Diabetes Insipidus: Celebrating a Century of Vasopressin Therapy

Abstract

Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

Neonatal Central Diabetes Insipidus Caused by Severe Perinatal Asphyxia

“…In neonate, CDI has been described as a complication of intrauterine and perinatal disease [3,4]. Some authors have suggested that possible causes of CDI may include asphyxia, severe infections, peri or intraventricular hemorrhage, and central nervous system abnormalities [1,2,4]. The state that is almost brain death caused by the severe perinatal asphyxia might develop in CDI.…”

“…CDI was diagnosed by the presence of hypernatremia (>150 mmol), high plasma osmolality (>300 mOsm), low urine osmolality (<300 mOsm/l), low plasma ADH levels, and recovery of serum sodium and urine osmolality after the administration of desmopressin [1][2][3]. In the present cases, hypernatremia, high plasma osmolality, low urine osmolality, and low plasma ADH levels (except case 1) with a good response to desmopressin (except case 3) easily led to the diagnosis of CDI.…”

“…Central diabetes insipidus (CDI) is the result of a deficiency of antidiuretic hormone (ADH) due to dysfunction of the posterior pituitary and/or hypothalamus [1,2]. CDI is an uncommon disorder characterized by polyuria, hypernatremia, high plasma osmolality, and low urine osmolality.…”

“…Water and electrolyte homeostasis in newborns is affected by postnatal physiological adaptation, and appropriate management is important, especially for the seriously ill newborn. Dehydration with hypernatremia can occur, associated with insensible water loss, high urine output, and reduced ability to secrete sodium in neonatal CDI cases [1,2]. Therefore, careful monitoring is needed to maintain water and electrolyte balance in neonatal CDI.…”

Drugs for the treatment of central diabetes insipidus: historical background and modern opportunities

“…Возможность применения меньших доз препарата снижает риск развития таких тяжелых состояний, как гипонатриемия и судорожный синдром. Все это де-лает десмопрессин препаратом выбора для лечения центрального и гестационного несахарного диа-бета [25,42,55]. Первые препараты синтетического вазопрессина были созданы еще в 1954 г., в основном применялись интраназально и обладали более низкой эффективно-стью и продолжительностью действия, по сравнению с питрессином [10], но с учетом отсутствия необходи-мости в парентеральном введении зачастую являлись более предпочтительными [49].…”