Glucose levels and insulin secretion during a 75 g glucose challenge test in normal pregnancy.

OBJECTIVES: The aim of the study was to evaluate glucose levels and insulin secretion early in pregnancy and at a time when gestational diabetes mellitus frequently occurs in order to define reference values for glucose tolerance during pregnancy. The results were also related to maternal factors that might identify subjects at risk of developing gestational diabetes mellitus as well as foetal factors that might be a result of impaired glucose tolerance during pregnancy. DESIGN: A prospective study. SETTING: All Caucasian women attending one antenatal out-patient care unit were offered a 75 g oral glucose tolerance test at the 17th and 32nd week of gestation. SUBJECTS: A total of 586 consecutive pregnant women were included in the study. All 586 women were examined by repeated blood glucose measurements and 298 agreed to perform oral glucose tolerance tests as well. MAIN OUTCOME MEASURES: Venous whole blood glucose values were measured in the fasting state and in samples obtained 15, 30, 45, 60, 75, 90 and 120 min after oral intake of 75 g glucose. Serum insulin and C-peptide were also measured at these times. In all subjects, a random blood glucose sample was taken at the first visit, and thereafter at the 20th, 30th and 36th week of gestation. Information was also obtained from all subjects regarding body mass index, weight gain during pregnancy, smoking habits, family history of diabetes and hypertension, hypertension during pregnancy, past obstetric history, parity, and fetal outcome. RESULTS: The glucose tolerance was significantly impaired at the 32nd week of gestation compared with the 17th week of gestation. The mean +2SD 2 h glucose value during the oral glucose tolerance test at the 32nd week of gestation was 8.0 mmol L-1. Impaired glucose tolerance was characterised by increased insulin resistance, with a significant rise in serum insulin and C-peptide concentrations and in the insulin/glucose index during the oral glucose tolerance test at the 32nd week of gestation. Maternal factors associated with an impaired glucose tolerance were a family history of diabetes mellitus, smoking, a weight gain more than 18 kg during pregnancy, and glucosuria, while a family history of hypertension and hypertension present during pregnancy were not. Foetal factors that might be a result of impaired glucose tolerance during pregnancy, e.g. macrosomia and prematurity as well as complicated deliveries such as vacuum extraction/forceps or Caesarean section, all tended to be associated with higher blood glucose values. The same pattern was seen when the Apgar score was < 7. CONCLUSIONS: The results from this study show that the present cut-off values for diagnosis of gestational diabetes mellitus should be revised. Even if some maternal factors might indicate an increased risk for impaired glucose tolerance during pregnancy, they are probably not enough to detect women with gestational diabetes mellitus. Therefore, a screening programme for gestational diabetes should be considered.

Postoperative studies on parathyroid hormone secretion in patients operated on for primary hyperparathyroidism.

The secretion of intact parathyroid hormone (PTH) was investigated in 11 patients operated on for parathyroid adenoma at 1 year after surgery and compared with that of seven healthy individuals and five patients operated on because of clinical and biochemical signs of primary hyperparathyroidism with equivocal diagnosis after surgery. The investigation was performed by infusing Na2EDTA and CaCl2 at constant rates. No significant difference was found in the suppressibility of PTH secretion by calcium. The set point (the calcium concentration required for half-maximal inhibition of PTH secretion) was slightly lower in patients (1.20 +/- 0.02 mmol/l) compared with healthy subjects (1.23 +/- 0.03 mmol/l; P < 0.05). During the hypocalcemic EDTA infusion, the secretion of PTH was higher in controls compared with patients (P < 0.01). By comparing the data from the infusion tests in patients operated on for parathyroid adenomas with the data obtained from the patients with equivocal diagnosis after parathyroid surgery, a good probability for the diagnosis could be obtained.

