bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparisons of in situ ionospheric density using ion velocity meters onboard FORMOSAT-7/COSMIC-2 and ICON missions
Authors: Choi Jong-Min , Lin Charles Chien-Hung , Panthalingal Krishanunni Rajesh , Park Jaeheung , Kwak Young-Sil , Chen Shih-Ping , Lin Jia-Ting , Chang Min-Ti
Published: January 2023

We report the preliminary inter-satellite comparisons of the in situ ion density measurements by the ion velocity meter (IVM) onboard FORMOSAT-7/COSMIC-2 (F7/C2) and Ionospheric Connection Explorer (ICON) missions, during the solar minimum period of December 2019 to November 2020. The initial comparisons reveal identical diurnal, seasonal, and latitude/longitude variations in the two ion-density measurements, with F7/C2 consistently yielding stronger values than ICON, which could partly result from the difference in their orbit altitudes. The diurnal variation in the equatorial region did not show any effect of pre-reversal enhancement (PRE) during 2019–2020. The daytime plasma distributions show larger ion densities over a narrow latitudinal belt around the geomagnetic equator in all seasons, and the low-latitude densities reveal signatures of hemispherical asymmetry, with larger values occurring in the summer hemisphere. The observations also reveal distinct wavenumber-4 longitudinal modulation, which is most prominent in equinox and becomes less distinguishable during December solstice months. The simultaneous observations from F7/C2 IVM and ICON IVM also provide opportunities to study the spatial configuration and time evolution of ionospheric irregularities in the equatorial and low latitude regions. The F7/C2 and ICON simultaneously observed the equatorial plasma bubbles (EPBs) occurring around Taiwan on 18 October 2020, and the observations are consistent with each other. The EPBs were also observed by an all-sky imager located in Taiwan, comparing the satellite observations.

Graphical Abstract
Eight-year catalog of deep short-term slow slip events at the Nankai trough based on objective detection algorithm using strain and tilt records
Authors: Yabe Suguru , Ochi Tadafumi , Matsumoto Norio , Itaba Satoshi , Kitagawa Yuichi , Matsuzawa Takanori
Published: January 2023

In subduction zones, slip deficit monitoring along the plate interface is important for understanding the seismogenesis of megathrust earthquakes. In the last two decades, aseismic slip transients, such as slow slip events (SSEs), which are usually synchronized with tectonic tremors, have been detected in subduction zones worldwide. Frequent SSEs are particularly important for releasing slip deficits during the inter-seismic periods of megathrust earthquakes. In southwest Japan, deep short-term SSEs have been primarily monitored with strain and tilt records because the SSEs in this region are small. However, strain and tilt records are so sensitive that they record not only SSEs, but also rainfall and local groundwater movements, which temporally affect the quality of data making it difficult to apply an automated detection algorithm. Therefore, previously reported short-term SSE catalogs, based on strain and tilt records, were created by visual inspections, although they are not suitable for generating a long-term catalog. In this study, a quantitative detection algorithm was developed to detect short-term SSEs using strain and tilt records. The problem of temporally varying data quality was solved by introducing the prior probability of log-normal distributions in the fitting variance. This method was applied to an 8-year (2013–2020) dataset of strains and tilts from southwest Japan. A total of 96 events were detected, among which, 78 corresponded with SSEs previously reported by the Geological Survey of Japan (GSJ). Although the GSJ catalog contained more events with smaller magnitudes, such events were difficult to distinguish from noise using the developed method. Three of the remaining 18 events were considered SSEs that were not reported in the GSJ catalog. Others could be artifacts because there were no obvious signals in the global navigation satellite system records (with events of magnitude > 6.0). Previous studies have suggested the existence of aseismic transients deeper or shallower than regular short-term SSEs in southwest Japan. However, detection results from this study did not confirm such events.

Graphical Abstract
Seismic reflection imaging of deep crustal structures using local earthquakes in the Kanto region, Japan
Authors: Shiraishi Kazuya , Watanabe Toshiki
Published: January 2023

We applied a novel method of passive seismic reflection imaging to actual local earthquake data collected by a dense seismic network in the Kanto region, Japan. This method, which implements reverse time migration (RTM), is based on the cross-correlation of wavefields that are extrapolated forward and backward in time from receiver locations using passively observed seismic records. Using multiple reflections between the Earth’s surface and subsurface boundaries, internal structures are imaged using many earthquakes without well-defined source information. The objective of this case study is to evaluate the possibility of acquiring seismic reflection images of the deep crustal structure by applying the RTM-based method using P-wave reflections in the earthquake data collected by a dense seismic network. The P-wave reflection profile along a 191-km-long pseudo-survey line down to a 100 km depth is obtained using the seismic records of hundreds of local earthquakes observed at 72 receiver stations. A P-wave velocity model for RTM imaging is extracted from an existing 3D model obtained by seismic tomography in a previous study. The resulting image shows several continuous reflectors at depths of 15–70 km. These reflectors correspond to the spatially variable velocity and suggest deep structures related to dual plate subduction in this region. Two eastward-dipping reflectors imaged at depths of 15–50 km are likely the top and bottom surfaces of the crust of the Philippine Sea slab, and the westward-dipping reflector at depths of 50–70 km implies the top surface of the Pacific slab. The en-échelon reflectors at depths of 15–20 km may be reflective boundaries between the upper and lower crust in the overlying Okhotsk plate. Our case study results confirm the possibility of obtaining profiles at higher resolutions than are typically obtained by earthquake-based seismic tomography and of imaging at depths beyond the limits of artificially controlled-source seismic surveys. Further implementation of the RTM-based imaging method will improve its potential use for subsurface imaging and monitoring from dense passive seismic data.

