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Biomedical subjects

M F Scanlon

Publications and source records attributed to M F Scanlon.

At least 127 records · Page 7Linked to original sources
PubMed1987

Clinical value of immunoradiometric assay of thyrotropin for patients with nonthyroidal illness and taking various drugs.

Using a two-site immunoradiometric assay, we measured concentrations of thyrotropin (TSH) in serum of 134 clinically euthyroid subjects, 93 patients with nonthyroidal illness, and 80 patients who were being treated with various drugs. Abnormal concentrations of TSH, free thyroxin, and free triiodothyronine, respectively, were recorded in serum of three (3.2%), 19 (20.4%), and 37 (39.8%) of the patients with nonthyroidal illness and in three (3.8%), five (6.3%), and 10 (12.5%) of the patients taking drugs. TSH could be detected in all patients' serum samples. We conclude that, for most patients without thyroid disease, a basal (i.e., unstimulated) measurement of their TSH concentration in serum will indicate their thyroid status more reliably than will assay of free thyroxin or free triiodothyronine.

Adolescent↗
PubMed1986

Trial of strategy for reducing the use of laboratory tests.

Clinical guidelines and a weekly review of medical records were introduced into a medical unit in a teaching hospital to promote a more discriminating use of laboratory tests. This strategy resulted in an immediate reduction in the average number of requests each week from 74 to 27 haematological tests (64%) and 158 to 58 biochemical tests (64%). During a period of 10 weeks after the strategy was introduced (the intervention period) the mean number of haematological tests for each person decreased from 2.0 during the baseline period to 1.1 (45% reduction; p less than 0.01) and the mean number of biochemical tests decreased from 4.4 to 2.7 (39%; p less than 0.0001). The decrease in the number of repeat requests was greater than that for new requests and accounted for half the reduction in use. There was no significant change in the number of tests requested from an adjacent medical unit that was not exposed to the interventions. This strategy is worthy of trial in other specialties and hospitals, but attention will have to be paid to possible difficulties in sustaining reductions in use over long periods of time.

Clinical Laboratory Techniques↗
PubMed1986

Inappropriate thyrotrophin secretion, increased dopaminergic tone and preservation of the diurnal rhythm in serum TSH.

A patient presented with mild hyperthyroidism, elevated serum T4 and T3, and an inappropriately raised serum thyrotrophin (TSH). There was no evidence of pituitary tumour (alpha-subunit secretion and CT scan of the pituitary were normal). The TSH response to TRH was greater than normal. The elevated TSH was suppressed by oral triiodothyronine (100 micrograms daily for 10 d). The normal diurnal variation of TSH was preserved. Intravenous injection of the dopamine receptor blocking agent domperidone led to a greater than normal elevation in TSH (maximum increments 18-20 mU/l). This increased dopaminergic tone was similar in studies carried out in the morning and late evening. The dopamine agonist bromocriptine (2.5 mg twice daily) failed to suppress serum TSH either acutely or over 6 weeks. The circadian rhythm was unaltered by this treatment. Basal serum prolactin levels were normal, and responded appropriately to TRH, domperidone and bromocriptine. These observations indicate that dopamine does not control the diurnal variation of TSH in nontumoral TSH-mediated hyperthyroidism. The increased dopaminergic tone demonstrated may be secondary to the primary failure of pituitary-thyroid feedback in the condition.

Adult↗
PubMed1986

The circadian variation of thyrotrophin in patients with primary thyroidal disease.

We have used a highly sensitive immunochemiluminometric assay (ICMA) for human TSH to study the effect of thyroid status on the circadian variation in TSH levels. Three subjects with Graves' disease, three with toxic multinodular goitre and three with euthyroid multinodular goitre were sampled every hour for 24 h. The results obtained were compared to those from five euthyroid control subjects. It was found that some patients with hyperthyroidism and suppressed basal TSH levels exhibited a 24 h secretory pattern similar to that seen in normal subjects with peak TSH levels occurring at night. In addition two subjects with a euthyroid multinodular goitre demonstrated levels of TSH below the normal range despite being clinically and biochemically euthyroid. TSH suppression in these subjects is probably related to some degree of thyroid autonomy and possible development of hyperthyroidism in the future.

Adult↗
PubMed1986

Lack of effect of muscarinic cholinergic blockade on the GH responses to GRF 1-29 and TRH in acromegalic subjects.

