Physiology
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Endocrine
An 82 year old patient presents with muscle weakness, fatigue and nausea. Blood tests demonstrate hyponatraemia. Further tests show low serum osmolality and raised urine osmolality and urinary sodium. She has recently started a new medication. Which of the following drugs is the most likely causative agent:
Answer:
The diagnosis is SIADH. SSRIs increase the release of ADH, and the reported incidence of hyponatraemia caused by their use varies widely from 0.5–32%. Hyponatraemia usually develops within the first few weeks of treatment and resolves within 2 weeks of stopping the drug. Older age and concomitant use of diuretics are the most important risk factors for development of SSRI-associated hyponatraemia. Other drugs commonly implicated in hyponatraemia include:- Diuretics (all types implicated, but thiazides are the commonest cause)
- Antipsychotics (e.g. haloperidol and phenothiazines)
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Anticonvulsants (e.g. carbamazepine)
- And, less commonly: sulphonylureas, tricyclic antidepressants, dopamine agonists, opiates, theophylline, chlorpropamide, clofibrate, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists (AIIRAs), melphalan, proton pump inhibitors, amiodarone, domperidone and MDMA ('ecstasy')
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Physiology / Endocrine / Pituitary Function
Last Updated: 21st April 2019
Diagnosis
Syndrome of inappropriate ADH (SIADH) is characterised by:
- euvolaemic hypo-osmolar hyponatraemia in the context of:
- a low serum osmolality (< 275 mosmol/kg)
- urine osmolality > 100 mosmol/kg and
- urine sodium > 30 mmol/L.
SIADH can only be diagnosed after the exclusion of hypothyroidism, total salt depletion and ACTH deficiency. ACTH deficiency appears identical to SIADH because it causes reduced excretion of free water, because cortisol deficiency leads to increased ADH activity. This is different from hyponatraemia caused by mineralocorticoid deficiency in Addison's disease.
Causes
The potential causes of SIADH are vast including:
- Malignancy:
- lung, lymphoma, gastrointestinal/pancreatic malignancy, genitourinary malignancy
- Neurological:
- malignancy, infection, trauma, haemorrhage
- Pulmonary:
- pneumonia, TB, abscess, malignancy
- Drugs:
- SSRIs, tricyclic antidepressants, anticonvulsants
- Miscellaneous:
- idiopathic, HIV, MS, Guillain-Barre, Acute Intermittent Porphyria
Idiopathic SIADH is a diagnosis of exclusion.
Management
Reversal or treatment of the cause of SIADH and fluid restriction are the key aspects of management. Strict fluid restriction (1 - 1.5 L/day) is poorly tolerated and difficult to achieve. Drug treatment of SIADH includes demeclocycline and ADH antagonists. Demeclocycline reduces renal response to ADH but its use is limited by side effects and unpredictable pharmacokinetics. ADH antagonists directly block ADH action and are of use in specific clinical situations.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
