The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression. Aim: The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort. Methods: Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI. Results: Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1-133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: -19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups. Conclusion: Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

In Vivo Two-Photon Microscopy Reveals Sensory-Evoked Serotonin (5-HT) Release in Adult Mammalian Neocortex.

The recent development of genetically encoded fluorescent neurotransmitter biosensors has opened the door to recording serotonin (5-hydroxytryptamine, 5-HT) signaling dynamics with high temporal and spatial resolution in vivo. While this represents a significant step forward for serotonin research, the utility of available 5-HT biosensors remains to be fully established under diverse in vivo conditions. Here, we used two-photon microscopy in awake mice to examine the effectiveness of specific 5-HT biosensors for monitoring 5-HT dynamics in somatosensory cortex. Initial experiments found that whisker stimulation evoked a striking change in 5-HT biosensor signal. However, similar changes were observed in controls expressing green fluorescent protein, suggesting a potential hemodynamic artifact. Subsequent use of a second control fluorophore with emission peaks separated from the 5-HT biosensor revealed a reproducible, stimulus-locked increase in 5-HT signal. Our data highlight the promise of 5-HT biosensors for in vivo application, provided measurements are carried out with appropriate optical controls.

Diagnosis and management of parathyroid carcinoma: a state-of-the-art review.

Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management.

The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review.

OBJECTIVE: Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). RESULTS AND CONCLUSIONS: Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

Temporal origin of mouse claustrum and development of its cortical projections.

The claustrum is known for its extensive connectivity with many other forebrain regions, but its elongated shape and deep location have made further study difficult. We have sought to understand when mouse claustrum neurons are born, where they are located in developing brains, and when they develop their widespread connections to the cortex. We established that a well-characterized parvalbumin plexus, which identifies the claustrum in adults, is only present from postnatal day (P) 21. A myeloarchitectonic outline of the claustrum can be derived from a triangular fiber arrangement from P15. A dense patch of Nurr1+ cells is present at its core and is already evident at birth. Bromodeoxyuridine birth dating of forebrain progenitors reveals that the majority of claustrum neurons are born during a narrow time window centered on embryonic day 12.5, which is later than the adjacent subplate and endopiriform nucleus. Retrograde tracing revealed that claustrum projections to anterior cingulate (ACA) and retrosplenial cortex (RSP) follow distinct developmental trajectories. Claustrum-ACA connectivity matures rapidly and reaches adult-like innervation density by P10, whereas claustrum-RSP innervation emerges later over a protracted time window. This work establishes the timeline of claustrum development and provides a framework for understanding how the claustrum is built and develops its unique connectivity.

A Comparison of the Blood Glucose, Growth Hormone, and Cortisol Responses to Two Doses of Insulin (0.15 U/kg vs. 0.10 U/kg) in the Insulin Tolerance Test: A Single-Centre Audit of 174 Cases.

Objective: The insulin tolerance test (ITT) is the gold standard endocrine test used to assess the integrity of the growth hormone (GH) and cortisol axes. The ITT has potential risks, and severe hypoglycaemia may necessitate intravenous glucose rescue. There is no clear consensus as to the optimal insulin dose for the ITT. Therefore, we sought to compare the standard dose (0.15 U/kg) and a low-dose ITT (0.1 U/kg). Design: Single-centre audit of ITT data (2012-2021). Patients and Measurements. Patients who underwent an ITT to assess possible GH deficiency/adrenal insufficiency were included. Glucose, GH, and cortisol were measured at baseline and 30, 45, 60, 90, and 120 minutes following I.V. insulin bolus (0.15 U/kg or 0.10 U/kg). Results: Of the ITTs performed, only 3/177 (1.7%) did not achieve adequate hypoglycaemia (≤2.2 mmol/L) with a single insulin dose. In total, 174 patients (43.5 ± 12.1 yrs, mean ± standard deviation) were included for analysis (0.15 U/kg: n = 113, 0.10 U/kg: n = 61). All 174 subjects had adequate hypoglycaemia regardless of baseline fasting blood glucose level or insulin dose. Neither nadir glucose nor glucose delta (i.e., baseline minus nadir) differed between insulin doses. Trends in both cortisol and GH responses over time were similar between groups, and a greater proportion of patients receiving the standard dose had an adequate cortisol response (77/106 (72.6%) vs. 32/60 (53.3%), p=0.01). The rates of glucose rescue did not differ in a subset of 79 patients, with on-demand glucose rescue in 4/35 (11%) for the standard dose and 2/44 (5%) for the low dose (p=0.25). Conclusions: Our results suggest that the low-dose ITT produces comparable glucose, cortisol, and GH responses to the higher dose. Given the risks associated with hypoglycaemia, the low dose appears to be preferable to the standard dose ITT in most circumstances.

Are we underutilising computer tomography colonography in Australia?

