diabetes insipidus [keywords]
- A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree. [JOURNAL ARTICLE]
- J Int Med Res 2016 Aug 25.
Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 (AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.
- A case of pituitary abscess presenting without a source of infection or prior pituitary pathology. [Journal Article]
- Endocrinol Diabetes Metab Case Rep 2016.
Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI) of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected preoperatively. She underwent transsphenoidal resection and purulent material was seen intraoperatively. Culture of the surgical specimen showed two species of alpha hemolytic Streptococcus, Staphylococcus capitis and Prevotella melaninogenica. Urine and blood cultures, dental radiographs and transthoracic echocardiogram failed to show any source of infection that could have caused the pituitary abscess. The patient was treated with 6weeks of oral metronidazole and intravenous vancomycin. After 6weeks of transsphenoidal resection and just after completion of antibiotic therapy, her headache and bitemporal hemianopsia resolved. However, nocturia and polydipsia from central diabetes insipidus and amenorrhoea from hypogonadotrophic hypogonadism persisted.Pituitary abscesses typically develop in patients who have other sources of infection or disruption of the normal suprasellar anatomy by either surgery, irradiation or pre-existing pathology; however, they can develop in the absence of known risk factors.Patients with pituitary abscesses typically complain of headache, visual changes and symptoms of pituitary hormone deficiencies.As other pituitary neoplasms present with similar clinical findings, the diagnosis of pituitary abscess is often not suspected until transsphenoidal resection is performed.Prompt surgical and medical treatment of pituitary abscess is necessary, which typically results in improvement in headache and visual changes; however, pituitary hormone deficiencies are typically often permanent.
- Shattering the rock: technique of bilateral optic nerve mobilization and drilling heavily calcified craniopharyngiomas for its excision. [JOURNAL ARTICLE]
- World Neurosurg 2016 Aug 17.
Resection of heavily calcified craniopharyngioma is a quite challenging. The stretched optic nerves, perforators and stalk are likely to be jeopardised further during attempts to break the calcified chunks especially through narrow corridors. The authors describe a surgical technique to mobilize bilateral optic nerves and drilling the calcified chunk to crumple it.This technique was used in 6 patients with heavily calcified craniopharyngiomas (2 recurrent), who had presented with progressive visual loss. Fronto-temporal craniotomy was used in 5 and Fronto-temporo-orbito-zygomatic craniotomy in one patient with a large retrosellar component. The sylvian fissure was widely split. Bilateral optic canal was deroofed and falciform ligament was cut to mobilize both optic nerves. The calcified tumor could be dissected and mobilized into the widened corridor where the tumor was drilled. Multiple holes were drilled in the calcified chunk to shatter it to small pieces. These pieces were then dissected from perforators and stalk, while protecting them.Symptoms improved in all patients. Gross total excision could be achieved in 3, near total in 2 (both recurrent) and subtotal in 1(due to extensive skull base involvement).. All patients had transient diabetes insipidus. Two patients who had preoperative hypopitutirism required long term postoperative hormonal replacement. There were no approach related complications.Mobilizing bilateral optic nerves improves the exposure and allows dissection of arachnoid from calcified craniopharyngiomas. Its drilling through widened corridor helps to shatter it. Using the technique, the neurovascular structures can possibly be better preserved whilst achieving maximal resection.
- INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA. [JOURNAL ARTICLE]
- Endocr Pract 2016 Aug 19.
Polydipsia and polyuria are a common reason for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made.The study was a retrospective chart review of children presenting to the Endocrine clinic with complaints of polydipsia and polyuria over a 5 year period.The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 boys) were reviewed. Central DI was diagnosed in 8 (20%) of the children, based on abnormal results on a water deprivation test. All but one patient had abnormal MRI findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs 4.18 ± 3.20 years, P=0.01) and had a higher propensity for cold beverages intake and unusual water seeking behaviors, compared to those without DI. They also had higher serum sodium and osmolality at baseline on a water deprivation test.The incidence of central DI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum sodium and osmolality on a water deprivation test.
