The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with decompensated heart failure.

The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with acute decompensated heart failure (HF) has not been evaluated yet. We conducted retrospective cohort analyses of outcomes among 231 consecutive patients with treated hypothyroidism who were admitted to internal medicine departments of Shamir Medical Center with HF (2011-2019). Patients were divided into three groups according to their thyroid-stimulating hormone (TSH) levels: well treated (TSH: 0.4-4 mIU/L), overtreated (TSH: <0.4 mIU/L), and undertreated (TSH: >4 mIU/L). The main outcomes were mortality and recurrent hospitalization within 3 months. Among 231 patients, 106 were euthyroid, 14 were overtreated, and 111 undertreated. Patients' mean age was 79.8 ± 9.4 years. In-hospital mortality occurred in 4.7% in euthyroid patients, 14.3% in the overtreated group, and 10.7% in the undertreated group (p = 0.183). Differences in 30-day (p = 0.287) and 90-day (p = 0.2) mortality or recurrent hospitalization (p = 0.438) were not significantly different as well. However, in patients who were markedly undertreated and overtreated (TSH: >10 mIU/L or below 0.4 mIU/L) compared with 0.4-10 mIU/L, a significant increase in 90-day mortality was observed (33.3% vs 15.1% p = 0.016). Treatment status was independently associated with 90-day mortality after controlling for confounders with an adjusted odds ratio of 3.55 (95% confidence interval: 1.39-9.06). Although mild under- or overtreatment of hypothyroidism does not have a significant detrimental effect on hospitalization outcomes of patients with acute decompensated HF, markedly under- and overtreatment are independently associated with rehospitalizations and 90-day mortality. Larger cohorts are needed to establish the relationship between treatment targets and hospitalization outcomes of patients at risk for HF hospitalization.

Is Familial Nonmedullary Thyroid Cancer A More Aggressive Type of Thyroid Cancer?

OBJECTIVES: Familial non-medullary thyroid cancer (FNMTC) is a distinct entity, increasingly diagnosed. By lacking an accurate genetic diagnostic test, its diagnosis is currently clinically based, with an ongoing debate over whether it has a more aggressive clinical behavior than sporadic non-medullary thyroid cancer (SNMTC). We seek to compare in this study, the clinicopathological variables, and the outcome of FNMTC versus SNMTC patients. METHODS: We retrospectively searched a database of 465 patients that underwent thyroidectomy at Assaf Harofeh Medical Center (91.4% between 1990 and 2019) for demographics, risk factors, medical history, diagnostic workup, primary treatment, follow-up, and disease outcome data. We compared 47 FNMTC versus 321 SNMTC patients, and FNMTC patients with ≥2 (n = 34) versus ≥3 (n = 13) first-relative affected members. RESULTS: There were no significant differences in demographics, histopathology, TNM stage, treatment, and disease outcome between the FNMTC and SNMTC groups. The T2 and T4 tumor stage in the ≥3-member group were 25% and 8.3% compared to 0% and 0% in the two-member group (P = .02 and P = ns, respectively). Also, LN involvement was significantly higher in the ≥3-member group (61.6% vs. 24.2%, respectively; P = .036). CONCLUSION: FNMTC is not a more aggressive disease than SNMTC, but this may not apply for the ≥3-affected-relatives group. A large multicenter study including only families with three or more affected relatives is needed. Until then, a family history of NMTC should not be overlooked. LEVEL OF EVIDENCE: 3/5 Laryngoscope, 131:E677-E681, 2021.

The Risk of Bone Fractures in Post-Poliomyelitis Patients Transitioning to Middle Adulthood.

ObjectiveWhile osteoporotic fractures are reported in up to 40% of adults with post-poliomyelitis syndrome (PPS), clinical guidelines regarding bone mineral density (BMD) and indications for treatment are scarce. We investigated the characteristics of PPS patients, focusing on fractures and osteoporosis as the primary outcomes. METHODS: A cross-sectional retrospective data analysis from medical records of 204 PPS patients regarding their clinical characteristics and long-term outcome, with emphasis on bone metabolism status. RESULTS: Our cohort included 53% women; mean age was 65 years at study entry and 1.7 years at the diagnosis of acute poliomyelitis. The lower limb was involved in 97.5% of patients, and the BMD in the affected limb tended to be lower than the unaffected, with a mean T-score of -1.64 vs. -1.19, respectively (P = .06). Recurrent falls were documented in 39.2% of patients, and osteoporosis in 20.6%, being more frequent in women (P = .003) and patients with fractures (P = .002). At least one fracture occurred in 52.2% of patients, and more than one in 40.3%. The median age for the first fracture was 57.5 years (range, 30 to 83 years), and most fractures occurred in the affected limb (73.2%). CONCLUSIONS: Underdiagnosis and delayed treatment of osteoporosis in late-adulthood post-poliomyelitis patients underlie the need for comprehensive clinical guidelines to manage these patients, including recommendations on bone health assessment, medical treatment, and their inclusion as a high-risk group for bone fractures.

