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1.
BMC Cancer ; 24(1): 572, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720306

ABSTRACT

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.


Subject(s)
Craniopharyngioma , Diabetes Insipidus, Neurogenic , Pituitary Neoplasms , Postoperative Complications , Humans , Craniopharyngioma/surgery , Craniopharyngioma/blood , Craniopharyngioma/complications , Female , Male , Retrospective Studies , Adult , Pituitary Neoplasms/surgery , Pituitary Neoplasms/blood , Pituitary Neoplasms/complications , Postoperative Complications/blood , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Adolescent , Middle Aged , Child , Young Adult , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/etiology , Neutrophils , Biomarkers/blood , Lymphocytes , Inflammation/blood , Leukocyte Count , Preoperative Period , Child, Preschool , Prognosis , ROC Curve
2.
Endocrine ; 84(2): 677-682, 2024 May.
Article in English | MEDLINE | ID: mdl-38155322

ABSTRACT

PURPOSE: In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. METHODS: All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. RESULTS: A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. CONCLUSION: Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.


Subject(s)
Arginine , Glycopeptides , Polydipsia , Polyuria , Humans , Polyuria/diagnosis , Polyuria/blood , Glycopeptides/blood , Child , Female , Male , Arginine/blood , Polydipsia/diagnosis , Polydipsia/blood , Diagnosis, Differential , Adolescent , Child, Preschool , Prospective Studies , Sensitivity and Specificity , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/blood , Infant
6.
Best Pract Res Clin Endocrinol Metab ; 34(5): 101398, 2020 09.
Article in English | MEDLINE | ID: mdl-32387127

ABSTRACT

The two main differential diagnoses of central diabetes insipidus are nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between those entities is essential as treatment differs substantially with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the indirect water deprivation test had several pitfalls, resulting in a low diagnostic accuracy. With the introduction of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of diabetes insipidus was new evaluated. While unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, a stimulation test is needed to differentiate patients with central diabetes insipidus from patients with primary polydipsia. Stimulation can either be achieved through hypertonic saline infusion or arginine infusion. While the former showed high diagnostic accuracy and superiority over the indirect water deprivation test in a recent validation study, the diagnostic accuracy for arginine-stimulated copeptin was slightly lower, but superior in test tolerance. In summary of the recent findings, a new copeptin based diagnostic algorithm is proposed for the reliable diagnosis of diabetes insipidus.


Subject(s)
Diabetes Insipidus/diagnosis , Diagnostic Techniques, Endocrine , Biomarkers/analysis , Biomarkers/blood , Diabetes Insipidus/blood , Diabetes Insipidus/etiology , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Nephrogenic/diagnosis , Diabetes Insipidus, Nephrogenic/etiology , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/etiology , Diagnosis, Differential , Diagnostic Techniques, Endocrine/trends , Humans , Neurophysins/blood , Neurophysins/physiology , Polyuria/blood , Polyuria/diagnosis , Polyuria/etiology , Protein Precursors/blood , Protein Precursors/physiology , Vasopressins/blood , Vasopressins/physiology
7.
Int Immunopharmacol ; 83: 106427, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32244049

ABSTRACT

Cancer immunotherapy is a breakthrough strategy entwined with toxicity. Immune-related hypophysitis is conventionally considered distinctive of cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. Immune-related central diabetes insipidus (CDI) is exceptional. CDI rarely manifests as hypernatremia, which is almost always euvolemic. We report a 71-years-old male patient with advanced lung cancer who experienced severe chronic hypernatremia presented as alterations in mental status five months after initiation of treatment with the anti-PD-1 checkpoint inhibitor nivolumab. Combination of persistenthypernatremia, polyuria, high plasma osmolality and hyposthenuria raised suspicion of diabetes insipidus, prompting measurement of serum concentration of arginine vasopressin(AVP). The inappropriately undetectable serum levels of AVP confirmed central diabetes insipidus (CDI). Nivolumab-related hypophysitis was recognized as possible cause of CDI. Further hormonal assessment excluded any endocrinopathy indicating disorder of posterior pituitary. Pituitary MRI was normal with persistence of hyperintensity of posterior pituitary on T1-weighted images (bright spot). The patient was scheduled to receive 1-deamino-8-D-arginine vasopressin (DDAVP), but he died suddenly due to cardiac arrest before initiation of treatment. Our report describes the first case of nivolumab related CDI, building on existing literature through: (I) underscoring hypovolemic hypernatremia as CDI manifestation; (ii) bringing into spotlight the rare anti-PD-1 treatment related hypophysitis; (iii) enriching the limited evidence on immune-related CDI. Increased awareness of nivolumab related CDI will enable prompt recognition and therapeutic intervention.


