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Biomedical subjects

M F Scanlon

Publications and source records attributed to M F Scanlon.

At least 91 records · Page 5Linked to original sources
PubMed1987

Effect of thyroxine replacement therapy on plasma insulin-like growth factor 1 levels and growth hormone responses to growth hormone releasing factor in hypothyroid patients.

The aim of this study was to evaluate the effect of T4 replacement therapy on plasma insulin-like growth factor 1 (IGF-1) levels in patients with primary hypothyroidism to see whether recovery of pituitary GH responsiveness to GRF was associated with increased plasma IGF-1 levels. IGF-1 levels and GH responses to GRF (1 microgram/kg) were measured in 21 patients with primary hypothyroidism before and after T4 replacement therapy. T4 increased plasma IGF-1 levels (57.2 +/- 4.4 vs 75.9 +/- 8.8 ng/ml, mean +/- SEM, P less than 0.05) and GH responses to GRF as assessed both by peak GH levels (9 +/- 1.5 ng/ml before treatment vs 16.7 +/- 3 ng/ml after treatment, mean +/- SEM, P less than 0.05) and area under curve (496 +/- 92 before treatment vs 896 +/- 161 after treatment, mean- +/- SEM, P less than 0.05). Linear regression analysis showed a positive correlation between free T3 and IGF-1 levels after treatment (r = 0.37, P less than 0.05) and a negative relationship between plasma IGF-1 levels before treatment and delta IGF following T4 replacement therapy (r = 0.45, P less than 0.025). However, no correlation was found between plasma IGF-1 levels and GH responses to GRF, suggesting that GH responses to GRF are of no predictive value in relation to the recovery of plasma IGF-1 levels following T4 replacement therapy in hypothyroid patients.

Adult↗
PubMed1987

Non-adenomatous inappropriate TSH hypersecretion and euthyroidism requires no treatment.

The syndrome of inappropriate TSH secretion is described in a euthyroid girl and her father. Based on nuclear T3 binding studies in fibroblasts, generalized tissue resistance was associated with a lower binding affinity for T3 in nuclear extracts suggestive of a structurally abnormal receptor for T3. Early recognition of the syndrome and observation of the short-term response to thyroid medication prevented unnecessary trials of antithyroid medication and later radical ablative thyroid treatment.

Child, Preschool↗
PubMed1987

Thyroid status in senile dementia of the Alzheimer type (SDAT).

Thyroid function was investigated in a group of 21 patients with severe senile dementia of the Alzheimer type (SDAT) and in a group of 17 age and sex matched normal controls. Free thyroid hormone levels (triiodothyronine (T3) and thyroxine (T4) were measured, as were also the thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) responses to thyrotrophin releasing hormone (TRH)). When compared to controls, patients demonstrated a significantly lower free T3 value (but not free T4), a blunted TSH response to TRH, slightly elevated basal PRL and GH values and a small GH response to TRH. However, all differences were small in biological terms and were within the laboratory's normal range. This emphasizes the relative normality of neuroendocrine function, particularly thyroid status, in SDAT.

Aged↗
PubMed1987

Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary.

Increases in plasma FFA levels inhibit GH responses to a variety of pharmacological and physiological stimuli. To gain further insight into the mechanism by which FFA exert their effect, we studied the plasma GH responses to GHRH-(1-44) (1 microgram/kg, iv) in normal subjects in whom plasma FFA levels were raised by a lipid-heparin infusion (250 mL 10% Intralipid plus 2500 U heparin). Paired tests were performed in 10 normal subjects, with and without lipid-heparin pretreatment. Lipid-heparin infusion from -30 to 120 min increased mean FFA levels from 0.41 +/- 0.03 (+/- SEM) to 3.12 +/- 0.40 mmol/L at 120 min. The mean plasma GH levels after GHRH administration were lower at all times; however, the values were significantly different (P less than 0.05) only at the later times (45, 60, and 90 min). When considered individually, an all or none pattern was observed; 5 subjects had no plasma GH response to GHRH, and 5 had no reduction. To investigate the time relationships between the FFA peak and subsequent GH blockade, a different protocol of paired tests was performed with GHRH with or without a different lipid-heparin infusion protocol. Lipid-heparin was infused from -90 to 0 min, with an additional heparin pulse at -15 min, to obtain a higher and earlier (0 min) FFA increase. FFA increased from 1.06 +/- 0.19 to 11.61 +/- 0.83 mmol/L at zero time. The GHRH-induced GH secretory peak (15.8 +/- 3.5 ng/ml) at 15 min was completely blocked (0.9 +/- 0.2 ng/ml), and the mean plasma GH levels were also lower at 30, 45, and 60 min. To determine whether the FFA-induced blockade of GH secretion was exerted in the pituitary, a series of in vitro studies was conducted using monolayer cultures of rat anterior pituitary glands, with GHRH concentrations of both 10(-10) and 10(-8) M and 10(-5) M forskolin to stimulate GH release. Both caprylic and oleic acid inhibited basal GH release and GHRH- or forskolin-induced GH release. PRL release was not altered, nor were toxic actions noted on the cells. In conclusion, FFA are able to block GH secretion directly at the pituitary level.