Graphical Abstract
A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial
Authors: Weir Christopher J. , Adamestam Imad , Sharp Rona , Ennis Holly , Heed Andrew , Williams Robin , Cresswell Kathrin , Dogar Omara , Pontefract Sarah , Coleman Jamie , Lilford Richard , Watson Neil , Slee Ann , Chuter Antony , Beggs Jillian , Slight Sarah , Mason James , Yardley Lucy , Sheikh Aziz
Published: January 2023

Background

Antimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+).

Methods

ePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measured objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses, to inform the future larger-scale trial design.

Discussion

This trial is essential to determine the feasibility of implementing the ePAMS+ intervention and measuring relevant outcomes, prior to evaluating its clinical and cost-effectiveness in a full scale hybrid cluster-randomised stepped-wedge clinical trial. Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences.

Trial registration

The qualitative and Fidelity Index research were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref: 19/NS/0174). The feasibility trial and quantitative analysis (protocol v1.0, 15 December 2021) were approved by the London South East Research Ethics Committee (ref: 22/LO/0204) and registered with ISRCTN (ISRCTN 13429325) on 24 March 2022
Applications of CRISPR/Cas genome editing in economically important fruit crops: recent advances and future directions
Authors: Ma Zhimin , Ma Lijing , Zhou Junhui
Published: January 2023

Fruit crops, consist of climacteric and non-climacteric fruits, are the major sources of nutrients and fiber for human diet. Since 2013, CRISPR/Cas (Clustered Regularly Interspersed Short Palindromic Repeats and CRISPR-Associated Protein) genome editing system has been widely employed in different plants, leading to unprecedented progress in the genetic improvement of many agronomically important fruit crops. Here, we summarize latest advancements in CRISPR/Cas genome editing of fruit crops, including efforts to decipher the mechanisms behind plant development and plant immunity, We also highlight the potential challenges and improvements in the application of genome editing tools to fruit crops, including optimizing the expression of CRISPR/Cas cassette, improving the delivery efficiency of CRISPR/Cas reagents, increasing the specificity of genome editing, and optimizing the transformation and regeneration system. In addition, we propose the perspectives on the application of genome editing in crop breeding especially in fruit crops and highlight the potential challenges. It is worth noting that efforts to manipulate fruit crops with genome editing systems are urgently needed for fruit crops breeding and demonstration.

Graphical Abstract
Severe osteoarthritis at unexpected age
Authors: Pekkolay Zafer , Ceylan Yusuf
Published: January 2023

Introduction

Acromegaly is a rare chronic endocrine disease caused by a growth hormone (GH) – producing adenoma, resulting in elevated GH and insulin-like growth factor-1 (IGF-1) concentrations. GH and IGF-1 are essential for normal growth, differentiation, and repair of cartilage and bone; however, excess GH and IGF-1, which are characteristic of acromegaly, lead to an arthropathy that resembles osteoarthritis. Patients with acromegaly, whether it's surgically treated or biochemically controlled, still have a high risk of developing arthropathy.

Clinical Case

A 49-year-old woman presents to the university hospital for a visit with a complaint of knee pain. Her medical history reveals that she received an acromegaly diagnosis in 2010 and had been treated with surgery. However, she was not remission after the surgery; the patient's IGF-1 level was 686 ng/ml (Normal range: 109–284) when she presented. Her medical history reveals that she has been taking analgesics for the last four years. She has received octreotide (once-monthly 10 mg) and cabergoline (once-weekly 1 mg). The last laboratory results showed that her IGF-1 level had decreased dramatically; to 125 ng/ml. Based on the complaint of knee pain, imaging studies, including an X-ray, showed severe osteoarthritis.

Conclusion

Acromegalic arthropathy is one of acromegaly's most critical functional disabilities. In our case, radiographic imaging studies at joint sites show severe osteoarthritis. Considering the patient's medical history, the cause of knee pain is osteoarthritis, which is also caused by acromegaly. We should also be aware that; long-term biochemical control of acromegaly may not prevent the progression of acromegalic arthropathy in many patients. The prevalence of clinical and radiological acromegalic osteoarthritis of the hip, hand and knee reaches even up to 80%.
Ectopic parathyroid adenoma with severe osteoporosis in premenopausal woman
Authors: Ahmadova Konul
Published: January 2023

Introduction

Primary hyperparathyroidism (PHPT) is defined as unsuppressed secretion of parathyroid hormone leading to a dysregulated bone and mineral metabolism and ultimately causing hypercalcemia. The main reasons for its development are parathyroid adenomas (PAs) with an estimated prevalence of 1–4/1.000 in the general population, predominant in postmenopausal women. Ectopic location of the parathyroid glad occurs in 6–16%.1 The most common location of ectopia is thymus, the next retroesophageal region and thyroid gland. We present a case of ectopic thymic parathyroid adenoma with severe clinical manifestations.

