DIABETES INSIPIDUS

POSTERIOR PITUITARY

vasopressin and oxytocin

Synthesized in specialized neurons

in the hypothalamus, the
neurohypophysialneurons.

Magnocellular neurons.

paraventricular and supraoptic nuclei

provasopressin
vasopressin (9
a.a), vasopressinneurophysin (95
a.a), vasopressin
glycopeptide, or
copeptin (39 a.a).

Basal plasma levels of vasopressin are

generally 0.5 to 2 pg/mL

280-295 mOsm/kg H2O

ADH <0.5 pg/mL maximal urine

osmolality <100 mOsm/kg H2O, 800 to
1000 mL/hour (18 to 24 L/day).

Vasopresina

DI

Excrecin de un gran volumen de orina,

hipotnica, inspida, usualmente
manifestada por Poliuria, y polidipsia.

50-60ml/kg/dia

DI Central

DI Nefrogenica

DI Gestacional

Polidipsia Primaria

DI CENTRAL

Inhabilidad para secretar (usualmente

sintetizar ADH) en respuesta a una osm
aumentada

DI central

Poliurea de aparicin rpida secundaria a

ciruga transcraneal en el ara del
hipotlamo

Trauma craneal con fracturas de base de

crneo

Si hay inconciencia puede acompaarse

de hipernatremia

DI central

Suele ser abrupto y comienza en das a

semanas

El problema inicial es el aumento de la

orina y la polidipsia

La mayora de los pacientes no reportan

poliuria hasta que el volumen de orina
excede 4 L/day,

DI Central

Few laboratory abnormalities are present at the time

of initial evaluation.
[Na] may be in the high-normal range, BUN may be
low
Uric acid is relatively high due to the modest volume
contraction and the lack of action of vasopressin on
V1a receptors in the kidney, which stimulate the
clearanceof uric acid.
Uric acid levels greater than 5 mg/dL can distinguish
diabetes insipidus from primary polydipsia

DI Central Causas

Osmoreceptor dysfunction (essential

hypernatremia, adipsic hypernatremia)

Because patients lack thirst, they are chronically

dehydrated, with increased serum sodium levels.

If sufficient fluid replacement is given to return

extracellular fluid volume to normal, these
patients are unable to regulate vasopressin by
osmolality and become polyuric, thereby
manifesting their underlying diabetes insipidus.

Inherited as an autosomal dominant

disease

Characterized by an asymptomatic
infancy and an onset later in childhood.

Defects in the signal peptide of the preprohormone or in the neurophysin

portion of the prohormone.

Myxedema and adrenal insufficiency

both impair the ability to excrete free
water by renal mechanisms.
Simultaneous occurrence of either of
these diseases with central diabetes
insipidus may mask the symptoms
Tumor of the hypothalamus or pituitary
Hypothyroidism or adrenal insufficiency

severe brain ischemia

DI Nefrogenica

Inhabilidad para responder normalmente

ante el estimulo de ADH

Niveles plasmticos de ADH

inapropiadamente aumentados en
relacin a la osm

Nephrogenic Diabetes
Insipidus

Mutations of the vasopressin V2 receptor

Vasopressin-induced water channel

aquaporin-2

Impairments in the signal transduction

system linking the V2 receptor and
aquaporin-2.

Nephrogenic Diabetes
Insipidus

Familial nephrogenic diabetes insipidus

is a rare disease

>90% are due to mutations of the V2

receptor.

X-linked recessive disease.

Nephrogenic Diabetes
Insipidus

Males who present with

vomiting, constipation,
failure to thrive, fever,
and polyuria during the
first week of life

Hypernatremia is found
with a hypotonic urine.

Nephrogenic Diabetes
Insipidus

Acquired during treatment with certain

drugs
demeclocycline (which is used to treat
inappropriate secretion of vasopressin),
lithium carbonate (used to treat bipolar
disorders),
Fluoride (previously used in fluorocarbon
anesthetics)
Electrolyte abnormalities such as
hypokalemia and hypercalcemia

DI Gestacional

Rara
Niveles aumentados de aminopeptidasa
cistina (oxitocinasa, vasopresinasa)
Suele acompaarse de preeclampsia,
higado graso, coagulopatias.

