An unusual cause of gynaecomastia in a male

Summary: Beta-human chorionic gonadotropin (βhCG) is normally produced by syncytiotrophoblasts of the placenta during pregnancy and aids embryo implantation. However, it is also secreted in varying amounts in non-pregnant conditions commonly heralding a neoplastic process. We present a case of 50-year-old man, who presented with bilateral gynaecomastia with elevated testosterone, oestradiol, suppressed gonadotropins with progressively increasing levels of human chorionic gonadotropin (hCG). Biochemical and radiological investigations including ultrasonography of testes, breast tissue, MRI pituitary and CT scan full body did not identify the source of hCG. FDG PET scan revealed a large mediastinal mass with lung metastasis. Immunostaining and histological analysis confirmed the diagnosis of primary choriocarcinoma of the mediastinum. It is highly aggressive and malignant tumor with poor prognosis. Early diagnosis and management are essential for the best outcome. Learning Points: High βhCG in a male patient or a non-pregnant female suggests a paraneoplastic syndrome. In the case of persistently positive serum hCG, exclude immunoassay interference by doing the urine hCG as heterophilic antibodies are not present in the urine. Non-gestational choriocarcinoma is an extremely rare trophoblastic tumor and should be considered in young men presenting with gynaecomastia and high concentration of hCG with normal gonads. A high index of suspicion and extensive investigations are required to establish an early diagnosis of extra-gonadal choriocarcinoma. Early diagnosis is crucial to formulate optimal management strategy and to minimize widespread metastasis for best clinical outcome

Hyperparathyroidism in Survivors of Childhood Malignancy after Total Body Irradiation

Objective: The risk of developing hyperparathyroidism (HPT) in adults after radiation exposure is higher than that of the general population. Extensive follow up guidelines of United Kingdom Children’s Cancer Study group (UKCCSG) or Scottish intercollegiate guidelines network (SIGN) do not recommend monitoring serum calcium or parathyroid hormone in patients treated for childhood malignancies. The aim of this study was to examine the occurrence of HPT in a cohort of survivors of childhood malignancy attending a late effects clinic after their treatment for haematological and non-haematological malignancies that included previous irradiation Design and methods: Study was performed in 105 patients attending a late effects clinic. These patients had received different modalities f treatment including surgery, chemotherapy, radiotherapy and bone marrow transplant for haematological and non-haematological malignancies in their childhood with. All patients had evaluation for thyroid and parathyroid disease with a clinical examination and biochemical investigations. Patients with hyperparathyroidism were treated with parathyroidectomy in the absence of thyroid disease and positive localization on imaging. This resulted in normalization of serum calcium. Conclusion: This data suggests that there is a significant risk of hyperparathyroidism in young females with haematological malignancies who received total body irradiation as a single fraction for bone marrow transplant

Glucagon Secreting Tumors and Glucagonoma Syndrome

Glucagonomas are the functioning neuroendocrine tumors. These arise from pancreatic islet α-cells. These tumors are extremely rare and have an annual incidence of 1 per 20-40 million population 80% of glucagon-expressing tumors are sporadic, and 20% are associated with genetic syndromes such as Multiple Endocrine Neoplasia-type 1. Glucagonoma typically occurs in the distal pancreas, and around 85% are in the body or tail. It tends to be large at the time of diagnosis. Most reported cases of glucagonoma are malignant and about 65-75% patients present with metastatic disease. The liver is usually the first site of metastases, followed by the involvement of peripancreatic lymph nodes. The term Glucagonoma syndrome and glucagonoma are often interchangeably used, but in fact, these are two distinct entities. Glucagonoma syndrome comprises of necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, diarrhea, venous thrombosis and neuropsychiatric disturbances in the presence of a glucagon-producing tumor of the pancreas. Tumors secreting glucagon can occur without the glucagonoma syndrome. The glucagonoma secretion depends on the expression of protein convertase enzyme PC1/3 or PC2 within the tumor itself. As a result of this expression, the clinical manifestations can be variable. The tumor can either present with hyperinsulinemic hypoglycemia in a patient with a previous history of diabetes or with the features of the glucagonoma syndrome. In cases where a tumor is localized surgery is the curative treatment. Reduction of the tumor bulk, removal of the primary by surgery and targeted therapy for the hepatic metastases are the favored approach even when there is the metastasis

Monogenic Diabetes due to ABCC8/KCNJ11 Mutation: Case Study and Review of Literature

Monogenic diabetes arises due to mutation in a single-gene and is recognized by their striking familial inheritance pattern. This form of diabetes is inherited in an autosomal dominant or recessive fashion, unlike polygenic Type 1 (autoimmune) or type 2 diabetes caused by the combined action of more than one gene [1-11]. Monogenic diabetes is classified into three main groups: Neonatal diabetes mostly presents in the first six months of birth, maturity onset diabetes of the young (MODY) and maternally inherited mitochondrial diabetes. These mutations run in the family and have a predictable course. Most of the monogenic diabetes is treated with oral medications like sulfonylurea rather than insulin. ABCC8/KCNJ11 gene mutations also cause monogenic diabetes. This gene mutation has been found in ~50% of congenital hyperinsulinemia (CHI) patients. In such cases diabetes commonly presents in the neonatal period (transient or permanent) or at adolescence / early adulthood [1]. We present a 58-year-old diabetic lady, who was detected with ABCC8 mutation during the cascade testing [8]. She was diagnosed with diabetes at the age of 12 [8]. Her son had history of neonatal hypoglycaemia and developed diabetes at the age of 15. He was the index case who was found to have ABCC8 mutation. The family has several other members diagnosed with diabetes. The aim of the article is to increase awareness and understanding of monogenic diabetes among the medical practitioners in adult population with diabetes so that the genetic testing can be offered in a cost effective manner

