Syndrome of inappropriate secretion of antidiuretic hormone

The syndrome of inappropriate antidiuretic hormone secretion, the Schwartz-Bartter syndrome ( SIADH , syndrome of inappropriate antidiuretic hormone secretion ) is characterized by increased secretion of ADH (vasopressin), which is not dependent on plasma osmolality . Most children have lung or intracranial disease, this syndrome can also arise iatrogenically (treatment of enuretics with adiuretin). Patients have normovolemia or relative hypervolemia. It is dilutional hyponatremia , serum hypoosmolality . Urinary sodium loss is slightly higher, certainly not reduced. There is low uricemia and increased uricosuria .

Etiologie[edit | edit source]

- CNS involvement: meningitis , encephalitis , brain abscess , tumor, trauma / hemorrhage , hydrocephalus
- malignancy: m. Hodgkin , neuroblastoma , lung , GIT and uropoietic tract tumors
- pulmonary involvement: pneumonia , TB , UPV , PNO , acute respiratory insufficiency , chronic obstructive pulmonary diseases
- drugs: DDAVP, paracetamol , indomethacin, barbiturates, carbamazepine, indapamide, SSRI, donepezil, thiazide diuretics

Physiology[edit | edit source]

ADH (antidiuretic hormone) , also known as arginine-vasopressin (AVP) is a nonapeptide that is synthesized in ncl cells. supraoptic and ncl. paraventricularis hypothalamus. It is transported by axonal transport to the neurohypophysis , from where it is released, together with the transport protein neurophysin, in response to a change in serum osmolality. A change in osmolality of ≥ 2% is already detected by osmoreceptors in the hypothalamus . Increased osmolality leads to an increase in ADH secretion, and conversely, a decrease in serum osmolality leads to suppression of ADH secretion. In the kidneys, ADH increases the permeability of the terminal part of the distal tubule and the collecting ducts in the medulla region by inducing specific membrane transport channels for water – aquaporins .

Patofyziologie[edit | edit source]

SIADH was first described by Schwartz in 1957. In SIADH , there is excessive release of ADH from the neurohypophysis (intracranial disease, drug induction: barbiturates, carbamazepine) or ectopic production of ADH occurs (tumors: lymphomas , Ewing's sarcoma ). An increased level of ADH occurs in pathological conditions that are associated with redistribution of blood in the vascular bed with subsequent hypovolemia in the area of the bulky vessels of the chest and in the left atrium. In bacterial and viral pneumonias, emphysema , cystic fibrosis , UPV causes increased pulmonary vascular resistance, reduced left atrial filling and increased ADH levels.

Increased secretion of ADH causes reabsorption of water in the collecting tubules of the kidneys. This gives rise to a tendency towards expansion of both intravascular and extravascular volume . This tendency is compensated by the increased secretion of atrial natriuretic peptide , which is why we find increased natriuresis despite a low level of plasma natremia. However, the cause of increased natriuresis in SIADH is not fully understood, other possibilities of increased natriuresis include increased glomerular filtration , reduced secretion of aldosterone . And it is the presence of higher natriuresis that is the main problem in differentiating SIADH from CSWS .

SIADH is accompanied by a slight increase in body water volume. The immediate response to a rapid drop in extracellular fluid osmolality is the passive movement of water from the extracellular space to the more hypertonic intracellular space. This leads to an expansion of organ cell volume ( brain swelling ). As most of the excess body water is found intracellularly, hyperhydration does not manifest itself clinically for a long time.

Diagnostics[edit | edit source]

Traditional SIADH criteria:

S-Na < 130 mmol/l
S-osmolalita < 280 mOsmol/l
U-Na > 20 mmol/l
U-osmolalita > S-osmolalita
normal thyroid , kidney and adrenal function
absence of peripheral swelling or dehydration

In the serum we find hyponatremia, hypoosmolality, normal or reduced potassium , urea, creatinine , uric acid . U-Na > 20 mmol/l (with low sodium intake, however, losses can be significantly lower). Intravascular volume is normal or slightly increased. Patients are normotensive. Another laboratory finding may be MAC with reduced AG , but there is no compensatory hypocapnia .

If there is any doubt in the diagnosis, determination of the serum or urinary concentration of ADH can be used. Under normal circumstances, ADH cannot be detected in hyponatremic states, on the contrary, we demonstrate increased levels in SIADH. However, ADH levels must be interpreted with caution, because ADH secretion is not only affected by osmolality, but also by stress, pain, increased intracranial pressure , etc.

Other possibilities are provided by the determination of the serum concentration of copeptin , which is secreted together with ADH in an equimolar amount, but is more stable than ADH.

Clinical picture[edit | edit source]

Clinical symptoms are a manifestation of brain edema . In the acute course, lethargy, apathy, disorientation, nausea, vomiting , muscle spasms , decreased deep muscle reflexes, pathological reflexes, and Cheyne-Stokes respiration appear . If hyponatremia develops over several days and weeks, the patient may be asymptomatic or with nonspecific symptoms such as nausea, vomiting, or lethargy. Rarely, rhabdomyolysis can also occur .

Symptomatology is not determined by the absolute value of natremia, but by the rate of its decrease. This should also be kept in mind during treatment. Prolonged hyponatremia must be corrected slowly, whereas acute neurological symptoms require prompt intervention.

Therapy[edit | edit source]

In the case of a chronic course, it is usually sufficient to restrict fluids to 2/3 (or less) of the daily requirement and after sodium substitution. In acute conditions and a critical value of natremia Na < 120 mmol/l, we administer 1/1 FR or hypertonic solutions (e.g. 3% NaCl 3 to 5 ml/kg iv as a slow bolus) + furosemide 1–2 mg/kg iv (can be repeated according to the answer and the state of the internal environment). As soon as the acute symptom subsides, we switch back to fluid restriction. The long-term goal of treatment is to correct hyponatremia within 48 hours. It is essential to eliminate the provoking cause.

A condition of treatment is monitoring of body weight, diuresis and internal environment, including correction of sodium and osmolality in serum and urine.

Another possibility is the use of vaptans - e.g. tolvaptan.

Pediatricians must keep in mind that hypoosmolal syndrome can also be induced iatrogenically by feeding large amounts of 5% or 10% glucose without ions!

Links[edit | edit source]

Source[edit | edit source]

HAVRÁNEK, Jiří: SIADH, syndrome of inadequate ADH secretion . (edited)
JAVORKA, Kamil. Medical physiology: a textbook for medical faculties. 2nd edition. Martin: Osveta, 2006. ISBN 8080632316 .

RUDNAY, Maroš, Petra HRABČÁKOVÁ and Ivica LAZÚROVÁ. Hyponatremia in syndrome of inappropriate vasopressin secretion (SIADH) – treatment options. Internal Medicine. 2012, year 58, vol. 1, p. 52-55,

VOKURKA, Martin and Jan HUGO, et al. The Great Medical Dictionary. 9th edition. Prague: Maxdorf, 2009. 1159 pp. ISBN 978-80-7345-202-5 .

ČESKA, Richard, et al. Internal 2nd edition. Prague: Triton, 2015. 909 pp. ISBN 978-80-7387-895-5 .

External links[edit | edit source]

SIADH and hyponatremia — interactive algorithm + test