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Biomedical subjects

P R Raggatt

Publications and source records attributed to P R Raggatt.

At least 19 recordsLinked to original sources
PubMed1998

Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders.

OBJECTIVE: To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders. DESIGN AND PATIENTS: The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays. RESULTS: The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min. CONCLUSIONS: The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.

Adult↗
PubMed1994

Second-trimester maternal serum screening using alpha-fetoprotein, human chorionic gonadotrophin, and unconjugated oestriol: experience of a regional programme.

Over a 2-year period from January 1991 to December 1992, second-trimester maternal serum screening for Down's syndrome using alpha-fetoprotein (alpha FP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) was made available to five health districts in East Anglia, with a total population of 1.2 million. Amniocentesis was offered when the risk of Down's syndrome at term was 1:200 or greater. 25,359 singleton pregnancies were screened, representing an uptake of 77 per cent. The recall rate for the 24 per cent of women who had not had a dating scan prior to the test was 9.4 per cent compared with 3.9 per cent for those who had been scanned (P < 0.0005). Seventy-five per cent (36/48) of Down's syndrome pregnancies were detected for a false-positive rate of 4.0 per cent. Twenty-five out of 36 of detected Down's syndrome pregnancies were dated by scan prior to sampling, and in the 11 remaining cases, the dates were confirmed by scan after a high-risk result was obtained. The exclusion of uE3 from the screening protocol would have reduced the detection rate to 52 per cent (25/48) for the same false-positive rate. Eighty-five per cent of women identified at high risk accepted the offer of an amniocentesis. Other fetal abnormalities detected were trisomy 18 (3), trisomy 13 (2), 45,X (6), 69,XXX (5), other chromosome abnormalities (9), open neural tube defects (26), hydrocephalus (7), abdominal wall defects (4), and steroid sulphatase deficiency (6).

Adult↗
PubMed1992

Abnormalities of the hypothalamo-pituitary-gonadal axis after head injury.

OBJECTIVE: We aimed to investigate the mechanisms of hypogonadism which develops after head injury. DESIGN: Pulsatile secretion of LH was studied in subjects 6-10 days after major head injury. PATIENTS: We studied five male subjects admitted with major head injuries and six healthy age-matched control subjects. MEASUREMENTS: During the pulsatility study, LH was measured at 5-minute intervals for 4 hours and 15-minute intervals for a further 2 hours. In addition, testosterone and LH were measured on Days 1-5, 14 and after 3-6 months. RESULTS: The analysis of pulsatile secretion of LH demonstrated an LH pulse frequency similar to control subjects, but a significantly reduced LH pulse amplitude (P less than 0.001, fixed threshold method; P less than 0.02, Detect method). Both testosterone and LH levels were reduced after injury with the nadir occurring on Day 4. CONCLUSIONS: Hypogonadism after head injury is due to defective LH secretion, with normal pulse frequency but a reduced pulse amplitude.

Adult↗
PubMed1989

Abnormalities of thyrotrophin (TSH) evening rise and pulsatile release in haemodialysis patients: evidence for hypothalamic-pituitary changes in chronic renal failure.

Using a sensitive enzyme amplified immunoassay for TSH, the evening rise and pulsatile release of TSH were studied in 10 men with chronic renal failure treated by haemodialysis. Compared to euthyroid male controls the evening rise of TSH was attenuated (median 0.066 vs 0.195 mU/l/h, P less than 0.01) and the rate of rise correlated with the TSH response to TRH (r = 0.93, P less than 0.001). All subjects showed TSH pulsatility in at least one method of data analysis but the less sensitive incremental method showed no significant difference in pulse frequency and amplitude between the two groups. However, with time series analysis, periodicity was shorter (median 45 vs 95 min, P = 0.013) and pulse amplitude smaller (median 0.06 vs 0.175 mU/l, P = 0.017) in renal patients. Pulse amplitude, but not periodicity, correlated with the TSH response to TRH (r = 0.68, P less than 0.05). In addition, serum total thyroxine, free thyroxine and free triiodothyronine concentrations were reduced, while serum prolactin and 17 beta-oestradiol concentrations were raised. These changes in TSH evening surge and pulsatile release may contribute to the reduction in thyroidal hormone concentrations seen in renal failure and emphasize the value of sensitive methods of hormone and pulse data analysis.

Adult↗
PubMed1989

Duplicates or singletons? An analysis of the need for replication in immunoassay and a computer program to calculate the distribution of outliers, error rate and the precision profile from assay duplicates.

The nature, frequency, statistics and methods of detection of both Gaussian and catastrophic errors in immunoassay are described. The method of sequential analysis is applied to the rates of catastrophic errors and is used to calculate the number of results which must be examined in order to achieve a stated confidence that the error rate is acceptable so that a rational decision on use of duplicate or singleton assay can be made. A simple computer program is described, which allows computation of the precision profile and an analysis of errors using accumulated data from duplicate assays. These methods have been applied to an enzyme amplification immunometric assay for thyroid-stimulating hormone (TSH) and an analysis is made of the errors detected in a sample of 1419 patient results.

Chemistry, Clinical↗
PubMed1989

The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women.

Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose.

Adrenal Cortex Hormones↗
PubMed1988

Hypothalamic hypogonadism following major head injury.

Endocrine studies, using the four hypothalamic releasing hormones, gonadotrophin releasing hormone, thyrotrophin releasing hormone, corticotrophin releasing hormone and growth hormone releasing hormone, were performed in 33 males after admission with a major head injury. The test was repeated 7 days later in all 33 patients and after 3-6 months in 21 patients. All patients had a period of unconsciousness followed by post-traumatic amnesia of greater than 24 h. The results obtained from investigating the gonadal axis are reported in this paper. The levels of total and free testosterone, basal FSH and basal LH fell significantly during the first 3 days after injury, when the LH and FSH responses to GnRH achieved their highest peak levels. This hormone pattern has not previously been reported in the gonadal axis and may be a consequence of hypothalamic dysfunction. The severity of the injury was negatively correlated to the testosterone concentration on admission and to the basal and peak FSH concentrations 1 week later. Persistent hypogonadism was found in five of the 21 patients retested after 3-6 months, with low testosterone concentrations and three continued to have an exaggerated LH response to GnRH. Thus major head injury frequently results in hypogonadism shortly after injury, with an increased gonadotrophin response to GnRH. In addition, a substantial minority of patients continue to be hypogonadal after 3-6 months. In view of these findings we strongly suggest that all patients should be endocrinologically assessed at intervals following severe head injury.

Adolescent↗
PubMed1987

Undescended testis and hormone levels in early pregnancy.

A case-control study was carried out on mothers of boys with undescended testis to investigate the hypotheses that raised maternal levels of oestrogen or reduced levels of human chorionic gonadotrophin in early pregnancy might be factors in the environment of the fetus associated with this condition. No significant difference in the levels of either of these hormones was found, though, if anything, levels of oestrogen may have been lower in cases than in controls, and not higher as previously postulated.

Chorionic Gonadotropin↗
PubMed1987

Pulsatile secretion of TSH in healthy subjects.

The physiological variations in serum TSH concentration have been investigated using an enzyme amplified immunoassay with improved sensitivity and precision. Blood samples were collected at regular intervals from 10 healthy volunteers during the period 1800 h to 0100 h. Spectral analysis followed by periodic regression analysis demonstrated significant serum TSH pulsatility with periodicities of 60 or 85-100 min. In addition, a significant (P less than 0.001) evening rise in serum TSH concentration was demonstrated in all subjects, with levels rising at around 21.30-22.00 h.

Adult↗
PubMed1987

Thyroid stimulating hormone measurement by an ultrasensitive assay during thyroxine replacement: comparison with other tests of thyroid function.

Serum thyroid stimulating hormone (TSH) was measured using a highly sensitive enzyme-amplified immunoassay in 37 clinically euthyroid patients receiving thyroxine replacement therapy and compared with other biochemical tests of thyroid function. A highly significant correlation (P less than 0.001) was found between the basal serum TSH and the increase in serum TSH concentration 20 min after the administration of thyrotropin releasing hormone (TRH). The basal serum TSH was negatively correlated with the serum total thyroxine (P = 0.05). When patients results were classified as abnormal or normal many discrepancies were noted between the various thyroid tests. A suppressed serum TSH was found in 65% of patients with a normal serum total thyroxine. However, in patients on thyroxine replacement therapy a basal TSH measured by enzyme-amplified immunoassay provides the same information as a TRH test.

Female↗
PubMed1986

The use of the simplex method for the optimisation of non-linear functions on a laboratory microcomputer.

The use of the microcomputer for the processing of analytical data in the laboratory is currently increasing. However, computational methods which have been used successfully on minicomputers may not be suitable for microcomputer implementation due to the lack of available precision. This paper describes a technique, namely the simplex method, which may be successfully applied to the processing of laboratory data on an 8-bit microcomputer. The method is used to optimise a non-linear function in order to fit a curve to radioimmunoassay (RIA) and immunoradiometricassay (IRMA) data. The microcomputer package described has been tested on laboratory data and is currently in use in a clinical biochemistry laboratory.

Biometry↗
PubMed1978

Hypothalamo-pituitary-thyroid function in anorexia nervosa: influence of weight gain.

The functional state of the hypothalamo-pituitary-thyroid axis was assessed in 14 women and girls with anorexia nervosa when at low body weight and again in 12 cases after they had gained weight. Mean serum thyroxine concentrations were low before and after weight gain. Mean serum triiodothyronine (T3) concentrations were substantially reduced at low weight and doubled after weight gain, the absolute values being linearly correlated with body weight expressed as a percentage of the ideal. Concentrations of reverse T3 were greatly increased in some patients initially and fell with weight gain. Basal concentrations of thyroid-stimulating hormone (TSH) were unchanged after weight gain but the TSH response to thyrotrophin-releasing hormone was significantly augmented; delayed patterns of response were found in seven out of 12 patients tested before and three out of 12 patients tested after weight gain. Changes in the hypothalamo-pituitary-thyroid axis are common in anorexia nervosa and probably represent both peripheral and central adaptations to the altered nutritional state.

Adolescent↗