Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Impact of allogeneic stem cell transplantation on thyroid function.

PURPOSE: Primary hypothyroidism is a main endocrine complication after allogeneic stem cells transplantation (allo-SCT) in children, but in adults data on post-SCT hypothyroidism are limited. The aims of this observational, cross-sectional study were to assess the prevalence of hypothyroidism in adult allo-SCT recipients according to time from transplantation, and to identify risk factors. METHODS: One hundred and eighty-six patients (M 104; F 82; median age 53.4 years) who underwent allo-SCT between January 2010 and December 2017 were enrolled and divided into three groups, according to time from allo-SCT (1-3 years; 3-5 years; > 5 years). Pre-transplant TSH and fT4 levels were available for all patients. After transplantation, TSH, fT4 and anti-thyroperoxidase antibodies (TPO-Ab) were evaluated. RESULTS: After a follow-up of 3.7 years, 34 (18.3%) patients developed hypothyroidism, with higher prevalence in females (p < 0.001) and in patients who received matched unrelated donor grafts (p < 0.05). No difference in prevalence was found at different time points. Patients who developed hypothyroidism showed higher rate of TPO-Ab positivity (p < 0.05) and higher pre-transplant TSH levels (median 2.34 µU/ml) compared to those with preserved thyroid function (median 1.53 µU/ml; p < 0.001). Multivariable analysis identified higher pre-transplant TSH levels as a positive predictor of hypothyroidism (p < 0.005). The ROC curve analysis identified a pre-SCT TSH cutoff of 1.84 µU/ml, which can predict hypothyroidism with sensitivity 74.1% and specificity 67.2%. CONCLUSIONS: About one out of four patients developed hypothyroidism after allo-SCT, with a greater incidence in females. Pre-transplant TSH levels seem to predict the onset of post-SCT hypothyroidism.

Transition in endocrinology: predictors of drop-out of a heterogeneous population on a long-term follow-up.

PURPOSE: To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. METHODS: Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007-2020) were retrospective evaluated. RESULTS: The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor's surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. CONCLUSION: This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed "one-size-fits-all model" is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

PURPOSE: Registered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D). METHODS: In a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021. RESULTS: During the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (p<0.0001 for both). At these time-points, HbA1c values were <7% in 61% and 57% of cases. HbA1c reduction was greater in patients with higher baseline HbA1c levels and it occurred irrespective of gender, age, insulin therapy and complications. The residual number of cases with HbA1c ≥9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was ≥5% in 21.2- 25.4% and ≥10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

Gestational Diabetes Mellitus: Clinical Characteristics and Perinatal Outcomes in a Multiethnic Population of North Italy.

AIM: To evaluate clinical characteristics and perinatal outcomes in a heterogeneous population of Caucasians born in Italy and High Migration Pressure Countries (HMPC) women with GDM living in Piedmont, North Italy. METHODS: We retrospectively analyzed data from 586 women referring to our unit (2015-2020). Epidemiological (age and country of origin) and clinical-metabolic features (height, weight, family history of DM, parity, previous history of GDM, OGTT results, and GDM treatment) were collected. The database of certificates of care at delivery was consulted in relation to neonatal/maternal complications (rates of caesarean sections, APGAR score, fetal malformations, and neonatal anthropometry). RESULTS: 43.2% of women came from HMPC; they were younger (p < 0.0001) and required insulin treatment more frequently than Caucasian women born in Italy (χ 2 = 17.8, p=0.007). Higher fasting and 120-minute OGTT levels and gestational BMI increased the risk of insulin treatment (OGTT T0: OR = 1.04, CI 95% 1.016-1.060, p=0.005; OGTT T120: OR = 1.01, CI 95% 1.002-1.020, p=0.02; BMI: OR = 1.089, CI 95% 1.051-1.129, p < 0.0001). Moreover, two or more diagnostic OGTT glucose levels doubled the risk of insulin therapy (OR = 2.03, IC 95% 1.145-3.612, p=0.016). We did not find any association between ethnicities and neonatal/maternal complications. CONCLUSIONS: In our multiethnic GDM population, the need for intensive care and insulin treatment is high in HPMC women although the frequency of adverse peripartum and newborn outcomes does not vary among ethnic groups. The need for insulin therapy should be related to different genetic backgrounds, dietary habits, and Nutrition Transition phenomena. Thus, nutritional intervention and insulin treatment need to be tailored.

