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Transient proximal tubular renal injury following Ecstasy ingestion.

Multiple renal adverse effects have been anecdotally reported with the ingestion of 3,4-methylenedioxymethamphetamine (Ecstasy), a widely used recreational drug. These side effects include acute renal failure, necrotizing vasculitis, and hyponatremia, the mechanisms for which are unknown. We report a case of transient acute proximal tubular injury and hyponatremia associated with Ecstasy use. An 18-year-old woman presented with new onset seizures and polydipsia. Her initial laboratory evaluation revealed hyponatremia (Na 117 mEq/L), polyuria (urine output >400 mL/h for several hours), renal glycosuria (blood glucose 120 mg/dL, urine glucose >1,000 mg/dL), and solute diuresis (urine osmolality 552 mOsm/kg H2O). Urine electrolyte values reflected a low tubular reabsorption of phosphorus (TRP) of 68.1% (expected TRP >85% at serum P 2.3 mg/dL) with an appropriate transtubular potassium gradient of 3.0 (serum K 3.7 mEq/L). Her hyponatremia was slowly corrected. A repeat TRP after 48 h had normalized to 86.5%, and her glycosuria resolved. An extensive toxin screen was later reported positive for Ecstasy. To our knowledge, this is the first example of an acute and transient proximal tubular injury with Ecstasy ingestion. This complication may become more apparent with increasing use of this drug.

Acute Disease↗

Bartter syndrome: benefits and side effects of long-term treatment.

The present study reports clinical and laboratory data of patients with Bartter syndrome at diagnosis and follow-up with emphasis on the long-term benefits and side effects of the pharmacological therapy, which includes indomethacin and potassium supplementation. We followed 12 children, 6 boys, with a median age at diagnosis of 24.5 months (range 7-137 months) and at the end of the study 157.5 months (range 26.0-224.0 months). All children presented with polyuria and polydipsia, dehydration, and metabolic and electrolyte disturbances with failure to thrive. However, at study entry 5 of 12 patients also had hypophosphatemia, which disappeared after a mean time of 50+/-22.4 months, 3 of 12 had nephrocalcinosis, and 2 of 12 had typical renal cysts. Despite treatment, hypokalemia was persistent in some patients. During long-term follow-up we observed recovery of growth velocity and adequate metabolic and electrolyte balance. However, we noticed renal and gastrointestinal complications: 2 patients had a perforated gastric ulcer, 1 had a gastric ulcer, and gastritis was detected in 3 children. A decreased glomerular filtration rate was observed in 2 patients during follow-up. Our data emphasize the need for regular surveillance of renal function and gastrointestinal endoscopy in these patients. As an alternative to indomethacin, we present our satisfactory preliminary results with rofecoxib.

Bartter Syndrome↗

Age-related pathophysiological changes in rat oligomeganephronic hypoplastic kidney.

Rat male hypogonadism (hgn/hgn) is accompanied by oligomeganephronic hypoplastic kidney (HPK), in which each kidney contains one quarter the number of nephrons present in a normal kidney. The nephrons of the HPK are extremely hypertrophied. These characters were apparently common to human oligomeganephronia (OMN). To determine the age-related changes in renal pathophysiology in HPK rats, we measured several parameters of renal function at 70 days, 140 days, 210 days, and 280 days of age. At all time points, relative kidney weight was significantly smaller in HPK rats than in their normal litter mates. In HPK rats, both polyuria and polydipsia became more severe with advancing age. Although creatinine clearance (Ccr) and urinary nitrogen clearance (Cun) were significantly lower in HPK than in normal rats, the values did not decrease with age. A severe form of glomerulosclerosis, as well as interstitial infiltration and cystic dilation of tubules with proteinaceous luminal casts, was observed in the inner cortex and medulla of HPK rats at advanced age. In these animals the surface glomeruli retained their functional architecture but were hypertrophied. Both mean blood pressure (MBP) and proteinuria became more elevated with age in HPK rats, and their urine samples included considerable amounts of high molecular weight protein. These results suggest that the HPK rat is a suitable model of human OMN.

Age Factors↗

Fabry disease and nephrogenic diabetes insipidus.

