Diabetes Insipidus & Syndrome of Inappropiate Antidiuretic Hormone
Diabetes Insipidus & Syndrome of Inappropiate Antidiuretic Hormone
SYNDROME OF
INAPPROPIATE
ANTIDIURETIC HORMONE
Javier Sevilla-Rodriguez, MD
Ponce Health Science University
What is ADH?
• ADH- Antidiuretic Hormone: helps to
control blood pressure by acting on the
kidneys and the blood vessels. Its most
important role is to conserve the fluid
volume of your body by reducing the
amount of water passed out in the urine.
• Patients with untreated central diabetes insipidus typically present with polyuria,
nocturia, and, due to the initial elevation in serum sodium and osmolality,
polydipsia
• They may also have neurologic symptoms related to the underlying neurologic
disease
• Idiopathic CDI — Approximately 30 to 50% of
cases of CDI are idiopathic, being associated
with destruction of the hormone-secreting cells
in the hypothalamic nuclei. It has been
suggested that an autoimmune process is
Pathophysiology involved in many, if not most, patients.
of Central
• Neurosurgery or trauma — CDI can be induced
Diabetes by neurosurgery (usually transsphenoidal) or
Insipidus trauma to the hypothalamus and posterior
pituitary. The incidence of CDI in these patients
varies with the extent of injury, ranging from 10
to 20 percent after transsphenoidal removal of
an adenoma limited to the sella to as high as 60
to 80 percent after removal of very large
tumors.
Pathophysiology of Nephrogenic
Diabetes Insipidus
• Lithium toxicity — These adverse effects are mediated by
lithium entry into the principal cells in the collecting tubule via
the epithelial sodium channel (ENaC). At cytotoxic
concentrations, lithium inhibits signaling pathways that
involve glycogen synthase kinase type 3 beta (GSK3beta),
resulting in dysfunction of the aquaporin-2 water channel.
• Hypercalcemia — Calcium-sensing receptors are also
expressed on the luminal membrane of the cells of the inner
medullary collecting duct (IMCD). By reducing calcium and
sodium reabsorption in the loop of Henle, hypercalcemia is
associated with an increase in calcium delivery to the luminal
IMCD calcium-sensing receptors; their activation reduces the
antidiuretic hormone-induced increase in water permeability
• Hypokalemia — Persistent severe hypokalemia (plasma
potassium concentration usually < 3 mEq/L) can impair
urinary concentrating ability. As with hypercalcemia, both
decreased collecting tubule responsiveness to ADH (which
may be mediated by decreased expression of aquaporin-2)
and diminished sodium chloride reabsorption in the thick
ascending limb have been demonstrated in experimental
animals.
DIAGNOSTIC AND
THERAPEUTIC
APPROACH DIABE
TES INSIPIDUS