Papers - KAIKITA Koichi
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The pivotal role of a novel biomarker of reactive oxygen species in chronic kidney disease Reviewed
Hirata Y., Yamamoto E., Tokitsu T., Fujisue K., Kurokawa H., Sugamura K., Sakamoto K., Tsujita K., Tanaka T., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
Medicine (United States) 94 ( 25 ) e1040 2015.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Medicine (United States)
Risk stratification of chronic kidney disease (CKD) is clinically important because such patients are at high risk of cardiovascular events. Although reactive oxygen species (ROS) are reported to be closely associated with the pathophysiology of CKD, there are few useful ROS biomarkers known for CKD patients. Hence, our objectives in this study were to investigate whether serum derivatives of reactive oxygen metabolites (DROM), a novel biomarker of ROS, is involved in the pathophysiology of CKD (case-control study), and is a significant predictor of future cardiovascular events in CKD patients (follow-up study). Patients with suspected coronary artery disease (CAD) were enrolled and underwent coronary angiography. Patients with CKD (estimated glomerular filtration ratio <60mL/min/1.73m 2 and/or proteinuria, n=324) were compared with those without CKD (non-CKD). Serum DROM was measured at stable conditions. A case-control study of the 324 CKD patients and 263 non-CKD patients was conducted after matching risk factors, and a follow-up study of the 324 CKD patients was performed. CKD patients were divided into low- and high-DROM groups using their median value (348 unit; called the Carratelli unit [U.CARR]), and followed until the occurrence of cardiovascular events. DROM levels were significantly higher in risk factors-matched CKD patients than in risk factors-matched non-CKD patients (347.0 [301.8-391.8] U.CARR vs. 338.5 [299.8-384.3] U.CARR, P=0.03). During mean 23±14 months follow-up of 324 CKD patients, 83 cardiovascular events were recorded. Kaplan-Meier analysis demonstrated a higher probability of cardiovascular events in CKD patients with high DROM than in those with low DROM (P<0.001, log-rank test). Multivariate Cox hazard analysis including significant predictors in simple Cox hazard analysis demonstrated that high DROM was a significant and independent predictor of cardiovascular events in CKD patients (hazard ratio: 1.76, 95% confidence interval: 1.10-2.82, P=0.02). In conclusion, serum DROM values were significant and independent predictors of cardiovascular events in CKD patients, indicating that the measurements of DROM might provide clinical benefits for risk stratification of CKD patients.
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Resonant cardiac chamber with diastolic thrill Reviewed
Kurokawa H., Misumi I., Honda T., Usuku H., Yasuda H., Kaikita K., Hokimoto S., Ogawa H., Nakatsuka D., Tabata M.
Journal of Echocardiography 13 ( 2 ) 69 - 71 2015.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Echocardiography
A 70-year-old man with a diastolic Levine V/VI musical murmur came to our department. Doppler color-flow imaging showed eccentric severe aortic regurgitation. M-mode echocardiography demonstrated fluttering of the anterior mitral leaflet and fine tremors at the aortic root. The curved M-mode representation of the myocardial strain rate showed that the basal septum was encoded in a mixture of blue and red spots during diastole, showing massive basal septal vibration. In the present case, the force of the regurgitant flow might have caused vibration of the basal septum, thereby possibly leading to distinct thrill.
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Arima Y., Hokimoto S., Akasaka T., Mizobe K., Kaikita K., Oniki K., Nakagawa K., Ogawa H.
Journal of Cardiology 65 ( 6 ) 494 - 500 2015.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiology
Aim: CYP2C19 polymorphism modulates platelet reactivity in coronary artery disease patients with stent implants. However, the impact of the CYP2C19 genotype on clopidogrel response and clinical outcome has not been fully understood to date. Methods: We enrolled 518 consecutive patients with acute coronary syndrome (ACS) (n = 214) and stable angina (SA) (n = 304). All patients received stent implants followed by dual antiplatelet therapy of aspirin and clopidogrel. We determined CYP2C19 phenotype, measured platelet reactivity, and assessed the risk of cardiovascular events. Results: During a median follow-up of 894 days, the rate of cardiovascular events was higher in patients of the ACS group than the SA group (ACS: 20.1%, SA: 12.5%, p = 0.015). The mean platelet reactivity was significantly higher in the CYP2C19 loss-of-function allele carriers of the two groups (ACS, non-carriers: 3909 ± 1836 AU min, carriers: 4854 ± 1594 AU min, respectively, p < 0.01; SA, 3606 ± 1579 AU min, 4381 ± 1373 AU min, ±SD, p < 0.01). In the ACS group, cardiovascular events were higher in the loss-of-function allele carriers (24.6%) versus non-carriers (11.1%, p< 0.05), but no such difference was noted in the SA group (carriers: 14.8%; non-carriers: 7.9%, p = 0.078). Furthermore, landmark analysis from 30 days did not show differences in ACS group (carriers: 14.8%, non-carriers: 11.1%, p = 0.315). Multivariate Cox proportional hazards analysis identified the presence of loss-of-function allele as an independent predictor of cardiovascular events (hazard ratio, 2.1, 95% CI, 1.194-3.587, p = 0.010). Conclusions: The impact of CYP2C19 loss-of-function gene on clinical outcome is more powerful in early phase of ACS compared with SA.
