[Peptide-producing tumors in the pancreas and gastrointestinal tract: syndrome, survey, therapy].
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Carcinoid Tumor↗
Biomedical subjects
L Wide
Publications and source records attributed to L Wide.
Defective regulation of the cytosolic Ca2+ activity in parathyroid cells from patients with hyperparathyroidism.
The parathyroid hormone (PTH) release and cytosolic Ca2+ activity were determined in normal bovine parathyroid cells and parathyroid cells obtained from patients with hyperparathyroidism (HPT). There was a sigmoid relation between the cytosolic Ca2+ activity and the extracellular calcium concentration between 0.5 and 6.0 mmol/l. The PTH release was inhibited in parallel with the rise in the cytosolic Ca2+ activity. Both the hormone release and the cytosolic Ca2+ activity were lower in cells from human adenomas and hyperplastic glands, and in comparison with the bovine preparations these cells had higher set points for the cytosolic Ca2+ activity and PTH release. There was a close correlation between the individual set points for the cytosolic Ca2+ activity and PTH release in a material containing both normal and pathological cells. The results indicate that the abnormal PTH release characteristic of HPT is due to a defective regulation of the cytosolic Ca2+ activity.
Adenoma↗
Bromocriptine-induced regression of a suprasellar extending prolactinoma during pregnancy.
A 21-year-old amenorrheic woman with hyperprolactinemia had rapid pituitary tumor enlargment during a bromocriptine-induced pregnancy. Before treatment the sella turcica was normal. In the 31st week of pregnancy she developed bitemporal hemianopsia and markedly decreased visual acuity. Computerized tomography showed a pituitary adenoma with suprasellar extension. Reinstitution of bromocriptine therapy resulted in rapid recovery of normal vision and radiologically verified tumor regression. Pregnancy continued to term and a healthy child was born. If pituitary tumor complications should occur during pregnancy, reinstitution of bromocriptine is the primary treatment of choice.
Adult↗
Effects of epinephrine and norepinephrine on serum parathyroid hormone and calcium in normal subjects.
Infusions with stepwise increasing concentrations of epinephrine (from 2.5 to 10 micrograms/min) and norepinephrine (0.5-2.0 micrograms/min) were given to normal subjects. During infusion of epinephrine there was a clear rise of the serum parathyroid hormone (PTH) levels already at the lowest concentration. Concomitantly there was a fall in the serum concentrations of calcium. The PTH levels returned to baseline promptly after termination of infusion whereas hypocalcaemia persisted up to 30 minutes, indicating a primary response of PTH to epinephrine. When propranolol was given prior to and during the epinephrine infusion no significant changes occurred for either PTH or calcium. During infusion of norepinephrine no consistent significant changes were noted for either PTH or serum calcium. Thus, our data do not support any concept of a basal adrenergic tone which normally modulates the secretion of PTH. However, during conditions of stress the beta-adrenergic stimulation night be of importance.
Adult↗
Insulin-induced hypoglycaemia stimulates secretion of parathyroid hormone.
In-vitro and in-vivo studies have suggested a role for the adrenergic system in the regulation of secretion of parathyroid hormone (PTH). In the present study the effects of insulin induced hypoglycaemia on serum concentrations of PTH, cortisol, calcium and phosphate were evaluated in ten healthy subjects. Maximum hypoglycaemia occurred 25 to 35 min after administration of insulin at a standard dose of 0.15 U/kg body weight. All this time there was a slight and transient increase of the serum calcium concentrations whereas there was a marked drop in the serum phosphate levels with a nadir 15 min after maximum hypoglycaemia. Cortisol levels were below baseline when blood glucose was as lowest but increased to a maximum level of 200% 60 minutes after maximum hypoglycaemia. Serum PTH levels increased significantly and reached a maximum of 130% of baseline values concomitant with maximum hypoglycaemia, whereafter they returned to pre-insulin-injection levels within 15 minutes. These findings indicate that during stress endogenous catecholamines affect the secretion of PTH which could be of physiologic importance. In five patients with primary hyperparathyroidism there was, however, no increase in the PTH levels, although they displayed the same response to hypoglycaemia for cortisol and phosphate. This supports previous suggestions that these patients have an impaired capacity to respond to circulating catecholamines.
