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.

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.

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.

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.

Splenectomy in patients with AIDS and AIDS-related complex.

OBJECTIVE: To study the effect of splenectomy in HIV-infected patients. DESIGN: A retrospective chart review of patients admitted to St Vincent's Hospital who had splenectomies and were HIV-positive. SETTING: All patients were treated at St Vincent's Hospital, New York City, New York, USA. PATIENTS: Only patients who were HIV-positive and who had had a splenectomy at St Vincent's Hospital were included. INTERVENTION: All patients had a splenectomy. MAIN OUTCOME MEASURES: The effect of the splenectomy in these HIV-positive patients was studied with respect to their operative morbidity and mortality, platelet counts, overall survival and the development of new opportunistic infections. RESULTS: All patients who did not have AIDS but did have thrombocytopenia responded to splenectomy in terms of their thrombocytopenia. None of them had an accelerated progression to AIDS. Most patients with AIDS and thrombocytopenia responded to splenectomy in terms of correcting their thrombocytopenia. CONCLUSIONS: Splenectomy as a treatment for thrombocytopenia is successful not only in HIV-positive patients without AIDS, but also in AIDS patients. However, in patients with disseminated Kaposi's sarcoma or Mycobacterium avium intracellulare, splenectomy may not be a factor for survival.

Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal prostaglandins.

To determine if renal functional alterations in diabetes mellitus could be related to disturbances of vasoactive systems, renal plasma flow (RPF), glomerular filtration rate (GFR), PRA (basal and stimulated), plasma catecholamine levels, and urinary excretion of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and kallikrein were determined in 21 patients with insulin-dependent diabetes mellitus (IDDM) of short duration and 15 normal subjects. In 7 additional patients with IDDM and in 4 normal subjects, the effect of lysine acetylsalicylate (LAS; 450 mg, iv) on GFR and RPF was studied. Patients with IDDM had higher RPF and GFR than normal subjects. Plasma norepinephrine and basal and stimulated PRA were significantly lower in IDDM than in the control group [161 +/- 82 (+/- SD) vs. 243 +/- 114 pg/ml, 0.19 +/- 0.20 vs. 1.15 +/- 0.33 ng/ml X h, and 0.93 +/- 0.82 vs. 2.8 +/- 1.73 ng/ml X h, respectively). No significant differences were found in the urinary excretion of PGE2, 6-keto-PGF1 alpha, and kallikrein in the two groups. LAS administration significantly reduced RPF (from 641 +/- 72 to 535 +/- 38 ml/min X 1.73 m2) and GFR (from 168 +/- 25 to 150 +/- 18 ml/min X 1.73 m2) in patients with IDDM, but not in normal subjects. In IDDM patients, there was a close direct correlation between the percent decrease in RPF and GFR induced by LAS and the baseline values of these parameters. The results suggest that in IDDM, there may be an imbalance between the degree of activation of the renin-angiotensin and sympathetic nervous systems and the renal production of PGs. The observation that LAS administration reduced RPF and GFR in these patients suggests that renal PGs are involved in the renal hyperperfusion of IDDM.

Thyroid disease in primary Sjögren syndrome. Study in a series of 160 patients.

We studied 160 consecutive patients (147 female and 13 male) with primary Sjögren syndrome (SS) to determine the prevalence and clinical significance of thyroid disease in a large series of patients with primary SS from our unit and to compare the prevalence and significance with those in 75 individuals without SS from a primary care center. Serum levels of thyroid hormones (free thyroxine, triiodothyronine, and thyroid-stimulating hormone) and autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) were measured in all SS patients and in 75 control patients. Fifty-eight (36%) of the 160 patients with primary SS had evidence of thyroid disease. Autoimmune thyroid disease (ATD) was diagnosed in 32 (20%) patients and nonautoimmune thyroid disease (NATD) in 26 (16%). No significant differences were found when these prevalences were compared with those in control patients. On the other hand, comparing those patients with altered hormonal profiles, patients with NATD showed mainly hyperthyroidism (10/17, 59% versus 2/20, 10% in patients with ATD, p = 0.001). Finally, when clinical and immunologic manifestations of SS were analyzed in patients with and without thyroid disease, respectively, we found that patients with thyroid disease had a higher prevalence of female gender (98% versus 88%, p = 0.03), antiparietal cell autoantibodies (33% versus 12%, p = 0.002), TgAb (30% versus 5%, p < 0.001), and TPOAb (40% versus 5%, p < 0.001). In conclusion, thyroid disease occurred in more than one-third of patients with primary SS; the main cause was ATD, which was present in 20% of the patients studied. We note that no significant differences were observed when the prevalence of thyroid disease (either ATD or NATD) was compared with that in a control group of similar age and gender. Our results indicate that middle-aged women (with or without SS) should be screened periodically for thyroid function.

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.

Novel point mutation in exon 10 of the RET proto-oncogene in a family with medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) may occur sporadically or as part of the autosomal dominant multiple endocrine neoplasia type 2 (MEN 2). Three hereditary forms of MEN 2 have been identified: MEN 2A, MEN 2B, and familial MTC (FMTC). Missense germ-line mutations in the RET proto-oncogene have been identified as cause of these endocrine diseases. Mutations are found in exons 10 and 11 in MEN 2A and FMTC families and in a small number of families in exons 13, 14, and 15. Although a strong correlation between codon mutations and phenotypes has been described, not all the expected cystein codon mutations have been found. Therefore, the more mutations are found, the better it is possible to establish phenotype-genotype correlations. We report on a novel RET mutation at codon 611 in a family with MTC without other clinical manifestations and of rather benign course.

The role of IGF binding protein-3 as a parameter of activity in acromegalic patients.