Subject(s)
Diabetes Insipidus, Neurogenic/chemically induced , Diabetes Insipidus, Neurogenic/diagnosis , Immunotherapy/adverse effects , Nivolumab/adverse effects , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Aged , Arginine Vasopressin/blood , Diabetes Insipidus, Neurogenic/blood , Humans , Hypernatremia/blood , Hypernatremia/chemically induced , Hypophysitis/blood , Hypophysitis/chemically induced , Hypophysitis/diagnostic imaging , Liver Neoplasms/drug therapy , Magnetic Resonance Imaging , Male
8.
J Clin Endocrinol Metab ; 105(7)2020 07 01.
Article in English | MEDLINE | ID: mdl-32236441

ABSTRACT

CONTEXT: Arginine stimulates pituitary hormones, like growth hormone and vasopressin, but its effect on the hypothalamic-pituitary-adrenal (HPA) axis is unknown. Arginine may also stimulate the HPA axis, possibly through a mechanism involving vasopressin. OBJECTIVE: To investigate the effect of arginine on adrenocorticotropic hormone (ACTH) and cortisol in subjects with and without vasopressin deficiency. DESIGN: Prospective study, University Hospital Basel. PARTICIPANTS: 38 patients with central diabetes insipidus, 58 patients with primary polydipsia, and 50 healthy controls. INTERVENTION: Arginine infusion with measurement of ACTH, cortisol and copeptin at baseline and 30, 45, 60, 90, and 120 minutes. RESULTS: We found different response patterns to arginine: in patients with diabetes insipidus (and low stimulated copeptin levels) median (interquartile range [IQR]) ACTH and cortisol increased from 22.9 (16.8, 38.7) to 36.6 (26.2, 52.1) ng/L and from 385 (266, 463) to 467 (349, 533) nmol/L, respectively. In contrast, median (IQR) ACTH and cortisol levels decreased in patients with primary polydipsia (despite high stimulated copeptin levels): ACTH from 17.3 (12.3, 23) to 14.8 (10.9, 19.8) ng/L and cortisol from 343 (262, 429) to 272 (220.8, 360.3) nmol/L; likewise, in healthy controls: ACTH from 26.5 (17.6, 35.7) to 14.8 (12.1, 22.7) ng/L and cortisol from 471 (393.3, 581.8) to 301.5 (206.5, 377.8) nmol/L. CONCLUSION: Diabetes insipidus is associated with increased responsiveness of ACTH/cortisol to arginine. In contrast, arginine does not stimulate the HPA axis in healthy controls or in primary polydipsia.


Subject(s)
Arginine/pharmacology , Diabetes Insipidus, Neurogenic/physiopathology , Hypothalamo-Hypophyseal System/drug effects , Pituitary-Adrenal System/drug effects , Polydipsia, Psychogenic/physiopathology , Adrenocorticotropic Hormone/blood , Adult , Diabetes Insipidus, Neurogenic/blood , Female , Glycopeptides/blood , Humans , Hydrocortisone/blood , Hypothalamo-Hypophyseal System/physiopathology , Male , Middle Aged , Pituitary-Adrenal System/physiopathology , Polydipsia, Psychogenic/blood , Prospective Studies , Young Adult
9.
Neuroendocrinology ; 110(6): 525-534, 2020.
Article in English | MEDLINE | ID: mdl-31484187

