Haemorrhagic pituitary tumours

In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI.     

Clues for early detection of autoimmune Addison's disease – myths and realities

Background

Early detection of autoimmune Addison's disease (AAD ) is important as delay in diagnosis may result in a life‐threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well‐described, but methodical investigations are scarce.

Objective

Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD .

Material and Methods

A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978–2016. Scrutiny of medical records provided patient data and laboratory values.

Results

Low sodium occurred in 207 of 247 (84%), but only one‐third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty‐three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L^?1 [1–668]) and significantly lower in individuals with adrenal crisis (38 nmol L^?1 [2–442]) than in those without (81 nmol L^?1 [1–668], P < 0.001).

Conclusion

The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD , and on clinical suspicion bring about assay of cortisol and ACTH . Presence of 21‐hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

     

Elevation of plasma neuropeptide Y-like immunoreactivity and noradrenaline during myocardial ischaemia in man

Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease. On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels. The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris. Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris. Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris. Levels of NPY-LI returned to normal within 25 h in all patients. Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels. A positive correlation was found between noradrenaline and NPY-LI in plasma. It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.     

Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses

BACKGROUND: The aim of this study was to investigate the influence of the antipsychotic agent olanzapine on glucose-insulin homeostasis to explain possible mechanisms behind olanzapine-associated weight gain. METHOD: Fourteen patients on treatment with olanzapine (all meeting DSM-IV criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose, insulin, the growth hormone (GH)-dependent insulin-like growth factor I, and the insulin-dependent insulin-like growth factor binding protein-1 (IGFBP-1) were analyzed, as well as GH, leptin, and blood lipid levels and the serum concentrations of olanzapine and its metabolite N-desmethylolanzapine. In addition, body mass index (BMI) was calculated. Moreover, weight change during olanzapine treatment was determined. RESULTS: Twelve of the 14 patients reported weight gain between 1 and 10 kg during a median olanzapine treatment time of 5 months, whereas data were not available for the other 2 patients. Eight patients (57%) had BMI above the normal limit. Eleven patients were normoglycemic, and 3 showed increased blood glucose values. Most patients (10/14; 71%) had elevated insulin levels (i.e., above the normal limit). Accordingly, the median value of IGFBP-1 was significantly lower for the patients in comparison with healthy subjects. Moreover, 8 (57%) of 14 patients had hyperleptinemia, 62% (8/13) had hypertriglyceridemia, and 85% (11/13) hypercholesterolemia. Weight change correlated positively to blood glucose levels and inversely to the serum concentration level of N-desmethylolanzapine. Additionally, the levels of blood glucose, triglycerides, and cholesterol correlated inversely to the serum concentration of N-desmethylolanzapine. CONCLUSION: Olanzapine treatment was associated with weight gain and elevated levels of insulin, leptin, and blood lipids as well as insulin resistance, with 3 patients diagnosed to have diabetes mellitus. Both increased insulin secretion and hyprleptinemia may be mechanisms behind olanzapine-induced weight gain. Moreover, it is suggested that the metabolite N-desmethylolanzapine, but not olanzapine, has a normalizing effect on the metabolic abnormalities.     

Predicting in-hospital mortality in acute myocardial infarction: impact of thrombolytic therapy on APACHE II performance

OBJECTIVE: To study the usefulness of the Second Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system for prognostication of in-hospital mortality in patients with acute myocardial infarction treated with thrombolysis. DESIGN: A prospective validation study was conducted at a medical intensive care unit at a university hospital. Over a 3-year period, 1714 patients with acute myocardial infarction were studied (mean age 72+/-10 years). Thrombolytic therapy was the prescribed treatment for 316 patients and total hospital mortality was 16%. RESULTS: The patients who received thrombolysis were younger, had higher blood pressure, lower heart and respiratory rates and higher Glasgow Coma Scale scores. Total in-hospital mortality was 9.5% in patients treated with thrombolysis and 17.1% in untreated patients (p < 0.01). Corresponding APACHE II predictions of mortality were 11.8 and 15.8% (p < 0.01). There was no significant difference between observed and predicted mortality. When a decision rule of 50% predicted risk of death was employed, sensitivity was 20% and specificity 99% in the thrombolytic group, while the corresponding figures in the nonthrombolytic group were 31% and 97%, respectively. CONCLUSIONS: In-hospital mortality in groups of patients treated with or without thrombolysis for acute myocardial infarction could be predicted with the APACHE II scoring system. Prognostication in individual patients is not possible with the APACHE II system.     

