Gudmar Lundqvist

PANCREATIC SOMATOSTATINOMA: Clinical Features and Physiological Implications

The first case of a tumour producing somatostatin-like immunoreactivity and bioactivity is presented. The pancreatic tumour was composed of cells indistinguishable from islet D cells. Radioimmunoassay of blood-samples obtained by tumour-vein catheterisation revealed very high levels of somatostatin immunoreactivity. On gel chromatography tumour extracts were found to contain at least 4 different immunoreactive components, one of which eluted in the position of synthetic somatostatin. Extracts from the tumour were potent in inhibiting insulin and glucagon secretion from isolated perfused porcine pancreas. Clinical abnormalities included hypochlorhydria, steatorrhoea, and diabetic glucose tolerance. Conceivably some of these abnormalities may be related to somatostatin hypersecretion from the pancreatic tumour.

Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival.

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotropin % levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.

Medical Treatment and Long-term Survival in a Prospective Study of 84 Patients With Endocrine Pancreatic Tumors

A prospective study was performed on 84 patients with neuroendocrine pancreatic tumors. Fifty‐nine (70%) had malignant tumors and received causal medical treatment. Streptozotocin in combination with 5‐fluorouracil or doxorubicin was used as first‐line treatment and produced overall objective responses in 20 of 44 (45%) patients with a median duration of response of 27.5 months. Thirty‐two patients who failed on chemotherapy subsequently received interferon treatment and 20 (63%) responded objectively with a median duration of 20.5 months. Octreotide, third‐line treatment in 14 patients, produced objective responses in four patients (28%) (median duration of response, 16 months). The median survival from diagnosis in malignant cases was 6.7 years. Even if none of the current medical therapies are curative for patients with malignant endocrine pancreatic tumors, a prolonged survival would be observed during the last decade. Since the age at diagnosis has not been dramatically reduced despite improvements in diagnostic methods, the prolonged survival might be attributed to causal medical treatment. Cancer 65:1883‐1890, 1990.

Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy.

Abstract. Twenty‐one patients with increased, thyroid‐stimulating‐hormone (TSH) concentrations in the serum while fasting were studied before and after substitution with l‐thyroxine. Nine patients had TSH values < 40 mU/1 and an average serum‐thyroxine value of 64 nmol/1. Twelve patients with TSH‐values > 40 mU/1 had an average serum‐thyroxine value of 23 nmol/1. On treatment TSH and thyroxine normalized (reference limits < 8 mU/1 and 65–160 nmol/1 respectively) as did also the response to a load with thyroid‐releasing hormone (TRH).

Lipoprotein-lipase activity in human skeletal muscle and adipose tissue in the fasting and the fed states☆

Sixteen healthy subjects, 7 females and 9 males, with a mean age of 25 years (range 22--29 years), were studied in the fasting state in the morning and 8 h later after partaking of breakfast, lunch and two small meals. The lipoprotein-lipase activity in the adipose tissue increased significantly from 80 +/- 32 to 117 +/- 61 nmol fatty acid released per gram and minute (nmol FA/g/min), whereas in skeletal-muscle tissue it decreased significantly from 25 +/- 11 to 17 +/- 9 nmol FA/g/min. The concentration of serum triglycerides increased significantly from 0.93 +/- 0.18 mmol/l (mean +/- SD) in the fasting state to 1.57 +/- 0.64 mmol/l in the fed state. In the fasting state the lipoprotein-lipase activity of skeletal muscle was inversely related to the ratio between the concentrations of insulin and glucagon.

Impaired glucose handling in active rheumatoid arthritis: Relationship to the secretion of insulin and counter-regulatory hormones

An intravenous glucose tolerance test was performed in 45 untreated patients with active inflammatory rheumatoid arthritis and in age- and sex-matched healthy subjects. The mean k value in the patients, which correlated to the inflammatory activity, was 1.0 +/- 0.05 (SEM), which was significantly lower (P less than .001) than in the controls (1.8 +/- 0.09). The basal serum insulin concentration and the maximum insulin response to glucose loading were significantly higher (P less than .001 and P less than .01, respectively) in the patient group. The patients had a normal basal concentration of growth hormone in the serum, but during glucose infusion the concentration increased. The plasma glucagon level was significantly lower than in the controls (P less than .001). The urinary output of cortisol and catecholamines was normal. It is concluded that impaired glucose handling in active chronic inflammatory disease cannot be explained as a stress reaction but may be due to peripheral insulin resistance mediated by the inflammatory process. A paradoxical increase in growth hormone secretion during glucose infusion may suggest that this hormone is one factor that influences glucose handling in chronic inflammation. The pathophysiologic relevance of altered glucose metabolism and enhanced insulin secretion is uncertain but may reflect a possible link with the proposedly increased risk of atherosclerotic cardiovascular disease in rheumatoid arthritis.

