Impact of evidence-based guidelines on healthcare utilisation and costs for disc related sciatica in the Netherlands: a population-based, cross-sectional study.

OBJECTIVE: The aim of this study was to assess the impact of high-quality evidence supporting surgical treatment of lumbar disc herniation (LDH) on healthcare practice in the Netherlands by examining changes in healthcare utilisation, including the timing of surgery, and the healthcare costs for patients with LDH. DESIGN: A retrospective, cross-sectional study was performed using population-based, longitudinal data obtained from the Dutch Healthcare Authority (2007-2020) and NIVEL's primary care (2012-2020) administrative databases. SETTING: The study was conducted within the healthcare system of the Netherlands. PARTICIPANTS: We included adults (≥18 years) who visited a Dutch hospital or a general practitioner (GP) for lumbar degenerative disc disease. Patients with LDH were identified based on registered diagnosis code, type of surgery (discectomy) and age (<56 years). MAIN OUTCOME MEASURES: The primary outcome measure was the difference in the annual number of LDH procedures following the publication of evidence-based guidelines in 2009 (comparing the periods 2007-2009 to 2017-2019). Secondary outcome measures focused on the timing of surgery and associated healthcare costs. To validate the outcomes, secondary outcomes also include the number of discectomies and the number of procedures in the younger age group (discectomies, laminectomies, and fusion surgery). RESULTS: The number of patients suffering from LDH increased from 55 581 to 68 997 (+24%) between 2007 and 2019. A decrease was observed in the annual number of LDH procedures (-18%), in the number of discectomies (-22%) and in the number of procedures for patients aged <56 years (-18%). This resulted in lower healthcare costs by €10.5 million annually. In 2012, 31% of all patients <56 years had surgery before 12 weeks from diagnosis at the GP, whereas 20% did in 2019. CONCLUSIONS: Healthcare utilisation for LDH changed tremendously in the Netherlands between 2007 and 2020 and seemed to be associated with the publication and implementation of evidence-based guidelines. The observed decrease in the number of procedures has been accompanied by a corresponding reduction in healthcare costs. These findings underscore the importance of adhering to evidence-based guidelines to optimise the management of patients with LDH.

Clinical assessment of a point-of-care assay to determine protective vaccinal antibody titers to canine viral diseases.

Guidelines recommend that dogs are vaccinated for canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) every 3 years. Alternatively, their antibody titers are measured and vaccines given when titers fall below a protective threshold. In this study, a point-of-care (POC) assay was compared to hemagglutination inhibition (for CPV) and virus neutralization (for CAV and CDV) assays to predict the need for revaccination Ninety-two dogs presented for vaccination were enrolled. The POC assay indicated protective titers against CDV in 79/80, CPV in 89/90, and CAV in 91/91 dogs with reference standard antibody measurements that were over a protective threshold. The sensitivity of the POC assay for to detect protective concentrations of CDV antibodies was 99% (95% confidence interval [CI 95%], 93.3-99.9%). Ten dogs were falsely considered protected against CDV by the POC assay with a specificity of 17% (CI 95%, 3.0-44.8%). The sensitivity of the POC assay for protective concentrations of CPV titers was 99% (CI 95%, 93.9-99.9%). The sensitivity of the POC assay to detect protective concentrations of CAV antibodies was 100% (CI 95%, 95.9-100%). Only classifying high-positive CDV and CPV titers on the POC assay as protective improved assay specificity to 100%, but sensitivity decreased to 51% and 76% respectively. This POC assay had a high sensitivity for the detection of protective antibody titers; however, some dogs were falsely categorized as protected, especially for CDV.

DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

OBJECTIVE: To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN: A population-based retrospective cohort study (2007-2017). SETTING: Ontario, Canada. METHODS: Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS: For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS: We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT: Potential twin-specific OGTT thresholds for GDM were identified.

Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.

PURPOSE: Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. METHODS: Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. RESULTS: AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. CONCLUSIONS: According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

Long-term remission and recurrence rate in a cohort of Cushing's disease: the need for long-term follow-up.

