The possible effect of anti-diabetic agents GLP-1RA and SGLT-2i on the respiratory system function.

Type 2 Diabetes (T2D) is a chronic disease with increasing incidence and prevalence and serious chronic complications, especially from cardiovascular system. However, other organs can be affected too. Several studies have associated T2D, especially when poorly controlled, with multiple pulmonary diseases. T2D is a common comorbidity among patients with asthma, Chronic Obstructive Pulmonary Disease (COPD), and Obstructive Sleep Apnea Syndrome (OSAS), and it is related to higher respiratory infection incidence, prevalence and severity. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are novel antihyperglycaemic agents with established cardiovascular benefits. There are also limited studies indicating their potential benefit in respiratory function. The aim of this article is to review data on the impact of GLP-1RA and SGLT-2i on respiratory function and describe the possible clinical benefits. Key findings indicate that GLP-1RA significantly improve lung function in patients with COPD, evidenced by improvements in spirometry measurements. Additionally, both GLP-1RA and SGLT-2i are associated with a decreased risk of severe and moderate exacerbations in COPD patients and have shown potential in reducing the incidence of respiratory disorders, including asthma and pneumonia. The mechanisms underlying these benefits are not yet fully understood and include multiple effects, such as anti-inflammatory action and oxidative stress reduction.

The role of kidney biopsy in deciphering diabetic versus non-diabetic origin of kidney disease among patients with type 2 diabetes mellitus and nephrotic range proteinuria: A retrospective study.

Background: Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The 'Gold standard' for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. Methods: Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). Results: Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD. Conclusion: This study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

Secondary diabetes mellitus in pheochromocytomas and paragangliomas.

Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.

The Role of Thyroid Disorders, Obesity, Diabetes Mellitus and Estrogen Exposure as Potential Modifiers for Pulmonary Hypertension.

Pulmonary hypertension (PH) is a progressive disorder characterized by a chronic in-crease in pulmonary arterial pressure, frequently resulting in right-sided heart failure and potentially death. Co-existing medical conditions are important factors in PH, since they not only result in the genesis of the disorder, but may also contribute to its progression. Various studies have assessed the impact of thyroid disorders and other endocrine conditions (namely estrogen exposure, obesity, and diabetes mellitus) on the progression of PH. The complex interactions that hormones may have with the cardiovascular system and pulmonary vascular bed can create several pathogenetic routes that could explain the effects of endocrine disorders on PH development and evolution. The aim of this review is to summarize current knowledge on the role of concomitant thyroid disorders, obesity, diabetes mellitus, and estrogen exposure as potential modifiers for PH, and especially for pulmonary arterial hypertension, and to discuss possible pathogenetic routes linking them with PH. This information could be valuable for practicing clinicians so as to better evaluate and/or treat concomitant endocrine conditions in the PH population.

Long-term outcome of differentiated thyroid cancer in children and young adults: risk stratification by ATA criteria and assessment of pre-ablation stimulated thyroglobulin as predictors of disease persistence.

PURPOSE: Differentiated thyroid cancer (DTC) has an increasing incidence in childhood and adolescence but long-term outcome data are limited. We aimed to identify possible risk factors associated with disease persistence, with special focus on the usefulness of ATA risk stratification system and pre-ablation stimulated thyroglobulin (Tg) levels. METHODS: We retrospectively studied 103 patients, 79 females (76.7%), aged 15.6 ± 3.2 years (range 5-21 years) who underwent total thyroidectomy for DTC. Patients were classified by ATA risk stratification criteria as low, intermediate, and high risk for recurrence. All, except five with papillary microcarcinoma, received radioactive iodine (RAI) treatment. RESULTS: At diagnosis, 44.7% of patients had cervical lymph node and 7.8% pulmonary metastases. Amongst the 72 patients with long-term follow-up data, 31.9% had persistent disease. Lymph node as well as pulmonary metastases and increased pre-ablation stimulated thyroglobulin (Tg) levels were associated with persistent disease. The risk of persistent disease was significantly higher in both the intermediate- (OR 17.95; 95% CI 2.66-120.94, p < 0.01) and high-risk (OR 17.65; 95% CI 4.47-69.74, p < 0.001) groups. ROC curve analysis showed that a pre-ablation Tg level higher than 14 ng/ml had a sensitivity of 94.7% to predict persistence, corresponding to a positive (PPV) and negative predictive values (NPV) of 66.7% and 93.8%, respectively. CONCLUSIONS: ATA risk stratification was validated in our population of children and young adults with DTC. Moreover, pre-ablation stimulated Tg levels of <14 ng/ml were associated with a low risk of long-term persistence and may therefore serve as a marker to identify patients who may need less intensive surveillance.