Fabry disease is a lysosomal storage disorder with kidney involvement. The initial manifestation of kidney disease is often impaired urinary concentrating ability in adolescence or young adulthood. We describe a boy diagnosed prenatally with Fabry disease who presented with polyuria, polydipsia, hypertension, hypokalaemia and proteinuria at 7 years of age. A formal water-deprivation test followed by vasopressin challenge confirmed nephrogenic diabetes insipidus. A renal biopsy revealed findings typical of Fabry disease. Angiotensin converting-enzyme therapy resulted in rapid improvement of symptoms, normalization of blood pressure and resolution of hypokalaemia and proteinuria. This child is the youngest reported Fabry disease patient with documented renal pathology and clinical manifestations of hypertension, proteinuria and nephrogenic diabetes insipidus.

Child↗

A case of nephrogenic diabetes insipidus with a novel missense mutation in the AVPR2 gene.

We describe a pediatric case of nephrogenic diabetes insipidus (NDI) with a novel missense mutation in the arginine vasopressin receptor 2 (AVPR2) gene. The patient, a 3-year-old boy, had polyuria (4357 ml/day, 7230 ml/m(2)/day) and polydipsia. Water deprivation testing demonstrated no decrease of urine volume, and urinary volume did not respond to subcutaneous injection of 0.1 U/kg pitressin. Molecular genetic analysis demonstrated that the patient had an AVPR2 missense mutation involving substitution of phenylalanine for tyrosine at position 205 (Y205F). It was also found that the patient's mother was heterozygous for this Y205F mutation. Analysis of the intermolecular interaction of the Tyr-205 hydrogen group by molecular modeling showed that Tyr-205 was located in transmembrane domain (TM) 5, and that its hydroxy group formed a hydrogen bond with Leu-169 main-chain =O located in TM 4. The mutation of Tyr-205 to phenylalanine would cause loss of this hydrogen bond and decrease or change the interaction between these TM coils, thus affecting the ability of AVP to bind to the receptor. According to this molecular model of AVPR2, the Y205F mutation would cause nephrogenic diabetes insipidus.

Base Sequence↗

Intracranial aneurysms in a child with autosomal recessive polycystic kidney disease.

Intracranial aneurysms (ICA) are a well-known feature of autosomal dominant polycystic kidney disease. There is only one report about ICA in an adult patient with autosomal recessive polycystic kidney disease (ARPKD). We observed a 2-year, 6-month old girl with ARPKD and multiple ICA. The family history is negative for kidney disease. The diagnosis of ARPKD was based on the typical findings in ultrasonography and computed tomography. Cystic ectasia of biliary ducts 6.3/4.8 cm in diameter was found in the liver. Arterial hypertension in a range of 140/100-170/120 mm Hg was registered. The child has polyuria, polydipsia and enuresis. Blood urea was 15 mmol/l, creatinine in a range of 120 to 75 micromol/l. One episode of vomiting, dizziness and lethargy was the reason for a brain magnetic resonance imaging. Multiple fusiform and saccular aneurysms in the branches of middle and posterior cerebral arteries were seen bilaterally. The girl is growing well without neurological symptoms during an observation period of 1.5 years. Blood pressure is well controlled with an ACE inhibitor (Enalapril 2.5 mg daily). It was concluded that ICA can be found in patients with ARPKD. Blood pressure control is essential to reduce the risk of intracranial hemorrhage.

Child, Preschool↗

Amphotericin B-induced partial nephrogenic diabetes insipidus in a child.

The case of a 12-year-old boy who developed polyuria and polydipsia while on amphotericin B treatment is discussed. The clinical and laboratory features are most consistent with partial nephrogenic diabetes insipidus. Several adult patients have been reported with amphotericin B-induced nephrogenic diabetes insipidus. To the knowledge of the authors, this is the first pediatric patient described with this condition. Pharmacological doses of antidiuretic hormone in conjunction with diuretic treatment significantly reduced the polyuria and alleviated the associated symptoms. The authors propose that in amphotericin B-induced partial nephrogenic diabetes insipidus, pharmacological doses of antidiuretic hormone may offer an additional benefit to commonly used diuretic therapy.

Amphotericin B↗

Parathyroid carcinoma: A rare case with mandibular brown tumor.

