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Biomedical subjects

O A Müller

Publications and source records attributed to O A Müller.

At least 55 records · Page 3Linked to original sources
PubMed1989

Early diagnosis of multiple endocrine neoplasia type IIa.

We report on incidental findings during family screening of two kindreds with multiple endocrine neoplasia type IIa. Pheochromocytoma and medullary thyroid carcinoma of considerable size were detected. The results underline the importance of early diagnosis of the syndrome, since the afflicted may be almost or wholly asymptomatic. High resolution chromosome banding studies were carried out in both families, but no abnormality was found. Linkage analysis using DNA markers closely related to the chromosomal locus at chromosome 10 was carried out and was positive in two asymptomatic offspring of one family, whereas the markers were not informative in a second family. We recommend early linkage analysis for establishing the genetic status in offspring of multiple endocrine neoplasia type IIa families to identify for further screening those who are predicted to be gene carrier.

Adrenal Gland Neoplasms↗
PubMed1989

Interaction of L-dopa and GHRH on GH secretion in normal men.

To determine how L-dopa stimulates GH secretion, we investigated its interaction with GHRH in vivo. Six normal men were studied on 4 occasions: 1) L-dopa-TRH: 500 mg L-dopa orally followed by 200 micrograms TRH 60 min later; 2) L-dopa-GHRH-TRH: 100 micrograms GHRH 1-44 iv 30 min after L-dopa followed by 200 micrograms TRH iv; 3) GHRH-TRH: 100 micrograms GHRH iv at 0 min, 30 min later 200 micrograms TRH iv; 4) TRH test: 200 micrograms TRH iv as a bolus. After L-dopa-TRH GH-levels increased significantly from 0.6 micrograms/l to 25.8 +/- 9.6 (SE) micrograms/l at 60 min. Only a slight TSH and no PRL increase was observed after L-dopa-TRH. After L-dopa-GHRH-TRH the GH-increase was significantly higher (45.7 +/- 11.1 micrograms/l) compared to L-dopa-TRH alone. GHRH-TRH increased GH-levels to 52.5 +/- 12.1 micrograms/l, which was not significantly different from the GH-levels obtained when L-dopa-GHRH-TRH were given. TRH increased serum TSH and PRL to 6.3 +/- 0.7 microU/ml and 715 +/- 136 microU/ml, respectively, which was significantly higher compared to the TSH responses after L-dopa-TRH. The PRL and TSH increase after TRH only was also higher (TSH-max: 5.7 +/- 0.5 microU/ml; PRL-max: 899 +/- 154 microU/ml) compared to the TSH and PRL responses after L-dopa-TRH. Our results show that the combination of L-dopa with GHRH leads to the same GH response as GHRH only. However, both responses are significantly higher than the one after L-dopa alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Endocrinological studies in alcoholics during withdrawal and after abstinence.

Several endocrine parameters were assessed in 35 alcoholic inpatients after admission to hospital, and 17 of the 35 were retested after several weeks of sobriety. No difference was found in clonidine-stimulated growth hormone (GH) secretion between male alcoholics and male healthy controls, but significant positive correlations of GH secretion and alcohol content in expired breath on admission and gamma-GT values after abstinence were observed. Nonsuppression in the dexamethasone suppression test was found in 17% of the patients on admission, which seemed to be due to alcohol withdrawal. Postdexamethasone cortisol levels were significantly positively correlated with the "apathic syndrome" (r = 0.40; p less than or equal to 0.05). About one-third of the patients showed a blunted response in the TRH-test both on admission and after abstinence. No significant influence of alcohol intake, withdrawal or familial disposition on prolactin values could be detected. The results of the TRH test and the DST point to similar endocrinological patterns in alcoholics as in depressive patients and thus support the hypothesis of a link between alcoholism and depression.

Adrenocorticotropic Hormone↗
PubMed1989

Acute dexamethasone suppression of ACTH secretion stimulated by human corticotrophin releasing hormone, AVP and hypoglycaemia.

