The occurrence of diabetic ketoacidosis in pregnancy compromises both the fetus and the mother. It usually occurs in the later stages of pregnancy and is also seen in newly presenting type 1 diabetes patients. Despite improvement in its incidence rates and outcomes over the years, it still remains a major clinical problem since it tends to occur at lower blood glucose levels and more rapidly than in non-pregnant patients often causing delay in the diagnosis. This article illustrates a typical case of diabetic ketoacidosis in pregnancy and reviews the literature to provide an insight into its pathophysiology and management.

There is still uncertainty about what is the most appropriate test for assessment of the integrity of the hypothalamo-pituitary-adrenal (HPA) axis. Many advocate the insulin tolerance test (ITT), but this is unpleasant and resource intensive, and may occasionally give misleading results. The conventional [250 microg tetracosactrin, ACTH-(1-24)] short synacthen test (SST) has been used as a simple alternative to the ITT, but it has produced some falsely reassuring results with potentially serious consequences. A low dose [1 microg tetracosactrin, ACTH-(1-24)] short synacthen test (LDSST) has recently been advocated as a more reliable and safer alternative to ITT. Some studies, however, have failed to demonstrate any difference between SST and LDSST. The purpose of this study was to assess the clinical usefulness of LDSST compared to SST and ITT in patients with pituitary disease. We studied 64 patients with suspected or proven pituitary disease. All patients underwent SST and LDSST. Forty-two patients underwent ITT. There was a high correlation between the ITT and LDSST peak cortisol responses (r = 0.89; P < 0.0001), the ITT and SST 30 min cortisol levels (r = 0.83; P < 0.0001), and the LDSST peak cortisol response and the SST 30 min cortisol level (r = 0.85; P < 0.0001). In the LDSST, all but six patients achieved maximal cortisol response by 30 min. A plasma cortisol cut-off of 600 nmol/L is more helpful than 500 nmol/L for clinical decision-making using either the SST 30 min cortisol level or the LDSST peak cortisol response. The sensitivity of the LDSST was 100% (cortisol response of >600 nmol/L indicates intact HPA axis), with no falsely reassuring results. SST (pass cortisol level, >600 nmol/L) was less sensitive than LDSST, it produced 2 of 64 (3%) falsely reassuring results. Even the ITT (pass cortisol level, >500 nmol/L) failed to identify one patient with clinically evident cortisol deficiency. The results of this study indicate that both SST and LDSST, at a cortisol cut-off of 600 nmol/L, are safe for the purpose of clinical decision-making with regard to steroid replacement therapy in patients with pituitary disease. As the LDSST produced no falsely reassuring decisions, we suggest that this could replace the SST and ITT for initial evaluation of the HPA axis in patients with pituitary disease. We suggest administering 1 microg tetracosactrin, i.v., with sampling at 0, 20, and 30 min.

Changes in lipid levels help to explain the results from risk factor modelling which show increased coronary risk in growth hormone deficient hypopituitary patients, particularly females. The abnormal lipid profile is characterized in both genders by an increase in the total to HDL ratio [corrected], an important parameter in the Framingham equation. The lipid abnormalities conferring increased risk is related to growth hormone deficiency either directly (LDL) or indirectly through increased central obesity (HDL) [corrected]. Adverse calculated coronary risk might provide a new objective indication for consideration of GH replacement therapy in adults.

Adult hypopituitarism is known to be associated with reduced life expectancy related to excess vascular events, and endothelial dysfunction is present in patients with this condition. We studied the relationship between biophysical and biochemical markers of endothelial dysfunction, including E-selectin, intercellular cell adhesion molecule-1, von Willebrand factor, and thrombomodulin in 52 adult patients with hypopituitarism and severe GH deficiency (<2 ng/ml on provocative testing) compared with 54 age-, sex-, and smoking-matched normal controls. We also examined endothelium-dependent dilatation of the brachial artery to postischemic occlusion and carotid artery morphology (intima-media thickness) by high-resolution ultrasonography. The patients were stable on conventional hormone replacement therapy but not on GH therapy, and none of the subjects had a known risk factor for vascular disease. Levels of E-selectin [57 +/- 3 vs. 49 +/- 2 ng/ml (mean +/- SEM)] (P < 0.043), intercellular cell adhesion molecule-1 (308 +/- 11 vs. 266 +/- 10 ng/ml) (P < 0.001), thrombomodulin (49 +/- 3 vs. 35 +/- 2 ng/ml) (P < 0.001), and von Willebrand factor (132 +/- 7% vs. 105 +/- 5%) (P < 0.004) were significantly higher in patients than in controls. Brachial artery endothelium-dependent dilatation was significantly lower in patients than in controls [4.7% (0.00-9.77) vs. 10.5% (6.4-16.2) (median, interquartile range)] (P < 0.001). This difference in endothelium-dependent dilatation was more marked in female patients than in controls (P < 0.003), although it disappeared when estrogen-sufficient female patients were compared with controls (P = 0.31). However, the female patients who were not replaced with estrogen continued to show a striking difference compared with estrogen-deficient control females (P < 0.004). There was no difference in carotid intima-media thickness between patients of either sex and controls. On univariate analysis, brachial artery endothelium-dependent dilatation correlated inversely with intercellular cell adhesion molecule-1 (r = -0.225, P < 0.033). Intercellular cell adhesion molecule-1 correlated positively with E-selectin (r = 0.466, P < 0.0001) and negatively with IGF-I (r = -0.238, P < 0.016). E-selectin correlated with thrombomodulin (r = 0.215, P < 0.034) and von Willebrand factor (r = 0.218, P < 0.03) and negatively with IGF-I (r = -0.255, P < 009). Thrombomodulin correlated positively with von Willebrand factor (r = 0.422, P < 0.0001) and inversely with IGF-I (r = -0.266, P < 0.008). These correlations persisted after correction for age, sex, body mass index, and waist to hip ratio, with the exception of IGF-I, which now correlated with thrombomodulin only. These results confirm significant endothelial dysfunction in hypopituitarism and provide insight into the relationship of biochemical and biophysical markers of early atherosclerosis in hypopituitary GH-deficient adults. The negative correlation of IGF-I with some biochemical markers of endothelial dysfunction and the predictive nature of GH de...

Biophysical test of endothelial function (FMD) improved after 12 months of GH therapy but there was no significant change in biochemical endothelial or inflammatory markers. Calculated coronary risk decreased mainly due to reduction in systolic and diastolic blood pressure and increase in HDL-cholesterol.