A Nationwide, Population-based Study of Intelligence and Hearing Loss Among 3,104,851 Adolescents.

PURPOSE: Epidemiological studies have demonstrated a relationship between general intelligence (GI) in youth and hearing loss (HL). However, no large-scale study assessed the relations of GI in late adolescence with conductive HL and sensorineural HL, stratified by severity. This study examined the connection between HL and GI in late adolescence. METHODS: Cross-sectional study on mandatory pre-military recruitment data recorded during 1967-2019 of patients aged 17-19. We compared GI between sensorineural HL, conductive HL, and those with normal hearing. In addition, we used logistic regression to measure the associations between HL and GI after adjuring for age, sex, education, and socioeconomic status. RESULTS: Among 3,104,851 adolescents assessed, 20,075 (0.6%) exhibited hearing loss (HL). We categorized general intelligence (GI) into three levels for analysis: low (lowest category), medium, and high (reference category). Adjusted odds ratios (ORs) revealed that sensorineural HL (SNHL) was associated with lower GI levels, with ORs ranging from 1.3 [95% CI 1.4-1.2] for the lowest GI category to 1.1 [95% CI 1.15-0.04] for the medium category. Conductive HL (CHL) also demonstrated significant associations, with ORs from 1.8 [95% CI 1.9-1.6] for the lowest GI level to 1.1 [95% CI 1.2-0.9] for medium. Further analysis revealed a statistically significant, severity-dependent relationship between SNHL and the odds of being in the lowest GI quartile (Q1). Specifically, the odds ratios for SNHL ranged from 1.2 [95% CI 1.1-1.3] to 1.3 [95% CI 1.1-1.5] as severity increased, indicating a strong link between greater SNHL severity and reduced cognitive performance. In contrast, CHL did not show a consistent correlation between its severity and GI outcomes, with an OR of 1.6 [95% CI 1.2-2.3] across severity levels. CONCLUSION: We report a strong relationship between HL and GI in late adolescence. Sensorineural HL, but not conductive HL, demonstrated a severity-based decline in GI. The results highlight the value of early, specifically targeted therapies for HL that consider its etiology and degree.

Efficacy and safety of SENS-401 in sudden sensorineural hearing loss: The AUDIBLE-S randomized placebo-controlled phase IIb trial.

PURPOSE: Safety and efficacy of SENS-401, a serotonin type 3 (5-HT3) receptor antagonist and calcineurin inhibitor, in patients with acute sudden sensorineural hearing loss (SSNHL). METHODS: Multicentre randomized, double blind, placebo-controlled trial enrolled adult subjects with sudden sensorineural hearing loss (SSNHL) or unilateral/bilateral acute acoustic trauma leading to SSNHL within 96 h of disease onset. Subjects were randomly assigned to one of the three oral dose groups: 29 mg, 43.5 mg or placebo given twice daily for 28 days. The primary endpoint was the change from baseline in Pure Tone Average (PTA) in the affected ear to the end of treatment visit (day 28). Subjects were further followed up 8 weeks after the end of the treatment period (day 84). RESULTS: A total of 115 subjects were randomized. SENS-401 was well tolerated. Although the primary efficacy endpoint was not met at day 28, post-hoc analyses revealed clinically significant and meaningful efficacy outcomes with SENS-401 when compared to placebo in a substantial group of participants diagnosed with idiopathic SSNHL and who had received corticosteroid treatment. Notable improvements were observed in the PTA change from baseline, the complete hearing recovery rate, and the Word Recognition Score (WRS), particularly at day 84. The responder rate consistently favored treated subjects over those who received the placebo. CONCLUSION: While the primary endpoint was not achieved at the end of the treatment period, the study revealed consistently positive efficacy results of clinical relevance in patients with idiopathic SSNHL who received SENS-401, particularly in the 8-weeks follow-up phase after the completion of the treatment.

Quality of life following lobectomy versus total thyroidectomy is significantly related to hypothyroidism.