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Hokimoto S., Akasaka T., Tabata N., Arima Y., Tsujita K., Sakamoto K., Kaikita K., Morita K., Kumagae N., Yamamoto E., Oniki K., Nakagawa K., Ogawa H.
Thrombosis Research 135 ( 6 ) 1081 - 1086 2015.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
Objectives The aim of this study was to investigate the effect of CYP2C19 polymorphism and co-therapy with esomeprazole on the antiplatelet efficacy of clopidogrel. Background The antiplatelet efficacy of clopidogrel depends on CYP2C19 polymorphism or the co-administration of some kind of proton pump inhibitor (PPI). Methods CYP2C19 genotype and the residual platelet reactivity (RPR) were measured in 361 coronary heart disease patients (male, mean age 69 yrs), and the risk of cardiovascular events over a 3-month follow-up was assessed to evaluate the impact of co-administration of esomeprazole during dual antiplatelet therapy with aspirin and clopidogrel. Results The values of RPR did not differ between esomeprazole and non-esomeprazole groups (4389 ± 1112 versus 4079 ± 1355 AU · min, P = 0.103). RPR value was higher in intermediate metabolizers (IM) than in extensive metabolizers (EM) (4089 ± 1252 versus 3697 ± 1215 AU · min P = 0.012) and, similarly, higher in poor metabolizers (PM) than in IM (4884 ± 1027 versus 4089 ± 1252 AU · min, P < 0.001). There were no differences in RPR between esomeprazole and non-esomeprazole groups according to CYP2C19 genotype (EM, 3954 ± 1192 versus 3645 ± 1220 AU · min, P = 0.361; IM, 4401 ± 1063 versus 4051 ± 1271 AU · min, P = 0.293; PM, 4917 ± 669 versus 4876 ± 1099 AU · min, P = 0.907, respectively). There was also no difference in clinical outcomes between esomeprazole and non-esomeprazole groups in the three-month follow-up (0% versus 0.92%, P = 0.487). Conclusions These results suggest that concomitant use of esomeprazole with clopidogrel is not associated with reduced antiplatelet efficacy of clopidogrel or increased risk of cardiovascular events, irrespective of CYP2C19 genotype.
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Hokimoto S., Sakamoto K., Akasaka T., Kaikita K., Honda O., Naruse M., Ogawa H., Arizono K., Fujisawa S., Fukui H., Fukushima J., Hara M., Higuchi S., Honda O., Ikezaki N., Ikezaki S., Imafuji M., Ishimatsu T., Iwashita H., Iwashita Y., Kawabata Y., Kawatomi M., Kimura S., Kodama M., Kugiyama A., Kuwahara K., Mabe K., Machida J., Maehara A., Matsunaga Y., Matsuoka N., Matsushita K., Matsushita K., Migita A., Miyamoto T., Miyanaka T., Mizutari K., Miyamoto Y., Nabekura Y., Motoyama T., Nagano H., Nagayoshi M., Nakamura T., Nakano T., Nakashita K., Nojiri A., Oda T., Otsuka Y., Sakaguchi S., Sakanashi T., Seto Y., Shimada H., Shimomura T., Tajiri M., Tajiri T., Takamiya T., Takeshita M., Terasaki H., Tsuru T., Tsuruta K., Tsuzaki S., Tsukamoto M., Uekihara S., Uemura S., Uchigashima H., Uemura S., Yamada K., Yano S., Yasumoto N., Tazoe N., Nishi K., Hokimoto S., Sakamoto K., Akasaka T., Kaikita K., Ogawa H.
