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JAMA. 2015 Mar 3;313(9):926-35. doi: 10.1001/jama.2015.0956.

The natural history of benign thyroid nodules.

Author information

1
Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma Sapienza, Roma, Italy.
2
Dipartimento di Scienze della Salute, Università di Catanzaro Magna Graecia, Catanzaro, Italy.
3
Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy10Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università di Bari Aldo Moro, Bari, Italy.
4
Unità di Endocrinologia, Ospedale di Tinchi-Pisticci, Matera, Italy.
5
Unità Operativa Semplice Dipartimentale di Endocrinologia, Ospedale di Bentivoglio, Bologna, Italy.
6
Dipartimento di Medicina, Università di Perugia, Perugia, Italy.
7
Unità Operativa di Endocrinologia, Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
8
Dipartimento di Medicina Clinica e Sperimentale, Università di Catania, Catania, Italy.
9
Unità Operativa di Endocrinologia, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
10
Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy.

Abstract

IMPORTANCE:

Detection of asymptomatic thyroid nodules has increased. Consensus is lacking regarding the optimal follow-up of cytologically proven benign lesions and sonographically nonsuspicious nodules. Current guidelines recommend serial ultrasound examinations and reassessment of cytology if significant growth is observed.

OBJECTIVE:

To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size.

DESIGN, SETTING, AND PARTICIPANTS:

Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed.

MAIN OUTCOMES AND MEASURES:

Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up.

RESULTS:

Nodule growth occurred in 153 patients (15.4% [95% CI, 14.3%-16.5%]). One hundred seventy-four of the 1567 original nodules (11.1% [95% CI, 10.3%-11.9%]) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 [95% CI 1.4-3.4] for 2 nodules; OR, 3.2 [95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 [95% CI, 4.4-18.0] for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 [95% CI, 1.7-4.9] for volumes >0.2 to <1 mL and OR, 3.0 [95% CI, 1.8-5.1] for volumes ≥1 mL), and male sex (OR, 1.7 [95% CI, 1.1-2.6]), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 [95% CI 0.3-0.9]). In 184 individuals (18.5% [95% CI, 16.4%-20.9%]), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% [95% CI, 0.0%-0.6%]). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% [95% CI, 7.5%-11.1%]), with detection of one cancer.

CONCLUSIONS AND RELEVANCE:

Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.

PMID:
25734734
DOI:
10.1001/jama.2015.0956
[Indexed for MEDLINE]

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