OBJECTIVE: The aim of the present study was to investigate the differences in quality of life (QOL) following complete or partial thyroidectomy and with regard to thyroid hormone replacement (LT4) therapy. STUDY DESIGN: Patients who underwent thyroidectomy were asked to complete the validated thyroid-specific ThyPRO QOL questionnaire at least 6 months following surgery. SETTING: Tertiary medical center. METHODS: Thyroid specific QOL questionnaire analysis. RESULTS: A total of 190 patients completed the ThyPRO questionnaire. Of them 89 patients had complete thyroidectomy and 101 patients had unilateral thyroid lobectomy. The total thyroidectomy group had significantly worse overall QOL self-assessment score than the lobectomy patients (p < 0.0001). Patients receiving LT4 therapy regardless of the extent of surgery, reported worse QOL compared to patients not receiving LT4. CONCLUSIONS: Quality of life following thyroid surgery is significantly related to hypothyroidism and the requirement for LT4 therapy, rather to the extent of surgery. The best QOL was reported in patients treated with lobectomy who did not require LT4 therapy.

Acute mastoiditis in infants younger than 6 months: is an alternative treatment protocol needed?

OBJECTIVES: Several studies have reported that younger children suffer from increased incidence and more severe episodes of acute mastoiditis (AM) than older children, whereas other researchers have found the opposite. The aim of our study was to describe the occurrence, clinical, and microbiological aspects of AM in children 6 months or younger, and compare them with the results in an older reference age band. METHODS: The medical files of children hospitalized with a diagnosis of AM during 2001-2016 were retrospectively reviewed. Diagnosis of AM was based on the presence of clinical signs of acute otitis media (AOM) accompanied by two or more of the following: auricle protrusion, retro-auricular erythema, swelling, and local tenderness. Children were divided into two age bands, 6 months or younger, and older than 6 months. RESULTS: Fifty patients in the young age band and 335 in the older reference age band were included. Bilateral AOM was identified in 14 (28%) children under 6 months, and 50 (14.9%) in the reference age band (p < 0.001). Fever, mean WBC, and CRP values were similar in both age bands; 4 (8%) children under 6 months had pre-auricular/zygomatic area swelling, as compared to 1(0.02%) in the reference age band (p < 0.001). Complication rates (subperiosteal abscess, sinus vein thrombosis, and epidural abscess) were similar in both age bands. All children were treated with myringotomy and IV antibiotics. Cortical mastoidectomy with the insertion of ventilation tube was performed in 10 (20%) children in the younger age band and 58(17.3%) in the reference age band. Streptococcus pneumoniae was the most common (38%) isolated bacteria in the younger age band, and Group A streptococcous (GAS) (20.6%) in the reference age band. CONCLUSIONS: AM in children 6 months or younger has similar presentation and characteristics as in older children. Pre-auricular swelling and bilateral AOM are more typical in the younger age band; Streptococcus pneumoniae is the most common pathogen in the younger children. We suggest that the treatment approach should be the same for both groups.

Accuracy, predictability and prognostic implications of fine-needle aspiration biopsy for parotid gland tumours: A retrospective case series.

OBJECTIVE: To evaluate the precision and utility of fine-needle aspiration (FNA) in differentiating between benign and malignant parotid tumours, and the implications of FNA results on management and outcomes. DESIGN: Retrospective case series. SETTING: Tertiary medical centre. PARTICIPANTS: All adults who underwent preoperative FNA, followed by postoperative histological examination, between 1986 and 2014. MAIN OUTCOME MEASURES: Differences in clinical management and outcomes of patients with parotid masses in light of FNA results. RESULTS: We analysed 505 samples from 485 patients. According to histopathological results, preoperative FNA successfully identified benign tumours in 89% of the cases (362/405) and only 59% of malignant tumours (59/100). Overall sensitivity and specificity of FNA in distinguishing between different subtypes of benign lesions were 80% and 99%, respectively, whereas positive predictive value (PPV) and negative predictive value (NPV) were 85% and 98%. Moreover, malignant lesions subtyping had high false-positive and false-negative rates with sensitivity, specificity, PPV and NPV of 44%, 100%, 75% and 99%, respectively. Additionally, when FNA falsely classified malignant tumours as benign, surgeries were inappropriately delayed and the durations of surgeries and hospitalisations were shorter, compared to true malignant FNA results. Interestingly, survival was not affected in falsely benign lesions that were mostly low-grade, conversely non-diagnostic FNA for malignant tumours resulted in decreased survival. CONCLUSIONS: Our findings highlight the limitations of FNA as a decision-making tool in preoperative evaluation of parotid masses. Clinicians should take into account that FNA is inaccurate for identifying specific subtypes of malignant lesions, which may eventually delay treatment and influence outcome.

