How Does The AJCC/TNM Staging System Eighth Edition Perform in Thyroid Cancer at A Major Middle Eastern Medical Center?

OBJECTIVE: The American Joint Committee on Cancer tumor node metastasis (TNM) staging system eighth edition (TNM-8) for differentiated thyroid cancer (DTC) has been introduced as a replacement for tumor node metastasis staging system seventh edition (TNM-7). We present the first study from a Middle Eastern population comparing these 2 versions of the TNM staging system. METHODS: We compared TNM-8 with TNM-7 in 701 patients with DTC seen during a 3-year period with a median age of 37 years (6-83) and a female-to-male ratio of 558 (79.6%) to 143 (20.4%). RESULTS: The number (%) of patients within each stage in TNM-7 and TNM-8, respectively, are as follows: stage I = 503 (71.6%) and 583 (83.2%), stage II = 52 (7.4%) and 81 (11.4%), stage III = 53 (7.6%) and 6 (0.9%), and stage IV = 93 (13.2%) and 31 (4.6%). Overall, 172 patients (24.5%) were downstaged in TNM-8 compared to that in TNM-7, as follows: 26, 30, and 24 patients from stages II, III, and IV in TNM-7 to stage I in TNM-8; 23 and 32 patients from TNM-7 stages III and IV to TNM-8 stage II; 6 patients from stage IVa in TNM-7 to stage III in TNM-8; and 31 patients from stage IVc in TNM-7 to stage IVb in TNM-8. TNM-7 and TNM-8 predicted the long-term outcome well (median follow-up, 7.9 years), but Kaplan-Meier analysis showed better separation of cancer-specific survival in TNM-8 compared to TNM-7. CONCLUSIONS: Compared with TNM-7, TNM-8 approximately downstaged a quarter of DTC patients and was more robust in separating the outcome of different stages over time.

The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis.

OBJECTIVE: To study the adrenocortical response to an acute coronavirus disease-2019 (COVID-19) infection. METHODS: Morning plasma cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate levels were measured in 28 consecutive patients with COVID-19 (16 men, 12 women, median age 45.5 years, range 25-69 years) on day 1 to 2 of hospital admission. These tests were repeated twice in 20 patients and thrice in 15 patients on different days. The hormone levels were correlated with severity of the disease. RESULTS: The median morning cortisol level was 196 (31-587) nmol/L. It was <100 nmol/L in 8 patients (28.6%), <200 nmol/L in 14 patients (50%), and <300 nmol/L in 18 patients (64.3%). The corresponding ACTH values had a median of 18.5 ng/L (range 4-38 ng/L), and the ACTH level was <10 ng/L in 7 patients (26.9%), <20 ng/L in 17 patients (60.7%), and <30 ng/L in 23 patients (82.1%). The repeated testing on different days showed a similar pattern. Overall, if a cutoff level of <300 nmol/L is considered abnormal in the setting of acute disease, 9 patients (32%) had cortisol levels below this limit, regardless of whether the test was done only once (3 patients) or 3 times (6 patients). When the disease was more severe, the patients had lower cortisol and ACTH levels, suggesting a direct link between the COVID-19 infection and impaired glucocorticoid response. CONCLUSION: Unexpectedly, the adrenocortical response in patients with COVID-19 infection was impaired, and a significant percentage of the patients had plasma cortisol and ACTH levels consistent with central adrenal insufficiency.

Efficacy and safety of empagliflozin: a "real-world" experience from Saudi Arabia.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new agents for treating type 2 diabetes. In addition to the glycemic benefits, these agents provide cardiorenal protection in patients with diabetes and without diabetes. There is consistent evidence that these agents increase the risk of genitourinary infections and dehydration, but randomized controlled trials have not included patients from the Middle East. OBJECTIVES: Determine the efficacy and safety of empagliflozin, specifically whether the genitourinary infection risk differs in our population and whether there is an increased risk of dehydration, ketoacidosis, hypoglycemia, and hospitalization with fasting. DESIGN: Retrospective review of medical records. SETTINGS: Department of medicine at tertiary care center. PATIENTS AND METHODS: We reviewed the electronic records of patients with type 2 diabetes who took empagliflozin from 1 December 2018 to 30 November 2019. We collected safety and efficacy data for 12 months from the initiation of treatment. MAIN OUTCOMES MEASURES: Glycemic and weight loss efficacy, risk of hospitalization due to hypoglycemia, dehydration, and genitourinary infections. SAMPLE SIZE: 637 patients. RESULTS: We observed an improvement in glycated hemoglobin, a 4.2% weight loss, improved left ventricular function, stable serum creatinine, and reduced albuminuria. Our patients did not have an increased risk of genitourinary infections, hypoglycemia, dehydration, ketoacidosis, or hospitalizations. Fasting did not increase the incidence of adverse events. CONCLUSIONS: Empagliflozin is safe and effective in our local population. We hypothesize that glycosuria induced by empagliflozin is not the sole contributor to the increased risk of genitourinary infections. Local hygiene and circumcision might reduce this risk. Empagliflozin can be used safely during fasting. LIMITATIONS: Retrospective design. CONFLICT OF INTEREST: None.

COVID-19 infection and thyroid function.

