Reliability of a computer-aided system in the evaluation of indeterminate ultrasound images of thyroid nodules.

Introduction: Computer-aided diagnostic (CAD) programs for malignancy risk stratification from ultrasound (US) imaging of thyroid nodules are being validated both experimentally and in real-world practice. However, they have not been tested for reliability in analyzing difficult or unclear images. Methods: US images with indeterminate characteristics were evaluated by five observers with different experience in US examination and by a commercial CAD program. The nodules, on which the observers widely agreed, were considered concordant and, if there was little agreement, not concordant or difficult to assess. The diagnostic performance of the readers and the CAD program was calculated and compared in both groups of nodule images. Results: In the group of concordant thyroid nodules (n = 37), the clinicians and the CAD system obtained similar levels of accuracy (77.0% vs 74.2%, respectively; P = 0.7) and no differences were found in sensitivity (SEN) (95.0% vs 87.5%, P = 0.2), specificity (SPE) (45.5 vs 49.4, respectively; P = 0.7), positive predictive value (PPV) (75.2% vs 77.7%, respectively; P = 0.8), nor negative predictive value (NPV) (85.6 vs 77.7, respectively; P = 0.3). When analyzing the non-concordant nodules (n = 43), the CAD system presented a decrease in accuracy of 4.2%, which was significantly lower than that observed by the experts (19.9%, P = 0.02). Conclusions: Clinical observers are similar to the CAD system in the US assessment of the risk of thyroid nodules. However, the AI system for thyroid nodules AmCAD-UT® showed more reliability in the analysis of unclear or misleading images.

One year of the pandemic - how European endocrinologists responded to the crisis: a statement from the European Society of Endocrinology.

Changes that COVID-19 induced in endocrine daily practice as well as the role of endocrine and metabolic comorbidities in COVID-19 outcomes were among the striking features of this last year. The aim of this statement is to illustrate the major characteristics of the response of European endocrinologists to the pandemic including the disclosure of the endocrine phenotype of COVID-19 with diabetes, obesity and hypovitaminosis D playing a key role in this clinical setting with its huge implication for the prevention and management of the disease. The role of the European Society of Endocrinology (ESE) as a reference point of the endocrine community during the pandemic will also be highlighted, including the refocusing of its educational and advocacy activities.

COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology.

BACKGROUND: COVID-19 has completely changed our daily clinical practice as well as our social relations. Many organs and biological systems are involved in SARS-Cov-2 infection, either due to direct virus-induced damage or to indirect effects that can have systemic consequences. Endocrine system is not only an exception but its involvement in COVID-19 is so relevant that an "endocrine phenotype" of COVID-19 has progressively acquired clinical relevance. AIM: We have been appointed by the European Society of Endocrinology (ESE) to update with the current statement ESE members and the whole endocrine community on the emerging endocrine phenotype of COVID-19 and its implication for the prevention and management of the disease. CONCLUSIONS: Diabetes has a major role in this phenotype since it is one of the most frequent comorbidities associated with severity and mortality of COVID-19. Careful management including treatment modifications may be required for protecting our patients rather with known diabetes from the most dangerous consequences of COVID-19 or hospitalized with COVID-19, but also in patients with SARS-CoV-2 induced newly onset diabetes. Obesity increases susceptibility to SARS-CoV-2 and the risk for COVID-19 adverse outcome. Adequate nutritional management needs to be granted to patients with obesity or undernourishment in order to limit their increased susceptibility and severity of COVID-19 infection. Lack of vitamin D, hypocalcemia and vertebral fractures have also emerged as frequent findings in the hospitalized COVID-19 population and may negatively impact on the outcome of such patients. Also, in patients with adrenal insufficiency prompt adaptation of glucocorticoid doses may be needed. Moreover, in this updated statement role of sex hormones as well as peculiar pituitary and thyroid aspects of COVID-19 have been included. Finally, in view of the mass vaccination, potential implications for endocrine patients should be considered.

Why don't corticotroph tumors always produce Cushing's disease?

OBJECTIVE: Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing's disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. DESIGN: We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. METHODS: We used Sanger sequencing, quantitative real-time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. RESULTS: We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro-functioning corticotroph tumors (all P < 0.05). Moreover, we found a positive correlation between PC2 and CPE gene and protein expression (rho ≥ 0.670, P < 0.009) in silent corticotroph tumors compared with functioning ones. CONCLUSIONS: By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro-functioning corticotroph tumor behaving as an intermediate state between micro-functioning and silent corticotroph tumors.

