Hepatic lipase and the clearing reaction: studies in euthyroid and hypothyroid subjects

Eight patients with primary hypothyroidism were compared to eleven euthyroid subjects with regard to the effects of a single i.v. dose of heparin on plasma lipoprotein concentrations (the "clearing reaction"). The hypothyroid patients were moderately hypercholesterolemic but had normal plasma triglyceride levels. Maximal activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were lower in the hypothyroid than in the normal subjects. The hypothyroid patients demonstrated a significant decrease in total plasma cholesterol levels after heparin injection (from 8.36 +/- 0.70 mmol/l to 7.55 +/- 0.62 mmol/l, P less than 0.02). The maximal activity of HL after heparin was significantly correlated to the decrease in plasma cholesterol levels (P less than 0.05) and in LDL-cholesterol levels (P less than 0.01). The euthyroid subjects demonstrated a smaller decrease in total plasma cholesterol concentrations (from 5.53 +/- 0.31 to 5.08 +/- 0.28 mmol/l, P less than 0.05). In this group, the fall in cholesterol levels was not correlated to maximal HL activity. The reduction in plasma triglyceride levels after heparin was similar and significant (P less than 0.01) in both groups. These data support the view that decreased activity of HL contributes to the dyslipoproteinemia seen in hypothyroidism. They are also in accordance with the notion that HL is involved in the elimination of cholesterol from plasma

Experimental hyperthyroidism in man: effects on plasma lipoproteins, lipoprotein lipase and hepatic lipase

We have studied the effects of triiodothyronine administration (20-40 micrograms three times daily over one week) in six healthy young men, on the activities of lipoprotein lipase and hepatic lipase and on plasma lipoprotein concentrations. Hepatic lipase activity in post-heparin plasma rose by 46 +/- 25% (p less than 0.025), whereas the activity of lipoprotein lipase did not change significantly. Plasma cholesterol concentrations decreased by about 20% (p less than 0.025), whereas there was no change in plasma triglyceride levels. The fall in plasma cholesterol could be accounted for by a reduction of HDL cholesterol (-11%, p less than 0.025) as well as LDL cholesterol (-27%, p less than 0.025). The data emphasize the role of hepatic lipase in the lipoprotein alterations associated with thyroid dysfunction

Treatment of hyperthyroidism: effects on hepatic lipase, lipoprotein lipase, LCAT and plasma lipoproteins

The activities of hepatic lipase and of lipoprotein lipase, the elimination rate of exogenous triglyceride and the cholesterol esterification rate were determined and related to plasma lipoprotein concentrations in 16 patients before and after treatment for hyperthyroidism. The activity of hepatic lipase was significantly higher (65%) before than after treatment, while the activity of lipoprotein lipase and the elimination rate of exogenous triglyceride remained unchanged. The endogenous cholesterol esterifying ability decreased after treatment, whereas no change occurred in the fractional cholesterol esterification rate measured with normal plasma as substrate. The concentrations of LDL-cholesterol and HDL-cholesterol increased significantly after treatment. The decrease in hepatic lipase activities was correlated to the decrease in S-T3 concentrations (r = 0.77, P less than 0.001) and to the increase in HDL-cholesterol concentrations (r = 0.51, P less than 0.05). The activities of lipoprotein lipase were positively correlated to the concentrations of HDL-cholesterol both before (r = 0.54, P less than 0.05) and after (r = 0.59, P less than 0.05) treatment. These results support the view that hepatic lipase and lipoprotein lipase are both important determinants of plasma HDL concentrations and suggest that an increased hepatic lipase activity contributes to the lower HDL levels in hyperthyroid patients

Classification of pituitary growth hormone producing adenomas according to SIPAP: application in clinical practice.

