Serum/plasma
Spot urine
24-h urine
Osmolality (mOsmol/kg)
298
86
–
Sodium (mmol/L)
147
16
114
Potassium (mmol/L)
4.1
3
21
Urea (mmol/L)
2.5
30
215
Creatinine (μmol/L)
58
1.9
13.6
Adjusted calcium (mmol/L)
2.34
–
–
ALT (iu/L)
35
–
–
TSH (miu/L)
1.5
–
–
Glucose (mmol/L)
5.1
–
–
Urine volume (L)
–
–
7.2
How would you exclude adrenal insufficiency in this patient?
Glucagon stimulation test. A 9 am cortisol of 402 nmol/L which peaked to 650 nmol/L at 150 min during an intra-muscular glucagon stimulation test, confirms adequate cortisol reserve. Subsequently, oral hydrocortisone was stopped. Cortisol deficiency reduces glomerular filtration and may lead to reduced water excretion hence, DI may be masked. A short Synacthen® test should not be used within 2 weeks of pituitary surgery as it may give a false positive result because the adrenal glands have not had a chance to atrophy.
How would you make the diagnosis of DI?
Water deprivation test. Water restriction in the normal individual results in secretion of ADH by the posterior pituitary in order to reclaim water from the distal renal tubules. Failure of this mechanism results in a rise in plasma osmolality due to water loss, and the production of a dilute urine with low osmolality. Response to administration of synthetic ADH, Desmopressin®, helps differentiate cranial DI from nephrogenic DI.
During water deprivation the patient did not conserve water and passed dilute urine. After administration of Desmopressin®, the urine osmolality increased to 758 mOsm/kg, confirming a diagnosis of cranial DI. A normal person will reduce their urine volume to less than 50 mL after 4 h of fluid restriction (unpublished data) and the urine osmolality approaches 750–1,000 mOsm/Kg. See Table 10.2.
Table 10.2
Water deprivation test results
Time | Urine volume (mL) | Urine osmolality (mOsm/kg) | Plasma osmolality (mOsm/kg) |
|---|---|---|---|
0800 am | 0 | 94 | 295 |
0900 am | 430 | 103 | 299 |
1000 am | 460 | 84 | 300 |
1100 am | 380 | 113 | 298 |
1200 pm | 375 | 117 | 302 |
1230 pm | Desmopressin ®administered 1 μg intramuscularly | ||
1300 pm | 110 | 246 | 299 |
1400 pm | 60 | 758 | 296 |
How do you treat the patient?
Patients with intact thirst mechanism are able to compensate for the fluid loss. However, inadequate thirst mechanism can lead to severe dehydration and hypernatremia. Hence, monitoring of fluid balance is essential. Desmopressin® 100 μg tablets once a day (perhaps given at night in the first instance) and titrated depending on the response. Intranasal and parenteral preparations are also available. The duration of action after oral administration ranges from 6 to 12 h. The response is seen as a decrease in urine output within 1–2 h.
Review of Diabetes Insipidus
Water constitutes approximately 50–60 % of total body weight in human adults. It is distributed between the extracellular and intracellular compartments.
There is a two part system regulating water and salt homeostasis. Antidiuretic hormone (ADH) is mainly involved in the regulation of water homeostasis and osmolality of body fluids. ADH is primarily under osmoregulation but is also stimulated by hypovolaemia or hypotension. The renin-angiotensin-aldosterone system (RAAS) is a more sensitive mechanism to restore changes in blood pressure and total body volume [1]. Other natriuretic peptides such as atrial natriuretic peptide and brain natriuretic peptide have been identified in water overload.
ADH also known as vasopressin, arginine vasopressin (AVP) is synthesised in the hypothalamus and stored in the posterior pituitary as a prohormone. It is released as an active hormone in response to changes sensed by central and peripheral osmoreceptors [2, 3]. The osmolality of extracellular fluid is maintained between 285 and 295 mOsm/kg of water in normal subjects through close interaction between the osmoreceptors and the hypothalamus. In the kidneys, ADH acts on the collecting duct and increases the permeability of water through aquaporin channels [4] in the apical plasma membrane of the principal cells. This results in increased water retention but since no ions are reabsorbed, the reduced urine volume has an increased osmolality. In response to high plasma osmolality the hypothalamus also stimulates the thirst mechanism to induce water consumption.
In diabetes insipidus (DI) patients are unable to secrete ADH and thereby conserve water and consequently produce large volume of dilute, tasteless (insipid) urine. Patients will experience extreme thirst and drink copious amount of water to maintain their water homeostasis. In diabetes mellitus, which is one of the most common causes of polyuria and polydipsia, the urine is sweet and hypertonic. DI is caused by two different mechanisms:
1.
Cranial DI – Inadequate synthesis of ADH in the hypothalamus or release from pituitary
2.
Renal DI – Inadequate renal response to ADH.
In cranial DI there is lack of ADH in the plasma, whereas in renal DI the ADH concentration in both plasma and urine is high.
Central DI
Central DI is caused by inadequate synthesis, storage or release of ADH. Disease affecting hypothalamus and/or pituitary can result in this condition. An intact thirst mechanism keeps the patient hydrated and their serum sodium concentration within the reference interval. During a water deprivation test there is no improvement in urine osmolality on dehydration, however, after the administration of Desmopressin® there is a marked increase in urine osmolality. Imaging of the brain is important to look for a lesion of the pituitary or the hypothalamus. The common pathological diseases in the brain causing central DI are listed in Table 10.3. More than half of the patients undergoing pituitary surgery develop transient DI within 24 h post-surgery and resolve spontaneously [5].
Table 10.3
Causes of DI
Cranial DI | Nephrogenic DI |
|---|---|
Idiopathic Tumour Craniophayringioma Meningioma Germinoma Metastatic disease Breast Lung Colon Kidney Melanoma Lymphoma and Leukaemia Trauma Head injury Post pituitary surgery Infection Encephalitis Meningitis Tuberculosis Infiltrative disease Histiocytosis Sarcoidosis Lymphocytic hypophysitis Pregnancy Transient DI due to placental vasopressinase Genetic DIDMOAD syndrome Mutation of arginine vasopressin-neurophysin II gene | Drug induced Lithium Carbamazepine
Related posts: Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|
