A very rare entity of diabetes insipidus associated with Edwards syndrome.

Edwards syndrome is the second most commonly seen trisomy. It was first described by John Hamilton Edwards in 1960. Although most cases result in termination or foetal loss, live births have been documented in 5%. Edwards syndrome is characterized by multisystem anomalies, of which holoprosencephaly (HPE) is observed in 4-8% of cases. The clinical findings correspond to the degree of HPE malformation. Convulsions and endocrinopathies are among the severe clinical findings. The most common endocrinopathies are central diabetes insipidus (DI), hypothyroidism, hypocortisolism and growth hormone deficiency. The coexistence of holoproencephaly and DI in Edwards syndrome was discussed under the light of literature.

Remission of congenital diabetes insipidus after eight years.

Septo-optic dysplasia (SOD) (De Morsier's syndrome) is a complex developmental disorder marked by variable and often incomplete formation of cranial midline structures, resulting in absence of the septum pellucidum, optic nerve hypoplasia, and hypothalamic-pituitary dysfunction. We describe a patient with SOD who manifested symptoms in the early neonatal period with severe deficiencies of multiple pituitary hormones including anti-diuretic hormone (ADH). Her congenital diabetic insipidus (DI), consequence of an anatomic defect, can be argued to be of the most severe type. Our patient resolved her severe DI 8 years after her initial presentation, suddenly requiring no further medical treatment for DI following longstanding pharmacological replacement of ADH. This is the first report of a patient with SOD with spontaneous resolution of congenital DI.

Diagnóstico diferencial de adenoma folicular y carcinoma papilar de tiroides mediante variables cariométricas. Matanzas 2013-2016 / Differential diagnosis of thyroidal follicular adenoma and papillary carcinoma by means of karyometric variables. Matanzas 2013-2016

RESUMEN Introducción: los carcinomas diferenciados de tiroides se originan en el epitelio folicular. De ellos el carcinoma papilar muestra una mayor incidencia. Una variante del mismo es la folicular, que en ocasiones muestra un patrón arquitectural que imita a un adenoma folicular. Objetivo: contribuir al diagnóstico diferencial entre el carcinoma papilar variante folicular y el adenoma folicular de tiroides, utilizando variables cariométricas de las células foliculares. Materiales y métodos: se aplicaron técnicas morfométricas a muestras de biopsias de tiroides con carcinoma papilar variante folicular y adenoma folicular, así como a muestras sin patología, en el período comprendido de enero de 2013 a diciembre de 2016, obtenidas en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas. Las técnicas aplicadas se basaron en las variables cuantitativas: área, perímetro y factor de forma nuclear de las células foliculares. Los resultados se expresaron en porcentajes; la media aritmética como medida de tendencia central; desviación típica, incluyéndose el cálculo de los valores máximo, mínimo y recorrido para cada variable comprendida en el estudio, reflejados en tablas y gráficos realizados a través del software Microsoft Office Excel. Resultados: se obtuvieron valores elevados de área y perímetro nuclear de las células foliculares del carcinoma papilar variante folicular con relación al adenoma folicular, mientras que el factor de forma no arrojó resultados significativos para la diferenciación de dichas enfermedades tiroideas. Conclusiones: la aplicación de técnicas morfométricas a variables cariométricas en el tiroides, para el diagnóstico diferencial entre el carcinoma papilar variante folicular y el adenoma folicular, ofrece resultados aplicables en estudios histopatológicos (AU).

ABSTRACT Introduction: differentiated thyroid carcinomas are originated in the follicular epithelium. Of them, the papillary carcinoma shows higher incidence. Follicular carcinoma, one of its variants, occasionally shows an architectural pattern imitating a follicular adenoma. Objective: to contribute to the differential diagnosis between the papillary carcinoma, follicular variant, and thyroid follicular adenoma, using karyometric variables of follicular cells. Materials and methods: morphometric techniques were applied to samples of biopsies of thyroids with papillary carcinoma, follicular variant, and follicular adenoma, and also to samples without any pathology, in the period from January 2013 to December 2016, gathered in the University Hospital Comandante Faustino Perez, of Matanzas. The applied techniques were based on quantitative variables: area, perimeter and nuclear form factor. Results were expressed in percentages; the arithmetic median as measure of central tendency; typical deviation, including the calculation of maximal, minimal values and the course for each variable included in the study, were drawn in tables and graphics using Microsoft Office Excel software. Results: highs values of area and nuclear perimeter of the follicular cells of the papillary carcinoma, follicular variant, were obtained, while the shape factor did not show significant results for those thyroidal diseases differentiation. Conclusions: the application of morphometric techniques to karyometric variables in the thyroids, for the differential diagnosis between the papillary carcinoma, follicular variant, in follicular carcinoma, offers results that can be applied in histopathological studies (AU).

Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus.

Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V2 receptor gene is encoded by three exons. The coding regions amplified by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in the second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular domain and a premature termination at codon 161. In another pedigree, a missense mutation (A-->G) was identified at nucleotide position 310 in the second exon. This point mutation, H80R, changes a histidine at codon 80 in the second transmembrane domain to an arginine that is more positively charged than histidine under the neutral environment. Each mutation cosegregated with the phenotype of diabetes insipidus and supposed to be a cause for resistance to arginine vasopressin.

Two distinct pathophysiological mechanisms in congenital nephrogenic diabetes insipidus.

V1 and V2 vasopressin receptor functions were studied in 2 patients with congenital nephrogenic diabetes insipidus. V1 receptor-mediated functions (increase in urinary prostaglandin E2 excretion and plasma cortisol levels) and Gs (guanine nucleotide-binding stimulatory protein) activity of erythrocyte membranes were normal in both patients. After infusion of 0.4 micrograms/kg dDAVP, a 57-yr-old male patient had no increase in plasma factor VIII coagulant, ristocetin cofactor, or fibrinolytic activity or change in von Willebrand factor multimers. In addition, he had no vasodilatory response to dDAVP, a response that occurs in normal subjects and patients with central diabetes insipidus. In contrast, a 25-yr-old female patient had normal hemostatic and vasodilatory responses to the infusion of dDAVP. These observations indicate that the cellular abnormalities in patients with congenital nephrogenic diabetes insipidus may be either at the V2 receptor or in the postreceptor (and Gs activity) cascade of events that mediate vasopressin-induced antidiuresis. Therefore, heterogeneity exists in the biochemical cause(s) of congenital nephrogenic diabetes insipidus in man.

Hereditary vasopressin resistance in man and mouse.

The DI +/+ Severe hereditary nephrogenic diabetes insipidus mouse is resistant to the antidiuretic action of vasopressin (VP) because of failure to accumulate cAMP and subsequent inability to form intramembranous particles on the apical (luminal) surface of kidney cells that normally respond to VP. The defect is primarily, if not exclusively, due to excessive activity of specific cAMP-phosphodiesterases. The abnormality can be overcome in vitro and in vivo by the phosphodiesterase inhibitor, rolipram. Most cases of hereditary NDI in man have sex-linked recessive inheritance, which appears to be due to an abnormality of the V2 receptor. The chromosomal locus of the defect is Xq28. Sporadic cases of congenital NDI have been described in females who appear to have a defect beyond the V2 receptor and the guanine nucleotide-binding stimulatory protein. There is no information on the biochemical defect in very rare cases with other types of inheritance patterns. No abnormalities of V1a and V1b receptor function have been found in patients with NDI. Mice and patients with NDI have evidence of increased AVP synthesis. AVP release in relation to plasma osmolality is increased in patients during infusion of hypertonic saline. This is the opposite of what has been described in patients with primary polydipsia (dipsogenic diabetes insipidus) who are chronically overhydrated. Together, these studies indicate that chronic dehydration and overhydration can cause up- and downregulation of the osmotic release of AVP.

Persistent central diabetes insipidus presenting in a very low birth weight infant successfully managed with intranasal dDAVP.

We report a case of a premature very low birth weight infant who presented shortly after birth with idiopathic central diabetes insipidus that persisted beyond the neonatal period and has been successfully managed with intranasal 1-desamino-8-D-arginine vasopressin. Although this condition is rare in neonates, early recognition, evaluation, and therapy may prevent more severe morbidity. Long-term successful management resulting in normal growth and development during infancy can be achieved with intranasal 1-desamino-8-D-arginine vasopressin therapy.

1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus.

