Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy.

PURPOSE: This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. METHODS: A clinical review. RESULTS: Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. CONCLUSION: Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit.

Molecular characteristics of isthmus papillary thyroid cancers: Supporting evidence for unfavorable clinical behavior.

BACKGROUND: Previous studies demonstrate isthmus thyroid nodules are more likely to be malignant than lobar nodules. Additional data suggest that isthmus papillary thyroid cancers (PTCs) are more aggressive than lobar PTCs. We hypothesize that isthmus PTCs have a more unfavorable molecular profile. METHODS: The Cancer Genome Atlas (TCGA) database was queried to analyze clinical, mutation and gene expression data of isthmus PTCs compared to non-isthmus PTCs. RESULTS: We analyzed characteristics of 472 â€‹PTCs, including 19 isthmus PTCs. There were no significant differences between isthmus and non-isthmus PTC demographic and clinical variables or the frequency of RAS family, fusion driver, TERT, and tumor suppressor gene mutations. There was a trend towards increased BRAF mutations (68% vs 55%, p â€‹= â€‹0.28). A more aggressive gene expression profile was observed in isthmus PTC compared to lobar/multifocal PTC with differences in ERK score (19.4 vs 7.71, p â€‹< â€‹0.05) and TDS score (-0.58 vs 0.02, p â€‹< â€‹0.05). CONCLUSIONS: These results provide a possible molecular explanation for the more aggressive behavior reported in isthmus PTCs.

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.

Papillary Thyroid Cancer in Thyroglossal Duct Cysts: A Pictorial Review and Case Series.

ABSTRACT: Thyroglossal duct cyst is the most common congenital neck mass, but the incidence of malignancy within a thyroglossal duct cyst is rare, estimated at 1%. Most cancers arising within thyroglossal duct cysts are incidentally detected after surgical excision. We present the preoperative radiologic findings of 8 patients with papillary thyroid cancer arising within a thyroglossal duct cyst, as evaluated on ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scan.

Protocol for Development of American Association of Clinical Endocrinology Clinical Practice Guidelines and Consensus Statements: Summary of Methodology, Process, and Policy - 2023 Update.

OBJECTIVE: This 2023 updated protocol summarizes the American Association of Clinical Endocrinology's (AACE's) new framework for the development of clinical practice guidelines and other guidance documents that includes changes to methodology, processes, and policies. METHODS: AACE has critically reviewed its development processes for guidance documents over the last several years against the National Academy of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines and the Council of Medical Specialty Societies Principles for Development of Specialty Society Clinical Guidelines to determine areas for improvement. RESULTS: The new AACE framework for development of guidance documents incorporates many changes, including a revised conflicts of interest (COI) policy; strengthened commitment to collection of disclosures and management of relevant COI during development; open calls to membership for authors; new requirements for authors; new diversity, equity, and inclusion (DEI) policy; new empanelment process that incorporates consideration of DEI; and adoption of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to increase the quality of evidence assessment and standardize recommendation grades and statements, among other improvements. CONCLUSIONS: AACE has revised its policies and adopted a completely new methodology for guideline development in support of the mission to elevate the practice of clinical endocrinology to improve patient care. With the use of an evidence-based medicine framework and by continually assessing and improving its processes for development of guidance, AACE strives to deliver trustworthy, unbiased, and up-to-date information that ensures clinician and patient confidence in AACE content. Further, AACE hopes that these enhancements foster a more collaborative approach to development and increase engagement with the worldwide medical community to improve global health.

American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach.

OBJECTIVE: The aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies. METHODS: A literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus. RESULTS: Immunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency. CONCLUSION: In recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions.

OBJECTIVE: The objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes. METHODS: A literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review. RESULTS: Minimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer. CONCLUSION: Surgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.