In order to obtain more insight into the mechanisms regulating endogenous ACTH secretion in humans we studied the inhibitory effect of acute i.v. dexamethasone administration on ACTH release under various conditions. Six male volunteers were subjected to six different protocols. After combined i.v. injection of 100 micrograms corticotrophin releasing hormone (CRH) and 100 micrograms growth hormone releasing hormone (GRH) there was the expected rise in ACTH (area under the curve, 1053 +/- 204 (SE) (pmol/l) min) and cortisol (59788 +/- 10098 (nmol/l) min) rise which was suppressed by prior i.v. injection of 2 mg dexamethasone (ACTH: 444 +/- 63 (pmol/l) min; cortisol: 28528 +/- 2152 (nmol/l) min). Insulin hypoglycaemia (IH) led to a more pronounced ACTH and cortisol rise compared with CRH (6307 +/- 817 (pmol/l) min and 82080 +/- 21934 (nmol/l) min, respectively) which was not completely suppressed by prior pretreatment with dexamethasone (ACTH, 580 +/- 103 (pmol/l) min; cortisol: 55649 +/- 5821 (nmol/l) min). Combined AVP/CRH injection (10 IU/100 micrograms) after pretreatment with dexamethasone (344 +/- 41 (pmol/l) min for ACTH; 32832 +/- 3173 (nmol/l) min for cortisol) could not reproduce the ACTH secretion following IH after pretreatment with dexamethasone (579 +/- 103 (pmol/l) min for ACTH and 55649 +/- 5821 (nmol/l) min for cortisol). In all subjects a saline control with 2 mg dexamethasone was performed. These findings confirm the acute inhibitory effect of glucocorticoids on CRH-stimulated ACTH secretion. Since CRH-induced ACTH secretion is almost completely abolished by administration of dexamethasone the ACTH rise following IH after dexamethasone can not be mediated by endogenous CRH alone. Moreover, since the addition of AVP to CRH (after dexamethasone suppression) could not reproduce the ACTH rise during IH after dexamethasone pretreatment, an additional, yet unknown factor stimulating ACTH secretion may be involved. In the same protocols, no significant difference could be observed comparing IH and GRH induced GH secretion (4948 +/- 1172 (mU/l) min vs 3596 +/- 820 (mU/l) min, NS); furthermore, in contrast to results obtained by chronic steroid administration, acute i.v. dexamethasone pretreatment did not affect IH or GRH-induced GH secretion (4110 +/- 666 (mU/l) min vs 2916 +/- 462 (mU/l) min, NS). The GRH-stimulated GH secretion (3596 +/- 820 (mU/l) min) was not suppressed by prior intravenous treatment with dexamethasone (2916 +/- 504 (mU/l) min, NS).

Adrenocorticotropic Hormone↗
PubMed1989

Interaction of clonidine and GHRH on GH secretion in vivo and in vitro.

UNLABELLED: To investigate the mechanism by which clonidine stimulates GH-secretion in vivo and in vitro, we studied its interaction with GHRH. In vivo: eight or six normal male subjects were submitted to five protocols: (1) 150 micrograms clonidine orally followed by 50 micrograms GHRH 1-44 i.v. 2 h later, (2) 50 micrograms GHRH 1-44 i.v. followed by 150 micrograms clonidine orally 2 h later, (3) 150 micrograms clonidine orally followed by GHRH i.v. 30 min later, (4) 300 micrograms clonidine orally followed by 50 micrograms GHRH i.v. 3 h later and (5) 50 micrograms GHRH i.v. followed by 300 micrograms clonidine orally 90 min later. In vitro: Rat anterior pituitary cells were coincubated with clonidine (10(-11), 10(-9), 10(-7) and 10(-5) M) and GHRH (0.005, 0.05, 10 nM) for 4 h. RESULTS: 150 micrograms clonidine alone does not stimulate GH-secretion. Furthermore, the GH-increase was not significantly different when GHRH bolus was given before, after or together with clonidine. When 300 micrograms clonidine was given before GHRH GH-levels were significantly higher (max 28.6 +/- 8.0 mU/l) at 90 min, compared to when clonidine was given after GHRH (max 7.8 +/- 3.6 mU/l). The GHRH bolus after clonidine led to a significantly lower GH-increase (max 31.6 +/- 17.0 mU/l) compared to the GHRH-induced GH-increase (max 47.2 +/- 13.0 mU/l) before clonidine. In vitro, clonidine had no stimulatory effect on GHRH-stimulated GH secretion. These findings are compatible with clonidine leading to stimulation of GH by inducing endogenous GHRH release.

Adult↗
PubMed1989

Nitroimidazole derivatives inhibit anterior pituitary cell function apparently by a direct effect on the catalytic subunit of the adenylate cyclase holoenzyme.