Increase of the lipoprotein‐lipase activity in human skeletal muscle during clof ibrate administration

Abstract. Lipoprotein‐lipase activity was determined in tissue from the skeletal muscle of the leg and the subcutaneous adipose tissue of the abdomen in fourteen patients before and after 1 month of clofibrate administration. The concentrations of serum triglycerides decreased by, on the average, 37% in a group of thirteen patients which mainly consisted of subjects with type‐IV hyperlipoproteinaemia. Clofibrate administration was associated with an average increase of the skeletal muscle‐tissue lipoprotein‐lipase activity of 50% (P< 0.005). There was a significant correlation between the percentage changes in skeletal muscle‐tissue lipoprotein‐lipase activity and those of the triglycerides concentrations and the K2‐values in an intravenous fat tolerance test during clofibrate treatment. Adipose‐tissue lipoprotein‐lipase activity did not change significantly. One patient with type‐I hyperlipoproteinaemia had very low values of skeletal muscle‐tissue lipoprotein‐lipase activity and moderately low adipose‐tissue lipoprotein‐lipase activity. In this patient, neither the tissue lipoprotein‐lipase activity nor the triglycerides concentration changed during clofibrate therapy. Fasting serum insulin concentrations decreased significantly during clofibrate administration and the percentage decrease was significantly correlated to the percentage increase of skeletal‐muscle lipoprotein‐lipase activity. It is suggested that the lowering of insulin levels is a possible mechanism through which glucagon activity is enhanced and this may increase skeletal muscle‐tissue lipoprotein‐lipase activity.

Impaired glucose handling in active rheumatoid arthritis: Effects of corticosteroids and antirheumatic treatment☆

Forty-two patients with active rheumatoid arthritis were studied serially with respect to glucose metabolism after the institution of different anti-inflammatory and antirheumatic therapies. Sixteen patients received 20 mg of prednisolone daily. After 1 week of treatment the mean k value in glucose tolerance tests increased from 1.0 +/- 0.1 (SEM) to 1.6 +/- 0.1 (P less than .001). The corticosteroid therapy thus restored the glucose tolerance to normal and significantly enhanced the insulin response (P less than .01). Corticosteroids also normalized the growth hormone response to glucose infusion but had no effect on plasma glucagon. Treatment with nonsteroidal anti-inflammatory drugs did not affect the k values nor the hormonal pattern either after short-term treatment or after three months of therapy, except for causing a minor increase in the plasma glucagon levels both before and after glucose infusion. The long-term effects of treatment with penicillamine (n = 4), chloroquine (n = 7), and immunosuppressive agents [corticosteroids combined with azathioprine or cyclophosphamide (n = 7)], were an improvement of the clinical state, a reduction of the inflammatory activity, and a reversal of the glucose handling to normal.

Serum gastrin determination with a radioimmunosorbent technique

A low utilization of antiserum has been reported in gastrin radioimmunoassay with a solid-phase procedure. As solid-phase immunoassays possess several advantages over their soluble counterparts for the assay of many hormones, a solid-phase radioimmunoassay for gastrin was examined. The results showed that this technique was suitable for gastrin determination without being wasteful to antibodies. Sensitivity and precision of the method were comparable to other investigations on gastrin immunoassay, as well as serum gastrin levels obtained for persons with no known gastro-intestinal disease, in patients with pernicious anemia and in patients with Zollinger-Ellison syndrome.

Islet structure and pancreatic hormone content of the developing chick embryo

Abstract Both the pancreatic content of insulin, glucagon, and somatostatin and the endocrine pancreatic morphology were studied at daily intervals in the pancreases of chick embryos aged 7 to 16 days. All three hormones were present in the 7-day-old embryos. The content of somatostatin and insulin remained low up to the thirteenth day of incubation when the accumulation rate of both these hormones considerably increased. Glucagon, however, exhibited an early rapid accumulation in the pancreas. Administration of exogenous glucagon caused a transitory delay of pancreatic glucagon accumulation whereas insulin accumulation was enhanced. Insulin injections caused severe malformations of the embryo and a grossly abnormal pancreatic morphology in about one-fifth of the embryos. Insulin-injected, but otherwise normal embryos showed a temporary delay in glucagon accumulation and a markedly reduced insulin accumulation throughout the period studied. The observations suggest that hormones of the endocrine pancreas may be involved in the metabolic regulation of the chick embryo at early stages of development.