Unchanged response to stimulation of pituitary hormone release after serial UV irradiation in men.

A group of 24 healthy young men were evaluated before and after serial suberythematous ultraviolet (UV) radiation: group I, control (no irradiation); groups II and III, 12 radiations in 4 weeks with two different spectra (both containing UV-B). Before the first and 2 days after the last exposure all the volunteers were given an intravenous injection of thyrotropin releasing hormone (TRH, protirelin 0.2 mg) and luteinizing hormone releasing hormone (LH-RH, gonadorelin 0.1 mg). The serum concentrations of TSH, follicle stimulating hormone, LH and prolactin were measured at 0, 20, 30, 45 and 60 min by radioimmunoassay. Neither basal nor stimulated levels of the pituitary hormones showed significant changes after UV radiation. The results showed that exposure to suberythematous doses of UV did not influence the regulation of pituitary hormones in these healthy individuals.

Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion.

It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 +/- 0.61 to 5.77 +/- 0.78 mmol/l and from 5.61 +/- 2.05 to 7.55 +/- 3.05 mmol/l, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose-stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesic effect of the somatostatin analogue octreotide in two acromegalic patients: a double-blind study with long-term follow-up.

Two acromegalic patients with severe headache were treated with the somatostatin analogue, octreotide (Sandostatin). A double-blind study of octreotide versus placebo in which pain intensity was measured using a visual analogue scale (VAS) was performed initially with these patients. A rapid (within 4-15 min) pain relief occurred lasting 2-8.5 h after injection of 100 micrograms of octreotide, an effect that was not reversed by intravenous (i.v.) naloxone. These 2 acromegalic patients then received treatment for 71 and 82 months, respectively, with doses starting at 500 micrograms/day and 1500 micrograms/day, respectively, without evidence of either tolerance or dependence, although the effect of octreotide on headache appears to be selective. No unwanted sedative effect has been observed. A screening procedure with injection of 50 micrograms of subcutaneous (s.c.) octreotide was performed in 11 other patients with chronic severe pain associated with various conditions. Only 3 patients (2 with diabetic polyneuropathy and 1 with bone pain associated with myelodysplastic syndrome) reported more than 50% pain relief. In the insulin-dependent diabetic patients the double-blind check was not performed due to the risk of octreotide-induced hypoglycemia. In the patient with bone pain the same double-blind check as in the acromegalic patients could not confirm the analgesic effect. It may thus be concluded that octreotide appears to be useful for the treatment of both chronic and acute severe painful conditions in acromegalic patients. However, since its analgesic effect in our patients was confined to headaches only, further controlled studies must be carried out in order to determine appropriate target groups.

Treatment of macroprolactinoma with the new potent non-ergot D2-dopamine agonist quinagolide and effects on prolactin levels, pituitary function, an the renin-aldosterone system. Results of a clinical long-term study.

The oral non-ergot D2-dopamine agonist quinagolide (CV 205-502, CAS 87056-78-8) has proven to be highly effective in suppressing elevated prolactin (PRL) levels. It was the aim of this study to search for possible interference of the drug with other endocrine systems which are partly under dopaminergic control, and to compare such effects to those of previously investigated prolactin inhibitors. Twelve patients suffering from macroprolactinoma were treated for at least 6 months with daily doses ranging from 50 up to 300 micrograms. During the first two months, individual doses were gradually increased either until serum PRL levels reached the normal range (n = 7) or until side effects made a further dose increase intolerable (n = 5). Mean basal PRL level fell from 255 +/- 65 (SEM) ng/ml before treatment to 19 +/- 8 ng/ml, after the definite dose was reached (p < 0.01). Luteinizing hormone (LH) rose from 0.6 +/- 0.8 (SD) to 1.7 +/- 1.6 mU/ml (p < 0.05). While basal levels of aldosterone, renin, follicle-stimulating hormone (FSH), triiodothyronine (T3), testosterone, and estradiol in females were not affected by the treatment, we found a significant rise in thyroxine (T4) and a decrease of estradiol in males. Blood pressure and renal clearances of creatinine, sodium, potassium, and chloride failed to show any significant change. Following stimulation with metoclopramide, aldosterone and renin rose sharply before treatment was initiated. When the test was repeated during treatment, the increase of plasma renin was slightly dampened, whereas the rise of aldosterone remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary adenomas: serum hormone levels and immunohistochemical staining for ACTH, GH and prolactin.

In 37 pituitary adenomas obtained by surgery the immunohistochemical staining for ACTH, GH and prolactin and the tumor size were related to the basal serum hormone levels. 5 adenomas were associated with Cushing syndrome, 9 with acromegaly, 17 with hyperprolactinemia and 6 were preoperatively diagnosed as inactive. A rather close correlation between immunoreactivity of tumor tissue and basal serum hormone levels was found for GH and prolactin whereas these two parameters were not significantly correlated in the corticotrophic adenomas examined. Furthermore there was no obvious correlation between serum hormone levels and tumor size. Several non immunoreactive adenomas showed slight hyperprolactinemia; all of them were macroadenomas with extended sellar lesions. This fact may be explained by disturbances in the hypothalamic-hypophyseal regulation of serum prolactin.

