Selective peripheral tissue response to high testosterone levels in an infertile woman without virilization signs.

Summary: Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2-3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation. Learning points: Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women. Very high total testosterone levels in women (>2-3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization. In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it. Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25-43% of cases. A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

Prenatal Breastfeeding Counseling Intervention in Women with Pre-Gestational Diabetes Mellitus-A Randomized Controlled Trial.

BACKGROUND: Data on breastfeeding rates and targeted interventions in women with pre-gestational diabetes mellitus are inconclusive. The aim of the study was to evaluate breastfeeding rates up to one year postpartum and whether targeted counseling towards the end of pregnancy can impact breastfeeding rates and duration. An additional goal was to evaluate whether counseling affected women's perceptions regarding breastfeeding. METHODS: Women with pre-gestational diabetes mellitus were cluster-randomized between 32 and 36 weeks of gestation, either to face-to-face instruction with a certified lactation consultant or to receive written information on breastfeeding. Thirty-eight women without diabetes served as controls and were given written information on breastfeeding. All women filled out a questionnaire regarding intended breastfeeding duration, exclusivity, and perceptions, before intervention and at three, six, and twelve months post-partum. RESULTS: Fifty-two women with pre-gestational diabetes mellitus consented to participate. All completed the questionnaires, 26 in each group. At three, six, and twelve months postpartum, rates of any breastfeeding were around 60%, 50%, and 30%, respectively. Approximately one-third breastfed exclusively in each group at three and six months. No significant difference in breastfeeding rates was noted between face-to-face instruction, written information, and controls. End-of-pregnancy counseling improved confidence in breastfeeding knowledge and confidence in being able to manage blood glucose. CONCLUSIONS: Breastfeeding rates in pre-gestational diabetes mellitus were comparable to those of women without diabetes and were unchanged by mode of instruction at the end of pregnancy. However, targeted diabetes-oriented breastfeeding instruction at the end of pregnancy improved knowledge and confidence among women with pre-gestational diabetes mellitus.

Persistent post-bariatric-surgery hypoglycemia: A long-term follow-up reassessment.

BACKGROUND AND AIM: Post-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events. METHODS AND RESULTS: Twenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively. Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death. CONCLUSIONS: PBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Prediabetes in pregnancy - follow-up, treatment, and outcomes compared to overt pregestational diabetes.

OBJECTIVE: There are limited data on follow-up, treatment, and maternal and fetal outcomes in women with prediabetes before or at the beginning of pregnancy. The aim of this study was to comprehensively characterize women with prediabetes compared to women with type 2 diabetes mellitus. STUDY DESIGN: This was a retrospective cohort data from a single medical center treating women with pregestational prediabetes mellitus (PDM). Women were compared to pregestational overt type 2 diabetes mellitus (T2DM). RESULTS: Data were collected from 120 women in the PDM group and 86 women in the T2DM group. Baseline characteristics were comparable, albeit women in the PDM group arrived at medical attention significantly later, 55% after 15 weeks gestation. Women with PDM needed significantly less treatment to achieve glycemic control and glycated hemoglobin remained lower throughout pregnancy. Maternal and fetal outcomes were similar between groups, although significantly higher rates of macrosomia and neonatal jaundice were observed in the T2DM group. CONCLUSIONS: The lack of clear guidelines causes a delay in the first prenatal visit of women with PDM. Comparable pregnancy outcomes may tip the balance toward acceptance of early treatment. Establishing clear guidelines will enable primary caregivers to refer prediabetic women sooner for lifestyle modifications and treatment if needed.

The association between an oral glucose tolerance test performed at term pregnancy and obstetric outcomes.

Aims: Assessing the value of oral glucose tolerance test performed at term pregnancy in identifying obstetric complications. Methods: Retrospective cohort study of women with a normal 50 g glucose challenge test who also had an oral glucose tolerance test at term (defined as at or after 37 weeks of gestation). Comparison between the pathological and normal oral glucose tolerance test groups was performed. Results: The mean glucose in the glucose challenge test of women in the normal oral glucose tolerance test (n = 256) group was lower than that in the pathological oral glucose tolerance test (N = 16) group (105 ± 17 mg/dl (5.8 ± 0.9 mmol/l) vs 117 ± 13 mg/dl (6.5 ± 0.7 mmol/l), p = 0.007). Relevant obstetrical complications did not differ significantly between the groups. Of note, in the pathological oral glucose tolerance test group only one woman delivered a macrosomic infant. Conclusions: A pathological oral glucose tolerance test performed at term was unable to identify women at risk for impaired glucose metabolism-related obstetric complications and is therefore of limited clinical value and seems to be unjustified.

