Sandbox:Vindhya

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2]

SIADH

Definition :The syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by the excessive release of serum antidiuretic hormone (ADH) relative to serum osmolality. It typically results in excessive water reabsorption in the collecting ducts and hyponatremia

Historical perspective: Described by researchers from Boston, Massachusetts and Bethesda, Maryland (including Dr Frederic Bartter) in two patients with lung cancer.[1] Criteria were developed by Schwartz and Bartter in 1967,[2].

Pathogenesis:

Causes: CNS disturbances:

• Stroke
• trauma
• infection
• psychosis

Drugs :

• amiodarone
• amitryptyline
• bromocriptine
• ciprpfloxacin
• chlorpropamide
• carbamazapine
• cyclophosphamide
• cisplatine
• SSRI
• vincristine
• vinblastine
• thioridazine
• thiothixene
• haloperidol
• MAOI
• melphalan
• methotrexate
• opiates
• NSAID
• IFN-alpha
• IFN-gamma
• clofibrate
• oxytocin
• hydrochlorthiazide
• desmopressin
• neuroleptic agents

• Surgery: associated with hyper secretion of ADH, a response that is mediated by pain afferents.

• Pulmonary disease: particularly pneumonia (viral, bacterial, tuberculous), can lead to the SIADH, although the mechanism by which this occurs is not clear.A

similar response may infrequently be seen with asthma, atelectasis, acute respiratory failure, and pneumothorax.

• Hormone deficiency: Hypopituitarism, hypothyroidism

• HIV infection

• Malignancy- Ectopic production of ADH due to tumors can cause SIADH. Most often due to small cell carcinoma of the lung. Less common causes of malignancy-associated SIADH include head and neck cancer, olfactory neuroblastoma,GI cancers,breast cancers...

PMID:27142293

• Genetics: clinical picture of SIADH may result from genetic disorders that result in antidiuresis. A mutation affecting the gene for the renal V2 receptor, which some investigators have named nephrogenic syndrome of inappropriate antidiuresis, has been found to cause clinically significant hyponatremia.

congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine.He X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors.conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

PMID:25449762

• Signs and symptoms:

In patients with SIADH there is too much water in the blood,this leads to low sodium in the body.

Hyponatremia is the most common manifestation. The symptoms are based on level of sodium.(hyponatremia: sodium level below 135meq/l)

When symptoms do occur, they may include any of the following:

• headache

• altered mental status

• frequent falls

• neurological manifestations such as lethargy, confusion...

in severe cases,seizures and coma may result.

In the diagnosis of SIADH it is important to ascertain the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements. SIADH should be treated to cure symptoms. While this is essential in the presence of severe symptoms, the indications for treatment in the presence of mild to moderate symptoms are currently unclear. Therapeutic modalities include nonspecific measures and means (fluid restriction, hypertonic saline, urea, demeclocycline), with fluid restriction and hypertonic saline commonly used.Recently vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH. Although clinical experience with vaptans is limited at this time, they appear advantageous to patients because there is no need for fluid restriction and the correction of hyponatremia can be achieved comfortably and within a short time. Vaptans also appear to be beneficial for physicians and staff because of their efficiency and reliability.

Diagnostic criteria of SIADH:

• Na<135mmol/litre
• decreased effective serum osmolality<275mosm/kg
• urine osmolality>100mosm/kg
• presence of underlying disorders;CNS,pulmonary,malignancies,medications
• normal adrenal and thyroid function
• urine Na concentration>40mmol/l,unless taking diuretics,(or) on a severe salt restriction.
• absence of edematous diseases(such as heart failure,nephrotic syndrome, liver cirrhosis)

Agents and means used in the treatment of SIADH.

Indirect modalities:

• treatment of underlying pathology
• salt restriction
• Hyper-tonic saline
• Loop diuretics
• Urea
• Demecloclycline, lithium
• Hemodialysis, CVVH(continuous veno-venous hemofiltration), SLED(slow, low-efficiency daily dialysis).

Direct modalities:

"Vaptan drugs": block action of vasopressin at it's receptors,(V1A,V1B,V2)

Prognosis:Patients with SIADH have different characteristics and a different prognosis according to SIADH etiology. Serum sodium concentration at short-term follow-up is predictive of long-term survival. These findings might have diagnostic and treatment-related implications. PMID:26563934