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. METHODS: A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). RESULTS: Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. CONCLUSIONS: Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano / Treatment of type 2 diabetes mellitus in elderly patients

La prevalencia de la diabetes mellitus tipo 2 (DM2) se incrementa marcadamente con la edad. El tratamiento antidiabético y los objetivos de control glucémico en el anciano con DM2 deben individualizarse en función de sus características biopsicosociales. En los pacientes de edad avanzada, en los que los beneficios de un tratamiento antidiabético intensivo son limitados, los objetivos básicos deben ser mejorar la calidad de vida, preservar la funcionalidad y evitar los efectos adversos, muy especialmente las hipoglucemias. El tratamiento de la DM2 en el anciano fue objeto de un consenso, publicado en 2012 y avalado por varias sociedades científicas españolas. Desde entonces, han aparecido nuevos grupos terapéuticos y evidencias que hacen recomendable su actualización. El presente documento se centrará en los aspectos terapéuticos de la DM2 en el paciente anciano, entendiendo como tal el tener una edad mayor de 75 años o presentar fragilidad (AU)

The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail (AU)

Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano / Treatment of type 2 diabetes mellitus in elderly patients

La prevalencia de la diabetes mellitus tipo 2 (DM2) se incrementa marcadamente con la edad. El tratamiento antidiabético y los objetivos de control glucémico en el anciano con DM2 deben individualizarse en función de sus características biopsicosociales. En los pacientes de edad avanzada, en los que los beneficios de un tratamiento antidiabético intensivo son limitados, los objetivos básicos deben ser mejorar la calidad de vida, preservar la funcionalidad y evitar los efectos adversos, muy especialmente las hipoglucemias. El tratamiento de la DM2 en el anciano fue objeto de un consenso, publicado en 2012 y avalado por varias sociedades científicas españolas. Desde entonces, han aparecido nuevos grupos terapéuticos y evidencias que hacen recomendable su actualización. El presente documento se centrará en los aspectos terapéuticos de la DM2 en el paciente anciano, entendiendo como tal el tener una edad mayor de 75 años o presentar fragilidad (AU)

The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail (AU)

[Treatment of type 2 diabetes mellitus in elderly patients]. / Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano.

The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail.

Treatment of type 2 diabetes mellitus in elderly patients. / Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano.

The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail.

Opposite changes in meteorin-like and oncostatin m levels are associated with metabolic improvements after bariatric surgery.

Bariatric surgery is currently the most effective therapy for type 2 diabetes. However, the mechanisms underlying its beneficial effects remain elusive. Here we studied the effects of bariatric surgery on circulating meteorin-like (Metrnl) and oncostatin m (OSM) levels, two hormones intimately linked to energy homeostasis. Metrnl and OSM levels were assessed at baseline, 6 and 12 months after laparoscopic sleeve gastrectomy (LSG) in 25 patients with obesity, as well as in 33 normal-weight controls. At baseline, patients with obesity showed lower Metrnl and higher OSM levels compared to controls. LSG increased Metrnl and decreased OSM levels, in correlation to improvements in glucose and lipid homeostasis. Our data indicate that LSG conversely modulated Metrnl and OSM levels, and suggest that a dual approach modulating these two molecules might provide a novel strategy for obesity and type 2 diabetes treatment.

Validation of PHPQoL, a Disease-Specific Quality-of-Life Questionnaire for Patients With Primary Hyperparathyroidism.