Postoperative Intracochlear Electrocochleography in Pediatric Cochlear Implant Recipients: Association to Audiometric Thresholds and Auditory Performance.

OBJECTIVES: The aim of this study was to compare intracochlear-recorded cochlear microphonics (CM) responses to behavioral audiometry thresholds in young children, with congenital hearing loss, 2 to 5 years after cochlear implantation early in life. In addition, differences in speech and auditory outcomes were assessed among children with and without residual hearing. DESIGN: The study was conducted at a tertiary, university-affiliated, pediatric medical center. CM responses by intracochlear electrocochleography technique were recorded from 102 implanted ears of 60 children and those responses correlated to behavioral audiometry thresholds at 0.125 to 2 kHz frequencies. All children had received Advanced Bionics cochlear implant with High Focus J1 or MidScala electrodes, along with extensive auditory rehabilitation before and after implantation, including the use of conventional hearing aids. Speech Spatial and Hearing Qualities, Category of Auditory Performance scale, and educational settings information were obtained for each participant. Those cochlear implantation (CI) outcomes were compared between children with or without residual CM responses. RESULTS: Two distinctive CM responses patterns were found among the implanted children. Of all ears diagnosed with cochlear hearing loss (n = 88), only in 29 ears, clear CM responses were obtained. In all other ears, no CM responses were obtained at the maximum output levels. The CM responses were highly correlated with coefficients ranging from 0.7 to 0.83 for the audiometric behavioral thresholds at 0.125 to 2 kHz frequency range. Of all ears diagnosed with auditory neuropathy syndrome disorder (n = 14), eight ears had residual hearing and recordable CM postimplantation. The other six ears showed no recordable CM responses at maximum output levels for all tested frequencies. Those showed supposedly better CM responses than the behavioral audiometry threshold, however with poor correlations with tested frequency thresholds. Children with residual hearing showed significantly better auditory outcomes with CI, compared with those without residual hearing. CONCLUSIONS: In children with congenital cochlear hearing loss, the objective CM intracochlear responses can reliably predict the residual audiometric threshold. However, in children with auditory neuropathy syndrome disorder, the CM thresholds did not match the behavioral audiometric responses. Postoperatively, children with recordable CM responses, showing preserved residual hearing, demonstrated better CI outcomes.

Balloon Eustachian tuboplasty in a professional Navy SEAL diver: case report.

Middle ear barotrauma due to dilatory Eustachian tube dysfunction (ETD) is probably the most common medical disorder related to diving. Moreover, ETD makes divers prone to other diving-related accidents, including inner ear barotrauma and alternobaric vertigo. Until the development of Eustachian tube balloon dilation no diving-compatible surgical options existed to effectively and safely prevent recurrence. We present a case of an Israeli Navy SEAL diver who dives in extreme strenuous combat-related closed-circuit rebreather (CCR) dives. Due to repeated middle ear barotrauma, the patient underwent Eustachian tube balloon dilation of the affected side. Following surgery, the patient returned to both CCR and scuba dives but still suffered from middle ear symptoms and repeated barotrauma hence was eventually disqualified from further combat diving.

[COCHLEAR IMPLANTS IN SINGLE-SIDED DEAFNESS].

INTRODUCTION: In normal hearing, the brain receives bilateral auditory input from both ears. In individuals with only one functioning ear listening in noisy environments and sound localization may become difficult. Historically, the impact of unilateral hearing loss in children had typically been minimized by clinicians, as it was assumed that one normal hearing ear provided sufficient auditory input for speech development and normal hearing experience. Data supporting the negative effects of unilateral deafness has been accumulating during the last decades. The effects of unilateral deafness extend beyond spatial hearing to language development, slower rates of educational progress, problems in social interaction and in cognitively demanding tasks. Until recently, treatments for single sided deafness were limited to routing signals from the deaf ear to the contralateral hearing ear either through conventional CROS aids or through bone anchored technologies. These technologies simply transfer sounds to the single functioning ear which allow sound awareness from the deaf side and minor improvement in hearing in noisy environments and localization. The cochlear implant is a surgically implanted electronic device that contains an array of electrodes which is placed into the cochlea, and stimulates the cochlear nerve. The cochlear implant bypasses the injured parts of the inner ear. Currently it is the only treatment to restore binaural hearing. This review aims to discuss the different aspects, the benefits and disadvantages of cochlear implantation in children with single sided deafness.

