Interindividual differences in the clinical effectiveness of liraglutide in Type 2 diabetes: a real-world retrospective study conducted in Spain.

AIMS: To study the response of clinical variables (HbA1c , body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real-world clinical setting, and to describe the evolution of HbA1c and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs). METHODS: We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0-12.0) months. RESULTS: Individuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m2 ), with inadequate HbA1c (68 mmol/mol [8.4%]), blood pressure and lipid levels. Upon liraglutide treatment, HbA1c , body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA1c response, whereas higher baseline HbA1c , longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA1c response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response. CONCLUSIONS: In this real-world study, we showed the effectiveness of liraglutide in improving body weight, HbA1c , mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA1c and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide.

Síncope e hipotiroismo. Una relación razonable / Syncope and hypothryroidism. A reasonable relation

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Incidence of Type 1 diabetes in children in Cáceres, Spain, during 1988-1999.

AIM: To determine the incidence of Type 1 diabetes in Cáceres in children less than 14 years of age. We tested for differences in incidence by age, sex and season at diagnosis. METHODS: All Type 1 diabetes cases with onset <14 years of age between 1988 and 1999 were recorded retrospectively. Pediatric Unit registries provided the primary source of ascertainment. The secondary independent data source was based on the registries of local Diabetic Associations, diabetes camp records and guarantee cards of blood-glucose meters. We used the capture-recapture method for ascertainment. RESULTS: During the 12-year period, 137 new cases of Type 1 diabetes were identified. Completeness of ascertainment was 99.2%. Average annual observed incidence was 16.8/100,000/year (95% C.I. 14.1-19.8). Age-standardised incidence (world population): 16.5/100,000/year (95% C.I. 13.9-19.6). Average annual incidence for 0-4, 5-9 and 10-13-year-old groups: 12.7/100,000 (95% C.I. 8.8-17.9), 18.2/100,000 (95% C.I. 13.7-23.8) and 19.1/100,000 (95% C.I. 14.2-25.1). The highest age-specific annual incidence rate was found in the 10-13-year age group. There was a seasonal onset pattern, with the highest incidence in autumn and winter. November was the month with the highest number of cases (22/137). CONCLUSION: Cáceres has a moderately high incidence of Type 1 diabetes in children less than 14 years of age, similar to that found in other more developed and densely populated regions of Spain, and in the range of other countries of northern Europe. These data do not support the hypothesis of a decrease in the incidence of the disease from north to south over Europe.

[Primary adrenal insufficiency and primary antiphospholipid syndrome]. / Insuficiencia suprarrenal primaria y síndrome antifosfolípido primario.

Primary adrenal insufficiency (PAI) is a rare complication of antiphospholipid syndrome (APS). The hypercoagulable state in the APS may lead to adrenal vein thrombosis and subsequently to hemorrhagic necrosis of the adrenal glands. This complication of APS is important to recognize because it may be fatal if untreated. We describe one case of PAI and primary APS, with magnetic resonance studies consistent with hemorrhagic necrosis of the adrenal glands.

Insuficiencia suprarrenal primaria y síndrome antifosfolípido primario / Primary adrenal insufficiency and primary antiphospholipis syndrome

La insuficiencia suprarrenal primaria (ISP) es una complicación excepcional del síndrome antifosfolípido (SAF). El estado de hipercoagulabilidad en el SAF puede causar una trombosis de las venas suprarrenales con posterior necrosis hemorrágica de las glándulas. Es importante reconocer esta complicación del SAF, ya que si no se trata adecuadamente puede ser fatal. Presentamos un paciente con ISP y SAF primario, con hallazgos en la resonancia magnética compatibles con necrosis hemorrágica de las glándulas suprarrenales (AU)

Cyclic Cushing's disease associated with primary empty sella.

A small number of cases of Cushing's disease (CD) associated with primary empty sella (ES) have been described in the literature. Pituitary microsurgery is the recommended treatment. An alternative is chronic treatment with ketoconazole, an inhibitor of adrenal cortisol synthesis. Cyclic Cushing's syndrome is characterized by episodic cortisol hypersecretion. CD is the most frequent etiology of cyclic Cushing's syndrome. To our knowledge, cyclic CD has not previously been reported in association with primary ES. We describe a patient with cyclic CD associated with primary ES who was initially treated with ketoconazole and subsequently cured by transsphenoidal surgery.

Incidence of type I diabetes among children and young adults (0-29 years) in the province of Badajoz, Spain during 1992 to 1996.

In this study, we determine the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-29-y-old group in Badajoz (the largest and least developed province of Spain). We test for differences in incidence by age at diagnosis, time cluster and sex. Diabetes clinics and periodic review of hospital administration data provided the primary source of ascertainment. The secondary independent data source was based on registries of local Diabetic Associations and guarantee cards of blood glucose meters. Data were collected retrospectively in the period 1992-95 and prospectively for 1996. During the 5-y period (1992-96), 186 new cases of Type I diabetes were identified. Completeness of ascertainment was 95%. Average annual incidence (95% CI) for the 0-14, 15-29 and 0-29-y-old groups was 17.6/100,000 (14.5-21.2), 8.8/100,000 (6.9-11.1) and 12.8/100,000 (11-14.7). The highest age-specific annual incidence rate was found in the 10-14 age group: 23.4/100,000 (17.6-30.4). The incidence in males (14.7/100,000/y) was higher than in females (10.7/100,000/y). There was a seasonal onset pattern, with the highest incidence in autumn and winter. October was the month with the highest number of new cases (29/186). The province of Badajoz has a moderately high incidence of Type I diabetes in 0-14-y-old children, similar to that found in other more developed and densely populated regions of Spain. These data contradict the hypothesis of a decrease in the incidence of the disease from north to south over Europe.

