Plasma arginine vasopressin and the syndrome of inappropriate antidiuretic hormone secretion in tuberculous meningitis.

Biochemical evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was documented in 17 of 24 (71%) children with tuberculous meningitis. Plasma arginine vasopressin concentrations in patients with signs of SIADH were significantly higher (median, 15.44 (range, 1.62 to greater than 24.52) pg/ml; n = 14) than those without (median, 1.91 (range, 0.44 to 4.91) pg/ml; n = 6) (P less than 0.002). Patients who developed evidence of SIADH were older than those who did not (median, 34 (range, 6 to 101) months vs. 10 (range, 6 to 38) months; P less than 0.007). Five patients with and none without died. In 9 patients evidence of SIADH developed only after hospitalization. These patients received a median of 58 (range, 28 to 109) ml/kg/day fluids (n = 7) before developing evidence of SIADH compared with 107 (range, 58 to 146) ml/kg/day received by patients who did not develop SIADH (n = 6) (P = 0.035). SIADH occurs commonly and its presence appears to influence the outcome of tuberculous meningitis in children.

Alpha 2-adrenoceptor levels on platelets of patients with major depressive disorders.

3H-p-Aminoclonidine binding to platelets of patients with primary, unipolar major depressive disorder was compared to that of a normal healthy control population. The variances of platelet alpha 2-adrenoceptor Kd and Bmax values in patients were significantly greater than in the control group. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax value of the depressed group was significantly lower than that of controls. We propose that an abnormal platelet alpha 2-adrenoceptor density may be used as a biological marker for major depressive disorder.

Imipramine binding sites on platelets of patients with major depressive disorder.

3H-Imipramine binding to platelets of patients with primary, unipolar major depressive disorder was investigated and compared to that of a normal, healthy control population. No significant differences could be demonstrated between either the Kd or the Bmax values of the two groups. A negative correlation was observed between imipramine Bmax values and the Hamilton anxiety ratings of the depressed patients. Patients who displayed psychomotor retardation tended to have lower platelet imipramine Bmax values than patients with psychomotor agitation. It is suggested that platelet imipramine Bmax values may be a biological marker for subtypes of depression.

Beta-adrenoceptors on lymphocytes of patients with major depressive disorder.

3H-Dihydroalprenolol binding to lymphocyte membranes of patients with primary, unipolar major depressive disorder was compared to that of a normal, healthy control population. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax values of the depressed patients were significantly lower than those of the controls. Positive correlations were observed between the lymphocyte beta-adrenoceptor Bmax values of the patients and their Beck self-evaluation and Hamilton depression ratings. We propose that decreased lymphocyte beta-adrenoceptor Bmax values may be used as a biological marker for major depressive disorder.

Noradrenergic function and hypothalamic-pituitary-adrenal axis activity in primary unipolar major depressive disorder.

Plasma levels of cortisol, norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in 16 drug-free patients with primary, unipolar major depressive disorder than in 20 controls. Plasma free MHPG and basal cortisol levels showed a significant positive correlation in the controls, but not in the patients. There were, however, significant positive correlations between cortisol and NE, as well as between NE and free MHPG levels in the patients. No correlations were observed between patient plasma NE levels and platelet alpha 2-adrenoceptor or lymphocyte beta-adrenoceptor Kd or Bmax values. These peripheral measures of noradrenergic function are proposed as useful markers for patients with primary, unipolar major depressive disorder with melancholia.

Arginine vasopressin concentrations in the cerebrospinal fluid of children.

Cerebrospinal fluid (CSF) arginine vasopressin (AVP) levels are reported in a group of 22 children (median age 24 months) investigated for possible bacterial meningitis and subsequently found not to be suffering from this disease. The mean CSF AVP concentration was 0.80 +/- 0.33 pg/ml. The results obtained in patients suffering from febrile convulsions (mean 0.71 pg/ml), other convulsive disorders (mean 0.80 pg/ml) and miscellaneous infectious diseases (mean 0.85 pg/ml) did not differ significantly from one another. Our findings confirm the presence of AVP in the CSF of children and provide reference values for further investigations into the functions of CSF AVP in children.

Genetic differences in the endocrine responses to the thyrotrophin-releasing hormone stimulation test in patients with a major depressive episode.

The thyrotrophin-releasing hormone (TRH) stimulation test is becoming useful in the diagnosis of depression, but the optimum concentration of TRH required remains uncertain. The test was performed on a carefully selected group of patients with primary unipolar major depressive episodes with melancholia, who were severely depressed, using TRH 200 micrograms and 500 micrograms (groups 1 and 2). The thyroid-stimulating hormone (TSH), growth hormone (GH) and prolactin (PRL) levels were measured in response to TRH. Responses obtained were compared with respect to hormonal and genetic subgroups. Comparing groups 1 and 2 revealed significant differences in the GH responses (P = 0,0059). A similar significant difference was found in the GH response (P = 0,0102) elicited by the women in each group. Comparison of the genetic subgroups of groups 1 and 2 revealed a significant difference in the PRL response of both the genetic spectrum (P = 0,0258) and the group without a genetic history (P = 0,0259) of alcoholism or depression. The TSH response in the genetic spectrum group was also significantly higher (P = 0,0008) in group 2. Further investigations of the responses elicited in the different genetic subgroups may reveal important variables for the investigation of the pathogenesis of depression.

Endocrine responses after thyrotrophin-releasing hormone stimulation and dexamethasone suppression tests in the major depressive syndrome.