[THE RELATIONSHIP BETWEEN HEARING LOSS AND COGNITIVE DECLINE IN THE ELDERLY AND THE EFFICIENCY OF HEARING REHABILITATION IN PREVENTING COGNITIVE DECLINE].

INTRODUCTION: The population of elderly patients in Israel is constantly increasing, and so is the prevalence of age-related morbidities. Age-related hearing loss is very common, affecting approximately a third of the population over 65 years of age. Dementia is also common in elderly patients, and its prevalence doubles every 5 years after the age of 65 years. Hearing loss has many negative effects, such as decreased quality of life, social isolation and depression. In the last two decades, researchers had shown a direct relationship between hearing loss and dementia. Successful hearing rehabilitation can mitigate these negative effects and recent studies demonstrated that rehabilitation with cochlear implants slowed cognitive decline. In most cases, hearing aids are used for rehabilitation. However, for many patients, conventional hearing aids are insufficient. Cochlear implants were found to be effective and safe for elderly patients with severe hearing loss, but commonly they do not refer for evaluation due to their age. In this review we present the scientific evidence regarding the negative effects of age-related hearing loss, the association between hearing loss and cognitive decline, and the role of cochlear implantation in improving quality of life and slowing cognitive decline.

Towards a Unified Testing Framework for Single-Sided Deafness Studies: A Consensus Paper.

BACKGROUND: While hearing aids for a contralateral routing of signals (CROS-HA) and bone conduction devices have been the traditional treatment for single-sided deafness (SSD) and asymmetric hearing loss (AHL), in recent years, cochlear implants (CIs) have increasingly become a viable treatment choice, particularly in countries where regulatory approval and reimbursement schemes are in place. Part of the reason for this shift is that the CI is the only device capable of restoring bilateral input to the auditory system and hence of possibly reinstating binaural hearing. Although several studies have independently shown that the CI is a safe and effective treatment for SSD and AHL, clinical outcome measures in those studies and across CI centers vary greatly. Only with a consistent use of defined and agreed-upon outcome measures across centers can high-level evidence be generated to assess the safety and efficacy of CIs and alternative treatments in recipients with SSD and AHL. METHODS: This paper presents a comparative study design and minimum outcome measures for the assessment of current treatment options in patients with SSD/AHL. The protocol was developed, discussed, and eventually agreed upon by expert panels that convened at the 2015 APSCI conference in Beijing, China, and at the CI 2016 conference in Toronto, Canada. RESULTS: A longitudinal study design comparing CROS-HA, BCD, and CI treatments is proposed. The recommended outcome measures include (1) speech in noise testing, using the same set of 3 spatial configurations to compare binaural benefits such as summation, squelch, and head shadow across devices; (2) localization testing, using stimuli that rove in both level and spectral content; (3) questionnaires to collect quality of life measures and the frequency of device use; and (4) questionnaires for assessing the impact of tinnitus before and after treatment, if applicable. CONCLUSION: A protocol for the assessment of treatment options and outcomes in recipients with SSD and AHL is presented. The proposed set of minimum outcome measures aims at harmonizing assessment methods across centers and thus at generating a growing body of high-level evidence for those treatment options.

Radiation-Induced Well-Differentiated Thyroid Cancer: Disease Characteristics and Survival.

BACKGROUND: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect of age at initial exposure on the outcome have yet to be determined. OBJECTIVES: To identify the characteristics of radiation-induced thyroid carcinoma. METHODS: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. RESULTS: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS). CONCLUSIONS: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

Is There Justification for Total Thyroidectomy in Low-Risk Papillary Thyroid Carcinoma? A Decision-Analysis Model.

BACKGROUND: Low-risk papillary thyroid carcinoma is commonly treated surgically. However, uncertainties exist in regard to the optimal extent of surgery. We approached this question using a decision-analysis model. METHODS: A Markov model was used to compare outcome between patients with small (1-2 cm) low-risk PTC treated by hemithyroidectomy or total thyroidectomy. Probabilities and utilities were derived from the literature. The model was evaluated with Monte Carlo simulation. Sensitivity analysis was used to determine which variables most affected the model. RESULTS: Hemithyroidectomy was associated with a minor increase in mortality risk. After incorporation of mortality risk, complications, and quality-of-life measures, hemithyroidectomy was found to be superior to total thyroidectomy, with an increasing benefit over time. Quality-of-life measures, especially disutility of disease recurrence and undergoing surgery, had the greatest effect on the incremental benefit of hemithyroidectomy. CONCLUSION: Based on our decision-analysis model, hemithyroidectomy is the preferred option in low-risk PTC.