OBJECTIVE: Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94% and recurrence rates between 3 and 46%, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center. METHODS: Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years. RESULTS: Thirty-five (85.4%) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5%) patients. Thirty-two (78%) patients achieved disease remission after the first treatment, 21 (65.6%) of them presented disease recurrence. Persistent disease was observed in 9 (22%) patients. Twelve (29.3%) subjects developed post-surgical adrenal insufficiency, 7 of which (70%) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol <3 µg/dl) in the immediate post-operative state. CONCLUSIONS: We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.

Pacing strategies during repeated maximal voluntary contractions.

PURPOSE: Pacing strategies have been reported to occur during continuous cyclical exercises. However, currently no studies have examined if pacing takes place during repeated maximal voluntary muscle contractions (MVCs). Accordingly, the purpose of this study was to examine if informing subjects on the number of MVCs they would perform would affect force and root mean squared electromyography (EMG), during similar fatiguing protocols. METHODS: Thirty well-trained male subjects completed three fatiguing protocols in a randomized order. In the control condition participants were informed they would perform 12 MVCs, and then completed all 12. In the unknown condition they were not told how many MVCs they would perform, but were stopped after 12. Lastly, in the deception condition they were initially told they would perform only 6 MVCs, but after the 6 contractions they were asked to perform a few more repetitions and were stopped after 12. RESULTS: Compared to the unknown condition, subjects demonstrated greater forces (p < 0.05, ES = 0.35-1.14, 2-7.5%) and biceps EMG (p < 0.05, ES = 0.6, 6%) in the deception condition during the first six MVCs. Additionally, under all conditions subjects applied greater forces in the last repetition (#12) relative to the previous one (#11) (p < 0.06, ES = 0.36-0.5, 2.8-3.8%). CONCLUSIONS: The anticipation of performing a certain number of MVCs led the subjects to utilize different pacing strategies. The results also question the assumption that subjects followed the instruction to exert maximal effort during repeated MVCs.

Efficacy and safety of long term treatment of unresponsive hypoparathyroidism using multipulse subcutaneous infusion of teriparatide.

Vitamin D nonresponsive hypoparathyroidism is uncommonly seen in the clinical practice. The use of new treatment modalities, including teriparatide administration, provides an alternative requiring its validation. We report the first case of hypoparathyroidism refractory to vitamin D that was successfully controlled for 5 years by teriparatide treatment. A 53-year-old woman presented severe hypoparathyroidism after thyroidectomy. No therapeutic response was obtained with oral and i. v. calcium and magnesium, or even with 5 µg calcitriol/day. Digestive disorders were ruled out and heterologous parathyroid transplant was ineffective. Subcutaneous (s. c.) recombinant human PTH 1-34 (rhPTH-teriparatide) plus oral calcitriol, calcium, and magnesium, were partially effective, but effectiveness of 20 µg teriparatide lasted less than 4 h and stable calcemia was not possible even with 4-6 injections/day. Multipulse s. c. pump driven infusion of teriparatide achieved complete normalization of serum calcium, phosphate, magnesium, calciuria, and magnesuria with relatively low teriparatide doses (25-35 µg/day) after the first day of treatment. Effectiveness of this treatment modality was maintained for 5 years. The only significant side effect observed during these years was the development of subcutaneous nodules with occasional insufficient control of calcemia. A gain in bone mineral density was observed after the first year of treatment, which had remained stable and within normal values, thereafter until now. No abnormalities in bone scintigraphy were detected in the follow-up. Vitamin D unresponsive hypoparathyroidism maybe safely and effectively controlled at long term by s. c. multipulse pump treatment recombinant human PTH.

Do thyroid cancer patients with basal undetectable Tg measured by current immunoassays require rhTSH testing?

