Capillary microarchitectural changes are independent of disease activity in acromegaly.

OBJECTIVE: Although atherosclerosis-related macrovascular complications are well known in acromegaly, studies on endothelial function and arteriolar level are contradictory. In order to test the hypothesis, microvascular changes associated with macrovascular changes in acromegaly, we aimed to evaluate microvascular changes in nailfold capillaries and carotid intima-media thickness (CIMT) in patients with acromegaly. DESIGN: In this cross-sectional observation study, of total 70 patients with acromegaly [ten (14.3 %) were active acromegaly (AA), 60 (85.7 %) were controlled acromegaly (CA)] and 74 healthy controls were enrolled. Microvascular structure was evaluated using the nailfold video capillaroscopy, and CIMT was measured using ultrasonography. RESULTS: The median number of capillaries was less [10 no./mm (min-max: 5-16) vs. 11 no./mm (min-max: 9-15); p = 0.001] in the acromegaly group than in the controls. Capillaries below 6-8 per/mm was more common in the acromegaly patients [six (8.6 %) vs. one (1.4 %); p = 0.046]. All capillaroscopic parameters were similar among the patients with CA or AA. CIMT levels were higher in the acromegaly group than in the control group [0.60 mm (0.43-0.86) vs. 0.38 mm (0.27-0.59); p < 0.001], and AA patients had higher CIMT than CA patients (p = 0.037). None of the clinical or laboratory parameters including growth hormone and IGF-1 were related to capillaroscopic parameters or CIMT. CONCLUSION: Decreased capillary number was the major capillaroscopic finding in acromegaly and there was no significant difference between active and controlled cases, but CIMT was found to be higher in the active group. Increased CIMT levels in acromegaly were not associated with capillary changes. Large-scale, prospective studies are needed to make a definite conclusion about the effect of the disease activity on nailfold capillaries and its association with macrovascular changes.

Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19.

PURPOSE: Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency. METHODS: Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined. RESULTS: Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype. CONCLUSION: 25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients.

Capillary microarchitectural changes in Cushing's syndrome.

PURPOSE: Macrovascular alterations are prominent in Cushing's syndrome (CS). Microvascular abnormalities are yet to be established. This cross-sectional observational study aimed to evaluate microvascular changes in nailfold capillaries and their association with disease status and carotid intima-media thickness (CIMT) as a marker of atherosclerosis. METHODS: A total of 70 patients with CS [46 (65.7%) ACTH-dependent pituitary adenoma and 24 (34.3%) adrenocortical adenomas] and 100 healthy controls were enrolled. The microvascular structure was evaluated using nailfold video-capillaroscopy (NVC). RESULTS: The median number of capillaries was less [10 mm (IQR: 2, min-max:7-14) vs. 11 mm (IQR: 2, min-max:9-19) (p < 0.001)], the median limb diameter and capillary width were wider in the CS group than in the controls (p = 0.016 and p = 0.002, respectively). Microhemorrhages within limited areas were more frequent in the CS group than in the controls (p = 0.046). Observed capillary changes were similar among the patients with CS with remission or active disease. CIMT levels were higher in the CS group than in the controls and similar in subjects with active disease and remission. Univariate logistic regression analyses revealed that the number of capillaries and capillary widths were associated with body mass index (BMI), the presence of type 2 diabetes mellitus, HbA1c, and CIMT. CONCLUSION: Morphologic alterations present similarly in nailfold capillaries in subjects with CS regardless of disease status, resembling changes in chronic atherosclerotic diseases. Microvascular changes in nailfold capillaries measured using NVC can be used as a marker in the assessment of cardiovascular risk in patients with CS.

Does concomitant prolactin measurement increase the accuracy of inferior petrosal sinus sampling?