Adult↗
PubMed1987

Alpha-adrenoreceptor blockade with thymoxamine reduces basal thyrotrophin levels but does not influence circadian thyrotrophin changes in man.

We have tested the hypothesis that alpha-adrenergic drive is involved in the nocturnal increase in TSH in man. Seven mildly hypothyroid women (basal TSH levels 5.0-11.0 mU/l), aged 38-60 years, and nine euthyroid women, aged 27-60 years, were studied. Subjects underwent alpha-adrenergic blockade by infusion of thymoxamine (210 micrograms/min from 19.00 to 24.00 h); the same women were used as controls, with saline infused on different nights. Subjects were not allowed to sleep during the study period. A clear evening rise in basal TSH levels was apparent in both normal subjects and patients. Although overall secretion of TSH was slightly decreased in normal subjects (mean +/- S.E.M. area under the curve, 29.93 +/- 0.96 vs 30.71 +/- 0.80 mU/l per h; P less than 0.05), thymoxamine infusion did not produce any major alteration in the gradual rise in TSH levels during the evening (incremental change above baseline +0.96 +/- 0.21 during control infusion and +0.97 +/- 0.27 mU/l during thymoxamine infusion). In mildly hypothyroid patients the TSH changes were exaggerated and alpha-adrenergic blockade caused a reduction in basal TSH levels and a delayed rise in TSH (incremental change above baseline +2.93 +/- 1.42 during control infusion and +2.26 +/- 0.73 mU/l during thymoxamine infusion; P less than 0.02). Overall TSH secretion was significantly decreased by thymoxamine (mean +/- S.E.M. area 106 +/- 2.45 mU/l per h vs 123.32 +/- 3.68 in the control study; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The role of calcium and calmodulin in mediating release of thyrotrophin-releasing hormone by cultured hypothalamic cells.

We have developed a fetal rat hypothalamic cell culture system for the study of factors controlling the acute release of TRH. Release of TRH by the cells has been characterized by reversed-phase high pressure liquid chromatography and about 86% of the total immunoreactivity in the medium co-eluted with synthetic TRH. Release of TRH by the cells in response to 56 mmol K+/l increased between days 5 and 9 of culture but reached a plateau thereafter. Cell contents of TRH did not change significantly between days 5 and 14 of culture. Release of TRH from the cells was stimulated by K+ (56 mmol/l), veratridine (100 mumol/l) and ouabain (100 mumol/l) to 550, 480 and 335% of basal release respectively over a 1-h period. Release of TRH was dependent upon calcium in that it was absent when calcium-free medium was used and could be blocked by verapamil (20 mumol/l); however it could not be blocked by nifedipine (50 mumol/l). The calcium ionophore blocked by nifedipine (50 mumol/l). The calcium ionophore A23187 (1 mumol/l) stimulated TRH release to 340% of basal release. Tetrodotoxin (1 mumol/l) completely abolished the release in response to veratridine but had no effect on the release stimulated by K+ (56 mmol/l). The calmodulin antagonists trifluoperazine and triflupromazine (50 mumol/l) inhibited veratridine-stimulated TRH release. This was at a site after calcium influx as they also inhibited A23187-stimulated TRH release. The highly specific calmodulin antagonist W7 (10 mumol/l) also inhibited both veratridine and A23187-stimulated TRH release whereas, at the same concentration, its inactive analogue W5 did not significantly inhibit TRH release in response to either stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Dopamine stimulates release of thyrotrophin-releasing hormone from perfused intact rat hypothalamus via hypothalamic D2-receptors.

We have studied the effect of dopamine together with agonist and antagonist drugs of different specificities on the release of TRH from the perfused, intact hypothalamus of the adult rat in vitro. Dopamine produced a dose-related stimulatory effect on TRH release with maximal effect being achieved at 1 mumol/l (increase over basal, 118 +/- 16.5 (S.E.M.) fmol TRH; P less than 0.001 vs basal). This effect was mimicked by the specific D2-agonist drugs bromocriptine (0.1 mumol/l) and LY 171555 (0.1 mumol/l) (increase over basal values, 137.5 +/- 13.75 fmol and 158.6 +/- 10.7 fmol respectively; P less than 0.001 vs basal), but not by the D1-agonist SKF 38393A. The stimulatory effect of dopamine (1 mumol/l) was blocked in a stereospecific manner by the active (D) but not by the inactive (L) isomers of the dopamine antagonist butaclamol. Similar blockade was achieved with the specific D2-antagonist domperidone (0.01 mumol/l) whereas the D1-antagonist SCH 23390 was only effective when used at a concentration 100 times greater. Lower concentrations (0.01 mumol/l) of this D1-antagonist did not block the stimulatory effect of dopamine. High-performance liquid chromatography characterization of the material secreted within the hypothalamus showed one single peak of immunoreactive material which coeluted with synthetic TRH. These data suggest that dopamine exerts a stimulatory role in the control of hypothalamic TRH release by acting at specific D2-receptors.

Animals↗
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↗