It is well known that muscarinic cholinergic blockade either reduces or abolishes stimulated GH release in normal subjects. In this study we have investigated whether cholinergic muscarinic blockade could reduce the GH responses to GRF 1-29 and TRH in acromegalic subjects. Eight acromegalic subjects underwent two GRF tests (GRF 1-29, 1 microgram/kg i.v.) with and without pirenzepine (0.6 mg/kg, i.v.). A further four of these patients received TRH (200 micrograms/kg, i.v.) on separate occasions with and without pirenzepine (0.6 mg/kg, i.v.). Cholinergic muscarinic blockade did not alter the GH responses to GRF and TRH in patients with acromegaly. These findings are in contrast with previous data reported on the effects of cholinergic blockade on stimulated GH levels in normal subjects and in patients with type I diabetes mellitus and are compatible with the view that somatotroph adenomas are functionally disconnected from hypothalamic control mechanisms.

Acromegaly↗
PubMed1986

The preoperative and postoperative investigation of TSH and prolactin release in the management of patients with hyperprolactinaemia due to prolactinomas and nonfunctional pituitary tumours: relationship to adenoma size at surgery.

We report here our results of the pre- and post-operative assessment of prolactin and TSH status in 41 hyperprolactinaemic patients who underwent pituitary surgery over a 5 year period. Preoperatively in patients with prolactinomas (n = 33) the TSH response to domperidone decreased with increasing adenoma size. When the data are expressed on a group mean basis the exaggerated TSH response to domperidone in preoperative prolactinoma patients was reduced significantly in patients rendered normoprolactinaemic by surgery but persisted in those who remained hyperprolactinaemic. Similarly the reduced preoperative PRL responses to domperidone and TRH were significantly increased by successful surgery. In contrast patients with stalk-compression hyperprolactinaemia (n = 6) due to larger lesions which were not prolactinomas all showed reduced or absent TSH responses to domperidone. The PRL responses to domperidone and TRH were reduced or absent both in patients with prolactinomas and in those with stalk-compression hyperprolactinaemia. All patients with stalk-compression hyperprolactinaemia showed a delayed pattern of TSH response to TRH with 60 min values being greater than 20 min ones. In contrast a normal pattern of TSH response to TRH was observed in all patients with hyperprolactinaemia due to prolactinomas. Postoperatively TSH and PRL responses were largely unchanged in patients with stalk-compression hyperprolactinaemia regardless of whether normoprolactinaemia was restored by surgery. In conclusion a reduced or absent PRL response to TRH or domperidone is not diagnostic of the presence of a prolactinoma since it occurs in hyperprolactinaemic patients with prolactinomas or stalk-compression. In contrast, the TSH response to acute dopamine antagonism is exaggerated in most patients with small prolactinomas but not in those with stalk-compression hyperprolactinaemia and we have found this to be helpful diagnostically since the presence of an exaggerated TSH response to dopamine antagonism is evidence against the presence of stalk-compression hyperprolactinaemia. The observation of a delayed TSH response to TRH in a hyperprolactinaemic patient should alert the clinician to the possibility of stalk-compression hyperprolactinaemia due to a large lesion which may not be a prolactinoma.

Adenoma↗
PubMed1986

The effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia.

To assess the effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia, six healthy male volunteers each underwent two insulin tolerance tests in random order, separated by at least 1 week with and without atropine. ACTH levels were significantly greater at +45 min (mean +/- SEM, 223 +/- 21 pg/ml vs 148 +/- 15 pg/ml, P less than 0.01) and at +120 min (54 +/- 11 pg/ml vs 29 +/- 10 pg/ml, P less than 0.05). beta-endorphin levels were significantly greater at +30 min (170 +/- 45 pg/ml vs 96 +/- 32 pg/ml, P less than 0.05) and at +105 min (81 +/- 14 pg/ml vs 54 +/- 7 pg/ml, P less than 0.01). Cholinergic blockade had no effect on plasma glucose or cortisol concentrations. This study demonstrates that cholinergic blockade with atropine facilitates the ACTH and beta-endorphin responses to insulin-induced hypoglycaemia without altering the cortisol responses.

Adrenocorticotropic Hormone↗
PubMed1986

Growth hormone responses to GRF 1-29 in patients with primary hypothyroidism before and during replacement therapy with thyroxine.