Adrenal metastatic melanoma first identified during pregnancy: a diagnostic challenge.

Adrenal nonadenomatous tumors (NAT) first identified during pregnancy are very rare and pose a diagnostic and therapeutic dilemma with significant risks for the mother and fetus. The aim of this study is to report a case of a large adrenal NAT identified in pregnancy and literature review. A literature search was conducted, and data were summarized. A 37-year-old primigravida woman, with a history of melanoma, excised 12 years before presentation without recurrence, presented at 35 weeks gestation due to intractable right flank pain. MRI demonstrated an eight cm, heterogeneous, septate, right adrenal mass suspected to be either pheochromocytoma/paraganglioma (PPGL), adrenocortical carcinoma or metastasis. Blood metanephrines were sent urgently to enable a safe delivery and were within normal range, as were cortisol and androgen levels. A biopsy was taken from a palpable breast mass as well as from an ovarian mass during the operation. At 36 weeks gestation, she was delivered by cesarean section. PET computed tomography performed after delivery revealed the extensive metastatic spread of recurring melanoma including the right adrenal gland. Timely diagnosis and management by a multidisciplinary team are important to avoid a catastrophic outcome. There is no consensus on optimal management and timing of delivery. PPGL should be ruled out before delivery.

Subacute Thyroiditis-Still a Diagnostic Challenge: Data from an Observational Study.

Background: Subacute thyroiditis (SAT) is a relatively common cause of thyroid disease. However, only a few studies evaluating SAT have been published in recent years with varying diagnostic criteria. We evaluate the clinical presentation and long-term outcome of isotope scan-confirmed SAT. Methods: A retrospective study of 38 patients with isotope scan-confirmed SAT was performed at a single isotope department. All patients were contacted for long-term follow-up. Results: The female/male ratio was 1.4:1, and mean age was 47 ± 14 years and 62 ± 12 years in women and men, respectively (p = 0.002). Almost half of the cases (42%) occurred during the summer. The most common symptoms were neck pain (74%) and weakness (61%). Palpitations, weight loss, heat intolerance, and sweating appeared in 50%, 42%, 21%, and 21%, respectively. Only half of the patients reported fever. TSH level was low in all patients, and mean FT4 and FT3 level were about twice the upper limit of normal range. Elevated CRP and ESR occurred in the majority (88%) of patients. The mean time period between the first clinic visit and performing thyroid function tests was 8 ± 7 days. One-third of the patients initially received a diagnosis of upper respiratory tract infection (URI). NSAIDs and steroids were prescribed to 47% and 8% of patients, respectively. Long-term follow-up of 33.5 months (range 9-52) revealed that 25% remained with subclinical or overt hypothyroidism. Conclusions: These data demonstrate that although SAT is a common entity, there is still a significant delay in diagnosis, and in a third of our patients, the initial diagnosis was URI, with 25% developing long-term hypothyroidism.

Posthemithyroidectomy Pregnancy Thyroid Function Surveillance: Frequency, Adherence, and Guideline Impact.

OBJECTIVE: Posthemithyroidectomy women are at an increased risk for gestational subclinical hypothyroidism. Therefore, the American Thyroid Association (ATA) recommends increased thyroid function surveillance for this subgroup of pregnant women. The purpose of this study was to evaluate the frequency of thyroid function surveillance during pregnancy in posthemithyroidectomy women and to evaluate the adherence to the 2017 ATA guidelines and its possible impact since being published on thyroid function surveillance rates. METHODS: A retrospective study of pregnant posthemithyroidectomy women operated at our institution between 1997 and 2020 was performed. The study cohort was subdivided by pregnancy dates before 2018 and 2018 onward to evaluate the impact of the 2017 ATA guidelines. Adherence to the guidelines was defined as at least 1 thyroid-stimulating hormone test in each trimester. RESULTS: After exclusions, a total of 120 pregnancies conceived by 66 women who underwent hemithyroidectomy surgeries were included in this study. Overall, serum thyroid-stimulating hormone examinations were performed during the first, second, and third pregnancy trimesters in 86.6%, 40%, and 16.6% of pregnancies, respectively (P <.005). The examination rate since 2018 was 88%, 40%, and 8% for the first, second, and third trimesters, respectively (P <.005). CONCLUSION: Adherence to the latest ATA guidelines is low, and its publication in 2017 did not increase the thyroid function surveillance rate in posthemithyroidectomy women. Better patient education regarding the risks of gestational hypothyroidism following hemithyroidectomy and improved communications among treating surgeons, obstetricians, and endocrinologists may improve these rates.

