Homocysteine and its relation to B-vitamins in Graves' disease before and after treatment: effect modification by smoking.

OBJECTIVES: To investigate plasma total homocysteine levels and its relation to B-vitamins and smoking in Graves' disease before and after antithyroid therapy. DESIGN: A longitudinal study taking place at four hospitals in Norway. METHODS AND SUBJECTS: Plasma total homocysteine, serum folate, serum cobalamin and riboflavin, flavin mononucleotide and flavin adenine dinucleotide in plasma were investigated in 182 patients with hyperthyroidism before treatment. The same parameters were reinvestigated in 112 of these patients after attaining euthyroid state. RESULTS: In hyperthyroidism, plasma total homocysteine was low, and inversely related to folate, cobalamin and riboflavin, and positively related to serum creatinine and age. Following antithyroid therapy, total homocysteine increased and the concentration of folate, cobalamin, riboflavin, flavin mononucleotide and flavin adenine dinucleotide decreased significantly. The most pronounced reduction (35%) was observed for flavin mononucleotide. In the hyperthyroid state, smokers had lower levels of folate and flavin mononucleotide than non-smokers. After restoration of euthyroidism, both folate and riboflavin were significantly lower in smokers than non-smokers. Plasma total homocysteine increased according to decreasing quartiles of B-vitamins. For riboflavin, this relation was confined to smokers. CONCLUSION: Plasma total homocysteine changes according to thyroid status. These changes may be partly attributable to altered folate, cobalamin but also riboflavin status, particularly in smokers.

[Surgical treatment of endocrine ophthalmopathy]. / Kirurgisk behandling av endokrin oftalmopati.

Thyroid ophthalmopathy is an inflammatory disorder of the extraocular muscles, orbital fat and orbital connective tissue that is most commonly seen in patients with Graves' hyperthyroidism. Inflammation is accompanied by deposition of extracellular matrix components, in particular glycosaminoglycans. The increase in the volume of the orbital contents may lead to periorbital swelling, extraocular muscle dysfunction, disfiguring proptosis, exposure keratitis, increased intraocular pressure and optic nerve compression. In many cases, surgical treatment is necessary for the rehabilitation of patients. In this report, we present a series of patients to illustrate relevant procedures and the results of surgical treatment in patients with thyroid ophthalmopathy. The records of all patients (66) with thyroid ophthalmopathy hospitalized in the Department of Ophthalmology, Haukeland University Hospital 1 April 1994-31 March 1998 were retrospectively evaluated. Orbital decompressions were performed in 43 patients (in 17 for compressive optic neuropathy), squint surgery in 13 patients, correction of eyelid retraction in 20 patients, and removal of excessive skin and fat from the eyelids in 11 patients. Average reduction of proptosis was 4 mm after lateral wall resection, and 6 mm after combined medial and lateral wall resection. Visual acuity improved in patients with compressive optic neuropathy to 6/6 or better in 18/20 eyes (postoperative data were not available for all patients), while that of the remaining two eyes was 6/9 and 6/24, respectively. Squint surgery was successful (no diplopia in primary or reading position) in eight patients after one procedure, and in four after two procedures. One patient has been scheduled for a third procedure due to a severe esotropia. In patients with thyroid ophthalmopathy, suboptimal treatment of the thyroid disorder may worsen the ophthalmopathy. 16 patients had their medication adjusted, ten were referred for thyroid surgery, and one for treatment with radioiodine. Treatment of patients with thyroid ophthalmopathy is a therapeutic challenge requiring close collaboration between different specialists. In severe cases, several surgical procedures may be needed. The complication rate is low, however, and for most patients the functional as well as the aesthetic situation is greatly improved.

Factors influencing reduction in blood pressure and left ventricular mass in hypertensive type-1 diabetic patients using captopril or doxazosin for 6 months.