In healthy subjects, intravenous infusion of the selective V2-vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 ng/kg in 10 min) causes a marked increase in heart rate with a slight decrease in diastolic blood pressure. These haemodynamic responses are associated with increments in the plasma levels of renin, noradrenaline (NA), clotting factor VIII (FVIII:C), von Willebrand factor (vWF:ag), and tissue-type plasminogen activator (t-PA), and a fall in the plasma level of plasminogen activator inhibitor (PAI). None of these changes was observed in 3 patients with congenital nephrogenic diabetes insipidus (NDI), who had a genetic defect of the V2-receptor. Plasma AVP levels in these patients were normal or slightly elevated, which makes it unlikely that the lack of DDAVP responsiveness was caused by down-regulation of vasopressin V1-receptors. In one NDI patient, arginine vasopressin (AVP) was given in incremental doses (62.5-4000 pg/kg/min). The heart rate and blood pressure responses to AVP were normal, indicating the absence of a V1-receptor defect. The responses of vWF:ag and t-PA to venous occlusion in the patients with NDI were similar to those in 5 healthy volunteers, which indicates that in NDI the endothelial release of both vWF:ag and t-PA is normal. We conclude that DDAVP causes its effects on heart rate and blood pressure, and on the plasma levels of renin, noradrenaline, FVIII:C, vWF:ag, and t-PA through V2-receptor stimulation.

Congenital nephrogenic diabetes insipidus in an adult.

A 35-year-old man with congenital nephrogenic diabetes insipidus (NDI) is reported. Renal biopsy revealed miniaturized and rounded mitochondria of the proximal tubular cells and decreased brush-borders. Trichlormethiazide combined with triamterene resulted in an apparent reduction of daily urine volume and concomitant increment in urine osmolarity. The present case seems rare in that some morphological changes in the renal tissues could be demonstrated in an adult case with congenital NDI.

Congenital central diabetes insipidus in two sibling Afghan hound pups.

Congenital central diabetes insipidus was determined to be the cause of polydipsia and polyuria in sibling pups. Both pups were lacking adequate plasma arginine vasopressin concentration, compared with that in control dogs. Microscopic abnormalities were confined to the brain and pituitary gland in one pup. Without breeding trials of these dogs or their relatives, it cannot be determined whether the cause was familial.

[Idiopathic retroperitoneal fibrosis disclosed by nephrogenic diabetes insipidus]. / Fibrose rétropéritonéale idiopathique révélée par un diabète insipide néphrogénique.

Nephrogenic diabetes insipidus is an exceptional complication of incomplete ureteric obstruction with hydronephrosis. We report one case of this condition revealing idiopathic retroperitoneal fibrosis. Pathogenic mechanisms are discussed.

[Congenital diabetes insipidus. Recent advances in molecular genetics]. / Diabètes insipides congénitaux. Acquisitions récentes en génétique moléculaire.

Hereditary diabetes insipidus can occur in two forms: the first, referred to as central diabetes insipidus, is responsive to vasopressin whereas the second, termed nephrogenic diabetes insipidus, is resistant to treatment. Recent advances in molecular genetics have contributed to elucidate the pathogenesis of these affections. Familial central diabetes insipidus depicts two unsimilar illnesses. The first, characterized by an autosomal dominant transmission, is of delayed onset and worsens progressively all through life. It is related to a heterozygous mutation of the vasopressin precursor gene mainly involving either the sequence encoding for the signal peptide or the one encoding for neurophysin II, the hormone carrier protein. Mutations described to date are responsible for impairment of vasopressin precursor transportation and processing. Therefore mutant protein accumulates in the posterior pituitary which is involved in the persistant bright spot seen on magnetic resonance imaging. The second illness or Wolfram syndrome, autosomal recessive, associates obligatory features: insulin-dependant diabetes, bilateral optic atrophy and more inconstantly: diabetes insipidus, deafness, genito-urinary and neuropsychiatric disturbances. The cause of this syndrome, still unknown, may involve mitochondrial ADN mutations. Familial nephrogenic diabetes insipidus, of neonatal onset, are mainly X-linked and associated to mutations in the V2 receptor gene. About 60 mutations have been described until now. Some rare cases, transmission of which is autosomal recessive, result from homozygous mutations of aquaporin 2 gene, a water channel involved in the water reabsorption in the renal collecting duct. Other mutations will be probably discovered in future. In conclusion, familial diabetes insipidus constitutes an interesting pathogenic model because it may be explained by impairment of vasopressin gene precursor as well as by abnormalities of renal receptor or post receptor mechanisms of the hormone.

[Polyuric dilatation of the urinary tract in congenital nephrogenic diabetes insipidus. Clinical and diagnostic aspects. Presentation of a case and review of the literature]. / La dilatación poliúrica del tracto urinario en diabetes insípida nefrogénica congénita. Aspectos clínicos y diagnósticos. Presentación de un caso con atrofia renal. Revisión de la literatura.