ABSTRACT

INTRODUCTION: Central diabetes insipidus (CDI) is a frequent complication of pituitary surgery, but its diagnosis lacks standardized criteria. Copeptin, a surrogate marker of arginine vasopressin release, is triggered by psycho-physical stresses such as pituitary surgery. Low postoperative copeptin could predict CDI onset. The aims of this study were the validation of copeptin as a predictor of post-neurosurgical CDI and the identification of the optimal timing for its determination. METHODS: Sixty-six consecutive patients operated for a hypothalamic-pituitary lesion were evaluated. Copeptin was determined preoperatively and at 1, 6, 12, 24 and 48 h post-extubation. Fifty-eight patients were reassessed after 3-6 months post-surgery to confirm transient (3 cases) or permanent CDI (5 cases) diagnosis. RESULTS: A marked copeptin peak was identified at 1 h after extubation, when a value below or equal to 12.8 pmol/L had a good accuracy in identifying CDI cases (AUC 0.866, 95% CI 0.751-0.941). Moreover, a copeptin peak above 4.2 pmol/L excluded permanent forms (AUC 1, 95% CI 0.629-1). Regression analysis identified copeptin as the only significant predictor of CDI (OR 0.86, 95% CI 0.75-0.98, p = 0.02). A copeptin T1/T0 ratio below or equal to 1.47 identified patients at risk of isolated biochemical alterations even in the absence of an overt CDI. CONCLUSIONS: A prompt increase of copeptin is expected at 1 h after extubation. The absence of this peak is a reliable predictor of post-neurosurgical CDI.


Subject(s)
Diabetes Insipidus, Neurogenic , Glycopeptides/blood , Hypothalamic Diseases/surgery , Neurosurgical Procedures/adverse effects , Pituitary Diseases/surgery , Postoperative Complications , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Time Factors , Young Adult
10.
Endocr J ; 67(3): 267-274, 2020 Mar 28.
Article in English | MEDLINE | ID: mdl-31748430

ABSTRACT

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia caused by impairment of arginine vasopressin (AVP) secretion. In this study, we evaluated plasma AVP concentrations during a hypertonic saline infusion test using a new AVP radioimmunoassay (RIA) which is now available in Japan. Thirteen control subjects, mostly with hypothalamo-pituitary disease but without CDI, and 13 patients with CDI were enrolled in the study. Whether or not subjects had CDI was determined based on the totality of clinical data, which included urine volumes and osmolality. Regression analysis of plasma AVP and serum Na concentrations revealed that the gradient was significantly lower in the CDI group than in the control group. The area under the receiver-operating-characteristic (ROC) curve was 0.99, and the <0.1 gradient cut-off values for the simple regression line to distinguish CDI from control had a 100% sensitivity and a 77% specificity. The ROC analysis with estimated plasma AVP concentrations at a serum Na concentration of 149 mEq/L showed that the area under the ROC curve was 1.0 and the <1.0 pg/mL cut-off values of plasma AVP had a 99% sensitivity and a 95% specificity. We conclude that measurement of AVP by RIA during a hypertonic saline infusion test can differentiate patients with CDI from those without CDI with a high degree of accuracy. Further investigation is required to confirm whether the cut-off values shown in this study are also applicable to a diagnosis of partial CDI or a differential diagnosis between CDI and primary polydipsia.


Subject(s)
Arginine Vasopressin/blood , Diabetes Insipidus, Neurogenic/diagnosis , Sodium/blood , Vasopressins , Diabetes Insipidus, Neurogenic/blood , Female , Humans , Male , Middle Aged , Polyuria/blood , Polyuria/diagnosis , Radioimmunoassay , Saline Solution, Hypertonic
11.
Eur J Endocrinol ; 181(3): 233-244, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31238300

ABSTRACT

BACKGROUND: Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. AIM: To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. PATIENTS AND METHODS: We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating. RESULTS: Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype-phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case. CONCLUSION: adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.


Subject(s)
Diabetes Insipidus, Neurogenic/diagnostic imaging , Diabetes Insipidus, Neurogenic/genetics , Mutation/genetics , Neurophysins/genetics , Protein Precursors/genetics , Vasopressins/genetics , Adolescent , Adult , Child , Child, Preschool , Diabetes Insipidus, Neurogenic/blood , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neurophysins/blood , Pedigree , Protein Precursors/blood , Vasopressins/blood , Young Adult
13.
Endocr Pract ; 24(11): 963-972, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30106630