The effect of doxazosin versus captopril on blood pressure, albuminuria, and left ventricular mass was studied in 33 hypertensive type-1 diabetic patients randomized to 6 months treatment with captopril (17 patients, mean daily dose 100 mg) or doxazosin (16 patients, mean daily dose 9 mg). Casual and 24-h ambulatory blood pressure (24hBP) were reduced from 163/95 to 144/83 mm Hg and 152/86 to 145/81 mm Hg, respectively, in the captopril group, and from 160/93 to 145/86 mm Hg and 156/86 to 147/79 mm Hg in the doxazosin group (all P < .05). The achieved 24hBP on treatment was positively associated with pretreatment levels of glycosylated hemoglobin (HbA1c) and plasma atrial natriuretic peptide (r = 0.53 and 0.59, respectively, both P < .01). Albuminuria did not change significantly in either group. Left ventricular hypertrophy was present in 13 patients (7 in the captopril and 6 in the doxazosin group). Left ventricular mass was reduced by an average of 27% and 23%, respectively, in these patients (both P < .01), but did not change significantly in patients without left ventricular hypertrophy. The reduction in left ventricular mass was positively associated with the presence of baseline left ventricular hypertrophy and inversely with dietary sodium intake and achieved casual blood pressure on treatment (R2 = 0.59, P < .001). We conclude that doxazosin and captopril used for 6 months are equally effective in reducing blood pressure and left ventricular hypertrophy in hypertensive type-1 diabetic patients; the antihypertensive effect is closely related to glycemic control; and dietary sodium intake and achieved casual blood pressure after treatment are independent determinants of the reduction in left ventricular mass seen in these patients.

Gastric meal accommodation and symptoms in diabetes. A placebo-controlled study of glyceryl trinitrate.

OBJECTIVE: To study mechanisms behind postprandial symptoms in patients with diabetes mellitus and the effect of nitric oxide (NO) on gastric accommodation and symptoms in these patients. DESIGN: A double-blind, placebo-controlled, randomized trial was designed in 20 patients with type 1 diabetes (10 male and 10 female, aged 35.3 +/- 7.6 years). METHODS: 0.5 mg sublingual glyceryl trinitrate (GTN), a donor of exogenous NO, or placebo was administered 5 min prior to a 500 ml soup meal. Gastric accommodation of the meal was assessed by abdominal ultrasound. Accommodation in proximal stomach was visualized in a sagittal area (Psa) and a frontal diameter (Pfd) and accommodation in distal stomach was visualized in a sagittal area of the antrum (Asa). Symptoms were assessed using visual analogue scales. RESULTS: Psa correlated significantly (r = 0.57, P = 0.015) with perception of fullness 5 min after the meal, whereas Pfd correlated significantly (r = 0.67, P = 0.004) with nausea at 15 and at 25 min after the meal. Asa correlated (r = 0.50, P = 0.05) with pain at 5 min, 10 min (r = 0.50, P = 0.05) and 25 min (r = 0.68, P = 0.007). GTN had no significant effect on Psa or Pfd, but reduced significantly (P = 0.05) Asa (1 3.5 +/- 4.5 cm2 with GTN vs 16.1 +/- 4.3 cm2 with placebo). GTN increased significantly (P = 0.04) the intragastric proximal/distal meal distribution ratio (proximal/distal sagittal area), but had no significant effect on symptom scores. CONCLUSION: In patients with diabetes, a large proximal stomach is associated with perception of fullness and a large antrum is associated with perception of pain after a meal. Sublingual administration of GTN prior to the meal decreases the antral area and improves the intragastric meal distribution, but fails to improve symptoms.

[Primary adrenal cortex insufficiency--a diagnostic challenge]. / Primaer binyrebarksvikt--en diagnostisk utfordring.

Primary adrenocortical insufficiency (Addison's disease) is characterised by weakness, tiredness, fatigue, weight loss, hypotension, hyperpigmentation and a craving for salt. Without treatment lethality is 100%; correctly treated, life expectancy is normal. Addison's disease may appear isolated or as part of a polyendocrine syndrome. Because several of the symptoms are unspecific and develop over the course of several years, many patients are not diagnosed before a life-threatening adrenal crisis develops. Autoimmune destruction of the adrenal cortex is the main cause of adrenocortical failure in the industrialised world. This condition is characterised by circulating autoantibodies against the steroidogenic enzyme 21-hydroxylase. These autoantibodies can now easily be quantified. More unusual causes of adrenocortical failure are tuberculosis, bleeding, metastasis and adrenoleukodystrophy. Using three cases we highlight the clinical, diagnostic and therapeutic aspects of adrenocortical failure.