- Two novel mutations in seven Czech and Slovak kindreds with familial neurohypophyseal diabetes insipidus-benefit of genetic testing. [Journal Article]
- Eur J Pediatr 2016 Sep; 175(9):1199-207.
Familial neurohypophyseal diabetes insipidus (FNDI) is a rare hereditary disorder with unknown prevalence characterized by arginine-vasopressin hormone (AVP) deficiency resulting in polyuria and polydipsia from early childhood. We report the clinical manifestation and genetic test results in seven unrelated kindreds of Czech or Slovak origin with FNDI phenotype. The age of the sign outset ranged from 2 to 17 years with remarkable interfamilial and intrafamilial variability. Inconclusive result of the fluid deprivation test in three children aged 7 and 17 years old might cause misdiagnosis; however, the AVP gene analysis confirmed the FNDI. The seven families segregated together five different mutations, two of them were novel (c.164C > A, c.298G > C). In addition, DNA analysis proved mutation carrier status in one asymptomatic 1-year-old infant.The present study together with previously published data identified 38 individuals with FNDI in the studied population of 16 million which predicts a disease prevalence of 1:450,000 for the Central European region. The paper underscores that diagnostic water deprivation test may be inconclusive in polyuric children with partial diabetes insipidus and points to the clinical importance and feasibility of molecular genetic testing for AVP gene mutations in the proband and her/his first degree relatives.• At least 70 different mutations were reported to date in about 100 families with neurohypophyseal diabetes insipidus (FNDI), and new mutations appear sporadically. What is New: • Two novel mutations of the AVP gene are reported • The importance of molecular testing in children with polyuria and inconclusive water deprivation test is emphasized.
- Physiological insights into novel therapies for nephrogenic diabetes insipidus. [JOURNAL ARTICLE]
- Am J Physiol Renal Physiol 2016 Aug 17.:ajprenal.00418.2016.
Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for Nephrogenic Diabetes Insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter. If it is possible to phosphorylate and/or increase the apical membrane accumulation of these proteins, independent of vasopressin or cAMP, one may be able to treat NDI. Sildenifil (through cGMP), Erlotinib, and Simvastatin, each stimulate AQP2 insertion into the apical plasma membrane. Some recent human data suggests that Sildenafil and Simvastatin may improve urine concentrating ability. ONO-AE1-329 (ONO) stimulates the EP4 prostanoid receptor (EP4), which stimulates kinases that in turn phosphorylate AQP2 and UT-A1. Clopidogrel is an P2Y12-R antagonist that potentiates the effect of vasopressin and increases AQP2 abundance. Metformin stimulates AMPK to phosphorylate and activate AQP2 and UT-A1, and increases urine concentrating ability in two rodent models of NDI. Since metformin, sildenafil, and simvastatin are commercially available and have excellent safety records, the potential for rapidly advancing them into clinical trials is high.
- Vhl deletion in renal epithelia causes HIF-1α-dependent, HIF-2α-independent angiogenesis and constitutive diuresis. [JOURNAL ARTICLE]
- Oncotarget 2016 Aug 12.
