Clinical and biochemical correlates of male hypogonadism in type 2 diabetes.

The origin of hypogonadism, a condition including both symptoms and biochemical criteria of androgen deficiency, in type 2 diabetes is poorly known. In a cross-sectional study of 267 unselected patients, we analyzed the potential correlation of several clinical and biochemical variables as well as chronic micro- and macrovascular diabetic complications with hypogonadism. Hypogonadism was present in 46 patients (17.2%) using a cutoff of total testosterone 10.4 nmol/L and in 31 (11.6%) with a cutoff of 8 nmol/L. Among these patients, hypogonadotropic hypogonadism was the most prevalent form (82.6%). Compared to eugonadal subjects, hypogonadal men had significantly lower glomerular filtration rate (67.1 ± 23.4 vs. 78.4 ± 24.6 mL/min/1.73 m2 , p = 0.005) and higher prevalence of chronic kidney disease (43.5% vs. 20.4%, p = 0.002), abnormal liver function tests (26.7% vs. 12%, p = 0.019), and psychiatric treatment (23.9% vs. 10.4%, p = 0.025). Total testosterone levels correlated inversely with age (R = -0.164, p = 0.007), fasting blood glucose (R = -0.127, p = 0.037), and triglycerides (R = -0.134, p = 0.029) and directly with glomerular filtration rate (R = 0.148, p = 0.015). Calculated free testosterone and bioavailable testosterone correlated directly with hemoglobin (R = 0.171, p = 0.015 and R = 0.234, p = 0.001, respectively). Multivariate logistic regression analysis, after adjusting for relevant confounding variables, showed that age >60 years (OR = 3.58, CI 95% = 1.48-8.69, p = 0.005), body mass index >27 kg/m2 (OR = 2.85, CI 95% = 1.14-7.11, p = 0.025), hypertriglyceridemia (OR = 2.16, CI 95% = 1.05-4.41, p = 0.035), glomerular filtration rate <60 mL/min/1.73 m2 (OR = 2.51, CI 95% = 1.19-5.29, p = 0.015), and abnormal liver function tests (OR = 3.57, CI 95% = 1.48-8.60, p = 0.005) were independently associated with male hypogonadism. Although older age, body mass index, and hypertriglyceridemia have been previously related to hypogonadism, our results describe that chronic kidney disease and abnormal liver function tests are independently correlated with hypogonadism in type 2 diabetic men.

Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm.

Adrenocortical oncocytic neoplasms (oncocytomas) are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol) and androgens (androstenedione and DHEAS), a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing's syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline) according to the Lin-Weiss-Bisceglia criteria.

Testosterone replacement therapy in hypogonadal men is associated with increased expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells.

BACKGROUND: Accumulated experimental data indicates that androgen therapy has effects on inflammation and protects from autoimmune disorders. Despite this, the in vivo effects of testosterone replacement therapy on human antigen-presenting cells-for example, monocytes and dendritic cells- remain unknown. OBJECTIVE, DESIGN AND PATIENTS: We monitored the effects of testosterone replacement therapy on the number and the functionality -as assessed by the expression of CD107b (lysosome-associated membrane protein 2, LAMP-2)- of resting and in vitro-stimulated peripheral blood (classical and nonclassical) monocytes and dendritic cells (myeloid and plasmacytoid) from hypogonadal men. RESULTS: Our results show that testosterone replacement therapy induces overexpression of CD107b by circulating monocytes and dendritic cells from hypogonadal men, both under resting (i.e. nonstimulated) conditions and after in vitro stimulation. CD107b overexpression mostly involved monocytes and in vitro stimulation with CpG oligodeoxynucleotides. Of note, a strong correlation was found between CD107b expression on monocytes and serum gonadotrophins levels. CONCLUSION: These results support the existence of an effect of testosterone therapy, and potentially also of gonadotrophins, on circulating antigen-presenting cells.

[Tethered cord syndrome in the adult]. / Síndrome de médula anclada en el adulto.