Clinical Case

A 43 years old woman patient applied to the clinic with complaint of bone pain, especially at the waist and hip. She had also difficulty in walking. Her laboratory tests were as follows; Ca: 9.65 mg/dl, albumin:45 g/dl, corrected Ca:9.25 mg/dl, phosphorus: 0.55 mmol/l (0.81–1.45), thyroid stimulating hormone (Tsh) 5.8 miu/l,Alp: 369 u/l, Pth: 442 pg/ml, vitamin D: 13 ng/mL, Mg:0.84 mmol/l. In radiologic findings; Hip and knee MRI revealed T1 hypointense, STIR and T2 hyperintense cystic lesion on the iliac wing of the left sacroiliac joint 36×13 mm in size, intraosseous cystic lesion on the right knee cap 16×26×27 mm in size. And cystic lesion was observed in the diaphysis region of the upper 1/3 of the right tibia 8×7×22 mm in size. The patient was found to be osteoporotic on dual energy X-ray absorptiometry (DEXA) scanning (Z score =−6.3 at the lumbar spine; Z score =-6.4 at the femur neck and Z score =-5.8 at the total femur). Neck ultrasound revealed an incidental thyroid nodule but no lesion suggestive of parathyroid adenoma was observed in ultrasonography. Vitamin D replacement therapy was started. After 4 weeks, laboratory tests were as follows; vitamin D:21 ng/ml, Pth:364 pg/ml, Ca: 10.65 mg/dl, albumin: 3.8 g/dl corrected Ca: 10.81, phosphorus: 0.73 mmol/l Alp:392 u/l, renal function tests were in the normal range. And 24-hour urinary calcium was 652 mg/day, fractional excretion of calcium (FeCa): 0.023. 24-hour urinary phosphorus: 29 mmol/day (normal). The patient was started on bisphosphonate therapy. Parathyroid sintigraphy was taken for localization purposes in the patient with hyperparathyroidism. In the early and late imaging of the anterior mediastinum, MIBI collection was detected behind the manubrium sterni with a size of 15×10 mm consistent with a parathyroid adenoma. The patient was consulted with thoracic surgery and the operation was performed. In the post-examination assays, Ca: 8.64 albumin: 3.8 g/dl corrected Ca: 8.75 mg/dl phosphorus: 2.54 mg/dl Pth: 41 pg/ml. Pathology resulted as ectopic thymic parathyroid adenoma.

Conclusion

Although ectopic parathyroid adenoma is not common in premenopausal women, it should be considered as a cause of severe osteoporosis.
Primary hyperparathyroidism and skull bone: Dicle sign
Authors: Pekkolay Zafer , Tuzcu Alpaslan Kemal
Published: January 2023

Introduction

In primary hyperparathyroidism, a brown tumor may be seen due to excessive osteoclastic activity. We will share the unusual localization of this tumor-like formation that primarily affects the lower and upper extremities.

Clinical Case

A 20-year-old female patient presented with complaints of weakness, headache, bone pain, and difficulty walking. He had a history of surgery for a pathological femur fracture in the past. In the evaluation, a diagnosis of primary hyperparathyroidism due to ectopic parathyroid adenoma was made. Brown tumor-like formations were also observed in the skull bone in the cranial tomography taken due to severe headache. An adenomectomy was performed on the patient whose parathyroid adenoma localization was detected in the scintigraphic examination. The patient, who developed post-operative hungry bone syndrome, was discharged approximately one month later due to the need for intravenous calcium. It lasted about one year after the patient's oral calcitriol and calcium treatment. She was followed up without treatment. At her last follow-up in June 2022, calcium, phosphorus, and parathormone levels were normal. The patient had no complaints.

Conclusion

Brown tumor is often seen in the bones of the hands, feet, and long bones. We detected it for the first time in the skull bone.
A rare disease: Familial hyperphosphatemic tumoral calcinosis
Authors: Akçay Seçkin , Dashdamirova Saida , Gözü Hülya
Published: January 2023

Introduction

Tumoral calcinosis (TC) is a rare disease characterized by soft tissue calcification as a result of repetitive trauma and prolonged pressure in periarticular areas of large joints; such as hip, knee, shoulder and elbow. There are three different forms; sporadic, familial and secondary TC due to chronic renal diseases, vitamin D hypervitaminosis. Familial hyperphosphatemic TC, which will be presented in this case, causes by relative deficiency or resistance of FGF-23, which is the critical regulatory hormone in the phosphorus metabolism.