Suprasellar extension independently predicts preoperative pituitary hormone deficiencies in patients with nonfunctioning pituitary macroadenomas: a single-center experience.

PURPOSE: Nonfunctioning pituitary adenomas (NFPAs) are among the commonest benign tumors of the pituitary. Hypopituitarism is frequently present at the time of diagnosis, and this has been attributed to stalk portal vessel compression and/or destruction of normal anterior pituitary cells. The aim of our study was to examine possible factors at diagnosis associated with the presence of hypopituitarism. METHODS: We retrospectively evaluated the records of patients with nonfunctioning pituitary macroadenomas from the database of our department. The inclusion criterion was the availability of imaging data regarding the extension of the lesion. RESULTS: A total of 148 patients (89 men, 60.1%) with nonfunctioning macroadenomas and available imaging data were identified. Mean age at diagnosis was 56.0 ± 14.5 years, and hypopituitarism was found in 66.2%. The maximum diameter of the adenoma, the patient's age at diagnosis, and compression of the optic chiasm were significant factors predicting the presence of hypopituitarism (OR 1.077, p = 0.006; OR 1.025, p = 0.045; and OR 2.893, p = 0.042, respectively). Suprasellar adenomas with extension to adjacent sinuses, although larger than those with only suprasellar extension, did not differ as to the degree of hypopituitarism. Moreover, in suprasellar adenomas, prolactin levels, albeit not independently, were also related to hypopituitarism (OR 1.035, p = 0.045). CONCLUSIONS: In patients with NFPAs, prognostic factors related to increased risk of hypopituitarism are age at diagnosis, size of the adenoma, and most importantly the presence of suprasellar extension. These data accentuate the necessity for surgical decompression in case of suprasellar extension, in order, apart from saving visual acuity, to possibly avoid or reverse hypopituitarism.

Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients.

PURPOSE: Glucocorticoid actions are mediated by the glucocorticoid receptor (GCR) whose dysfunction leads to glucocorticoid tissue resistance. Our objective was to evaluate GCR-α and GCR-ß expression and key steps in the GCR signalling cascade in critical illness. METHODS: Expression of GCR and major GCR-target genes, cortisol, adrenocorticotropin (ACTH) and cytokines was measured in 42 patients on ICU admission and on days 4, 8, and 13. Twenty-five age- and sex-matched subjects were used as controls. RESULTS: Acutely, mRNA expression of GCR-α was 10-fold and of GCR-ß 3-fold the expression of controls, while during the sub-acute phase expression of both isoforms was lower compared to controls. Expression of FKBP5 and GILZ decreased significantly. Cortisol levels remained elevated and ACTH increased during the 13-day period. CONCLUSIONS: GCR expression and hypothalamic-pituitary-adrenal axis function undergo a biphasic response during critical illness. The dissociation between low GCR expression and high cortisol implies an abnormal stress response.

Decreased glucocorticoid receptor expression during critical illness.

