EFFECT OF INJECTION SITE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF SUBCUTANEOUSLY ADMINISTERED LUTEINIZING HORMONE RELEASING HORMONE

Serum concentrations of LHRH and the subsequent LH responses were compared following s.c. injections of 20 micrograms LHRH into the upper arm and the lower abdominal wall, in 9 hypogonadal women responsive to pulsatile LHRH therapy. Tests were carried out at the two sites in random order. Peak LHRH concentrations were reached by 5 min after upper arm and by 20 min after lower abdominal wall injections, the maximum concentrations being significantly greater following injections into the former. There was no increase in LH until 10 min and then maximum concentrations were reached at 30 min following injection into both sites. There was no significant correlation between the LHRH increments and the LH response but there was a negative correlation between the Ponderal Index of the patients and the LHRH increments following injections into the lower abdominal wall only. There was no significant overall difference between the LH increments related to the site of injection, but the order of injections affected the responses. When upper arm injections were given first the LH responses were significantly greater, but when lower abdominal wall was injected first the subsequent responses to upper arm injections were impaired. A possible reason for this is that the absorption from the lower abdominal wall was delayed so prolonging the exposure of the pituitary gonadotrophs to LHRH, resulting in pituitary desensitization at the time of the second test.     

THE ROLE OF A HIGHLY SENSITIVE AMPLIFIED ENZYME IMMUNOASSAY FOR THYROTROPHIN IN THE EVALUATION OF THYROTROPH FUNCTION IN HYPOPITUITARY PATIENTS

Using a highly sensitive amplified enzyme-linked immunoassay (AEIA) for thyrotrophin (TSH), we have assessed the ability of a single basal measurement of TSH to predict the subsequent response of TSH to TRH in a group of 11 patients with known pituitary pathology and some evidence of hypopituitarism. All patients were clinically euthyroid. Basal levels of AEIA-TSH ranged from less than 0.2 mU/l ('undetectable') to 0.9 mU/l; within this range there was no correlation with the subsequent TSH levels at 30 min in the TRH test. The TSH response in the TRH test did not correlate with the direct measurements of prevailing thyroid hormone levels (Total T4 or Free T4). We suggest that in patients with pituitary disease, the formal TRH test yields additional information regarding residual thyrotroph function that cannot reliably be predicted by a single basal TSH value, even when measured by a sensitive method. The current and potential thyroid status in patients with hypopituitarism must continue to rest on the overall picture provided by clinical assessment, direct measurement of thyroid hormones and the TRH test response. A basal TSH alone gives little useful information regarding thyroid status in such patients.     

An Evaluation of the Distinction of Ectopic and Pituitary ACTH Dependent Cushing's Syndrome by Clinical Features, Biochemical Tests and Radiological Findings

The efficiency of various laboratory and radiological investigationsin the differentiation of ectopic from pituitary dependent Cushing'ssyndrome was studied, based on findings in 23 patients withverified Cushing's disease and seven patients with the ectopicACTH syndrome. Clinical features strongly favouring the ectopic type were malesex and history for less than 18 months. Basal biochemical featuresstrongly indicating the ectopic syndrome included plasma K⁺<3.0 mmol/l and HCO₃ >30 mmol/l; serum cortisol at 9 a.m.or midnight of > 800 nmol/l; urine free cortisol > 1300nmol/24 hours; plasma ACTH > 100 ng/1. In the high-dose dexamethasone suppression test, suppressionby < 50 per cent of 9 a. m. serum cortisol, urine free cortisolor 17-oxogenic steroids was usually indicative of an ectopicsource of ACTH. A mean suppressed value of > 450nmol/l forthe 9 a.m. and midnight cortisol combined occurred in all ofthose with the ectopic syndrome, but in none of the 23 patientswith Cushing's disease. For urine free cortisol, a mean suppressedvalue of < 1000 nmol/24 hours was found in all patients withCushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of     

Factors affecting the cutting ability of sonic files

The aim of this study was to investigate the cutting ability of sonic files. A model system was developed and the following variables evaluated: file type, Heliosonic or Shaper; file length, 21 or 29 mm; power, air inlet ring opening of half or fully open; stroke length, 2 or 4 mm; stroke rate, one or two cycles per second; and load 50 or 100 g. A 26 full-factorial analysis with two replications into the effect of the above variables on the cutting ability of the MM1500 sonic instrument was performed. A new size 25 file was used for each cut, together with water irrigation, and the substrate used was 1-mm thick sections of bovine bone. The differences between the variables were significant (ANOVA, P< 0.001). However, examination of the F-values showed that the most significant variable to affect cutting was load, followed by power, file type, stroke length and stroke rate, with the least significant variable being file length. The most significant interaction was between rate and length of stroke. An increase in stroke rate from one to two cycles per second at a stroke length of 2 mm produced an increase in cutting for both the Heliosonic and Shaper files. However, at the longer stroke length of 4 mm, the same increase in rate resulted in a decrease in cutting for the Shaper files. Therefore, it is suggested that operators should press the file against the canal wall and move it slowly to maximize cutting.