Clinical Case

A 38-year-old male patient was referred from the nephrology department for hyperphosphatemia. He underwent 14 operations mass lesions, which were painful, progressively enlarging, in the different regions. His first operation at the age of 11 for a lesion in the right knee. Pathologic diagnoses of surgical specimens were reported as tumoral calcinosis. The patient was followed up by different orthopedic clinics from the age of 11, and was operated as new masses appeared. He does not have any complaints other than the pain in the periods when the lesions appear. He has 4 siblings without any known diseases, and his parents were third degree consanguineous. In physical examination, blood pressure was 115/72 mmHg, pulse was 76/min, and temperature was 36.7°C. Her height was 183 cm, and weight was 82 kg, BMI: 24.5 kg/m2. In laboratory tests, serum calcium 10.1 mg/dl, serum phosphate 6,8 mg/dl, parathormone 25 pg/ml, 25-OH Vitamin D 19 ng/ml, creatinine 0.9 mg/dl, alkaline phosphatase 71 U/l, 24-h urinary calcium 129 mg/day and 24-h urinary phosphate 205 mg/day. Bone mineral density at the femoral neck was 1.258 g/cm2, Z score was -1.6, and BMD at the lumbar spine was 1.081 g/cm2, Z score was -0.9. In bone survey, we detected that mild right-facing rotoscoliosis in the thoracolumbar region, increased calcification of the costosternal cartilages, osteophytic tapering in the thoracic region, intracranial calcification in the parietal region, L3-L4 level syndesmophyte, irregularity and adjacent soft tissue calcification at the distal phalanx level of the first toe of the right and left foot (Fig 1). We recommended the patient to avoid trauma and a low phosphorus diet. Maintenance dose vitamin D replacement and phosphorus-binding treatment (calcium-asetate 700 mg 3×2) with meals were started. When phosphate reduction could not be achieved, sevalemer 800 mg 3×3 was added with gradually increasing, phosphorus level dropped to 5.2 mg/dl. Genetic analysis revealed GALNT3 homozygous mutation. Genetic counseling and eye examination were recommended.

Conclusion

TC should also be considered in patients with a history of multiple surgery due to soft tissue masses, especially in the presence of hyperphosphatemia. In our case, a mutation was detected at a rather late age, and phosphorus-lowering therapy was started at the age of 38 years and genetic counseling should be offered to these patients at an early age.
A case of malign insulinoma diagnosed with liver metastasis
Authors: Şehit Kara Canan , Ilik Abdullah , Öztürk Figen , Abdulrezzak Ümmühan , Ibrahim Karahan Ökkeş , Sözüer Erdoğan , Bayram Fahri
Published: January 2023

Introduction

Insulinoma is a rare neuroendocrine tumor originating from pancreatic beta cells and is the most common cause of hyperinsulinemic hypoglycemia. Herein, a rare case of metastatic insulinoma in which many treatment alternatives were used will be presented.

Clinical Case

A 52-year-old male patient with no known history of chronic disease applied to us with complaints of numbness in the hands, inability to wake up in the morning and fainting. The patient, who worked as a professional referee, stated that he went to football matches with sugar in his pocket and ate sugar when he felt bad during the football matches. The patient needed to eat many times during the day. It was learned that the patient was treated with the diagnosis of transient ischemic attack and vertigo in another hospital where he applied with these complaints. In our hospital, random glucose was determined as 30 mg/dl. Prolonged fasting test was performed. Plasma glucose: 28 md/dl, insülin: 30,81 Uıu/ml, c-peptid 6,17 ng/ml were measured at 6th hour of the test. In abdominal computarized tomography, a 6.5×9.5 cm mass in the tail section of the pancreas and a subcentimetric metastatic nodular lesion in liver were detected. The patient diagnosed with metastatic insulinoma and distal pancreatectomy and liver metastasectomy operations were performed. Pathological examination showed insulinoma in the pancreas and neuroendocrine tumor metastasis in the liver (figure 1). No hypoglycemia was seen after operation. In the postoperative 24th month, fasting plasma glucose: 176 mg/dl and HBA1c: 8.6 were found and diabetes mellitus was diagnosed, insulin detemir was started. At the postoperative 36th month, a metastatic nodular lesion was detected in the liver. Fine needle aspiration biopsy was performed and in pathological examination, neuroendocrine carcinoma metastasis is seen. Octreotide LAR 20 mg/month treatment was started. In the follow-up, another metastasis was detected in two separate foci in liver so, patient's treatment was changed to lanreotide 120 mg/month. Four sessions of radiofrequency ablation were performed to the metastatic liver lesions. The patient is still being followed up by us and has no complaints of hypoglycemia. Plasma glucose values are in the normal range and Hba1c varies between 7.1–7.6%.

Conclusion

Although insulinoma cases are mostly benign, metastatic cases can also be seen rarely. The main treatment of the disease is surgery. Somatostatin analogues can be used in postoperative recurrence or inoperable metastatic disease. Radiofrequency ablation has an important role in local treatment.
Successful use of liraglutide in a female patient with type 1 Gaucher disease, type 2 diabetes mellitus and obesity
Authors: Topaloğlu Ömercan , Ayhan Ihsan , Tekin Sakin , Arık Mina , Bayraktaroğlu Taner
Published: January 2023

Introduction

Gaucher disease is a rare lysosomal storage disease, and caused by a mutation in the GBA1 gene with an autosomal recessive inheritance. Type 1 nonneuronopathic form is the most common form of the disease which commonly presents with painless splenomegaly, anemia, or thrombocytopenia, chronic fatigue, hepatomegaly (with or without abnormal liver function test findings), bone pain, or pathologic fractures. Type 2 and type 3 Gaucher disease may be associated with neurological abnormalities. Weight gain or the development of type 2 diabetes mellitus (T2D) was associated with Gaucher disease under enzyme replacement therapy in a few studies in the literature. In this case, we aimed to show the successful use of liraglutide in the management obesity in a patient with type 1 Gaucher disease and T2D.