INTRODUCTION: In critically ill patients, the hypothalamic-pituitary-adrenal axis is activated, resulting in increased serum cortisol concentrations. However, in some patients, especially those with sepsis, cortisol levels are relatively low for the degree of illness severity. Therefore, in the present project, we aim to characterize the time course of glucocorticoid receptor (GCR) alpha and beta expression in peripheral polymorphonuclear cells of critically ill septic or nonseptic patients using real-time PCR. DESIGN: A prospective observational study conducted on 32 critically ill adults not receiving steroids, in a university-affiliated, multidisciplinary intensive care unit (ICU). Blood samples were collected for measurement of glucocorticoid receptor expression within 24-48 hours of admission to the ICU and at days 4, 8 and 13 after admission, reflecting the acute and chronic phase of the illness. RESULTS: During ICU stay, patients expressed over time reduced levels of both GCR-α and GCR-ß mRNA. More specifically, GCR-α mRNA expression was decreased fourfold 4 days after admission (P < 0.0001) and remained low up to 2 weeks after admission (P < 0.001). On the other hand, GCR-ß mRNA levels remained stable shortly after admission, but approx. one week after admission, its levels decreased threefold (P < 0.01) and remained reduced up to 2 weeks after admission (P < 0.001). DISCUSSION: Our results suggest that critically ill patients have highly variable expression of alpha and beta GCR, and moreover, the levels of both receptors decrease during ICU stay. Taken together, these might explain the differential responsiveness of patients to exogenous steroid administration or to endogenous cortisol secretion.

Endocrine responses after a single bout of moderate aerobic exercise in healthy adult humans.

Exercise is a stress stimulus for the human organism affecting the homeostatic mechanisms of the body, depending on the type, duration, intensity and frequency of exercise. The aim of this study was to determine the effects of a moderate aerobic exercise bout on the Hypothalamo-Pituitary-Adrenal (HPA) axis acute hormonal responses in healthy adult humans. Twelve healthy male and female volunteers (age: 30.6 ± 4.4 years), performed a single bout of a 30-minute aerobic exercise at 70% of VO2max on a treadmill, following standard diet. Blood samples were collected before (t0), at the end of the exercise bout (t30), and 30 min after the completion of exercise (t60). Serum adrenocorticotropic hormone (ACTH), cortisol (COR), aldosterone (ALDO) and renin (REN) were measured. One-way ANOVA was used for statistics. ACTH and COR decreased after exercise, reaching significance (p < 0.01) 30 min after the completion of the exercise bout. ALDO increased at the end of exercise and remained elevated 30 min after its completion. REN significantly increased at the end of exercise (p < 0.05) and remained elevated. The exercise regimen used in this study had beneficial effects on the stress axis, suggesting that specific exercise protocols can be characterised by mild physiological stress-inducing effects hence be prescribed for special diseased populations.

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview.

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.

Differentiated thyroid cancer in childhood: a literature update.

Differentiated thyroid cancer in childhood is rare. Apart from family history, radiation exposure is a major risk factor. Although its clinical course is quite aggressive with higher rates of lymph node and pulmonary metastases as compared to adults, the final outcome tends to be favorable with mortality rates less than 2%. We herein review the clinical picture, genetic background response to treatment and recurrence rates of differentiated thyroid cancer in children and young adolescents are thoroughly reviewed and the main differences with adult differentiated thyroid cancer are highlighted.

Therapeutic trends and outcome of acromegaly: a single center experience over a 40-year period.

OBJECTIVE: To evaluate the therapeutic trends and long-term outcome of treatment modalities for acromegaly in our center over a 40-year period. DESIGN: We retrospectively studied 321 acromegalic patients (145 males/176 females) diagnosed and treated from the 1970s until September 2013. Patients were divided into two subgroups: group A consisted of 166 patients diagnosed before 1990 and group B of 155 patients diagnosed after 1990. Outcome was assessed with GH (random and/or post OGTT) and IGF1 measurements. RESULTS: More group A than group B patients were submitted to radiotherapy (57.8% vs 16.8% patients, respectively, p <0.001). In contrast, more patients of group B were offered surgery (70.3% vs 42.1% in group A, p <0.001) and/or medical treatment (70.3% vs 23.4% in group A, p <0.001). At latest follow-up, 68.4 % of patients in group B achieved GH <2.5 µg/l after treatment vs 39.8% in group A, p=0.001, 46.9% of patients in group B achieved GH <1 µg/l vs 20.3% in group A, p=0.001 and 47.1% of patients in group B achieved during OGTT GH nadir <0.4 µg/l vs 18.6% in group A, p=0.001. CONCLUSIONS: Transsphenoidal resection and medical treatment resulted in improved outcome in acromegalic patients treated over the last 20 years. However, the disease still remains uncontrolled in a considerable number of patients.

