Sodium thiocyanate

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: epidemiological study

Adequacy of study:

supporting study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: An epidemiological study was performed in an industrial area in Germany to study the role of thiocyanate in the etiology of goiter. No guideline required, not under GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2006

Materials and methods

Study type:

cohort study (prospective)

Endpoint addressed:

not applicable

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Test material

Test material information

Constituent 1

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study):
1) if the prevalence of goiter is correlated with urinary SCN- excretion,
2) if patients with goiter have a decreased urinary I-/SCN- ratio and
3) if the I-/SCN- ratio is a better risk predictor for prevalence of goiter than urinary I2 or SCN2 excretion alone?

METHOD OF DATA COLLECTION
- Type: Questionnaire / other: urine samples
- Details: Probands were asked to give a spot urine sample and to fill in a questionnaire, asking for frequencies of intake of food with high I- content, such as milk and milk products, fish, cereals, meat products, iodized table salt as well as intake of I- containing tablets, pregnancy or lactation period and a history of smoking.

STUDY PERIOD: 2002

SETTING: All probands lived in the area of Halle/ Leipzig (Saxony), a former industrial region

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): No data
- Selection criteria: "healthy" volunteers from Halle/Leipzig area.
- Total number of subjects participating in study: 708
- Sex/age/race: no data
- Smoker/nonsmoker: both included, one of the questions of the questionnaire
- Total number of subjects at end of study: 708
- Matching criteria: sex, area when the probands live.
- Other: None


COMPARISON POPULATION
Not included.

HEALTH EFFECTS STUDIED
- Disease(s):
- ICD No.:
- Year of ICD revision:
- Diagnostic procedure:
- Other health effects:


OTHER DESCRIPTIVE INFORMATION ABOUT STUDY:

Exposure assessment:

not specified

Details on exposure:

The I-, creatinine and SCN- concentrations in spot urine samples were determined in 708 probands. Exposure to CN was not determined.

Statistical methods:

Statistical analyses were performed using SPSS software, version 10.0 (SPSS GmbH Software, Munich, Germany). We used means instead medians for statistical analysis of I- and SCN- excretion levels because there was a symmetrical distribution of the data. Moreover, the statistical bias in large cohorts (>500 probands) is lower when using mean values than median values as mean values better describe metric variables than the median values. Multivariable comparisons between the groups were performed with ANOVA (endpoints thyroid volume and urinary I- excretion). Adjustmentswere made for age, smoking and gender. A value of P<0.05 was considered statistically significant.

Results and discussion

Results:

Evaluation in a region with borderline Iodine deficiency shows that subjects with goiter (n = 79, 11%) had significantly higher urinary SCN- excretions than subjects without (3.9 +/- 2.8 vs 3.1 +/- 3.4 mg SCN-/g creatinine) and significantly lower urinary I-/SCN- ratios than patients without thyroid disorders (41 +/- 38 vs 61 +/- 71 µg I-/mg SCN-/l). Mean urinary I- excretions were not different between subjects with or without goiter. This indicates that in the region examined the uptake and availability of Iodide is comparable between subjects, and that occurrence of goiter is related to higher SCN to Iodide ratio.
Smokers showed significantly elevated urinary SCN-/creatinine ratios in comparison to non-smokers (4.3 +/- 4.3 vs 2.4 +/- 2.1 mg SCN-/g creatinine). ANOVA revealed a prediction of thyroid volume through age (P < 0.001), gender (P < 0.001), body weight (P < 0.05) and smoking (P < 0.05). Prevalence of goiter increases with age and decreases with increased Iodine intake.

Confounding factors:

The authors are aware that investigating ‘healthy’ volunteers can cause a selection bias. However, randomly selecting volunteers by outward manifestation of a ‘disease’ is a valid model for a clinical prospective trial and can be used in cohort and cross-sectional studies aiming at decreasing selection bias.

Strengths and weaknesses:

No data

Any other information on results incl. tables

Table 1 Characteristics of the overall study population.
	Males	Females	Study population
Probands*	132 (19%)	576 (81%)	708 (100%)
Age** (years)	31±12	36±13	35±13
Goiter*	9 (7%)	70 (12%)	79 (11%)
Thyroid nodules*	26 (20%)	179 (31%)	205 (29%)
Nodular goiter*	7 (5%)	49 (9%)	56 (8%)
Previous thyroidectomy*	2 (2%)	14 (2%)	16 (2%)
Pregnancy/lactation period*		23 (4%)	23 (4%)
*Number of probands; **Mean±S.D.