Analysis of failure following transoral laser surgery for early glottic cancer.

This study aimed at clarifying further the clinical behavior of early glottic cancer following transoral laser surgery and to determine, using retrospective analysis, whether the site of tumor involvement along the vocal fold has prognostic significance. The study included all patients treated with transoral laser surgery, for early glottic cancer (T1/T2N0M0) between May 1998 and January 2012 in a university affiliated tertiary care medical center. Data on demographics, site and extent of disease, treatment and outcome were collected and analyzed. Patients with insufficient data and/or follow-up of <2 years were excluded from the study. One-hundred and twenty-one patients were eligible for the study. Mean follow up time was 6.7 years (range 2-12 years). Overall recurrence rate following primary transoral laser surgery was 16.5 %. Histological grade was associated with higher recurrence rate (p = 0.008). Anterior commissure involvement was associated with reduced disease-free survival and tumors extending to the middle third of the true vocal fold were associated with lower recurrence rate. As per the results, anterior extension of glottic tumors is associated with higher recurrence rate compared to middle vocal fold extension, presumably due to earlier detection, better visualization and different biological behavior pattern of middle vocal fold tumors. Patients with higher grade tumors should be closely monitored for disease recurrence.

Value of ultrasound in detecting central compartment lymph node metastases in differentiated thyroid carcinoma.

The value of ultrasound in detecting central compartment lymph node metastasis in patients with well-differentiated thyroid carcinoma (WDTC) is unclear. Prospective patients with WDTC attending a university-affiliated tertiary medical center between July 2010 and June 2011 underwent neck ultrasound for detection of central compartment lymph node metastases prior to surgery. Central lymph node dissection was performed during the initial surgery regardless of ultrasound findings. The sensitivity and specificity of preoperative ultrasound in detecting central lymph node metastases were calculated according to the final histopathological results. Sixty-four patients met the study criteria. Twenty-four had pathologic central compartment lymph nodes according to preoperative ultrasound, 20 of which were confirmed by histological examination. One patient was found to have pathological central lymph nodes by histology which was not detected by US. Sensitivity of preoperative ultrasound was 95%, specificity 90%, and negative and positive predictive values 97 and 83%, respectively. Preoperative ultrasound may serve as an accurate and important tool for deciding the extent of surgery in WDTC.

Treatment decisions and adherence to guidelines in the treatment of low risk papillary carcinoma of the thyroid.

BACKGROUND: Treatment guidelines for well-differentiated papillary thyroid carcinoma (PTC) are based on retrospective studies and vary among professional thyroid associations. OBJECTIVES: To evaluate physician adherence to guidelines, overall and by specialty. METHODS: Questionnaires on the approach to low risk PTC were distributed among 51 surgeons and endocrinologists treating patients with PTC in tertiary medical centers. RESULTS: A wide range of answers was recorded among physicians regarding the danger posed by low risk PTC to the patient's life, urgency with which treatment should be administered, type of treatment, and risks associated with this treatment. There was a significant between-group difference in treatment preference: endocrinologists chose total thyroidectomy with radioactive iodine, while surgeons favored hemithyroidectomy alone. CONCLUSIONS: There is a wide difference in treatment recommendations between treating physicians and different specialties with regard to low risk PTC. The wide variation within and between soecialties may be explained by biases.

Cognitive processing speed improvement after cochlear implantation.

