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diabetes insipidus [keywords]
- Characterization of Three Vasopressin Receptor 2 Variants: An Apparent Polymorphism (V266A) and Two Loss-of-Function Mutations (R181C and M311V). [Journal Article]
- PLoS One 2013; 8(6):e65885.
Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting β-arrestin. The etiology of NSIAD in the patient with V266A V2R remains unknown.
- Clinical features of patients with non-Hodgkin's lymphoma metastasizing to the pituitary glands. [JOURNAL ARTICLE]
- Oncol Lett 2013 May; 5(5):1643-1648.
It is rare for systemic non-Hodgkin's lymphoma (NHL) to metastasize to the hypothalamus and pituitary glands. The present study describes two patients with NHL and diabetes insipidus (DI) and 17 patients from the literature in order to analyze the clinical features of patients with NHL metastasizing to the pituitary glands. Diffuse large B cell lymphoma (DLBCL) was observed to be the most common type of NHL involving the hypothalamus-pituitary axis. A total of 11 patients (57.9%) had been diagnosed with DI (post-pituitary involvement), five (26.3%) with anterior hypopituitarism and three (15.8%) with posterior and anterior hypopituitarism. Only two cases exhibited simultaneous endocrine and lymphoma manifestations; the majority of cases (68.4%) exhibited lymphoma manifestations first. To make an etiological diagnosis of NHL with metastases to the pituitary glands, it is necessary to find that NHL exists in other regions of patient's body. Biopsy of the sellar may have significant meaning, but this examination may difficult to perform. Chemotherapy for NHL relieves pituitary impairment symptoms and improves the overall examination results. Additionally, magnetic resonance imaging (MRI) of the pituitary gland has a certain differential diagnostic value as the T1- and T2-weighted imaging (WI) signals from patients with systemic NHL with pituitary involvement are low.
- Clinical Characteristics and Pituitary Dysfunction in Patients with Metastatic Cancer to the Sella. [JOURNAL ARTICLE]
- Endocr Pract 2013 Jun 11.:1-16.
Objective:Metastatic disease to the sella is uncommon and there are limited available data regarding the clinical aspects of this disease. We sought to characterize the clinical demographics of sellar metastases.
Methods:Retrospective chart review of adults at Stanford University Medical Center from 1980 to 2011 with metastatic disease to the sella.
Results:13 subjects were identified (9 F). The mean age at diagnosis was 55 years (range: 25-73 y). 6 (46%) had breast carcinoma, 3 (23%) had renal cell carcinoma, 2 (15%) had squamous cell carcinoma of the head and neck, 1 had bronchoalveolar carcinoma of the lung, and 1 had nodular sclerosing Hodgkin's lymphoma. The most common presenting signs and symptoms were headache (58%), followed by fatigue (50%), polyuria (50%), visual field defects (42%), and ophthalmoplegia (42%). 75% presented with at least one pituitary hormone insufficiency, including 6 (50%) with diabetes insipidus (DI). 8 (67%) subjects had secondary hypothyroidism, and 5 (45%) had secondary adrenal insufficiency. Of the patients with stalk involvement, 86% had DI. All patients had a prior diagnosis of malignancy for a mean duration of 95 months.
Conclusion:In this retrospective review, the most common neoplastic sources to the sella were breast and renal cell carcinoma. Secondary hypothyroidism was the most common endocrine abnormality, followed by DI, and adrenal insufficiency. New onset central hypothyroidism and diabetes insipidus along with known malignancy in a patient with a sellar lesion should raise the suspicion of a metastatic source.
- Clinical characteristics and management of cranial diabetes insipidus in infants. [JOURNAL ARTICLE]
- J Pediatr Endocrinol Metab 2013 Jun 8.:1-6.
Aim:Cranial diabetes insipidus (CDI) is rare in infants with no guidelines on its management. We describe the first case series, characterizing the clinical features and treatment challenges. Method: Retrospective case note review of infants diagnosed with CDI between April 1992 and February 2011.
Results:Nineteen infants (52% male) were identified. Eight were born preterm. Median (range) age at diagnosis was 24 days (5-300); preterm babies were younger at diagnosis (21 vs. 46 days). In 58% (11/19) of infants, hypernatraemia was discovered incidentally. In 37% of cases there was associated midline anomalies, however, only four patients (21%) had absent posterior pituitary signal on a magnetic resonance imaging brain scan. The most frequent (5/19) underlying diagnosis was septo-optic dysplasia. Eight patients had isolated CDI and 11 had multiple pituitary hormone deficiencies. Isolated CDI tended to be more common in preterm, compared to term babies (p=0.11). Des-amino arginine vasopressin (DDAVP) was administered intranasally in eight and orally in 11 infants. Plasma sodium nadir following DDAVP administration was lower following intranasal compared to an oral route of administration (median: 128 vs. 133 mmol/L, p=0.022). No cases resolved on follow-up.
Conclusions:CDI in infants is often diagnosed incidentally. Aetiology, clinical, and imaging features are very variable, with some differences between preterm and term infants. Oral DDAVP appears to be superior to intranasal with less pronounced serum sodium fluctuations.
