J. Endocrinol. Invest.
35: 407-412, 2012
Relationship between metabolic syndrome and multinodular
non-toxic goiter in an inpatient population from a geographic area
with moderate iodine deficiency
D. Rendina1,2, G. De Filippo1, G. Mossetti1, G. Zampa1, R. Muscariello1, G. Benvenuto2, C.L. Vivona2,
S. Ippolito3, F. Galante3, G. Lombardi3, B. Biondi3, and P. Strazzullo1
1Department of Clinical and Experimental Medicine, Federico II University, Naples; 2Spinelli Hospital, Belvedere Marittimo
(Cosenza); 3Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy
ABSTRACT. Background: Obesity and insulin resistance pre-
dispose individuals to the development of both metabolic syn-
drome and non-toxic nodular thyroid diseases. Aim: The aim of
this observational, cross-sectional study is to evaluate the re-
lationship between metabolic syndrome and multinodular non-
toxic goiter in an inpatient population from a geographic area
with moderate iodine deficiency. Subjects and methods: We
examined 1422 Caucasian euthyroid inpatients. Thyroid vol-
ume was determined by ultrasound of the neck. A fine-needle
aspiration biopsy was performed to evaluate single thyroid
nodules and dominant nodules 15 mm in euthyroid multin-
odular goiter. The diagnosis of metabolic syndrome was made
according to the criteria of the American Heart Associa-
tion/National Heart, Lung, and Blood Institute. Results: Of the
sample, 277 patients had clinical evidence of multinodular non-
toxic goiter, 461 met the criteria for the diagnosis of metabol-
INTRODUCTION
Multinodular goiter is a clinically recognizable enlarge-
ment of the thyroid gland characterized by excessive
growth and the structural and/or functional transforma-
tion of several areas within the normal thyroid tissue. In
the absence of thyroid dysfunction, autoimmune thyroid
disease, thyroiditis, and thyroid malignancy, it is referred
to as multinodular non-toxic goiter (1). Multinodular non-
toxic goiter is a frequent thyroid disorder, particularly in
geographic areas with iodine deficiency, and its patho-
genesis results from the interaction among environmen-
tal, hormonal, and genetic factors (1, 2). At variance, soli-
tary thyroid nodule shows a different etiopathogenetic
pattern (1-3).
Metabolic syndrome is a constellation of interrelated risk
factors carrying an increased risk of atherosclerotic car-
diovascular disease, Type 2 diabetes mellitus, and all-
cause mortality (4-6). Despite the fact that different def-
initions of metabolic syndrome have been proposed,
there is general consensus regarding its main compo-
BB and PS equally contributed to this work.
Key-words: Cross-sectional study, fine-needle aspiration biopsy, goiter, metabolic
syndrome, ultrasound scan.
Correspondence: G. Mossetti, MD, Department of Clinical and Experimental Medi-
cine, Federico II University Medical School, Via S. Pansini, 5 - 80131 Naples, Italy.
E-mail: giumosse@unina.it
Accepted March 30, 2011.
First published online July 5, 2011.
407
DOI: 10.3275/7842
ic syndrome, and 132 were found to have both conditions. Af-
ter adjusting for age, gender, body mass index, nicotinism,
parity, alcohol intake, thyroid function, and metabolic syn-
drome-related pharmacological treatment, metabolic syn-
drome was found to be an independent risk factor for the oc-
currence of multinodular non-toxic goiter. The relationship be-
tween metabolic syndrome and multinodular non-toxic goiter
was apparent in both men and women. Conclusions: In this
study of euthyroid inpatients, we demonstrate that metabol-
ic syndrome is an independent risk factor for the occurrence of
multinodular non-toxic goiter in a geographic area with mod-
erate iodine deficiency. We propose that patients meeting the
criteria for metabolic syndrome should be screened for the
presence of multinodular non-toxic goiter.
(J. Endocrinol. Invest. 35: 407-412, 2012)
2012, Editrice Kurtis
nents: obesity, hypertension, and abnormalities in car-
bohydrate and lipid metabolism (4-6).
Both pathologies (i.e., metabolic syndrome and multin-
odular non-toxic goiter) are quite frequent in the adult
populations of industrialized countries, and clinical data
indicate that some constitutive traits of metabolic syn-
drome could influence thyroid size and the occurrence
of thyroid nodules in the absence of clinical or subclinical
thyroid dysfunction; this may occur independently of the
pleiotropic effects of thyroid hormones on energy home-
ostasis, lipid and glucose metabolism, and blood pres-
sure (7-13). Moreover, despite the fact that the clinical
expression of each of the constitutive traits of metabolic
syndrome appears strictly interrelated to the others, it is
not clear whether metabolic syndrome is itself associat-
ed with multinodular non-toxic goiter.
The primary objective of this cross-sectional study was to
evaluate the possible relationship between metabolic syn-
drome and multinodular non-toxic goiter in an inpatient
population from Calabria, Southern Italy, a geographic area
characterized by moderate iodine deficiency (14). The sec-
ondary aim of the study was to evaluate the relationship
between each of the constitutive traits of metabolic syn-
drome and the occurrence of multinodular non-toxic goiter.
METHODS
Study population
Between January 1, 2004 and December 31, 2005, 2632 Cau-
casian patients who were consecutively referred to the Spinelli
D. Rendina, G. De Filippo, G. Mossetti, et al.
Hospital, Belvedere Marittimo (Cosenza, Italy), were considered
for possible participation in the study [male:female (M:F) 0.93;
mean age 64.719.4 yr; body mass index (BMI) 26.34.2 kg/m2].