INTRODUCTION: The tethered cord syndrome (TCS) is a congenital malformation with a pathologic fixation of the spinal cord in the spinal canal. It presents clinically as musculoskeletal, cutaneous, urological and neurological manifestations. The diagnosis is based on the clinical manifestations and on the MRI (Magnetic Resonance Imaging) of the lumbar spine. It is usually diagnosed in childhood, but the symptoms can appear in adult life. METHOD: We reviewed all the cases of TCS in the adult diagnosed in our hospital between 1998 and 2005. The following parameters were evaluated: mean age at onset, initial symptoms, signs, MRI findings and outcome. RESULTS: Four 22 to 72 year old patients were diagnosed. The age at onset varied from 16 to 52 years old and the diagnosis took between 2 and 20 years to be established. The most frequent initial symptoms were the muscular atrophy and the motor weakness in the lower extremities. Two patients exhibited cutaneous stigmata (one had hypertrichosis and the other one a lipoma in the sacrum area) and one a partial agenesis of the sacrum. The most frequent MRI finding was a low lying cord with a lipoma in the sacrum area. In three patients the cord was detethered surgically, but only two of them improved. CONCLUSIONS: The TCS is an uncommon disease in adult, which is usually diagnosed very late in the adult. Because of its insidious and non specific symptomatology, and of its potential surgical treatment, it should be considered in the differential diagnosis of medullar syndromes and polyneuropathies.

Trocar site hernia after laparoscopic ventral hernia repair.

BACKGROUND: The incidence of trocar site hernia (TSH) after laparoscopic ventral hernia repair (LVHR) is reported to be low. The present study investigates the associated risk factors, with a view to preventing this complication. METHODS: A retrospective study was made of the incidence of TSH in a personal series of LVHR, recording anthropometric and clinical data on the patients. Risk factors were assessed by bivariate and multivariate analyses. The patients were subjected to clinical and telephone follow-up. RESULTS: In a series of 27 LVHR, the incidence of TSH was 22% (6 patients). The use of meshes larger than 10 x 15 cm for LVHR was the only TSH risk factor to reach statistical significance. Female gender and diabetes showed a higher incidence in the TSH group. CONCLUSIONS: The use of large meshes may be a risk factor for TSH. We believe this to be due to dilatation of the trocar orifice during introduction of the mesh, and also to postoperative retraction of the mesh.

Linfangiosarcoma sobre un linfedema crónico postmastectomía: síndrome de Stewart-Treves / No disponible

En 1948, Stewart y Treves comunicaron la aparición de unlinfangiosarcoma en el brazo edematoso de 6 pacientes sometidasa mastectomía radical por cáncer de mama. El síndromede Stewart-Treves describe la presentación de un linfangiosarcomao de un hemangiosarcoma sobre un linfedema crónico.Comunicamos el caso de una mujer de 74 años que fue sometidaa mastectomía radical derecha con radioterapia 23 añosantes y que consultó por la aparición de lesiones cutáneas enforma de placas violáceas en el brazo homolateral que llegarona hacerse nodulares. Tras la biopsia, el análisis histopatológicoconfirmó el diagnóstico de linfangiosarcoma. El estudio de extensiónfue negativo para metástasis. Se decidió la amputaciónde la extremidad. Seis meses más tarde, se diagnosticóuna metástasis cerebral y la paciente falleció poco tiempo después.Las opciones terapéuticas en estos casos (amputación,radioterapia y quimioterapia) son muy agresivas y ofrecen pobresresultados. Sólo un diagnóstico muy precoz, basado en lasospecha clínica, puede mejorar el pronóstico de esta complicaciónde la linfadenectomía axilar. La biopsia es obligatoriaante cualquier lesión sospechosa(AU)

In 1948, Stewart and Treves reported a lymphangiosarcomain 6 patient’s edematous arm after radical mastectomy forbreast cancer. Stewart-Treves syndrome describes a cutaneouslymphangiosarcoma or hemangiosarcoma that develops inlong-standing chronic lymphedema. We report a 74-year-oldwoman who was submitted to a right mastectomy and radiotherapy23 years before. She developed a chronic lymphedemain the same limb and fast-growing purplish lesions on thearm. These lesions became nodular. After the biopsy examinationthey were diagnosed as lymphangiosarcoma. The studyfor metastatic extension was negative. It was decided the amputationof the limb. Six months after the treatment, a brainmetastasis was diagnosed and the patient died. The therapeuticpossibilities (amputation, radiotherapy, chemotherapy) arevery aggresive and offer poor results. The physician mustmaintain a high index of suspicion in diagnosing this complicationof lymphadenectomy. If there is any doubt, biopsy is mandatory(AU)

Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency.