Gallstones in acromegalic patients undergoing different treatment regimens.

The frequency of gallstones during long-term treatment with the somatostatin analogue octreotide reported in different studies varies from 0% to 50%, the reason for this variation being unknown. Therefore, we examined 58 acromegalic patients undergoing different treatment regimens for the frequency of gallstones. Thirteen were treated with octreotide, 20 with bromocriptine, and 25 had no medical treatment after successful neurosurgery. Also, 58 patients without known gallbladder disease served as controls. The postprandial gallbladder contraction was also investigated in 27 acromegalic patients (10 with octreotide, 10 with bromocriptine, and 7 with no medical therapy). Ten of the 58 acromegalic patients were found to have gallstones, 4 of 25 receiving no medical treatment, 4 of 20 treated with dopamine agonists, and 2 of 13 treated with octreotide. In 9 of the 58 control patients, gallstones were detected. Although in the octreotide group the gallstones were newly formed under therapy, there was no difference in gallstone prevalence between the different treatment regimens and the control group. However, the postprandial gallbladder contraction was significantly more often inhibited during octreotide therapy, and this effect was most pronounced during the first hours following injection. Differences in the timing of injections therefore may be an explanation of the variable incidence of cholelithiasis in the different studies.

Bromocriptine treatment over 12 years in acromegaly: effect on growth hormone and prolactin secretion.

It is not known whether bromocriptine treatment in acromegaly can be implemented for a life-long period. To elucidate this problem, the secretory GH and PRL states of 12 patients with acromegaly were determined, before bromocriptine treatment, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years; mean +/- SD) and during two-weeks long drug withdrawal after long-term treatment, respectively. Before therapy, all patients showed a non-sufficient GH suppression after oral glucose load (greater than 2 micrograms/l), whereas under dopaminergic treatment the post-glucose GH levels of three patients fell below 2 micrograms/l; normal IGF-I concentrations were found in five patients. However, under bromocriptine, only two patients showed GH suppressions below 2 micrograms/l following glucose, accompanied with normal IGF-I levels. During bromocriptine withdrawal, GH secretion at 60 min in the oral glucose tolerance test increased significantly (17.0 +/- 15.5 vs 5.7 +/- 5.2 micrograms/l; p less than 0.01); the mean IGF-I level rose from 2.1 +/- 0.8 to 4.9 +/- 2.2 kU/l (p less than 0.01). IGF-I was normal during bromocriptine cessation in only one patient; none of the 12 patients showed a GH suppression below 2 micrograms/l after oral glucose load. Under dopaminergic treatment hyperprolactinemia could not be detected. In conclusion, bromocriptine led to a stable suppression of both GH hypersecretion and--if present--concomitantly elevated PRL levels. Severe side effects or a further tumor growth could not be observed. Thus, the data of the longest follow-up investigation that has so far been published indicate that effective life-long bromocriptine therapy seems to be possible in selected patients with acromegaly.

[Anal incontinence in patients with Addison's disease: a gluco- and mineralocorticoid independent sphincter malfunction?]. / Anale Inkontinenz bei Patienten mit Morbus Addison: Eine gluko- und mineralokortikoid-unabhängige Sphinkterstörung?

Anorectal motor function was evaluated in 15 female patients with Addison's disease and androgen deficiency and 15 age-matched healthy volunteers. Medical history revealed symptoms of faecal incontinence in 5 patients. The patients showed decreased maximum retention volumes (p less than 0.01) in the rectal saline infusion test. Lowered anal sphincter resting (p less than 0.01) and squeeze pressure (p less than 0.01) was demonstrated in patients with adrenocortical insufficiency. No differences between patients and controls were found in respect of perception volume, minimal distension volume for sphincter relaxation and rectal compliance by means of intrarectal balloon distension. Electromyography of the external anal sphincter was performed in 8 patients and showed no evidence for a neurogenic defect. Relevant morphological changes of the anorectum could be excluded endoscopically in 13 of the 15 patients. Therefore impaired anorectal muscular function is responsible for faecal incontinence in patients with Addison's disease and androgen deficiency. Further investigations will show, whether these findings are the consequence of lowered androgen production.

Prevalence of HLA-DQ beta chain non-Asp alleles in type I (insulin-dependent) diabetics with young and older ages of onset.