Polidipsia Primaria

Trastorno de ingesta excesiva de lquidos

Niveles sricos de ADH bajos, pero

apropiados para la osm.

schizophrenia, mania, or obsessivecompulsive disorder

DIAGNOSTICO

water deprivation test

Dx Etiolgico

MRI of the
hypothalamicpituitary area

Immediate
suprasellar region
of the
hypothalamus, the
pituitary stalk, and
the posterior
pituitary within the
sella turcica

Primary tumors, especially

craniopharyngioma and suprasellar
germinoma

Metastatic tumors; and infiltrative

diseases can also cause diabetes
insipidus by infiltration of the pituitary
stalk, which is then thickened on MRI.

T1-weighted MRI, the vasopressin and

oxytocin stored in neurosecretory granules
in the posterior pituitary are visualized as a
bright spot in the sella turcica.

Tumors that cause central diabetes insipidus

are most often benign primary intracranial
tumors such as craniopharyngioma,
ependymoma (suprasellar germinoma), and
pinealoma, which arise in the third ventricle.

Tratamiento

Rehidratacin Oral o IV (puede

llegar a ser inconveniente)
La meta es Reducir la cantidad de
poliurea y polidipsia, a un nivel tolerable
Evitar retencin e hiponatremia

Tratamiento

Desmopresina

Tabletas de 0.1 or 0.2 mg oral

Spray dosis de 10 g en 100 L

Botella de spray con cateter rhinal

50 to 200 L (5 to 20 g)

Tratamiento

Iniciar Con dosis Bajas

Media 0.1-mg tableta, 5 g by the rhinal
tube, or a single 100 L spray of 10 g
Al acostarse y al siguiente determinar la
duracion de la accion con la poliurea
Duracin de una sola dosis 6-24hrs
Suele ser necesaria cada 12hrs spray
nasal
8-12hrs con tabletas

Tratamiento

Px con DI parcial
Chlorpropamide 100 to 500 mg/dia
Aumenta los efectos de ADH en el tubulo
renal
Efecto antidiuretico de 1-2 dias
Efecto maximo en una semana

Tratamiento

Indometacina

Diurticos Tiazidas

DI NEFROGENICA:
Amiloride, clorotiazida, Indometacina
Suspender Agente Causal (litio)

Tratamiento

DI Gestacional:

Desmopresina

DI post operativa-trauma craneal

Puede ser transitoria, requiere

observacion antes de indicar tx.

Complicaciones

Hipernatremia

Hemorragia Subaracnoidea

Hemorragia intraparanquimatosa

Hiponatremi
a
persistente
Produccin
de
Osmolitos
organicos

Adaptacin

Si ocurre adaptacin, una disminucin

drstica de la osm srica puede llevar a
edema Cerebral
Prevenir con desmopresina
Dar agua con la meta de reducir osm de
1 mEq cada 2 hrs.

Bibliografa

Ananthakrishnan S. Diabetes insipidus in pregnancy: etiology, evaluation,

and management. Endocr Pract. 2009;15:377-382. Review of diabetes
insipidus in pregnancy, emphasizing the need for increased awareness of the
syndrome to permit early diagnosis and appropriate treatment to reduce
maternal and fetal morbidity.
Los EL, Deen PM, Robben JH. Potential of nonpeptide (ant)agonists to rescue
vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic
diabetes insipidus. J Neuroendocrinol. 2010;22: 393-399. V2R-specific cellpermeable agonists are promising therapeutics.
Noda Y, Sohara E, Ohta E, et al. Aquaporins in kidney pathophysiology. Nat
Rev Nephrol. 2010; 6:168- 178. Recent advances in understanding the
pathophysiology of the multiple kidney aquaporin water channels, including
their role in nephrogenic diabetes insipidus.
Ross HE, Young LJ. Oxytocin and the neural mechanisms regulating social
cognition and affiliative behavior. Front Neuroendocrinol. 2009;30:534-547.
Brain oxytocin is an important modulator of social behavior