Androgens are considered to have immunomodulatory effects but their cellular mechanisms of action remain largely unknown. In the present study we prospectively analyzed the serial effects of androgen-replacement therapy on both the distribution of peripheral blood lymphocytes, monocytes and dendritic cells as well as on the production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines by circulating monocytes and CD33 myeloid, CD16 and plasmacytoid dendritic cell subsets, the most potent antigen-presenting cells (APCs) in type-2 diabetic men with partial androgen deficiency. Analyses were performed before therapy and at 1, 3, 6 and 12 months after treatment with 150 mg testosterone enanthate every 2 weeks in a group of 13 type-2 diabetic men. Our results show for the first time that testosterone-replacement therapy is associated with a reduction or complete abrogation of spontaneous ex vivo production of IL-1beta, IL-6 and TNFalpha by APCs. Meanwhile, the in vitro production of inflammatory cytokines by these cells after stimulation with lipopolysaccharide plus recombinant human interferon-gamma remained unchanged, suggesting that APCs preserve their constitutive machinery to produce inflammatory cytokines under androgen treatment. These results confirm and extend previous observations about the anti-inflammatory effects of androgen therapy on APCs in a new, previously unexplored model of androgen deficiency; namely, aging type-2 diabetic men. A decreased production of inflammatory cytokines by APCs might have important consequences for sex differences in susceptibility to autoimmune diseases, inflammatory response to injury and atheromatosis.

Hiperandrogenismo / Hyperandrogenism

El hiperandrogenismo es un problema endocrinológico frecuente en mujeres adultas. Su manifestación más habitual es el hirsutismo, acompañado o no de trastornos menstruales y con menor frecuencia de virilización. Se presenta un caso clínico de hiperandrogenismo con amenorrea secundaria y virilización en una mujer en edad fértil. Se evalúa el papel de las diferentes determinaciones hormonales y técnicas de imagen en el diagnóstico etiológico de este cuadro

Hyperandrogenism is one of the most common endocrine diseases affecting adult women. Clinical presentation includes hirsutism, with or without menstrual disturbances (oligomenorrhea, amenorrhea) and, less frequently, virilization. We report the case of a woman of reproductive age with hyperandrogenism, secondary amenorrhea, and virilization. The diagnostic role of laboratory tests and imaging techniques is discussed

Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control.

Aging in the male is associated with both a higher incidence of type 2 diabetes and hypogonadism. However, little information is available about the complex of symptoms and hormonal changes related to partial androgen deficiency in aging (called andropause) in type 2 diabetic men. Here, for the first time, we used a combination of clinical and hormonal criteria to define andropause and to analyze the relationships between the androgen environment and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/- SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of the diabetic men. The fraction of diabetic men with subnormal levels of total testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69 years) and 36% (> 70 years). The corresponding figures for subnormal values of free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group of type 2 diabetic men, no significant linear correlations between total or free testosterone with fasting plasma glucose, insulin, C-peptide, or fructosamine values could be established. Total testosterone was positively correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01). Although fasting plasma glucose was marginally higher in aging type 2 diabetic patients with andropause than in those without andropause (162 +/- 6.9 v 139 +/- 8.9, mean +/- SEM, P =.05), there were no differences between both subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c) levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men with clinical features of andropause associated with subnormal concentrations of serum testosterone. The treatment induced significant increases in total plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL, mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6 months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall glycemic control. These data show a high prevalence of andropause in aging type 2 diabetic men and suggest that the endogenous androgen environment, as well as correction of the partial androgen deficiency, do not have a meaningful effect on glycemic control.

Adenoma ovárico de células de Leydig: una rara causa devirilización asociada a factores de riesgo cardiovascular / Leydig cell ovarian adenoma: a rare cause of virilization associated with cardiovascular risk factors

La masculinización de la mujer adulta ovirilismo es un trastorno endocrino infrecuente debido a un exceso de secreción androgénica causado por tumores adrenales u ováricos 1. Dentro de estos últimos, los más comunes son los de células de Sertoli-Leydig (androblastomas), si bien otros tipos patológicos, como los tumores de la granulosa-teca, de células hiliares, de células lipoideas y de restos adrenales, también pueden generar el cuadro1. Presentamos un caso clínico de virilización debido a un adenoma de células de Leydig, un tumor ovárico raro que sólo representa un 0,1% de los tumores ováricos. Describimos su asociación con factores de riesgo cardiovascular y el efecto de la corrección permanente del hiperandrogenismo sobre los mismos (AU)