DIABETES INSIPIDUS Richard Sachson MD

Anatomy of the neurohypophysis Anatomy of the neurohypophysis

Magnetic resonance imaging of posterior pituitary gland Magnetic resonance imaging of posterior pituitary gland

Chemical structure of vasopressin Chemical structure of vasopressin

The gene that encodes AVP-NP is located on the short arm of chromosome 20 Vasopressin Is Encoded in a Gene That Also Encodes Neurophysin II, an AVP- Binding Protein Signal Peptide AVP NeurophysinGlycopeptide (Copeptin) Exon 1 Exon 2 Exon 3 Its three exons encode a signal peptide, the vasopressin molecule, its neurophysin binding protein, and a terminal glycoprotein. The precursor is processed to yield equimolar quantities of vasopressin and NP II.

How Vasopressin Works

Physiologic regulation of vasopressin Physiologic regulation of vasopressin

Plasma osmolality and plasma vasopressin concentration Plasma osmolality and plasma vasopressin concentration

Urine osmolality and plasma vasopressin concentration Urine osmolality and plasma vasopressin concentration

Water deprivation test in normal person Water deprivation test in normal person

Water deprivation test in diabetes insipidus Water deprivation test in diabetes insipidus

Urine osmolality during water deprivation Urine osmolality during water deprivation

Plasma arginine vasopressin vs. serum osmolality concentration Plasma arginine vasopressin vs. serum osmolality concentration

Thirst, plasma arginine vasopressin, and plasma osmolality in dipsogenic DI Thirst, plasma arginine vasopressin, and plasma osmolality in dipsogenic DI

Relationship of plasma and urinary AVP to plasma osmolality ©Copyright Science Press Internet Services

Differential Diagnosis of Hypotonic Polyuria ©Copyright Science Press Internet Services

Causes of nephrogenic diabetes insipidus Causes of nephrogenic diabetes insipidus

Agents that alter the response of the collecting duct to vasopressin Agents that alter the response of the collecting duct to vasopressin

Inherited Nephrogenic Diabetes Insipidus Is (Mostly) X-Linked 90% of patients are males with X-linked recessive form of the disease Less than 10% of familial nephrogenic DI has been transmitted as autosomal recessive or autosomal dominant trait Reviewed for your reading pleasure in Ann Rev Physiol 63:607 (2001)

Clinical Features Of X-linked Nephrogenic Diabetes Insipidus Untreated nephrogenic DI results in repeated episodes of dehydration in early infancy Early recognition and therapy (abundant water intake, low sodium diet, hydrochlorothiazide) may allow normal mental development and (maybe) normal growth

Most V2 Receptor Mutations Are in Transmembrane Domains of the Protein Morello and Bichet 2001; Ann Rev Physiol 63:607 V2 Receptor is a G-protein coupled receptor with seven transmembrane domains

Genetic mutations in the aquaporin 2 gene Genetic mutations in the aquaporin 2 gene

The Rarest Form Of Inherited Nephrogenic Diabetes Insipidus Is Due to Mutations In A Water Channel Gene AQP2 is encoded by a gene on chromosome 12 Most mutations are recessive, but some transmit a dominant phenotype

Causes of central diabetes insipidus Causes of central diabetes insipidus

Genetic mutations in neurogenic diabetes insipidus Genetic mutations in neurogenic diabetes insipidus

Genetic mutations in the vasopressin 2 receptor gene Genetic mutations in the vasopressin 2 receptor gene

Agents that alter vasopressin release Agents that alter vasopressin release

Treatment of diabetes insipidus Treatment of diabetes insipidus

Diabetes insipidus in pregnancy associated with abnormally high circulating vasopressinase activity J. A. Durr, J. G. Hoggard, J. M. Hunt, and R. W. Schrier NEJM :1070

Aggravation of subclinical diabetes insipidus during pregnancy Y Iwasaki, Y Oiso, K Kondo, S Takagi, K Takatsuki, H Hasegawa, K Ishikawa, Y Fujimura, S Kazeto, and A Tomita Aggravation of subclinical diabetes insipidus during pregnancy Y Iwasaki, Y Oiso, K Kondo, S Takagi, K Takatsuki, H Hasegawa, K Ishikawa, Y Fujimura, S Kazeto, and A Tomita NEJM :522

TERMINATION OF DEHYDRATION TEST 5% Loss of body wt 5% Loss of body wt Posm > Posm > Na >150 Na >150 Uosm >600 Uosm >600 SG >1.020 SG >1.020

PT JL TIMEVOLuSGuOSMNapOSMWT 7 PM AM 30 2: