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Objective: To clarify whether random C-peptide is a valuable test in the classification of diabetes.Research Design and Methods: All C-peptide measurements conducted in the diabetic population of Skaraborg (280,539 inhabitants and 3.2% diabetes) between 1995 and 1998 (3,115 samples) were considered, but only patients with well-defined diabetes type (1,449 samples from 1,093 patients) were analyzed for the correlation between diabetes type and C-peptide concentration. Serum C-peptide was measured after fasting over night (fCP), after glucagon stimulation (gCP), and randomly (rCP) without considering previous meals at an ordinary visit to the diabetic clinic (rCP). Receiver Operating Characteristic (ROC) curves were constructed to illustrate the power of the different C-peptide protocols and to determine the optimal cut-off values.Results: Although all three tests had high discriminative power, the ROC curves demonstrated that rCP was superior to fCP and gCP in discriminating type 1 from type 2 diabetes. The optimal cut-off value for rCP was 0.50 nmol/L, for fCP 0.42 nmol/L, and for gCP 0.60 nmol/L.Conclusions: rCP is more powerful than fCP and gCP in distinguishing type 1 from type 2 diabetes and can therefore be recommended as a classification tool, particularly in outpatients. [ABSTRACT FROM AUTHOR]

A 39-year-old woman had suffered from congestive heart failure of unknown cause for 3.5 years before a phaeochromocytoma was diagnosed. After pretreatment with phenoxybenzamine, the tumour was removed by surgery resulting in disappearance of signs of heart disease. The patient was followed for 16 years: at that time she was free of symptoms and X-ray and echocardiography showed only a slightly enlarged heart and a minor impairment of left ventricular performance. Six similar cases from the literature are reviewed. The significance of catecholamines in causing heart disease in patients with phaeochromocytoma is discussed. [ABSTRACT FROM PUBLISHER]

Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune beta-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of beta-cell function show that LADA patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even though it may take up to 12 years until beta-cell failure occurs in some patients, impairments in the beta-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive beta-cell failure might be a more adequate concept. In agreement with proved impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of choice.

In 1993-1996, islet autoantibodies, C-peptide, and HLA-DQ genotypes were evaluated in 345 insulin-treated diabetic patients of all ages from the Skaraborg Diabetes Registry 5-6 years after their diagnosis and in 216 control subjects from the Skaraborg County, Sweden, population. The aims of this study were to clarify the importance of age at diagnosis of diabetes for HLA-DQ associations in patients with classic type 1 diabetes and whether patients considered to have latent autoimmune diabetes of the adult differed in their human leukocyte antigen (HLA) associations. An abnormally low fasting C-peptide value was used as the definition of type 1 diabetes, found in 182 of 345 (53%) patients. No major associations between age at diagnosis and HLA susceptibility or protective genotypes were detected in type 1 diabetic patients. Among the 163 patients with preserved beta-cell function, the frequency of HLA protective genotypes was clearly decreased (5% vs. 42%) in the 46 of 163 with islet antibodies compared with the 117 of 163 antibody-negative patients. The authors conclude that there were no major effects of age at diagnosis on HLA-DQ associations in classic type 1 diabetic patients, whereas lack of HLA-DQ protective genotypes was a feature of patients with slow-progressing type 1 diabetes (latent autoimmune diabetes of the adult).

Objective: Our objective was to analyze the prevalence, incidence, and mortality of diabetes in a population of 280,539 inhabitants., Research Design and Methods: The incidence, prevalence, and deaths from diabetes at all ages of a population have been prospectively followed in the county of Skaraborg, Sweden, since 1991., Results: The annual incidence of diabetes per 100,000 inhabitants in 1991-1995 was (mean +/- 95% CI) 14.7 +/- 3.2 for type 1 diabetes (diagnosed at 24.1 +/- 2.2 years of age) and 265.6 +/- 16.1 for type 2 diabetes (diagnosed at 66.6 +/- 0.6 years of age). The incidence of type 2 diabetes was significantly (P < 0.001) higher among men. There was no significant change in the age at diagnosis of diabetes. Although the incidence rate and the age at diagnosis were constant, the prevalence of diabetes increased by 6% each year. The relative mortality risk for diabetic patients was almost four times higher than expected. The median age at death, however, increased significantly, from 77.2 to 80.2 years (P < 0.05), during the study., Conclusions: The prevalence but not the incidence rate of diabetes increased during the years 1991-1995. Although diabetic patients showed a high relative mortality, increased survival apparently explains the increase in prevalence of diabetes in the country of Skaraborg.

The aim of this investigation was to study the effect of beta-adrenoceptor blockade on alterations in protein metabolism induced by administration of 3,5,3'-triiodothyronine (T3) to man. Urinary excretion of 3-methylhistidine and plasma concentrations of amino acids were measured in seven healthy subjects following 1 weeks's administration of T3 alone or T3 in combination with the selective beta 1-adrenoceptor blocking agent metoprolol or the non-selective beta-adrenoceptor blocking agent propranolol. Urinary excretion of 3-methylhistidine and plasma concentrations of valine, methionine, lysine, tyrosine, phenylalanine, isoleucine, leucine, and total essential and branched chain amino acids increased following administration of T3, probably in part reflecting accelerated muscle proteolysis. Neither metoprolol nor propranolol normalized 3-methylhistidine excretion or plasma concentrations of amino acids during T3 treatment. The results indicate that metabolic alterations induced by T3 and giving rise to enhanced 3-methylhistidine excretion and elevated concentrations of plasma amino acids are not normalized by beta-adrenoceptor blockade.

Myelolipoma of the adrenal gland is a benign tumour composed of fat and haematopoietic cells. It is usually asymptomatic and discovered as an incidental finding at autopsy. Only twenty-five patients have previously been described in whom an adrenal myelolipoma had been removed surgically. The patient reported in this paper had a myelolipoma in his left adrenal gland. The tumour was diagnosed by intravenous pyelography, ultrasonography, arteriography and computed tomography. No endocrine symptoms were present and hormonal analyses were normal. Surgical excision of the tumour was performed with an uneventful postoperative course. The diagnosis should be considered in patients with a suprarenal mass manifesting features that are atypical of other tumours of this region.

Sixty-four patients with pheochromocytoma were operated upon at Sahlgrenska Hospital during 1956-82. The excretion of adrenaline and/or noradrenaline as well as their metabolites was high at each observation in 28 subjects with sustained hypertension, one patient, however, showing only slightly increased excretion of adrenaline at one observation. Another of the hypertensive patients consistently displayed normal amounts of vanilmandelic acid and metanephrines. Most of 28 patients with paroxysmal hypertension showed similar results. In five subjects with few attacks, however, normal findings were obtained on one or several occasions. Among the remaining patients the excretion of catecholamines was normal in the face of severe hypertension in two, the high blood pressure being probably due to diseases other than pheochromocytoma. Five normotensive subjects without hypertensive attacks presented variable findings. The results from analyses of catecholamines were somewhat more helpful than those from measurements of vanilmandelic acid, which failed completely in one hypertensive patient and in three others with paroxysmal attacks.

In a series of 53 pheochromocytoma patients operated on at Sahlgren's Hospital during 1956-82, a positive linear correlation is established between the 24-hour urinary excretion of vanilmandelic acid (mumol/24 h) and tumour mass (g). A similar correlation was found between the excretion of metanephrines and tumour mass in 33 subjects. The patients were subgrouped according to their type of hypertension. A statistically significant correlation between vanilmandelic acid excretion and tumour mass persisted in groups IA (sustained hypertension without attacks), IB (sustained hypertension with attacks), and II (paroxysmal hypertension) but not in group III (miscellaneous patients). There was also a correlation between metanephrine excretion and tumour mass in groups IB (n = 8) and II (n = 12). In 10 patients with the syndrome of multiple endocrine neoplasia, a positive correlation was found between tumour mass and the excretion of vanilmandelic acid, metanephrines and adrenaline.

Seventeen patients with insulin-dependent diabetes mellitus, all below the age of 45 years, were studied. Five of them had retinopathy but no other micro- or macrovascular diabetic complications. None of them had any other concurrent disorder or were on any medication but insulin. The results were compared to those of 17 healthy volunteers of comparable age. There was no difference between the two groups in venous platelet counts, serum production of thromboxane B2 (TXB2), ADP-induced platelet aggregation or bleeding times. As compared to the controls, the diabetics had significantly elevated blood glucose and glycosylated hemoglobin values. The mean plasma values of beta-thromboglobulin, platelet factor 4 and TXB2 were significantly lower in the patients than in the controls. Thus, our results do not lend support to the current concept that platelet reactivity is enhanced in diabetes mellitus.

Total blood volume (TBV), red cell volume (RCV) and plasma volume (PV) were determined in 15 pheochromocytoma patients (9 males and 6 females) prior to and during preoperative treatment with phenoxybenzamine. Seventeen healthy male volunteers served as controls. Untreated male patients did not differ from the controls with respect to TBV, RCV or PV. In the total group of pheochromocytoma patients, phenoxybenzamine, in a dose of 145.6 +/- 45.2 (SD) mg/day over 14.3 +/- 5.7 (SD) days, induced significant increases in TBV (+9.4%) and PV (+14.5%), whereas RCV remained unchanged. During phenoxybenzamine, the mean PV in male patients significantly exceeded the control mean. We conclude that pheochromocytoma patients adapt their TBV to excessive catecholamine production and that they rarely present with profound hypovolemia. Moderate but higher doses of phenoxybenzamine than previously recommended induced marked increases in TBV secondary to PV expansion. Phenoxybenzamine counteracts the development of hypovolemia most effectively, thereby constituting one of several important measures for successful surgical management of pheochromocytoma patients.

Despite the increasing use of beta-blocking agents alone as preoperative treatment of patients with hyperthyroidism, there are no controlled clinical studies in which this regimen has been compared with a more conventional preoperative treatment. Thirty patients with newly diagnosed and untreated hyperthyroidism were randomized to preoperative treatment with methimazole in combination with thyroxine (Group I) or the beta 1-blocking agent metoprolol (Group II). Metoprolol was used since it has been demonstrated that the beneficial effect of beta-blockade in hyperthyroidism is mainly due to beta 1-blockade. The preoperative, intraoperative, and postoperative courses in the two groups were compared, and patients were followed up for 1 year after thyroidectomy. At the time of diagnosis, serum concentration of triiodothyronine (T3) was 6.1 +/- 0.59 nmol/L in Group I and 5.7 +/- 0.66 nmol/L in Group II (reference interval 1.5-3.0 nmol/L). Clinical improvement during preoperative treatment was similar in the two groups of patients, but serum T3 was normalized only in Group I. The median length of preoperative treatment was 12 weeks in Group I and 5 weeks in Group II (p less than 0.01). There were no serious adverse effects of the drugs during preoperative preparation in either treatment group. Operating time, consistency and vascularity of the thyroid gland, and intraoperative blood loss were similar in the two groups. No anesthesiologic or cardiovascular complications occurred during operation in either group. One patient in Group I (7%) and three patients in Group II (20%) had clinical signs of hyperthyroid function during the first postoperative day. These symptoms were abolished by the administration of small doses of metoprolol, and no case of thyroid storm occurred. Postoperative hypocalcemia or recurrent laryngeal nerve paralysis did not occur in either group. During the first postoperative year, hypothyroidism developed in two patients in Group I (13%) and in six patients in Group II (40%). No patient had recurrent hyperthyroidism. The results suggest that metoprolol can be used as sole preoperative treatment of patients with hyperthyroidism without serious intra- or postoperative complications. Although the data indicate that the risk of postoperative hypothyroidism is higher after preoperative treatment with metoprolol than with an antithyroid drug, a longer follow-up period than 1 year is needed to draw conclusions regarding late results.