It is well known that hypothyroidism is frequently associated with impaired GH responses to different stimuli. In the present study we have evaluated GH responses to GH-releasing factor (GRF) in patients with primary hypothyroidism before and during T4 replacement therapy. Fourteen patients (age range 26-60 years) underwent two GRF tests (1 microgram/kg) before and during replacement therapy (150 micrograms/d). Administration of T4 increased peak GH responses to GRF in 9 patients and in the group as a whole (mean +/- SEM, 17.0 +/- 2.8 vs 32.6 +/- 5.7 mU/l, P less than 0.02). When the data are analysed by means of area under the curve (AUC), the GH response to GRF was increased by T4 in 10 patients and in the group as a whole (mean +/- SEM, 51.7 +/- 14.3 vs 101.5 +/- 28.1, P less than 0.02). These data indicate that thyroid hormone replacement therapy enhances the responsiveness of the somatotroph to GRF 1-29 in patients with primary hypothyroidism.

Adult↗
PubMed1986

Cholinergic muscarinic receptor blockade with pirenzepine abolishes slow wave sleep-related growth hormone release in normal adult males.

Cholinergic pathways play an important role in the regulation of GH secretion from the anterior pituitary gland, and in this study we have investigated whether cholinergic muscarinic receptor blockade with pirenzepine displayed any inhibitory action on slow wave sleep-related GH release in normal subjects. Six adult males (ages 24-37 years) were studied in a randomized order and fasted from 1800 h on each study day. All subjects showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 4-50 mU/l). In contrast, pirenzepine treatment (100 mg p.o. at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. These data demonstrate clearly that cholinergic muscarinic receptor blockade completely abolishes slow wave sleep-related GH release in normal adult subjects. Because of the striking effects it is reasonable to conclude that acetylcholine plays an important stimulatory role in mediating slow wave sleep-related GH release. This finding may have investigational and therapeutic applications in young patients with Type 1 diabetes mellitus since GH is implicated in some acute metabolic and chronic microvascular complications of this disease.

Adult↗
PubMed1986

Thyroid function in patients with hyperprolactinaemia: relationship to dopaminergic inhibition of TSH release.

It has been reported recently that patients with hyperprolactinaemia may develop hypothyroidism as a consequence of the increased inhibition of TSH release by dopamine which occurs in the majority of such patients. In this study we have evaluated thyroid function in a large number of hyperprolactinaemic patients in order to delineate more precisely the relationship between thyroid status, free thyroid hormone levels and the control of TSH release by dopamine. Biochemical euthyroidism was present in the majority of the hyperprolactinaemic patients. Our data indicate that the increased dopaminergic inhibition of TSH release does not lead to hypothyroidism. Instead, the slightly elevated basal TSH levels and TSH responses to TRH (within the normal range) may reflect the operation of a compensatory mechanism to maintain euthyroidism in the face of te increased inhibition of TSH release by hypothalamic dopamine.

Adult↗
PubMed1986

Influence of dopaminergic, adrenergic and cholinergic blockade and TRH administration on GH responses to GRF 1-29.

In order to establish the influence of dopaminergic, alpha-adrenergic and cholinergic pathways on GRF-mediated GH release we have studied the GH responses to GRF 1-29 (100 or 50 micrograms as i.v. bolus) alone and in combination with metoclopramide (MCP, 10 mg, i.v.), thymoxamine (THYM, 210 micrograms/min, 150 min infusion), and atropine (1.2 mg, i.v.). We have also investigated any possible interaction between TRH and GRF in view of the reported inhibitory effects of TRH infusion on stimulated GH release. Dopaminergic and alpha-adrenergic blockade with MCP and THYM respectively, did not have any effect on the GH responses to GRF. This lack of effect strongly suggests that any action which these neurotransmitters may exert on GH secretion is not at a pituitary level. TRH did not modify the GH response to GRF suggesting that the inhibitory effect on stimulated GH secretion is exerted at a hypothalamic level. In contrast, GH responses to GRF were significantly reduced by prior administration of atropine. These data support the view that cholinergic pathways play an important role in the regulation of GH secretion and such control may be exerted at both hypothalamic and pituitary levels.

Adult↗
PubMed1986

Differential production of SRIF 14 and 28 by fetal rat hypothalamic cells enriched by velocity sedimentation.