Adult↗
Screening for multiple endocrine neoplasia syndrome (type 1) in patients with primary hyperparathyroidism.
In 63 consecutive patients with primary hyperparathyroidism (HPT) a prospective screening study was undertaken for coexistent multiple endocrine neoplasma-(MEN)-syndrome type 1. The screening consisted of a clinical examination, a radiological examination of the sella turcica with skeletal tomography (and in equivocal cases computed tomography), visual field examination by perimetry and a hormonal evaluation including measurements of the serum levels of prolactin, gastrin, pancreatic polypeptide (PP) and subunits of human chorionic gonadotrophin (HCG-alpha and -beta). Clinical examination did not reveal any signs of endocrine disease suggestive of a MEN-1 syndrome. In only one case there was a radiological abnormality of the sella turcica; this patient had an empty sella syndrome and a raised serum prolactin value. All other prolactin values were within the normal range. In 41% of the patients raised serum gastrin levels were found; these tended to normalize after parathyroidectomy. As a group, patients with raised gastrin values were older than the others and generally they had hypo- or achlorhydria. The serum PP levels were raised in 28% of the patients but there was no clinical evidence of a pancreatic tumour in any of these cases, and the serum HCG-alpha and -beta levels were within the normal range in all patients but two. We conclude that the incidence of MEN-1 syndrome in unselected patients with primary HPT must be low, and that investigations for this syndrome are justified only in HPT patients with specific symptoms or with a positive family history.
Adult↗
Effects of physical exercise on serum calcium and parathyroid hormone.
The effects of physical exercise on plasma ionized calcium, total serum calcium and parathyroid hormone (PTH) concentrations were evaluated in healthy subjects submitted to work on an ergometer bicycle. When the workload was increased stepwise there was a significant increase (P less than 0.001) in the calcium concentrations (ionized calcium from 1.13 +/- 0.03 (SD) to 1.24 +/- 0.03 mmol 1(-1) and total calcium from 2.35 +/- 0.07 to 2.48 +/- 0.07 mmol 1(-1] when the workload exceeded approximately 65% of the estimated maximum--i.e. a load that caused accumulation in blood of lactic acid. The rise in plasma ionized calcium was, therefore, presumably largely attributed to the acidosis but reduction of plasma volume and influx from extracellular sources might also have contributed. Beta blockade (with oral intake of propranolol) reduced physical capacity, shortened the duration of work and caused less acidosis. These factors were probably responsible for a smaller rise in ionized calcium during beta blockade (7 +/- 4%) than in control studies (21 +/- 5%) without medication in subjects examined during short-term maximal exercise. Long-term (1 h) steady-state work which caused fatigue without producing lactic acidosis did not affect the calcium concentrations. Despite the effects of work on calcium levels there was no discernible suppression of the PTH concentrations. This might have been due to a concomitant stimulation of PTH secretion by work.
Adult↗
Effects of high intake of dietary animal protein on mineral metabolism and urinary supersaturation of calcium oxalate in renal stone formers.
The metabolic effects of a high protein diet (HPD) were studied in eight patients with idiopathic recurrent calcium oxalate stones. On the HPD there was a 35% increase in urinary calcium concomitant with increased excretion of cyclic AMP and hydroxyproline. These findings point to an enhanced resorption of bone, possibly secondary to increased renal loss of calcium. The urinary citrate decreased by 25% along with reduced serum standard bicarbonate and urinary pH. The high formation of acid metabolites might also have adverse effects on calcium balance and bone. Urinary oxalate excretion was not affected nor were there any significant changes in the calculated urinary supersaturation of calcium oxalate, if changes in urinary citrate, pH, sulphate, sodium, phosphate and volume were also considered. This study suggests that the possible negative influence on the propensity to form renal stones of a diet rich in animal protein is probably due to reduced urinary inhibitory activity.
Adult↗
Higher plasma disappearance rate in the mouse for pituitary follicle-stimulating hormone of young women compared to that of men and elderly women.