OBJECTIVE: The production of insulin-like growth factor binding protein-3 (IGFBP-3), the main IGF-I binding protein, is regulated by GH, and its serum levels are increased in acromegaly. We investigated its potential value as a parameter of acromegaly activity or remission in comparison with IGF-I, taking GH suppression below 2 microg/l after glucose load as the normal standard. METHODS: Data from 40 acromegalic patients (12 males and 28 females, aged 28 to 79 years) were obtained retrospectively from stored samples. From these, 145 pairs of IGF-I/IGFBP-3 values were collected; in 67 of them, simultaneous measurement of GH after glucose loading allowed their classification as active or inactive acromegaly. Relationships between IGF-I, IGFBP-3 and GH after glucose load were assessed, as well as differences between IGF-I and IGFBP-3 levels in active and inactive acromegaly. RESULTS: Significant positive correlation between IGF-I and IGFBP-3 in 145 samples was observed (r=0.49, P<0. 0001). As for the 67 samples in which activity or remission could be defined in terms of GH after glucose load, 50 were active and 17 inactive. Both IGF-I and IGFBP-3 significantly correlated with minimum GH (r=0.53, P<0.0001 and r=0.41, P<0.001 respectively). For both parameters, significant differences of means between active and inactive cases were observed (623+/-296 vs 300+/-108 ng/ml, P<0.0001 for IGF-I, and 4.1+/-1.3 vs 3.2+/-0.9 microg/ml, P<0.006 for IGFBP-3). Yet, when comparing in individual cases their classification as active or inactive with the finding of normal or increased IGF-I and IGFBP-3, among active cases 16% appeared as normal according to IGF-I, and 50% appeared as normal in terms of IGFBP-3. Among inactive cases, 23.5% appeared as active according to IGF-I, while 17.5% appeared as active in terms of IGFBP-3. CONCLUSION: Even though IGFBP-3 reflects GH secretion, it offers no advantage over IGF-I in the assessment of acromegaly, and it may underestimate disease activity in acromegalic patients.

Role of thyroid hormones on serum leptin levels.

Leptin is an adipose tissue hormone whose plasma levels reflect energy stores. Although pathological thyroid function is related to changes in energy expenditure and body composition, its possible influence on leptin levels remains to be determined. The objective of the study was to provide new data on the relationship between plasma leptin levels and thyroid function. Sixteen patients with primary autoimmune hypothyroidism, and seventeen patients with primary autoimmune hyperthyroidism were prospectively studied from the time of clinical diagnosis and then every 6-8 weeks until thyroid function was completely restored (plasma tri-iodothyronine, free thyroxine and TSH within normal ranges). Fasting immunoreactive plasma leptin levels and body composition (bioelectrical impedance) were assessed at every visit. Plasma leptin levels were correlated with percentage body fat, as previously described, both at the time of diagnosis (r=0.60, P<0.001) and after normalisation of thyroid function (r=0.63, P< 0.001). There was no correlation between serum leptin and thyroid hormone levels at any time during the study. Plasma leptin levels as well as percentage body fat (BF) did not change significantly from the beginning until the end of the study, either in the hypothyroid (leptin: 14.54+/-2.61 vs 16.92+/-2.61 ng/ml, BF: 25.25+/-2.47 vs 25.90+/-3.22%) or in the hyperthyroid (leptin: 10.69+/-1.81 vs 12.36+/-2.19 ng/ml, BF: 22.01+/-2.31 vs 25.39+/-1.13%) group of patients. In conclusion, these results suggest that thyroid function per se is not a major determinant of plasma leptin levels.

Predictors of bone mineral density reduction in adolescents with anorexia nervosa.

OBJECTIVES: To determine which variables are associated with a significant reduction in bone mineral density (BMD) in adolescent anorexia nervosa and to establish guidelines for indication of bone densitometry. METHOD: One hundred seventy patients (treated from 1997 until 1999), aged 10 to 17 years, with a DSM-IV diagnosis of anorexia nervosa were evaluated by dual-energy-x-ray absorptiometry in the lumbar spine (L2-L4) and the femoral neck. The results were compared with the normative data for BMD values by age and sex in Spanish adolescents. RESULTS: 44.1% of patients had osteopenia at the lumbar spine and 24.7% at the femoral neck. The following variables were related to osteopenia: more than 12 months since onset of the disorder (p < .001), more than 6 months of amenorrhea (p < .001), body mass index <15 (p < .001), calcium intake <600 mg/day (p < .01), and <3 hours/week of physical activity (p < .001). In a stepwise logistic regression analysis to predict reduced spinal BMD, 3 variables-months elapsed since the onset of weight loss, calcium intake, and body mass index--correctly classified 78.8% of patients. CONCLUSIONS: Adolescent anorexia nervosa patients with the characteristics outlined above are at high risk of reduced BMD, and densitometry is recommended to determine the degree of osteopenia.

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.

IgD myeloma: immunology and ultrastructure.

A case of multiple myeloma producing IgD-M component with light chains of lambda type is reported. It involved the skeleton and was complicated by compression of the spinal cord and massive extension to the pleura. The urine contained lambda Bence Jones protein. Under the electron microscope, the neoplastic plasma cells showed dissociation between nuclear and cytoplasmic maturation.

Idiopathic hypoparathyroidism associated with adult rheumatoid arthritis.

A 48-year-old female patient with adult onset idiopathic hypoparathyroidism diagnosed at the age of 28 years developed a typical seropositive rheumatoid arthritis (RA) at 46 years of age after several years of evolution of a palindromic rheumatism. Only one case of an association between idiopathic hypoparathyroidism and RA has been described in the medical literature. Autoimmunity seems to play a pivotal role in the aetiopathogenesis of both diseases, and could explain the nature of this association; nevertheless, a chance association could not be excluded.