Clinical Case

A 41-year-old female patient was presented with weight gain. The patient had a history of type 1 Gaucher disease for 20 years ago, T2D for 10 months, and primary hyperparathyroidism for 1 month. She underwent splenectomy at 4-year-old, and partial hepatectomy 1 year ago. She had been taking imiglucerase 60 IU/kg every 15 days, metformin 1000 mg 2×1/day, and duloxetine 60 mg/day. No history of smoking or alcohol use was present. Maternal history revealed also T2D. On physical examination, height was 153 cm, body weight 72.8 kg, body mass index 31.1 kg/m2. Vital signs and systemic examination findings were unremarkable with the exception of central obesity. Laboratory evaluation revealed that fasting blood glucose level was 120 mg/dL, HbA1c 6.6%, ALT 81 U/L, AST 53 U/L, and creatinine 0.8 mg/dL. Abdominal sonography revealed grade 2 hepatosteatosis and hepatomegaly with a diameter of 160 mm, but no cholelithiasis or pancreatic mass. Based on history, physical examination and work-up, no contraindications were detected for GLP1 receptor agonist therapy. Liraglutide (3.0 mg/day subcutaneous) was prescribed. It was initiated with a low dose (0.6 mg/day), and the dose was increased gradually. In the follow-up, the patient lost 3.5 kg (at about 4.8%), and BMI was decreased to 29.6 kg/m2 one month later. HbA1c level was measured as 6.3%, ALT 41 U/L, AST 33 U/L, and creatinine 0.8 mg/dL. The patient did not complain any side effect which might be potentially associated with Liraglutide.

Conclusion

With the successful use of liraglutide in a patient with a diagnosis of Gaucher, both weight control was achieved and liver function tests secondary to hepatosteatosis and perhaps gaucher's disease were improved. Our patient has an important feature with liraglutide being used for the first time in Gaucher's disease in the literature. In conclusion, liraglutide can be safely used in Gaucher patients for control obesity and especially in patients with hepatic dysfunction due to central adiposity.
Beneficial outcomes of glucagon like peptide-1 agonist therapy in a patient with Bardet Biedl syndrome and kidney transplant
Authors: Erturk Banu , Oguz Seda Hanife , Yildiz Bulent Okan
Published: January 2023

Introduction

Bardet Biedl syndrome (BBS) is a rare hereditary disorder characterized by early-onset obesity, metabolic syndrome, type 2 diabetes, hypogonadism, polydactyly and renal failure. There is lack of data on the use of glucagon-like peptide-1 receptor agonist (GLP-1RA) for management of patients with BBS and kidney transplant. Herein, we report our findings on body weight, graft kidney function and metabolic parameters in a patient with BBS and kidney transplant.

Clinical Case

A 35-year-old man with BBS was referred to our clinic for morbid obesity, diabetes and dyslipidemia. He also had retinitis pigmentosa, acanthosis nigricans, hypertension and hypogonadotropic hypogonadism, but no polydactyly. Due to polycystic kidney disease, the patient underwent cadaveric kidney transplantation ten years ago. He quickly gained weight after starting glucocorticoids following the kidney transplant. Current medical treatment consisted of metformin 1000 mg BID, testosterone 250 mg injection every three weeks, amlodipine 5 mg daily, mycophenolate mofetil 500 mg BID, and cyclosporin 25 mg BID. His body mass index (BMI) was 45 kg/m2, body fat percentage was 41%, waist and hip circumferences were 120 and 125 cm, respectively. On laboratory examination, his fasting plasma glucose and glycated hemoglobin (HbA1c) levels were 140 mg/dL and 7.8%, respectively. A low-density lipoprotein level of 178 mg/dL, a high-density lipoprotein level of 45 mg/dL, and a triglyceride level of 200 mg/dL were found in the lipid profile. His serum creatinine and estimated glomerular filtration rate (eGFR) were 1.9 mg/dL and 66.3 mL/min/1.73 m2, respectively. The initial treatment strategy was lifestyle changes and dietary management which did not result in significant weight loss after 6 months. Following a thorough discussion on medical treatment options with the patient, exenatide was started considering obesity, diabetes and patient preference for affordability. Initial dose of 5 mcg BID was gradually titrated up to 10 mcg BID, with frequent monitoring of his kidney function tests. Over a 6-month period, exenatide treatment resulted in significant weight loss, with a reduction in BMI to 40 kg/m2, body fat percentage to 35%, waist and hip circumferences to 114 and 120 cm, respectively. HbA1c decreased from 7.8% to 6.2%, and eGFR increased from 66.3% to 84.2%. His hypertension, dyslipidemia, and urinary protein: creatinine ratio also significantly improved. He has maintained his weight and glycemic control during further follow up of 10 months.

Conclusion

Weight management in BBS could be challenging, and kidney transplantation may make it even more difficult. Here we show that GLP-1RA use results in significant weight loss along with improvements in glycemic control, metabolic parameters, and renal function in a patient with BBS and kidney transplant. More data are needed to confirm long term efficacy and safety of GLP-1RA in these patients.
Skin tags are all over the body
Authors: Pekkolay Zafer , Akkum Aylin
Published: January 2023

Introduction

Skin tags are reflections of insulin resistance on the skin. It is generally observed in the head and neck region.