Female mice were injected iv with extracts of different human pituitaries and the recovery of hFSH in plasma and the disappearance rates of the hormone from the circulation were measured. In the first samples taken 5 min after injection, the recovery of pituitary FSH of young women (52%) was significantly lower (P less than 0.001) than that of men (64%) and elderly women (63%). The plasma concentration of human FSH was measured in the mice up to 242 min after injection. During this period the disappearance rate of the FSH of a young woman continued to be higher than that of the man and the elderly woman. The plasma disappearance curves were multiexponential and gave a poor fit in a two-component exponential model, probably due both to distribution into more than one compartment and to heterogeneity of the material investigated. The MCR and the t1/2 of irreversible loss of human FSH from the circulation were therefore also calculated from graphic integration of the areas under the disappearance curves extrapolated to 480 min. The values obtained in this way for MCR of FSH of a young and an elderly woman and a man were 2.4, 1.4, and 1.7 ml/h, respectively, and the values for t1/2 were 19, 33, and 28 min, respectively. The differences between these values for FSH of the three individuals were highly significant (P less than 0.001). The results indicate that the relatively low in vivo biological activity reported for pituitary FSH of young women compared to that of men and elderly women is due to more rapid clearance of the hormone from the circulation of the test animal.
Adolescent↗
Effects of 1,25- and 24,25-dihydroxycholecalciferol on parathyroid hormone release from human parathyroid cells in vitro.
The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) on parathyroid hormone (PTH) release from human parathyroid cells were investigated using an in vitro system of dispersed cells. The cells were obtained from 7 patients with primary hyperparathyroidism (HPT) and adenoma, 4 patients with primary HPT due to hyperplasia and 2 patients with parathyroid hyperplasia secondary to chronic renal failure. The dispersed cells were incubated in tissue culture medium at low, normal and high external calcium concentrations for 2-16 h. There was a gradual suppression of PTH release (5-55%) when the calcium concentration in the medium was increased from 0.5 to 3.0 mM, thus indicating retained regulation of hormone release. The addition of 1,25-(OH)2D3 in concentrations of 0.1 and 1 ng/ml and of 24,25-(OH)2D3 in concentrations of 1.0 and 10 ng/ml during the incubations did not further affect the amount of PTH released by the cells. The concentrations of the different vitamin D metabolites tested closely correspond to levels observed under normal physiological conditions and during treatment with high doses of vitamin D in vivo. Thus, the findings contradict the idea of any direct short-term regulatory effect of either 1,25-(OH)2D3 or 24,25-(OH)2D3 on the secretion of PTH from hyperfunctioning human parathyroid tissue.
24,25-Dihydroxyvitamin D 3↗
A stimulation test with calcitonin for differential diagnosis of hypercalcaemia.
Experimental studies have suggested that in primary hyperparathyroidism (HPT) the cells of the hyperfunctioning parathyroid tissue retain some capacity for stimulation and that an increase in secretion of parathyroid hormone (PTH) can occur when the extracellular calcium concentration is lowered within the hypercalcaemic range. We have tested this hypothesis in 23 patients with HPT, 10 patients with hypercalcaemia of other origin (7 of whom had disseminated malignant disease) and 17 normal subjects. In all three groups a single injection of 100 MRC units of salmon calcitonin caused a reduction in serum calcium of approximately 3 to 5%. In the hypercalcaemic patients this reduction was correlated to the basal calcium level (r = -0.57, P less than 0.01). In the patients with HPT, although they all remained hypercalcaemic, the decrease in serum calcium was associated with a mean increase in serum PTH of 10%. Only in 2 patients did such an increase fail to occur despite an adequate decrease in serum calcium. These 2 patients had high basal PTH levels and the lack of response might have been due to a high degree of autonomous parathyroid function. Calcitonin also reduced serum calcium and increased serum PTH in normal subjects. None of the patients with hypercalcaemia of other origin than primary HPT displayed a secretory PTH response to serum calcium reduction. Thus, this test could be of practical clinical value, particularly in patients with borderline PTH values. A calcitonin-induced rise in PTH while serum calcium is lowered within the hypercalcaemic range strongly suggests primary HPT.