Particular HLA-DQ beta chain alleles were reported as immunogenetic markers of type I diabetes mellitus with young onset of the disease. In a homogeneous German population, we studied HLA-DR specificities and HLA-DQ beta chain alleles in young-onset (less than 21 years of age; n = 185) and adult-onset (greater than 40 years of age; n = 48) insulin-dependent diabetics. In both cohorts of type I diabetics, the HLA-DR3 and -DR4 specificities were significantly increased. The presence of an HLA haplotype with an amino acid other than aspartic acid at position 57 of the DQ beta chain was significantly associated with type I diabetes in both cohorts (etiologic fraction: 93% and 73%). We conclude that the presence of DNA sequences coding for an amino acid other than aspartic acid at the 57th position of the DQ beta chain provides a molecular risk marker for type I diabetes of both and adult onset.

Effect of bromocriptine withdrawal in acromegaly on body composition as assessed by bioelectrical impedance analysis.

To evaluate the effect of bromocriptine withdrawal after dopaminergic long-term treatment (15.0 +/- 6.8 mg/day, mean +/- SD) in 12 acromegalic patients on body composition, bioelectrical impedance was measured before and at the end of two weeks of drug withdrawal. During withdrawal basal hGH and IGF-I increased from 2.5 +/- 1.9 micrograms/l and 2.1 +/- 0.8 kU/l to 9.1 +/- 11.7 micrograms/l and 4.9 +/- 2.2 kU/l, respectively, and the hGH secretion deteriorated significantly both after oral glucose load and in the TRH test, indicating recurrence of active acromegaly. Reactance and resistance decreased by 5 +/- 4 and 23 +/- 19 omega, respectively (p less than 0.01), whereas body weight remained constant (+0.4 +/- 2.1 kg). Bioelectrical impedance analysis indicated evident shifts in body composition, i.e. a significant reduction of body fat (-2.0 +/- 1.7 kg) and a simultaneous increase in both lean body mass (+2.4 +/- 2.2 kg) and total body water (+1.8 +/- 1.6 l). The changes in body composition were related to a combined effect of unsuppressed hypersomatotropism and the lack of bromocriptine actions other than inhibition of hGH secretion (for example stimulation of the renin-angiotensin-aldosterone system by both the recurred hypersomatotropism and the absence of dopaminergic bromocriptine effects). We conclude that bioelectrical impedance analysis is a good additional tool to assess the pathophysiological effects of bromocriptine withdrawal in long-term treated acromegalic patients.

[Somatomedin C level and stimulation of growth hormone and adrenal cortex function by administration of releasing hormones and physical exertion in patients with obesity]. / Somatomedin-C-Spiegel und Stimulation von Wachstumshormon und Nebennierenrindenfunktion durch Gabe von Releasing-Hormonen und körperliche Belastung bei Patienten mit Adipositas.

In a clinical study on potential determinants underlying the impairment of growth hormone stimulation in obese human subjects, we examined in 20 otherwise healthy adult obese subjects (14 females, six males, age 18 to 40 years, body mass index greater than 29 kg/m2) the responses of growth hormone (hGH), adrenocorticotropic hormone (ACTH) and cortisol to releasing hormone stimulation (growth hormone-releasing hormone and corticotropin-releasing hormone) and the responses of hGH, ACTH, cortisol and free fatty acids (FFA) to physical exercise. Subjects with somatomedin-C levels less than or equal to 0.7 U/ml (group 1) were more obese than subjects with somatomedin-C levels greater than 0.7 U/ml (group 2) (p less than 0.01). In group 1, hGH increased by 4.3 +/- 1.2 ng/ml in response to releasing hormone administration and by 0.9 +/- 0.3 ng/ml in response to physical exercise (normal responses, increase by greater than 7 ng/ml), in group 2, hGH increased by 6.7 +/- 1.4, and 2.4 +/- 0.8 ng/ml, respectively (p less than 0.05 vs. group 1). Moreover, FFA stimulation by physical exercise was blunted in group 1 (p less than 0.05 vs. group 2). In contrast, ACTH stimulation was found increased in group 1 in comparison to group 2, particularly in response to physical exercise (p less than 0.01), and resulted in enhanced cortisol stimulation (p less than 0.05). Thus, impaired hGH stimulation in obese human subjects is not explained by an altered relationship between hGH and somatomedin-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of ischemic pain threshold and reactive hyperemia in autonomic diabetic neuropathy and silent myocardial ischemia]. / Vergleich von Ischämieschmerzschwelle und reaktiver Hyperämie bei autonomer diabetischer Neuropathie und stummer Myokardischämie.