Gastric meal accommodation studied by ultrasound in diabetes. Relation to vagal tone.

BACKGROUND: Disturbed gastric meal accommodation may cause abdominal symptoms in patients with functional dyspepsia and diabetes mellitus who have poor vagal control of gastric motility. In the present study we aimed to explore the relation between gastric meal accommodation and vagal tone in diabetic patients with vagal neuropathy. METHODS: Twenty patients with diabetes (DM) (insulin-dependent type; 10 men and 10 women, aged 35.3 +/- 7.6 years) and 20 healthy controls (HC) (10 men and 10 women; aged 34.7 +/- 10.7 years) were studied. Proximal gastric size was assessed with ultrasound in a sagittal area and a frontal diameter. Distal gastric (antrum) size was assessed in a sagittal area. Vagal tone was assessed non-invasively by recording of respiratory sinus arrhythmia (RSA) in beats per minute. RESULTS: Proximal sagittal area was significantly (P = 0.03) smaller in DM (18.5 +/- 5.5 cm2) than in HC (22.2 +/- 4.6 cm2). Proximal frontal diameter did not differ significantly (P = 0.60) between DM and HC (5.9 +/- 1.1 cm versus 5.7 +/- 0.8 cm). Antral area, too, did not differ significantly (P = 0.59) between DM and HC (14.5 +/- 4.1 cm2 versus 13.6 +/- 5.8 cm2). Proximal/distal meal distribution ratio, defined as proximal sagittal area/distal sagittal area, was significantly (P = 0.05) smaller in DM (6.8 +/- 0.6) than in HC (9.9 +/- 5.5). Vagal tone was significantly (P = 0.03) lower in DM (4.5 +/- 1.9 beats/min) than in HC (6.3 +/- 2.7 beats/min). Vagal tone tended (r = 0.33, P = 0.06) to correlate with proximal sagittal area in DM and HC pooled. Vagal tone correlated (r = 0.34, P = 0.05) with proximal frontal diameter in DM and HC pooled. A significant negative correlation (r = -0.39, P = 0.03) was observed between vagal tone and antral area in DM and HC pooled. CONCLUSIONS: Patients with diabetes and low vagal tone have an impaired postprandial gastric meal distribution characterized by a small proximal stomach and a small proximal/distal meal distribution ratio.

Plasma total homocysteine levels in hyperthyroid and hypothyroid patients.

We found a higher plasma concentration of total homocysteine (tHcy), an independent risk factor for cardiovascular disease, in patients with hypothyroidism (mean, 16.3 micromol/L; 95% confidence interval [CI], 14.7 to 17.9 micromol/L) than in healthy controls (mean, 10.5 micromol/L; 95% CI, 10.1 to 10.9 micromol/L). The tHcy level of hyperthyroid patients did not differ significantly from that of the controls. Serum creatinine was higher in hypothyroid patients and lower in hyperthyroid patients than in controls, whereas serum folate was higher in hyperthyroid patients compared with the two other groups. In multivariate analysis, these differences did not explain the higher tHcy concentration in hypothyroidism. We confirmed the observation of elevated serum cholesterol in hypothyroidism, which together with the hyperhomocysteinemia may contribute to an accelerated atherogenesis in these patients.

Lower postprandial gastric volume response in diabetic patients with vagal neuropathy.