Long-term changes in gastrin, cholecystokinin and insulin in response to oxytocin treatment

The present study was designed to investigate how repeated injections of oxytocin influence plasma levels of vagally controlled hormones such as gastrin, cholecystokinin (CCK), insulin and somatostatin, as well as of endogenous oxytocin and glucose. Since oxytocin may enhance the activity of centrally located alpha2-adrenoreceptors, a second aim of this study was to explore whether these receptors are involved in the effects. For this purpose, oxytocin (1.0 mg/kg) or NaCl was given subcutaneously (s.c.) once a day during 5 days to male rats. Rats were decapitated 1, 3 and 10 days after the last injection, blood was collected and hormone levels were radioimmunoassayed. The oxytocin treatment caused an elevation of plasma levels of oxytocin 1 day (p < 0.05) but not 3 and 10 days after treatment. Gastrin levels were decreased on day 1, 3 and 10 (ANOVA; p < 0.01). In addition, both insulin and CCK levels were decreased in response to the oxytocin treatment when measured 3 and 10 days after the last injection (ANOVA; insulin p < 0.01, CCK p < 0.05). When the alpha2-adrenoreceptor agonist clonidine (2.5 microgram/kg intracerebroventricularly) was administered 3 days after the 5-day treatment period with oxytocin or saline, plasma levels of insulin and CCK increased significantly (p < 0.05) in the oxytocin-treated rats, when compared to saline-treated controls receiving clonidine only. No change in glucose or somatostatin levels was found in response to the oxytocin treatment. In conclusion, these results show that oxytocin induces long-lasting changes in plasma levels of gastrin, CCK and insulin, without affecting somatostatin or glucose levels. These effects may be mediated by changes in vagal nerve activity.     

Oxytocin causes a sustained decrease in plasma levels of corticosterone in rats.

The aim of this study was to investigate how oxytocin (OXT) influences plasma levels of ACTH and corticosterone in rats. A single injection of OXT (1 mg/kg s.c.) caused a transient increase in ACTH and corticosterone. In contrast, 1 mg/kg OXT (but not 10-100 microg/kg) decreased corticosterone, but not ACTH levels, 6 h after the injection. OXT (1 mg/kg s.c.) administered once a day for 5 days, decreased cortiocosterone for 10 days after the last injection. An acute challenge with ACTH increased corticosterone to the same level in rats pretreated with OXT and controls. Dexamethasone decreased corticosterone to equal levels in both groups. Thus, OXT seems to be able to stimulate as well as to inhibit the activity within the HPA-axis within a short- and a long-term perspective, respectively.     

The growth hormone, prolactin and TSH response to TRH and L-dopa in patients with hyperprolactinaemia and a normal-sized sella turcica may denote a pituitary adenoma

Forty-one patients with hyperprolactinaemia and suspected prolactinomas were studied. Growth hormone (GH) and thyrotropin (TSH) secretory patterns after thyrotropin releasing hormone (TRH) were affected in the majority of patients. The disturbances were observed regardless of tumour size as indicated by the radiological sella size. In patients with hyperprolactinaemia and normal-sized sella turcica, an abnormal GH and TSH response to TRH can be helpful in the diagnosis of a microadenoma. The hyperprolactinaemia per se and its effect on dopaminergic hypothalamic neurones may be the cause of the GH and TSH response. By contrast, many patients with macroprolactinomas showed insufficient GH secretory capacity.     

Autoantibodies against alpha -MSH,ACTH, and LHRH in anorexia and bulimia nervosa patients

The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing alpha-melanocyte-stimulating hormone (alpha-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN andor BN patients studied had in their plasma Abs that bind to melanotropes andor corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to alpha-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with alpha-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with alpha-MSH or adrenocorticotropic hormone. Additionally, 3 ANBN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to ANBN staining. These data provide evidence that a significant subpopulation of ANBN patients have autoantibodies that bind to alpha-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitryLHRH system andor in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to andor could be involved in the pathophysiology or clinical presentation of ANBN, and to what extent increased stress is an important factor for production of these autoantibodies.