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: Intracranial:

• Tumor
• meningitis
• encephalitis
• abscess
• vasculitis
• subarachnoid hemorrhage
• subdural hemorrhage
• traumatic brain injury

Drugs :

• amiodarone
• tricyclic antidepressants
• bromocriptine
• quinolones
• chlorpropamide
• carbamazapine
• cyclophosphamide
• cisplatin
• SSRI
• vincristine
• vinblastine
• thioridazine
• thiothixene
• haloperidol
• MAOI
• melphalan
• methotrexate
• opiates
• NSAID
• IFN-alpha
• IFN-gamma
• clofibrate
• oxytocin
• hydrochlorthiazide
• desmopressin
• neuroleptic agents
• prostaglandins
• phenothiazines
• 3,4-methylenedioxymethamphetamines
• leveteiracetam

• Pulmonary disease: particularly pneumonia (leigonella ,mycoplasma, tuberculosis),abscess,vasculitis.

• Malignancy:
• small cell lung cancer
• pancreatic
• genitourinary
• gastrointestinal
• mesothelioma
• lymphoma
• sarcoma

• Miscellaneous:
• Multiple sclerosis
• Guillian barre syndrome
• Acute intermittent porphyria
• HIV
• Idiopathic
• surgery
• hormone deficiency: hypopituitirarism,hypothyroidism

6 Zilberberg MD, Exuzides A, Spalding J, Foreman A, Jones AG, Colby C & Shorr AF. Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study. BMC Pulmonary Medicine 2008 8 16. 7 Sherlock M, O’Sullivan E, Agha A, Behan LA, Rawluk D, Brennan P, Tormey W & Thompson CJ. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clinical Endocrinology 2006 64 250–254.

• 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.

• 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.

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