Background In 1997, the SIPAP classification was introduced, a guide designed for MRI, to characterize pituitary adenomas with emphasis on extrasellar extensions and impact on adjacent structures. To our knowledge no previous evaluation of the inter-observer agreement of the SIPAP classification has been performed. Purpose To evaluate the inter-observer agreement of the SIPAP classification. Material and Methods Sixty patients operated on for growth hormone producing pituitary adenomas at Lund University Hospital 1991-2007 had an assessable preoperative MRI scan. Forty-five of them also had an assessable postoperative MRI scan. The mean time between surgery and postoperative MRI scans was 11 months. Two observers evaluated all the MRI scans independently. The outcome of the evaluation is presented as the percentage of concordance in each of the evaluated directions and the degree of discrepancy for each of the directions evaluated. Results In 284 (79%) of 360 preoperative gradings both observers agreed completely. In 17 of the 60 preoperative MRI scans, both observers made identical assessments according to the SIPAP classification in all the six different directions of tumor extension. In 76 gradings the results differed between the observers. The difference was 1 grade (or less) in 69 cases. In 230 (85%) of 270 postoperative gradings the results were identical for both observers. In 18 of the 45 postoperative MRI scans, both observers made the same assessments according to the SIPAP classification in all the six different directions of tumor extension. In 40 gradings the results differed between the observers. The difference was 1 grade (or less) in all 40 cases. Conclusion We found a relatively high inter-observer agreement both pre- and postoperatively, supporting the usefulness and easy applicability of the SIPAP system for grading of pituitary adenomas pre- as well as postoperatively

Increase in hepatic lipase activity after testosterone substitution in men with hypogonadism of pituitary origin

Ten men with hypogonadism of pituitary origin were studied before and during testosterone substitution therapy with regard to effects on the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma, and on plasma lipoprotein concentrations. The mean (+/- SEM) testosterone level increased from 1.8 +/- 0.5 to 16.3 +/- 2.4 nmol/l. The mean activity of HL rose from 327.1 +/- 35.2 to 432.8 +/- 57.2 mU/ml (p less than 0.02), while the activity of LPL did not change significantly, 71.0 +/- 9.1 mU/ml before and 62.2 +/- 3.8 mU/ml after treatment. No significant alterations in lipoprotein concentrations were recorded. These results indicate that a normal testosterone level is of importance for maintaining the activity of HL in men, thereby contributing to the sex difference previously recorded for HL activity

An early post-operative ACTH suppression test can safely predict short- and long-term remission after surgery of Cushing’s disease

Purpose: The present study evaluates the usefulness of an ACTH suppression test shortly after surgery, and to determine optimal cut-off values of included laboratory analyses, in predicting short- and long-term remission after surgery of Cushing’s disease. Methods: A 48 h suppression test with betamethasone 2 mg/day applied after 45 transphenoidal adenomectomies in 28 patients was evaluated. Receiver operating characteristic (ROC)-curves were created for the included assays: plasma cortisol, plasma adrenocorticotropic hormone (ACTH) and urinary free cortisol (UFC). Plasma levels of cortisol and ACTH were measured both at 24 and 48 h. Youden’s index was used to determine cut-off with the highest sensitivity and specificity in predicting short- (3 months) and long-term (5 years or longer) remission. The area under curve (AUC) illustrated the clinical accuracy of the different assays. Results: Plasma cortisol after 24 h with betamethasone was most accurate in predicting both short- and long-term remission. 3 months remission with cut-off 107 nmol/L: sensitivity 0.85, specificity 0.94, positive predictive value (PPV) 0.96 and AUC 0.92 (95% CI 0.85–1). 5 years remission with cut-off 49 nmol/L: sensitivity: 0.94, specificity 0.93, PPV 0.88, AUC 0.98 (95% CI 0.95–1). Analyses of ACTH or UFC did not improve diagnostic accuracy. Conclusions: A 48 h, 2 mg/day betamethasone suppression test after transphenoidal surgery of Cushing’s disease could predict short- and long-term remission with a high accuracy. Suppression of plasma cortisol after 24 h with betamethasone to values excluding Cushings disease in the diagnostic setting yielded the highest accuracy in predicting long-term remission

