Severe hyponatremia caused by secondary adrenal insufficiency in a patient with giant pituitary prolactinoma.

A 55-year-old-man was admitted to Saiseikai Central Hospital, Tokyo, Japan, complaining of nausea and appetite loss, and was found to have severe hyponatremia. Despite severe hyponatremia and plasma hypo-osmolarity, urinary sodium excretion was not reduced. A brain magnetic resonance imaging (MRI) scan revealed a giant pituitary prolactinoma, and endocrinological tests showed a markedly increased prolactin level. Despite the observation that the basal plasma ACTH level was normal, serum cortisol and urinary cortisol excretion levels were low. Rapid ACTH loading sufficiently stimulated an increase in serum cortisol levels, suggesting secondary adrenal insufficiency. Notably, loading of CRH induced a good ACTH response; however, the serum cortisol response remained low. In contrast, the continuous daily administration of exogenous ACTH dramatically increased serum cortisol levels. These discrepant responses may have been caused by the low biological activity of innate ACTH. Following partial resection of the prolactinoma, postoperative adjuvant therapy with cabergoline effectively reduced prolactin levels, but did not improve the hyponatremia. In contrast, hydrocortisone replacement therapy recovered the serum sodium level to the normal range. The present case is the first report describing a link between severe hyponatremia and biologically inactive circulating ACTH as a likely result of giant prolactinoma.

Effects of combined antihypertensive therapy with losartan/hydrochlorothiazide on uric acid metabolism.

OBJECTIVE: The Jikei Optimal Antihypertensive Treatment (JOINT) study originally evaluated the effect of a fixed-dose formulation of losartan (LOS) (50 mg) plus 12.5 hydrochrolthiazide (HCTZ) for achieving better blood pressure (BP) control in patients with uncontrolled hypertension. This study is a sub-analysis of the JOINT study, focusing on the effect of LOS/HCTZ on the uric acid (UA) metabolism. METHODS: Among 228 participants in the JOINT study, a total of 164 patients whose blood and urinary UA specimens were available were included in the present analyses. RESULTS: Six months after switching from the prior antihypertensive agent(s) to a single tablet formulation of LOS/HCTZ, the overall serum UA concentration (sUA) increased from 6.0 ± 1.6 mg/dL to 6.2 ± 1.6 mg/dL (p=0.029). The urinary UA/creatinine (Cr) ratio increased from 0.45 +/- 0.21 to 0.50 +/- 0.25 (p=0.014), and the fractional excretion of UA (FEUA) also increased, from 7.1 +/- 3.6 to 7.0 +/- 4.3, p=0.04). Multivariate regression analyses of the basal parameters showed the change in sUA (ΔUA) to correlate with the basal sUA (ß=-0.483, p<0.001), estimated glomerular filtration rate (eGFR) (ß=-0.202, p=0.007) and systolic BP (ß=0.147, p=0.038). In addition, the ΔUA also correlated with the changes in the estimated glomerular filtration rate (ΔeGFR) (ß=-0.332, p<0.001). When the patients were classified into two groups depending on their basal sUA, those with a basal sUA ≥ 7 mg/dL exhibited a decrease in their sUA, whereas the rest of those with a sUA <7 mg/dL experienced an increase. Furthermore, patients who had previously been treated with LOS alone had a greater increase in the sUA than those treated with an angiotensin II blocker (ARB) other than LOS alone. CONCLUSION: Antihypertensive therapy with a single tablet formulation of LOS/HCTZ is considered to be a useful option for controlling both BP and sUA, especially in uncontrolled hypertensive patients with hyperuricemia.

Augmented antihypertensive effect of a fixed combination formula of candesartan and hydrochlorothiazide combined with furosemide in a patient on peritoneal dialysis.

A 38-year-old female patient on peritoneal dialysis (PD) due to type 1 diabetic nephropathy with a well-preserved residual renal function did not respond well to the conventional antihypertensive therapy consisting of candesartan, furosemide, and bunazosin. Switching candesartan for a fixed combination formula of candesartan plus hydrochlorothiazide (HCTZ) while the rest of the other two agents remained unchanged led to the remarkable reduction in both systolic and diastolic blood pressure (BP) without significant changes in the cardiothoracic ratio (CTR), body weight (BW), and residual renal function. This case suggests that when used in combination, diuretics acting on different functional segment of the nephron hold greater potential for enhanced antihypertensive effect, especially in patients on PD whose residual renal function is well preserved. A small dose of HCTZ with an angiotensin II receptor blocker (ARB) may partially explain the therapeutic benefit of this combination therapy in terms of a reliable hypotensive effect, a better adherence, and fewer side effects.

[Study on the predictors for superimposed preeclampsia in patients with IgA nephropathy].

OBJECTIVE: Pregnancy in chronic kidney disease (CKD) patients is often associated with hypertension and/or the worsening of renal function and neonatal death. The present study explored the clinical characteristics of predictive factors for hypertension in biopsy-proven IgA nephropathy patients with superimposed preeclampsia (SPE). PATIENTS AND METHODS: The subjects were 34 Japanese women with IgA nephropathy whose renal specimen for histological tests was obtained before pregnancy. We retrospectively investigated the relevant clinical factors to explain a rise in blood pressure (BP). The histological findings were evaluated with respect to the quantitative measurements of both global glomerulosclerosis and interstitial damage. RESULTS: Renal biopsies before pregnancies showed that the global glomerular sclerosing index and interstitial damage in the SPE group were significantly higher than in the normal group. The prevalence of SPE was 38.2 % (normal pregnancy 21, SPE 13 cases). The neonatal death rate was 3.0 % (1/34)overall. Just before conception, systolic blood pressure (SBP), serum creatinine (Cr)and blood urea nitrogen (BUN) concentration in the SPE were significantly higher than in normal pregnancies. In contrast, CCr and eGFR were lower in the SPE group than in the normal group. At delivery, serum Cr, BUN and uric acid (UA) concentration in the SPE group were significantly higher than in the normal group. In contrast, CCr and eGFR were lower in the SPE than in the normal group. At delivery, correlation analysis revealed a significant correlation between SBP or diastolic BP (DBP) and the histological severity, between SBP or DBP and daily protein excretion, and between SBP or DBP and serum Cr concentration. With respect to the birth weight of newborns, there was a significant negative correlation between the birth weight and the global glomerular sclerosing rate, and between the birth weight and serum Cr concentration or BUN. A stepwise multiple regression analysis showed that predictive factors for a rise in SBP during pregnancy were the degree of interstitial damage and daily urinary protein excretion. These results suggest that renal function, the magnitude of urinary protein excretion, serum Cr, BUN, UA concentrations, and the severity of histological abnormalities are all associated with SPE occurrence. The predictors of a rise in BP were interstitial damage and urinary protein excretion at pregnancy. In addition, Receiver Operating Characteristic (ROC) analysis showed that both glomerular sclerosis and interstitial damage could be potential predictors for SPE. CONCLUSION: Histological severity in renal biopsy, urinary protein excretion and renal function are associated with SPE in patients with IgA nephropathy. Among these associations, the histological findings and urinary protein excretion may serve as useful predictors for a rise in BP.