INTRODUCTION: Prolactin (PRL) measurement during inferior petrosal sinus sampling (IPSS) can be helpful to improve the accuracy. We aimed to evaluate the effect of measuring PRL levels as a predictor for the accuracy of IPSS and evaluate its impact on the lateralization of adenomas. METHODS: In this retrospective cohort study, we reviewed 51 patients who had undergone IPSS for the investigation of ACTH-dependent hypercortisolism. RESULTS: Forty-nine patients had proven Cushing's disease (CD), one had EAS, and the remaining one patient had adrenal adenoma. Forty-seven patients had an above 2 ACTH IPS/P ratio at baseline, and all the post-corticotropin-releasing hormone (CRH) ACTH IPS/P ratios of patients with proven CD were above 3. In these two patients whose ACTH IPS/P ratio at baseline was below 2, PRL IPS/P ratios were above 1.8 in only the dominant side, which was considered secondary to a prolactin intersinus gradient due to the biological effects of the tumor. PRL-adjusted ACTH IPS/P ratios were > 1.3 in all patients with proven CD; it was 0.7 in the patient with EAS. Surgically confirmed positive lateralization was observed in 55.1% of patients with the ACTH gradient, but when PRL-adjusted ACTH IPS/IPS ratios were used in addition to the ACTH gradient, the ratio increased to 67.3%. CONCLUSION: Although PRL-adjusted ACTH IPS/P ratios can be helpful to improve the accuracy of results during IPSS procedures, a prolactin intersinus gradient towards the ACTH-dominant side in patients with CD may invalidate PRL as an indicator of pituitary venous outflow.

Skin autofluorescence Is associated With low bone mineral density in type 2 diabetic patients.

Although the risk of bone fracture is increased in type 2 diabetes (T2DM), bone mineral density (BMD) is increased rather than decreased. Accumulation of advanced glycation end products (AGEs) adversely influences the fracture resistance of bone in T2DM. We hypothesized that SAF is also associated with BMD levels in type 2 diabetic patients and aimed to evaluate the association of SAF with BMD and the presence of osteoporosis. This cross-sectional case-control study included 237 patients with T2DM (F/M: 133/104, 56.2±11.9 yrs) and 100 age- and sex-matched controls (F/M: 70/30, 54.8±8.8 yrs). Skin autofluorescence, a validated non-invasive measure of tissue AGEs, is used to detect the accumulation of AGEs in skin collagen using AGE Reader (DiagnOptics B.V., Groningen, The Netherlands). In addition, BMD was measured with DEXA (Lunar DPX-L). Patients with T2DM had higher SAF values compared to control group (2.21±0.53 AU vs. 1.79±0.33 AU, p < 0.001). Male subjects had higher SAF compared to women (2.34±0.53 AU vs. 2.11±0.50 AU, p < 0.001). Subjects with below -2.5 femoral neck or lumbar T scores had higher SAF measurements compared to subjects with normal T scores (2.46±0.53 AU vs. 2.18±0.52 AU, p = 0.006). Femoral neck BMD was lower in subjects with T2DM (0.946±0.345 g/cm2 vs. 1.005±0.298 g/cm2, p = 0.002). There was a negative correlation between SAF and femoral neck BMD (r=-0.24, p < 0.001), femoral neck T scores (r=-0.24, p < 0.001), L1-4 BMD (r=-0.10, p = 0.005), L1-4 T score (r=-0.16, p=0.001) and a positive correlation between SAF and age (r=0.44, p < 0.001), body mass index (r:0.16, p = 0.002) and HbA1c (r=0.37, p < 0.001). Accumulation of skin AGEs was increased, and BMD levels were decreased in diabetic patients. A negative association between SAF and BMD was detected, indicating a relationship between higher AGE accumulation and low BMD and osteoporosis in diabetic patients. Long-term prospective studies are needed to identify the practical use of SAF measurement in diabetic bone disease.

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients.

PURPOSE: Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients. METHODS: Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13 years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients. RESULTS: Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R2 37.8%, p = 0.027). CONCLUSION: As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

Morbid obesity leads to increased skin autofluorescence independent of metabolic syndrome components.