Adult↗
Subcutaneous pulsatile LH-RH therapy of secondary amenorrhoea.
A novel promising approach to the treatment of anovulatory infertility has been investigated during the last few years. Pulsatile long-term subcutaneous administration of low doses of LH-RH given by means of small portable computerized infusion pumps has proved to be practical, safe and effective for induction of follicular maturation and ovulation in women with amenorrhoea due to inadequate pituitary gonadotrophin secretion.
Abdominal Muscles↗
Induction of male puberty by long-term pulsatile subcutaneous LH-RH therapy.
Prolonged low dose LH-RH treatment was given to induce puberty in a 17.8-year-old male with hypogonadotrophic hypogonadism. The patient had developed panhypopituitarism after transcranial surgery of a craniopharyngioma at the age of 16.8 years. One year after the operation he had no signs of pubertal development and was of short stature. A small portable automatically-timed infusion pump, connected to a subcutaneous (s.c.) catheter, was used for the 328-day-long treatment, which was given in periods of between 16 to 185 days. Twenty micrograms of LH-RH s.c. was given every 90 min. Growth hormone therapy, 8 IU intramuscularly (i.m.) twice weekly, was instituted at the same time. During the prolonged LH-RH treatment the gonadotrophin secretion normalized. The serum concentration of testosterone increased to the normal range of adult males. Rapid pubertal progression occurred with development of pubic hair to adult type and increase in size of the penis. Testicular volume increased from 2 to 12 ml. Nocturnal emissions occurred after 30 weeks of pulsatile LH-RH treatment and sperms were found in the ejaculate after 43 weeks. The height of the patient increased from 162 to 176 cm. Thus, chronic pulsatile low dose LH-RH treatment can induce normal pituitary - gonadal function with pubertal maturation and spermatogenesis in primary male hypogonadotrophic hypogonadism.
Adolescent↗
Long-term subcutaneous pulsatile low dose LH-RH administration for treatment of infertile men with secondary hypogonadotrophic hypogonadism.
Chronic pulsatile subcutaneous low dose LH-RH treatment was given to three infertile men with longstanding (2-4 years) secondary hypothalamic pituitary failure. Before the therapy they had very low serum concentrations of gonadotrophins and testosterone. They were impotent and could not produce any ejaculate for sperm analysis. The pulsatile LH-RH treatment, which was continued up to 250 days, was given by means of a small portable automatically-timed infusion pump. Fifty microliter of the LH-RH solution was infused during one min every 90 min. The LH-RH doses were 1, 5 and 20 micrograms. The serum concentrations of the gonadotrophins and testosterone were normalized in the three patients within 10 days of pulsatile low dose LH-RH therapy. Libido and potency returned. The first ejaculates contained no sperms. With continued LH-RH treatment spermatogenesis was induced and normalized. Two of the men fertilized their wives. The pregnancy tests were positive after 181 and 230 days of treatment, respectively. Two healthy girls have been born. Paternity tests were positive. The third man is still receiving pulsatile LH-RH therapy. He has up till now been treated for four months. Chronic pulsatile s.c. low dose LH-RH administration is a very promising new therapy for those hypogonadal men who previously have required human gonadotrophin treatment to restore fertility.
Abdominal Muscles↗
Peptide contraception in women. Inhibition of ovulation by chronic intranasal LRH agonist therapy.
Seventy-one healthy female volunteers used the LRH superagonist D-Ser(TBU) 6-EA10-LRH (buserelin) for contraception during 3-26 months. One daily dose of 200-600 micrograms was administered by the nasal route. No pregnancy occurred during the 628 treatment months. The bleeding pattern varied from fairly regular menstrual bleedings (n = 26) to oligomenorrhoea (n = 27) and amenorrhoea (n = 18). No severe or dysfunctional bleeding disturbances were observed. No signs of hyperplastic changes of the endometrium were found in 57 endometrial biopsies. After cessation of the long-term treatment normal ovulation and menstruation returned after 41.3 days, on average. Thus, intranasal administration of an LRH agonist for inhibition of ovulation is a promising new contraceptive method for women.
