Abstract
A 39-year-old male diabetic patient associated with painful diabetic neuropathy was treated with carbamazepine (CBZ) at 400 mg daily for nine days, but obtained no pain relief with this medication. After withdrawal of CBZ, symptoms such as general malaise and anorexia rapidly developed. Laboratory examination revealed hyponatremia (118 mEq/L) and hyposmolarity (244 mOsm/L), and successive water restriction (500 ml/day) for nine days restored these abnormalities to normal levels (140 mEq/L, 290 mOsm/L). These findings led us to suspect the coexistence of the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and prompted us to elucidate its cause.
Furthr physical and laboratory examinations did not show any endocrinological and neurological disorders, nor the presence of malignancy in respiratory and digestive organs.
Water loading test (20ml/kg orally) was performed twice at the eraly stage after development of hyponatremia and at the late stage of admission when serum Na and plasma osmolarity levels were almost within normal ranges. Total urine volume over 4 hours reached only to the level of 25% and 35% of the loaded water volume, respectively. The free water clearance failed to rise and plasma ADH response was not suppressed. In a hypertonic saline loading test (2.5% NaCl 650 ml intravenously), which was performed twice, plasma ADH level did not start to rise until plasma osmolarity reached the level of 310 mOsm/L. Moreover, there was no correlation between plasma ADH and plasma osmolarity levels (r=0.1493).
Re-administration of CBZ 400 mg daily for nine days failed to produce recurrence of hyponatremia even though the serum concentration of CBZ was kept within the level of 8.6-9.4μg/ml. However, serum Na level was found to be 129 mEq/L on the fourth day after stopping CBZ administration and persisted at a similar level for seven days. The direct induction of SIADH could not be attained by re-administration of CBZ. However, when the process of recognition of hyponatremia was taken into consideration, it might not be deniable that CBZ played any role in occurrence of SIADH.
These results showed that in this case, there was no integrity in the regulation of water metabolism through the neurohypophysial ADH system, which ascending stimuli reach via osmoreceptors, and volume and/or baroreceptors. The cause of this disorder might be related to diabetic autonomicdysfunction. Moreover, it might also be possible that CBZ administration was instrumental in disclosing this potential abnormality to develop SIADH.