Parathyroid hormone secretion after operation for primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with a defective regulation of the secretion of parathyroid hormone (PTH). Thus in pHPT, higher than normal calcium concentrations are required to inhibit PTH release. However, it is not known if this defective regulation is normalized by removal of the parathyroid adenoma (i.e., whether the regulation of PTH secretion is normal in the remaining glands). In this study we therefore investigated the PTH secretion in patients operated on for parathyroid adenoma 1 year after operation. METHODS: Na2 ethylenediamine tetraacetic acid and CaCI2 were infused at constant rates in six patients operated on for parathyroid adenoma and six healthy individuals. Serum levels of intact PTH and ionized calcium were determined during the infusions. RESULTS: No significant differences between the two groups were found in baseline levels of serum ionized calcium and PTH. Furthermore, no significant differences between patients and control subjects were found in the maximum serum PTH levels during the hypocalcemic infusion of ethylenediamine tetraacetic acid or in the minimum serum PTH levels during the calcium infusion. In contrast, the set point (the calcium concentration required for half-maximal inhibition of PTH secretion) was significantly lower in the patients (1.20 +/- 0.01 mmol/L) compared with control subjects (1.22 +/- 0.01 mmol/L; p < 0.05). CONCLUSIONS: We conclude that the elevation of set point in patients with parathyroid adenoma is corrected by successful operation. This suggests a monoclonal origin of parathyroid adenomas.

Intact parathyroid hormone assay is superior to mid region assay in the EDTA-infusion test in hyperparathyroidism.

We examined the use of an intact parathyroid hormone two-site immunoradiometric assay compared with a mid region parathyroid hormone radioimmunoassay in ethylene diamine tetraacetic acid-infusion test in 15 patients with hyperparathyroidism. During the test, plasma intact parathyroid hormone levels increased by 240 +/- 43%, whereas the plasma levels of mid molecule parathyroid hormone increased by only 65 +/- 17%, which is significantly lower (P less than 0.01). Four patients had no increase in plasma mid molecule parathyroid hormone level but still a large increase in plasma intact parathyroid hormone level (P less than 0.01). Thus, plasma measurement of intact parathyroid hormone is superior to that of mid molecule parathyroid hormone in the ethylene diamine tetraacetic acid-infusion test in patients with hyperparathyroidism.

Intraoperative fall in plasma levels of intact parathyroid hormone after removal of one enlarged parathyroid gland in hyperparathyroid patients.

Plasma levels of intact parathyroid hormone (PTH) were measured intraoperatively before and after removal of one enlarged gland in 20 hyperparathyroid patients. In 13 patients with a single parathyroid adenoma, plasma levels of intact PTH-(1-84) had declined at 15 min after removal of the adenoma by 86.5 +/- 4.4% of baseline in the antecubital vein and by 85.6 +/- 4.2% in the ipsilateral internal jugular vein. In seven patients with parathyroid hyperplasia, the corresponding figures for decline at 15 min after removal of one enlarged parathyroid gland were only 26.6 +/- 6.4% and 7.8 +/- 29.4%. The fall in PTH levels was significantly less in hyperplasia than in adenoma (p less than 0.001). Thus 15 min after removal of one enlarged parathyroid gland, the decline in plasma level of intact PTH may distinguish between single adenoma and multiglandular disease as the cause of hyperparathyroidism.

Halothane, enflurane and isoflurane anaesthesia for adenoidectomy in children, using two different premedications.

In 48 children subjected to adenoidectomy, comparisons of airway problems, heart rates, cardiac arrhythmias, ventilation and stress hormone reactions were studied during halothane, enflurane and isoflurane anaesthesia. Sixteen children were anaesthetized with either of the three agents and eight patients in each group received diazepam 0.25 mg kg-1 and atropine 0.015 mg kg-1 rectally (DA) as premedication and the remainder diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and scopolamine 0.01 mg kg-1 (DMS) rectally. All children were intubated and breathing spontaneously. Equianaesthetic inspired concentrations of halothane, enflurane and isoflurane were used. Airway problems were of the same magnitude during halothane and isoflurane anaesthesia but were less frequent with both agents compared with enflurane anaesthesia. DMS reduced the number of airway reactions in all groups. Respiratory rates were uninfluenced by anaesthesia, intubation and surgery during enflurane anaesthesia. Cardiac arrhythmias were less frequent with enflurane and isoflurane than with halothane. Plasma ACTH and cortisol were similar with all three agents. During induction of anaesthesia in the DA-premedicated halothane group, however, plasma catecholamines were higher than in the group which received DMS, in contrast to the findings during enflurane and isoflurane anaesthesia. The DMS premedication decreased the response of plasma ACTH, cortisol and plasma catecholamines to surgery.

