Leif Wide

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.

Inhibition of ovulation in women by chronic treatment with a stimulatory lrh analogue — A new approach to birth control?

A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5 microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular menuration and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.

The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women

OBJECTIVE To investigate the basal levels of gonadotrophins and sex steroids, with special reference to the effects of obesity and body fat distribution, In premenopausal women, both those with polycystic ovary syndrome (PCOS) and those with normal ovaries and regular menstrual cycles.

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.

Radioimmunosorbent assay for proteins. Chemical couplings of antibodies to insoluble dextran

Abstract The use of immunosorbents for radioimmunoassays of proteins and polypeptides has considerably simplified these methods. The immunosorbents were prepared by chemical coupling of antibodies to derivatives of insoluble dextran (Sephadex). Four coupling methods were compared: three cyanogen halide methods and one isothiocyanato-method. It was concluded that immunosorbents prepared by CNBr-activation of Sephadex are stable for at least three months, have a high antigen binding capacity, have a very small tendency for nonspecific adsorption, and are easiest to prepare in comparison with the other immunosorbents investigated. This method is recommended for the preparation of immunosorbents to be used in the radioimmunosorbent assay system.

Hypocalcemia and parathyroid hormone secretion in critically ill patients.

Objective: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. Design: Combined cross‐sectional and prospective study. Setting: ICU in a university hospital. Patients: Thirteen patients with sepsis and 13 patients who underwent major surgery. Interventions: None. Measurements and Main Results: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean ± SD, 1.03 ± 0.08 mmol/L; reference value, 1.10‐1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy‐terminal cross‐linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394 ± 536 pg/mL for tumor necrosis factor‐α and 5676 ± 5190 pg/mL for interleukin‐6, both normally <10‐20). The Ca2+ concentration was inversely related to tumor necrosis factor‐α and interleukin‐6 (r2 = .35 − .42; p < .01), as well as to procalcitonin (r2 = .71; p < .01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p < .05), when compared with matched healthy controls. Conclusion: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

VARIATION IN LH AND FSH RESPONSE TO LH-RELEASING HORMONE DURING THE MENSTRUAL CYCLE

Synthetic luteinizing hormone‐releasing hormone (LRH) was injected intravenously in a dose of 100 μg. to test the capacity of the pituitary to respond to LRH with a release of luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) in 16 healthy regularly menstruating women. A total of 28 LRH tests were performed during different stages of the menstrual cycle. Venous blood was obtained before and at frequent intervals during the first two hours after the LRH injection and assayed for LH, FSH and in five tests also for thyrotrophic (TSH) and growth hormone (GH). No consistent change of TSH or GH was observed after LRH. In all the 28 LRH tests there was a significant increase of LH and in tests also of FSH. The mean LH and FSH increase was 292 and 40 per cent, respectively. The maximum response was usually observed after 30 to 45 minutes. There was a pronounced variation in the response to LRH in the course of the menstrual cycle. During the late follicular phase the average LH response was 4‐ to 6‐fold that obtained in the early and mid‐follicular phase. An increased pituitary responsiveness was also found in the luteal phase. It was suggested that this variation in the response to LRH is due to the changes of the ovarian secretion of oestrogens during the menstrual cycle. In one amenorrhoeic woman exogenous oestrogen was found to enhance the LH response to LRH.

INTRANASAL GONADOTROPIN-RELEASING HORMONE AGONIST AS A CONTRACEPTIVE AGENT

The stimulatory luteinising hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered intranasally once daily to twenty-seven regularly menstruating women to determine its efficacy as a contraceptive agent. Ovulation was inhibited during all but 2 of the 89 treatment months. The failures were due to initial technical problems with the nasal spray. Twenty-one of the twenty-seven women had slight menstrual-like anovulatory bleeds during the 3--6 month trial. The remaining six women were amenorrhoeic. Ovulatory menstrual cycles rapidly returned after discontinuation of treatment. There were no serious side-effects.

Clinical course and outcome of pregnancies in amenorrhoeic women with hyperprolactinaemia and pituitary tumours

Seventeen term pregnancies occurred in 14 amenorrhoeic women with hyperprolactinaemia and radiological evidence of pituitary tumour. The abortion rate was high (32%). All but one of the term pregnancies occurred after ovulation-inducing treatment with human gonadotrophins and bromocriptine (four and 12 pregnancies respectively). Two of the 14 women had visual complications during pregnancy, but neither had serious residual visual impairment. Two patients had possible pituitary enlargement during pregnancy. Bromocriptine may be the most suitable primary treatment for many infertile women with prolactin-secreting tumours. Tumour complications during pregnancy are a definite risk, but most pregnancies went uneventfully to term. Patients with pituitary tumour should be carefully evaluated before starting ovulation-inducing treatment with bromocriptine alone, and they should be told of the possible risks and of the advantages and disadvantages of pretreatment with irradiation or surgery. Patients should be carefully monitored during pregnancy and have their visual fields checked frequently. If visual complications due to tumour enlargement occur during a pregnancy, reinstituting bromocriptine may be the treatment of choice. If this fails, other forms of treatment such as induction of labour, high-dose corticosteroid treatment, pituitary implantation of yttrium-90, or surgery may be effective.

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).