmental disorders, including autism spectrum disorder [42]. A modified vasopressin, 1- deamino-8-D-arginine-vasopressin (dDAVP), has been successfully intranasally used in patients with central diabetes insipidus. Buccal administration of oxytocin in pregnant women at term is followed by uterine contractions and increased plasma concentrations of oxytocin. However, their oral bioavailability was only 0.1–0.2% in healthy volunteers. Arginine-vasopressin, oxytocin, and their synthetic analogues were incubated in human small intestinal fluid from healthy volunteers. The quantification of degradation was carried out by reversed-phase high performance liquid chromatography (RP-HPLC). Arginine-vasopressin was completely degraded in 30 min, while dDAVP remained 50% of the intact after 35 min. Oxytocin showed much more stability than dDAVP and arginine-vasopressin [43].
Fatal fulminant hepatitis induced by combined ipilimumab and nivolumab therapy despite favorable histologic response and confirmed by autopsy in a patient with clear cell renal cell carcinoma
Published in Immunological Medicine, 2021
Terufumi Kubo, Taro Sugawara, Tomoyo Shinkawa, Tomoyo Kurisu, Nodoka Kouzen, Toshiaki Tanaka, Fumimasa Fukuta, Kouji Yamasaki, Shintaro Sugita, Kazuhiko Matsuo, Rena Morita, Yoshihiko Hirohashi, Tomohide Tsukahara, Takayuki Kanaseki, Tadashi Hasegawa, Naoya Masumori, Toshihiko Torigoe
We also found neurohypophysitis with infiltration of a high number of CD8-positive/TIA-1-positive cells in this patient at autopsy. Although we did not perform a detailed clinical examination to make a diagnosis of diabetes insipidus, the polyuria noted in our patient in the 3 days after admission was assumed to be due to CTL-mediated destructive neurohypophysitis resulting in central diabetes insipidus. Blood ADH level on the first day after admission was higher than normal, which is consistent with tissue destruction caused by inflammation. Thus far, there has been only one report of ICI (PD-L1 blocker)-induced diabetes insipidus [10]. CTLA-4 blockade often causes adenohypophysitis but not neurohypophysitis [11,12]. This is the first case of histologically proven ICI-induced neurohypophysitis.
Not so sweet diabetes: a rare case of postpartum central diabetes insipidus
Published in Journal of Obstetrics and Gynaecology, 2022
Xi May Zhen, Kirby Wong, Amelia Fernandes, Anne-Maree Kean
We present a rare case of postpartum central diabetes insipidus (DI) in a 36 year old woman. DI occurring during pregnancy and the postpartum period can be due to central causes, nephrogenic causes, or transient gestational DI due to excess vasopressinase activity (Hague 2009). The incidence of DI during pregnancy and the immediate puerperium is difficult to estimate, but previous reports have suggested that the incidence may be around 2–4 cases per 100,000 gestations (Durr and Lindheimer 1996). Diagnosis is sometimes delayed as the symptoms of polyuria and polydipsia may initially be attributed to pregnancy-induced changes. Untreated DI can be exacerbated by reduced fluid intake during labour and delivery, leading to serious neurological sequelae for mother and baby.