Urate and arteriosclerosis in primary hyperparathyroidism

OBJECTIVE: An increased mortality due to cardiovascular disease has been reported in patients with primary hyperparathyroidism (pHPT). An association between urate and cardiovascular disease has been suggested. Metabolic abnormalities in pHPT may include urate. We therefore evaluated the metabolic arteriosclerotic risk profile in pHPT with special focus on the role of urate. DESIGN: Retrospective analysis of data before and 1 year after surgery for pHPT. PATIENTS: 130 consecutive patients, over the age of 44 years, who underwent surgery for pHPT. MEASUREMENTS: Biochemical variables known to reflect risk of arteriosclerotic disease (AD) and renal function tests including measurement of glomerular filtration rate (GFR) were investigated before and 1 year after surgery. RESULTS: pHPT patients with AD (n = 40) were older and had higher serum levels of urate and triglyceride, and more impaired renal function in comparison with patients without AD. PTH and calcium values did not differ. Multiple logistic regression analysis indicated that urate was an independent risk factor for AD in pHPT (P < 0.01). Three variables were shown to be positively associated with urate; male gender (P < 0.01), fasting blood glucose (P < 0.05) and serum level of triglyceride (P < 0.05). CONCLUSIONS: Urate was found to be an independent risk factor for arteriosclerotic disease in primary hyperparathyroidism. Serum level of urate could (in addition to gender) be associated with a metabolic disorder comprising increased glucose and triglyceride levels

Increased plasma levels of islet amyloid polypeptide in patients with primary hyperparathyroidism

Amylin, also named islet amyloid polypeptide (IAPP), is a protein that is processed and released from pancreatic beta-cells in parallel with insulin. Islet amyloid polypeptide is currently studied with regard to a role for insulin resistance in non-insulin-dependent diabetes. To elucidate a possible function of IAPP for impaired glucose tolerance in primary hyperparathyroidism (pHPT), we studied plasma IAPP levels during an oral glucose tolerance test (OGTT) in seven pHPT patients before and 8 weeks after surgery and in six healthy subjects. The B-glucose level of the patient groups was 4.34 +/- 0.12 mmol/l before and 3.97 +/- 0.16 mmol/l after surgery (NS), while the serum level of insulin was significantly higher before (16.9 +/- 2.8 mlU/l) than after (8.9 +/- 1.9 mlU/l) the operation (p < 0.05), indicating a moderately increased insulin resistance in pHPT. The basal plasma levels of IAPP were significantly higher in pHPT patients before than 8 weeks after surgery (9.71 +/- 1.05 and 4.30 +/- 0.82 pmol/l, respectively: p < 0.01). When compared to the plasma IAPP level of the controls at 1.80 +/- 0.38 pmol/l, pHPT patients had higher IAPP values both before (p < 0.01) and at 8 weeks after (p < 0.05) operation. There was a significant correlation between the serum levels of insulin and plasma levels of IAPP in pHPT patients before (r = 0.87, p < 0.01) as well as 8 weeks after surgery (r = 0.69, p < 0.05). The area under the curve for IAPP during OGTT in pHPT patients was 1872.4 +/- 187.7 pmol.min/l, which is significantly higher than after surgery (1010.8 +/- 93.7 pmol.min/l) (p<0.05) and compared to the area for the controls at 840.3 +/- 49.9 pmol.min/l (p<0.01). In conclusion, pHPT is associated with an increased plasma level of IAPP, correlated to the serum insulin level, but persistently higher than in controls also 8 weeks after surgery. Possibly, increased IAPP levels can have a role for impaired glucose tolerance in pHPT. The hyperparathyroid state might have a specific role for the release of this peptide, otherwise closely connected to insulin secretio

Captopril suppression: Limitations for confirmation of primary aldosteronism.

INTRODUCTION: : The aldosterone/renin ratio (ARR) is the first line screening test for primary aldosteronism (PA). However, in hypertensive patients with an increased ARR, PA needs to be confirmed by other means. METHODS: : A 25 mg oral captopril test was performed in 16 healthy subjects to obtain reference values for aldosterone and ARR at 120 minutes after the test. Subsequently these data were applied to 46 hypertensive patients screened for PA with an increased ARR. RESULTS: : At 120 minutes after the captopril test ARR decreased in healthy subjects within a narrow range, but remained high in patients with PA and in patients with primary hypertension, especially for those with low renin characteristics. At 120 minutes after captopril, the range of ARR in primary hypertensive patients overlapped in 88% of the cases with the range of the ARR in the PA patients. Sensitivity and specificity of basal ARR and ARR after the captopril test to diagnose PA, calculated as receiver operator characteristics, showed an area under the curve of 0.595 for basal ARR and 0.664 for ARR at 120 minutes after the test. CONCLUSION: : The ARR at 120 minutes after the captopril test is only marginally better than basal ARR in diagnosing PA in hypertensive patients screened with an increased ARR. Owing to an overall limited capacity to clearly discriminate PA from primary hypertension, the test could not therefore be recommended for the confirmatory diagnosis of PA