Neuroendocrine predictors of vasoplegia after cardiopulmonary bypass.

PURPOSE: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. METHODS: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. RESULTS: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73-0.94; OR 1.17, 95% CI 1.04-1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8-0.93; p < 0.001). CONCLUSION: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.

Untreated adult GH deficiency is not associated with the development of metabolic risk factors: a long-term observational study.

PURPOSE: Uncertainties exist about the predictors of the severity of the clinical picture of GH deficiency (GHD) syndrome. Aim of the study was to evaluate, in adult patients with GHD, the predictors of the development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis. METHODS: We retrospectively studied 327 adult patients (age 47.1 ± 17.1 years) with untreated severe GHD (mean follow-up 110.9 ± 56.8 months). GHD was defined by GHRH + arginine test using BMI cut-offs. The possible development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis was investigated by Kaplan-Meier survival analysis. For each clinical outcome, either a univariate or multivariate analysis according to the Cox proportional-hazards model was performed to identify those factors that were associated with the development of the event. RESULTS: GH secretion parameters were not associated with the outcomes. Hypercholesterolemia was positively and negatively predicted by a BMI ≥ 30 kg/m2 (HR 2.50, p 0.00) and the dose of l-thyroxine possibly in place (HR 0.98, p 0.02), respectively. Hypertension was positively predicted by a BMI ≥ 30 kg/m2 (HR 2.64, p 0.00) and IGF-I SDS values (HR 2.26, p 0.00). Diabetes mellitus was positively predicted by hypertension (HR 11.76, p 0.01). Osteoporosis was positively and negatively predicted by hypercholesterolemia (HR 3.25, p 0.01) and hypertension (HR 0.21, p 0.00), respectively. CONCLUSIONS: The severity of the impairment of GH secretion does not predict the development of the clinical picture of GHD syndrome: untreated adult GHD does not increase the development of metabolic risk factors in hypopituitaric patients.

Correction to: Transsphenoidal surgery for pituitary adenomas: early results from a single center.

Unfortunately in the original publication, the affiliation of the author Paolo Marzullo was incorrect. The author inadvertently missed out to include his second affiliation.

Transsphenoidal surgery for pituitary adenomas: early results from a single center.

OBJECTIVE: To evaluate early results of transsphenoidal surgery for pituitary adenomas. DESIGN: Retrospective evaluation of 90 consecutive patients undergoing endoscopic pituitary adenoma surgery (2007-2016) at "Maggiore della Carità" Hospital in Novara, Italy. Age at diagnosis, sex, symptoms at presentation, hormonal and radiological data, complications of surgery, and short-term follow-up information were collected. RESULTS: The majority of patients were male (M/F: 1.5/1, mean age at diagnosis 62.1 ± 1.5 years mean ± SEM). Most patients (91.1%) presented with a macroadenoma (27.4 mm ± 1.1 mm mean ± SEM), while 77.8% were non-functioning pituitary adenomas. Clinical presentations related to mass effect were visual impairment (74.0%) and/or hypopituitarism (55.1%). The main surgery complication was insipidus diabetes (12.2%), followed by cerebral hemorrhage (4.4%), cerebrospinal fluid (CSF) leaks (4.4%), syndrome of inappropriate antidiuresis (SIAD) (2.2%), and epistaxis (2.2%); only one patient died because of stroke. Risk of complications was not associated with tumor size (OR = 0.588, 95% CI 0.967-1.081, p = 0.443). Visual function improved in 70.6% of patients, while recovery of normal pituitary function occurred in 48.1%. Early neuroimaging studies demonstrated no residual tumor in 27.6% of patients. Invasion of cavernous sinus (OR = 3.293, 95% CI 0.897-16.738, p = 0.05) and maximum tumor diameter (OR = 6.857, 95% CI 1.039-1.309, p < 0.01) were associated with an unfavorable surgical outcome. CONCLUSIONS: Transsphenoidal endoscopic surgery for pituitary adenomas is safe and is frequently followed by improvement in visual symptoms, whereas recovery of pituitary function is less common. In our patients, complete surgical removal of adenomas is comparable to that of other series, but further investigations will be necessary to clarify the long-term risk of tumor recurrence.