Ventilation, ventilatory carbon dioxide and hormonal response during halothane anaesthesia and surgery in children after midazolam premedication.

In 14 intubated, spontaneously breathing children with body weight (bw) ranging from 8.3 to 25.6 kg, the influence of midazolam 0.1 mg kg-1 i.m. (group M0.1, n = 7) and 0.2 mg kg-1 i.m. (group M0.2, n = 7) as premedication, on sedation, ventilation, ventilatory response to carbon dioxide and hormonal stress response was studied in connection with minor surgical procedures during halothane anaesthesia. The concentrations of catecholamines, ACTH and cortisol were measured immediately after induction, during undisturbed anaesthesia, during surgery and 15 min after the end of the surgical procedure. Sedation was better and plasma catecholamine concentrations during undisturbed anaesthesia were less in children receiving the larger dose of midazolam. During surgery and in recovery there were no differences in hormone concentrations. In recovery, the concentrations of all hormones were significantly greater compared with during undisturbed anaesthesia. During surgery, VE and respiratory rate were somewhat lower in group M0.2 while E' CO2 was similar. A dose dependent depression of the response to carbon dioxide was found. However, clinically, the ventilatory response to carbon dioxide after surgery was considered to be adequate in both groups.

Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery.

Clonidine was administered intravenously in an attempt to limit sympatico-adrenal activity and thereby reduce the incidence of arterial hypertension associated with coronary artery by-pass graft surgery (CABG). Forty patients scheduled for CABG were assigned to two groups. Twenty patients received clonidine 4 micrograms kg-1 before surgery, 2 micrograms kg-1 after cardiopulmonary by-pass and 1 microgram kg-1 when the skin was sutured. The other 20 patients served as controls. All patients were anesthetized with fentanyl, droperidol, nitrous oxide and alcuronium. During surgery 5 min after sternotomy, mean arterial pressure was 13 mmHg lower (P less than 0.01) in the clonidine group, while after operation the difference between the groups was negligible. Both during and after surgery the plasma catecholamine concentrations were significantly lower in the clonidine group (P less than 0.01). The greatest difference between the groups was seen 90 min after operation, when plasma noradrenaline and plasma adrenaline concentrations in the clonidine group were less than 1/3 of those in the control group (P less than 0.01). As judged by catecholamine concentrations clonidine was effective in attenuating sympatico-adrenal hyperactivity during and after surgery. Postoperative arterial hypertension was not reduced, however, and it is concluded that other factors besides sympatico-adrenal hyperactivity must be important.

Maternal and fetal endocrine stress response at vaginal delivery with and without an epidural block.

Maternal and fetal stress response at vaginal delivery were studied in 19 normal parturients at term. Ten patients to whom an epidural block (group EA) had been administered were compared with 9 patients (group NEA) who used only nitrous oxide for pain relief. Plasma concentrations of ACTH, cortisol, 17-alpha-hydroxyprogesterone, blood glucose and catecholamines were measured in maternal and umbilical vein blood at delivery and in maternal vein blood 30 minutes after delivery. At delivery maternal plasma concentrations of ACTH, cortisol and catecholamines were lower in the EA group compared with in the NEA group. There were no differences in umbilical plasma concentrations of the studied stress variables between the two groups. A linear relation was demonstrated between maternal and umbilical vein cortisol concentration. In both the EA and NEA group a significant fall in ACTH, 17-alpha-hydroxyprogesterone and catecholamine concentrations were demonstrated 30 minutes after delivery, whereas cortisol and blood glucose were virtually unchanged. It was found that epidural anesthesia reduced the maternal stress hormones at delivery but seemed to have little or no effect on the fetal endocrine stress hormones.

Endocrine response to surgery in children after premedication with midazolam or papaveretum.