Clinical Case

A fifty-year-old male patient was admitted to the outpatient clinic due to obesity. He complained of not being able to lose weight despite diet and exercise. The patient's weight was 163,8 kg, height 175 cm, and BMI 53.5. Widespread skin tags on the patient's neck and whole body were remarkable. There were prominent acanthosis nigricans in the neck and axilla. The patient had been receiving treatment for Type 2 Diabetes Mellitus for eight years. He was using metformin 2000 mg/day, gliclazide 30 mg/day and pioglitazone 30 mg/day. Fasting insulin level was 15.46 mU/L, fasting glucose level was 165 mg/dL, HbA1c was 9.6%, and HOMA-IR was 6.29. In addition to the treatment he received, lifestyle changes (exercise, healthy diet) were recommended to the patient, and orlistat 360 mg/day was started.

Conclusion

Skin tags are mostly seen on the neck and nape. It was observed widely throughout the body in our patient.
Xanthomatous sypophysitis secondary to a ruptured Rathke's cleft cyst
Authors: Gezer Emre , Çabuk Burak , Yaprak Bayrak Büşra , Cantürk Zeynep , Çetinarslan Berrin , Selek Alev , Sözen Mehmet , Köksalan Damla , Ceylan Savaş
Published: January 2023

Introduction

Hypophysitis (HP) is a rare disease which develops secondary to chronic or acute inflammation of the pituitary gland and may cause symptoms related to pituitary dysfunction and mass compression. HP can be classified based on the anatomical location of pituitary involvement (adenohypophysitis, infundibulo-neurohypophysitis, or panhypophysitis), the etiology (primary or secondary), and the histopathology (lymphocytic, granulomatous, xanthomatous, IgG4, necrotizing, or mixed forms). Lymphocytic HP is the most common subtype of primary HP, while xanthomatous HP (XHP) is considered the rarest form, with 35 reported cases, to date. In our report, we describe a case with panhypopituitarism due to XHP secondary to the rupture of an Rathke's cleft cyst (RCC).

Clinical Case

A 35-year-old woman was initially admitted to a Gynecology clinic with a 2-year history of amenorrhea and headache. She was started on cabergoline 0.5 mg twice a week for macroprolactinoma. Due to persistent amenorrhea with low gonadotropins, she was referred to our Endocrinology clinic. Her pituitary function profile revealed panhypopituitarism (Table 1) and a 13×11×12 mm sized sellar mass with diffuse enhancement which sustained toward the infundibulum and dura was observed on the gadolinium-enhanced pituitary MRI. The patient underwent an endoscopic endonasal transsphenoidal approach for tumor resection and thick yellowish fluid draining from the lesion was observed (Figure 1). The histopathological diagnosis was reported as a rupture of an Rathke's cleft cyst and a xanthomatous hypophysitis. The surgery did not improve the symptoms/pituitary functions, however, headache recovered immediately after the first dose of high dose methylprednisolone treatment.

Conclusion

The exact mechanism by which XHP occurs still remains unclear. The development of the characteristic histopathological lesion which consists of lipid-laden “foamy” histiocytes and CD68 positive macrophages has been previously attributed to the extension of an autoimmune/lymphocytic spectrum. On the other hand, various recent case presentations have reported to consider the inflammatory process of XHP related to the rupture of a RCC.

XHP is an uncommon inflammatory process of the pituitary gland which should be included in the differential diagnoses, if a patient presents with headache, panhypopituitarism and if yellowish fluid is drained from a cystic lesion intraoperatively. In agreement with the recent reports, our case presentation may also indicate a recommendation to classify XHP as secondary hypophysitis which could be caused by a ruptured cystic lesion. Here, we present a patient with XHP which developed as an inflammatory response to a ruptured RCC and the transsphenoidal surgery did not improve the symptoms/pituitary functions, while headache recovered immediately after the first dose of high dose methylprednisolone treatment.
Gastrointestinal carcinoma first presenting as pituitary mass: recognition of a rare case and multidisciplinary approach for the management of pituitary metastases
Authors: Costanza Flavia , Chiloiro Sabrina , Giampietro Antonella , Pontecorvi Alfredo , De Marinis Laura , Bianchi Antonio
Published: January 2023

Introduction

PMs (pituitary metastases) are rare and only a few cases are reported in the literature. In half of the documented cases, PMs originate from breast and lung cancers, rarely from other sites. They can grow rapidly and present local invasiveness, leading to acute onset of neurological symptoms, such as headache, visual and oculomotor disturbances, or endocrinological signs, such as diabetes insipidus and hypopituitarism. Their rarity and the lack of specific clinical and radiological features often impede their differentiation from other more common sellar area lesions, particularly when history of malignancy is absent. As PMs can be life-threatening, they must be recognized and treated promptly. Management of PMs may also be difficult because the prognosis depends on the course of the primary neoplasm. The case presented below is one of the few documented cases in the world of a pituitary metastasis from a primary gastrointestinal carcinoma.