Computed tomography colonography (CTC) is a safe and accurate tool for colorectal cancer (CRC) screening in both symptomatic and asymptomatic patients. CTC requires dedicated radiological expertise and demonstrates a high sensitivity and specificity in polyp detection, which is similar to optical colonoscopy (OC). Newer preparation techniques for CTC, such as faecal tagging without catharsis might further improve both the tolerability and accuracy of the test. While exposure to ionising radiation, lack of capacity for therapeutic intervention and potentially diminished sensitivity for flat serrated polyps are limitations of CTC, the technique has a role in select populations. CTC should be considered in frail or elderly patients at high anaesthetic risk for OC, patients with stricturing colonic lesions as well as incomplete colonoscopy, or in patients at risk of delayed access to timely OC. With an ever-growing demand for endoscopic services, increased utilisation of CTC could reduce waiting times for colonoscopy, thereby broadening access to timely and effective CRC screening. Further research is required to improve further the detection of flat lesions, including sessile serrated polyps.

Multiple electrolyte disturbances as the presenting feature of multiple endocrine neoplasia type 1 (MEN-1).

Summary: A 49-year-old teacher presented to his general physician with lethargy and lower limb weakness. He had noticed polydipsia, polyuria, and had experienced weight loss, albeit with an increase in central adiposity. He had no concomitant illnesses and took no regular medications. He had hypercalcaemia (adjusted calcium: 3.34 mmol/L) with hyperparathyroidism (parathyroid hormone: 356 ng/L) and hypokalaemia (K: 2.7 mmol/L) and was admitted for i.v. potassium replacement. A contrast-enhanced CT chest/abdomen/pelvis scan revealed a well-encapsulated anterior mediastinal mass measuring 17 × 11 cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 2 cm right inferior parathyroid lesion. On review of CT imaging, the adrenals appeared normal, but a pancreatic lesion was noted adjacent to the uncinate process. His serum cortisol was 2612 nmol/L, and adrenocorticotrophic hormone was elevated at 67 ng/L, followed by inadequate cortisol suppression to 575 nmol/L from an overnight dexamethasone suppression test. His pituitary MRI was normal, with unremarkable remaining anterior pituitary biochemistry. His admission was further complicated by increased urine output to 10 L/24 h and despite three precipitating factors for the development of diabetes insipidus including hypercalcaemia, hypokalaemia, and hypercortisolaemia, due to academic interest, a water deprivation test was conducted. An 18flurodeoxyglucose-PET (FDG-PET) scan demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga DOTATE-PET scan, the mediastinal mass was moderately avid, and the 32 mm pancreatic uncinate process mass showed significant uptake. Genetic testing confirmed multiple endocrine neoplasia type 1. Learning points: In young patients presenting with primary hyperparathyroidism, clinicians should be alerted to the possibility of other underlying endocrinopathies. In patients with multiple endocrine neoplasia type 1 (MEN-1) and ectopic adrenocorticotrophic hormone syndrome (EAS), clinicians should be alerted to the possibility of this originating from a neoplasm above or below the diaphragm. Although relatively rare compared with sporadic cases, thymic carcinoids secondary to MEN-1 may also be associated with EAS. Electrolyte derangement, in particular hypokalaemia and hypercalcaemia, can precipitate mild nephrogenic diabetes insipidus.

Contribution of Interneuron Subtype-Specific GABAergic Signaling to Emergent Sensory Processing in Mouse Somatosensory Whisker Barrel Cortex.

Mammalian neocortex is important for conscious processing of sensory information with balanced glutamatergic and GABAergic signaling fundamental to this function. Yet little is known about how this interaction arises despite increasing insight into early GABAergic interneuron (IN) circuits. To study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex, specifically the role of INs in early speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity and showed refinement over the period leading to active whisking onset. To test the contribution of IN subtypes, we conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked cortical activity in an age- and layer-dependent manner. Silencing SST + INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP + IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results show that these IN subtypes contribute to early sensory processing over the first few postnatal weeks.

International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers.

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.

Identification of an optimal prolactin threshold to determine prolactinoma size using receiver operating characteristic analysis.

Prolactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 µg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 µg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.

Calcitonin-secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis.

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

IgG4-related hypophysitis in adolescence.

OBJECTIVES: IgG4-related hypophysitis is a novel clinical disease entity, which is typically seen in the sixth decade of life and is typically complicated by hypopituitarism. We describe an adolescent female with IgG4-related hypophysitis with normal pituitary function and summarize the relevant literature. CASE PRESENTATION: A 11.8-year-old girl presented with headache and left VI cranial nerve palsy. MRI brain identified an enlarged pituitary gland. Endocrine investigations revealed normal pituitary function. She underwent a transsphenoidal biopsy of the pituitary gland, and histological examination confirmed the diagnosis of IgG4-related hypophysitis. Serum IgG4 concentrations were normal and no evidence of other organ involvement was found. Although the patient tested strongly positive for TB on an interferon gamma release assay, pituitary biopsy was negative for granuloma formation and acid-fast bacilli (Ziehl-Neelson staining). IgG4-related hypophysitis was treated with oral prednisolone and mycophenolate-mofetil with a good response. CONCLUSIONS: We describe to the best of our knowledge, the youngest patient in the published literature with IgG4-related hypophysitis presenting without pituitary insufficiency. A literature review identified only five cases of IgG4-related hypophysitis in adolescence. Serum IgG4 concentrations were normal in all, except one of the adolescent patients reported so far, and appear unhelpful in diagnosis in this age group.