UNLABELLED: Poor relaxation in the stomach after a meal may contribute to disturbed gastric emptying and abdominal discomfort in patients with diabetes mellitus. In this study we aimed to compare barostat-recorded postprandial volume responses in these patients to those in healthy controls, and to study the relationship between the proximal volume responses, antral filling and vagal neuropathy. We compared 14 consecutively recruited patients with type 1 diabetes mellitus (DM) to 18 healthy controls (HC) with respect to meal-induced gastric volume response assessed by a barostat, antral area recorded by ultrasound, and vagal tone assessed by respiratory sinus arrhythmia (RSA). Meal-induced volume response of the proximal stomach (area under time-volume curve 0-30 min) was significantly (P = 0.04) lower in DM than in HC, 49.4 min.mL +/- 60.7 vs. 114.9 min.mL +/- 100.8. Antral area was significantly larger in DM than in HC, both fasting (4.3 cm2 +/- 1.9 vs. 3.0 cm2 +/- 0.9) and 10 min after ingestion of meat soup (11.8 cm2 +/- 3.4 vs. 8.8 cm2 +/- 2.9), P = 0.03 and P = 0.02, respectively. Vagal tone was significantly (P = 0.01) lower in DM than in HC. 3.7 beats min-1 +/- 2.3 vs. 6.1 beats min-1 +/- 2.2. No significant correlation was observed between the proximal volume responses and antral widening. Maximal gastric volume response correlated significantly with vagal tone (r = 0.77, P = 0.002). CONCLUSIONS: patients with diabetes mellitus type 1 have impaired meal-induced volume response, possibly as a consequence of reduced vagal tone.

Thyroid antibodies in northern Norway: prevalence, persistence and relevance.

OBJECTIVES: To investigate the prevalence and persistence of thyroid autoantibodies in a population sample and to assess the development of biochemical hypothyroidism (defined as an elevated serum thyrotropin [TSH] concentration) in relation to their presence. DESIGN AND SETTING: A cross-sectional and longitudinal study based on the Tromsø Study in 1979-80 and 1986-87. SUBJECTS AND MAIN OUTCOME MEASURES: From 2551 random participants in 1979-80 aged 34 +/- 8.4 (mean +/- SD) years, sera were available in 2513 and 2504 persons for determination by passive haemagglutination of the antibody to thyroid microsomal antigen (anti-Tm) and of the antibody to thyroglobulin (anti-Tg). Total thyroxine (TT4) and TSH were measured in 114 of 176 antibody-positive subjects and in 101 controls. After 7 years, anti-Tm and anti-Tg were remeasured in 1939 and 1931 subjects, and TT4 and TSH in 92 of the initially antibody-positive subjects and in 69 controls. RESULTS: Anti-Tm occurred more frequently than anti-Tg (in 6.1 vs. 2.8%; P < 0.001). Anti-Tm (P < 0.001) and anti-Tg (P = 0.027) were both more common in women than in men. The prevalence of anti-Tm (P = 0.025), but not of anti-Tg, increased with age. Changes in titre levels after 7 years were mostly small or moderate. Both in women (P = 0.005) and in men (P < 0.001) the TSH concentrations increased with increasing levels of anti-Tm, whereas in men, the concentrations also increased with increasing anti-Tg levels (P < 0.001). Biochemical hypothyroidism developed with a 2.7% yearly incidence only in antibody-positive subjects, all except one of whom had anti-Tm. CONCLUSIONS: The prevalences of thyroid antibodies were comparable to those found in similar studies in other areas. Their presence was associated with the development of biochemical hypothyroidism.

Wide gastric antrum and low vagal tone in patients with diabetes mellitus type 1 compared to patients with functional dyspepsia and healthy individuals.