One of the earliest requirements for the formation of a solid tumor is the establishment of an adequate blood supply. Clear cell renal cell carcinomas (ccRCC) are highly vascularized tumors in which the earliest genetic event is most commonly the biallelic inactivation of the VHL tumor suppressor gene, leading to constitutive activation of the HIF-1α and HIF-2α transcription factors, which are known angiogenic factors. However it remains unclear whether either or both HIF-1α or HIF-2α stabilization in normal renal epithelial cells are necessary or sufficient for alterations in blood vessel formation. We show that renal epithelium-specific deletion of Vhl in mice causes increased medullary vascularization and that this phenotype is completely rescued by Hif1a co-deletion, but not by co-deletion of Hif2a. A physiological consequence of changes in the blood vessels of the vasa recta in Vhl-deficient mice is a diabetes insipidus phenotype of excretion of large amounts of highly diluted urine. This constitutive diuresis is fully compensated by increased water consumption and mice do not show any signs of dehydration, renal failure or salt wasting and blood electrolyte levels remain unchanged. Co-deletion of Hif1a, but not Hif2a, with Vhl, fully restored kidney morphology and function, correlating with the rescue of the vasculature. We hypothesize that the increased medullary vasculature alters salt uptake from the renal interstitium, resulting in a disruption of the osmotic gradient and impaired urinary concentration. Taken together, our study characterizes a new mouse model for a form of diabetes insipidus and non-obstructive hydronephrosis and provides new insights into the physiological and pathophysiological effects of HIF-1α stabilization on the vasculature in the kidney.
- Sellar Wegener Granulomatosis Masquerading as Cabergoline-Resistant Prolactinoma. [JOURNAL ARTICLE]
- World Neurosurg 2016 Aug 10.
Pituitary manifestation of Wegener granulomatosis (WG) is extremely rare. When there is pituitary involvement, the granulomatous inflammatory lesions involving the pituitary gland may appear several months to years after the primary diagnosis.We present a case of a 32-year-old woman who presented with galactorrhea, amenorrhea, and elevated serum prolactin levels. Imaging demonstrated a sellar lesion with characteristics of a pituitary macroadenoma. Treatment with cabergoline was initiated, but the tumor continued to grow over a 6-month period. Subsequent surgical exploration revealed a chronic inflammatory lesion; the patient was subsequently diagnosed with WG based on laboratory evaluation and further systemic manifestations. She had a favorable clinical and radiological response with immunosuppressive doses of glucocorticoids and rituximab.This appears to be the first reported case of a patient with unknown WG in whom the diagnosis was established after she presented with a sellar lesion mimicking a prolactin-secreting pituitary adenoma on initial presentation requiring surgical resection. The only endocrine abnormality discovered was moderate hyperprolactinemia. Sellar lesions with only moderate elevations in serum prolactin, particularly those that are refractory to medical management with a dopamine agonist, should prompt further investigation to confirm the diagnosis. WG should be part of the differential diagnosis of inflammatory lesions in the sella, identification of which can facilitate early diagnosis and treatment of this systemic disease for optimal outcome.
- Pituitary tuberculoma: A consideration in the differential diagnosis in a patient manifesting with pituitary apoplexy-like syndrome. [Journal Article]
- IDCases 2016.:63-6.
Pituitary tuberculoma is extremely rare, even in endemic regions of tuberculosis and much less frequently as a presentation of pituitary apoplexy. We describe a 25-year-old female presented with sudden onset of headache and vision loss of left eye which mimicking symptoms of pituitary apoplexy. MRI of the pituitary gland showed a rim-enhancing lesion at the intrasellar region extending into the suprasellar area, but absence of posterior bright spot with enhancement of the pituitary stalk. Pituitary hormonal evaluation revealed panhypopituitarism and diabetes insipidus. An urgent transphenoidal surgery of the pituitary gland was undertaken for which the histopathology showed necrotizing granulomatous inflammation with infarcted adjacent pituitary tissue. Despite negative fungal and AFB staining, pituitary tuberculoma was presumptively diagnosed based on imaging, pathology and the high incidence of tuberculosis in the country. After the course of anti-tuberculosis therapy, the clinical findings were dramatically improved, supporting the diagnosis. Pituitary tuberculoma is extremely rare in particular with an apoplexy-like presentation but should be one of the differential diagnosis list of intrasellar lesions in the patient presenting with sudden onset of headache and visual loss. The presence of diabetes insipidus and thickened with enhancement of pituitary stalk on MRI were very helpful in diagnosing pituitary tuberculosis.
- Lithium Poisoning. [JOURNAL ARTICLE]
- J Intensive Care Med 2016 Aug 11.
Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.