OBJECTIVE: To evaluate the predictive value of disease free status of basal thyroglobulin (Tg) in differentiated thyroid carcinoma (DTC). DESIGN: Basal and recombinant human TSH (rhTSH) stimulated Tg measured with a commercial immunoassay (Liaison DiaSorin, Italial), neck ultrasonography (US) and fine needle aspiration cytology if required were performed in DTC patients followed prospectively for 6.8 years in a university hospital. 92 consecutive DTC patients were included. 74 patients with basal and stimulated Tg <1.0 ng/ml and Tg antibodies and US negative were considered as disease-free and persistent/recurrent disease was detected in 18 patients. In 25/74 disease-free patients rhTSH test was repeated within one year. RESULTS: 63/92 patients had undetectable basal Tg (<0.5 ng/ml), with rhTSH-Tg <0.5 ng/ml in 52, in 6 rhTSH-Tg between 0.5 and 1 ng/ml, in 2 between 1-2 ng/ml (disease-free after 3 years of follow-up) and >2.0 ng/ml (mean 4.1±2.4 ng/ml) in another 3, with US lymphatic metastasis confirmed histologically. Disease-free state was predicted with a sensitivity (S) of 66.7% and specificity (Sp) of 75.7% for basal Tg-0.5 ng/ml, and S 100% and Sp 85.1% for stimulated Tg-0.92. rhTSH test and US were repeated within one year in 25 disease-free patients with Tg<1.0 ng/ml. No further elevation below 1 ng/ml was observed. CONCLUSIONS: Low risk patients with undetectable basal Tg measured with current commercially available immunoassays should be followed with at least one rhTSH stimulated Tg and neck US because of the insufficient predictive value for recurrence/persistent disease of basal Tg.

The efficacy of octreotide LAR as firstline therapy for patients with newly diagnosed acromegaly is independent of tumor extension: predictive factors of tumor and biochemical response.

Surgical outcome of acromegaly depends on the preoperatory tumor size and extension. Somatostatin analogues are also a highly effective treatment for acromegalic patients. Nevertheless, the response of GH-secreting adenomas to primary medical therapy is variable. The aim of the present study was to evaluate the efficacy of octreotide LAR as primary therapy for acromegalic patients as a function of initial tumor extension. We performed a multicentre, prospective, observational and analytical study recruiting 19 "naive" acromegalic patients (5 microadenomas, 10 intrasellar, and 4 extrasellar macroadenomas). All of them were treated with octreotide LAR for 12 months. Basal GH and fasting IGF-I concentrations, and tumor volume were measured at baseline and after 6 and 12 months of treatment. Six patients withdrew the study. The patients who completed the protocol showed a significant reduction of tumor volume (25+/-23%, Wilk's lambda=0.506, F=4.400, p=0.046) independently of tumor extension at study entry (Wilk's lambda=0.826, F=0.452, p=0.769). A shrinkage >25% of baseline tumor volume was achieved in 8 (42%) patients with no differences between tumor extension subgroups. Basal GH levels (76+/-18%) and fasting IGF-I (52+/-31%) decreased throughout the study. Six (46%) patients normalized their IGF-I levels. Octreotide LAR is an effective first-line treatment for a large group of acromegalic patients independent of initial tumor extension.

Effectiveness of retinoic acid treatment for redifferentiation of thyroid cancer in relation to recovery of radioiodine uptake.

BACKGROUND: Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid neoplasia that have lost radioiodine (131I) uptake with heterogeneous results. AIM: Retrospective analysis of the recovery rate of 131I uptake after RA treatment in patients from 11 Spanish hospitals. METHODS: Twenty-seven patients (14 men, 13 women) with papillary [21], follicular [4], and oncocytic [2] thyroid cancer initially treated with total thyroidectomy plus 131I, and with 131I negative metastatic disease, were given 13-cis RA (0.66-1.5 mg/kg for 5-12 weeks) followed by a therapeutic 131I dose (3700-7400 MBq); 3 months later thyroglobulin levels and computed tomography imaging were performed. RESULTS: In 9 out 27 cases (33%) (8 papillary, 1 follicular) optimal positive 131I scan was observed after RA treatment; in the remaining 18, 10 had a suboptimal uptake (7 papillary, 2 follicular, 1 oncocytic) and in the rest there was no 131I uptake recovery (6 papillary, 1 follicular, 1 oncocytic). In 17 positive responses to RA (either optimal or suboptimal) in which image follow-up was available, decrease or stabilization of metastatic growth was observed in 7, while tumor mass increased at short term in the remaining 10. No major side effects were detected. CONCLUSION: Quite a high rate of 131I uptake recovery after RA treatment may be obtained in advanced differentiated thyroid cancer, but the potential modification of the natural course of the disease is uncertain. A better biological characterization of these tumors allowing the identification of potential responders to RA may improve the outcome of RA coadjuvant therapy.

A short acute octreotide test for response prediction of long-term treatment with somatostatin analogues in acromegalic patients.