Treating varicocele in 2018: current knowledge and treatment options.

PURPOSE: Varicocele is defined as a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow through the internal spermatic vein. The prevalence of clinically relevant varicocele ranges from 5 to 20% in the male population and is often associated with infertility and reduction of sperm quality. In this review, the pathophysiology and clinical aspects of varicocele are reviewed along with therapeutic options and treatment effects on sperm parameters and fertility both in adult and in pediatric/adolescent subjects. METHODS: We conducted a Medline and a PubMed search from 1965 to 2018 to identify publications related to varicocele clinical aspects, treatment procedures and treatment outcomes. Keywords used for the search were: "varicocele", "varicocelectomy", "sclerotherapy", "male infertility", "subfertility", and "semen abnormalities". RESULTS: Data from a large number of studies in adolescent and adult males indicate that varicocele correction improves semen parameters in the majority of patients, reducing oxidative stress and improving sperm nuclear DNA integrity either with surgical or percutaneous approach. CONCLUSIONS: Varicocele repair seems to represent a cost-effective therapeutic option for all males (both adolescent and adults) with a clinical varicocele in the presence of testicular hypotrophy, worsening sperm alterations or infertility. On the other hand, some investigators questioned the role of varicocelectomy in the era of assisted reproduction. Thus, a better understanding of the pathophysiology of varicocele-associated male subfertility is of paramount importance to elucidating the deleterious effects of varicocele on spermatogenesis and possibly formulating new treatment strategies.

Serum uric acid potentially links metabolic health to measures of fuel use in lean and obese individuals.

BACKGROUND AND AIMS: Uric acid (UA) is a byproduct of the high-energy purine metabolism and is conventionally regarded as a marker of cardio-metabolic impairment. Its potential relationship with energy homeostasis is unknown to date. METHODS AND RESULTS: In a cross-sectional study on 121 otherwise healthy obese and 99 sex- and-age-matched lean subjects, UA levels were analyzed in relation to metabolic health, inflammatory markers, respiratory quotient (RQ) and resting energy expenditure (REE) as assessed by indirect calorimetry, fat mass (%FM) and fat-free mass (FFM) as determined by bioimpedance analysis. As expected, obese and lean subjects differed in BMI, glucolipid homeostasis, leptin and insulin levels, inflammatory markers, %FM and FFM (p < 0.001 for all). Likewise, UA levels (p < 0.001) and rates of hyperuricaemia (40.5% vs 3.0%, p < 0.0001) were also higher in obese than lean controls. Further, indirect calorimetry confirmed that obesity increased REE and decreased RQ significantly (p < 0.001). Beyond the expected metabolic correlates, in individual and merged groups UA levels were associated negatively with RQ and positively with REE (p < 0.0001 for both). In multivariable regression analysis, significant independent predictors of UA were BMI and sex. When BMI was replaced by measures of body composition, %FM and FFM emerged as significant predictors of serum UA (p < 0.0001). CONCLUSIONS: A potential link relates serum UA to measures of resting energy expenditure and their determinants.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

OBJECTIVE: Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. DESIGN: Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. RESULTS: The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. CONCLUSIONS: We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.

Measurement of height velocity is an useful marker for monitoring pituitary function in patients who had traumatic brain injury.