CONTEXT: Health-related quality of life (HRQoL) is impaired in primary hyperparathyroidism (PHPT) but instruments to specifically assess this are scarce. OBJECTIVE: Validate the new disease-specific Primary Hyperparathyroidism Quality of Life (PHPQoL) questionnaire in usual clinical practice. DESIGN: Observational, prospective, and multicenter. SETTING: Public hospital ambulatory care. PATIENTS: Patients with PHPT of both sexes, aged more than or equal to 18 years either initiated treatment for PHPT (group A) or had stable PHPT, not requiring therapy (group B). Patients in group A had at least one surgical criterion according to the 2009 Third International Workshop on Management of Asymptomatic PHPT. INTERVENTION: Sociodemographic, clinical, and HRQoL data (PHPQol, Short Form-36, Psychological Well-Being Index, and patients' self-perceived health status) were collected. Group A underwent 4 evaluations (baseline, 3 ± 1, 6 ± 1, and 12 ± 2 months after a therapeutic intervention) and group B 2, at baseline and 1 month later to assess test-retest reliability. RESULTS: A total of 182 patients were included (104 group A, 78 group B) with a mean age (SD) of 61.4 (12.1) years; 79.7% were women. Group A increased PHPQoL score (SD) (better HRQoL) (52 ± 23 at baseline; 62 ± 24 at 12 months; P < .001). At baseline, symptomatic patients had a lower PHPQoL score (worse) than asymptomatic ones (51 ± 21 vs 68 ± 21; P < .001). Correlations were seen between PHPQoL and Short Form-36, Psychological Well-Being Index, and self-perceived health status (P < .001). PHPQoL had good internal consistency (Cronbach's α = 0.80), test-retest reliability (group B, intraclass correlation coefficient > 0.80), and sensitivity to detect HQRoL changes over time. CONCLUSIONS: PHPQoL is a valid HRQoL measure to assess the impact of PHPT on health perception in clinical practice.

Hacia un manejo integral del paciente con diabetes y obesidad. Posicionamiento de la SEMI, SED, redGDPS, SEC, SEEDO, SEEN, SEMERGEN y SEMFYC / Position statement of the SEMI, SED, redGDPS, SEC, SEEDO, SEEN, SEMERGEN y SEMFYC

La obesidad y el sobrepeso constituyen la principal causa modificable de diabetes tipo 2 (DM2). En el momento del diagnóstico de la diabetes tipo 2 se debe establecer el grado de obesidad según el índice de masa corporal y, en los pacientes con sobrepeso, determinar el perímetro de la cintura. El adecuado tratamiento de la DM2 requiere un abordaje simultáneo del sobrepeso/obesidad y el resto de factores de riesgo cardiovascular, como la hipertensión, la dislipemia o el tabaquismo. Las intervenciones no farmacológicas (dieta, ejercicio) con beneficio demostrado en la prevención y tratamiento del paciente con DM2 y sobrepeso/obesidad deben seguir un enfoque individualizado y multidisciplinario, con programas estructurados dotados de recursos específicos. La ganancia de peso asociada al tratamiento antidiabético puede dificultar el control glucémico, comprometer la adherencia al tratamiento, empeorar el perfil de riesgo vascular de los pacientes y limitar los beneficios cardiovasculares del tratamiento. Por ello, es importante evitarla; una medida que resulta coste-efectiva. Los fármacos antidiabéticos con beneficios sobre el peso corporal también han demostrado su beneficio en pacientes con un índice de masa corporal<30kg/m2. Globalmente, el tratamiento del paciente con DM2 y obesidad dependerá tanto del grado de obesidad como de la comorbilidad asociada. Los ensayos clínicos de intervención en DM2 deben contemplar objetivos combinados que incluyan no solo el control glucémico, sino otras variables como el riesgo de hipoglucemia y el efecto del tratamiento sobre el peso corporal (AU)

Obesity and excess weight are the main preventable causes of type 2 diabetes (DM2). When diagnosing type 2 diabetes, clinicians should establish the degree of obesity according to the body mass index (BMI) and, for patients with excess weight, measure the waist circumference. The proper treatment of DM2 requires a simultaneous approach to excess weight/obesity and the other cardiovascular risk factors, such as hypertension, dyslipidaemia and smoking. Nondrug interventions (e.g., diet and exercise) have proven benefits in preventing and treating patients with DM2 and excess weight/obesity and should follow an individual and multidisciplinary approach, with structured programs equipped with specific resources. Weight gain associated with antidiabetic treatment can hinder glycaemic control, compromise treatment adherence, worsen the vascular risk profile and limit the cardiovascular benefits of treatment. Therefore, it is significant to avoid weight gain, a measure that can be cost-effective. Antidiabetic drugs with benefits in body weight have also demonstrated their benefit in patients with BMIs <30. In general, the treatment of patients with DM2 and obesity will depend both on the degree of obesity and the associated comorbidity. Clinical trials on DM2 intervention should consider combined objectives that include not only glycaemic control but also other variables such as the risk of hypoglycaemia and the effect of treatment on body weight (AU)

Position statement of the SEMI, SED, redGDPS, SEC, SEEDO, SEEN, SEMERGEN y SEMFYC.