Nitroimidazole derivatives dose-dependently decreased basal and CRF-stimulated ACTH release, basal and GRF-stimulated rat GH release, and basal rat PRL release in primary cultures of rat anterior pituitary cells. In addition, basal and CRF-stimulated mRNA coding for the ACTH precursor were reduced after preincubation with the nitroimidazole derivatives. Miconazole, econazole, isoconazole, clotrimazole, and bifonazole had similar or more pronounced effects on anterior pituitary function compared to ketoconazole, whereas metronidazole and etomidate were less effective. The positive correlation between the number of phenylated side-chains or phenolic rings of the imidazole molecule and the efficacy to inhibit activity on pituitary hormone secretion suggests a structure-activity relationship of these compounds. The effects of the nitroimidazole derivatives on anterior pituitary hormone release and biosynthesis were mediated by cAMP. Thus, basal and CRF-, cholera toxin-, and forskolin-stimulated adenylate cyclase activities in rat anterior pituitary cell membranes determined by cAMP formation were suppressed by the nitroimidazole derivatives. Pertussis toxin did not diminish the nitroimidazole derivative effect on cAMP formation. The adenylate cyclase inhibitory effect of these substances was independent of the presence of GTP in the assay system, underlining a direct effect on the catalytic subunit. In addition, basal and forskolin-stimulated cAMP generation in membranes of S49 lymphoma cyc-variants, which lack a functional Gs protein, was efficiently suppressed (by up to 90%) by the nitroimidazole derivatives. In conclusion, ketoconazole and other nitroimidazole derivatives inhibit anterior pituitary hormone synthesis and secretion apparently by a direct effect on the catalytic subunit of the adenylate cyclase system.

Adenylyl Cyclase Inhibitors↗
PubMed1989

Effects of repetitive administration of thyrotropin-releasing hormone at short intervals in acromegaly.

We investigated the pattern of GH secretion in response to repetitive TRH administration in patients with active acromegaly and in normal subjects. Nine acromegalic patients and 10 normal subjects received three doses of 200 micrograms of TRH iv at 90-min intervals. There was a marked serum GH rise in acromegalic patients after each TRH dose (net incremental area under the curve [nAUC]: first dose = 4448 +/- 1635 micrograms.min.l-1; second dose = 3647 +/- 1645 micrograms.min.l-1; third dose = 4497 +/- 2416 micrograms.min.l-1; NS), though individual GH responses were very variable. In normal subjects TRH did not elicit GH secretion even after repeated stimulation. Each TRH administration stimulated PRL release in acromegalic patients, though the nAUC of PRL was significantly higher after the first (1260 +/- 249 micrograms.min.l-1) than after the second and the third TRH administration (478 +/- 195 and 615 +/- 117 micrograms.min.l-1, respectively; P less than 0.01). In normal subjects too, PRL secretion was lower after repeated stimulation (first dose = 1712 +/- 438 micrograms.min.l-1; second dose = 797 +/- 177 micrograms.min.l-1; third dose = 903 +/- 229 micrograms.min.l-1 P less than 0.01), though different kinetics of PRL secretion were evident, when compared with acromegalic patients. TSH secretion, assessed in only 4 patients, was stimulated after each TRH dose, though a minimal but significant reduction of nAUC of TSH after repeated TRH challenge occurred. Both T3 and T4 increased steadily in the 4 patients. The same pattern of TSH, T3, and T4 secretion occurred in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1989

Human corticotropin-releasing hormone during pregnancy.

Elevated irCRH levels up to 14 ng/ml were measured in 176 females in the last trimester. The highest maternal CRH levels were found in those females in whom the period from the onset of labour to full dilatation of the cervix and the time span of delivery were shortest. irCRH in amniotic fluid (120 +/- 180 pg/ml; n = 14) was in the same range as in umbilical cord plasma (233 +/- 188 pg/ml; n = 66) and 20-fold lower than in prepartal maternal plasma (5.38 +/- 4.49 ng/ml; n = 66). irCRH in maternal plasma correlated highly to irCRH in umbilical cord plasma (p less than 0.001; n = 66). After delivery irCRH disappeared from maternal plasma with a half-life of 50 minutes (n = 14). One day postpartum irCRH levels (n = 22) were undetectable. The height of the irCRH levels in the various biological fluids did not correlate to the mode or the pathological events of delivery (n = 43). Maternal ACTH levels above the normal range were encountered only in women immediately prepartal and did not correlate to the CRH levels (253 +/- 229 pg/ml; n = 66). Cortisol levels were higher in maternal plasma than in umbilical cord plasma due to elevated CBG (n = 78). Free cortisol levels were higher in the 3rd trimester than in the 1st (2.18 +/- 0.16 vs 1.16 +/- 0.73 ng/ml; n = 42). irCRH in maternal and umbilical cord plasma correlated to the hPl and estriol levels (p less than 0.001 and p less than 0.05; n = 66). We conclude that irCRH is secreted by the placenta into both maternal and fetal circulation. Though placental CRH is undistinguishable from hypothalamic CRH, the biological significance of placental CRH remains open. Our data show that placental CRH might be responsible for the changed function of the adrenal gland during pregnancy, with higher free cortisol levels in the last trimester. The extremely elevated ACTH levels during labour and delivery indicate that CRH is not the only mediator of stress-induced ACTH secretion in the regulation of the maternal hypothalamo-pituitary-adrenal axis.