The Logic of Developing Neocortical Circuits in Health and Disease.

The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention.

Prolactinoma in childhood and adolescence-Tumour size at presentation predicts management strategy: Single centre series and a systematic review and meta-analysis.

OBJECTIVE: To report the clinical presentation, management and outcomes of young patients with prolactinomas (<20 years) and conduct a systematic review and meta-analysis. PATIENTS AND DESIGN: Clinical, biochemical and radiological data (1996-2018) were collected from our centre. A systematic review and meta-analysis of published literature (1994-2019) on prolactinoma (age <20 years) were conducted. Both random and fixed effects meta-analysis were used to pool outcomes across studies. RESULTS 1 CASE SERIES: Twenty-two patients (14 females) were identified; median age at diagnosis 15.7 years (range 13-19); 12 patients (6 females) had a macroprolactinoma. Seven patients (macroprolactinoma-6) had associated pituitary hormone deficiencies at presentation. Five patients (4 males) underwent surgical resection due to poor response to cabergoline or apoplexy. Patients undergoing surgery had larger tumours (p < .02) and higher serum prolactin concentration (p < .005). All patients with macroprolactinoma >20 mm required surgical intervention. RESULTS 2 SYSTEMATIC REVIEW AND META-ANALYSIS: We selected 11 studies according to strict inclusion criteria describing 275 patients. Macroprolactinoma was more common in girls (78.7% [95% CI 70.5-85.9]) than boys and was more frequent than microprolactinoma (56.6% [95% CI 48.4-64.5]). In males, only 6/57 (10.5%) of tumours were microprolactinoma as compared to 102/198 (51.5%) microprolactinoma in females (risk difference -0.460; [95% CI -0.563 to -0.357]; p < .001). Surgery was first-line therapy in 18.9% patients, with another 15.4% requiring it as a second line (overall 31.3%). CONCLUSIONS: Macroprolactinoma, particularly if >20 mm, usually requires multimodal therapy including surgical intervention. While overall prolactinomas in <20 years age group are more common in females, the proportion of macroprolactinoma vs microprolactinoma is greater in males, particularly for large invasive tumours. Microprolactinoma is a rare diagnosis in adolescent males.

Ectopic hyperprolactinaemia due to a malignant uterine tumor resembling ovarian sex cord tumors (UTROCST).

PURPOSE: Moderate hyperprolactinaemia (2-5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. METHODS: We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. RESULTS: Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. CONCLUSIONS: Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.

Male Obesity Associated Gonadal Dysfunction and the Role of Bariatric Surgery.

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction.

Laparoscopic Adjustable Gastric Banding-Should a Second Chance Be Given?

BACKGROUND: Obesity is a chronic relapsing-remitting disease and a global pandemic, being associated with multiple comorbidities. Laparoscopic adjustable gastric banding (LAGB) is one of the safest surgical procedures used for the treatment of obesity, and even though its popularity has been decreasing over time, it still remains an option for a certain group of patients, producing considerable weight loss and improvement in obesity-associated comorbidities. METHODS: The aim of this study was to evaluate the impact of weight loss following LAGB on obesity-associated comorbidities, and to identify factors that could predict better response to surgery, and patient sub-groups exhibiting greatest benefit. A total of 99 severely obese patients (81.2% women, mean age 44.19 ± 10.94 years, mean body mass index (BMI) 51.84 ± 8.77 kg/m2) underwent LAGB in a single institution. Results obtained 1, 2, and 5 years postoperatively were compared with the pre-operative values using SPPS software version 20. RESULTS: A significant drop in BMI was recorded throughout the follow-up period, as well as in A1c and triglycerides, with greatest improvement seen 2 years after surgery (51.8 ± 8.7 kg/m2 vs 42.3 ± 9.2 kg/m2, p < 0.05, 55.5 ± 19.1 mmol/mol vs 45.8 ± 13.7 mmol/mol, p < 0.05, and 2.2 ± 1.7 mmol/l vs 1.5 ± 0.6 mmol/l). Better outcomes were seen in younger patients, with lower duration of diabetes before surgery, and lower pre-operative systolic blood pressure. CONCLUSIONS: Younger age, lower degree of obesity, and lower severity of comorbidities at the time of surgery can be important predictors of successful weight loss, making this group of patients the ideal candidates for LAGB.