The Challenges of Treating Glucokinase MODY during Pregnancy: A Review of Maternal and Fetal Outcomes.

Background: The optimal treatment strategy for the follow-up and management of women with glucokinase maturity-onset diabetes of the young (GCK−MODY)during pregnancy remains unknown. Data regarding maternal and fetal outcomes are lacking. Aim: This paper summarizes the existing literature regarding the maternal and fetal outcomes of women with glucokinase MODY to guide future treatment strategy. Methods: A literature search was conducted in Pubmed, Embace, and Cochrane library with citation follow-up using the terms: glucokinase, MODY, diabetes, pregnancy, gestation, and outcomes. We searched for articles with known fetal mutational status. Relevant outcomes included: birthweight, large for gestational age (LGA), small for gestational age (SGA), macrosomia, cesarean delivery (CD), shoulder dystocia, congenital anomalies, miscarriages, preterm births, and long-term outcomes. Results: Fourteen relevant manuscripts were identified describing maternal and fetal outcomes. The percentage of LGA and macrosomia in 102 glucokinase -unaffected offspring (GCK−) was significantly higher than in the glucokinase -affected offspring (GCK+) (44% vs. 10%, p < 0.001 and 22% vs. 2%, p < 0.001, respectively). Among the 173 GCK(+) offspring, only 5% were SGA, which can be expected according to the normal distribution. We observed higher rates of CD and shoulder dystocia in the GCK(−) offspring. Conclusions: GCK(−) offspring have significantly higher birthweights and more birth complications. The optimal treatment strategy to guide management should take into consideration multiple variables other than fetal mutational status.

Severe post-gastric bypass hypoglycemia in pregnancy.

Post-bariatric surgery hypoglycemia (PBH) is a serious and relatively prevalent complication of bariatric surgery and is often underdiagnosed due to unawareness. PBH can have a profound effect on health and quality of life. Data regarding the natural history and management of PBH during pregnancy are lacking. Here we describe a case of a 34-year-old woman who presented with intractable PBH during the second trimester of her third pregnancy, three years after a Roux-en-Y gastric bypass (RYGB). Treatment with nifedipine showed partial response and eventually intravenous (IV) glucose was needed until birth.

Is Telemedicine the Preferred Visit Modality in Patients with Type 1 Diabetes?

BACKGROUND: The COVID-19 pandemic limits access to diabetes clinics. Remote communication by phone calls and WhatsApp messages became available in the past years. However, the current need to avoid face-to-face meetings necessitates further expansion of telemedicine services. There are limited data whether the option of virtual meetings is a preferred therapeutic modality for patients with type 1 diabetes (T1D). OBJECTIVE: To assess in a cohort of T1D patients, their preference and perception of telemedicine. METHODS: T1D patients who are followed in a hospital-affiliated diabetes clinic were asked to fill a structured questionnaire aimed to determine their attitude towards telemedicine and their preference of virtual versus conventional visits. The questionnaire was offered to consecutive T1D patients who visited the clinic between August to October 2020. RESULTS: Seventy one T1D patients that fulfilled the questionnaire were included. Median age was 38 years, 39% were male, and median duration of diabetes was 18 years. Fourteen percent of the participants preferred only virtual visits, 24% only conventional visits and 62% preferred a combination of these modalities. Sex, origin, education, duration of diabetes, mode of insulin treatment and distance from the clinic were not associated with patients' preference, but older patients (≥ 61 years) tended to prefer conventional visits. Sixty-six percent felt confident in their ability to download data from their personal medical devices. CONCLUSIONS: Patients from a wide range of treatment modalities are willing to use telemedicine. However, virtual meetings cannot fully replace conventional visits in T1D especially in the older age group.

Following the COVID-19 Experience, Many Patients with Type 1 Diabetes Wish to Use Telemedicine in a Hybrid Format.