Circulation Journal 79 ( 6 ) 1269 - 1276 2015.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation Journal
Background: Cardiovascular disease is a major cause of mortality in hemodialysis patients. The aim was to assess the relationship of various invasive cardiovascular procedures (ICP) to clinical outcome in hemodialysis patients. Methods and Results: A total of 5,813 patients at 76 facilities were on maintenance hemodialysis in Kumamoto Prefecture. Of these, 4,807 patients at 58 institutions were enrolled. Of 4,807 patients, 212 ICP (4.4%) were performed for various cardiovascular diseases in 189 patients (3.9%). ICP included PCI (n=80), endovascular treatment (n=59), radiofrequency catheter ablation (n=8), implantation of permanent pacemaker (n=15) and ICD (n=5), thoracotomy for valvular diseases (n=16), CABG (n=14), bypass surgery for peripheral artery disease (PAD; n=8), and artificial vessel replacement for aneurysm or aortic dissection (n=7). The overall mortality rate was 10.1% (19/189 patients). The mortality rate was highest in patients who underwent ICP for PAD, compared with other ICP (PAD, 18.2%; non-PAD, 6.7%, P=0.017). Infection and PAD were significant predictors of mortality (infection: OR, 8.30; 95% CI: 1.29–65.13, P=0.027; PAD: OR, 3.76; 95% CI: 1.35–10.48, P=0.012). The presence of inflammation/malnutrition factors was associated with high mortality (OR, 15.49; 95% CI: 3.22–74.12, P=0.0006). Conclusions: In this community-based registry study of 4,807 hemodialysis patients, the mortality rate of PAD patients was high despite ICP.
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Impact of left ventricular hypertrophy on impaired coronary microvascular dysfunction Reviewed
Tsujita K., Yamanaga K., Komura N., Sakamoto K., Miyazaki T., Ishii M., Tabata N., Akasaka T., Sueta D., Arima Y., Kojima S., Yamamoto E., Yamamuro M., Tanaka T., Izumiya Y., Tayama S., Nakamura S., Kaikita K., Hokimoto S., Ogawa H.
International Journal of Cardiology 187 ( 1 ) 411 - 413 2015.5
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Marume K., Hokimoto S., Tabata N., Akasaka T., Tsujita K., Sakamoto K., Yamamoto E., Yamamuro M., Kaikita K., Oniki K., Nakagawa K., Ogawa H.
International Journal of Cardiology 187 ( 1 ) 231 - 233 2015.5
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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A case of repetitive and simultaneous stent thromboses Reviewed
Sueta D., Hokimoto S., Enomoto K., Ono T., Tabata T., Kajiwara I., Kaikita K., Saruwatari J., Oniki K., Nakagawa K., Ogawa H.
International Journal of Cardiology 186 210 - 212 2015.5
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Misumi I., Honda T., Kusuhara K., Yasuda H., Kaikita K., Hokimoto S., Ogawa H.
Journal of Medical Ultrasonics 42 ( 2 ) 239 - 241 2015.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Ultrasonics
We report an increase in E/e′ ratio after treatment of heart failure (HF) in two patients. In case 1, the E/e′ ratio increased from 15 to 18 after treatment of HF. In case 2, the E/e′ ratio also increased from 24 to 35. Although a high E/e′ ratio suggests high pulmonary artery wedge pressure and worsening HF, the ratio may increase after improvement of HF. In the present cases of diastolic dysfunction, the high E wave did not change, but the e′ wave decreased relatively. This report may suggest difficulty in evaluating hemodynamic status based on the E/e′ ratio in patients with diastolic dysfunction.
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Yamamoto M., Tsujita K., Yamanaga K., Komura N., Sakamoto K., Kojima S., Yamamoto E., Tanaka T., Yamamuro M., Izumiya Y., Nakamura S., Kaikita K., Hokimoto S., Ogawa H.
Journal of Cardiology Cases 11 ( 4 ) 120 - 123 2015.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiology Cases
We present a case of ST-segment elevation myocardial infarction in the territory of an anomalous left circumflex coronary artery running through the retroaortic region. In vivo coronary imaging with intravascular ultrasound visualized the usual atherosclerotic change and subsequent plaque rupture and thrombus formation at the culprit lesion. The clarification of pathologic mechanisms underlying the myocardial infarction case could provide information about pathophysiology of atherosclerotic development in anomalous left circumflex coronary artery, and could help in decision-making regarding the management strategy.<. Learning objective: Intravascular ultrasound (IVUS) imaging indicated that ordinary atherosclerosis could develop at retroaortic anomalous course of left circumflex coronary artery (LCX) despite absence of mechanical cause of ischemia. IVUS screening could provide significant information about pathophysiology of atherosclerotic development in anomalous LCX, and could help in decision-making regarding the management strategy. The images and discussion have high educational value for clinical cardiologists alike.>.