Obesity and excess weight are the main preventable causes of type 2 diabetes (DM2). When diagnosing type 2 diabetes, clinicians should establish the degree of obesity according to the body mass index (BMI) and, for patients with excess weight, measure the waist circumference. The proper treatment of DM2 requires a simultaneous approach to excess weight/obesity and the other cardiovascular risk factors, such as hypertension, dyslipidaemia and smoking. Nondrug interventions (e.g., diet and exercise) have proven benefits in preventing and treating patients with DM2 and excess weight/obesity and should follow an individual and multidisciplinary approach, with structured programs equipped with specific resources. Weight gain associated with antidiabetic treatment can hinder glycaemic control, compromise treatment adherence, worsen the vascular risk profile and limit the cardiovascular benefits of treatment. Therefore, it is significant to avoid weight gain, a measure that can be cost-effective. Antidiabetic drugs with benefits in body weight have also demonstrated their benefit in patients with BMIs <30. In general, the treatment of patients with DM2 and obesity will depend both on the degree of obesity and the associated comorbidity. Clinical trials on DM2 intervention should consider combined objectives that include not only glycaemic control but also other variables such as the risk of hypoglycaemia and the effect of treatment on body weight.

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.

The usefulness of the leuprolide stimulation test as a diagnostic method of idiopathic central precocious puberty in girls.

Central precocious puberty (CPP) diagnosis is based on clinical evaluation, but hormonal evaluation is crucial. The aim of the study was to evaluate the usefulness of the leuprolide stimulation test for diagnosis of idiopathic CPP. Sixty-one girls, aged 5-8 years, were evaluated retrospectively for premature breast development. According to clinical evolution, 28 had progressive puberty and 33 nonprogressive puberty. All underwent a leuprolide stimulation test. Cutoff points, sensitivity, and specificity for gonadotropins and estradiol were determined by receiver operating characteristic (ROC) curves. Cutoff points for CPP were: baseline LH: > 0.1 mUI/l, FSH: > 2.3 mUI/l, LH/FSH ratio: > 0.23, estradiol: > 12 pg/ml; and stimulated LH: > 5.5 mUI/l, LH/FSH ratio: > 0.24, estradiol: > 79.67 pg/ml. The best diagnostic efficiency for progressive puberty were stimulated LH/FSH ratio (sensitivity: 100%, specificity 94%) followed by stimulated LH (sensitivity: 93%, specificity: 100%). Stimulated LH/FSH ratio and LH resulted in the most useful parameters for the diagnosis of CPP. Stimulated estradiol did not add more information.

Glucose impairment and ghrelin gene variants are associated to cognitive dysfunction.

BACKGROUND AND AIMS: Cognitive state and brain volume have been related to body mass index, abdominal fat, waist-hip ratio, components of metabolic syndrome (MS) and ghrelin. Genetic variations within the ghrelin gene have been recently associated to MS. The aim of our study was to investigate cognitive state by Mini-Mental State Examination (MMSE) in relation to MS components (ATP-III criteria) and ghrelin gene polymorphisms in dwelling individuals aged ≥70. METHODS: 280 subjects (137 men/143 women, age 77.03 ± 5.92) from the Mataró Ageing Study were included. Individuals were phenotypically characterized by anthropometric variables, lipids, glucose, blood pressure and MMSE. SNPs -501AC (rs26802), -994CT (rs26312), -604GA (rs27647), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene were studied. Genotypes were determined by polymerase chain reaction and SNapshot minisequencing. RESULTS: 22.1 % had MMSE <24. MMSE <24 was associated with age (p < 0.001), female gender (p = 0.016), low education (p < 0.001) and glucose impairment or diabetes (p = 0.040). MMSE was influenced by obesity, central obesity, MS and glucose impairment. This latter association remained significant after adjustment by gender, age, alcohol, educational level, GDS and ApoE genotype (p = 0.009). Ghrelin SNPs were associated to MMSE: M72L C/A genotype showed lower score than C/C (p = 0.032, after adjusting for confounders 0.049); L90G A/T genotype showed lower score than A/A (p = 0.054, after adjusting 0.005). MMSE <24 was associated to L90G (39.1 % in A/T genotype vs 19.3 % in A/A, p = 0.026, after adjusting for confounders p = 0.002, OR 6.18 CI 1.93-21.75). CONCLUSIONS: Glucose impairment and L90G Ghrelin gene variant influence cognitive function in old dwelling individuals participating in the Mataró Ageing Study.

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.

Growth hormone treatment for sustained pain reduction and improvement in quality of life in severe fibromyalgia.

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time.