BACKGROUND: Obesity, diabetes mellitus, and metabolic syndrome (MetS) are associated with increased accumulated skin advanced glycation end products. We aimed to evaluate the association of MetS components with skin autofluorescence (SAF) in patients with morbid obesity. METHODS: Eight hundred and one patients with morbid obesity and 94 age-matched controls with normal body mass index (BMI) and normal glucose metabolism were included. Advanced glycation end products (AGEs) were measured using SAF in the forearm, with an AGE reader. RESULTS: The prevalence of MetS in patients with morbid obesity was 65.5% (n = 525). Type 2 diabetes mellitus (type 2 DM) and hypertension were present in 40.9% (n = 328) and 43.7% (n = 357). Patients with morbid obesity and those with MetS had higher SAF measurements compared with the control group, 1.85 ± 0.44 arbitrary unit (AU) and 1.86 ± 0.43 AU vs. 1.72 ± 0.30 AU, respectively (p = 0.016). There was no difference in SAF levels between patients with and without MetS. SAF measurements of patients without MetS were not statistically different from the control group (p = 0.076). Patients with five MetS criteria had higher SAF measurements compared with patients with fewer MetS components (p = 0.019). There was no difference in SAF levels between patients with type 2 DM, impaired glucose metabolism, and patients with normal glucose metabolism (p = 0.513). DISCUSSION: Although MetS and type 2 DM are known as factors related to increased SAF levels, obesity can cause elevated SAF measurements in different ways independent of concomitant comorbid diseases. Larger studies with longer follow-ups are needed to enlighten the underlying mechanism.

Determinants of remission in a case series of medullary thyroid carcinoma

Background/aim: We aimed to present the clinical results of patients with medullary carcinoma under follow-up in our center and to determine parameters affecting remission and lymph node metastases. Material and methods: A retrospective analysis was performed of the medical records of 27 patients with MTC who were followed up between 2004 and 2020. Results: The mean age at diagnosis was 47.7 ± 14 years. The mean follow-up was 7.29 ± 4.9 years. Metastatic neck lymphadenopathy was detected in eight (29.6%) patients; none had distant metastasis at the time of diagnosis. The median tumor diameter was 1.50 (range: 0.4­6) cm. The median postoperative calcitonin level was 3.3 (range, 0.5­871) ng/L. Relapse occurred in 2 (range, 1­14) years after the first surgery in three (11.1%) patients. In the last visit, 7 (25.9%) patients had a structural incomplete response, and three (11.1%) patients had a biochemical incomplete response. Seventeen (59.3%) patients were in remission, no patients died of MTC or any other cause. Elevated postoperative calcitonin level was a significant prognostic parameter for remission (p = 0.12) and lymph node metastasis (p < 0.001). Conclusion: Elevated postoperative calcitonin level and perithyroid soft tissue invasion were significant prognostic parameters for remission and lymph node metastasis. Postoperative calcitonin level and calcitonin doubling time should be considered for prognostic and survival risk assessments.

Preoperative plasmapheresis experience in Graves' disease patients with anti-thyroid drug-induced hepatotoxicity.

Hepatotoxicity is a rare but serious side effect of antithyroid drug (ATI) therapy in Graves' disease patients. Cessation of ATI drug is needed in most of the patients if liver enzymes highly elevated or in case of agranulocytosis. Permanent therapy, surgery or radioactive iodine ablation are the treatment choices to ensure euthyroidism in active Graves' disease patients. Therapeutic plasma exchange (TPE) can be an option to ensure euthyroidism, especially in patients scheduled for urgent surgery. In the present study, we present consecutive five cases of methimazole related severe hepatotoxicity that underwent TPE before thyroid surgery. The median number of apheresis sessions was 3 (range: 2-5). Free triiodothyronine (FT3) 65-83 %, free thyroxine (FT4) 22-66 %, thyrotropin receptor antibodies (TRAB) 55-96 % decreases were observed. All patients underwent total thyroidectomy. TPE is an effective method to reduce serum FT3, FT4, TRAB levels in the short term to provide better thyroid hormone status before urgent surgery in ATI induced toxic hepatitis patients.

Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1-5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues.

OBJECTIVE: To determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1-5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs). METHODS: A total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors. RESULTS: Several variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p < 0.05 for all), and other SSTRs did not differ between the groups (p > 0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p < 0.05 for all). CONCLUSIONS: Lack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.

Non-pituitary growth hormone enables colon cell senescence evasion.

DNA damage-induced senescence is initially sustained by p53. Senescent cells produce a senescence-associated secretory phenotype (SASP) that impacts the aging microenvironment, often promoting cell transformation. Employing normal non-tumorous human colon cells (hNCC) derived from surgical biopsies and three-dimensional human intestinal organoids, we show that local non-pituitary growth hormone (npGH) induced in senescent cells is a SASP component acting to suppress p53. npGH autocrine/paracrine suppression of p53 results in senescence evasion and cell-cycle reentry, as evidenced by increased Ki67 and BrdU incorporation. Post-senescent cells exhibit activated epithelial-to-mesenchymal transition (EMT), and increased cell motility. Nu/J mice harboring GH-secreting HCT116 xenografts with resultant high GH levels and injected intrasplenic with post-senescent hNCC developed fourfold more metastases than did mice harboring control xenografts, suggesting that paracrine npGH enables post-senescent cell transformation. By contrast, senescent cells with suppressed npGH exhibit downregulated Ki67 and decreased soft agar colony formation. Mechanisms underlying these observations include npGH induction by the SASP chemokine CXCL1, which attracts immune effectors to eliminate senescent cells; GH, in turn, suppresses CXCL1, likely by inhibiting phospho-NFκB, resulting in SASP cytokine downregulation. Consistent with these findings, GH-receptor knockout mice exhibited increased colon phospho-NFκB and CXCL1, while GH excess decreased colon CXCL1. The results elucidate mechanisms for local hormonal regulation of microenvironmental changes in DNA-damaged non-tumorous epithelial cells and portray a heretofore unappreciated GH action favoring age-associated epithelial cell transformation.

WIP1 is a novel specific target for growth hormone action.

DNA damage repair (DDR) is mediated by phosphorylating effectors ATM kinase, CHK2, p53, and γH2AX. We showed earlier that GH suppresses DDR by suppressing pATM, resulting in DNA damage accumulation. Here, we show GH acting through GH receptor (GHR) inducing wild-type p53-inducible phosphatase 1 (WIP1), which dephosphorylated ATM and its effectors in normal human colon cells and three-dimensional human intestinal organoids. Mice bearing GH-secreting xenografts exhibited induced colon WIP1 with suppressed pATM and γH2AX. WIP1 was also induced in buffy coats derived from patients with elevated GH from somatotroph adenomas. In contrast, decreased colon WIP1 was observed in GHR-/- mice. WIP1 inhibition restored ATM phosphorylation and reversed GH-induced DNA damage. We elucidated a novel GH signaling pathway activating Src/AMPK to trigger HIPK2 nuclear-cytoplasmic relocation and suppressing WIP1 ubiquitination. Concordantly, blocking either AMPK or Src abolished GH-induced WIP1. We identify WIP1 as a specific target for GH-mediated epithelial DNA damage accumulation.

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.

BACKGROUND: The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection. METHODS: This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded. RESULTS: A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001). CONCLUSION: Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

Corticomedullary Mixed Tumor of the Adrenal Gland with Apparent 18F-Fluorodeoxyglucose Activity But No 68GA-DOTATATE Uptake on Positron Emission Tomography/Computed Tomography.

