Severe Hyponatremia Masking Central Diabetes Insipidus in a Patient with a Lung Adenocarcinoma

Abstract

Altered natremia is a common electrolyte disorder in clinical practice and a paraneoplastic manifestation. The syndrome of inappropriate antidiuretic hormone secretion is the first diagnostic suspicion in a patient with cancer and hyponatremia, although entities such as adrenal insufficiency primary or secondary to metastatic involvement must be taken into account. Likewise, immunorelated endrocrinopathies such as hypophysitis have been reported after the introduction of checkpoint inhibitors. A 46-year-old man diagnosed with metastatic adenocarcinoma of the lung with severe hyponatremia (111 mmol/L) consulted due to altered level of consciousness. The initial cranial CT scan did not reveal pituitary brain metastatic involvement; however, an MRI could not be performed due to the patient’s clinical situation and subsequent exitus. The water restriction test confirmed the diagnostic suspicion of central diabetes insipidus. Medical treatment with desmopressin was started to avoid fluid depletion with improvement of natremia figures. It represents an exceptional case of central diabetes insipidus masked by severe hyponatremia in a patient with metastatic lung adenocarcinoma without initial evidence of pituitary metastatic involvement by CT imaging in treatment with nivolumab (anti-PD-1 agent). Secondary adrenal insufficiency due to pituitary metastatic involvement and endocrinologic toxicity immunorelated to the new checkpoint inhibitors should be considered as possible etiologic agents of central diabetes insipidus, even with hyponatremia.

Diabetes insipidus: A rare endocrine complication of immune check point inhibitors: A case report and literature review

“…From the 14 patients presenting with CDI with available data on their treatment, 5 had been treated with monotherapy with CTLA-4 Abs, 6 with monotherapy with PD1-Abs whereas 3 cases had been treated with combination treatment (CTLA-4 Abs and PD-1 Abs). Regarding our case, this is the fourth case of nivolumab-induced CDI published in the literature ( 11 , 15 , 20 ) and the first female patient presenting with nivolumab-induced CDI. In two other cases CDI was induced by a combination treatment with nivolumab and ipilimumab ( 9 , 13 ).…”

“…Patients treated with ICIs rarely develop CDI secondary to an autoimmune process involving the hypothalamo-posterior pituitary region. Dysregulation of the posterior pituitary-hypothalamic axis induced by ICI has been reported in 13 case reports that are available in the current literature (summarized in Table II ), ( 1 , 7-16 , 20 , 21 ). Almost all patients developed CDI with a substantial delay from treatment administration, ranging from 28 to 270 days, except in one case where CDI developed immediately after sintilimab, a PD-1 inhibitor ( 14 ).…”

“…Finally, we ended-up to only 13 cases reports reporting data on DI among ICI treated patients (Flow diagram). A total of 14 patients presenting with DI post-immunotherapy with predominance of the male sex (11 males vs. 1 female, in 2 patients sex was not specified) were described (Table V), (1,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)20,21). All patients had been treated with ICIs for solid malignancies except two cases treated for Hodgkin lymphoma and acute myeloid leukaemia.…”

The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events

“…ICI treatment has been reported to dysregulate the posterior pituitary–hypothalamic axis in 15 individual cases (12 males and 3 females) included in Table 2 [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Most patients developed CDI after a period ranging from 28 to 270 days following treatment, with the exception of one patient who developed CDI immediately after receiving sintilimab, a PD-1 inhibitor [ 61 ].…”

“…At least five patients [ 52 , 57 , 59 , 63 , 64 ] had received ICIs as first-line systematic therapy for advanced disease. Notably, in one case, whole brain radiotherapy had preceded the ICI therapy, and thus, the mechanism of panhypopituitarism was not clear [ 53 ].…”