デメクロサイクリンによるADH分泌異常症候群の治療

TREATMENT FOR SYNDROME OF THE INAPPROPRIATE SECRETION OF THE ANTIDIURETIC HORMONE (SIADH) WITH DEMECLOCYCLINE HYDROCHLORIDE (DMC)

I．はじめに

　1967年BartterとSchwartz^1）がADH （抗利尿ホルモン）の不適正な分泌によつて血清Naの低下等を来たす症候群をSIADH （syndrome of inappropriate ADHsecretion）と命名し，詳細な報告および考察をして以来，気管支癌，肺炎，中枢神経系疾患（髄膜炎，頭部外傷^13,14,16），脳腫瘍^8），くも膜下出血，ギランバレー症候群等^5））における本症候群の報告^{1,2,6,8,11,12,15,20,21,26,27）}がなされてきた。気管支癌等における本症候群の発生は癌組織からのADHあるいは類似物質の産生および放出が原因とされているのに対し，中枢神経疾患における本症候群は，視床下部下垂体系の障害に起因する事が推定され，急性間歇性ポルフィリン症のSIADH例^20）では剖検脳において視索上核，室傍核の広汎な神経細胞の消失が観察され，この推定をうらづけている。腫瘍組織自体からADHが産生される場合は長期にわたりSIADHが続き治療は困難な場合が多い。一方中枢神経疾患では疾患の急性期に本症候がみられる事が多く，原疾患の治癒に伴ない本症候群も消失する事が多い^1）。したがつて疾患の急性期にのみ本症候群の治療を行なえばよいわけであるが，ときには本症候群が長期にわたり持続し，原疾患と本症候が悪循環を形成する場合も稀でなく，適切な治療を早期から行なう事が必要と思われる。

Two patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been successfully treated with demeclocycline hydrochloride (DMC). One case is a 49 year old male operated on for the anterior communicating aneurysm, after the operation he developed typical features of the SIADH. Diagnosis was established by 12 hours' complete water restriction and water loading test. In this case, curiously enough, after 12 hours' complete water restriction, serum ADH was below 1.25pg/ml (in normal cases 3.4-9.0 pg/ml). After 20 ml/kg of water load orally for 30 minutes, serum ADH was 6.8; 2.4;4.5;2.5;2.3 for 30min.; 1; 2; 3; 4 hours respectively after the beginning of water load. Serum ADH was continuously dete-cted during the test, that is, antidiuretic hormone was inappropriately secreted. After the test, he received 1200 mg of DMC daily orally. Immediately after the DMC administration, the urinary sodium excretion began to decrease but on the second day it elevated transiently, and finally on the 5th day after the beginning of the DMC administration,serum Na level reached to its normal value.

The second case is a 66 year old male with the intracerebral hematoma in the left parieto-occipital region probably resulting from hemorrhage due to the pericapillary adenocarcinoma cell infiltration. In this case also, the SIADH was diagnosed by water restriction (12 hours') and water loading test (20 ml/kg/30 min./orally). After water restriction, the serum ADH was below 2.0pg/ml. In this case also, serum ADH was continuously detected during the test as seen in Fig. 4. After the test, DMC was administered by the gastric tube (300 mg, 4 times/day). Urinary sodium excretion fell rapidly after the beginning of DMC treatment. Serum sodium reached to its normal value on the 4th day. In this case, the transient rise of urinary sodium excretion observed in the first case was not detected.

DMC suppresses the tubular action of antidiuretic products and its action is selective, dose dependent and reversible without significant side effects. It induces production of hypotonic urine and corrects hyponatremia despite large fluid intakes. DMC appears to be the treatment of choice for the SIADH in the neurosurgical field.