Diagnosis and Treatment > Medication

You are looking at 1 - 2 of 2 items for :

  • Levothyroxine x
Clear All
Isabella Lupi Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Isabella Lupi in
Google Scholar
PubMed
Close
,
Alessandro Brancatella Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Alessandro Brancatella in
Google Scholar
PubMed
Close
,
Mirco Cosottini Neuroradiology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

Search for other papers by Mirco Cosottini in
Google Scholar
PubMed
Close
,
Nicola Viola Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Nicola Viola in
Google Scholar
PubMed
Close
,
Giulia Lanzolla Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Giulia Lanzolla in
Google Scholar
PubMed
Close
,
Daniele Sgrò Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Daniele Sgrò in
Google Scholar
PubMed
Close
,
Giulia Di Dalmazi Section of Endocrinology, Department of Medicine and Aging Sciences, Ce.S.I-Me.T., “G.D’Annunzio” University of Chieti-Pescara, Chieti, Italy

Search for other papers by Giulia Di Dalmazi in
Google Scholar
PubMed
Close
,
Francesco Latrofa Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Francesco Latrofa in
Google Scholar
PubMed
Close
,
Patrizio Caturegli Division of Immunology, Department of Pathology, Johns Hopkins University, Baltimore Maryland, USA

Search for other papers by Patrizio Caturegli in
Google Scholar
PubMed
Close
, and
Claudio Marcocci Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Claudio Marcocci in
Google Scholar
PubMed
Close

Summary

Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.

Learning points:

  • PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade.

  • Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities.

  • Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease.

  • PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases

Open access
Ploutarchos Tzoulis Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

Search for other papers by Ploutarchos Tzoulis in
Google Scholar
PubMed
Close
,
Richard W Corbett Department of Medicine, Imperial College London, London, UK

Search for other papers by Richard W Corbett in
Google Scholar
PubMed
Close
,
Swarupini Ponnampalam Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

Search for other papers by Swarupini Ponnampalam in
Google Scholar
PubMed
Close
,
Elly Baker Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

Search for other papers by Elly Baker in
Google Scholar
PubMed
Close
,
Daniel Heaton Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

Search for other papers by Daniel Heaton in
Google Scholar
PubMed
Close
,
Triada Doulgeraki Medical School, University of Athens, Athens, Greece

Search for other papers by Triada Doulgeraki in
Google Scholar
PubMed
Close
, and
Justin Stebbing Department of Surgery and Cancer, Imperial College London, London, UK

Search for other papers by Justin Stebbing in
Google Scholar
PubMed
Close

Summary

Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.

Learning points:

  • Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.

  • Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.

  • Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.

  • Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.

Open access