Response to Comment on Hughes et al. An Early Pregnancy HbA1c ≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes. Diabetes Care 2014;37:2953–2959

Hughes, Ruth; Moore, Michael C.; Gullam, Joanna; Rowan, Janet

doi:10.2337/dc15-0401

Cited by 51 publications

(7 citation statements)

References 5 publications

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“…Single hormone deficiency - ACTH in isolated ACTH deficiency [34, 45, 70, 86] or insulin in T1DM [132, 139, 140, 142]) are more commonly reported than single hormone excess - thyroxine in Graves’ disease [102] and ACTH in Cushing’s syndrome [127]. Occasionally, the endocrinopathy may present with symptoms of one hormone excess followed by symptoms that reflect the same hormone’s deficiency - hyperthyroidism progressing to hypothyroidism [116].…”

Section: Discussionmentioning

confidence: 99%

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Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Tan

Iyengar

Mizokami-Stout

et al. 2019

Clin Diabetes Endocrinol

141

149

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BackgroundSince 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug’s AEs (which may change during a drug’s life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O’Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed.MethodsIn July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles’ references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized.ResultsOne hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing’s syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis.ConclusionsThe spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.Electronic supplementary materialThe online version of this article (10.1186/s40842-018-0073-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Onset of symptoms can occur as early as 1 week [140] or as late as 416 weeks [102] with most in the first 20 weeks.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Tan

Iyengar

Mizokami-Stout

et al. 2019

Clin Diabetes Endocrinol

141

149

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“…In our review of literature, we found some case reports that demonstrated incidence of DKA starting as early as 1 week and ranging up to 5 months after beginning treatment with nivolumab and pembrolizumab. [3, 4] Our index case also falls into this time period since the patient was diagnosed with DKA about 3 months after initiation of combination checkpoint inhibitor therapy, which led to our initial assumption that it was indeed IDDM. Unfortunately human leukocyte antigen (HLA) typing, anti-GAD65, IA-2 and ZnT8 antibody testing was not obtained as part of the initial workup, which are useful in the diagnosis of IDDM, nor did he have any prior testing done before initiation of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Only few cases of immunotherapy related fulminant diabetes mellitus have been reported so far. [3–5]…”

Section: Introductionmentioning

confidence: 99%

Combined checkpoint inhibitor therapy causing diabetic ketoacidosis in metastatic melanoma

Changizzadeh¹,

Mukkamalla²,

Armenio³

2017

j. immunotherapy cancer

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BackgroundThere has been a significant improvement in survival of advanced malignancies with the advent of checkpoint inhibitors. These newer treatment modalities come with a wide spectrum of unique side effects, termed immune related adverse events (irAE), ranging from mild skin rash to severe colitis. Included in that spectrum is the rare side effect of autoimmune diabetes mellitus. Despite a few case reports illustrating the incidence of autoimmune diabetes associated with immunotherapy, there has not been much mentioned about exacerbation or acceleration of hyperglycemia in non-autoimmune settings leading to de novo diagnosis of type 2 diabetes mellitus.Case presentationWe report the case of a 42 year old man with metastatic melanoma and no prior history of diabetes mellitus, who presented with diabetic ketoacidosis (DKA) after 3 cycles of combination checkpoint inhibitor therapy using nivolumab and ipilimumab. New onset diabetes mellitus was diagnosed on the basis of elevated hemoglobin A1c, in the absence of prior personal or family history. Autoimmune or type 1 diabetes mellitus was ruled out with normal levels of anti-glutamic acid decarboxylase 65 (GAD65) antibody, zinc transporter 8 (ZnT8) antibody, and islet antigen-2 (IA-2) antibody.ConclusionsThis case report highlights the importance of recognizing rare but serious adverse events related to immunotherapy and incorporation of appropriate tools for early identification and management in national cancer treatment guidelines.

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“…Another question is whether blocking the immune checkpoints breach the tolerance and enable the pathological T cells to react with self‐antigen? In fact, some autoimmune endocrinopathies have been reported in trials involving anti‐PDL‐1 and anti‐CTLA‐4 monoclonal antibodies, including autoimmune diabetes …”

Section: Negotiators With Biological Barriersmentioning

confidence: 99%

Biohybrid Nanoparticles to Negotiate with Biological Barriers

Mohammadi

Corbo

Molinaro

et al. 2019

Small

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Incapability of effective cross-talk with biological environments has partly impaired the in vivo functionality of nanoparticles (NPs). Homing, biodistribution, and function of NPs could be engineered through regulating their interactions with in vivo niches. Inspired by communications in biological systems, endowing a "biological identity" to synthetic NPs is one approach to control their biodistribution, and immunonegotiation profiles. This syntheticbiological combination is referred to as biohybrid NPs, which comprise both i) engineerable, readily producible, and trackable synthetic NPs as well as ii) biological moieties with the capability to cross-talk with immunological barriers. Here, the latest understanding on the in vivo interactions of NPs, biological barriers they face, and emerging methods for quantitative measurements of NPs' biodistribution are reviewed. Some key biomolecules that have emerged as negotiators with the immune system in the context of cancer and autoimmunity, and their inspirations on biohybrid NPs are introduced. Critical design considerations for efficient cross-talk between NPs and innate and adaptive immunity followed by hybridization methods are also discussed. Finally, clinical translation challenges and future perspectives regarding biohybrid NPs are discussed.

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Response to Comment on Hughes et al. An Early Pregnancy HbA1c ≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes. Diabetes Care 2014;37:2953–2959

Cited by 51 publications

References 5 publications

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Combined checkpoint inhibitor therapy causing diabetic ketoacidosis in metastatic melanoma

Biohybrid Nanoparticles to Negotiate with Biological Barriers

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