2.1

Study population

A randomized, case–control retrospective chart review was conducted for patients presenting with differentiated thyroid carcinoma (DTC) to the Penn State Hershey Medical Center Otolaryngology outpatient clinic between January 1, 2005 and December 31, 2012. DTC patients were selected by using ICD-9 code 193 “malignant neoplasm of the thyroid gland.” Patients were excluded from the study for the following reasons: DTC could not be confirmed pathologically or cytologically, any evidence of undifferentiated thyroid cancer, or if height or weight was not documented. The study included 107 patients diagnosed with DTC from which 48 (9 males, 39 females) cases fit the study criteria. Characteristics of each patient’s tumor, the date of diagnosis, age at diagnosis, sex, ethnicity, height, weight, history of diabetes, and other co-morbidities were recorded. The case group was compared to two different control groups for a total of 172 control patients.

The control groups consisted of two independent populations within the study timeline. Group 1 consisted of 70 patients diagnosed primary hyperparathyroidism (PHPTH) who presented to the Otolaryngology outpatient clinic with documented euthyroid state. Group 2 consisted of 102 systematically sampled patients selected from the Internal Medicine (IM) clinic. PHPTH patients were selected using ICD-9 codes 227 and 252 (benign neoplasm of the parathyroid gland and primary hyperparathyroidism, respectively). Parathyroid disease type, patient age and date of PHPTH diagnosis, serum TSH levels, sex, race, height, weight, history of diabetes, and other comorbidities were documented. Patients with history of thyroid dysfunction, thyroid cancer, unconfirmed diagnosis of primary hyperparathyroidism, a history of gastrointestinal bypass or gastrointestinal cancer, or a history of multiple endocrine neoplasia were excluded.

The Internal Medicine control patients were systemically sampled at a rate of 2 controls to 1 DTC case. A randomly selected calendar date was chosen, then every 5th patient presenting to the IM outpatient clinic from that date in each year (2005 through 2012) was selected until the matching quota was reached. A history of diabetes, age, sex, race, height, weight, and other comorbidities were recorded. The only exclusion criterion for this group was any history of thyroid cancer.

This study was approved by the organization’s institutional review board.

2.2

Anthropometric analysis

Body Mass Index (BMI) was determined by dividing weight in kilograms by height in meters squared (kg/m ² ). BMI data were collected to as far back as 2 years prior to the diagnosis of DTC and as recently as the most recent available BMI data after diagnosis of DTC. The weight data for both control groups were collected to as many as 3 years preceding diagnosis of hyperparathyroidism (PHPTH group) or 3 years preceding year of presentation (IM group). The most recently available weight was recorded as well. BMI was categorized as underweight (< 18.5 kg/m ² ), normal weight (18.5–24.9 kg/m ² ), overweight (25.0–29.9 kg/m ² ), or obese (≥ 30 kg/m ² ) according to the World Health Organization definition. The body fat percentage was estimated from BMI by using the formula of Deurenberg et al. : body fat percentage = (1.20 × BMI) + (0.23 × Age) − (10.8 × Sex) − 5.4, where age is in years and sex is set to 0 for women and 1 for men. Body surface area (BSA) was calculated from height and weight by using the formula of Du Bois and Du Bois : BSA = (0.007184) × (Weight ^0.425 ) × Height ^0.725 ).

2.3

Statistical analysis

Exposure variables consisted of the most recent BMI within 6 months prior to diagnosis of DTC and any diagnosis of DM. Also evaluated was a “historical BMI” variable assessing whether a patient had met clinical criteria for obesity 1 to 2 years prior to diagnosis of PHPTH or 1 to 2 years prior to the control reference date. The time frame for this measure was determined in order to preserve sufficient sample size in the case group. Multivariate logistic regressions adjusting for gender, age, race, and year of BMI were used to assess the odds ratio (OR) of DTC with both BMI and DM. Furthermore, multivariate logistic regression was used to analyze the historical relationship of BMI with DTC. Anthropometric measurements were examined as continuous variables and treated as categorical variables either as quartiles or tertiles following prior usage in literature. BMI histograms of DTC case patients were used as comparisons against both control groups. The Mann–Whitney U test was used to compare continuous variables between cases and controls as appropriate. Percentages may not total 100% as a result of rounding.