Targeting fidelity of pharmaceutical systems models by optimization of precision on parameter estimates

Quantitative models have gained momentum to drive the development of pharmaceutical processes. The assessment of the prediction fidelity of these models is key to provide interpretability of process phenomena and to enable decision-making. Evaluating parametric uncertainty is paramount when the focus is on systems models, which combine different sub-models together, and, thus, parameters related to previous units may strongly impact the prediction of one final output. A framework is proposed to assess reliability in model predictions, where the precision of parameter estimates is explicitly optimized to target pre-set tolerance requirements on process key performance indicators and product critical quality attributes. A direct compression systems model for the manufacturing of oral solid dosage products is used as a case study. Results show that the proposed methodology is effective at guaranteeing the target model fidelity and at quantifying the maximum acceptable uncertainty in the estimates of model parameters

Gastrointestinal symptoms in acromegaly: A case control study

BACKGROUND Acromegaly is a chronic disease caused by a pituitary somatotroph adenoma resulting in excess secretion of growth hormone, which leads to excess secretion of Insulin like growth factor 1 from the liver, causing abnormal soft tissue growth. There is increasing awareness that diseases affecting connective tissue are associated with an increase in functional gastrointestinal symptoms. Data was collected from patients with a confirmed diagnosis of acromegaly to evaluate the intensity, variety and impact of abdominal symptoms in comparison with a control group who were healthy participants recruited from the local fracture clinic. AIM To evaluate the frequency type and burden of abdominal symptoms in acromegaly in comparison with a control group. METHODS Medical documentation of patients with a diagnosis of acromegaly treated in one tertiary medical centre between 2010 and 2017 has been analysed. Data was collected from patients with confirmed acromegaly, using the Short Form Health Survey (SF36) and Rome IV Diagnostic questionnaire for Functional Gastrointestinal Disorders in Adults (R4DQ) and compared to a sex- and age-matched control group, to assess the burden of abdominal symptoms. Microsoft Excel and IBM SPSS v 25 were used for data analysis. RESULTS Fifty patients with acromegaly (24 male and 26 females; age range 23-64 years, mean 43) and 200 controls (96 male and 104 females; age range 18-84, mean 42.4) were recruited. 92% (46 out of 50) of patients with acromegaly reported abdominal symptoms and 78% (39 out of 50) had at least one functional gastrointestinal disorder according to the Rome IV diagnostic criteria, compared to 16% of controls (OR > 1, P 1, P 1, P < 0.001) as compared to the control group. CONCLUSION Upper and lower functional gastrointestinal tract disorders (defined by Rome IV diagnostic criteria) are significantly more prevalent in patients with acromegaly compared with healthy age and sex matched controls in our study. Functional constipation is the most commonly reported problem. Poorer quality of life may in part be attributable to the increased prevalence of abdominal symptoms

Full and fast calibration of the Heston stochastic volatility model

This paper presents an algorithm for a complete and e cient calibration of the Heston stochastic volatility model. We express the calibration as a nonlinear least-squares problem. We exploit a suitable representation of the Heston characteristic function and modify it to avoid discontinuities caused by branch switchings of complex functions. Using this representation, we obtain the analytical gradient of the price of a vanilla option with respect to the model parameters, which is the key element of all variants of the objective function. The interdependency between the components of the gradient enables an e cient implementation which is around ten times faster than a numerical gradient. We choose the Levenberg-Marquardt method to calibrate the model and do not observe multiple local minima reported in previous research. Two-dimensional sections show that the objective function is shaped as a narrow valley with a flat bottom. Our method is the fastest calibration of the Heston model developed so far and meets the speed requirement of practical trading

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.Peer reviewe

Replay Attacks and Defenses Against Cross-shard Consensus in Sharded Distributed Ledgers

We present a family of replay attacks against sharded distributed ledgers targeting cross-shard consensus protocols, such as the recently proposed Chainspace and Omniledger. They allow an attacker, with network access only, to double-spend or lock resources with minimal efforts. The attacker can act independently without colluding with any nodes, and succeed even if all nodes are honest; most of the attacks can also exhibit themselves as faults under periods of asynchrony. These attacks are effective against both shard-led and client-led cross-shard consensus approaches. We present Byzcuit-a new cross-shard consensus protocol that is immune to those attacks. We implement a prototype of Byzcuit and evaluate it on a real cloud-based testbed, showing that our defenses impact performance minimally, and overall performance surpasses previous works