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Yamanaga K., Tsujita K., Komura N., Kaikita K., Sakamoto K., Miyazaki T., Saito M., Ishii M., Tabata N., Akasaka T., Sato K., Horio E., Arima Y., Kojima S., Tayama S., Nakamura S., Hokimoto S., Ogawa H.
American Journal of Physiology - Heart and Circulatory Physiology 308 ( 5 ) H478 - H484 2015.3
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Physiology - Heart and Circulatory Physiology
Endothelial and vascular smooth muscle dysfunction of epicardial coronary arteries play a pivotal role in the pathogenesis of vasospastic angina (VSA). However, coronary microvascular (MV) function in patients with VSA is not fully understood. In the present study, subjects without coronary obstruction were divided into two groups according to the acetylcholine provocation test: VSA group (n = 29) and non-VSA group (n = 21). Hyperemic MV resistance (hMR) was measured using a dual-sensor (Doppler velocity and pressure)-equipped guidewire, and guidewire-derived hemodynamic parameters were compared. There were no between-group differences in clinical demographics, including potential factors affecting MV function (e.g., diabetes). Although coronary flow velocity reserve was similar between the two groups [2.4 ± 1.0 (VSA group) vs. 2.4 ± 0.9 (non-VSA group); P ± 0.8], coronary vessel resistance and hMR were significantly elevated in the VSA group compared with the non-VSA group (2.6 ± 3.1 vs. 1.2 ± 0.8, P = 0.04; 1.9 ± 0.6 vs. 1.6 ± 0.5, P = 0.03, respectively). Coronary vasospasm, older age, E/e’, and estimated glomerular filtration rate were significantly associated with MV dysfunction [defined as ≥ median value of hMR (1.6)] in univariate analysis. Coronary vasospasm most strongly predicted higher hMR in multivariate logistic regression analysis (odds ratio, 4.61; 95% confidence interval, 0.98 –21.60; P = 0.053). In conclusion, coronary MV resistance is impaired in patients with VSA compared with non-VSA patients, whereas coronary flow velocity reserve is maintained at normal levels in both groups. In vivo assessment of hMR might be a promising index of coronary MV dysfunction in patients with VSA.
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Hirata Y., Yamamoto E., Tokitsu T., Kusaka H., Fujisue K., Kurokawa H., Sugamura K., Maeda H., Tsujita K., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
Journal of the American Heart Association 4 ( 2 ) 2015.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the American Heart Association
BACKGROUND: Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD.
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Gender differences in impact of CYP2C19 polymorphism on development of coronary artery disease Reviewed
Hokimoto S., Tabata N., Akasaka T., Arima Y., Kaikita K., Morita K., Kumagae N., Oniki K., Nakagawa K., Ogawa H.
Journal of Cardiovascular Pharmacology 65 ( 2 ) 148 - 152 2015.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiovascular Pharmacology
The aim was to clarify whether CYP2C19 polymorphism is associated with the development of coronary artery disease (CAD). This study enrolled 723 patients with CAD (men 71%, 70 years) and healthy subjects undergoing a medical checkup (n = 453) as controls (men 69%, 53 years). We analyzed the incidence of CYP2C19 polymorphism and its association with the development of CAD in the absence of diabetes, dyslipidemia, and chronic kidney disease to minimize the influence of conventional coronary risk factors. In the analysis without risk factors, there was no difference in the incidence of the CYP2C19 genotype between CAD (n = 115) and control (n = 194) groups [extensive metabolizer, intermediate metabolizer, poor metabolizer (PM) in non-risk CAD: 33%, 46%, 21%, respectively; in non-risk control: 31%, 52%, 17%, respectively]. Analysis between CAD and control groups by the χ test showed that there was significant difference in distribution of CYP2C19 genotype in women alone (P = 0.025) but not in total subjects (P = 0.471) or men (P = 0.678), respectively. CYP2C19 PM was an independent predictor of CAD risk in women alone (odds ratio, 10.717; 95% confidence interval, 1.753-65.505; P = 0.010) but not in men. CYP2C19 PM status might be associated with the development of CAD as a disease susceptibility gene, especially in women.
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Hirata Y., Yamamoto E., Tokitsu T., Kusaka H., Fujisue K., Kurokawa H., Sugamura K., Maeda H., Tsujita K., Yamamuro M., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
International Journal of Cardiology 179 305 - 308 2015.1
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Sueta D., Hokimoto S., Tayama S., Tsujita K., Sakamoto K., Yamamoto E., Tanaka T., Izumiya Y., Yamamuro M., Yamanaga K., Akasaka T., Tababa N., Arima Y., Kaikita K., Ogawa H.
