P. H. Baylis

The short Synacthen and insulin stress tests in the assessment of the hypothalamic–pituitary–adrenal axis

OBJECTIVE The best dynamic test for the assessment of the hypothalamic–pituitary–adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic–pituitary–adrenal axis.

A New Sensitive Radioimmunoassay for Plasma Arginine Vasopressin

A new extremely sensitive radioimmunoassay to measure plasma AVP has been developed. Antiserum to AVP of high affinity (Keq = 1.1 X 10(12) 1/mol), raised in rabbits, showed little cross-reaction with related analogues (LVP less than 0.03%, AVT, DDAVP, OXT less than 0.01). The specific activity of 125I-AVP (chloramine T method) was 1400-1750 Ci/mmol. The limit of detection of plasma AVP, after extraction of 2 ml plasma with Florisil, was 0.3 pmol/1. Coefficient of variations of plasma control (2 pmo1/1) were 9.7% (intraassay) and 15.3% (inter-assay), n = 15. Osmotic stimulation by hypertonic saline infusion caused a linear response in plasma AVP in normal subjects, but plasma AVP remained undetectable in patients with cranial diabetes insipidus. Suppression of AVP secretion by a standard oral water load and by alcohol and fluid in volunteers produced low or undetectable values of plasma AVP. In a patient with the syndrome of inappropriate antidiuresis, plasma AVP concentration was grossly elevated.

Glomerular Ultrafiltration in Normal and Preeclamptic Pregnancy

GFR and renal plasma flow (RPF) decrease in preeclampsia, a serious hypertensive complication of pregnancy. Serial data derived in late pregnancy (LP) and >5 mo postpartum (PP) in 13 healthy controls and 10 preeclamptic women (13 and 5, respectively) returning PP for theoretical analysis of neutral dextran sieving curves (theta(D)), are presented and are used to calculate the key determinants of glomerular ultrafiltration. Normal LP hyperfiltration was associated with increases in RPF and the ultrafiltration coefficient (K(f)), as well as in the nondiscriminatory shunt pathway (omega(0)) and the SD of pore size (S). Preeclamptic LP showed the largest omega(0) and S values, indicating a loss of size-selectivity, accompanying reduced K(f) and RPF, both of which are implicated in the relative hypofiltration. Despite a 100-fold increase in urinary albumin excretion (UAE), LP preeclamptic theta(D) values were reduced for the equivalent neutral dextran (36A), providing indirect evidence for a loss of glomerular barrier charge-selectivity. All the determinants of GFR and all modeled parameters were comparable across both groups PP, strong evidence that preeclamptic glomerular dysfunction resolves.

OSMOREGULATION OF VASOPRESSIN SECRETION AND THIRST IN HEALTH AND DISEASE

Our understanding of the mechanisms that regulate water balance in mammals began over 40 years ago with the classic studies of Professor E. B. Verney and his colleagues in Cambridge, England. In a series of experiments on conscious, trained dogs with permanent exteriorized carotid arteries to allow rapid injections of solutions into the cerebral circulation, Verney demonstrated that hypertonic solutions of sodium chloride, sucrose and glucose caused antidiuresis; observations which formed the basis of the concept of the ‘osmoreceptor’. Verney proposed that cells within the central nervous system altered their volume thus regulating the release of an antidiuretic hormone which acted upon the kidney (Verney, 1947). The results of subsequent experiments suggested that these osmotically sensitive cells were located in the anterior hypothalamus (Jewel1 & Verney, 1957). Recent work from independent laboratories has identified probably the most important putative osmoreceptor concerned with the vasopressin secretion, the organum vasculosum of the lamina terminalis which is an area within the circumventricular organs of the anterior hypothalamus (McKinley et al., 1978; Thrasher er al., 1982). There is evidence that other sites associated with the circumventricular organs (e.g. the subfornical organ) might also act as osmoreceptors (Iovino & Steardo, 1984; Ferguson & Kasting, 1986), and possibly even the supra-optic nucleus itself, which synthesizes most of the osmoregulated vasopressin, may play a similar role (Leng et al., 1985). Progress in characterization of the functional aspects of osmoregulated vasopressin secretion was hampered by the lack of sensitive and reproducible assays to measure circulating vasopressin. UntiI the early 1970s only bioassays were available; but a major advance in our understanding of osmoregulation was heralded by the development of specific and sensitive radioimmunoassays able to detect vasopressin at the extremely low concentrations found in the body fluids of mammals (Robertson etal., 1970; Oyama et al., 1971). Over the next decade, the functional characteristics of osmoregulated vasopressin release were defined in healthy man (Robertson et al., 1976), data which confirmed Verney’s original observations in the dog. In more recent years physiological and

