Permanent diabetes insipidus in a patient with mesothelioma treated with immunotherapy

Our plain-English summary of Permanent diabetes insipidus in a patient with mesothelioma treated with immunotherapy, by L. Brilli, L. Calabrò, M. Campanile, et al (Archives of Endocrinology and Metabolism, 2020).

The study

• Authors: L. Brilli, L. Calabrò, M. Campanile, T. Pilli, C. Agostinis, A. Cerase, M. Maio, M.G. Castagna
• Journal: Archives of Endocrinology and Metabolism
• Published: 2020;64(4):483-486
• Type of article: Case report
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Checkpoint inhibitors have substantially improved the prognosis for patients with advanced malignancy. Treatment with immunomodulants has the ability to reactivate the immune system against tumor cells, but can also trigger the development of immune-related adverse events that reflects a loss of tolerance of the immune system for self-antigens. Regarding the endocrine system, thyroid and pituitary are the most frequent glands involved; in particular hypophysitis is commonly observed with anti-CTLA4 with a variable impaired anterior pituitary dysfunction (mainly ACTH and TSH dysregulation) while a posterior pituitary dysfunction has been rarely described. A 68-year-old man with a diagnosis of metastatic mesothelioma started in September 2016 first-line treatment with tremelimumab and durvalumab. After 3 cycles he presented sudden onset of polydipsia and polyuria without other symptoms. Diagnostic work-up, including a water deprivation test, established a diagnosis of central diabetes insipidus. Patient started sublingual desmopressin 60 mcg three times a day, that was subsequently increased up to 480 mcg/die. At magnetic resonance imaging the posterior lobe of pituitary gland did not show high signal intensity on T1-weighted images. After regression of diabetes insipidus symptoms under desmopressin, patient restarted cancer treatment and received additional 10 doses without worsening of endocrinological toxicity or further treatment-related toxicities, maintaining the same desmopressin dosage. Posterior pituitary dysfunction has been rarely observed in patients treated with immunomodulants. To our knowledge, this is the first observation of permanent central diabetes insipidus in patients treated with combined immune checkpoint inhibitors (tremelimumab and durvalumab).

In plain English

This was a case report from Italy about one 68-year-old man with metastatic mesothelioma and more than 10 years of asbestos exposure. The article does not say whether the mesothelioma was pleural or peritoneal. It concerned diabetes insipidus that began during cancer treatment and that the authors attributed to the drug combination, not an effect of asbestos. In September 2016 he started two immunotherapy drugs, tremelimumab and durvalumab, within the NIBIT-MESO-1 study. At week 24 he developed sudden heavy thirst and urination, passing 4000 mL of urine a day while drinking 3200 mL. Tests, including a water deprivation test, led to a diagnosis of central diabetes insipidus, a shortage of the hormone vasopressin causing very high urine output. His anterior pituitary function was normal. He was treated with desmopressin, raised up to 480 mcg a day. After a 28-day pause he received 10 more doses of cancer treatment without worsening side effects. He was still taking desmopressin six months after cancer treatment stopped in April 2018. The authors concluded that, to their knowledge, this was the first reported case of isolated and permanent diabetes insipidus with this drug combination.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 68-year-old Caucasian man with metastatic mesothelioma, admitted to hospital in March 2017; authors based at the University Hospital of Siena, Italy
• Exposure: The patient had more than 10 years of asbestos exposure; no fiber type or job is given. The exposure studied in the report was immunotherapy: tremelimumab 1 mg/kg every 4 weeks for 4 cycles and durvalumab 20 mg/kg every 4 weeks for 13 cycles, within the NIBIT-MESO-1 study
• Main results:
  • The patient had a partial response of the cancer on CT scan after the 3rd cycle (week 12)
  • At week 24 the patient developed sudden excessive thirst with excessive urination, including at night
  • The patient's urine output was 4000 mL/day against a fluid intake of 3200 mL/day
  • The patient's thyroid function and anterior pituitary function were normal
  • In the water deprivation test, the patient's sodium rose to 150 mEq/L after 10 hours and to 152 mEq/L two hours later, with 3.8% weight loss and plasma osmolality of 299 mOsm/L
  • MRI showed no brain metastases. The posterior lobe of the patient's pituitary gland did not show the usual bright signal on T1-weighted images
  • The patient started on desmopressin 60 mcg three times a day; the dose was gradually increased up to 480 mcg/day
  • After a 28-day pause, the patient received 10 more doses of cancer treatment without worsening hormone problems or other treatment-related side effects
  • Cancer treatment stopped in April 2018 because the disease progressed. The patient was still taking desmopressin at the last follow-up visit, 6 months later
  • The patient was not given corticosteroids
  • The authors stated their belief that the combined treatment caused damage extensive enough that the posterior pituitary had little chance to recover
• The authors' conclusion: The authors stated that, to their knowledge, this was the first reported case of isolated and permanent central diabetes insipidus in a patient treated with the tremelimumab plus durvalumab combination
• Limitations the authors state:
  • There was no pituitary imaging from before cancer treatment to compare with
  • Urine osmolality could not be measured at the hospital
  • Corticosteroids, had they been given, could have changed the course of the diabetes insipidus
  • The missing pituitary bright spot on MRI can occur in normal people, so MRI alone is not sufficient for diagnosis

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Immunotherapy, checkpoint inhibitors, Prognosis, Immune-Related Adverse Events, Tremelimumab, Durvalumab (Imfinzi).

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