Adolescent↗
PubMed1989

Evaluation of selective transsphenoidal adenomectomy by endocrinological testing and somatomedin-C measurement in acromegaly.

A series of 29 previously untreated patients with acromegaly underwent transsphenoidal adenomectomy. Pre- and postoperative evaluation consisted of measuring growth hormone (GH) secretory dynamics during an oral glucose tolerance test (OGTT), the insulin hypoglycemia test, and the thyrotropin- and gonadotropin-releasing hormone (TRH/GnRH) test, and by obtaining the basal somatomedin-C level. After surgery, clinical and biochemical amelioration was achieved in all but two patients. In the whole group, basal GH and somatomedin-C levels decreased from a mean (+/- standard error of the mean) of 52.3 +/- 12.7 to 11.1 +/- 6.3 ng/ml and from 7.6 +/- 0.7 to 2.5 +/- 0.5 U/ml, respectively. Application of different criteria of cure revealed that 19 patients (66%) had basal GH levels below 5 ng/ml, 17 patients (59%) had normal somatomedin-C values, 16 patients (55%) had complete GH suppression (less than 1 ng/ml) during OGTT, and 13 patients (45%) met the above-mentioned criteria with disappearance of the paradoxical GH response to TRH/GnRH test. Evaluation of GH secretion by insulin hypoglycemia testing was useless in assessing the outcome after neurosurgery. When only patients with a normal somatomedin-C level and complete GH suppressibility during OGTT were considered "cured," the main favorable prognostic factor was intrasellar tumor localization, since 15 (75%) of 20 patients were "cured," as opposed to only one (11%) of nine with extrasellar extension of the adenoma. During the follow-up period, no tumor recurrence was detected in any of the "cured" patients. In these subjects somatomedin-C levels remained stable in all except two patients, who showed a slow increase within the normal range of somatomedin-C concentration. These data confirm that transsphenoidal surgery is the most effective form of treatment in previously untreated acromegalic patients and that normalization of somatomedin-C levels reflects normal GH secretion. Measurement of somatomedin-C could replace more extensive endocrinological testing during monitoring of treated acromegalic patients.

Acromegaly↗
PubMed1988

Transsphenoidal surgery with the additional use of the Nd-Yag-laser.

100 Patients with pituitary adenomas were operated upon by the transsphenoidal route with additional use of the Nd-Yag-Laser. For this purpose, a suitable microsurgical handpiece has been developed. The energy output used in these operations was 30 W with a coagulation time not exceeding two seconds. Both the selectivity and radicality of the surgical procedure was documented by endocrinological investigation as well as by ophthalmological testing and radiological follow-up using high resolution CT and, more recently, Magnetic Resonance Imaging. When compared with the series of other authors, the selectivity as reflected by testing the anterior lobe functions pre- and postoperatively was not altered by the additional use of the Laser. The Nd-Yag-Laser seems to be a useful device in transsphenoidal surgery due to its potent coagulation effect and comfortable handling. If applied in a correct manner, there is no risk of additional damage to normal pituitary tissue and the surrounding structures. The possibility of coagulating tumour remnants, which cannot be removed by curettage, may increase also the radicality of the procedure.

Adenoma↗
PubMed1988

Effects of theophylline infusion on the growth hormone (GH) and prolactin response to GH-releasing hormone administration in acromegaly.

Since theophylline has been shown to blunt the GH response to growth hormone-releasing hormone (GHRH) in normal subjects, we investigated whether the same effect of theophylline administration could be reproduced in patients with active acromegaly. Ten acromegalic patients received on two different days 100 micrograms GHRH iv alone and the same GHRH dose during a constant infusion of theophylline (3.56 mg/min), beginning 2 h before GHRH administration. In the whole group theophylline did not affect basal GH secretion significantly (from a mean of 44.6 +/- 14.4 at 0 min to 41.8 +/- 13.5 ng/ml at 120 min). However, the amount of GH released after GHRH stimulation was lower when theophylline was concomitantly infused (7525 +/- 3709 ng min/ml vs. 12038 +/- 6337 ng min/ml; p less than 0.05). The inhibitory effect of theophylline was not homogeneous, since either marked or minimal reductions of the GHRH-stimulated GH secretion occurred. Serum PRL levels increased after GHRH administration in 6 patients and theophylline infusion had no influence upon this response. Peak GHRH levels were not different in both studies (14.9 +/- 1.7 and 17.1 +/- 4.0 ng/ml, respectively). Free fatty acid levels rose progressively during theophylline administration (from 0.66 +/- 0.10 at 0 min to 1.04 +/- 0.10 mEq/l at 240 min) and were significantly higher than after GHRH stimulation alone from 180 min up to the end of the test. Our results demonstrate that in active acromegaly theophylline blunts the GH response to GHRH, though this effect is not uniformly seen in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1988

