Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10-46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common (n = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors.
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PMID:Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up. 3306 79

Nivolumab, a fully human IgG4 immune checkpoint inhibitor (ICI) antibody, has been approved for a variety of cancers. Several endocrine-associated immune-related adverse events have been reported, but the incidence rate is relatively low. This is a case of a patient with gastric cancer who underwent nivolumab therapy, leading to type 1 diabetes as well as adrenocorticotropic hormone (ACTH) deficiency and hypothyroidism almost simultaneously. A 70-year-old man with no previous history of diabetes was treated with nivolumab monotherapy for gastric cancer in November 2018. After 8 courses of nivolumab, he was diagnosed with type 1 diabetes associated with ICI; consequently, insulin therapy was initiated in March 2019. In April 2019, he was transported to hospital due to suffering from prolonged hypoglycemia, disturbed consciousness, and fever. He frequently experienced episodes of hypoglycemia, with poor controlled glycemia. His disturbed consciousness and fever also sustained. Further investigation of his hormones revealed low cortisol and ACTH levels, as well as hypothyroidism. His blood glucose control was improved after the introduction of hydrocortisone and thyroid hormone; he became alert and afebrile. In January 2020, he received a followed-up in an outpatient setting under insulin, hydrocortisone, and thyroid replacement therapy. Endocrine defect associated with ICIs, especially type 1 diabetes or ACTH deficiency, is a rare condition. To the best of our knowledge, this is the 1st case of multiple endocrinopathies simultaneously induced by nivolumab. Various endocrine concomitant defects should be taken into consideration when treating with nivolumab.
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PMID:Type 1 Diabetes, ACTH Deficiency, and Hypothyroidism Simultaneously Induced by Nivolumab Therapy in a Patient with Gastric Cancer: A Case Report. 3317 83


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