The usefulness of the acute octreotide test in the selection of acromegalic patients for chronic somatostatin depot analogues treatment is controversial. The aim of the present study was to determine its accuracy for chronic response prediction, and the reliability of a short version of the classic 6-hour test. The data from 26 acromegalics (19 women, 7 men, mean age 52.6+/-13.1 years) studied with an acute octreotide test (6 hours sampling for GH measurement after octreotide 100 microg s. c.) were retrospectively analyzed. Eighteen of them followed chronic somatostatin depot analogues treatment for 12 months. GH nadir was always detected at 2 hours (mean decrease 75.9+/-24%). GH levels at 2 hours positively correlated with the other time-points (r(s) 0.97, 0.98, 0.97, 0.96 at 3, 4, 5 and 6 h, respectively; p<0.0001). During chronic treatment with maximal effective dose for 12 months, 61% of the patients achieved IGF1 <3 SD and 22% reached IGF1 <2 SD. GH nadir correlated with IGF1 decrease at 12 months (r(s) 0.76, p<0001). GH nadir of 9.2 ng/ml predicts IGF1 <3 SD with 82% sensitivity and 58% specificity (75% PPV, 67% NPV); for IGF1<2 SD, 75% sensitivity and 58% specificity are obtained for GH nadir 3.6 ng/ml, with 33% PPV and 89% NPV. Acute octreotide test reliably predicts response to long-term treatment; the short, 2-hour version is fully informative for therapeutic decisions in acromegalic patients.

Metanefrinas plasmáticas: mayor eficacia en el diagnóstico bioquímico del feocromocitoma / Plasma metanephrines: improved accuracy in the biochemical diagnosis of pheochromocytoma

Introducción: La aproximación óptima al diagnóstico bioquímico del feocromocitoma es tema de debate debido a la posibilidad de determinar las metanefrinas plasmáticas libres, que muestran un elevado poder diagnóstico. Además, presentan la ventaja de eliminar los inconvenientes relacionados con las muestras de orina de 24 h. El objetivo del estudio es analizar la eficacia en el diagnóstico de feocromocitoma de las metanefrinas plasmáticas libres fraccionadas. Material y métodos: A todos los individuos evaluados para la detección de feocromocitoma durante un año en nuestro hospital (n = 137) se les determinaron las concentraciones de metanefrinas y catecolaminas totales en orina y, paralelamente, de las metanefrinas plasmáticas libres mediante inmunoensayo. Resultados: Se diagnosticaron 5 feocromocitomas, confirmados histológicamente. Las metanefrinas plasmáticas no presentaron ningún resultado falso negativo y sólo un falso positivo. Las catecolaminas y las metanefrinas en orina no ofrecieron ningún falso negativo, aunque mostraron, respectivamente, 12 y 13 falsos positivos, lo que dio como resultado una especificidad significativamente inferior a las metanefrinas plasmáticas. Conclusión: La determinación de las metanefrinas plasmáticas libres mediante técnicas de inmunoensayo supone la incorporación de una prueba de gran eficacia para el diagnóstico del feocromocitoma asequible para una gran mayoría de laboratorios; por tanto, es una alternativa válida a las determinaciones urinarias (AU)

Introduction: The optimal approach to the biochemical diagnosis of pheochromocytoma is currently being debated, due to the possibility of determining plasma free metanephrines, which show high diagnostic accuracy. In addition, evaluation of this parameter in plasma samples would overcome the problems associated with collecting 24-hour urine samples. The aim of this study was to assess the diagnostic efficacy of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma. Material and methods: In all patients evaluated for pheochromocytoma over a 1-year-period in our hospital (n = 137), urinary excretion of total metanephrines and catecholamines was determined in parallel with plasma free metanephrine concentrations through immunoassay. Results: Five histologically confirmed pheochromocytomas were diagnosed. Plasma metanephrines gave no false negative results and only one false-positive result. Urinary catecholamines and metanephrines gave no false-negative results but produced 12 and 13 false positive results, respectively. Thus their specificity was significantly lower than that of plasma free metanephrine determination. Conclusion: Determination of plasma free metanephrines concentrations through immunoassay is a highly effective technique for the diagnosis of pheochromocytoma that can be used in most laboratories. Consequently, it is a valid alternative to urinary determinations (AU)

Acromegalia y cáncer (consecuencias prácticas) / Acromegaly and cancer (practical effects)