A 2017 SURVEY OF THE CLINICAL PRACTICE PATTERNS IN THE MANAGEMENT OF RELAPSING GRAVES DISEASE.

OBJECTIVE: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists. METHODS: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse. RESULTS: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI ( P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment. CONCLUSION: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin.

Adherence to ATA 2015 guidelines in the management of unifocal non-invasive papillary thyroid cancer: a clinical survey among endocrinologists and surgeons.

BACKGROUND: Despite updated guidelines, management of thyroid nodules remains controversial. We aim to check implementation of new guidelines by ear-nose-throat (ENT) surgeons and endocrinologists. METHODS: A questionnaire was e-mailed including demographic data and an index case: a healthy 26-year-old women with a 3-cm Bethesda III (B3) atypia of undetermined significance solitary nodule and eventually papillary thyroid cancer (PTC). RESULTS: Respondent rate was 50.5%, 93 endocrinologists, 55 surgeons. For this case, 77.4% would repeat fine-needle aspiration (FNA), 25.3% order molecular analysis and 22.6% do surgery. If repeated FNA remained B3, 51% would choose surgery, 17.3% molecular analysis and 31.6% follow-up only. If repeated FNA was B6, 58.5% would recommend total (TTx) and 41.5% hemithyroidectomy (HTx). In pathologically confirmed PTC after HTx, 42.4% would recommend completion, 26.8% radioactive iodine (RAI) treatment. For a > = 4-cm tumor, 49.2% would recommend TTx. For a tumor 2-4 cm, 41% would recommend TTx. Variables favoring TTx were family history and radiation exposure. Only 17.4% would prefer TTx when small benign contralateral tumor is present. Reassessment at 1 year with undetectable thyroglobulin (Tg) included stimulated Tg (stTg) (72.5%), neck US only (27.5%) and combined US-stTg (59.4%); only 10.3% would order a diagnostic scan. For recurrence in two (13-9 mm) lymph nodes, 59.3% recommend reoperation, 16.3% RAI and 24.4% active surveillance. There were no major differences between endocrinologists and ENT surgeons. CONCLUSIONS: We report a considerable lack of adherence to new guidelines, with only 50% recommending HTx for a 4-cm unifocal low-risk PTC tumor.

Thyroid Disease in Pregnancy: A Clinical Survey among Endocrinologists, Gynecologists, and Obstetricians in Israel.

OBJECTIVES: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel. METHODS: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified. RESULTS: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions. CONCLUSIONS: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.

Reassessment of Differentiated Thyroid Cancer Patients Using the Eighth TNM/AJCC Classification System: A Comparative Study.

BACKGROUND: Facing the prevailing concept that increased diagnosis with no change in mortality drives the increased incidence of differentiated thyroid cancer (DTC), considerable modifications have been introduced in the new edition of the tumor node metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to compare a group of DTC patients before and after restaging, by mortality, disease severity, and disease outcomes. METHODS: DTC patients (N = 433) were restaged according to the eighth TNM/AJCC edition, and the results were compared to the seventh edition for clinicopathologic data, treatment modalities, and disease outcomes. RESULTS: When switched to the eighth edition, 97.5% of patients fell into stage I-II compared to 76.4% before, and only 11/102 patients remained in stages III-IV. Disease-specific mortality was recorded in 11/433 patients, six of whom were in stages I-II upon restaging, compared to none before (p > 0.05). In addition, more recurrences were seen in stages II (p = 0.05) and III (p = 0.03) using the eighth edition compared to the seventh edition. Stage II was affected the most, with recurrence risk increasing from 29% to 76% (p = 0.001) and persistence at last visit from 19% to 43% when switching to the eighth edition (p = 0.01). Considering stages I and II together, the recurrence risk increased from 16.7% to 28.2% (p = 0.01), lymph node metastases from 1.9% to 26.5% (p = 0.01), and persistence at last visit from 10% to 15% (p > 0.05). Of the 129 patients in the 45- to 54-year-old age group, 53 shifted to stage I (20 from stage II, 29 from stage III, and 4 from stage IV) and five shifted to stage II (all from stage IV). When comparing this age group in stage II only, the eighth edition showed more lymph node metastases (p = 0.001), more distant metastases (p = 0.003), higher recurrence risk (p = 0.002), and more persistence at the last visit (p > 0.05). CONCLUSION: The eighth TNM/AJCC edition provides a more accurate system to discriminate mortality and persistence in DTC patients. Yet, the severity of disease, especially in the 45- to 55-year-old age group and in stage II patients, should not be underestimated following the downstaging of these patients.