Autonomous neuropathy in patients with diabetes is associated with dysmotility and abdominal discomfort. The disturbances resemble to some extent those seen in patients with functional dyspepsia. To gain further insight into the disorders, we compared patients with long-standing diabetes, patients with functional dyspepsia, and healthy individuals with respect to abdominal symptoms, width of gastric antral area, and autonomic nerve function. We investigated 42 type I diabetic outpatients by structured interview for abdominal discomfort, ultrasonography of the gastric antrum, assessment of vagal and sympathetic nerve function by respiratory sinus arrhythmia and skin conductance, and measurement of blood sugar and HbA1c. Immediately after a standard meal of soup with meat, 21 (50%) of the 42 patients with diabetes complained of abdominal discomfort (pain, bloating, fullness), which was significantly less frequent (95% CI of difference 0.03-0.5) than previously seen in patients with functional dyspepsia (76%), and significantly more frequent (95% CI of difference 0.3-0.6) than that seen in healthy individuals (4%). Bloating was the most marked postprandial complaint. Mean fasting antral area was significantly wider in patients with diabetes (mean 4.9 cm2, SD 1.7) compared to healthy individuals (mean 3.5 cm2, SD 1.2), 95% CI of difference 0.6-2.2 cm2. Mean postprandial antral area was 14.8 cm2 (SD 4.6) in the patients with diabetes, which is insignificantly wider than in patients with functional dyspepsia (mean 13.0 cm2, SD 4.0) but significantly wider (95% CI of difference 1.9-6.5 cm2) than that seen in healthy individuals (mean 10.6 cm2, SD 3.8). The mean respiratory sinus arrhythmia was 0.7 beats/min (SD 0.7) in the patients with diabetes, which was insignificantly lower than that seen in patients with functional dyspepsia (2.1 beats/min, SD 4.5), and significantly lower (99% CI of difference 3.8-7.1 beats/min) compared to healthy individuals (6.2 beats/min, SD 3.8). It is concluded that patients with diabetes have a wider gastric antrum and more discomfort after a meal than healthy individuals. Compared to patients with functional dyspepsia, patients with diabetes have a wider postprandial antrum but fewer symptoms. The very low vagal tone seen in patients with diabetes may play an important role in the pathogenesis of their gastric motility disturbance and postprandial abdominal discomfort.

[Osteoporosis drugs prescribed on blue forms!]. / Osteoporosemedikamenter på blåresept!

The National Insurance Administration, through the system of blue prescription forms, refunds part of the cost of drugs used to treat a number of chronic diseases. To obtain a refund, the indication for prescribing the drug must be included in the list of diagnoses which entitle a refund through the system. The list is a long one, and costs are refunded for prophylactic drugs (e.g. against hypertension and hypercholesterolemia), drugs to alleviate symptoms (e.g. for certain skin diseases and heart failure) and curative measures. The qualitative criteria for a refund, over and above the diagnosis, are not precisely defined, and doctors are free to choose the drug they prefer, regardless of price. The authors discuss whether the list of diagnoses should be extended to include osteoporosis, and recommend that doctors should be able to prescribe the relevant preventive and palliative drugs on a blue form. Many think that this refund system is a good initiative.

Tumour volume reduction following gamma knife radiosurgery: the relationship between X-ray and histological findings.

The case histories of two young ladies with Cushing's disease are described. Both patients were treated first with Gamma Knife radiosurgery and subsequently by microsurgery. The radiosurgery caused a marked reduction in tumour volume but only a partial relief of the endocrinopathy. Comparison of the histological findings with the radiological findings following radiosurgery indicates that confluent necrosis is not a prerequisite for a reduction in tumour volume. It seems more likely that the reduction in tumour volume is related to changes in cellular dynamics.

[Rapid calcium infusion in the diagnosis of hypoglycemia]. / Hurtig kalsiuminfusjon ved utredning av hypoglykemi.

The diagnosis of beta cell tumours of the pancreas is a clinical problem. It is also difficult to exclude this diagnosis in patients who are suspected of suffering from recurrent hypoglycemia, but do not have beta cell tumours. The most widely used diagnostic procedure has been suppression of endogenous insulin production with prolonged fasting up to 72 hours. This procedure is troublesome to the patient, time-consuming and expensive, and demands the complete cooperation of the patient. Therefore several diagnostic tests have been developed, but none has been generally accepted. A newly described test involving calcium infusion, 2 mg/kg in one minute, seems to give a diagnostic response in most patients with insulinomas, few false positive results and few side effects. We have used this test for four years and found it safe and easy to perform. It has given diagnostic response in three patients with insulinomas and no false positive results in 27 other patients.

[Extreme disorders of acid-base and electrolyte balance. Diagnosis and treatment illustrated by two cases]. / Ekstreme forstyrrelser i syre-base- og elektrolyttbalansen. Diagnostikk og behandling illustrert ved to pasienteksempler.

There are multiple causes of acid-base disturbances. We report on two patients with serious imbalance in electrolyte- and acid-base status. Both patients were conscious on admission. According to the literature, this was unexpected. The article focuses on the importance of relating electrolyte- and acid-base disturbances.