Dispersed day-17 fetal rat hypothalamic cells have been enriched according to size by velocity sedimentation prior to culture, and the SRIF production by these enriched populations was compared with that of other enriched cell fractions and with mixed-cell cultures. Cultures of mixed cells produced 100-400 pg SRIF/10(6) cells/4 h over a period of 28 days. Total SRIF production by mixed cells was inversely proportional to seeding density over the range 0.25-1 X 10(6) cells/ml/well and SRIF 14 and 28 were secreted in a ratio of approximately 6:1. Although secretory rates by low cell densities remained higher than those by high cell densities, SRIF production decreased with time at all seeding densities (up to 21 days). Dispersed fetal hypothalamic cells were enriched according to size by allowing them to sediment over 4 h through a shallow gradient of BSA in culture medium and subsequent cell fractions developed widely differing morphologies in monolayer cultures. In contrast to mixed-cell cultures, SRIF production at 8 days by both large and small cells were directly proportional to initial seeding density. Furthermore, the smaller cells secreted very much less SRIF than the larger cells (100 pg/10(6) cells/4 h vs. 1,300 pg/10(6) cells/4 h), whereas there was little difference in overall SRIF content (350 pg/10(6) cells vs. 400 pg/10(6) cells). Characterisation by HPLC of the SRIF content and secretion of smaller cells revealed SRIF 14 to 28 ratios of 7:1 and 3:1, respectively. In contrast in the large cells, the ratio was 1:1 for both content and secretion. Therefore, these cell groups contain and secrete different proportions of these 2 molecular forms of SRIF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Thyrotropin regulates thyrotroph responsiveness to dopamine in vitro.

The effect of conditioned vs. fresh culture medium on the dopaminergic inhibition of TSH and PRL secretion by primary cultures of male rat anterior pituitary cells has been studied. In the presence of conditioned medium (that had been in contact with the cells over the 3-day culture period) 10(-6) M dopamine (DA) inhibited PRL secretion by 50% and TSH secretion by 30%. After 4 h of incubation with fresh medium 10(-6) M DA still inhibited PRL secretion by 50% but increased TSH release by 20%. TSH release was rapid and could be prevented by 10(-6) M prazosin, an alpha 1 adrenoreceptor antagonist. Fresh medium did not alter TRH induced TSH release. In parallel cultures and under identical conditions fresh medium reduced [3H]dihydroergocryptine (DHE) binding to DA receptors from 2.5 +/- 0.4 fmol/10(5) cells to 0.95 +/- 0.3 fmol/10(5) cells (means +/- SEM, n = 5, P less than 0.001). The effect of fresh medium was dose dependent against the dopaminergic inhibition of TSH secretion and against DA receptor binding. If 1 mU TSH was included, in fresh medium, the dopaminergic inhibition of TSH secretion remained unchanged and [3H]DHE binding to DA receptors did not fall. The rank order of potency of thyroid stimulators was bovine TSH (21 U/mg) greater than semipurified bovine TSH (Thytropar, 1.4 U/mg) greater than endogenous rat TSH (0.03 U/mg expressed as NIADDK-rat TSH-RP2) greater than Graves' immunoglobulin G (0.01 U/mg) when either DA or bromocriptine was used as the dopaminergic agonist. When anterior pituitary cells from hypothyroid rats were examined, the effects of culture medium on the dopaminergic inhibition of TSH and on DA receptor binding were approximately twice those observed in normal cells, but the inclusion of 1 mU TSH in the fresh medium completely prevented the loss of DA function and binding. PRL, human CG, ACTH, insulin, glucagon, and heat-inactivated TSH were unable to prevent the effect of medium replacement on dopaminergic inhibition of TSH and DA receptor binding. The data suggest a mechanism whereby TSH may control its own secretion via DA.

Adrenocorticotropic Hormone↗
PubMed1986

Hypothalamic D2 receptors mediate the preferential release of somatostatin-28 in response to dopaminergic stimulation.

