Central diabetes insipidus

Diabetes mellitus develops due to inadequate synthesis and / or secretion of antidiuretic hormone (central form), or the inability of the kidneys to respond adequately to circulating vasopressin (renal form).

In endocrinological practice, diabetes insipidus of central origin is one of the main causes of polyuria .

Central (hypothalamic, neurogenic, vasopressin-sensitive), diabetes insipidus develops the pathology structure vasopressin gene, in the case of surgical injury vasopressin neurons in congenital anatomical defects of the hypothalamus or pituitary tumors, infiltrative, autoimmune and infectious diseases that damage neurons vasopressin or fiber tracts with increased vasopressin metabolism. In approximately 10% of cases of central non-sugar diabetes in children, the etiology of the disease is unclear.
Genetic causes

Familial autosomal dominant central diabetes insipidus manifests during the first half of the first decade of a child’s life (1-6 years). Initially normal, vasopressin secretion gradually decreases with age, with the subsequent development of diabetes insipidus (Pedersen ea, 1985). Patients respond adequately to vasopressin replacement therapy. The disease has a high penetrance, but its expression may vary in the same family, and perhaps spontaneous improvement in the average age of e g eneticheskim disease locus is a gene-arginine vaso-Pressigny (A \ / P) -neyrofizin II (NPII), ka rtirovanny on chromosome 20r13 . This gene produces a pre-pro-precursor protein (prepressofizin), synthesized on ribosomes and contains a signal peptide and 9-amino acid AVP-peptide (encoded by exon 1), AUR-binding protein neurophysin II, NPII (partially encoded in each of the exons 1, 2 and 3), and copertin, vasopressin-glycopeptide, VGP with no proven function .

The precursor polypeptide is produced in the large-cell neurons of the supraoptic and paraventricular nuclei of the hypothalamus, where processing is initiated with the removal of the signal peptide and subsequent glycosylation and packaging of the propeptide. The packaging places the AVP precursor portion in a neurophysin M-binding pocket, which stimulates dimerization and promotes packaging in neurosecretory granules. The prohormone is enzymatically cleaved to three peptides – arginine-vasopressin, neurophysin and vasopressin-glycopeptide inside neurosecretory granules during axonal transport to the neuro-pituitary. These neurosecretory granules generate a high-intensity bright neurohypophysis bright spot on T1-weighted MRI images.

The familial form of the disease is due to mutations in the AVP-N gene. Mutations in this gene are found in both the pre-pro-AVP-NPM precursor signal peptide and NPII itself. Four mutations leading to a decrease in the activity of signal peptidases to remove the signal peptide from the precursor polypeptide are described in the signal peptide. Other mutations include a missense mutation in a sequence that encodes vasopressin and 12 missense mutations, 1 deletion and 5 nonsense mutations in a sequence that encodes NPII.

These data indicate the importance of neurophysin in the intracellular sorting and packaging of vasopressin into secretory granules. The product of a pathological gene can cause neuronal degeneration and cell death, explaining that the normal vasopressin allele cannot compensate for the pathological allele.

Vasopressin deficiency is also defined in hereditary DIDMOAD syndrome, including diabetes insipidus, diabetes mellitus, optic nerve atrophy, and deafness. The gene for this syndrome, also known as the Wolfram syndrome, is mapped on chromosome 4p.

Axons of vasopressin containing large-cell neurons descend into the posterior lobe of the pituitary, their length is about 10 mm. Trauma, accompanied by a fracture of the skull base, can cause swelling around these axons, leading to transient or persistent diabetes insipidus. About half of patients with fractures of the Turkish saddle acquire persistent diabetes insipidus, with a delayed onset of development 1 month after trauma, during which axon neurons undergo retrograde degeneration.

local_offerevent_note November 2, 2019

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