A thyroxine absorption test followed by weekly thyroxine administration: a method to assess non-adherence to treatment.

OBJECTIVE: For patients who remain hypothyroid despite the administration of what would seem adequate doses of levothyroxine (L-T4), the underlying cause can be difficult to determine. The possibility of a biological cause should first be explored; however, in the majority of cases, poor adherence to medication is likely to be the main cause of treatment failure. When non-adherence is suspected but not volunteered, options to confirm the suspicion are limited. In this study, we identified patients for whom known drugs and pathological causes of L-T4 malabsorption were excluded, and despite often high doses of L-T4, the patients remained hypothyroid. DESIGN: Using a weight-determined oral L-T4 bolus administration, absorption was initially assessed in 23 patients. In nearly all patients, this was shown to be maximal at 120 min post-ingestion. This was then followed by the continued administration of a weekly T4 bolus for a 4-week period after which TSH and free T4 (fT4) levels were recorded. RESULTS: All patients showed a rise in fT4 at 120 min following the administration of the L-T4 bolus, with a mean increase of 54±3% from baseline. Following the treatment period, using an equivalent weekly L-T4 dose, which was significantly less than that of the daily dose taken by the patients before the test, TSH reduced from baseline in ~75% of cases. CONCLUSION: Using this combination of tests allows significant malabsorptive problems to be identified first and then potential non-adherence to be demonstrated. A management plan can then be implemented to increase adherence, aiming to improve treatment outcomes.

Combining growth hormone releasing hormone-arginine and synacthen testing diminishes the cortisol response.

OBJECTIVES: The GHRH/arginine test and short synacthen test (SST) have been validated as safe alternatives to the insulin tolerance test for the assessment of the GH reserve and hypothalamic-pituitary-adrenal axis integrity, respectively. However, these two tests are usually performed separately. The objective was to see whether the synacthen and GHRH/arginine tests could be combined to save time and blood samples and minimize inconvenience to patients. PATIENTS/METHODS: Twenty-four consecutive patients with adult onset pituitary disease requiring pituitary function testing were randomized to receive sequentially and in random order a SST, a GHRH/arginine test, and a combined SST and GHRH/arginine test on three different visits separated by at least 1 wk. RESULTS: There was no difference in basal cortisol or ACTH values for the SST done alone or during the combined test. However, when GHRH/arginine was given with synacthen, patients had a lower peak cortisol response with a mean difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P < 0.001), and one patient with a normal response on the SST had a subnormal cortisol response in the combined test. Similar lower peak cortisol responses were observed in males and females with combined test. The difference between the peak cortisol responses showed no significant correlation with age (r = 0.123; P = 0.58) or with the body mass index (r = -0.376; P = 0.09). There was no difference in GH measurements between the GHRH/arginine test done alone or in combination with the SST. CONCLUSIONS: Combining the SST and GHRH/arginine test results in a lower cortisol response to synacthen. For this reason, the combined test cannot be recommended to assess the integrity of cortisol and GH reserve using current diagnostic criteria.

Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia.

OBJECTIVE: Conventional hydrocortisone therapy in adrenal insufficiency cannot provide physiological replacement. We have explored the potential of circadian delivery of hydrocortisone as proof of concept for such therapy delivered in modified-release tablet formulation. METHODS: We investigated whether the circadian intravenous infusion of hydrocortisone could improve control of ACTH and androgen levels. Two healthy subjects, two patients with Addison's disease and two patients with congenital adrenal hyperplasia (CAH) were studied. RESULTS: In patients on thrice daily oral hydrocortisone, peak serum cortisol levels were higher than in normal subjects and overnight levels were very low. Patients had very high plasma ACTH levels before their morning dose of hydrocortisone, both at the beginning and at the end of their conventional oral therapy: mean +/- SEM 311.8 +/- 123.2 and 311.2 +/- 85.4 ng/l, respectively. In the patients with CAH, serum 17-hydroxyprogesterone levels were also elevated: 550 and 642 nmol/l at the beginning and 550 and 777 nmol/l at the end of conventional treatment, respectively. The overall 24-h mean cortisol levels were similar for conventional oral hydrocortisone and the circadian infusion. At 0700 h, ACTH levels were much higher on conventional treatment than after circadian infusion: mean +/- SEM 311.2 +/- 85.4 vs. 70.5 +/- 45.0 ng/l, respectively (P < 0.05). The same pattern was observed in 17-hydroxyprogesterone levels, which were 550 and 777 nmol/l after conventional treatment and 3 and 64 nmol/l after circadian infusion. CONCLUSIONS: In patients with poor biochemical control of Addison's disease and CAH, a 24-h circadian infusion of hydrocortisone can decrease morning ACTH and 17-hydroxyprogesterone levels to near normal.

Hypopituitary patients prefer a touch-screen to paper quality of life questionnaire.

UNLABELLED: Health Related Quality of Life questionnaires are frequently used for research, however only recently has their use been recommended in the routine clinical management of pituitary patients. Questionnaires frequently have complex scoring systems, and may be cumbersome, limiting widespread application. Touch-screen technology can overcome these limitations. We have developed a touch-screen 'Questions on Life Satisfaction-Hypopituitarism' QLS-H (Flash 5 Action script, program design by IG) questionnaire and compared its use and accuracy with a paper version questionnaire in 50 pituitary patients who were attending routine clinics. The HRQoL Z-score for the patient group was lower than the average for the normal UK population, as might be predicted for this patient group. There was no statistically significant difference between scores obtained by the touch-screen and paper questionnaires; mean (SD) Z score was -1.33 (1.4) for touch-screen and -1.26 (1.5) for paper. The touch-screen was preferred by 80% of patients, and quicker to complete (<5min). Additionally, there were significant errors in 14 (28%) of manually scored paper questionnaires. IN CONCLUSION: Touch-screen QLS-H questionnaires have advantages over the paper version for the routine clinical assessment of patients with hypopituitarism.

Powered prosthetic hands in very young children.

Myoelectric prostheses are generally not provided in the United Kingdom for children before the age of 3 1/2 years. Following the introduction of a smaller sized electric hand in the United Kingdom in 1993 the authors decided to introduce electrically powered hands for a group of congenital upper limb deficient children at a much younger age compared to normal practice. Eleven children were introduced to powered prosthetic hands at an average age of 20.6 months. At the review carried out for the purpose of this paper. 72.7% of these children appeared to be successfully using these powered prostheses. Fitting these young children with powered prostheses and encouraging acceptance and operation of the prostheses appeared to be much less of a problem than might have been anticipated. The parents of all these children have very much liked the introduction of powered hands at this early age and have contributed positively to the prosthetic programme. The authors' experience suggests that introduction of a powered prosthesis at a much earlier age can be a more suitable alternative than provision of a body-powered prosthetic device while waiting to reach an older age before a powered prosthesis is considered.