ABSTRACT

OBJECTIVE: The water deprivation test (WDT) is widely used for the differential diagnosis of the polyuria-polydipsia syndrome (PPS). However, it is inconvenient and may not always be precise in differentiating partial forms of diabetes insipidus (DI) from primary polydipsia (PP). The aim of this study was to evaluate the results of a combined outpatient and inpatient overnight WDT protocol that included an overnight unsupervised period concerning its feasibility and safety. METHODS: We performed a retrospective analysis of clinical data and laboratory results of 52 patients with PPS undergoing WDT at a single center. RESULTS: PP was the most frequent diagnosis, followed by complete central DI (cCDI), partial central DI (pCDI), and nephrogenic DI (NDI). Over 90% of the patients showed an expected increase in serum osmolality at the end of the dehydration period. There were no reports of complications during the overnight deprivation period. Post-dehydration urine osmolality and urine-to-serum osmolality ratio significantly differentiated all the groups ( P<.05), except for cCDI and NDI, which could be differentiated by basal and post-dehydration vasopressin (AVP) levels ( P<.05 for both). Although these measurements were useful for differentiating patients according to their allocation groups, results from WDT and direct AVP levels may often require a comprehensive diagnostic approach, particularly in the challenging groups of PP and pCDI. CONCLUSION: A combined outpatient and inpatient overnight WDT protocol is safe and feasible when the test is performed with special care at experienced centers. Newer diagnostic tools are expected to improve the accuracy of PPS diagnosis. ABBREVIATIONS: AQP2 = aquaporin-2; AVP = vasopressin; CDI = central diabetes insipidus; cCDI = complete central diabetes insipidus; DDAVP = desmopressin; DI = diabetes insipidus; IQR = interquartile range; MRI = magnetic resonance imaging; Na+ = sodium; NDI = nephrogenic diabetes insipidus; pCDI = partial central diabetes insipidus; PP = primary polydipsia; PPS = polyuria-polydipsia syndrome; S_osm = serum osmolality; U_osm = urine osmolality; WDT = water deprivation test.


Subject(s)
Ambulatory Care , Diabetes Insipidus, Nephrogenic/diagnosis , Diabetes Insipidus, Neurogenic/diagnosis , Hospitalization , Polydipsia, Psychogenic/diagnosis , Polyuria/diagnosis , Water Deprivation , Adolescent , Adult , Aged , Child , Diabetes Insipidus, Nephrogenic/blood , Diabetes Insipidus, Neurogenic/blood , Female , Humans , Male , Middle Aged , Neurophysins/blood , Osmolar Concentration , Polydipsia/blood , Polydipsia/diagnosis , Polydipsia, Psychogenic/blood , Polyuria/blood , Protein Precursors/blood , Retrospective Studies , Syndrome , Vasopressins/blood , Young Adult
14.
Pituitary ; 21(4): 384-392, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29623580

ABSTRACT

PURPOSE: Severe fluctuations in plasma sodium concentration and plasma osmolarity, including central diabetes insipidus (CDI), may have significant influence on postoperative morbidity and mortality after pediatric brain tumor surgery.The aim of this study was to describe the frequency, severity and neurological consequences of these fluctuations in pediatric brain tumor survivors. METHODS: A retrospective, multi-institutional chart review was conducted among all children who underwent brain tumor surgery in the sellar or suprasellar region in seven university hospitals in the Netherlands between January 2004 and December 2013. RESULTS: Postoperative CDI was observed in 67.5% of 120 included children. Fluctuations of plasma sodium concentration ≥ 10 mmol/L/24 h during the first ten postoperative days were seen in 75.3% of patients with CDI, with a maximum delta of 46 mmol/L/24 h. When compared to patients without CDI, altered mental status occurred more frequently in patients with postoperative CDI (5.1 vs. 23.5% respectively, p = 0.009). Low plasma sodium concentration was related to altered mental status and the occurrence of seizures. Frequency and severity of fluctuations in plasma sodium concentration during the first ten postoperative days were significantly higher in patients with permanent CDI at last follow-up than in patients with transient CDI or without CDI (p = 0.007). CONCLUSION: Postoperative CDI is a common complication after pediatric brain tumor surgery in the sellar or suprasellar region. Extreme plasma sodium concentrations and large intra-day fluctuations still occur and seem to influence the postoperative neurological course. These results illustrate the need for intensive monitoring in a highly experienced center.