Administration, Intranasal↗
An investigation of biochemical and radiographic signs of hyperparathyroidism in chronic renal disease.
One hundred and twelve randomly selected patients with renal disease (22 on conservative treatment, 35 on haemodialysis and 55 with functioning kidney transplants) were subjected to a longitudinal and follow-up study of biochemical and radiographic signs of secondary hyperparathyroidism (HPT). Special interest was directed towards diagnostic criteria leading to the decision to perform parathyroid surgery, which had been undertaken in 18 patients. The five patients selected for parathyroidectomy while on conservative treatment were clearly distinguishable from the rest of the patients in this group, on the basis of hypercalcaemia, massive elevation of serum parathyroid hormone and radiographic abnormalities, findings which did not occur in patients in whom parathyroid surgery had not been considered. Six patients underwent parathyroidectomy while on haemodialysis. Preoperatively hypercalcaemia was observed in five and this was the only finding separating these patients from non-operated patients. Radiographic abnormalities were observed in only one operated patient. After kidney transplantation, long-standing hypercalcaemia was observed in 27% of patients. Seven patients underwent parathyroidectomy, hypercalcaemia being the indication for surgery in all cases. Hypercalcaemic patients could not be separated from normocalcaemic patients regarding any other determined biochemical variable, or regarding the incidence of osteonecrosis of weight-bearing joints, which was found in 18% of transplanted patients, and which was the only cause of major symptomatic bone disease observed in this study. The findings of hypercalcaemia as a major deciding factor for parathyroid surgery, a low incidence of radiographic bone disease, and absence of major symptomatic bone disease referable to HPT, are in keeping with a more liberal attitude to parathyroidectomy in chronic renal disease than has been stated in other recent reports. With a more expectant attitude and with more active medical treatment some of the operations performed on the patients in this study might have been avoided but, in general, the favourable outcome after surgery and the low overall incidence of clinical problems referable to bone disease at our unit would seem to support our active approach to parathyroid surgery.
Adolescent↗
Human gonadotropin therapy. I. Serum estradiol and progesterone patterns during conceptual cycles.
Hormone patterns during 43 conceptual cycles induced by human gonadotropins in 37 women with anovulatory infertility were analyzed. The treatment was monitored by daily determinations of estradiol (E2) in serum. The incidence of both multiple pregnancies and abortions during the gonadotropin therapy was high (30%). When the hormone patterns during the human menopausal gonadotropin-induced conceptual cycles were compared with spontaneous conceptual cycles, it became evident that the ovaries were hyperstimulated during the follicular and luteal phases of the induced cycle. The mean serum E2 level at induction of ovulation did not differ between treatment courses resulting in single or multiple pregnancies. The endogenous estrogen secretion at the initiation of treatment was lower in the multiple pregnancy group than in the single pregnancy group. The active phase, i.e., when the estrogens progressively increase during the late follicular phase of the induced cycle, was found to be prolonged in the multiple pregnancy group. The prolonged follicular stimulation by human menopausal gonadotropin might explain why multiple ovulations and pregnancies occur. Thus, both the duration of the active phase of follicular stimulation and the E2 level at the day of induction of ovulation by human chorionic gonadotropin should be determined for optimal monitoring of human gonadotropin therapy.
Adult↗
Human gonadotropin therapy. II. Serum estradiol and progesterone patterns during nonconceptual cycles.
Hormone patterns during 113 nonconceptual gonadotropin-induced cycles of 65 infertile anovulatory women were analyzed. All but one women ovulated, i.e., the ovulation rate was 98%. Signs of defective corpus luteum function were observed during 8 cycles, and anovulation occurred in 11 treatment cycles. The duration of the active phase of the follicular stimulation was shorter during cycles with defective luteal phases and anovulatory cycles. The mean estradiol level at induction of ovulation by human chorionic gonadotropin did not differ between the groups. Premature ovulation was observed in six treatment cycles. No case of severe hyperstimulation was encountered. The hormone pattern during gonadotropin-induced conceptual cycles did not differ in comparison with gonadotropin-induced nonconceptual ovulatory cycles.
Adult↗