There were no pregnant women in the study population.
For patients admitted more than once (1547, 54.9%), only the in-
formation collected during the first hospitalization was consid-
ered for the present study.
Pre-defined exclusion criteria were as follows: previous partial
or total thyroidectomy, thyroid dysgenesis, clinical or sub-clini-
cal thyroid dysfunction [sub-clinical thyroid dysfunction is de-
fined as serum free T4 (FT4) and free T3 (FT3) levels within their
respective reference ranges in the presence of abnormal serum
TSH levels (15)], instrumental and biochemical evidence of thy-
roiditis [ultrasonic pattern suggestive of thyroiditis and\or de-
tectable serum levels of anti-thyroperoxidase antibodies (Ab-
TPO)] (16, 17), pharmacological treatment with drugs that could
influence thyroid function (15), acute or chronic renal failure [es-
timated glomerular filtration rate <60 ml/min/1.73 m2
(http://www.kidney.org/PROFESSIONALS/kdoqi/guidelines_ckd/
toc.htm)], major debilitating physical illnesses and/or malignant,
suspicious or non-diagnostic fine-needle aspiration biopsy
(FNAB) thyroid histological specimen. Fourty-nine patients were
excluded because of an incomplete data set, and 50 were ex-
cluded for not providing informed consent for the study. A to-
tal of 1422 individuals (M:F 0.84; mean age 64.217.8 yr; BMI
26.24.7 kg/m2) were included in the present analysis (Fig. 1). All
were born and lived in Calabria, Southern Italy, and were of Cau-
casian origin. Reasons for inpatient admission, according to the
Clinical Classification Software (CCS) (http://www.hcup-
us.ahrq.gov/reports/natstats/his96/clinclas.htm), were as follows:
endocrine, nutritional and/or metabolic diseases (CCS diagnos-
tic category 3), no.=144 (10.1%; 86 females); heart diseases (CCS
diagnostic category 7.2), no.=460 (32.3%, 252 females); cere-
brovascular diseases (CCS diagnostic category 7.3), no.=90
(6.3%, 44 females); diseases of the veins and lymphatics (CCS
408
diagnostic category 7.5), no.=15 (1.1%, 8 females); respiratory
diseases (CCS diagnostic categories 8), no.=340 (23.9%, 185 fe-
males); gastrointestinal, liver, biliary tract, and pancreatic dis-
eases (CCS diagnostic categories 9), no.=230 (16.2%, 130 fe-
males); kidney, urinary system, genital, and breast diseases (CCS
diagnostic categories 10), no.=50 (3.5%, 22 females) and signs,
symptoms, factors influencing health care (CCS diagnostic cat-
egories 17), no.=93 (6.5%, 47 females).
The study was conducted in accordance with the Declaration of
Helsinki and was approved by the local Ethics Committee.
Study procedures
The patients weight and height were recorded at the time of ad-
mission, and BMI was calculated. Blood pressure (BP) was also
taken within 3 h of admission, according to published guidelines
(http://siia.it/sez/formazione-aggiornamento/linee-guida/): 3 mea-
surements were obtained while the subject was seated, and the
average of the last 2 measurements was used in the analysis. A
fasting venous blood sample was used to determine serum levels
of glucose, total and HDL-cholesterol, triglycerides, creatinine,
Ab-TPO, FT3, FT4, and TSH. Serum FT3 and FT4 levels were mea-
sured by specific radioimmunoassay (RIA) (Techno-Genetics, Mi-
lan, Italy). TSH was determined with an ultrasensitive immunora-
diometric assay (Techno-Genetics, Milan, Italy). Serum TPO-Ab
values were evaluated by specific RIA (SELco anti-TPO; Medipan,
Berlin, Germany).
An ultrasonic study of the neck in multiple anatomic planes was
performed in each subject using a Philips HP Agilent Sonos
4500 system with a 9-11 MHZ convex ultrasound transducer.
Thyroid volume was estimated according to published criteria
(8, 16). All examinations were performed separately by two radi-
ologists, and data analysis was performed by another investiga-
tor. An ultrasound-guided FNAB was performed in a) single nod-
ules 10 mm; b) single nodules 8.5 mm with ultrasonic and col-
or-Doppler features predictive of malignancy; and c) dominant
Fig. 1 - Flow-chart of the study. The ter-
ritory of the Local Health Authority Pao-
la-Cosenza 1 is highlighted in gray. a)
Thyroidectomy was performed in 34/67
patients (35.82%) for benign thyroid dis-
eases. b) Thyroid dysgenesis was char-
acterized in all cases by thyroid hemia-
genesis (3/4 right thyroid lobe). c) Nor-
mal range for TSH serum levels =0.5-4.5
mUI/l (15). Of the sample, 155 patients
(68.9%) showed TSH serum levels <0.5
mUI/l, and the remaining 70 subjects
showed TSH serum levels >4.5 mUI/l. d)
Amiodarone (no.=279), lithium (no.=4)
and interferon (no.=21) (15). e)
Renal Failure: Estimated glomerular fil-
tration rate <60 ml/min/1.73 m 2
(http://www.kidney.org/PROFESSIONA
LS/kdoqi/guidelines_ckd/toc.htm). f)
Non-negative histological specimen
was seen in 2 patients with malignant
histological specimen, 5 with suspicious
histological specimen, and 5 with non-
diagnostic histological specimen.