The effect of two premedications on the sympatho-adrenal and endocrine stress-response to minor surgery under halothane anaesthesia was investigated in 16 children. One group (n = 9) was premedicated with midazolam, 0.1 mg kg-1, and atropine 0.2-0.4 mg i.m. The other group (n = 7) received papaveretum 0.4 mg kg-1 and hyoscine 0.008 mg kg-1 i.m. Plasma concentrations of catecholamines, ACTH and cortisol were measured during undisturbed anaesthesia, during surgery and 15 min post-operatively. There were no differences in catecholamine concentrations between the groups. Prior to surgery, plasma ACTH was significantly lower (P less than 0.05) in the papaveretum group. During surgery, plasma cortisol and plasma ACTH were significantly lower after papaveretum premedication. Post-operatively there were no differences. End-tidal CO2 concentrations were similar in the two groups. It was concluded that the endocrine stress-response immediately after induction of anaesthesia and during surgery was lower after papaveretum than after midazolam premedication.

Adrenergic hyperactivity and epidural block in severe tetanus. A case report.

In a 69-year-old man with severe tetanus, sympatho-adrenal overactivity was successfully treated with a lumbar epidural block. Cardiovascular disturbances were reduced and fluctuations in plasma catecholamines were decreased. The duration of other manifestations of tetanus was, however, not influenced by the epidural block in this case.

Catecholamine and endocrine response in children during halothane and enflurane anaesthesia for adenoidectomy.

In 28 children undergoing adenoidectomy, plasma concentrations of catecholamines, ACTH and cortisol were measured. Fourteen children were anaesthetized with halothane (seven non-intubated, seven intubated) and 14 with enflurane (seven non-intubated, seven intubated). During undisturbed anaesthesia, plasma catecholamines were significantly higher with halothane than with enflurane (P less than 0.05). Immediately after surgery, catecholamines were increased up to 300% in the halothane groups. In the enflurane groups, however, the catecholamine concentrations remained unchanged. This difference between the two agents, after surgery, was statistically significant (P less than 0.01 for intubated and P less than 0.001 for non-intubated children). Fifteen minutes postoperatively no difference was found in plasma concentrations between the groups. In all four groups, plasma concentrations of ACTH and cortisol increased similarly during the procedure. It was concluded that plasma catecholamines were higher during halothane than during enflurane anaesthesia in children undergoing adenoidectomy. This difference may be caused by a stimulating effect of halothane on the endogenous catecholamine release. This increased sympathomimetic response during halothane anaesthesia was correlated to the incidence of ventricular arrhythmias previously found with this agent during adenoidectomy.

Normal reference interval for thyrotropin response to thyroliberin: dependence on age, sex, free thyroxin index, and basal concentrations of thyrotropin.

We measured the thyrotropin response (delta TSH) to 200 micrograms of thyroliberin in 131 subjects without thyroid dysfunction or other disease and with basal values for thyroid function that were within the normal reference intervals for our laboratory. By univariate and multivariate statistical methods we found delta TSH to be significantly influenced by the basal concentration of thyrotropin (TSH0) and the free thyroxin index (FT4I). When the effects of variations in TSH0 and FT4I were eliminated, delta TSH in men under 40 years of age did not differ from that in women. A decrease in delta TSH with increasing age was found in men but not in women. Thus a reference interval for delta TSH should consider TSH0, FT4I, and, in men, age. On the basis of multiple linear regression analysis, we constructed a formula for delta TSH reference intervals that takes into account individual values for TSH0 and FT4I. The formula should be applicable for women, regardless of age, up to 77 years and for men under 40 years. For older men a correction for the age-related decrease in delta TSH must be applied.

Influence of premedication on the sympathetic and endocrine responses and cardiac arrhythmias during halothane anaesthesia in children undergoing adenoidectomy.

The occurrence of cardiac arrhythmia was investigated in 80 children during halothane anaesthesia for adenoidectomy. Two different premedications were studied. Forty children (group A) were premedicated with diazepam 5 mg rectally and atropine 0.3-0.4 mg sublingually and 40 (group B) received a rectal solution including diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and hyoscine 0.01 mg kg-1. In 17 of these children (nine in group A and eight in group B) plasma concentrations of catecholamines, ACTH and corticosteroids were measured. In group A the mean plasma concentration of catecholamines increased more than 300% during surgery, while it was virtually unchanged in group B (P less than 0.01). Plasma concentrations of ACTH, cortisol and 17-alpha-hydroxyprogesterone were also greater in group A than in group B. The occurrence of ventricular arrhythmias in group A was significantly more frequent (20.0%) than in group B (2.5%) (P less than 0.05). It was concluded that in these two comparable groups of patients ventricular arrhythmia during halothane anaesthesia was almost eliminated by the use of more effective premedication, as a result of decreases in the sympathetic and endocrine responses to surgery.