Chemotherapy and endocrine function in lung cancer.

To investigate whether cyclic chemotherapy for lung cancer influenced endocrine function, we monitored thyroxine, cortisol, testosterone, sex hormone binding globulin (SHBG), estradiol, FSH, LH, and transcortin every three weeks in 12 male patients. Treatment regimens consisted of cisplatin and etoposide in 9 patients, or vincristine, doxorubicin, and cyclophosphamide in 3 patients. SHBG and FSH level were significantly elevated after 6 to 9 weeks of therapy, whereas the other variables were unchanged. The results suggest that the therapy induces endocrine gonadal dysfunction. The increments in SHBG levels reflect a considerable fall in free testosterone, and may effect alterations in total androgen/estrogen ratios. The mechanism underlying the increased SHBG levels is unknown.

ACTH deficiency, hyperprolactinemia and benign intracranial hypertension. A case report.

A 26-year-old female with ACTH deficiency, hyperprolactinemia and benign intracranial hypertension is reported. Her symptoms of adrenocortical insufficiency and persistent amenorrhea appeared after her last child birth one year previously. During an infectious disease she became critically ill with hypotension and was treated with iv penicillin. A bacterial infection was, however, not diagnosed. After 4 days she developed symptoms and signs of intracranial hypertension. She improved gradually within 10 days without specific therapy against the intracranial pressure. Endocrine investigation disclosed a secondary adrenocortical failure. The lesion appeared to be located in the pituitary gland since plasma ACTH and cortisol did not respond to CRH. A moderately elevated serum PRL was found, whereas the pituitary reserves of TSH, GH, LH and FSH were normal, as was a computed tomographic scan of the pituitary gland. The patient was given cortisone substitution therapy and recovered immediately. Within the following year she regained normal menstruations and became pregnant. A possible autoimmune etiology of her isolated ACTH deficiency precipitated in the puerperium is discussed.

Effect of different beta-blocking drugs and adrenaline on the conversion of thyroxine to triiodothyronine in isolated rat hepatocytes.

The in vitro effect of various selective and non-selective beta-blocking drugs and adrenaline on the conversion of thyroxine (T4) to triiodothyronine (T3) was studied in suspensions of isolated rat hepatocytes after 90 min of incubation. Compared with the untreated controls propranolol caused a dose-related inhibition of the T4 to T3 conversion in conc of 100, 200 and 400 microM. The other beta-blocking drugs studied, timolol, oxprenolol, atenolol and metoprolol, were without any effect on this in vitro conversion. Propranolol did not interfere with the cellular association of T4 or the degradation of T4 and T3. Adrenaline 200 microM caused a small decrease of T3 in the medium and a corresponding increase in the intracellular content of T3. The inhibitory effect of propranolol 200 microM was not antagonized by equimolar concentrations of adrenaline. Our study suggests that the inhibitory effect of propranolol on the conversion of T4 to T3 in hepatocytes is caused by a direct chemical effect of the drug unrelated to its beta-blocking and membrane stabilizing properties.

Influence of glucose, insulin and sera from diabetic patients on the prostacyclin synthesis in vitro in cultured human endothelial cells.

The effects of glucose, insulin and sera from Type 1 (insulin-dependent) diabetic patients on the synthesis of prostacyclin in vitro were studied in confluent primary cultures of human endothelial cells. The stable metabolite, 6-keto-prostaglandin F1 alpha, was measured in growth medium after 24 h of incubation with endothelial cells in a buffer incubated with the cells for 10 min on a rocker platform, and in a buffer solution of ruptured cells. Glucose (11, 15, 20 or 25 mmol/l) and glucose (11 mmol/l) plus insulin (10(3), 10(4) or 10(6) mU/l) in growth medium did not have any effects on the prostacyclin synthesis. The prostacyclin synthesis was significantly reduced in cell cultures incubated with medium supplemented with 10% serum from patients with Type 1 diabetes (p less than 0.01) compared with cultures incubated with pooled serum from healthy blood donors. These data suggest that diabetic sera inhibit the prostacyclin synthesis in cultured endothelial cells unrelated to the glucose and insulin levels.