Clinical Case

A 76-year-old woman, with no history of malignancy, presented with headache, dizziness and diplopia. Neurologic examination was remarkable for complete left ophthalmoplegia associated with sensitivity deficit in the left half face. Radiologic investigations documented a voluminous sellar and suprasellar formation, with extension in the ipsilateral cavernous sinus, compressing the optic chiasm and ipsilateral temporal lobe. The mass appeared heterogeneous as component of apoplectic infarction. Left cavernous sinus syndrome in apoplectic macroadenoma was diagnosed. Surgical removal of the lesion was performed through a transsphenoidal endoscopic endonasal approach. The histological exam disclosed a metastasis of adenocarcinoma with widespread necrotic-haemorrhagic elements. The immunohistochemical profile suggested an origin from a primary gastrointestinal carcinoma. Hormone replacement therapy and adjuvant therapy were instituted, although radiological investigations failed to identify the site of the primary gastrointestinal carcinoma. Postoperative MRI showed a parasellar residual tumor, which was radiologically stable at 6-month follow-up. The patient will undergo a radiotherapy and neurosurgical evaluation.

Conclusions

Clinicians should consider the possibility of PMs in patients with symptoms and signs that may suggest the presence of a pituitary mass. Since PMs can be cancer first manifestation, the recognition of PMs determines the referral to adequate oncological therapy. Prognosis is usually poor and it's difficult to estimate as it varies significantly depending on the systemic disease and the primary histology. Recognition and management of PMs remain complex and require a multidisciplinary team of endocrinologists, oncologists, neurosurgeons and neuroradiologists.
Keep looking until you find
Authors: Tuomola Nelli
Published: January 2023

The patient is 24-years old male with no previous medical history. He has worked for the last 3 years in the packaging line of Divigel, the estradiol gel of the pharmaceutical company Orion. He sought medical attention 11/2014 due to soreness of both breasts, that had continued for a few weeks.

In laboratory tests taken in primary health care, E2 was elevated at 0.49 nmol/l (reference range <0.15 nmol/l), LH immeasurably low (1,7–8,6 U/l), testosterone 33 nmol/l (10–38 nmol/l). Liver and thyroid values were normal. An ultrasound examination of the breasts revealed gynecomastia: mammary gland tissue was seen under the nipple on both sides, 2 cm on the left, 1.5 cm on the right. The ultrasound examination of the testicles did not reveal any abnormality.

The patient was referred to the endocrinology outpatient clinic. E2 was then 0,236 nmol/l, testosterone 42, free testosterone 547 pmol/l (190–560 pmol/l), SHGB 51 (18–54 nmol/l), LH <0,10 U/l, FSH 0,12 U/l (1,5–12,4 U/l), PRL 426 (86–324 mU/l), hCG elevated 37 U/l (<2 U/l) and free β-hCG 5,8 pmol/l (<2 pmol/l).

In 12/2014, the patient underwent a CT scan of the body and ultrasound examination of the testicles was repeated: no abnormality was found in either examination. 18F-FDG PET/CT of the body was performed in the same month, also with normal findings. At the beginning of 2015, MRI examinations of the mediastinum, lower and upper abdomen, and head were performed; no explanation was found. Cerebrospinal fluid hCG, which was low <1,0 IU/l, and S-AFP, which was 2 kU/l (<10 kU/l), were also checked.

At follow-up, hCG continued to rise to 135 U/l and E2 to 0.424 nmol/l.

Imaging studies were repeated: CT of the body was performed in 11/2015 and 8/2015, ultrasound examination of the testicles in 4/2015, 8/2015 and 12/2015. In 3/2016, a 11C-metionine PET/MRI of the body was performed. No abnormal findings were found.

In the sixth ultrasound examination of the testicles in 6/2016, a 5×6 mm low-echo, solid tumor was finally found on the surface of the left testicle at the very front edge. No abnormalities were found in the right testicle.

Testicular operation was performed 6/2016. Findings suitable for seminoma were found in the ice section, after which the left testicle was removed. Histopathological findigs were consistent with seminoma. In immunostaining, the tumor cells were PLAP- and CD117-positive, and a widely positive reaction was seen around the tumor in the seminiferous tubules, consistent with carcinoma in situ findings. CD30-, CKPan-, hCG-, inhibin- and AFP-stainings were negative. The findings were consistent with seminoma, and no other germ cell tumor components were found.

After surgery, E2 and hCG values normalized. Abdominal CT examination did not reveal any metastases. Follow-up by an oncologist continued for five years, and no signs of recurrence were found.

Sometimes we know what we are looking for, but reaching a diagnosis may require persistence and repeated examinations.
A rare case of Riedel's thyroiditis: Immunoglobulin G4-related thyroid disease
Authors: Özer Özge , Yorulmaz Göknur , Badak Bartu , Tekin Emel
Published: January 2023

Introduction

Riedel's thyroiditis is a rare thyroiditis in which normal thyroid tissue is replaced by dense fibrous connective tissue. Its etiology is not fully known. An autoimmune process is thought to exist. In this disease group, lymphoplasmocytic tissue infiltration, mostly consisting of IgG4 (+) plasma cells and small lymphocytes, is seen accompanying fibrosis. In our case, we presented a very rare case of Reidel's thyroiditis.