During the years 1956-1982, 64 pheochromocytoma patients were operated upon without mortality. Twenty-eight patients had sustained hypertension and 29 paroxysmal hypertension only. In two patients high blood pressure was not related to pheochromocytoma and five subjects were normotensive. In two women the pheochromocytoma demonstrated malignancy by widespread metastases. Sixteen patients also had neuroectodermal manifestations other than pheochromocytoma. Preoperatively, heart disease was found in most of the hypertensive patients aged 50 years or more at operation, but was uncommon in the others. In these subjects, heart disease persisted after surgery. Young subjects with sustained hypertension were not less affected by preoperative cerebrovascular accidents than older subjects. After surgery, hypertension persisted in 12 patients, and was easily controlled by drug therapy in eight. Nine patients died 7 months-18 years after surgery. In no case was the death directly associated with the pheochromocytoma disease. Three died from other neuroectodermal abnormalities. The 55 surviving patients have been followed up for a mean of 12 years after surgery. During the observation time the survival of the pheochromocytoma patients was similar to that of the normal population. At the end of the study, 44 out of the 55 surviving patients were free from symptoms.

An epidemiological study of 439 cases (184 males, 255 females) of pheochromocytoma (paraganglioma) diagnosed in Sweden from 1958-81 is presented. From the mid 1960's an average of 22 cases have been diagnosed each year. In 255 cases, the pheochromocytoma was diagnosed by clinical examination and/or surgery. In 184 cases (40%), the diagnosis was achieved by autopsy and out of which 60 (14% of all cases) were reported as incidental findings. Ninety-five pheochromocytomas (22%) were located outside the adrenals. The average (+/- SD) age at diagnosis for the total study population was 55.8 +/- 17.7 years. Clinically diagnosed tumour cases were significantly younger (48.5 +/- 16.3 years) compared to cases diagnosed at autopsy (65.8 +/- 14.0). Pheochromocytomas were more common among women than among men. The age specific incidence rate increased continuously for both sexes from the youngest to the oldest age groups. The average incidence of pheochromocytoma in the 24 counties of Sweden was 2.1 cases per million inhabitants per year, range 0.9-5.3. A North to South gradient was noted with a higher incidence in the Southern parts of the country. Whether this is due to a real geographical variation of incidence, to a larger number of unreported cases in the Northern parts, or to presence of families with Sipple's syndrome in the South is unclear.

QRS amplitudes (S1 + R5), Minnesota Code ECG abnormalities and QTc intervals were analyzed in ECGs from 31 pheochromocytoma patients on admission to hospital, after 17 +/- 7.2 (SD) days of preoperative phenoxybenzamine therapy in a dosage of 148 +/- 45.0 (SD) mg/day and after a mean postoperative follow-up of 6 years. QRS voltage decreased significantly from 3.37 +/- 1.48 on admission, to 2.26 +/- 0.69 mV at postoperative follow-up (p less than 0.001). The prevalence of total Minnesota Code changes increased or was unchanged on the different occasions. Severe to moderate changes, however, became less prevalent, while mild changes increased. The QTc interval was 0.44 +/- 0.04 s on admission and 0.41 +/- 0.02 s at follow-up (p less than 0.01). No significant differences were observed during treatment with phenoxybenzamine. Pathological ECGs are common findings in patients with pheochromocytoma and significant improvements occur after surgery. Significant effects of phenoxybenzamine therapy were only found in patients with sustained hypertension.

Three cases of pheochromocytoma diagnosed ante partum are reported. The first woman received phenoxybenzamine for 72 days until operation and the other 2 were given the drug for 2 and 3 days, respectively. Healthy infants were delivered by cesarean section followed by removal of the pheochromocytomas. The 29 cases reported in the literature of pheochromocytoma diagnosed ante partum and treated with alpha-receptor blockade are reviewed with respect to results of treatment. It is concluded that pheochromocytoma diagnosed during the 1st trimester is probably best managed by tumor resection as soon as possible. In order to avoid the risk of abortion during surgery in cases diagnosed in the 2nd trimester, the patient may well be brought to term under adequate treatment with an alpha-receptor blocking agent, when the infant is delivered by cesarean section followed by tumor removal. Third-trimester cases should be managed in the same way.