La relación entre acromegalia y riesgo incrementado de cáncer se basa en datos derivados de la epidemiología de la acromegalia, la mortalidad del panhipopituitarismo (incluido el déficit de hormona del crecimiento [GH]), los conocimientos sobre riesgo de diversos tumores sólidos en la población general en función de los valores plasmáticos de IGF1, y la información obtenida de diversos modelos experimentales sobre el papel de la GH, los factores de crecimiento y sus proteínas de transporte como reguladores de apoptosis, mitogénesis y proliferación celular.Se presenta un caso clínico de una paciente de 61 años, con historia prolongada de estreñimiento, y diagnosticada de acromegalia 8 años antes; a pesar de la cirugía, la radioterapia y el tratamiento farmacológico con análogos de somatostatina y dopaminérgicos no se ha logrado el control de la enfermedad. Se discute en esta paciente el riesgo de desarrollar cáncer de colon, la posible influencia del mal control de su enfermedad hipofisaria sobre este riesgo, y la estrategia de un seguimiento más adecuado de acuerdo con la información existente en la bibliografía (AU)

Focal segmental glomerular sclerosis in two patients with Addison's disease: any more than fortuitous development of glomerular disease?

Adjustment of the mineralocorticoid activity under substitution therapy is of primary importance in Addison's disease. We report the clinical and biological conditions of 2 patients with Addison's disease who developed nephrotic proteinuria during their deficient mineralocorticoid state. Renal biopsy was performed and the specimens processed using conventional histochemistry, Congo red staining, and indirect immunofluorescence. The renal biopsy specimens showed focal segmental glomerular sclerosis and nodular deposits of IgM and C3. Negative for Congo red staining. Serum complement, circulating immune complexes, and anti-DNA and hepatitis B and C and human immunodeficiency virus antibodies were all normal or negative. Absence of vesicoureteral reflux was assessed by X-ray studies. Our observations suggest that deficiency in mineralocorticoid substitution therapy inducing a status of hyperreninemia could play a role in the development of focal segmental glomerulosclerosis in patients with Addison's disease.

Acromegaly Quality of Life Questionnaire (ACROQOL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties.

OBJECTIVE: To develop a disease-specific questionnaire suitable to measure health-related quality of life (HRQOL) in acromegaly (ACROQOL). DESIGN, PATIENTS AND MEASUREMENTS: For the development of the ACROQOL questionnaire different sources of information were used: First, a literature search was performed to identify relevant papers describing the impact of acromegaly in HRQOL. Second, 10 endocrinologists identified the main domains of impact on HRQOL in patients with acromegaly. Third, 10 in-depth, semistructured interviews were conducted in acromegalic patients to identify domains and items related to the self-perceived impact of acromegaly in patients' life. Qualitative analyses of the information were performed identifying domains and items to be included in the questionnaire. Those items considered ambiguous, complicated to read, double-barrelled, with jargon terms, too long, or negatively worded were excluded. Each remaining item was subsequently rated by the same panel of endocrinologists and experts in HRQOL evaluation, and assessed according to clarity of wording, frequency of occurrence and importance among patients with acromegaly. Analysis of internal consistency of the questionnaire was evaluated with a Cronbach's Alpha. A preliminary questionnaire was administered to 72 patients with acromegaly. Rasch analysis (dichotomous logistic response model) of the answers given by these patients allowed parameter estimates and model data fit indices to be computed and misfitting items deleted. Frequency of occurrence and degree of agreement with the statements were selected as response choices in a 5-point Likert type scale. RESULTS: The following domains related to HRQOL in acromegaly were identified: physical and psychological functions, social, daily activities, symptoms, cognition, general health perception, sleep, sexual function, pain, energy and body image. An initial set of 204 expressions were identified from the initial transcripts of the patient interviews. After elimination of ambiguous or unclear expressions, 142 items remained drafted in question form. From the quantitative analysis of the item rank position within each of the three areas of clarity, frequency and importance, the 38-item questionnaire was produced, with satisfactory internal consistency (Cronbach's Alpha 0.94). Rasch analysis produced a further reduction to the final 22-item questionnaire (Cronbach's Alpha 0.91) containing two scales that evaluate physical (eight questions) and psychological aspects related to appearance and personal relations (seven items each). The evaluation of the item parameters confirmed the construct validity of the new instrument. The substantial reliability of the questionnaire suggested the sample was well targeted by the questionnaire. The initial Spanish version was translated into English and presented to five English-speaking Australian patients with acromegaly to assess and correct for comprehension, clarity, cultural relevance and suitable wording. CONCLUSIONS: We present the ACROQOL questionnaire, developed and preliminarily validated to specifically assess HRQOL in patients with acromegaly.

