A 75-year-old woman was admitted to the Jikei University Hospital due to impaired consciousness and status epilepticus. She was referred to the hospital's outpatient clinic 24 days before admission to investigate a progressive mass-like lesion with a maximum diameter of 30 mm that was located on her left upper lung. Positive results from an interferon-gamma-release assay (T-spot.TB assay, Oxford Immunotec Ltd. Marlborough, MA, USA) and a tuberculosis polymerase chain reaction (PCR) led to a diagnosis of pulmonary tuberculosis 16 days before admission. A sputum culture showed that the patient was positive for tuberculosis, and the diagnosis was later confirmed. The patient was prescribed four anti-tuberculosis medications (isoniazid, rifampicin, ethambutol, and pyramide). She did not start taking full doses of the medications until two days prior to her admission due to anxiety over the side effects. Her medical history included hypertension, gastric ulcer and hyperlipidemia, but she had been healthy until admission. On the day of admission, she was found lying on the floor at her home and was transported to the hospital. At the emergency room, she developed generalized seizures five times and was admitted to the intensive care unit to undergo treatment for statue epilepticus.
On admission, the patient was unconscious (Glasgow Coma Scale, E1V1M3) with a body temperature of 37C, a heart rate of 108/min, a respiratory rate of 18 breaths/min, a saturation level of 99% on room air and a blood pressure of 160/90 mmHg. Physical examinations showed normal breath and heart sounds and no swelling of her extremities. Neurological examinations revealed an increase of muscle tonus, especially in the lower limbs. Biochemical examinations showed hyponatremia (120 mEq/L) with low serum osmolality (253 mOsm/kg), high urinary osmolality (458 mOsm/kg), and a normal urinary sodium concentration (81 mEq/L) (Table). Despite the patient's severe hyponatremia, her serum antidiuretic hormone (ADH) level was not decreased (3.3 pg/mL); it was close to the upper limit of the normal range (0.3-4.2 pg/mL). The patient's thyroid, kidney, and adrenal functions were normal. The fact that her blood urea nitrogen (BUN) to creatinine (Cr) ratio was 6.6 and the fact that she did not experience severe diarrhea or vomiting implied that she was clinically euvolemic. Based on these laboratory findings, this patient met the criteria for SIADH, which were as follows: decreased effective osmolality; urinary osmolality, >100 mOsm/kg of water; clinical euvolemia; urinary sodium concentration, >40 mmol/L; and normal thyroid and adrenal functions. Chest radiography and computed tomography (CT) showed a wedge-shaped infiltrative shadow with small tree-in-bud satellite lesions in the left upper lobe of the lung (Fig. 1). With the exception of pulmonary tuberculosis, contrast-enhanced CT of the whole body did not reveal any malignant or infectious diseases. Brain magnetic resonance imaging (MRI) revealed no abnormalities and electroencephalograms, which were taken three times, were all normal. A cerebrospinal fluid examination (CSF) showed no increase in the cell count (0 cells/uL) or the total protein level (47 mg/dL), no decrease in the glucose (102 mg/dL), and was culture-negative for tuberculosis and bacteria. Repeated blood cultures were also negative for bacteria. She was not taking any medicines that have previously been reported as a potential cause of SIADH. It was therefore concluded the patient's SIADH was caused by pulmonary tuberculosis. Among the prescribed medications, only isoniazid has the potential to lead to seizures. However, this possibility was excluded due to a lack of complications during re-administration. Accordingly, we concluded that the patient's status epilepticus could be attributed to hyponatremia, which had caused by pulmonary tuberculosis-associated SIADH.
The patient did not develop seizures after infusion of fosphenytoin sodium hydrate. Her level of consciousness improved after an infusion of saline to treat her abnormal serum sodium concentration, and she became conscious on the second day after admission (Fig. 2). Rhabdomyolysis occurred due to the patient's status epilepticus, and her creatine kinase (CK) levels increased (6,630 IU/L). SIADH did not recur after the patient resumed taking the anti-tuberculosis medicines and she was discharged from the hospital on the 22nd day after admission. The fact that she improved with treatment verified our diagnosis.