Parathyroid carcinoma constitutes less than 1 % of primary hyperparathyroidism. The male to female ratio is approximately equal and the mean age at presentation is 40 years. In about half of the patients there is a palpable cervical mass, and serum calcium level is usually above 14 mg/dl. In a case report we present a 21-year-old man with a non-tender, non-mobile bulging mandibular mass. He suffered from fatigue, recent weight loss, hoarseness, polydipsia, polyuria, hematuria, recurrent renal stones and bouts of constipation and diarrhea. A mandibular biopsy confirmed brown tumor. Serum calcium level was 15.4 mg/dl. Cervical ultrasound revealed a hypoecho area suspicious of parathyroid adenoma. Parathyroid carcinoma was later confirmed and en bloc resection was performed. During a two-year follow up there has been no evidence of recurrence or hypercalcemia. This unique case of parathyroid carcinoma in conjunction with brown tumor is the second reported case worldwide.

Adenoma↗

Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients.

Congenital nephrogenic diabetes insipidus (NDI) is, in most instances, a rare X-linked recessive renal disorder (MIM 304800) characterized by the clinical symptoms of polyuria, polydipsia, and dehydration. The X-linked NDI is associated with mutations of the arginine vasopressin receptor type 2 (AVPR2) gene, which results in resistance to the antidiuretic action of arginine vasopressin (AVP) in the renal tubules and collecting ducts. Identification of mutations in the AVPR2 gene can facilitate early diagnosis of NDI, which can prevent serious complications such as growth retardation and mental retardation. We analyzed three unrelated Chinese NDI families and identified three mutations: R106C, F287L, and R337X. In addition, an A/G polymorphism at cDNA nucleotide position 927 (codon 309L) was identified. A functional expression assay of the R106C and F287L mutants in COS-7 cells revealed that both mutants show significant dysfunction and accumulate intracellular cyclic adenosine monophosphate in response to AVP hormone stimulation. These results facilitate the diagnosis of NDI at the molecular level in the Chinese population, and provide insight into the molecular pathology of NDI.

Amino Acid Sequence↗

An unusual case of insomnia associated with Whipple encephalopathy: first case reported from Greece.

Whipple disease is a relapsing systemic illness caused by Tropheryma whippelii. Central nervous system involvement occurs in 5%-40% of all patients. Hypothalamic manifestations occur in 31% of Whipple encephalopathy, including polydipsia, hyperphagia, change in libido and insomnia. We report a case of a 48-year-old man with severe insomnia, depression, dementia, dysarthria, myoclonic movements of the limbs and ophthalmoplegia. The diagnosis of Whipple encephalopathy was confirmed by PCR analysis of blood and faeces. He received a full dose of antibiotic treatment. Despite clinical improvement, resolution of the lesions detected in MRI scan of the brain and negative results of the PCR in blood, faeces and cerebrospinal fluid six months later, insomnia persisted and finally subsided after the administration of carbamazepine (600 mg/day). Our case supports the finding that carbamazepine might be useful in the treatment of insomnia associated with Whipple encephalopathy.

Analgesics, Non-Narcotic↗

Dipsogenic diabetes insipidus: report of a novel treatment strategy and literature review.

Dipsogenic diabetes insipidus is a syndrome of disordered thirst, in patients without psychiatric disease, which may be confused with partial central diabetes insipidus. Distinguishing these entities involves monitored water testing. Therapy with antidiuretic hormone in patients with dipsogenic diabetes insipidus is thought to be contraindicated for fear of inducing water intoxication. We report a case of a 26-year-old woman without psychiatric illness referred for longstanding polyuria and polydipsia. Otherwise healthy, she complained of near-constant thirst and frequent urination, causing severe disruption of her personal and professional life. She had been consistently eunatremic and polyuric, with low urine osmolality. Results of extensive water testing revealed intact urinary concentrating and diluting capacity, physiologic though blunted antidiuretic hormone (ADH) release, and an abnormally low thirst threshold, consistent with the diagnosis of dipsogenic diabetes insipidus. To control her polyuria we initiated treatment with intermittent, low-dose, intranasal desmopressin and strict water restriction during drug dosing. In follow-up she reported excellent control of polyuria and significant functional improvement. The reviewed literature demonstrates a limited number of reports about dipsogenic diabetes insipidus, and no prior report of a similar treatment strategy. Dipsogenic diabetes insipidus is an uncommonly (and not universally) recognized disorder, requiring monitored testing in order to distinguish it from incomplete forms of central diabetes insipidus. Though therapy with desmopressin cannot be recommended based on the results of a single case, the outcome presented here is intriguing and suggests that larger studies in such patients is warranted to assess the broader application of such an intervention.

