Permanent diabetes insipidus in a patient with mesothelioma treated with immunotherapy

SUMMARY 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).

Asociación de diabetes insípida central y diabetes mellitus tipo 2 / Association between central diabetes insipidus and type 2 diabetes mellitus

La diabetes insípida central es una enfermedad rara del hipotálamo y de la neurohipófisis, y muy inusualmente se halla en el adulto con diabetes mellitus 2. Se manifiesta por un síndrome poliúrico polidípsico, que debe diferenciarse de la diabetes mellitus mal controlada. Ante la similitud de ambas entidades, y lo infrecuente de su coexistencia, se dificulta su sospecha. Se presenta el caso de un hombre de 72 años de edad, con diabetes mellitus 2 y pobre control de la misma (hiperglucemias de ayuno mayores a 180 mg/dl) que cursó un síndrome poliúrico de larga data. La hipernatremia y la osmolalidad plasmática elevadas, junto a una osmolalidad urinaria baja llevaron a la sospecha de diabetes insípida, que posteriormente se confirmó con la prueba de deshidratación y la administración de desmopresina s.c. Con un aumento del 61% de la osmolalidad urinaria calculada una hora post desmopresina s.c. fue diagnosticada como diabetes insípida del tipo central. La resonancia magnética nuclear mostró una mancha brillante con neurohipófisis normal, contribuyendo al diagnóstico de la forma idiopática.

Central diabetes insipidus is a rare disease of the hypothalamus and neurohypophysis. It is very unusually found in the adult with type 2 diabetes mellitus. It is manifested by a polydipsic polyuric syndrome, which must be distinguished from the poorly controlled type 2 diabetes mellitus. Given the similarity of both entities and the unusual nature of their coexistence, their suspicion is difficult. The case of a 72-year-old male with type 2 diabetes mellitus with poor insulin control (fasting hyperglycemia greater than 180 mg/dl) who had a long-standing polyuric syndrome is here presented. Hypernatremia and plasma osmolality elevated together with a low urinary osmolality led to the suspicion of diabetes insipidus, which was subsequently confirmed by the dehydration test and the administration of desmopressin sc. With 61% increase in the calculated urinary osmolarity one hour post desmopressin s.c., diabetes insipidus of central type was diagnosed. Nuclear Magnetic Resonance showed a bright spot with normal neurohypophysis, contributing to the diagnosis of the idiopathic form.

Perianal Langerhans cell histiocytosis: a rare presentation in an adult male

Langerhans cell histiocytosis (LCH) is a rare disease characterized by a proliferation of cells that show immunophenotypic and ultrastructural similarities with antigen-presenting Langerhans cells of mucosal sites and skin. LCH in adults is rare, and there are still many undiagnosed/misdiagnosed patients. We describe LCH involvement of the perianal region of a 33-year-old male with a previous history of diabetes insipidus. The differential diagnosis and all the reported cases of LCH of the perianal skin involvement since its description in 1984 till 2016 are discussed. LCH should be considered in the differential diagnosis of perianal ulceration, especially in young patients where topical drug treatment has failed. The history of previous central diabetes insipidus of unknown etiology demands imaging studies in order to rule out central involvement of the disease.

Central diabetes insipidus: alert for dehydration in very low birth weight infants during the neonatal period. A case report / Diabete insípido central: alerta para desidratação no período neonatal em recém-nascidos de muito baixo peso. Um relato de caso

CONTEXT: Central diabetes insipidus (CDI) is a rare cause of hypernatremia during the neonatal period. The diagnosis is particularly difficult in very low birth weight (VLBW) newborns. CASE REPORT: We report on a preterm newborn who presented CDI soon after birth. On the third day of life, signs of dehydration were present despite normal fluid supply. The diuresis rate was 4.4 ml/kg/h. Although the fluid supply was then increased, the dehydration continued, with hypernatremia, normal glycemia, diuresis of 7.4 ml/kg/h and urine density of 1005 mOsmol/l. Thus, a diagnostic hypothesis of diabetes insipidus was raised. A test with a nasal vasopressin analogue (dDAVP) was performed and CDI was confirmed. Reduction of the fluid supply became possible through appropriate treatment. CONCLUSION: The diagnosis of CDI is rarely made during the neonatal period, especially in VLBW newborns, because of the difficulty in detecting elevated diuresis. Persistent hypernatremia, usually accompanied by hyperthermia despite abundant fluid supply, weight loss and low urine osmolality are important signs of alert. .