31 patients with coronary artery disease (11 patients with diabetes mellitus and autonomic neuropathy. 10 patients with diabetes without neuropathy, and 10 patients with asymptomatic myocardial ischemia) participated in a study designed to investigate whether there is a difference in forearm skeletal muscle ischemia and pain threshold. The degree of ischemia was determined by plethysmographically measured reactive hyperemia. There was no difference in maximum reactive hyperemia after passive forearm ischemia of 5-min duration in the three groups. After symptom-limited ischemic work, there was significantly more reactive hyperemia in patients with silent myocardial ischemia as compared to diabetic patients. Exercise time was longer in patients with silent myocardial ischemia (153 +/- 51 s) than in patients with diabetic neuropathy (139 +/- 45 s) and diabetics without neuropathy (120 +/- 45 s). Pain as a cause of termination of symptom-limited ischemic forearm exercise occurred less frequently in patients with diabetic neuropathy (2/11) and patients with silent myocardial ischemia (3/10) as compared to patients with diabetes without neuropathy. Patients with silent myocardial ischemia had a higher ischemic tolerance in the ischemic working forearm than did diabetic patients with and without neuropathy. In patients with neuropathy, however, ischemic pain occurred less frequently at the same ischemic work level compared to diabetics without neuropathy. Therefore, diabetic neuropathy appears to facilitate the occurrence of silent myocardial ischemia. The data presented here suggest that there is a qualitative difference in ischemic tolerance between patients with silent myocardial ischemia and patients with diabetic neuropathy.

[The influence of autonomic diabetic neuropathy and human atrial natriuretic peptide on adrenal gland function in postural changes]. / Einfluss der autonomen diabetischen Neuropathie und des humanen atrialen natriuretischen Peptids auf das Verhalten der Nebennierenfunktion bei Anderung der Körperhaltung.

To investigate the influence of postural changes on plasma renin activity (PRA), plasma levels of human atrial natriuretic peptide (hANP) and on aldosterone in diabetes mellitus and autonomic neuropathy, ten patients with diabetes mellitus and autonomic neuropathy and ten patients with diabetes mellitus but without autonomic neuropathy were studied. Ten healthy subjects served as controls. Patients and controls were in supine position for 60 minutes, then changed posture sequentially to sitting (90 minutes) and to upright position (15 minutes). In controls, PRA was increased upon sitting and in the upright position, while hANP was decreased. Patients with autonomic neuropathy differed from controls in impaired renin stimulation, whereas in patients without autonomic neuropathy PRA responses to postural changes were only slightly decreased. In both groups of patients, the normal hANP responsiveness to postural changes was lacking. There were no differences in aldosterone levels between patients and controls. In patients with high basal hANP levels due to elevated systolic blood pressure renin responses to postural changes were decreased in comparison to those patients with low basal hANP levels. Thus, in patients with diabetes mellitus increased hANP levels which are not decreased in response to upright standing may contribute to the development of hyporeninism and its sequelae.

[Long-term treatment of acromegaly with the somatostatin analog octreotide (Sandostatin). On the predictive significance of acute tests]. / Langzeitbehandlung der Akromegalie mit dem Somatostatinanalogon Octreotid (Sandostatin). Zur prädiktiven Bedeutung von Akuttests.

Twelve acromegalic patients were treated (mean +/- SD) 26 +/- 15 months with daily doses of 440 +/- 330 micrograms of the somatostatin analogue octreotide acetate (SMS 201-995, Sandostatin). The levels of somatomedin-C (Sm-C) decreased by 63% from 8.1 +/- 7.7 U/ml to 3.0 +/- 1.3 U/ml. Before starting therapy a long oral glucose tolerance test (oGTT) and a TRH test were performed both without and after s.c. injection of 100 micrograms octreotide. Under long-term treatment with octreotide four of twelve patients reached normal Sm-C-values. The GH levels of all of these patients were continuously suppressed to less than 2 ng/dl in an oGTT after a test dose of 100 micrograms octreotide s.c. till the end of the test (5 1/2 hours after octreotide injection). The other eight patients had a relief of acromegalic symptoms and five had a decrease of their Sm-C-levels, but none of them reached normal Sm-C-values. None of these patients had a continuous suppression of GH after a test dose of octreotide in an oGTT. Hyperprolactinemia (n = 4) was observed only in those patients with an insufficient response to octreotide. The GH-response to TRH showed neither without nor after injection of octreotide a correlation with the results of long-term treatment. Thus it is concluded that GH-suppression in a long oGTT after administration of a test dose of 100 micrograms octreotide acetate s.c. allows to identify those acromegalic patients who will benefit from long-term treatment with the somatostatin analogue octreotide acetate.

Abnormalities in cholesterol metabolism cause peripheral neuropathy and dementia in AIDS--a hypothesis.

The AIDS dementia complex and peripheral neuropathy in AIDS are considered to be direct or indirect manifestations of HIV infection, yet the pathogenesis in unclear. There are parallels between AIDS and Tangier disease clinically and histopathologically and in lipid metabolism. The neurological disorders in AIDS may be caused by dysfunction of cellular cholesterol transport. Substitution of high density lipoprotein is recommended in the treatment of severe polyneuropathy and dementia in AIDS.