[Thyrotropin-producing hypophyseal adenomas]. / Adenomas hipofisarios productores de tirotropina.

Thyrotropin (TSH)-producing adenoma or TSH-oma is an uncommon entity. Most cases correspond to macroadenomas, and microadenomas are exceptional. The differential diagnosis should include mainly hypophyseal resistance to thyroid hormones, which can be difficult because of normal findings of imaging studies of the pituitary gland in some cases of TSH-oma and also because of the clinical and biochemical heterogeneity of both entities. Hypophyseal surgery is the treatment of choice for TSH-omas, although clinical and biochemical recovery of hyperthyroidism is not achieved in a considerable proportion of cases. When surgery fails or is contraindicated, radiotherapy and somatostatine analogues are therapeutic alternatives. We report here two cases of TSH-producing microadenoma which were confirmed after hypophyseal surgery.

[Ketoconazole in the control of arterial hypertension in Cushing's syndrome]. / Ketoconazol en el control de la hipertensión arterial en el síndrome de Cushing.

OBJECTIVE: To determine the usefulness of ketoconazole for the control of arterial hypertension (AH) in Cushing syndrome (CS) as temporary treatment. PATIENTS AND METHODS: Fifteen cases of CS were collected (eleven cases of Cushing disease, two cases of ectopic secretion of ACTH, one case of adrenal adenoma, and one case of adrenal carcinoma). The clinical characteristics as well as laboratory data of patients with AH and the response to therapy were studied. RESULTS: Six patients (40%) had AH. A significant difference was observed of an older age, a higher frequency of association with diabetes mellitus and a higher 24 hour free urine cortisol (FUC) for patients with AH compared with non hypertensive patients. Ketoconazole was efficient for controlling AH in five cases, and in all of them the return to normal levels of 24 hour FUC was achieved. A failure of AH control under treatment with ketoconazole occurred in the only case of adrenal carcinoma. There was no significant secondary adverse reaction to ketoconazole. CONCLUSIONS: Ketoconazole is an efficient drug for the control of AH in CS and is well tolerated. In our series, the return to normal levels of FUC was associated with control of AH.

[Cushing's syndrome: clinical study of fifteen cases]. / Síndrome de Cushing: estudio clínico de quince casos.

OBJECTIVE: To study the epidemiological and clinical features and diagnostic tests of Cushing's syndrome (CS) of non-iatrogenic etiology, because of there are few similar studies in the last ten years. METHODS: Fifteen cases of CS were diagnosed from 1992 to 1997 at our hospital. We describe the epidemiological, clinical, biochemical, radiologic, therapeutic and evolutive characteristics. RESULTS: Both diabetes mellitus and hypertension were observed in 40% of patients. The frequency of etiologies was: Cushing's disease, 66.6%; ectopic ACTH syndrome, 13.3%; adrenal adenoma, 6.6%; adrenal carcinoma, 6.6%; and undiagnosed, 6.6%. The 24-hour urine free cortisol (UFC) and the overnight 1 mg oral dexamethasone suppression test yielded 93.3 and 100% diagnostic sensitivity for CS, respectively. The overnight 8 mg oral dexamethasone suppression test, the metyrapone test and the 7 mg intravenous dexmethasone test had 75, 50 and 60% diagnostic sensitivity for Cushing's disease, respectively. Ketoconazole treatment had success in to normalize the 24-hour UFC in all patients, except for the case of adrenal carcinoma. CONCLUSIONS: The Cushing's disease was the most common form of CS. The 24-hour UFC and overnight 1 mg oral dexamethasone suppression test were good screening studies. Ketoconazole was successful in normalizing the adrenal cortex function.

[Advances in pharmacological treatment of pituitary adenomas]. / Avances en el tratamiento farmacológico de los adenomas hipofisarios.

In last years, advances in endocrinological and neuroradiological research have lead to an earlier recognition and more effective management of pituitary tumours. At the same time, pharmacological investigation has allowed the development of useful drugs in the treatment of pituitary adenomas, either as an exclusive therapy or as an aid to surgery and radiotherapy. In this article we review indications and dosage of recently developed drugs for different types of hormone-secreting pituitary adenomas.

[Subtotal thyroidectomy. A treatment to keep in mind in amiodarone-induced thyrotoxicosis]. / Tiroidectomía subtotal. Un tratamiento a tener en cuenta en la tirotoxicosis inducida por amiodarona.

Amiodarone is an antiarrhythmic drug, frequently used in cardiology, which may produce secondary effects on the thyroid function. These effects can range from subtle changes in peripheral hormones without clinical manifestations, to severe forms of hypothyroidism or hyperthyroidism. The evolution of amiodarone-induced-hyperthyroidism can be mild, requiring only the withdrawal of the drug, or very severe, requiring an aggressive therapy with multiple drugs which may in some cases be fatal in spite of this therapy. Recently, the increase in the usage of this drug has produced reports of severe amiodarone-induced-thyrotoxicosis requiring surgery in some cases (subtotal or total thyroidectomy). A case of amiodarone-induced-thyrotoxicosis in its more aggressive form, which required intensive pharmacological treatment ultimately combined with surgery, is presented here.