CONTEXTO: Diabete insípido central (DIC) é uma rara causa de hipernatremia durante o período neonatal. O diagnóstico é difícil, particularmente em recém-nascidos (RN) de muito baixo peso (RNMBP). RELATO DE CASO: Relatamos um RN que apresentou DIC logo após o nascimento. No terceiro dia de vida, apresentava sinais de desidratação, embora estivesse recebendo aporte adequado de líquidos. A diurese aferida era de 4,4 ml/kg/h. Apesar do aumento do aporte hídrico, manteve-se desidratado, com hipernatremia, valores normais de glicemia e diurese de 7,4 ml/kg/h com densidade urinária de 1005 mOsmol/l. Desta forma, a hipótese diagnóstica de diabete insípido foi considerada. O teste com análogo da vasopressina (dDAVP) foi realizado e DIC foi confirmado. A redução do aporte de líquidos foi possível com o tratamento adequado. CONCLUSÃO: O diagnóstico de DIC raramente é realizado durante o período neonatal, particularmente em RNMBP, devido à dificuldade em detectar diurese aumentada. Hipernatremia persistente, geralmente acompanhada de hipertermia, apesar do abundante aporte de água, perda de peso e osmolaridade urinaria baixa, são importantes sinais de alerta. .

Sheehan's syndrome with central diabetes insipidus / Síndrome de Sheehan e diabetes insípido central

Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

A síndrome de Sheehan está relacionada à ocorrência de hipopituitarismo pós-parto, geralmente precedido por hemorragia pós-parto. Essa condição clínica ainda constitui causa comum do hipopituitarismo observado em países em desenvolvimento como a Índia. Essa síndrome se caracteriza pela insuficiência da glândula hipofisária anterior, porém com a conservação das funções da glândula hipofisária posterior. A disfunção da hipófise posterior, sob a forma de diabetes insipidus central, é algo raramente observado em pacientes que apresentam a síndrome de Sheehan. Neste artigo, descrevemos o caso de uma jovem que, após o sexto parto, apresentou hemorragia pós-parto grave, seguida pela evolução de pan-hipopituitarismo que foi confirmado por pesquisa hormonal e exames de imagem que evidenciaram sela vazia. A jovem também apresentou poliúria. Os resultados do teste de privação de água e exame de resposta à vasopressina indicaram diabetes insípido central. A paciente fazia uso contínuo de desmopressina para controlar a poliúria.

Hematologic and Clinical Features of 3q21q26 Syndrome: Extremely Poor Prognosis and Association with Central Diabetes Insipidus / 대한진단검사의학회지

BACKGROUND: 3q21q26 syndrome includes chromosomal abnormalities of inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes hematological diseases by the leukemogenic mechanism that the enhancer of ribophorin I gene in 3q21 induces the transcription of ecotropic viral integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26 syndrome may be preceded by diabetes insipidus (DI), particularly when combined with monosomy 7, and is a unique disease entity. METHODS: From May 2001 to June 2006, a total of 5 patients with hematologic malignancy were found to have 3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and association with DI were investigated. RESULTS: The rearrangement type of 3q21q26 was inv(3)(q21q26) in four patients and t(3;3)(q21; q26) in one. These patients' French American British types were AML M1, M2, M4 and M7, showing evident dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were observed. The platelet count was relatively high as AML. All the five patients were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days after being diagnosed with DI. While DI was well controlled with oral desmopressin, leukemia was refractory to chemotherapy. CONCLUSIONS: This study supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with DI is a disease of unique characteristics. In the relation between DI and monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired abnormality of hematopoietic cells affects production of DDAVP by neurohormonal cells in hypothalamus. The mechanism needs further study, and this research should contribute to the understanding of genetic roles in leukemia appearing in different forms.