The finding of a somaticdeletion in RET exon 15 clarified the sporadic nature of amedullary thyroid carcinoma suspected to be familial.

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between both is important for future clinical management. We report a family initially described as a familial MTC by pentagastrin stimulation test and clinical outcome, in which we found a 12 bp deletion within the catalytic domain of the protooncogene RET in the index case tumor alone. Linkage study suggests that it is a sporadic MTC. Therefore, in view of these results, in kindred with just one MTC case, borderline pentagastrin test values must be carefully assessed. In addition, this and other mutations can help us to understand some features about domains that play an important role in the normal function of this tyrosine kinase receptor and involved in MTC.

Screening of selected genomic areas potentially involved in thyroid neoplasms.

Loss of heterozygosity (LOH) studies have been used to identify sites harbouring tumour suppressor genes (TSGs) involved in tumour initiation or progression. To further elucidate the genetic mechanisms for follicular and papillary thyroid tumours development, we studied the frequency of LOH in 36 thyroid tumours (21 follicular thyroid adenomas (FAs) and 15 papillary thyroid carcinomas (PTCs)) on 10 specific genomic areas: 3p22, 3p25, 7q21, 7q31, 10q23, 10q25-26, 11q13, 11q23, 13q13 and 17p13.3-13.2 using 20 polymorphic markers. We have selected these areas for two reasons: (a) Even though LOH in thyroid neoplasms has been described in some of these areas, results are controversial, and (b) we have also studied areas described as involved in other epithelial or endocrine tumour types, but not studied up to now in thyroid neoplasms. Two areas showed a high percentage of LOH: 7q31 and 11q23. A 62% LOH was found at 7q31 in the FAs, suggesting, as other authors have proposed, that at least one TSG must be present in the vicinity of the c-met locus. The second area in frequency was at the 11q23 locus, with a 45% LOH in the FAs. This area was studied because it has been described as being involved in the development of epithelial and endocrine cancers. This locus had not been studied before in thyroid neoplasms. This result is interesting because the LOH11CR2A gene is localised at this locus. We suggest that this gene and/or an other TSG nearby may be involved in the progression to FA. In our study, a low percentage of LOH was found in the PTC samples, indicating that TSGs present in the areas we have studied are not significantly involved in their progression. Our data also suggest that TSGs located in areas where no LOH was detected (PTEN, MEN1, Cyclin D1, BRCA2 and RFC3) are not involved or do not have an important role in tumour progression.

Adolescent anorexia nervosa: the catch-up effect in bone mineral density after recovery.

OBJECTIVE: To determine whether bone mineral density (BMD) loss can be reversed in adolescent anorexic patients. METHOD: A prospective study with 108 anorexia nervosa patients (DSM-IV) from 12 to 17 years of age at the Eating Disorders Unit in the Hospital Clinic of Barcelona (Spain). They were first evaluated by dual-energy x-ray absorptiometry in lumbar spine and femoral neck consecutively from 1997 until 1999 and reexamined after 6 to 30 months. Results were compared with normative values of bone mass. RESULTS: Patients with poor outcome (n = 44) had a bone mass loss. Patients with good short-term outcome were divided in two groups. The group with normal BMD at first evaluation (n = 41) had a bone mass gain per year of 3.0% at lumbar spine and 0.5% at femoral neck. The group with low BMD at first evaluation (n = 23) had an increase per year of 9.1% at lumbar spine and 4.5% at femoral neck. In a multiple linear regression analysis with the variables body mass index, age, months with menstruation, and BMD zscore at first evaluation, the only predictor of BMD increase was the first z score both at the lumbar spine (coefficient R = 0.64; p < .001) and at the femoral neck (coefficient R = 0.5; p < .001). CONCLUSIONS: There is a catch-up effect in adolescent patients with low BMD but good short-term outcome.