Corticomedullary mixed tumor (CMT) is a single adrenal tumor mass composed histologically by an admixture of adrenal cortical and medullary cells. It is a rare condition, with approximately 20 cases reported to date. To our knowledge, the positron emission tomography (PET) imaging findings of this mostly benign tumor have not been reported in the literature. We present a case of CMT who was evaluated with both 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATATE. The hypermetabolic tumor seen on 18F-FDG PET/computed tomography scan showed no abnormal uptake by 68Ga-DOTATATE.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

OBJECTIVE: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. METHODS: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. RESULTS: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. CONCLUSION: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

The association of free testosterone levels with coronavirus disease 2019.

BACKGROUND: Angiotensin-converting enzyme 2 and transmembrane protease serine 2 are critical factors of virus transmission. Expression of angiotensin-converting enzyme 2 is highest in testes, and testicular function and testosterone levels were affected by coronavirus disease 2019. Low testosterone levels are related to infections, especially respiratory tract infections, and could worsen clinical conditions by exacerbating cytokine storms and increasing pro-inflammatory cytokines. OBJECTIVES: We aimed to evaluate the acute and chronic effects of coronavirus disease 2019 on gonadal functions. Our second aim was to detect the relationship between free testosterone levels and disease prognosis and determine the impact of low-free testosterone on admission to the intensive care unit. METHODS: Eighty-one patients with reverse-transcription polymerase chain reaction-confirmed coronavirus disease 2019 were enrolled. Twenty-nine patients were assessed again for 6 months post-coronavirus disease 2019 follow-up, and seven of them had a semen analysis. Serum follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, and total testosterone levels were measured. RESULTS: In this observational study, 71.6% (n = 58) of patients had low free testosterone levels at baseline, in which 69% were considered secondary hypogonadism. A longer length of hospitalization and increased inflammatory markers (d-dimer, high-sensitive C-reactive protein, and procalcitonin) were detected in the low-free testosterone group. Follicle-stimulating hormone, total, free, and bioavailable testosterone levels were lower in patients who required admission to the intensive care unit. Free testosterone levels were inversely correlated with the length of hospitalization and prognostic disease factors. Oligozoospermia and impaired progressive motility were present in 42.8% (3/7) of the patients. In 6 months post-coronavirus disease 2019 follow-up, out of 29 patients, 48.2% still had low testosterone levels. CONCLUSION: A high rate of hypogonadism (71.6%) was found, especially secondary hypogonadism, and about half of the patients had hypogonadism in the sixth months' follow-up. Low free testosterone levels were correlated with inflammatory parameters, and it is related to the intensive care unit admission. Studies with long-term follow-up data in larger groups are needed to determine persistent hypogonadism and impaired spermatogenesis.

Preoperative plasmapheresis in patients with Graves' disease intolerant to antithyroid drugs.

Antithyroid drugs (ATDs) are the mainstay of treatment for Graves' disease with possible detrimental adverse effects. Surgery or radioactive iodine (RAI) ablation is the second choice among the treatment options in cases of non-remission. Normalization of serum thyroid hormone levels as much as possible is required before surgery or RAI to prevent thyrotoxic crisis in patients with uncontrolled Graves' disease. In recent decades, therapeutic plasma exchange (TPE) has been used in the treatment of thyroid storm, drug-induced hepatotoxicity and agranulocytosis, or patients with hyperthyroidism scheduled for emergency surgery. TPE is an effective method to reduce serum FT3, FT4, and TRAB levels in severe hyperthyroid conditions. Although TPE-related complications are rare, the risk of bleeding needs to be taken into consideration in patients who were scheduled for surgery within 24 h after TPE. In terms of reducing intraoperative bleeding, patients can be referred to surgery 24-48 h after TPE, or fresh frozen plasma transfusion can be the preferred treatment for emergency cases.

Seven cases of parathyroid carcinoma and review of the literature.