Subject(s)
Brain Neoplasms/blood , Brain Neoplasms/surgery , Postoperative Period , Sodium/blood , Adolescent , Child , Child, Preschool , Diabetes Insipidus, Neurogenic/blood , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies
15.
Medicina (B Aires) ; 78(2): 127-130, 2018.
Article in Spanish | MEDLINE | ID: mdl-29659364

ABSTRACT

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.


Subject(s)
Diabetes Insipidus, Neurogenic/complications , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diagnosis, Differential , Aged , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/urine , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/urine , Gadolinium DTPA , Humans , Magnetic Resonance Imaging , Male , Osmolar Concentration , Pituitary Gland, Posterior
16.
Medicina (B.Aires) ; 78(2): 127-130, abr. 2018. graf, tab
Article in Spanish | LILACS | ID: biblio-954962

ABSTRACT

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.


Subject(s)
Humans , Male , Aged , Diabetes Insipidus, Neurogenic/complications , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diagnosis, Differential , Osmolar Concentration , Pituitary Gland, Posterior , Magnetic Resonance Imaging , Gadolinium DTPA , Diabetes Insipidus, Neurogenic/urine , Diabetes Insipidus, Neurogenic/blood , Diabetes Mellitus, Type 2/urine , Diabetes Mellitus, Type 2/blood
17.
Endocrine ; 57(1): 166-174, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28597171

ABSTRACT

PURPOSE: Central diabetes insipidus is characterised by arginine vasopressin deficiency. Oxytocin is structurally related to vasopressin and is synthesised in the same hypothalamic nuclei, thus we hypothesised that patients with acquired central diabetes insipidus and anterior hypopituitarism would display an oxytocin deficiency. Moreover, psychological research has demonstrated that oxytocin influences social and emotional behaviours, particularly empathic behaviour. We therefore further hypothesised that central diabetes insipidus patients would perform worse on empathy-related tasks, compared to age-matched and gender-matched clinical control (clinical control-isolated anterior hypopituitarism) and healthy control groups. METHOD: Fifty-six participants (age 46.54 ± 16.30 yrs; central diabetes insipidus: n = 20, 8 males; clinical control: n = 15, 6 males; healthy control: n = 20, 7 males) provided two saliva samples which were analysed for oxytocin and completed two empathy tasks. RESULTS: Hypopituitary patients (both central diabetes insipidus and clinical control groups) had significantly lower oxytocin concentrations compared to healthy control participants. Hypopituitary patients also performed significantly worse on both the reading the mind in the eyes task and the facial expression recognition task compared to healthy control participants. Regression analyses further revealed that central diabetes insipidus patients' oxytocin concentrations significantly predicted their performance on easy items of the reading the mind in the eyes task. CONCLUSIONS: Hypopituitarism may therefore be associated with reduced oxytocin concentrations and impaired empathic ability. While further studies are needed to replicate these findings, our data suggest that oxytocin replacement may offer a therapeutic approach to improve psychological well-being in patients with hypopituitarism.


Subject(s)
Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/psychology , Empathy/physiology , Facial Recognition , Oxytocin/blood , Adult , Female , Humans , Hypopituitarism/blood , Hypopituitarism/psychology , Male , Middle Aged , Personality
18.
Endocr J ; 64(6): 645-650, 2017 Jun 29.
Article in English | MEDLINE | ID: mdl-28420857

ABSTRACT

We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma osmolality (300 mOsm/kgH2O) and low urinary osmolality (92 mOsm/kgH2O) were observed at the admission to our hospital. Plasma arginine vasopressin (AVP) level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality. Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine osmolality increased in response to desmopressin. The diagnosis of central diabetes insipidus was made from these results. Magnetic resonance imaging (MRI) of hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti-rabphilin-3A antibodies that have been recently reported as a biomarker of lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus continued after delivery, suggesting that polyuria was not mainly due to excessive vasopressinase activity or reduced renal sensitivity to AVP by prostaglandin E2 that can cause temporal polyuria during pregnancy. We therefore clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo-neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy. This case suggested the usefulness of anti-rabphilin-3A antibodies for the etiological diagnosis of central diabetes insipidus during pregnancy.


