A case of primary hypothalamic malignant lymphoma with diabetes insipidus

A case of primary malignant lymphoma involving the hypothalamus is reported. A 31-year-old man was admitted with progressive disorientation. A computed tomography (CT) scan demonstrated a normodense, homogenously enhanced, and nodular shaped mass lesion involving the suprasellar region and extending to the third ventricle. In view of marked cerebral edema, dexamethasone was intravenously administered, at a dose of 4 mg/4 hr, and gradually tapered off. CT scans obtained 10 days after the admission revealed dramatic regression of the lesion, which corresponded with the clinical remission. However, on the 4th day after the discontinuance of corticosteroid, a CT scan demonstrated the recurrence of the mass lesion. Because of the rapid deterioration of consciousness and the progressive enlargement of the mass and dilatation of the ventricles, partial removal of tumor and ventricular drainage were carried out on the 24th day after admission. Dexamethasone was intravenously administered again at a dose of 4 mg/4 hr. A CT scan obtained five days after the operation showed complete disappearance of the lesion, and the patient had became almost alert. CT scans obtained on the 18th day and the 35th day after the operation showed complete disappearance of the mass. However, Magnetic Resonance Imaging revealed a localized area of abnormal signal intensity in the hypothalamus. Diabetes insipidus was continuously observed from the time of admission. A concomitant change of beta-2-microglobulin (beta-2-MG) and immunoglobulin (IgA, IgG, IgM) concentrations in serum and cerebrospinal fluid (CSF) with clinical profiles and CT findings were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nephrogenic diabetes insipidus: identification of the genetic defect

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of arginine vasopressin. The disease gene has been assigned to the subtelomeric region of the X chromosome long arm by demonstrating close linkage between NDI and several X-chromosomal DNA markers. The finding of closely linked genetic markers is useful in the diagnosis of NDI. Receptor studies in patients have indicated that NDI might be due to the absence or an abnormality of the adenylate cyclase-bound vasopressin type 2 receptor. This assumption was supported by the discovery of functional vasopressin V2 receptor activity in somatic cell hybrid cell lines that carried at least the distal part of the human X chromosome long arm. Definite evidence for a V2 receptor defect being the cause of NDI was found in a recent study demonstrating point mutations in the V2 receptor gene from affected individuals. Direct mutation analysis is now applicable for accurate carrier detection and early (prenatal) diagnosis.     

Nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800) who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800). In these families, mutations have been identified in the aquaporin-2 gene (AQP2) (OMIM 107777), which codes for the vasopressin-sensitive water channel. Most missense AVPR2 mutations lead to receptors that are trapped intracellularly; a few mutant receptors reach the cell surface but are unable to bind AVP or to properly trigger an intracellular cyclic adenosine monophosphate signal. Similarly, most AQP2 mutant proteins are also misrouted. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value because early diagnosis and treatment can avert the physical and mental retardation associated with repeated episodes of dehydration.     

Nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine-vasopressine (AVP). Polyuria, with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. Hypercalcemia, hypokaliemia, lithium administration and chronic renal failure are the principal causes of acquired nephrogenic diabetes insipidus. About 90 percent of patients with congenital nephrogenic diabetes insipidus are males with X-linked recessive nephrogenic diabetes insipidus who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. The gene is located in chromosome region Xq28. In about 10 percent of the families studied, congenital nephrogenic diabetes insipidus has an autosomal recessive or autosomal dominant mode of inheritance. In these cases, mutations have been identified in the aquaporin-2 gene (AQP2), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter's syndrome and Cystinosis. Identification of the molecular defect underlying congenital nephrogenic diabetes insipidus is of immediate clinical significance because early diagnosis and treatment of affected infants can avert the physical and mental retardation associated with episodes of dehydration.     

Posttraumatic diabetes insipidus

The authors report seven patients with fractures of the sella turcica. Four of them developed Diabetes Insipidus as a consequence of their traumata. The importance of computed tomography as a diagnostic procedure is paramount in order to make early diagnosis of this potential life-threatening condition possible.     

Propofol and diabetes insipidus

A case in which the intraoperative administration of propofol was strongly associated with an acute episode of diabetes insipidus is presented.     

Nephrogenic diabetes insipidus.

In spite of its rare incidence, the inherited renal tubular disorder nephrogenic diabetes insipidus (NDI) has in the past 10 years attracted the attention of a varied group of medical doctors and basic scientists. With the identification of the two genes involved in NDI, namely the vasopressin type-2 receptor (V2R) and the aquaporin-2 water channel (AQP2) genes, the identification of a large number of different mutations in these genes, and the subsequent functional characterization of mutant V2Rs and AQP2s, our insight into the renal cellular mechanisms involved in diuresis and antidiuresis has increased considerably. We are now entering an exciting new period in the development of new therapeutic strategies for disorders of water balance.     

