High-Specific-Activity 131 I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma.

PATIENTS AND METHODS: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background. RESULTS: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis. CONCLUSIONS: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.

The effect of hormonal secretion on survival in adrenocortical carcinoma: A multi-center study.

BACKGROUND: Current evidence suggests that cortisol secreting adrenocortical carcinoma has worse prognosis compared to non-secreting adrenocortical carcinoma. However, the effect of other secretory subtypes is unknown. METHODS: This multicenter study within the American-Australian-Asian Adrenal Alliance included adults with adrenocortical carcinoma (1997-2020). We compared overall survival and disease-free survival among cortisol secreting, mixed cortisol/androgen secreting, androgen secreting, and non-secreting adrenocortical carcinoma. RESULTS: Of the 807 patients (mean age 50), 719 included in the secretory subtype analysis: 24.5% were cortisol secreting, 13% androgen secreting, 28% mixed cortisol/androgen, 32.5% non-secreting, and 2% were mineralocorticoid secreting. Median overall survival and disease-free survival for the entire cohort were 60 and 9 months, respectively. Median overall survival was 36 months for cortisol, 30 for mixed, 60 for androgen secreting, and 115 for non-secreting adrenocortical carcinoma, P < .01. Median disease-free survival was 7 months for cortisol, 8 for mixed, 10 for androgen, and 12 for non-secreting adrenocortical carcinoma, P = .06. On multivariable analysis of age, sex, Ki67%, secretory subtype, stage, resection, and adjuvant therapy, predictors of worse overall survival were older age, higher Ki67%, stage IV, mixed secreting, R1, and no adjuvant therapy, P < .05. On subgroup analysis of R0 resection, predictors of worse overall survival included older age and higher Ki67%. Ki67% ≥40, stage III and cortisol secretion were associated with worse disease-free survival. CONCLUSION: Mixed cortisol/androgen secreting adrenocortical carcinoma was associated with worse overall survival, while cortisol or androgen secreting alone were not. Notably, among patients after R0 resection, secretory subtype did not affect overall survival. Cortisol secreting adrenocortical carcinoma demonstrated worse disease-free survival. Ki67% remained a strong predictor of worse overall survival and disease-free survival independent of stage.

Adjuvant therapy in adrenocortical carcinoma: prognostic factors and treatment options.

Adrenocortical carcinoma (ACC) is a rare cancer with high recurrence rates and heterogeneous clinical behavior. The role of adjuvant therapy remains unclear because of the challenges in collecting high-quality data for a rare cancer. The current treatment recommendations and guidelines for adjuvant therapy are mostly derived retrospectively from national databases and the treatment outcomes of patients seen in referral centers. To better select patients for adjuvant therapy, multiple factors need to be considered including staging, markers of cellular proliferation (such as Ki67%), resection margins, hormonal function, and possibly genetic alterations of the tumor as well as patient-related factors such as age and performance status. Adjuvant mitotane remains the most commonly used adjuvant therapy in ACC based on clinical practice guidelines, though emerging data from ADIUVO trial (mitotane vs observation in low-risk ACC) suggest that mitotane use in low-risk patients may not be needed. An ongoing clinical trial (ADIUVO-2) is evaluating the role of mitotane vs mitotane combined with chemotherapy in high-risk ACC. The use of adjuvant therapy has been controversial but can be justified in select patients with positive resection margins or after the resection of localized recurrence. A prospective study is needed to study the role of adjuvant radiation in ACC as radiation is expected to help only with local control without impact on distant microscopic metastases. There are no recommendations or published data about using adjuvant immunotherapy in ACC, but this may be a future study after establishing the efficacy and safety profile of immunotherapy in metastatic ACC.

Post-bariatric Surgery Outcomes and Complications in Patients with Celiac Disease: a Matched Case-Control Study.

PURPOSE: The shift towards an obese phenotype in celiac disease (CD) patients increases risk of morbidity and mortality. Bariatric surgery (BS) is the gold standard treatment for obesity. Few studies have explored the role of BS in patients with CD. This study aimed to assess the effectiveness and safety of BS in this population. MATERIAL AND METHODS: This is a retrospective matched case-control (1:5) study of adult patients with confirmed CD who underwent BS at our institution from 1998 to 2018. Demographics, operative data, post-operative outcomes, complications, and nutritional parameters were collected. RESULTS: Seventy-eight patients (mostly Caucasian females) were included. Thirteen had confirmed CD and were compared with 65 controls. The most common type of BS was the RYGB. The percent of total body weight loss (%TWL) was similar for both groups at 6, 12, 18, 24, and 36 months, with the highest weight loss being at 12 months: %TWL 28.4 (20.2-38.4) for CD, n=13; vs. 29.1 (19.6-39.3) for non-CD, n=49; p=0.8. Obesity-associated co-morbidities greatly and comparably improved in both groups. Patients with CD had no complications after BS. Post-BS malodorous and oily stools were more common among patients with CD (23.1% vs. 4.6%, p=0.03). Micronutrient deficiencies were common and comparable among both groups with iron and vitamin D being the most common deficiencies. Gluten-free diet (GFD) non-adherence post-operatively was associated with a higher incidence of post-BS abdominal pain (60.0% vs. 0.0%, p=0.012). CONCLUSIONS: BS is safe and effective in patients with CD. Close monitoring is necessary to ensure compliance with GFD and vitamin supplementation. KEY POINTS: • Bariatric surgery leads to significant weight loss in celiac disease (CD) patients. • Mid- and long-term weight loss does not differ between patients with and without CD. • Obesity-associated co-morbidities significantly improve after surgery in CD patients. • The incidence of post-surgical complications is not higher in CD patients.