Adult↗

Diabetes insipidus caused by isolated intracranial metatstases in patient with breast cancer.

We present a case of late recurrence of breast cancer manifested with diabetes insipidus caused by isolated intracranial metastases. A 57-year-old postmenopausal woman was diagnosed with breast cancer and underwent radical mastectomy, without any adjuvant therapy. Seventeen years later, she presented with polyuria, polydipsia, weight loss, weakness, diffuse bone pain, hoarseness and mild dyspnoea. Cranial CT revealed several dural masses in the frontal, parietal and occipital lobes and along the falx cerebri. The diagnosis of central diabetes insipidus without impairment of anterior pituitary function was based on the clinical symptoms, laboratory tests and imaging findings. The patient was successfully treated with desmopressin acetate and letrozole, and remained alive and ambulating 22 months after initial presentation with diabetes insipidus.

Antineoplastic Agents↗

Intracranial aggressive fibromatosis presenting as panhypopituitarism and diabetes insipidus.

Aggressive fibromatosis (AF) is a rare, locally aggressive, proliferative fibroblastic lesion affecting musculoaponeurotic structures, most often, of the limbs and trunk. Intracranial AF is extremely rare and requires aggressive treatment to prevent recurrence. We present a case of a 34 year-old male with AF involving intracranial structures causing panhypopituitarism and diabetes insipidus. Patient was admitted to hospital because of polyuria, polydipsia, and loss of libido, impotence, hearing loss, and gait disturbance. On cranial magnetic resonance imaging, the lesion extended through the sphenoid sinus into the both pterygoid recesses, destroying the left lateral wall of the sphenoid sinus and invading the retroorbital area. There was also a distinct lesion in the hypothalamic area. The tumor was markedly isointense on both T2- and T1-weighted images relative to gray matter, and enhanced strongly after administration of gadolinium. The patient underwent partial resection of the lesion via a transcranial approach. The pathological examination of the mass was reported as AF. No other sites were found to be involved by thorax and abdominal tomography. Hormonal assessment of hypothalamic-pituitary dysfunction revealed panhypopituitarism with central diabetes insipidus. Replacement therapy was instituted. In this case, standard treatment of wide-field surgical resection was impossible. On the basis of reports that radiotherapy is an effective treatment for this kind of tumor, we administered radiation to the affected area, since chemotherapy and hormonal treatment of non-resectable tumors are not satisfactory. To our knowledge, this is the first reported case of AF presenting as panhypopituitarism with central diabetes insipidus.

Adult↗

Testicular sarcoidosis.

A 20 year old black man presented with shortness of breath, hilar adenopathy, monoarticular arthritis, polydipsia and polyuria, and bilateral testicular masses. Transbronchial biopsy revealed noncaseating granulomas consistent with sarcoidosis. Subsequent work-up demonstrated hypothalamic dysfunction, and joint fluid analysis was consistent with sarcoid arthropathy. Concern over the possibility of a testicular neoplasm led to right testicular biopsy which revealed noncaseating granulomas consistent with testicular sarcoidosis. A short course of steroid therapy resulted in clinical improvement and complete resolution of the remaining left testicular mass.

Adult↗

Nephronophthisis.

Twenty-one patients with nephronophthisis are described with a follow-up of one to 16 years (mean 9.3 years). In 10 patients, there was a familial incidence. Autosomal recessive appears the likely mode of inheritance with a 20 per cent incidence noted (seven of 35) following correction for the bias of ascertainment by removing the probands. Seven patients had an associated and characteristic retinal degeneration from infancy. Associated neurologic problems, including mental retardation, seizures and cerebellar ataxis, were also seen in some patients. Previously described skeletal abnormalities and hepatic fibrosis were not seen in any of our patients. All presented at an advanced stage of chronic renal failure, usually associated with a history of polydipsia and polyuria from infancy. Renal cysts were noted in only one of the nine patients in whom tissue was obtained by needle biopsy. In seven patients in whom tissue was available at nephrectomy or autopsy, cysts were noted in six although only in two were they localized to the medulla. Eighteen patients have undergone dialysis, and 12 patients have received a renal transplant with no evidence of recurrence of the original disease. Sixteen patients are still alive. Many synonyms for nephronophthisis have appeared, with medullary cystic disease being the most common. Our experience suggests that nephronophthisis is a common cause of chronic renal failure and has commonly associated nonrenal abnormalities.