We have studied the effect of dopamine (DA) together with agonist and antagonist drugs of varying specificity on the release of immunoreactive forms of somatostatin (SS) from the perfused, adult rat hypothalamus in vitro. Levels of SS increased from 14.7 +/- 3.7 pg (mean +/- SE) under basal conditions to 137 +/- 23.0 pg after exposure to 10(-6) M DA. This dopaminergic effect was mimicked by the specific D2 agonists bromocriptine (10(-7) M) and LY 171555 (10(-6) M) but not by the D1 agonist SKF 38393A (10(-6) M). The stimulatory action of DA (10(-6) M) was blocked by the active (d) but not the inactive (l) isomer of butaclamol (10(-7) M). Similar blockade was achieved with the specific D2 antagonists metoclopramide (10(-8) M) and domperidone (10(-8) M), whereas the D1 antagonist SCH 23390 partially blocked the stimulation of DA but only when used at X100 greater concentration (10(-6) M). SCH 23390 (10(-8) M) did not affect the dopaminergic stimulation of SS release. HPLC characterization of the immunoreactive forms of SS yielded two peaks which corresponded to SS-28 and SS-14. The ratio of these forms varied significantly under different conditions. In the basal state the ratio of SS-28 to SS-14 was 1:4.4; in response to stimulation with DA, the ratio was 1:1.7 and in response to depolarization with 60 mM K+ the ratio was 1:3.1. In conclusion, the stimulatory action of DA on SS release is mediated via hypothalamic D2 receptors. Furthermore dopaminergic stimulation increases the molar ratio of SS-28 to SS-14 in the total immunoreactive SS which is released.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Atropine blockade of growth hormone (GH)-releasing hormone-induced GH secretion in man is not exerted at pituitary level.

The role of acetylcholine (Ach) in the regulation of human GH secretion was assessed using atropine, which selectively blocks cholinergic muscarinic receptors. Paired tests were performed in seven normal subjects using GH-releasing hormone (GHRH) 1-44 (1 microgram/kg iv), with and without atropine pretreatment (1 mg im). The GHRH 1-44-induced GH secretory peak [20.7 +/- 4.5 (SEM) ng/ml] was completely blocked by atropine administration (2.3 +/- 0.6 ng/ml) (P less than 0.01). To determine whether this atropine blockade was at the pituitary level, a series of in vitro studies were conducted using monolayer cultures of cells from bovine anterior pituitary glands. GHRH 1-44 (10(-8) M) stimulated bovine GH release (11.1 +/- 1.5 micrograms/ml) as compared to control values (5.1 +/- 0.4 microgram/ml) (P less than 0.01). This response was not altered by 10(-6) M atropine (14.9 +/- 0.9 microgram/ml). Similar results were obtained with GHRH, 10(-9) M, with or without atropine, 10(-7) M. Addition of 10(-6) M Ach to the incubation medium significantly increased bovine GH release (12.7 +/- 1.2 microgram/ml) and the effect of 10(-6) M Ach and 10(-8) M GHRH was additive (20.9 +/- 2.1 micrograms/ml) (P less than 0.01). Similar results were obtained with Ach, 10(-5) M, and GHRH, 10(-9) M. Atropine or eserine alone did not alter basal GH secretion, and atropine blocked Ach-stimulating activity. In conclusion, atropine blockade of GHRH-induced GH secretion appears to be exerted at a site other than pituitary.

Acetylcholine↗
PubMed1986

Growth hormone responses to growth hormone-releasing factor (1-29) in euthyroid, hypothyroid and hyperthyroid rats.

In order to investigate whether the impaired GH secretion associated with hypothyroidism and hyperthyroidism is due to a hypothalamic or a pituitary disorder, we have studied plasma GH responses to GH-releasing factor (1-29) (GRF) in euthyroid, hypothyroid and hyperthyroid rats. Hypothyroid rats showed a significant (P less than 0.001) reduction in GH responses to GRF (5 micrograms/kg) at 5 min (350 +/- 35 vs 1950 +/- 260 micrograms/l), 10 min (366 +/- 66 vs 2320 +/- 270 micrograms/l) and 15 min after GRF injection (395 +/- 72 vs 1420 +/- 183 micrograms/l; mean +/- S.E.M.) compared with euthyroid rats. Hyperthyroid rats showed a significant (P less than 0.05) decrease in GH responses to 5 micrograms GRF/kg after 30 min (200 +/- 14 vs 325 +/- 35 micrograms/l) but not at other time-points, or after the administration of 1 microgram GRF/kg. These data indicate that in hypothyroidism and perhaps hyperthyroidism there is an alteration in the responsiveness of the somatotroph to GRF administration.

Animals↗