Clinical Case

We report the case of a 46-year-old woman who came to the general surgery department with an enlargement at the base of her neck. Among the patient's complaints were dysphonia, a feeling of pressure and pain in the neck. She had no history of thyroid disease. Laboratory findings; TSH 0.06 uIU/ml (0.27–4.2), fT3 2.69 pg/mL (2.3–4.5), fT4 1.81 ng/dl (0.93–1.70), crp 73.6 mg/l (0.0–5.0), sedimentation 90 mm/h (0–20), leukocytes 11.74 10^3/ul (4.49–12.68), absolute neutrophil count 9.22 10 ^3/ul (1.9–7.9). Trucut biopsy was performed with the preliminary diagnosis of malignancy due to the history of a mass growing in a short time on the neck of the patient. Pathology result; “Intense fibrosis increase, severe lymphoplasmacytic cell infiltration rich in IgG4 positive cells. Thyroid follicle epithelial cells with ck7, panck, pax8, thyroglobulin, ttf1 positive and cea, ck20, alk negative Intense plasma cells with CD38 have polyclonal staining with kappa and lambda, and IgG4/IgG ratio > 50%. In the background, cd3, pax5 and bcl2 and T cell-rich reactive inflammatory cells are accompanied. Obliterative vascular structures were noted in rust and elastic histochemical stains, and storiform fibrosis was observed in places on the ground. When histopathological and immunohistochemical findings are evaluated together, it is primarily compatible with IgG4-related disease/reidel thyroiditis.'' She was then referred to the endocrinology department. The serum IgG4 level was found to be above normal. She was started on steroid treatment with 64 mg daily methylprednisolone. A weekly control plan was made. In these controls, the steroid dose was gradually reduced. In the follow-up one week later, it was observed that the patient's CRP and sedimentation returned to normal values. There was also a decrease in enlargement in the neck area. In the third month of the treatment, the patient didn't want to continue the treatment. She did not visit our clinic for the next 3 months. Then, she came for the control after three months without treatment. Biochemistry and thyroid function tests were normal. The swelling in the neck area of the patient was completely gone.

Conclusion

Reidel's thyroiditis is a very rare disease with publications on the basis of case reports in the literature. Therefore, there are no broad-spectrum clinical studies. Clarity on treatment approaches was also not provided. We also benefited from case reports while managing our patient's treatment. We believe that our case will contribute to the literature for the same purpose.
A case of Tocilizumab-induced thrombocytopenia in steroid-resistant Graves orbitopathy
Authors: Cuculescu Victoria , Vudu Stela , Rizov Cristina , Vudu Lorina
Published: January 2023

Introduction

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). It is more common in women, but men have more severe evolution of the disease. GO appears in 25–70% of patients with GD and can have a severe evolution in 5% cases and even lead to sight loss. In mild forms local treatment is often sufficient to alleviate eye symptoms. However, in moderate-to-severe cases systemic glucocorticoids are used, combined or not with immunosuppressive drugs. In moderate-to-severe glucocorticoid-refractory cases, conventional and biological immunosuppressive drugs have been used, among which is treatment with Tocilizumab (TCZ) – a monoclonal antibody targeting the interleukin-6 receptor, involved in GO's pathogenesis.

Clinical Case

A 49 years old former smoking Caucasian man was admitted to the endocrinology unit with asymmetrical bilateral exophthalmos, spontaneous and movement induced retrobulbar pain, hyperlacrimation. He has been diagnosed with Graves disease 9 months prior to the admission to our clinic. At that time the patient was treated with antithyroid drugs and oral prednisolone. The clinical activity score – CAS 7/7 points confirmed an active form of GO. Laboratory findings revealed a suppressed TSH 0.01 UI/ml, increased freeT4 40,1 pmol/l, positive TR-Ab (30,04 IU/L). Treatment with high-dose regimen of i.v. methylprednisolone (Mt), cumulative dose 5.75 g in 12 weeks was applied. The patient was soon thereafter admitted repeatedly for evaluation: a non-response to Mt has been established, occurrence of diplopia, convergent strabismus, therefore a second-line treatment with tocilizumab (TCZ) was considered. His blood platelet count before TCZ was 158×10*9. The patient received the first 8 mg/kg dose of i.v. TCZ and showed an improvement in the CAS score (5/7 points), however 1 month later, the platelet count had decreased to 48×10*3 and further treatment with TCZ has been postponed until thrombocyte count increases above 100×10*9. His oral medicines were thiamazole and levothyroxine. Other causes of thrombocytopenia (HIV, Hepatitis C, Ebstein-Barr virus, Helicobacter pylori, liver disease) have been excluded. 7 weeks later thrombocyte count increased spontaneously to 102×10*3 and TCZ treatment has been resumed.

Discussion. The mechanism of thrombocytopenia induced by TCZ is dependent on its effect on IL-6 receptor, which stimulates thrombopoiesis through thrombopoietin induction. Clinical studies prove the effectiveness of TCZ in the treatment of GO, but side effects limit its use. Older age and low platelet count before TCZ treatment were associated with the development of thrombocytopenia after treatment.

Conclusion

Thrombocytopenia induced by tocilizumab is tolerable. However, in patients with known risk factors, close monitoring of platelet counts is recommended. An individual approach is appropriate, considering the high cost of the drug, side effects and comorbidities.