2.1

Study population

A randomized, case–control retrospective chart review was conducted for patients presenting with differentiated thyroid carcinoma (DTC) to the Penn State Hershey Medical Center Otolaryngology outpatient clinic between January 1, 2005 and December 31, 2012. DTC patients were selected by using ICD-9 code 193 “malignant neoplasm of the thyroid gland.” Patients were excluded from the study for the following reasons: DTC could not be confirmed pathologically or cytologically, any evidence of undifferentiated thyroid cancer, or if height or weight was not documented. The study included 107 patients diagnosed with DTC from which 48 (9 males, 39 females) cases fit the study criteria. Characteristics of each patient’s tumor, the date of diagnosis, age at diagnosis, sex, ethnicity, height, weight, history of diabetes, and other co-morbidities were recorded. The case group was compared to two different control groups for a total of 172 control patients.

The control groups consisted of two independent populations within the study timeline. Group 1 consisted of 70 patients diagnosed primary hyperparathyroidism (PHPTH) who presented to the Otolaryngology outpatient clinic with documented euthyroid state. Group 2 consisted of 102 systematically sampled patients selected from the Internal Medicine (IM) clinic. PHPTH patients were selected using ICD-9 codes 227 and 252 (benign neoplasm of the parathyroid gland and primary hyperparathyroidism, respectively). Parathyroid disease type, patient age and date of PHPTH diagnosis, serum TSH levels, sex, race, height, weight, history of diabetes, and other comorbidities were documented. Patients with history of thyroid dysfunction, thyroid cancer, unconfirmed diagnosis of primary hyperparathyroidism, a history of gastrointestinal bypass or gastrointestinal cancer, or a history of multiple endocrine neoplasia were excluded.

The Internal Medicine control patients were systemically sampled at a rate of 2 controls to 1 DTC case. A randomly selected calendar date was chosen, then every 5th patient presenting to the IM outpatient clinic from that date in each year (2005 through 2012) was selected until the matching quota was reached. A history of diabetes, age, sex, race, height, weight, and other comorbidities were recorded. The only exclusion criterion for this group was any history of thyroid cancer.

This study was approved by the organization’s institutional review board.

2.2

Anthropometric analysis

Body Mass Index (BMI) was determined by dividing weight in kilograms by height in meters squared (kg/m ² ). BMI data were collected to as far back as 2 years prior to the diagnosis of DTC and as recently as the most recent available BMI data after diagnosis of DTC. The weight data for both control groups were collected to as many as 3 years preceding diagnosis of hyperparathyroidism (PHPTH group) or 3 years preceding year of presentation (IM group). The most recently available weight was recorded as well. BMI was categorized as underweight (< 18.5 kg/m ² ), normal weight (18.5–24.9 kg/m ² ), overweight (25.0–29.9 kg/m ² ), or obese (≥ 30 kg/m ² ) according to the World Health Organization definition. The body fat percentage was estimated from BMI by using the formula of Deurenberg et al. : body fat percentage = (1.20 × BMI) + (0.23 × Age) − (10.8 × Sex) − 5.4, where age is in years and sex is set to 0 for women and 1 for men. Body surface area (BSA) was calculated from height and weight by using the formula of Du Bois and Du Bois : BSA = (0.007184) × (Weight ^0.425 ) × Height ^0.725 ).

2.3

Statistical analysis

Exposure variables consisted of the most recent BMI within 6 months prior to diagnosis of DTC and any diagnosis of DM. Also evaluated was a “historical BMI” variable assessing whether a patient had met clinical criteria for obesity 1 to 2 years prior to diagnosis of PHPTH or 1 to 2 years prior to the control reference date. The time frame for this measure was determined in order to preserve sufficient sample size in the case group. Multivariate logistic regressions adjusting for gender, age, race, and year of BMI were used to assess the odds ratio (OR) of DTC with both BMI and DM. Furthermore, multivariate logistic regression was used to analyze the historical relationship of BMI with DTC. Anthropometric measurements were examined as continuous variables and treated as categorical variables either as quartiles or tertiles following prior usage in literature. BMI histograms of DTC case patients were used as comparisons against both control groups. The Mann–Whitney U test was used to compare continuous variables between cases and controls as appropriate. Percentages may not total 100% as a result of rounding.