Thyroid Storm in a Patient With COVID-19.

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19. METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed. RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with proptosis and chemosis, tachycardia, diffusely enlarged goiter with bruit, and fine tremor. Laboratory results demonstrated a thyroid-stimulating hormone level of <0.01 mIU/L (normal range [NR], 0.44-5.3 mIU/L), free thyroxine level of 5.34 ng/dL (NR, 0.64-1.42 ng/dL), total triiodothyronine level of 654 ng/dL (NR, 87-178 ng/dL), and thyroid-stimulating immunoglobulin level of 7.18 IU/L (NR, 0.00-0.55 IU/L). Thyroid ultrasound revealed heterogeneous echotexture with increased vascularity. Nasopharyngeal COVID-19 testing was positive. She was treated promptly with propranolol, propylthiouracil, and hydrocortisone with improvement in symptoms, and later switched to methimazole. Her COVID-19 course was uncomplicated, and she left the hospital with minimal respiratory symptoms. CONCLUSION: Thyroid storms are one of the more prevalent endocrine emergencies and are often precipitated by acute events including infections. Patients with thyroid storms may have concomitant SARS-CoV-2 infection that could influence the clinical course and severity of the disease. In patients with symptoms of thyrotoxicosis and respiratory symptoms, clinicians should consider performing a COVID-19 test.

Initial and subsequent 3-year cost after hospitalization for first acute ischemic stroke and intracerebral hemorrhage.

AIMS: To examine 1) the major drivers of index hospitalization and 3-year post-acute follow-up care, 2) cost for rehabilitation and homecare, and 3) indirect cost from lost productivity after acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Retrospective study of adults hospitalized with AIS (n = 811) and ICH (N = 145) between 2003 and 2014. Direct costs standardized to Medicare reimbursement rates were captured for hospitalization and 3-year follow-up or death. Adjusted cost estimates were assessed using generalized linear modeling with gamma distribution. Costs for rehabilitation, home healthcare, and lost productivity were assessed using sets of cost captured through literature review. RESULTS: Calculated as mean cost per person: hospitalization $18,154 for AIS and $24,077 for ICH; monthly 3-year aggregate $5138 for AIS and $8172 for ICH; 3-year inpatient rehabilitation $4185 for AIS and $4196 for ICH; homecare $19,728 for AIS and $14,487 for ICH; indirect cost from lost productivity $77,078 for AIS and $56,601 for ICH. Age < 55 years, being non-white, and stroke severity were strongly associated with greater hospitalization cost for AIS and ICH. Hyperlipidemia incurred lower while cancer, coronary artery disease, asthma/chronic obstructive pulmonary disease, heart failure, and anemia incurred higher 3-year aggregate cost for AIS. Cancer and diabetes mellitus incurred higher 3-year aggregate cost for ICH. CONCLUSIONS: We provide estimates of direct and indirect costs incurred for acute and continuing post-acute care through a 3-year follow-up period after first-ever AIS and ICH with important comparisons for predictors between index hospitalization and 3-year post-stroke costs.

Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis.

Objectives: The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival. Methods: Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2). Results: In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58-0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups. Conclusions: In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.

Drivers of the Decision to Biopsy and Follow-Up of Small Suspicious Thyroid Nodules.

OBJECTIVE: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center. METHODS: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied. RESULTS: We identified 141 nodules in 129 patients: mean age 58.1±14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5-188.7]), radiology recommendation for biopsy (OR 2.6 [1.8-3.9]) and radiology report of the nodule as "suspicious" (OR 2.1 [1.4-3.2]). Patient's age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations. CONCLUSION: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules. ABBREVIATIONS: ATA = American Thyroid Association; OR = odds ratio.

Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis.

OBJECTIVE: To examine the effect of HLP, defined as having a pre-existing or a new in-hospital diagnosis based on low density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL during index hospitalisation or within the preceding 6 months, on all-cause mortality after hospitalisation for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and to determine whether HLP modifies mortality associations of other competing comorbidities. A systematic review and meta-analysis to place the current findings in the context of published literature. DESIGN: Retrospective study, 1:1 propensity-score matching cohorts; a meta-analysis. SETTING: Large academic centre, 1996-2015. PARTICIPANTS: Hospitalised patients with AMI or ADHF. MAIN OUTCOMES AND MEASURES: All-cause mortality and meta-analysis of relative risks (RR). RESULTS: Unmatched cohorts: 13 680 patients with AMI (age (mean) 68.5 ± (SD) 13.7 years; 7894 (58%) with HLP) and 9717 patients with ADHF (age, 73.1±13.7 years; 3668 (38%) with HLP). In matched cohorts, the mortality was lower in AMI patients (n=4348 pairs) with HLP versus no HLP, 5.9 versus 8.6/100 person-years of follow-up, respectively (HR 0.76, 95% CI 0.72 to 0.80). A similar mortality reduction occurred in matched ADHF patients (n=2879 pairs) with or without HLP (12.4 vs 16.3 deaths/100 person-years; HR 0.80, 95% CI 0.75 to 0.86). HRs showed modest reductions when HLP occurred concurrently with other comorbidities. Meta-analyses of nine observational studies showed that HLP was associated with a lower mortality at ≥2 years after incident AMI or ADHF (AMI: RR 0.72, 95% CI 0.69 to 0.76; heart failure (HF): RR 0.67, 95% CI 0.55 to 0.81). CONCLUSIONS: Among matched AMI and ADHF cohorts, concurrent HLP, compared with no HLP, was associated with a lower mortality and attenuation of mortality associations with other competing comorbidities. These findings were supported by a systematic review and meta-analysis.