 

Table 2 Urinary SCN-and I-excretions and urinary I-/SCN-ratios of the overall study population.
	Urinary SCN-excretion** (mg SCN-/g creatinine)	Urinary I-excretion** (mg I-/g creatinine)	Urinary I-/SCN-ratio** (mg I-/mg SCN-)/l	Thyroid volume** (ml)
Study population (n=708*)	3.2±3.3 [f]	108±81	58±68 [f]	13±7
Normal thyroid volume (n=629*)	3.1±3.4 [a, b]	102±96	61±71 [c]	11±4
(Nodular) goiter (n=79*)	3.9±2.8 [a]	96±74	41±38 [c]	28±11
Males with goiter (n=9)	4.0±3.0	75±21	26±13 [e]	45±18
Males with normal thyroid volume (n=123)	2.8±2.6	76±45	49±50 [e]	13±5
Females with goiter (n=70)	4.0±2.8 [b]	114±92	43±40 [d]	26±8
Females with normal thyroid volume (n=506)	3.2±3.5	117±86	63±75 [d]	10±4
Thyroid nodules (n=205*)	3.5±3.5	108±115	57±62	16±10
Males (n=132*)	2.9±2.6	79±44	47±49	15±10
Females (n=576*)	3.3±3.5	120±127	61±72	12±7
Pregnancy/lactation period (n=23*)	4.1±3.7 [f]	145±272	41±68 [f]	13±6
SCN-excretion and I-excretion were correlated with creatinine excretion in every spot urine sample to minimize bias through kidney function and variable 24-hour urinary volume. Alphabetic characters in brackets [a–f] demonstrate the corresponding differences at the significantP,0.05 level. *Number of probands; **Mean±S.D.

 

Table 3 Urinary SCN-and I-excretions and urinary I-/SCN-ratios of 491 probands with known smoking behaviour.
	Urinary SCN-excretion** (mg SCN-/g creatinine)	Urinary I-excretion** (mg I-/g creatinine)	Urinary I-/SCN-ratio** (mg I-/mg SCN-)/l	Thyroid volume** (ml)
Smoker (n=124*)	4.3±4.3 [j, l]	114±79 [1]	45±47 [k, l]	14±8
Smoker with normal thyroid volume (n=99*)	4.2±4.6	124±83	51±51	11±6
Smoker with goiter (n=25*)	4.8±3.1 [l]	79±44 [l]	21±13 [l]	26±7
Smoker with thyroid nodules (n=37*)	4.0±3.3	101±63	42±43	18±8
Nonsmoker (n=367*)	2.4±2.1 [j]	113±88	60±61 [k]	13±8
Nonsmoker with normal thyroid volume (n=324*)	3.1±3.4	113±87	61±63	11±4
Nonsmoker with goiter (n=43*)	3.0±1.9	114±94	51±48	28±12
Nonsmoker with thyroid nodules (n=116*)	3.2±3.9	133±113	67±71	15±10
SCN-excretion and I-excretion were correlated with creatinine excretion in every spot urine sample to minimize bias through kidney function and variable 24-hour urinary volume. Alphabetical characters in brackets [j–l] demonstrate the corresponding differences at the significantP,0.05 level. *Number of probands; **Means±S.D.

Applicant's summary and conclusion

Conclusions:

In summary, the investigation shows that age, gender, bodyweight and smoking (increased SCN- levels by CN- inhalation) were predicting factors for thyroid volume. The urinary I-/ SCN- ratio was able to detect probands with an increased risk for goiter, in contrast to urinary I- excretion levels alone.

Executive summary:

Objective: Thiocyanate (SCN-) has concentration dependent antithyroid properties and a role in the etiology of goiter has been suggested in several studies. In 1991 an epidemiological survey conducted in the region of Halle/Leipzig (Saxony), an area with significant air pollution, suggested an inverse relationship between urinary iodine (I-) /SCN- excretion and goiter prevalence. 10 years later, we reinvestigated the same industrial area to clarify if the situation has changed after the elimination of most industrial waste products and moreover, if SCN- excretion levels alone or in combination with air pollution or smoking as a SCN- source are critical for thyroid function.

Design and methods: We investigated a cohort of 708 probands for I-, SCN- and creatinine excretion in spot urine samples and determined the prevalence of goiter and thyroid nodules by high resolution ultrasonography.

Results: Probands with goiter (n = 79, 11%) had significantly higher urinary SCN- excretions than probands without (3.9±2.8 vs 3.1±3.4 mg SCN-/g creatinine) and significantly lower urinary I-/SCN- ratios than patients without thyroid disorders (41±38 vs 61±71 mg I-/mg SCN-/l). Mean urinary I- excretions were not different between probands with or without goiter. Smokers showed significantly elevated urinary SCN-/creatinine ratios in comparison to non-smokers (4.3±4.3 vs 2.4±2.1mg SCN-/g creatinine). ANOVA revealed a prediction of thyroid volume through age (P < 0.001), gender (P<0.001), body weight (P <0.05) and smoking (P <0.05).

Conclusions: In our investigation, age, gender and smoking (raising SCN- levels by CN2 -inhalation) were predictive for thyroid volume and the urinary I-/SCN- ratios were able to detect probands with an increased risk of developing goiter in contrast to urinary I- excretion levels alone. These

data suggest, that in an era and area of decreased cyanide pollution, SCN- may remain a cofactor in the multifactorial aetiology of goiter.