Context: COVID-19 is a new viral infection affecting mainly the respiratory system with involvement of many other organs. Thyroid dysfunction has been described in COVID-19 but data are still unclear and conflicting on its frequency, severity and relationship with the outcome. Patients and methods: We assessed thyroid function tests (TFT) in 50 patients admitted to our institution with confirmed COVID-19 infection. We excluded patients known to have thyroid diseases or taking drugs that may affect thyroid function. Serum free thyroxine (FT4), thyrotropin (TSH) and triiodothyronine (T3) were measured once or more during the first 10 days after admission. In about 50 % of the cases, a follow up TFT was obtained during the first year after discharge (at a median follow up of 6 months). Results: We included 50 patients, 29 males (58 %) and 21 females (42 %). The median age was 47 years (range 25-89). Overall, TFTs were completely normal in all patients except for minor transient abnormalities in 5 patients (10 %) as follows: three patients had a mild transient elevated TSH, one had a mild transient suppressed TSH and one patient had a mildly low FT4 with normal TSH. There were no differences between the follow up TFTs obtained after discharge and TFTs obtained during admission in the acute phase. Conclusion: In this study, thyroid dysfunction during acute COVID-19 infection was rare, mild and transient. However, the study might not be powered enough to detect an association between thyroid dysfunction and the severity of illness and further studies are needed to assess this issue. Late-onset thyroid dysfunction does not seem to occur in COVID-19 infection during the next year after discharge.

Natural Course of the American Thyroid Association Response to Therapy Statuses (Dynamic Risk Stratification) in Differentiated Thyroid Cancer.

The concept of response to therapy in differentiated thyroid cancer (DTC) was introduced as a dynamic risk stratification used to assess the status of the disease at the time of the evaluation during the follow-up and the risk of recurrence in the future. Our aim in this study was to evaluate the natural course over time of different response to therapy statuses. METHODS: We studied 501 nonselected DTC patients (102 males and 399 females) with a median age of 37 years (interquartile range [IQR] 29-48). All patients underwent near-total or total thyroidectomy followed by I-131 ablation (initial management). RESULTS: Of the 501 patients, 387 patients (77.2%) did not have any additional therapuetic interventions after the initial management. In this group, the response to therapy status at the time of the first evaluation after I-131 (median 17 months, IQR 14-22) was an excellent response in 258 (66.7%), an indeterminate response in 101 (26.1%), biochemically incomplete in 17 (4.4%), and structurally incomplete in 11 patients (2.8%). The status changed spontaneously without any intervention in many of them. At the last follow-up visit (median duration 101 months, IQR 71-126), 357 patients (92.2%) achieved an excellent response, 4 (1%) an indeterminate response, 8 (2.1%) a biochemically incomplete status, 16 (4.1%) a structurally incomplete status, and 2 (0.5%) died secondary to DTC with a structurally incomplete status. The response to therapy in the other 114 patients who underwent additional interventions changed from before intervention to the last evaluation as follows: excellent response, 0 to 60 patients (52.6%), indeterminate response, 20 (17.5%) to 1 patient (0.9%), biochemically incomplete 25 (21.9%) to 10 patients (9%), and structurally incomplete 69 (60.5%) to 43 patients (37.7%). Overall, at the last evaluation, 417 (83.2%) were in an excellent response, 5 (1%) in an indeterminate response, 18 (3.6%) in a biochemically incomplete status, 50 (10.2%) in a structurally incomplete status, and 11 (2.2%) died secondary to DTC with a structurally incomplete status. CONCLUSIONS: The response to therapy at the initial evaluation is predictive of the long-term outcome. Most patients with the indeterminate response and some in the biochemically incomplete statuses spontaneously regress to an excellent status. Mortality and progression of DTC occur mostly in the structurally incomplete status.

Course and Predictive Factors of Incomplete Response to Therapy in Low- and Intermediate-Risk Thyroid Cancer.

CONTEXT: Controversy surrounds the extent and intensity of the management of American Thyroid Association (ATA) intermediate- and low-risk patients with differentiated thyroid cancer (DTC). Understanding the natural history and factors that predict outcome is important for properly tailoring the management of these patients. OBJECTIVE: This work aims to study the natural course and predictive factors of incomplete response to therapy in low- and intermediate-risk DTC. PATIENTS AND METHODS: We studied a cohort of 506 consecutive patients [418 women (82.6%) and 88 men (17.4%)] with low and intermediate risk with a median age of 35 years (interquartile range [IQR], 27-46 years). We analyzed the natural course and the predictive factors of biochemically or structurally incomplete response. RESULTS: Of 506 patients studied, 297 (58.7%) patients were in the low-risk group and 209 (41.3%) were in the intermediate-risk group. Over a median follow-up of 102 months (IQR, 66-130 months), 458 (90.5%) patients achieved an excellent response, 17 (3.4%) had a biochemically incomplete status, and 31 (6.1%) had a structurally incomplete status. In univariable and multivariable analyses, age (≥ 33 years) (P < .0001, odds ratio 1.06 [1.04-1.08]) and lateral lymph node metastasis (LNM; P < .0001, odds ratio 3.2 [1.7-5.9]) were strong predictive factors for biochemically and structurally incomplete response to therapy. Sex, tumor size, multifocality, extrathyroidal extension, and lymphovascular invasion did not predict incomplete response to therapy. CONCLUSIONS: Patients with low- and intermediate-risk DTC have favorable outcomes. Age and lateral LNM are strong predictors of an incomplete response to therapy. This suggests that older patients and those with LNM should be managed and followed up more actively than younger patients and those without LNM.

Comparing the utility of 30- and 60-minute cortisol levels after the standard short synacthen test to determine adrenal insufficiency: A retrospective cross-sectional study.

Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 µg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level.Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value.Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ±â€Š286.58, 722 ±â€Š327.11, and 827 ±â€Š369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST (P-value < .0001).Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226 nmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.