To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale-GCS, Glasgow outcome scale-GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the "Regina Margherita" Hospital, in Turin and "Maggiore della Carità Hospital" in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV <25th centile, but no one had HV < the 3rd centile limit. At T12, among the 20 patients with HV <25th centile, in 13 patients the HV was below the 25th centile and GHRH + Arginine test has been performed. Four subjects demonstrated an impaired GH peak and were classified as GH deficiency (GHD). Of these 4 subjects, 3 subjects showed isolated GHD, while one patient showed multiple hypopituitarism presenting also secondary hypocortisolism and hypothyroidism. The GCS at admission and GOS do not correlate with the onset of hypopituitarism. A simple measurement of the height velocity at least 1 year after the TBI, is enough to recognize patients with a pituitary impairment related to GH deficiency. We suggest to follow-up paediatric population who had TBI with auxological evaluations every 6 months, limiting hormonal evaluation in patients with a reduction of height velocity below the 25th centile limit.

Quality of life, mood disturbances and psychological parameters in adult patients with GH deficiency.

An increased prevalence of depression, emotional lability, decreased energy levels, and poor quality of life have been reported in adults with GH deficiency (GHD). The impairment of psychological parameters depends on the aetiology of GHD and the presence of other pituitary hormone deficiencies because of hormonal effects on neural cell metabolism. Cognitive dysfunctions appear to be specifically related to GHD itself, whereas the lower emotional well-being and reduced motor performance are attributed to other pituitary hormone deficiencies. Traumatic Brain Injury causes very often hypopituitarism and GHD as well as other many psychological symptoms: cognitive impairment, sleeping disorders, and depression. Many neurobehavioral symptoms of postconcussion syndrome (PCS) are the same suffered by adult GHD and hypopituitaric patients but there are no data about the occurrence of hypopituitarism in PCS. In some studies treatment with rhGH is reported to have a beneficial effect and GHD could contribute itself to the global impairment of psychological dysfunctions. The link between psychosocial impairments and GHD is not fully understood. The effects of long-term rhGH therapy on cognitive functions are largely unknown. Thus, long-term placebo-controlled double-blind studies are required to investigate whether psychological dysfunctions are reversible on GH substitution.

Clinical-pathological changes in differentiated thyroid cancer (DTC) over time (1997-2010): data from the University Hospital "Maggiore della Carità" in Novara.

Differentiated thyroid cancer (DTC) is an important clinical entity in our population (Novara, Piedmont, Italy) which is characterized by important environmental influences, as iodine deficiency (ID) and subsequent supplementation, thyroiditis and occupational exposure. To evaluate the features of DTC in our population 20 years after the iodine-prophylaxis pondering the effects of the introduction of the new guidelines for diagnosis and management of DTC after 2005. 322 patients [244 females, age: mean (±SD) 53.8 ± 15.8 years] treated for DTC in a tertiary care center between 1997 and 2010 were retrospectively evaluated. Medical history, demographics, and pathological features were considered. Patients were subdivided into two groups: A (n = 139, diagnosis 1997­2005) and B (n = 183, diagnosis 2006­2010). The population of group A showed a mild ID, while normal iodine status was recorded in group B. A significant increase in histological tumor-associated thyroiditis was found from group A to B (p = 0.021). Recurrent or persistent diseases were found to be correlated with lymph nodes metastases and/or a distant disease at diagnosis, stimulated thyroglobulin levels at the first follow-up and an additional radioiodine therapy. Twenty percent of our patients were females employed in textile industries. The tumor-related inflammation and the occupational exposure should be considered as important factors in the pathogenesis of DTC. Further studies are required in order to confirm our findings.

International migration and biodemographical behaviour: a study of Italians in Belgium.

This paper describes the matrimonial and reproductive behaviour of Italians who migrated to Belgium after the Second World War. Migrants were either already married, or later became married, to other Italians. Among the children of migrants, men equally chose Italian or Belgian wives but women tended to prefer Italian partners. Italian-Belgian marriages were more frequent among the better educated groups. Family size is smaller among migrants marrying after migration and in heterogamous marriages. Significant differences in birth intervals are found when marriage occurred before or after migration, between generations, and between homogamous and heterogamous marriages.