Adolescent↗

Diabetes insipidus associated with dysplastic pancytopenia.

This case report describes a 60-year-old man who presented with a three-year history of generalized malaise, decreased libido, polyuria, and polydipsia. He had been previously investigated for pancytopenia, and found to have a hypoplastic bone marrow. A diagnosis of central diabetes insipidus was established; the patient was also found to have a number of other defects in his hypothalamic-pituitary function. Hematologic studies again revealed peripheral pancytopenia associated with a hypoplastic megaloblastic bone marrow. Computed axial and nuclear magnetic resonance tomography failed to establish the nature of the morphologic lesion in the hypothalamus. A possible relationship between the hematologic and endocrine disturbance is discussed.

Bone Marrow↗

Hyponatremic encephalopathy: is central pontine myelinolysis a component?

PURPOSE: Severe hyponatremia is often associated with permanent brain damage. There has been substantial controversy about whether central pontine myelinolysis (CPM), a rare neurologic disorder of uncertain etiology, can complicate either hyponatremia or its therapy. This study was undertaken to determine how often hyponatremic patients with the clinical diagnosis of CPM actually have the disorder as an integral structural component of their encephalopathy. PATIENTS: Analyses were carried out in 20 patients who had severe symptomatic hyponatremia and a presumptive diagnosis of CPM, based on clinical and/or neuroradiologic findings. All had been referred for neuroradiology consultation. The mean age (+/- SD) was 47 +/- 14 years, the lowest serum sodium level was 104 +/- 8 mM, and 85% of the patients were female. The etiologies were diverse and included postoperative status, thiazide diuretics, polydipsia, infection, acute renal failure, chronic alcoholism with emesis, and beer potomania. METHODS: The original and subsequent films of 20 patients were reevaluated retrospectively by two neuroradiologists. The clinical course was also reevaluated, and in eight patients, the postmortem brain findings were reviewed. The diagnosis of CPM was made only on the basis of strict criteria relating to either (1) pathologic findings of CPM on postmortem examination; or (2) computed tomographic scan and/or magnetic resonance imaging findings diagnostic of CPM. RESULTS: No pontine lesions were present in 15 of 20 patients in whom the diagnosis of CPM had initially been made. All 15 had extrapontine demyelinating lesions but the pons was normal. Two others had only lateral pontine lesions, so that only three of 20 patients had definite CPM. All but one of the 20 hyponatremic patients had a definite hypoxic event prior to any therapy with intravenous sodium chloride. The involved brain areas included basal ganglia, thalamus, cortical gray matter, and periventricular white matter, areas often affected by hypoxia. Each of the three patients in whom unequivocal findings of CPM were present had long histories of chronic alcoholism and hepatic cirrhosis. CONCLUSIONS: These results suggest that: (1) Neither hyponatremic encephalopathy nor its therapy is commonly associated with CPM; (2) Patients with chronic alcoholism who also become hyponatremic can develop pontine demyelinating lesions; (3) Most patients with symptomatic hyponatremia who are diagnosed as having CPM in fact have diffuse cerebral demyelinating lesions with a normal pons; (4) The distribution of cerebral demyelinating lesions in patients with hyponatremic encephalopathy is compatible with hypoxic damage.

Adult↗

Optic nerve hypoplasia associated with absent septum pellucidum and hypopituitarism.

Five children had bilateral optic nerve hypoplasia, absent septum pellucidum, and hypopituitarism. Absence of the septum pellucidum was shown by computed axial tomography. All of the children were first-born. One of the children was definitely not mentally retarded and one at age 7 months was developing normally. All of the children had severe visual impairment and nystagmus. Pupillary responses varied. Ocular deviations included one with exotropia and three with esotropia. The extent of pituitary hormone deficiency varied. One child was symptomatic from birth, having severe hypoglycemia and seizures. Two children had prolonged neonatal jaundice. One unusual case had growth hormone deficiency with a normal growth curve. Another child with diabetes insipidus had dehydration and polyuria without polydipsia.

Adult↗