The aim of this investigation was to compare the effects of a beta 1-selective adrenoceptor blocking agent and an antithyroid drug on urinary excretion of creatinine (Cr) and 3-methylhistidine (3-MH) and plasma concentrations of amino acids in hyperthyroid patients. beta-adrenoceptor blocking agents are increasingly used in the treatment of hyperthyroid patients, and the effects on clinical signs and symptoms mainly reflect beta 1-adrenoceptor blockade. The consequences of this treatment on metabolic alterations in hyperthyroidism are not fully known. In the present study, 30 hyperthyroid patients were randomized to preoperative treatment with the antithyroid drug methimazole + thyroxine (group I) or the beta 1-selective adrenoceptor blocking agent metoprolol (group II). Urinary excretion of Cr and 3-MH and plasma concentrations of amino acids were measured at the time of diagnosis, following preoperative treatment and 6 months postoperatively. Serum triiodothyronine (T3) was comparably elevated in the two groups of patients at the time of diagnosis and was normalized during preoperative treatment in group I but remained elevated during preoperative treatment in group II. Urinary excretion of creatinine was lower at the time of diagnosis than postoperatively, suggesting reduced muscle mass during hyperthyroidism. Urinary excretion of Cr increased during preoperative treatment in group I but was not significantly altered during treatment with metoprolol. The 3-MH/Cr ratio, which was higher at the time of diagnosis than postoperatively, indicating accelerated protein breakdown in skeletal muscle during hyperthyroidism, was reduced during preoperative treatment in group I but not in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty patients undergoing operation for phaeochromocytoma were investigated in the pre- and postoperative states with respect to fasting blood glucose levels. When 6 previously known or suspected diabetics were excluded, preoperative diabetes (fasting blood glucose levels greater than or equal to 7.0 mmol/l) were found in 3 of 13 (23%) with sustained hypertension, in 6 of 12 (50%) with sustained hypertension associated with paroxysms and in 4 of 24 (17%) with paroxysmal hypertension. None of the 5 patients with atypical clinical symptoms had glucose levels greater than or equal to 7.0 mmol/l. In the groups of patients with particularly high urinary excretion of catecholamines and vanilmandelic acid higher blood glucose levels were also found. The postoperative blood glucose levels in the follow-up study were normal and less than 5.8 mmol/l in all cases except in 3 of the 4 still living patients with a previously known diabetes and in 1 patient with a malignant tumour. Thus, manifest diabetes, defined as fasting glucose levels greater than or equal to 7.0 mmol/l, is frequently present in patients with phaeochromocytoma (24% in the present study) and the diabetes is reversed by removal of the tumour.

Protein metabolism in skeletal muscle tissue was studied in three groups of patients undergoing thyroid surgery: group I (n = 8), hyperthyroid patients preoperatively treated with an antithyroid drug and T4; group II (n = 8), hyperthyroid patients preoperatively treated with the beta 1-selective adrenoreceptor blocking agent metoprolol; group III (n = 5), euthyroid patients operated on for nodular goiter or adenoma. The study was prospective and hyperthyroid patients were randomly allocated to one of the two preoperative regimens. During operation a biopsy was taken from the sternohyoid muscle and rates of protein synthesis and degradation were measured in incubated muscle tissue. Clinical improvement was equal in the two groups of hyperthyroid patients during preoperative treatment but serum T3 concentrations remained elevated in patients treated with metoprolol. Thus, these patients were biochemically hyperthyroid at the time of operation. The rate of protein degradation was significantly higher in hyperthyroid patients treated with metoprolol than in patients of groups I and III. A significant positive correlation was found between serum T3 and rate of protein degradation in skeletal muscle. Protein synthesis rates were similar in the three groups of patients. This study demonstrated for the first time increased proteolysis in skeletal muscle tissue from patients with high serum T3 concentrations. The results indicate that changes of skeletal muscle protein metabolism in hyperthyroid patients are not normalized by beta 1-blockade despite the fact that this treatment effectively controlled symptoms and signs of hyperthyroidism.