The effects of dexamethasone 1 mg on plasma cortisol levels and of thyrotrophin-releasing hormone (TRH) 200 micrograms on thyrotrophin (TSH), growth hormone and prolactin levels in 107 patients with a major depressive disorder (MDD) were compared with those in 87 healthy subjects. Individual hormonal responses and combinations of hormonal responses after administration of dexamethasone and TRH were evaluated as diagnostic aids for MDD by calculating sensitivity, specificity and efficiency for single and multiple hormonal abnormalities. In patients suffering from MDD, 65% of men, 74% of reproductive women and 71% of menopausal or hysterectomized (H/M) women had abnormal responses (sensitivity) to a dexamethasone suppression test (DST). When the DST and TSH responses to TRH were combined, 85% of men, 87% of reproductive women and 84% of H/M women had abnormal results. If the efficiency of the different combinations of hormone responses is calculated, a totally different picture emerges.

Inappropriate antidiuretic state in long-term psychiatric inpatients.

To investigate the occurrence of an inappropriate antidiuretic state in a long-term psychiatric inpatient population, 690 patients underwent serum sodium determination. Forty-four patients (6.4%) had levels less than 133 mmol/l. Fifteen of these patients could be investigated further and the biochemical findings in all were consistent with an inappropriate antidiuretic state. Evidence of previous episodes of water intoxication was found in 80% of these patients. Although more than one possible cause was present in most patients, the two factors most strongly incriminated in the pathogenesis of the inappropriate antidiuretic state were the drugs carbamazepine and hydrochlorothiazide.

Endocrine function in alcoholic Korsakoff's syndrome.

Hypothalamic-pituitary function was studied by means of several dynamic endocrine tests in 19 patients with alcoholic Korsakoff's syndrome, 17 non-amnesic alcoholics and 21 non-alcoholic controls. The responses of thyroid stimulating hormone, prolactin, follicle stimulating hormone, and luteinizing hormone to a combined thyrotropin releasing hormone and gonadoliberin stimulation test did not differ significantly. For the dexamethasone suppression test, the Korsakoff patients had significantly higher basal serum cortisol and 08:00 hr post-dexamethasone cortisol levels than non-alcoholic controls. These findings raise the possibility that chronically elevated cortisol levels may contribute to cognitive impairment in alcoholic Korsakoff's syndrome.

Measurement of micro-albuminuria in patients with diabetes mellitus.

Persistent micro-albuminuria (MA) in patients with diabetes mellitus identifies a high-risk group for the development of vascular complications. Since the methodology involved in measuring MA has not been standardised, MA in 40 diabetic patients was measured in order to compare nephelometry with radio-immunoassay (RIA). The effect of storage (7 days), the influence of freezing and thawing on MA levels, and possible differences between glass and plastic containers were also assessed. An excellent correlation (r = 0.971) was found between RIA and nephelometry. Urine could be safely stored at 4 degrees C in either plastic or glass containers without any significant influence on MA concentrations. It is concluded that nephelometry is an excellent method for accurately measuring MA.

The thyrotropin releasing hormone stimulation test in alcoholism.

The mechanism for a blunted thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in alcoholics is not known. We performed a combined TRH and gonadoliberin stimulation test on three well-defined groups of nondepressed alcoholic men. Group A comprised patients with acute withdrawal symptoms (n = 28), group B patients abstinent for 5-8 weeks (n = 29) and group C patients who had been abstinent for > 2 years (n = 16). Twenty-two healthy male volunteers were used for comparison. A blunted TSH response to TRH (delta TSH < 5 microU/l) occurred only in groups A (39%) and B (17%). In group A delta TSH showed a significant negative correlation with the severity of withdrawal symptoms and a significant positive correlation with serum magnesium levels. In group B, patients with a family history of alcoholism had significantly lower delta TSH levels than those without such a family history. Groups did not differ with respect to basal and delta prolactin, and TSH responses were not significantly associated with vitamin deficiency, cortisol levels or free thyroid hormone levels. We conclude that TRH stimulation test blunting appears to be related to factors operating in the withdrawal state and improves with continued abstinence. A possible role of genetic factors and serum magnesium needs to be further explored.

Endemic goitre among undernourished schoolchildren in eastern Caprivi, Namibia.

A cross-sectional study on a 20% random sample of 380 children, aged 6-18 years, from 8 primary schools in the Cuando River area of eastern Caprivi, Namibia, was done to determine the prevalence of goitre and to investigate related hormonal and nutritional factors. Of the children 34.5% had goitre. Reduced plasma free thyroxine concentrations in the more severely goitrous children, compared with matched non-goitrous children (P = 0.0007), implicated dietary iodine deficiency as the causative factor. Their diet was inadequate in energy and most nutrients according to World Health Organisation criteria. Retarded growth, indicated by their low body weight and height in relation to age, were observed in a large proportion (45.6-73%) of the children. These findings suggest that dietary iodine deficiency was the most likely cause for the endemic goitre in these children, who were predisposed to nutritional disorders by long-term undernourishment.

Raised intracranial pressure, the syndrome of inappropriate antidiuretic hormone secretion, and arginine vasopressin in tuberculous meningitis.

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mmHg, range 8.4-50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8-42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.

Vasopressin secretion and memory impairment in alcoholic Korsakoff's syndrome.

The response of arginine vasopressin (AVP) to an intravenous hypertonic saline infusion was investigated in 19 patients with alcoholic Korsakoff's syndrome, 17 non-amnesic alcoholics and 21 non-alcoholic controls. Compared with non-alcoholic controls the Korsakoff patients had elevated basal AVP levels and showed erratic fluctuation of AVP secretion, not related to changes in serum sodium levels. The non-amnesic alcoholics had a similar, but less severe derangement. Neuropsychological tests revealed significant correlations between basal AVP levels and memory performance in the non-amnesic alcoholics, raising the possibility of a common lesion--most likely in the diencephalon--for memory impairment and AVP dysregulation in chronic alcoholics.