Exaggerated corticotrophic cell response to human corticotropin-releasing hormone in two patients during long-term carbamazepine treatment.

Carbamazepine, a tricyclic anticonvulsant with chemical resemblance to imipramine, has been recently successfully introduced as a prophylactic agent and acute treatment modality for manic-depressive illness (Ballenger and Post 1980; Okuma 1983; Post et al. 1984). The interest in carbamazepine emerges from its ability to dampen paroxysmal neuronal activity not only in epilepsy, but also in those particular systems that appear to be involved in the etiology of episodic affective illness (Post et al. 1983). These affective episodes are frequently associated with endocrine irregularities of the hypothalamic-pituitary-adrenocortical (HPA) axis, including increased cortisol secretion (Halbreich et al. 1985), nonsuppression of corticosteroids following dexamethasone, and blunted corticotropin (ACTH) release after stimulation with human corticotropin-releasing hormone (h-CRH) (Holsboer et al. 1986, 1987) or its heterologous ovine analog (Gold et al. 1986). Some recent reports have shown that carbamazepine treatment may interfere with HPA physiology, as it induces Dexamethasone Suppression Test (DST) nonsuppression (Privitera et al. 1982; Rubinow et al. 1984) and enhances mean urinary free cortisol secretion (Rubinow et al. 1986). To further explore the pathophysiology of this phenomenon of an altered HPA function, we conducted h-CRH tests in six patients in stable remission from major depression during long-term carbamazepine treatment to look for possibly drug-induced modulations. In two of six patients, we observed highly abnormal ACTH responses.

Adrenocorticotropic Hormone↗
PubMed1988

Blunting of ACTH response to human CRH in depressed patients is avoided by metyrapone pretreatment.

The current concept that blunted adrenocorticotropic hormone (ACTH) response to human corticotropin-releasing-hormone (h-CRH) in depression is primarily determined by elevated circulating plasma cortisol levels is still unproven. We tested this hypothesis by comparing ACTH release following intravenous administration of 100 micrograms h-CRH in 10 normal controls and in 21 inpatients with a major depressive episode. Eleven of these depressed patients were pretreated with an oral dose of 2 g metyrapone, which inhibits cortisol biosynthesis by blocking C-11 beta-steroid-hydroxylase. This intervention deprives the entire system of cortisol, which is the major feedback signal for the regulation of ACTH secretion at various pituitary and limbic sites. ACTH responses, assessed as areas-under-time-course-curves, were: in normal controls, 6.8 +/- 2.4 (SD) pg/ml/min x 10(3); in unmedicated patients, 2.6 +/- 1.1 pg/ml/min x 10(3); and in metyrapone pretreated patients, 9.0 +/- 6.7 pg/ml/min x 10(3). Thus, ACTH release in unmedicated depressed patients was significantly (p less than 0.001, Mann-Whitney U-test) blunted when compared with normal controls. In contrast, this blunting was completely avoided after metyrapone pretreatment, which resulted in net ACTH responses that were indistinguishable from those of the controls.

Adrenocorticotropic Hormone↗
PubMed1988

Acute adrenocortical stimulation by recombinant gamma interferon in human controls.

We examined the effect of 20 micrograms recombinant gamma-interferon (rec-gamma-IFN) upon corticotropin (ACTH) and cortisol secretion in 10 healthy male controls. We observed that rec-gamma-IFN enhances cortisol secretion with maxima around 3 hours after injection of the test dose. This effect was suppressible by a single dose of 1.5 mg dexamethasone and was not associated with increased ACTH secretion. Rec-gamma-IFN also failed to enhance ACTH secretion from a pituitary cell culture. From these data we conclude that rec-gamma-IFN acts on lymphoid cells which in turn release a yet unidentified substance that directly activates the adrenocortex in a feedback controlled manner.

Adrenal Cortex↗