Massive polyuria existing in congenital nephrogenic diabetes insipidus can cause a more or less severe dilatation of the urinary tract in absence of obstruction. Clinical and diagnostic aspects of this pathology are presented relating then with other types of diabetes insipidus. One case of bilateral severe dilatation with evolution towards renal atrophia is presented. Mechanical obstruction was discarded. The disease was refractory to urinary concentration tests and therapy to reduce urine volume. The possible etiopathological mechanisms of functional obstruction and surgical alternatives directed to preserve the kidney function are explained and discussed. The current literature is reviewed but the cases reported are few due to the low incidence of urological affectation. Presence of kidney atrophia is exceptional.

[Congenital nephrogenic diabetes insipidus]. / Diabète insipide néphrogénique congénital.

Congenital nephrogenic diabetes insipidus is a rare hereditary disease characterized by a renal insensitivity to circulating vasopressin. Genetic linkage studies have demonstrated that the gene responsible for congenital nephrogenic diabetes insipidus is located in region 28 of the X chromosome long arm. That the gene coding for the vasopressin V2 receptor is also located in the q28-qter of chromosome X suggests that the signalisation defect in congenital nephrogenic diabetes insipidus is at the level of the receptor itself. Indeed, congenital nephrogenic diabetes insipidus is a genetically heterogeneous disease since several point mutations in the vasopressin V2 receptor gene nucleotide sequence have been observed in different families of afflicted patients. Moreover, the observation that one of these mutations leads to a lack of cyclic AMP production in response to vasopressin confirms that mutations of the vasopressin V2 receptor sequence are the molecular defects responsible for congenital nephrogenic diabetes insipidus.

[Vasopressin type 2 receptor mutations in congenital diabetes insipidus].

Congenital nephrogenic diabetes insipidus is a rare inherited disorder, which is characterized by the inability of the kidney to concentrate urine due to unresponsiveness to antiduretic hormone arginine vasopressin. Defects must be present somewhere in a vasopressin signal transduction pathway in kidney collecting duct. Recent genetic analysis demonstrated that mutations in vasopressin type 2 receptor and water channel aquaporin 2 are responsible for x-linked and autosomal recessive form, respectively. Expression studies of mutant proteins showed that most of the mutations cause severe functional defects, which are compatible with clinical phenotypes. These advances help understanding of molecular mechanism underlying this disease and therefore improve diagnostic and therapeutic approaches.

Diabetes mellitus vs diabetes insípida y un factor común: la poliuria. Presentación de un caso / Diabetes mellitus versus diabetes insipidus and a common factor: polyuria. Case presentation

La diabetes mellitus es una enfermedad crónica no trasmisible muy frecuente en la ciudad de Matanzas, se presenta en cualquier grupo etáreo, siendo tipo I o tipo II. En la diabetes tipo I, el cuerpo no produce insulina. En la diabetes tipo II, la más común, el cuerpo no produce o no usa la insulina adecuadamente. Sin suficiente insulina, la glucosa permanece en la sangre, provocando múltiples complicaciones tanto agudas como crónicas. La diabetes insípida es un trastorno poco común del metabolismo del agua. Esto quiere decir que el balance entre la cantidad de agua o líquido que usted toma no corresponde con el volumen de excreción urinaria. Es causada por una falta de respuesta o una respuesta deficiente a la hormona antidiurética vasopresina. Esta hormona controla el balance hídrico mediante la concentración de orina. Los pacientes con diabetes insípida orinan mucho, por lo cual necesitan beber bastantes líquidos para reemplazar los que pierden. Se presenta un paciente de 45 años con antecedentes de salud que debutó con una diabetes insípida y un año más tarde con una diabetes mellitus tipo II concomitando ambas, corroborándose por los complementarios correspondientes y mejorando con tratamiento (AU).

Diabetes mellitus is a non-transmissible chronic disease, very frequent in the city of Matanzas, which is present in any age group, and is classified as type I and type II. In the type I diabetes, the body does not produce insulin. In the type II diabetes, the most common one, the body does not produce or does not use it effectively. Without enough insulin, glucose remains in the blood, causing several complications, both acute and chronic. The diabetes insipidus is a few common disorder of the water metabolism. That means that the balance between the quantity of water or any other fluid someone drinks does not coincide with the volume of the urinary excretion. It is due to a lack of answer or a deficient answer to the anti-diuretic hormone vasopressin. This hormone controls the water balance through the urine concentration. The patients with diabetes insipidus urinate a lot, so they need to drink many liquids to replace those they lose. It is presented the case of a patient aged 45 years, with health antecedents, that debuted with diabetes insipidus and a year later with a concomitant type II diabetes mellitus. The complementary tests confirmed that and the patient got better with the treatment (AU).

Diabetes mellitus vs diabetes insípida y un factor común: la poliuria. Presentación de un caso / Diabetes mellitus versus diabetes insipidus and a common factor: polyuria. Case presentation

La diabetes mellitus es una enfermedad crónica no trasmisible muy frecuente en la ciudad de Matanzas, se presenta en cualquier grupo etáreo, siendo tipo I o tipo II. En la diabetes tipo I, el cuerpo no produce insulina. En la diabetes tipo II, la más común, el cuerpo no produce o no usa la insulina adecuadamente. Sin suficiente insulina, la glucosa permanece en la sangre, provocando múltiples complicaciones tanto agudas como crónicas. La diabetes insípida es un trastorno poco común del metabolismo del agua. Esto quiere decir que el balance entre la cantidad de agua o líquido que usted toma no corresponde con el volumen de excreción urinaria. Es causada por una falta de respuesta o una respuesta deficiente a la hormona antidiurética vasopresina. Esta hormona controla el balance hídrico mediante la concentración de orina. Los pacientes con diabetes insípida orinan mucho, por lo cual necesitan beber bastantes líquidos para reemplazar los que pierden. Se presenta un paciente de 45 años con antecedentes de salud que debutó con una diabetes insípida y un año más tarde con una diabetes mellitus tipo II concomitando ambas, corroborándose por los complementarios correspondientes y mejorando con tratamiento (AU).

Diabetes mellitus is a non-transmissible chronic disease, very frequent in the city of Matanzas, which is present in any age group, and is classified as type I and type II. In the type I diabetes, the body does not produce insulin. In the type II diabetes, the most common one, the body does not produce or does not use it effectively. Without enough insulin, glucose remains in the blood, causing several complications, both acute and chronic. The diabetes insipidus is a few common disorder of the water metabolism. That means that the balance between the quantity of water or any other fluid someone drinks does not coincide with the volume of the urinary excretion. It is due to a lack of answer or a deficient answer to the anti-diuretic hormone vasopressin. This hormone controls the water balance through the urine concentration. The patients with diabetes insipidus urinate a lot, so they need to drink many liquids to replace those they lose. It is presented the case of a patient aged 45 years, with health antecedents, that debuted with diabetes insipidus and a year later with a concomitant type II diabetes mellitus. The complementary tests confirmed that and the patient got better with the treatment (AU).

Importancia del seguimiento a largo plazo de la diabetes insípida; de hipofisitis linfocitaria a germinoma / Importance of long-term follow-up of diabetes insipidus; from lymphocytic hypophysitis to germinoma

Se describe el caso de un trastorno del eje hipotálamo hipofisario en un niño de 10 años que comenzó con diabetes insípida y evolucionó a un panhipopituitarismo. En estos casos siempre se debe sospechar una lesión hipotalámica oculta y realizar seguimiento. A los 3 años, se detectó la aparición de lesiones en el tallo hipofisario. Los marcadores tumorales fueron negativos pero la lesión creció y fue biopsiada. El resultado anatomopatológico fue de hipofisitis linfocitaria. En el seguimiento hubo un aumento de los marcadores tumorales, por lo que se realizó una nueva biopsia que fue diagnóstica de germinoma. La hipofisitis linfocitaria es muy rara en estas edades y algunos casos son diagnosticados finalmente de germinoma. El interés radica en resaltar la importancia del seguimiento de los casos de diabetes insípida central y en cuestionar un posible diagnóstico de hipofisitis linfocitaria, o mejor infundibuloneurohipofisitis linfocitaria, muy raro en estas edades y que puede enmascarar un germinoma, con muy pocos casos reportados

A case is presented of a 10-year old boy who had a hypothalamic-pituitary axis disorder. He initially presented with diabetes insipidus that progressed to panhypopituitarism. A hidden hypothalamic lesion should be suspected in all these cases, and should be followed up. New lesions were found in the pituitary stem three years later. Although tumor markers were negative, there was an increase in size, and a biopsy was performed. The histopathology reported a Lymphocytic Hypophysitis. There were increases in the tumor markers during the follow-up, thus a second biopsy was performed, with the diagnosis of Germinoma. Lymphocytic Hypophysitis is an uncommon diagnosis in children. Few cases have been reported, and in some cases, they were later diagnosed with Germinoma. We believe this case highlights the importance of the follow-up of children with Central Diabetes Insipidus with a normal MRI, as well as not taking the diagnosis of Lymphocytic Hypophysitis/ lymphocytic Infundibular neurohypophysitis as definitive, as it is a rare diagnosis at thisage, and could mask a Germinoma, as recorded in some cases