Evidence of Subcutaneous Tissue Lipolysis Enhancement by Endogenous Cortisol in Critically Ill Patients Without Shock.

BACKGROUND/AIM: Cortisol is involved in in many aspects of adipose tissue metabolism. A positive association between plasma cortisol and lipolysis has been observed. Critically ill patients exhibit 'lipemia of sepsis'. The aim of the present study was to study, in septic ICU patients, adipose tissue lipolysis in relation to tissue cortisol using microdialysis (MD). PATIENTS AND METHODS: We studied 17 mechanically-ventilated patients (9 men; mean±SD age=63±19 years) with a diagnosis of severe sepsis. Upon ICU admission, an MD catheter was inserted under sterile conditions into the subcutaneous adipose tissue of the upper thigh. On days 2, 3 and 4, MD samples were collected six times per day for glycerol (used as an index of lipolysis) and tissue cortisol determinations. The mean of these six collections was used for analysis (normal values for adipose tissue glycerol <200 µmol/l). Statistics were carried-out with analysis of covariance (ANCOVA) and linear regression. RESULTS: More than half of the samplings (19/31) indicated accentuated lipolysis with above-normal MD glycerol levels. By ANCOVA, MD glycerol (log values) was associated with MD cortisol (log values) (p=0.012) and was not associated with age or day of sampling. Furthermore, MD glycerol (log values) was positively correlated to MD cortisol (log values) (r=0.490, p=0.012). DISCUSSION: Changes in interstitial/tissue cortisol may not be reflected in (total) plasma cortisol concentration. Thus, it is interesting that we observed, albeit weak, an association between tissue lipolysis (via MD glycerol levels) and MD cortisol, verifying (although modestly so) the well-known association between lipolysis and cortisol.

CLINICAL PRESENTATION AND LONG-TERM OUTCOME OF PATIENTS WITH ECTOPIC ACTH SYNDROME DUE TO BRONCHIAL CARCINOID TUMORS: A ONE-CENTER EXPERIENCE.

OBJECTIVE: To describe the diagnostic features and long-term outcome of patients with bronchial carcinoid tumors with ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), treated in our department. METHODS: We studied 10 cases with EAS and histologically confirmed bronchial carcinoid tumors, diagnosed from 1992 until 2006. Diagnosis was based upon blood, urine, radiologic, and interventional tests. Disease status at the time of the last follow-up was the primary outcome measure. RESULTS: Clinical manifestations included Cushingoid features (100%), psychiatric symptoms (90%), hypertension (70%), diabetes/impaired glucose tolerance (40%), osteoporosis (10%), and hypokalemia (10%). The average time from the onset of symptoms until diagnosis was 14.2 ± 17.0 months. None of the patients exhibited a positive cortisol or ACTH response to corticotropin-releasing hormone (CRH) test, and none showed a positive gradient on bilateral inferior petrosal sinus sampling (BIPSS). All tumors were identified by computed tomography and by octreotide scintigraphy in 8 patients. All patients underwent surgical resection of the tumor, and 2 patients had adjuvant radiation therapy. The mean follow-up was 126.6 ± 63.3 months. At latest follow-up, 8 patients were in remission and 2 had recurrence of the EAS; both had a multifocal tumor. The 2 patients submitted to adjuvant radiation therapy were in remission at their latest follow-up, despite local invasion and lymph node metastases. CONCLUSION: CRH test and BIPSS are the most useful methods in diagnosing EAS. For localization, repeated imaging studies are necessary. Surgical treatment is effective in most cases. Adjunctive radiotherapy may be useful in patients with lymph node metastases. Patients with multifocal disease should be monitored for potential recurrence.

Cytomegalovirus reactivation in a general, nonimmunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers.