Acquired nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI can be either a congenital or an acquired disorder. Acquired NDI most commonly is secondary to drugs such as lithium or metabolic disturbances, such as hypokalemia and hypercalcemia. Disturbance of the aquaporin-2 shuttle is the underlying molecular basis of acquired NDI. NDI is diagnosed with the help of a water-deprivation test. Patients with the disorder will have a urinary osmolality of less than 300 mosm/kg H2O despite water deprivation. On administration of aqueous vasopressin, patients with NDI will show little or no increase in urine osmolality. Therapy consists of identifying and correcting the underlying disorder, or withdrawing the offending drug. Other treatment options that may be beneficial include diuretics, nonsteroidal anti-inflammatory drugs, decreased dietary solute intake, and desmopressin (DDAVP).     

Nephrotic syndrome complicated by idiopathic central diabetes insipidus

Background

There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP).

Case-Diagnosis/Treatment

We report a 12-year-old boy with steroid-dependent NS complicated by idiopathic central diabetes insipidus (CDI). He did not develop edema during his first relapse of NS after developing CDI, despite having hypoalbuminemia. He had polydipsia, polyuria, low urine osmolality, and a low serum arginine AVP level. His fractional excretion of sodium was only slightly low. Endocrinological testing and magnetic resonance imaging revealed idiopathic CDI. After starting desmopressin therapy, he developed edema when his NS relapsed.

Conclusions

This is the first known reported case of NS in a patient with CDI. The findings suggest that appropriate AVP secretion in response to an increase in serum osmolality caused by renal sodium retention is necessary for excess extracellular fluid accumulation in NS. Further investigation is needed to more fully understand the role of AVP in edema formation in NS.     

Familial central diabetes insipidus detected by nocturnal enuresis

A 10-year-old male referred to our clinic with the chief complaint of nocturnal enuresis also complained of daytime polyuria, frequency, and polydipsia. The clinical diagnosis was central diabetes insipidus. Since the patient's father had complained of similar symptoms, the arginine vasopressin-neurophysin II gene was examined. This revealed a single base substitution in one of two alleles in the patient, his father, and his grandfather (a C to T transition at nucleotide position 280 at codon 19 in the first exon). In conclusion, a history of polyuria or polydipsia should be carefully noted and the urinary volume and urine gravity or osmolarity examined in cases of nocturnal enuresis.     

Parapubic hernia and diabetes insipidus

According to the current literature parapubic hernia is regarded as a relatively rare pathology. The causative defect is usually related to pelvic surgery, traumatism, or bone malformation. Surgical treatment is difficult, because aponeurotic tissue on which to anchor a mesh on the caudal aspect of the defect is missing. This report describes a case of an incisional pubic hernia related to megabladder in a woman affected by diabetes insipidus and with a past clinical history of multiple pelvic interventions. As far as we are aware this report adds a new pathogenetic issue for parapubic hernias not previously described in the literature.     

Olanzapine intoxication-related transient diabetes insipidus

Olanzapine is a second-generation atypical antipsychotic agent approved for the treatment of psychotic disorders and mania. The effects of olanzapine intoxication include central nervous system depression, hyperthermia, myosis, tachycardia, and orthostatic hypotension. Heretofore, only one case has been reported to develop polyuria after olanzapine overdose (560 mg). We describe a case that developed diabetes insipidus following massive olanzapine ingestion and returned to normal after desmopressin treatment.     

Molecular genetic study of congenital nephrogenic diabetes insipidus and rescue of mutant vasopressin V2 receptor by chemical chaperones

AIM: X-linked nephrogenic diabetes insipidus is a rare disease caused by mutations in the arginine vasopressin V2 receptor (AVPR2) gene, which encodes vasopressin V2 receptor (V2R). More than a half of reported mutations in AVPR2 are missense mutations, and a large number of missense mutant receptors fail to fold properly and therefore are not routed to the cell surface. METHODS: We analysed the AVPR2 gene in 14 unrelated patients with X-linked nephrogenic diabetes insipidus, and found 13 different mutations including eight missense point mutations. The cellular expression patterns of three missense mutant (A98P, L274P and R113W) and wild-type V2R were determined in transfected COS-7 cells. RESULTS: In contrast to wild-type V2R, the cell-surface expressions of mutant receptors were totally (A98P and L274P) or partially (R113W) absent. Instead, they were retained intracellularly. However, treatment of cells with two chemical chaperones (100 mmol/L trimethylamine oxide or 2% dimethyl sulfoxide) or incubation at 26 degrees C restored the cell-surface expressions of mutant receptors. CONCLUSION: These data show that some chemical chaperones correct the mistrafficking of misfolded A98P, L274P and R113W V2R. Thus, we believe that a therapeutic strategy based on chemical chaperones in patients with these mutations is worth trying.