Subject(s)
Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Autoantibodies/analysis , Autoimmune Hypophysitis/diagnostic imaging , Diabetes Insipidus, Neurogenic/etiology , Nerve Tissue Proteins/antagonists & inhibitors , Pituitary Gland/diagnostic imaging , Pregnancy Complications/diagnostic imaging , Vesicular Transport Proteins/antagonists & inhibitors , Adult , Autoimmune Hypophysitis/immunology , Autoimmune Hypophysitis/pathology , Autoimmune Hypophysitis/physiopathology , Biomarkers/blood , Biomarkers/urine , Diabetes Insipidus/diagnosis , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/urine , Diagnosis, Differential , Female , Humans , Hypernatremia/etiology , Magnetic Resonance Imaging , Organ Size , Pituitary Gland/pathology , Pregnancy , Pregnancy Complications/immunology , Pregnancy Complications/pathology , Pregnancy Complications/physiopathology , Pregnancy Trimester, Third , Prenatal Diagnosis , Rabphilin-3A
19.
J Clin Endocrinol Metab ; 100(7): E946-54, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25919460

ABSTRACT

CONTEXT: Central diabetes insipidus (CDI) can be caused by several diseases, but in about half of the patients the etiological diagnosis remains unknown. Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among cases of idiopathic CDI; however, the differential diagnosis from other pituitary diseases including tumors can be difficult because of similar clinical and radiological manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy. OBJECTIVE: The study was designed to identify the autoantigen(s) in LINH and thus develop a diagnostic test based on serum autoantibodies. DESIGN: Rat posterior pituitary lysate was immunoprecipitated with IgGs purified from the sera of patients with LINH or control subjects. The immunoprecipitates were subjected to liquid chromatography-tandem mass spectrometry to screen for pituitary autoantigens of LINH. Subsequently, we made recombinant proteins of candidate autoantigens and analyzed autoantibodies in serum by Western blotting. RESULTS: Rabphilin-3A proved to be the most diagnostically useful autoantigen. Anti-rabphilin-3A antibodies were detected in 22 of the 29 (76%) patients (including 4 of the 4 biopsy-proven samples) with LINH and 2 of 18 (11.1%) patients with biopsy-proven lymphocytic adeno-hypophysitis. In contrast, these antibodies were absent in patients with biopsy-proven sellar/suprasellar masses without lymphocytic hypophysitis (n = 34), including 18 patients with CDI. Rabphilin-3A was expressed in posterior pituitary and hypothalamic vasopressin neurons but not anterior pituitary. CONCLUSIONS: These results suggest that rabphilin-3A is a major autoantigen in LINH. Autoantibodies to rabphilin-3A may serve as a biomarker for the diagnosis of LINH and be useful for the differential diagnosis in patients with CDI.


Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Autoantibodies/blood , Diabetes Insipidus, Neurogenic/immunology , Nerve Tissue Proteins/immunology , Vesicular Transport Proteins/immunology , Adaptor Proteins, Signal Transducing/metabolism , Adult , Animals , Autoantigens/immunology , Autoimmune Diseases/blood , Autoimmune Diseases/immunology , Autoimmune Diseases/metabolism , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/metabolism , Diagnosis, Differential , Female , HEK293 Cells , Humans , Lymphocytes/immunology , Male , Nerve Tissue Proteins/metabolism , Pituitary Gland, Posterior/immunology , Pituitary Gland, Posterior/metabolism , Rats , Rats, Sprague-Dawley , Vesicular Transport Proteins/metabolism , Young Adult , Rabphilin-3A
20.
J Clin Endocrinol Metab ; 100(6): 2275-82, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25923040

ABSTRACT

CONTEXT: Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. OBJECTIVE: The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. DESIGN: This was a prospective multicenter observational cohort study. SETTING: Three Swiss or Canadian referral centers were used. PATIENTS: Consecutive pituitary surgery patients were included. MEASUREMENTS: Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. RESULTS: Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. LIMITATIONS: Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. CONCLUSIONS: In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.


Subject(s)
Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/surgery , Glycopeptides/blood , Pituitary Gland/surgery , Postoperative Complications/diagnosis , Adult , Aged , Diabetes Insipidus, Neurogenic/blood , Diabetes Insipidus, Neurogenic/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/epidemiology , Postoperative Period , Prognosis , Treatment Outcome , Water-Electrolyte Imbalance/blood , Water-Electrolyte Imbalance/diagnosis , Water-Electrolyte Imbalance/epidemiology
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