Antidiuretic hormone (ADH), or
arginine vasopressin (AVP), is primarily regulated through plasma osmolarity, as well as non-osmotic stimuli including blood volume and stress. Links between water-
electrolyte and carbohydrate metabolism have also been recently demonstrated. AVP acts via the intermediary of three types of receptors: V1a, or V1, which exerts vasoconstrictive effects; pituitary gland V1b, or V3, which participates in the secretion of
ACTH; and renal V2, which reduces the excretion of pure water by combining with
water channels (
aquaporin 2). Antidiuresis syndrome is a form of euvolaemic, hypoosmolar hyponatraemia, which is characterised by a negative free water clearance with inappropriate urine osmolality and intracellular hyper-hydration in the absence of renal, adrenal and thyroid insufficiency. Ninety percent of cases of antidiuresis syndrome occur in association with hypersecretion of
vasopressin, while
vasopressin is undetectable in 10% of cases. Thus the term "antidiuresis syndrome" is more appropriate than the classic
name "syndrome of inappropriate ADH secretion" (
SIADH). The clinical symptoms, morbidity and mortality of hyponatraemia are related to its severity, as well as to the rapidity of its onset and duration. Even in cases of moderate hyponatraemia that are considered asymptomatic, there is a very high risk of falls due to gait and attention disorders, as well as
rhabdomyolysis, which increases the fracture risk. The aetiological diagnosis of hyponatraemia is based on the analysis of calculated or measured plasma osmolality (POsm), as well as blood volume (skin tenting of
dehydration, oedema). Hyperglycaemia and hypertriglyceridaemia lead to hyper- and normoosmolar hyponatraemia, respectively.
Salt loss of gastrointestinal, renal, cutaneous and sometimes cerebral origin is hypovolaemic, hypoosmolar hyponatraemia (skin tenting), whereas oedema is present with hypervolaemic, hypoosmolar hyponatraemia of
heart failure,
nephrotic syndrome and
cirrhosis. Some endocrinopathies (
glucocorticoid deficiency and
hypothyroidism) are associated with euvolaemic, hypoosmolar hyponatraemia, which must be distinguished from
SIADH. Independent of
adrenal insufficiency, isolated
hypoaldosteronism can also be accompanied by hypersecretion of
vasopressin secondary to hypovolaemia, which responds to
mineralocorticoid administration. The causes of
SIADH are classic: neoplastic (notably
small-cell lung cancer), iatrogenic (particularly
psychoactive drugs,
chemotherapy), lung and cerebral. Some causes have been recently described: familial hyponatraemia via X-linked recessive disease caused by an activating mutation of the
vasopressin 2 receptor; and
corticotropin insufficiency related to
drug interference between some inhaled
glucocorticoids and
cytochrome p450 inhibitors, such as the antiretroviral drugs and
itraconazole, etc.
SIADH in marathon runners exposes them to a risk of hypotonic
encephalopathy with fatal cerebral oedema.
SIADH treatment is based on water restriction and
demeclocycline.
V2 receptor antagonists are still not marketed in France. These aquaretics seem effective clinically and biologically, without demonstrated improvement to date of mortality in eu- and hypervolaemic hyponatraemia. Obviously treatment of a corticotropic deficit, even subtle, should not be overlooked, as well as the introduction of
fludrocortisone in isolated
hypoaldosteronism and discontinuation of iatrogenic drugs.