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Fasting and postprandial lipid abnormalities in hypopituitary women receiving conventional replacement therapy
K A al-Shoumer1, K H Cox, C L Hughes
1Unit of Metabolic Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, United Kingdom.
Insights
Hypopituitarism is linked to unhealthy lipid profiles, especially in women, increasing vascular disease risk. Standard hormone replacement therapy does not fully correct these dangerous lipid and lipoprotein changes.
Area of Science:
- Endocrinology
- Cardiovascular Disease Research
- Metabolic Disorders
Background:
- Hypopituitary patients exhibit increased mortality, primarily from vascular disease.
- Lipid and lipoprotein metabolism is crucial for cardiovascular health.
Purpose of the Study:
- To investigate circulating lipid and lipoprotein concentrations in hypopituitary women and men compared to controls.
- To assess the impact of conventional hormone replacement therapy on lipid profiles.
Main Methods:
- Two studies were conducted: a cross-sectional overnight fast study and a 24-hour ambulatory monitoring study.
- Measurements included triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, apolipoprotein B, apolipoprotein A1, and lipoprotein(a).
Main Results:
- Hypopituitary women showed elevated fasting triglycerides, total cholesterol, LDL cholesterol, and apolipoprotein B compared to controls.
- Postprandial and 24-hour measurements revealed significantly higher triglyceride and total cholesterol levels in hypopituitary women.
- While less pronounced, hypopituitary men also had a higher proportion with elevated total and LDL cholesterol.
Conclusions:
- Hypopituitarism, even with standard hormone replacement, is associated with adverse lipid and lipoprotein profiles, particularly in women.
- These lipid alterations may contribute to the increased vascular morbidity and mortality observed in hypopituitary patients.
Abstract:
Hypopituitary patients, particularly women, have excess mortality, mostly due to vascular disease. We have studied circulating lipid and lipoprotein concentrations, fasting and over 24 h, in hypopituitary women and men and in matched controls. Firstly, 67 hypopituitary patients (36 women) and 87 normal controls (54 women) were studied after an overnight fast. Secondly, 12 patients (6 women) and 14 matched controls (7 women) were studied over 24 h of normal meals and activity. The patients were all GH deficient and were replaced with cortisol, T4, and sex hormones where appropriate, but not with GH. In the first study, circulating triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol were measured after an overnight fast. In the second study, fasting levels of apolipoprotein B, apolipoprotein A1, and lipoprotein(a) were also measured, and then circulating triglyceride and total cholesterol concentrations were measured over 24 h. Fasting concentrations of triglyceride (mean +/- SEM, 1.73 +/- 0.22 vs. 1.11 +/- 0.09 mmol/L; P = 0.0025), total cholesterol (6.45 +/- 0.25 vs. 5.59 +/- 0.21 mmol/L; P = 0.002), LDL cholesterol (4.58 +/- 0.24 vs. 3.80 +/- 0.19 mmol/L; P = 0.007), and apolipoprotein B (135 +/- 10 vs. 111 +/- 9 mg/dL; P = 0.048) were elevated in hypopituitary compared to control women. The lipid alterations were observed in older and younger women and occurred independently of sex hormone or glucocorticoid replacement. Fasting values were not significantly different in hypopituitary and control men. Patients and controls (women and men) had similar fasting HDL cholesterol, apolipoprotein A1, and lipoprotein(a) concentrations. Although the differences that existed in fasting lipid values were most marked in women, the men were also abnormal in this respect, in that a higher proportion of hypopituitary than control men had total and LDL cholesterol above recommended values (> or = 6.2 and > or = 4.1 mmol/L, respectively). In the postprandial period (0730-2030 h), the areas under the curve (AUC) for circulating triglyceride and total cholesterol were significantly higher in hypopituitary than control women (P = 0.0089 and P = 0.0016, respectively). The AUC for triglyceride and total cholesterol over 24 h were also significantly increased (P = 0.009 and P = 0.0004, respectively). No significant differences were observed for postprandial and 24-h AUC for triglyceride and total cholesterol concentrations in men. We conclude that hypopituitarism with conventional replacement therapy is associated with unfavorable fasting and postprandial lipid and lipoprotein concentrations, particularly in women. The changes may contribute to the observed increased vascular morbidity and mortality.