- Do Antidepressants Lower the Prevalence of Lithium-associated Hypernatremia in the Elderly? A Retrospective Study. [Journal Article]
- Can Geriatr J 2013; 16(2):38-42.
Clinically important measures of lithium-induced nephrogenic diabetes insipidus (NDI) such as hypernatremia have not been well-studied. This is especially relevant for the elderly who, in comparison to younger adults, may become symptomatic and require hospitalization with relatively small elevations in sodium levels. We hypothesized that antidepressant use, which has been associated with the syndrome of inappropriate antidiuretic hormone secretion, has a protective effect against lithium-associated hypernatremia in the elderly.Retrospective cohort study of 55 geriatric psychiatry outpatients followed at tertiary-care hospitals. Patients using lithium and antidepressants were compared with those using lithium alone for prevalence rates of hypernatremia during a 15-year observational period.The prevalence of hypernatremia was less in patients who had concurrent use of lithium and antidepressants, as compared to lithium alone 3/35 (8.6%) vs. 8/20 (40%), OR 0.14, p = .011.Our results suggest that elderly lithium patients are less likely to develop hypernatremia if they are taking antidepressants concurrently. Whether antidepressants may be useful in the prevention of lithium-associated hypernatremia should be assessed in future prospective observational or treatment studies.
- Urinary concentration: different ways to open and close the tap. [JOURNAL ARTICLE]
- Pediatr Nephrol 2013 Jun 6.
Nephrogenic diabetes insipidus (NDI) provides an excellent model for the benefits and insights that can be gained from studying rare diseases. The discovery of underlying genes identified key molecules involved in urinary concentration, including the type 2 vasopressin receptor AVPR2 and the water channel AQP2, which constitute obvious pharmacologic targets. Subsequently developed drugs targeting AVPR2 not only provide potential benefit to some patients with NDI, but are now used for much more common clinical applications as diverse as nocturnal enuresis and heart failure. Yet, the story is still evolving: clinical observations and animal experiments continue to discover new ways to affect urinary concentration. These novel pathways can potentially be exploited for therapeutic gain. Here we review the (patho)physiology of water homoeostasis, the current status of clinical management, and potential new treatments.
- Development of central diabetes insipidus following electroconvulsive therapy: results of a prospective pilot study. [Journal Article]
- J ECT 2013 Jun; 29(2):e29-30.
The objective of this study was to examine the occurrence of laboratory abnormalities and symptoms of central diabetes insipidus (CDI) in patients receiving acute electroconvulsive therapy (ECT) series.We prospectively investigated adult psychiatric inpatients for objective and subjective evidence of CDI at baseline and after their sixth ECT.Although participants did not report any CDI symptoms, two thirds had clinically important decreases in urine osmolality (>200 mOsm/kg), and two thirds had serum sodium increases of 5 mmol/L following exposure to ECT.Our findings suggest that objective evidence of CDI can occur following the administration of ECT series, even in the absence of symptomatic complaints.
- Suprasellar pediatric craniopharyngioma resection via endonasal endoscopic approach. [JOURNAL ARTICLE]
- Childs Nerv Syst 2013 May 24.
PURPOSE:Purely endoscopic endonasal approaches to surgical resection of pediatric suprasellar craniopharyngiomas are uncommonly performed. The aim of the study is to assess the feasibility and to describe the short-term outcomes of endonasal endoscopic approaches for the gross total resection of suprasellar craniopharyngiomas in the pediatric population.
METHODS:A combined neurosurgical-otolaryngologic team performed gross total resection of craniopharyngiomas in seven pediatric patients (mean age 9.6 years) at The Children's Hospital of Philadelphia over 2011-2012. Short-term outcomes were analyzed over a mean follow-up period of 6.3 months.
RESULTS:All tumors involved the sellar and/or suprasellar space and contained some cystic component. The mean maximal tumor diameter was 31.5 mm (range 18.5-62.0 mm). Using a binostril approach, gross total tumor resection was obtained in all patients (100 %). All patients with preoperative visual dysfunction demonstrated improvement in visual acuity. New or stable panhypopituitarism was observed in all cases. All patients developed postoperative diabetes insipidus, and cerebrospinal fluid leak occurred in one patient (15 %).
CONCLUSIONS:Complete radiographic resection of pediatric craniopharyngioma can be achieved via a purely endoscopic endonasal approach. In particular, this approach can be performed safely using the "two-nostrils-four-hands" technique with intraoperative neuronavigation. This approach should be highly considered in patients with progressive visual dysfunction. Further studies are needed to characterize the long-term surgical and clinical outcome of pediatric patients treated with this surgical approach.
- Congenital partial arhinia: a rare malformation of the nose coexisting with holoprosencephaly. [Journal Article]
- Turk J Pediatr 2012 Jul-Aug; 54(4):440-3.
Complete or partial arhinia is a rare defect of embryogenesis characterized by congenital absence of the soft tissue of the nose and nasal structures. It is generally associated with other craniofacial or somatic anomalies, including midline defects such as cleft palate, highly arched palate, absence of paranasal sinuses, and palatal and ocular abnormalities. Less than 40 patients with arhinia have been reported so far,. We report herein on a patient with partial arhinia and holoprosencephaly presenting with respiratory insufficiency and diabetes insipidus.