International Journal of Cardiology 182 ( C ) 85 - 87 2015
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Ishii M., Hokimoto S., Akasaka T., Fujimoto K., Miyao Y., Kaikita K., Oshima S., Nakao K., Shimomura H., Tsunoda R., Hirose T., Kajiwara I., Matsumura T., Nakamura N., Yamamoto N., Koide S., Oka H., Morikami Y., Sakaino N., Matsui K., Ogawa H.
Circulation Journal 79 ( 5 ) 1115 - 1124 2015
Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation Journal
Background: The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants. Methods and Results: This study included 5,801 consecutive patients (males, 4,160; age, 69.7}11.1 years, mean } SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mildto- moderate CKD (30≤eGFR<60, n=1,956) and severe CKD (eGFR <30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31–0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively). Conclusions: In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events.
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Hokimoto S., Mizuno Y., Sueta D., Morita S., Akasaka T., Tabata N., Harada E., Arima Y., Yamamuro M., Tanaka T., Yamamotoa E., Sakamoto K., Tsujita K., Kaikita K., Yasue H., Ogawa H.
International Journal of Cardiology 182 ( C ) 171 - 173 2015
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Tokitsu T., Yamamoto E., Hirata Y., Fujisue K., Sugamura K., Maeda H., Tsujita K., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
Journal of Hypertension 33 ( 9 ) 1780 - 1790 2015
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Hypertension
Objective: Recent studies have shown that inter-arm blood pressure differences (IAD) may be a risk factor for cardiovascular events; however, none have addressed them in patients with coronary artery disease (CAD). Methods: We measured blood pressure bilaterally with the ankle brachial index (ABI) in 657 patients with suspected CAD and assessed the presence of CAD by coronary angiography, and the severity of coronary atherosclerosis with the Gensini score. Results: Mean IADs were significantly greater in risk factor matched patients with CAD than in those without it (P=0.01), whereas Gensini scores were significantly greater in those with high IAD (≥10 mmHg) than in those with low-IAD (P=0.01) according to cross-sectional analysis. Patients with high IAD had a significantly greater probability of cardiovascular events than those in whom it was low (log-rank test, P<0.01, mean follow-up range; 827.3±268.1 days). The presence of hypertension, ABI, usage of calcium channel blocker and high IAD were independent predictors of cardiovascular events according to longitudinal analysis (IAD; hazard ratio: 2.90, 95% confidence interval: 1.41-5.94, P<0.01) in these patients. Patients with high IAD and peripheral artery disease had the highest Gensini scores according to cross-sectional analysis (P<0.01) and highest probability of cardiovascular events according to longitudinal analysis (log-rank test, P<0.001). Conclusion: IADs were increased in CAD patients and correlated with its severity. Greater than 10mmHg of IAD was independently associated with future cardiovascular events. Assessing IAD by ABI measurement may facilitate risk stratification in CAD patients.
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Hokimoto S., Tabata N., Akasaka T., Arima Y., Tsujita K., Yamamoto E., Izumiya Y., Yamamuro M., Sakamoto K., Kaikita K., Sugamura K., Ogawa H.
International Journal of Cardiology 177 ( 2 ) 723 - 725 2014.12
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Marume K., Arima Y., Igata M., Nishikawa T., Yamamoto E., Yamamuro M., Tsujita K., Tanaka T., Kaikita K., Hokimoto S., Ogawa H.
Journal of Cardiology Cases 10 ( 6 ) 226 - 230 2014.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiology Cases
A 58-year-old man was admitted for non-ST-elevation myocardial infarction. A medicated stent was used for severe coronary artery stenosis. However, consciousness level progressively deteriorated after angioplasty. Computed tomography showed no brain lesion but laboratory tests showed hyponatremia (serum sodium: 113. meq./l) and urine analysis showed syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH was first suspected to be drug-induced by enalapril. However, hyponatremia persisted even after withdrawal of enalapril and required oral sodium intake. Hormone assays indicated secondary adrenal insufficiency, which was caused by adrenocorticotropic hormone (ACTH) deficiency. Furthermore, in addition to ACTH deficiency, adult growth hormone deficiency was diagnosed following tests. Treatment with hydrocortisone relieved hyponatremia and re-institution of enalapril did not reduce serum sodium concentration. The final diagnosis was hyponatremia caused by hypopituitarism.<. Learning objective: Secondary adrenal insufficiency with subsequent hypopituitarism should be suspected in cases with sudden-onset and prolonged hyponatremia in acute illness. Furthermore, the management of hypopituitarism should include assessment of growth hormone release to exclude growth hormone deficiency.>.