Metoprolol, fentanyl and stress responses to microlaryngoscopy. Effects on arterial pressure, heart rate and plasma concentrations of catecholamines, ACTH and cortisol.

Forty patients undergoing microlaryngoscopy were anaesthetized with thiopentone and nitrous oxide. Twenty patients received metoprolol 200 mg in a slow-release tablet once daily for 4 days up to, and including, the morning of operation, and 10 mg i.v. shortly before induction of anaesthesia. The other patients received placebo tablets and physiological saline i.v., instead. Both groups of 20 patients were further subdivided, half of the patients receiving fentanyl 1.0-1.5 mg during anaesthesia, the effect of which was antagonized by naloxone at the end of the procedure. The other patients received saline i.v. instead of fentanyl or naloxone. Metoprolol decreased heart rate and the general level of arterial pressure during anaesthesia, but did not affect the fluctuations in pressure. Arterial plasma noradrenaline concentrations during microlaryngoscopy were enhanced by metoprolol, in comparison with placebo, the reverse being the case for cortisol concentrations. Fentanyl decreased arterial pressure and plasma ACTH and cortisol concentrations regardless of whether the patient had received metoprolol. Plasma adrenaline and noradrenaline concentrations were decreased by fentanyl in the patients receiving metoprolol.

Influence of premedication on plasma ACTH and cortisol concentrations in children during adenoidectomy.

The endocrine response to stress, as reflected by the plasma concentrations of ACTH and cortisol, was investigated in 14 children receiving two different premedications during halothane anaesthesia for adenoidectomy. Seven children (group A) were premedicated with diazepam 5 mg rectally and atropine 0.3-0.4 mg sublingually and seven (group B) received a rectal combination of diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and hyoscine 0.01 mg kg-1. Before and after surgery plasma concentrations of ACTH and cortisol were lower in group B than in group A. In group A mean values for ACTH increased from 40.7 ng line-1 before adenoidectomy to 352.9 ng litre-1 (P less than 0.001) after adenoidectomy. The corresponding increase in group B was from 12.1 ng litre-1 to 82.1 ng litre-1 (P less than 0.01). In group A mean cortisol concentrations increased from 235.7 nmol litre-1 to 655.7 nmol litre-1 after adenoidectomy (P less than 0.01) and in group B from 121.4 nmol litre-1 to 427.9 nmol litre-1 (P less than 0.01). End-tidal carbon dioxide tension was approximately the same in both groups. It was concluded that the combination of diazepam, morphine and hyoscine decreased the endocrine response to stress.

The nature of mannose-containing material which accumulates in cultured fibroblasts from patients with mannosidosis.

Fibroblasts from a patient with mannosidosis were grown in a medium containing a radioactive monosaccharide (D-[U-14C]mannose or N-acetyl-D-[1-14C]-glucosamine). An accumulation of radioactive material was observed. It was possible to prevent the accumulation to a certain degree by the addition of human liver alpha-D-mannosidase to the fibroblast medium. After six days of fibroblast culture the majority of the accumulated material had a molecular weight in the oligosaccharide range and was stationary during high-voltage electrophoresis. Paper chromatography of the stationary material separated three radioactive compounds with the same chromatographic mobilities as the oligosaccharides alpha-D-Man-(1 leads to 3)-beta-D-Man-(1 leads to 4)-D-GlcNAc (I), alpha-D-Man-(1 leads to 2)-alpha-D-Man-(1 leads to 3)-beta-D-Man-(1 leads to 4)-GlcNAc (II), and alpha-D-Man-(1 leads to 2)-alpha-D-Man-(1 leads to 2)-alpha-D-Man-(1 leads to 3)-beta-D-Man-(1 leads to 4)-GlcNAc (III) previously isolated from the urine of patients with mannosidosis. Degradation of the three radioactive compounds with jack bean alpha-mannosidase gave D-mannose and a disaccharide (containing D-mannose and N-acetyl-D-glucosamine). Thus the three main compounts observed in the fibroblasts from patients with mannosidosis are most probably identical to the oligosaccharides I--III.