THE EFFECT OF VASOPRESSIN INFUSION ON GLUCOSE METABOLISM IN MAN

Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down gly‐cogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4±9 ± 0±1 to a peak of 5±70±2 mmol/1 (P<0<001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3‐hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11±9 ± 0±43 to 13±38 · 0±63 μmol/kg/min (P < 0·001). Infusion of AVP also increased plasma glucagon concentrations from 38 ± 8 to 79 ± 20 pg/1 (P < 0·01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.

VARIATION IN OSMOREGULATION OF ARGININE VASOPRESSIN DURING THE HUMAN MENSTRUAL CYCLE

Osmoregulation of vasopressin secretion was studied in eight healthy women in the follicular and luteal phases of the menstrual cycle. Basal plasma osmolality in the luteal phase was significantly lower than in the follicular period (282·4±0·6, 285·6 ± 1·1 mmol/kg, respectively, P<0·05). Plasma AVP (pAVP) and plasma osmolality (pOsm) were measured during the infusion of 850 mmol/1 saline in both phases of the cycle, and linear regression analyses of these data gave the following regression equations (i) follicular, pAVP = 0·43 (pOsm‐284), r=+0·93, (ii) luteal, pAVP = 0·31 (pOsm‐279), r=+0·95. Both the slope and abscissal intercept were significantly different (P<0·01). Osmotic threshold for thirst sensation in the luteal phase was lower than the follicular (293±2, 297±1 mmol/kg, P<0·005). We conclude that, in the luteal phase, the threshold for AVP release and the gain or sensitivity of the osmostat are reduced together with lowering of the thirst threshold, which account for the lower basal luteal plasma osmolality.

Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma

objective  In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.

Hypothalamic adipsic syndrome: diagnosis and management

Patients with hypothalamic adipsic syndrome, especially in conjunction with diabetes insipidus, pose management difficulties. They are at risk of both under‐ and over‐hydration. We present 4 patients with hypothalamic adipsic syndromes, due to different causes, illustrating the practical difficulties encountered in this condition. The principles of management, with a sliding scale of water intake related to changes in daily body weight, are discussed.

Plasma oxytocin, arginine vasopressin and atrial natriuretic peptide responses to insulin-induced hypoglycaemia in man

The changes in blood glucose, plasma oxytocin, plasma vasopressin, plasma atrial natriuretic peptide, serum osmolality, haematocrit and blood pressure were measured in response to acute insulin‐induced hypoglycaemia in six normal male subjects. After the i.v. administration of insulin (015 U/kg), plasma concentrations of oxytocin and vasopressin increased rapidly in all subjects and were maximal 15 min after the acute hypoglycaemic reaction (R). Haematocrit increased at the time of the hypoglycaemic reaction, but there was no change in serum osmolality. Systolic blood pressure rose and diastolic blood pressure fell, but mean arterial blood pressure remained unchanged. No changes were demonstrated in plasma concentrations of atrial natriuretic peptide. The release of oxytocin and vasopressin in response to acute hypoglycaemia in man is probably caused by stimulation of the posterior pituitary gland via hypothalamic activation, and not by stimulation of osmoreceptors or baroreceptors.

Adipsic hypothalamic diabetes insipidus after clipping of anterior communicating artery aneurysm.

It is not usually possible to cure lymphoedema but an active and enthusiastic approach can achieve great benefit. Most patients require only conservative treatment but if this is rigorously applied the results can be good. A short period oftreatment in hospital using a Lymphapress can alter the patients perception of the leg and engender enthusiasm for self treatment; cellulitis must be avoided by rigorous attention to hygiene. A few patients benefit from operation, but,this must never be carried out for cosmetic reasons. Those with heavy cumbersome legs can have the volume of subcutaneous tissue removed (Homans operation) and the results are usually good if the indications for operation are correct. Such operations may also permit support hosiery to fit better. A small group may benefit from operations to relieve lymphatic obstruction (mesenteric Hleal bridging operation or direct lymphovenous anastomosis) but this group do not impinge On the mass of patients who should be treated conservatively.