BACKGROUND: The COVID-19 pandemic has brought to light both challenges and unique opportunities regarding type 1 diabetes (T1D) management, including the usage of telemedicine platforms. METHODS: This study was conducted in a tertiary hospital diabetes clinic. All consecutive T1D patients during March and June 2021 were asked to fill out a structured anonymous questionnaire that aimed to determine their preference regarding continuous use of a virtual platform. RESULTS: In total, 126 T1D patients answered the questionnaire, of whom 51% were under the age of 40, half were men, half used insulin pumps, and 69% used continuous glucose monitoring. During the pandemic, the exposure of patients to virtual visits has grown about twofold, from 29% to 53%. Of the respondents, 49% expressed an interest in future usage of a virtual platform, but most of them preferred use in a hybrid manner. We found an association between preference to use telemedicine in the future and younger age, previous virtual platform experience, and confidence in being able to download data. CONCLUSIONS: Our data demonstrate that the COVID-19 experience has led to a growing interest of T1D patients in using the hybrid format of telemedicine. However, we still need to better understand who will benefit most from this platform and assess its cost-effectiveness and organization.

Moderate Iodine Deficiency Is Common in Pregnancy but Does Not Alter Maternal and Neonatal Thyroid Function Tests.

Introduction: An Israeli national survey found that 85% of pregnant women had urinary iodine content (UIC) levels below the adequacy range (<150 µg/L). Widespread desalinated water usage and no national fortification plan are possible causes. Studies assessing relationships between iodine status and maternal and neonatal thyroid function provided varying results. Our aims were to determine whether iodine deficiency was associated with altered maternal or neonatal thyroid function and the factors leading to iodine deficiency. Methods: A cross-sectional study including 100 healthy women without prior thyroid disease, in their first trimester of a singleton pregnancy were recruited from an HMO clinic in central Israel. The women were followed from their first trimester. All women completed a 24-h dietary recall and life habits questionnaires. We tested for UIC, maternal and neonatal thyroid function, maternal autoantibodies, and neonatal outcomes. Results: Median UIC in our cohort was 49 µg/L [25%-75% interquartile range (IQR) 16-91.5 µg/L], with 84% below adequacy range. No correlation was found between iodine deficiency and maternal or neonatal thyroid function which remained within normal ranges. Antibody status did not differ, but thyroglobulin levels were significantly higher in iodine insufficient subjects. UIC was higher in women consuming an iodine containing supplement. There was no association between UIC and dietary iodine content or water source. Conclusions: Moderate iodine deficiency is common in our healthy pregnant women population. Our data imply that moderate iodine deficiency in pregnancy seem sufficient to maintain normal maternal and neonatal thyroid function.

Single liver metastasis of a follicular variant of papillary thyroid carcinoma: a rare pattern of organ spread.

SUMMARY: Well-differentiated thyroid cancer (WDTC), including papillary, follicular, and Hurthle-cell types, is characterized by a slow course and usually remain localized to the thyroid. However, a minority of these cases develop distant metastases with the most common sites being lungs, bones, and lymph nodes. Liver metastases of WDTC are rare and are usually found along with other distant metastases sites and in a multiple or diffuse pattern of spread. The recognition of distant metastasis in WDTC has a significant impact on the treatment and prognosis. However, because of their low incidence and awareness, distant metastases are often diagnosed late. Herein, we describe a case of a 71 years old woman who during routine surveillance of a follicular variant of papillary thyroid cancer (FV-PTC), 5 years after being treated for her primary thyroid tumor, was found to have a single liver metastasis and underwent liver segmental resection. This case highlights the importance of maintaining vigilant surveillance of patients with WDTC, and illustrates the possibility of unique metastasis at unexpected sites. Further studies are needed to understand the organ tropism of some WDTC leading to distant metastases development and to better prediction of an aggressive course. LEARNING POINTS: WDTC patients with distant metastases have a poor prognosis with a 10-year survival of about 50%. The most common sites of distant metastases are lung, bone and lymph nodes. Liver metastases are rare in WDTC, are usually multiple or diffuse and are found along with other distant metastases sites. Single liver metastasis of WDTC is an unexpected pattern of spread, and very few cases are reported in the literature. Rare sites of distant metastases in WDTC can manifest many years after the primary tumor, stressing the importance of maintaining vigilant surveillance. More studies are needed to predict which WDTC tumors may develop a more aggressive course, allowing clinicians to individualize patient management.

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus.

Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral, or fungal infections are well recognized to activate the coagulation system, COVID-19-associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS-13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS-13 has been reported. Also, an imbalance between ADAMTS-13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS-13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment, and improve clinical prognosis.

A Single Synonymous Variant (c.354G>A [p.P118P]) in ADAMTS13 Confers Enhanced Specific Activity.

Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased protein expression levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding a plasma protease responsible for von Willebrand Factor (VWF) degradation. In the current study, we investigated the potential mechanism(s) behind the increased protein expression levels from this variant and its effect on ADAMTS13 physico-chemical properties. Cell-free assays showed enhanced translation of the c.354G>A variant and the analysis of codon usage characteristics suggested that introduction of the frequently used codon/codon pair(s) may have been potentially responsible for this effect. Limited proteolysis, however, showed no substantial influence of altered translation on protein conformation. Analysis of post-translational modifications also showed no notable differences but identified three previously unreported glycosylation markers. Despite these similarities, p.P118P variant unexpectedly showed higher specific activity. Structural analysis using modeled interactions indicated that subtle conformational changes arising from altered translation kinetics could affect interactions between an exosite of ADAMTS13 and VWF resulting in altered specific activity. This report highlights how a single synonymous nucleotide variation can impact cellular expression and specific activity in the absence of measurable impact on protein structure.

SYMPTOMATIC AND ASYMPTOMATIC HYPOGLYCEMIA POST THREE DIFFERENT BARIATRIC PROCEDURES: A COMMON AND SEVERE COMPLICATION.

Background: The prevalence of post-bariatric surgery hypoglycemia (PBH) remains unclear due to diagnostic criteria variability, types of bariatric procedures and possible unawareness. Objective: To determine the frequency, pattern and severity of symptomatic and asymptomatic hypoglycemia in subjects post three different bariatric procedures performed >1 year before evaluation and a group of obese subjects before surgery. Design and Setting: Observational cohort study. Fifty-one consecutive patients participated: post Roux-en-Y gastric-bypass (RYGB) (n=16), post omega-loop gastric-bypass (OLGB) (n=12), post sleeve-gastrectomy (SG) (n=15), obese subjects before surgery (controls) (n=8). Hypoglycemic events (glucose ≤54 mg/dL) and severe hypoglycemia (glucose ≤40 mg/dL) were evaluated by symptoms' questionnaire, mixed-meal tolerance test (MMTT) and continuous glucose monitoring (CGM). Results: According to questionnaires, meal-related complaints were reported in 11 (26%) of the surgical group and in one control subject. During MMTT, 88%, 82% and 67% experienced hypoglycemia in RYGB, OMGB and SG groups, respectively, vs. none of the controls (P<0.001). Severe hypoglycemia occurred in 38%, 45% and 7% in RYGB, OMGB and SG groups, respectively (P=0.025), but only 10 of the total operated patients (24%) reported any symptoms. During CGM, fasting hypoglycemic events occurred more in RYGB and OLGB vs. SG group: 55%, 63% and 17% respectively (P=0.036). Conclusions: PBH is very common after RYGB, OMGB and SG and can be severe especially following bypass procedures. Our results show that hypoglycemia occurs not only postprandially but also in the fasting state, especially following bypass procedures. In most cases, there were no specific complaints, possibly leading to its underestimation.

von Willebrand factor/ADAMTS-13 interactions at birth: implications for thrombosis in the neonatal period.

von Willebrand factor (VWF) and its cleaving protease ADAMTS-13 (A Disintegrin and Metalloproteinase with Thrombospondin type 1 motif, member 13) are essential components to hemostasis. These plasma proteins have also been implicated in a number of disease states, including those affecting children. The best described abnormality is the congenital form of thrombotic thrombocytopenic purpura (TTP) resulting from germline mutations in the ADAMTS-13 gene. The VWF/ADAMTS-13 interaction has more recently emerged as a causative risk factor in the pathogenesis of pediatric stroke and secondary microangiopathies. There is now increasing interest and need to measure these coagulation factors during the neonatal period and throughout childhood. Methods adopted from a multitude of technically diverging studies have been used to understand their role during this period. To date, studies of VWF/ADAMTS-13 in this group of patients have reported conflicting results, which makes interpreting values in the clinical setting especially challenging. In this review we describe the historical evolution of the methodology used to measure VWF/ADAMTS-13 and how it may influence the results obtained during the first days of life. We review the individual assays used to analyze VWF/ADAMTS-13 as well as published reference values. Finally, we bring attention to the potential pathophysiologic role of VWF/ADAMTS-13 in neonatal thrombosis. This has significant implications because the pathologic processes that explain thrombosis in neonates remain poorly characterized and thromboembolism remains a significant source of morbidity and mortality, particularly in sick children.

A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER.

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

pNET co-secreting GHRH and calcitonin: ex vivo hormonal studies in human pituitary cells.

UNLABELLED: Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary-cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient. LEARNING POINTS: Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed.Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion.Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells.