Acquired forms of central diabetes insipidus: Mechanisms of disease.

Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80-90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.

Central diabetes insipidus in children: Diagnosis and management.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of conditions (genetic, congenital, inflammatory, neoplastic, traumatic) that arise mainly from the hypothalamus. The differential diagnosis between diseases presenting with polyuria and polydipsia is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating the sellar-suprasellar region in CDI. Pituitary stalk size at presentation is variable and can change over time, depending on the underlying condition, and other brain areas or other organs - in specific diseases - may become involved during follow up. An early diagnosis and treatment are preferable in order to avoid central nervous system damage and the risk of dissemination of germ cell tumor, or progression of Langerhans Cell Histiocytosis, and in order to start treatment of additional pituitary defects without further delay. This review focuses on current diagnostic work-up and on the role of neuroimaging in the differential diagnosis of CDI in children and adolescents. It provides an update on the best approach for diagnosis - including novel biochemical markers such as copeptin - treatment and follow up of children and adolescents with CDI; it also describes the best approach to challenging situations such as post-surgical patients, adipsic patients, patients undergoing chemotherapy and/or in critical care.

Nephrocalcinosis among children at king hussein medical center: Causes and outcome.

Nephrocalcinosis (NC) is defined as deposition of calcium crystals in the renal parenchyma and tubules. This is a retrospective review of all the data of 63 children presented to Pediatric Nephrology Clinic at King Hussein Medical Center (KHMC) over a 15-year period with bilateral NC. We determine their causes, clinical presentation and evaluate their growth and renal function during their follow-up. Thirty-five (55.5%) cases were males and 28 (44.5%) were females. The median (range) age at presentation was four (2-192) months. The most common leading cause to NC was hereditary tubulopathy in 48% followed by hyperoxaluria in 35%. The cause of NC remained unknown in 3% and Vitamin D excess accounts for 5% of the cases. The most presenting symptom was a failure to thrive (68%) and the second most common symptom was abdominal pain and recurrent urinary tract infection was found in 40%, polyuria and polydipsia were found in 32% of cases, and 16% of cases were diagnosed incidentally. At a median follow-up of 38 (14-200) months, estimated glomerular filtration rate had decreased from 84.0 (42-110) mL/min per 1.73 m2 body surface area to 68.2 (10-110) mL/min/1.73 m2 body surface (P = 0.001). This study illustrated the need for a national registry of rare renal diseases to help understand the causes of these conditions in our populations and provide support to affected patients and their families.

INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA.

OBJECTIVE: Polydipsia and polyuria are common reasons 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 (CDI) 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. METHODS: 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. RESULTS: The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (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 = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality. CONCLUSION: The incidence of CDI 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 Na and osmolality on a WDT. ABBREVIATIONS: BMI = body mass index CDI = central diabetes insipidus DI = diabetes insipidus Na = sodium WDT = water deprivation test.

The pathway to diagnosis of type 1 diabetes in children: a questionnaire study.

OBJECTIVE: To explore the pathway to diagnosis of type 1 diabetes (T1D) in children. DESIGN: Questionnaire completed by parents. PARTICIPANTS: Parents of children aged 1 month to 16 years diagnosed with T1D within the previous 3 months. SETTING: Children and parents from 11 hospitals within the East of England. RESULTS: 88/164 (54%) invited families returned the questionnaire. Children had mean±SD age of 9.41±4.5 years. 35 (39.8%) presented with diabetic ketoacidosis at diagnosis. The most common symptoms were polydipsia (97.7%), polyuria (83.9%), tiredness (75.9%), nocturia (73.6%) and weight loss (64.4%) and all children presented with at least one of those symptoms. The time from symptom onset to diagnosis ranged from 2 to 315 days (median 25 days). Most of this was the appraisal interval from symptom onset until perceiving the need to seek medical advice. Access to healthcare was good but one in five children presenting to primary care were not diagnosed at first encounter, most commonly due to waiting for fasting blood tests or alternative diagnoses. Children diagnosed at first consultation had a shorter duration of symptoms (p=0.022) and children whose parents suspected the diagnosis were 1.3 times more likely (relative risk (RR) 1.3, 95% CI 1.02 to 1.67) to be diagnosed at first consultation. CONCLUSIONS: Children present with the known symptoms of T1D but there is considerable scope to improve the diagnostic pathway. Future interventions targeted at parents need to address the tendency of parents to find alternative explanations for symptoms and the perceived barriers to access, in addition to symptom awareness.

The clinical pattern of diabetes Insipidus in a large university hospital in the Middle East.

Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of high serum osmolality, hypernatremia and low urine osmolality due to increased urine output confirmed the diagnosis. Water deprivation test was required in some cases with non-classic presentations. Appropriate brain imaging was performed whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients, 15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7% (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was due to variable aetiology. Though CDI was the commonest, NDI was not a rare encounter in our community, possibly because of high consanguineous marriages.