PURPOSE: Cytomegalovirus (CMV) reactivation, a significant cause of morbidity and mortality in immunosuppression, may affect "immunocompetent" seropositive critically ill patients. The aim of this prospective, observational study was to define the incidence, risk factors, and the association with morbidity and mortality of CMV reactivation in a general population of critically ill immunocompetent patients. We also studied the relationship between reactivation and patients' inflammatory response, as expressed by cytokine levels and stress up-regulation by salivary cortisol. METHODS: This study included mechanically ventilated CMV-seropositive patients. A quantitative real-time polymerase chain reaction (PCR) was performed for CMV plasma DNAemia determination, upon intensive care unit (ICU) admission and weekly thereafter until day 28. Cytomegalovirus reactivation was defined as CMV plasma DNAemia greater than or equal to 500 copies/mL. Upon ICU admission, interferon γ, interleukin (IL) 10, IL-17A, IL-2, IL-6, and tumor necrosis factor α were quantified in plasma, and morning saliva was obtained to measure cortisol. Disease severity was assessed by Acute Physiology and Chronic Health Evaluation II score, whereas the degree of organ dysfunction was quantified by Sequential Organ Failure Assessment score. Mortality, duration of mechanical ventilation, and ICU length of stay were recorded. RESULTS: During the study period, 80 (51 men) patients with a median age of 63 years fulfilled the inclusion criteria. Reactivation of CMV occurred in 11 patients (13.75%). Median day of reactivation was day 7 post ICU admission. Total number of red blood cell units transfused (odds ratio [OR], 1.50; confidence interval [CI], 1.06-2.13; P = .02) and C-reactive protein levels upon ICU admission (OR, 1.01; CI, 1.00-1.02; P = .02) were independently associated with CMV reactivation. High IL-10 was marginally related to reactivation (P = .06). Sequential Organ Failure Assessment scores were higher in the group with CMV reactivation compared with patients without reactivation during the entire 28-day observation period (P < .006). Salivary cortisol, mortality, length of ICU stay, and duration of mechanical ventilation were similar in the 2 groups. CONCLUSIONS: Cytomegalovirus reactivation occurred in 13.75% of critically ill, immunocompetent patients. The degree of inflammation and the total number of transfused red blood cells units constituted risk factors. Cytomegalovirus reactivation was associated with more severe of organ dysfunction, but not with a worse clinical outcome.

Longitudinal assessment of adrenal function in the early and prolonged phases of critical illness in septic patients: relations to cytokine levels and outcome.

CONTEXT: Adrenal dysfunction remains a controversial issue in critical care. The long-stay intensive care unit (ICU) population may be at increased risk of adrenal insufficiency. OBJECTIVE: We aimed to determine whether adrenal dysfunction develops during the course of sepsis. DESIGN: This is a prospective observational longitudinal study. SETTING: The study was conducted in the ICU of a secondary/tertiary care hospital. PATIENTS: We studied 51 consecutive mechanically ventilated patients with sepsis. INTERVENTION: We measured cortisol, ACTH, cortisol-binding globulin, cytokines, and cortisol 30 minutes after 1 µg ACTH(1-24), upon sepsis diagnosis and every 3 to 4 days, until Day 30 or until recovery or death. MAIN OUTCOME MEASURES: We looked for changes in baseline and stimulated cortisol levels and its relationship to ACTH levels, sepsis severity or survival. RESULTS: Baseline and stimulated cortisol levels did not vary significantly. Septic patients with shock had higher baseline (20 ± 6 vs 17 ± 5 µg/dL, P = .03) and stimulated cortisol levels (26 ± 5 vs 23 ± 6 µg/dL, P = .04), compared with those without shock. On Day 1, ACTH levels could not predict cortisol levels (R(2) = 0.06, P = .08). ACTH levels increased significantly after Day 10 and, at this time point, they related to cortisol levels (R(2) = 0.35, P < .001). Development of septic shock, or resolution from it, was not associated with changes in baseline, stimulated cortisol levels, or the cortisol increment. There was much inpatient variability in the diagnosis of adrenal dysfunction at different time points. CONCLUSIONS: Total cortisol levels relate both to the severity and outcome of sepsis and remain fairly unchanged during the course of illness. Initially, cortisol levels are largely ACTH independent, whereas ACTH increases and correlates with cortisol levels later on. Adrenal dysfunction does not seem to be a major problem during the prolonged phase of sepsis. Although not significant, the variation in cortisol levels may be such that classification of patients varies, questioning the utility of arbitrary cut-offs to define adrenal dysfunction in septic patients.

Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid cancer: is there an association? A case report and literature review.

Type 1 diabetes mellitus (T1DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency. Associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, can coexist in patients with T1DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase (anti-tTG-IgA), thyroglobulin, and thyroid peroxidase (anti-TG, anti-TPO), as well as antibodies against gastric parietal cells. Children with T1DM may also develop organ-specific multiple autoimmunity, with the coexistence of one or more autoimmune disorders. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. We present a child with T1DM and multiple autoimmunity including autoimmune Hashimoto's thyroiditis (HT), who developed thyroid cancer. The literature on the prevalence of associated autoimmunity in children with T1DM and the prevalence, pathogenesis, and timely diagnosis of thyroid cancer among patients with HT is also reviewed.

X-linked adrenoleukodystrophy: are signs of hypogonadism always due to testicular failure?

We present the clinical and hormonal findings of a young male with X-linked adrenoleukodystrophy (X-ALD), with special emphasis on the biochemical and clinical pattern of hypogonadism. A patient, with primary adrenal insufficiency since the age of 5 years, developed progressive neurological symptoms at the age of 29. Diagnosis of X-ALD was established by elevated serum very long chain fatty acids (VLCFAs) and genetic testing. His sexual body hair was sparse. Hormonal investigations revealed normal testosterone and inappropriately elevated LH levels. Androgen receptor gene analysis was negative for mutations or polymorphic variants associated with decreased receptor activity. Signs of hypogonadism in patients with confirmed X-ALD are not exclusively due to primary testicular failure. Tissue specific androgen resistance represents an alternative possibility. Since no loss-of-function mutations were detected in the androgen receptor, it is speculated that the patient's androgen resistance could be part of a functional defect mediated through VLCFA accumulation at the testosterone receptor and/or post-receptor levels.

Impact of early vs late postoperative radioiodine remnant ablation on final outcome in patients with low-risk well-differentiated thyroid cancer.

OBJECTIVE: Postoperative radioiodine remnant ablation (RRA) represents an adjunctive therapeutic modality in patients with differentiated thyroid cancer (DTC). The impact of late vs early RRA on the outcome of DTC is currently unclear. The aim of the study was to evaluate the outcome of patients with DTC according to RRA timing. DESIGN RETROSPECTIVE STUDY PATIENTS: A total of 107 TNM stage 1 DTC patients were divided into two groups. In group A (n = 50), RRA was administered in less than 4·7 months median 3·0 (range 0·8-4·7), while in group B (n = 57) in more than 4·7 months median 6 (4·8-30·3) after thyroidectomy. Remission was achieved when stimulated serum Tg levels were undetectable, in the absence of local recurrence or cervical lymph node metastases on the neck ultrasound. RESULTS: All patients underwent near-total thyroidectomy. The mean age at diagnosis was 49·3 years (range: 18-79 years). There were no statistically significant differences in the histological subtype, the TNM stage, the dose of radioiodine and the time of follow-up, between the two groups. After the RRA treatment, 44 group A patients (88%) were in remission and 6 (12%) in persistence; while in group B, 52 (91·2%) were in remission, 1 (1·8%) in persistence and 4 (7%) in recurrence. At their latest follow-up median 87·3 (23·3-251·6 months), all patients were in remission, either as a result of further iodine radioiodine therapy (in 11 patients) or watchful monitoring. CONCLUSIONS: The timing of RRA seems to have no effect on the long-term outcome of the disease. Therefore, urgency for radioiodine ablation in patients with low-risk thyroid cancer is not recommended.