Parathyroid cancer is a rare malignancy and an uncommon cause of hyperparathyroidism. In the present study, we present seven cases of parathyroid carcinoma. The female ratio was 5/7 (71.4%). Median age at diagnosis was 47 years, and median follow-up duration was 60 months (IQR 29-75). Mean calcium level at diagnosis was 12.7 mg/dL (range, 11.3-13.9), and mean parathormone level was 1115 ng/L (IQR 287-1470). Two patients (28.5%) had a palpable neck mass. Coexisting brown tumor was present in three patients (42.8%), and nephrolithiasis was found in one patient (14.2). Average tumor size was 29 mm (IQR 28-40). Capsular and vascular invasion were detected in six patients (85.7%), intrathyroidal spread was observed in two patients (28.5%), and soft tissue invasion was seen in three patients (42.8%). Parathyroid adenoma was present in one patient and parathyroid gland hyperplasia in another patient. Adjuvant radiotherapy was given to four patients (57.1%). There was no metastatic disease or death. At the last visit, two patients had increased parathormone levels and no additional focus could be detected in either. Patients with markedly elevated parathormone and calcium levels and a palpable larger mass on the neck should be evaluated for parathyroid cancer. En bloc resection is the mainstay treatment. Despite contradictory results, adjuvant radiotherapy to the neck may help to reduce the risk of local recurrence in patients with microscopic residual parathyroid carcinoma.

Determinants of High-Dose Insulin Usage and Upper Extremity Muscle Strength in Adult Patients With Type 2 Diabetes.

OBJECTIVES: In this study, we aimed to determine the association between upper extremity muscle strength and insulin dose in patients with type 2 diabetes. METHODS: A total of 236 patients with type 2 diabetes under insulin treatment for at least 1 year were included in this cross-sectional study. Patients were divided into 3 groups based on their total daily insulin dose (TDID): group 1, TDID >2 U/kg/day or >200 units/day; group 2, TDID 1 to 2 U/kg/day or 51 to 199 U/day; and group 3, TDID <0.5 U/kg/day or 50 U/day. High-dose insulin use was defined as total daily insulin dose >2 U/kg or >200 U/day. Muscle strength was measured using a handgrip dynamometer. RESULTS: High-dose insulin users were younger and had higher measures of generalized and central obesity and glycated hemoglobin. There was no significant difference in muscle strength between the groups. Low muscle strength was seen in 26.7% of all patients. Patients with low muscle strength were older, had lower insulin dose treatment and had better glycemic control than patients with normal muscle strength. Handgrip strength was inversely correlated with age, body mass index and duration of diabetes, but not with TDID. CONCLUSIONS: Patients with type 2 diabetes with high-dose insulin use had similar upper extremity muscle strength measurements with standard-dose insulin users. Studies with more patients are needed to determine the relationship between muscle mass, muscle strength and high-dose insulin use.

Efficacy and Safety of Stereotactic Radiotherapy in Cushing's Disease: A Single Center Experience.

OBJECTIVE: To determine the efficacy and safety of stereotactic radiotherapy (RT) in patients with Cushing's disease (CD). METHODS: The study included 38 patients [31 patients who received gamma knife radiosurgery (GKS) and 7 patients who received cyberknife hypofractionated RT (HFRT)] with CD. Hormonal remission was considered if the patient had suppressed cortisol levels after low dose dexamethasone, normal 24-hour urinary free cortisol (UFC), and lack or regression of clinical features. RESULTS: Biochemical control after RT was observed in 52.6% of the patients with CD and median time to hormonal remission was 15 months. Tumor size control was obtained in all of the patients. There was no significant relationship between remission rate and laboratory, radiological and pathological variables except for preoperative UFC. Remission rate was higher in patients with lower preoperative UFC. Time to remission increased in parallel to postoperative cortisol and 1mg DST level. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to hormonal remission. CONCLUSION: In this current single center experience, postoperative cortisol and 1mg DST levels were found as the determinants of time to remission. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to biochemical control . This latter finding might suggest a radioprotective effect of cortisol lowering medication use on peri-RT period.