Background: Untreated hearing loss has an effect on cognition. It is hypothesized that the additional processing required to compensate for the sensory loss affects the cognitive resources available for other tasks and that this could be mitigated by a hearing device. Methods: The impact on cognition of cochlear implants (CIs) was tested in 100 subjects, ≥60 years old, with bilateral moderately-severe to profound post linguistic deafness using hearing aids. Data was compared pre and 12 and 18 months after cochlear implantation for the speech spatial qualities questionnaire, Mini Mental State Examination (MMSE), Trail making test B (TMTB) and digit symbol coding (DSC) from the Wechsler Adult Intelligence Scale version IV and finally the timed up and go test (TUG). Subjects were divided into young old (60-64), middle old (65-75) and old old (75+) groups. Cognitive test scores and times were standardized according to available normative data. Results: Hearing significantly improved pre- to post-operatively across all age groups. There was no change post-implant in outcomes for TMTB, TUG or MMSE tests. Age-corrected values were within normal expectations for all age groups for the TUG and MMSE. However, DSC scores and TMTB times were worse than normal. There was a significant increase in DSC scores between baseline and 12-months for 60- to 64-year-olds (t[153] = 2.608, p = 0.027), which remained at 18 months (t[153] = 2.663, p = 0.023). Discussion: The improved attention and processing speed in the youngest age group may be a consequence of reallocation of cognitive resources away from auditory processing due to greatly improved hearing. The oldest age group of participants had cognition scores closest to normal values, suggesting that only the most able older seniors tend to come forward for a CI. Severe to profoundly deaf individuals with hearing aids or cochlear implants were still poorer than age-equivalent normally hearing individuals with respect to cognitive flexibility, attention, working memory, processing speed and visuoperceptual functions. Due to a lack of data for the TUG, TMTB and DSC in the literature for hearing impaired individuals, the results reported here provide an important set of reference data for use in future research.

The protective effect of aspirin-induced temporary threshold shift in an animal model of cisplatin-related ototoxicity.

PURPOSE: The purpose of this study was to evaluate whether induction of temporary threshold shift (TTS) with aspirin prior to cisplatin exposure can prevent or minimize cisplatin detrimental effects on hearing. METHODS: We randomly divided BALB mice into three groups: (1) cisplatin only, (2) aspirin only, and (3) combined aspirin/cisplatin. Cisplatin was administered as a single intraperitoneal injection of 14 mg/kg. Aspirin was administered for three weeks via intraperitoneal injection of 200 mg/kg sodium salicylate, twice daily. Air conduction thresholds were recorded using Auditory Brainstem Responses (ABR). Cochleae were harvested and cochlear hair cells were counted using a scanning electron microscope (SEM). RESULTS: Aspirin-induced TTS have reached an average of 30.05±16.9 dB after 2 weeks. At 60 days, cisplatin-only treated mice experienced an average threshold shifts of 50.7 dB at 4 kHz, 35.16 dB at 8 kHz, 70 dB at 16 kHz, 53.1 dB at 32 kHz. All threshold shifts were significantly worse than for cisplatin/aspirin treated mice with TTS of 11.85 dB at 4 kHz, 3.58 dB at 8 kHz, 16.58  dB at 16 kHz, 20.41 dB at 32 kHz (p < 0.01). Cochlear cell count with SEM has shown reduction in the number of both inner and outer hair cells in the mid-turn in cisplatin treated mice. CONCLUSION: Aspirin induced TTS can protect from cisplatin-induced ototoxicity. This beneficial effect was demonstrated by auditory thresholds as well as SEM. Larger pre-clinical and clinical studies are still needed to confirm these findings.

Early death from papillary thyroid carcinoma.

PURPOSE: The natural history of papillary thyroid carcinoma (PTC) is characterized by a slow growth rate and an excellent prognosis at 20 and 30 years. However, there is a small subset of patients with poorer outcome. METHODS: Twenty patients who died of PTC within 10 years of diagnosis were studied to identify prognostic indicators and biological markers of early death. Findings were statistically compared with a previous review of all patients with PTC treated in the same institute and studies in the literature. RESULTS: The study group included 6 men and 14 women with a mean age of 65 years at diagnosis. Average tumor size was 3.6 cm; 16 patients had extracapsular extension. All tumor samples studied histologically stained poorly for p53, Ki67, and CD34. Regional metastases were present in half the patients, and distal metastases in all. All patients had an advanced disease stage (Tumor, Node, Metastases classification), and only 4 had a low score on the Metastases, Age, Completeness of resection, local Invasion, tumor Size risk stratification. Analysis of the findings against data in the literature for the whole population of patients with PTC, who had a considerably better survival (<8% mortality within 8-15 years vs 100% within 10 years in our sample), yielded significant differences for rates of extrathyroidal extension (P = .0001), regional metastases (P = .016), and distant metastases (P = .0001). CONCLUSION: Extrathyroid extension, late regional metastases, and distant metastases may be risk factors for early death from PTC.