Keywords
Epidemiology - Middle East - thyroid cancer - thyroidectomy - UAE
Introduction
Over the past few decades, the incidence of thyroid cancer has increased dramatically,
with variation in rates geographically. In the United States, the yearly incidence
of thyroid cancer has tripled between 1975 and 2009 from 4.9/100,000 to 14.3/100,000.[[1]] In the Middle East region, thyroid cancer accounts for 9% of all malignancies,
which is drastically higher than what is seen in the United States (US) where the
rate is 2.9%.[[2]] The association between female gender and thyroid cancer is known and has been
described previously. In the US, thyroid cancer affects women at a rate of 6.5–21.4/100,000,
and it is also the second most common malignancy in middle age women in Saudi Arabia.[[3]] In the Arabian Gulf countries, thyroid cancer is considered the fifth most common
cancer overall, with 5587 cases reported between 1998 and 2007.[[4]]
Presentation of thyroid carcinoma varies greatly, from well differentiated to undifferentiated
lesions, and is indicative of the prognostic outcome of the patient. Both patient
and tumor related factors influence the variability. Patient factors include age at
diagnosis, gender, predisposing events (radiation, history of iodine deficiency),
family history, and other endocrine malignancies. Tumor related factors to be taken
into account include size, histological type and level of differentiation, and extent
of tumor spread.[[5]]
Globally, papillary thyroid carcinoma (PTC) was reported as the most common subtype
of thyroid cancer followed by follicular thyroid carcinoma (FTC), medullary thyroid
carcinoma (MTC), and anaplastic thyroid carcinoma (ATC).[[6]],[[7]] Similarly, PTC was the most common subtype of thyroid cancer in Saudi Arabia accounting
for up to 87.7% of all thyroid cancer cases.[[8]],[[9]]
In the United Arab Emirates (UAE), there are no recent data published regarding the
incidence and prevalence of thyroid cancer. The most recent data showed that 135 patients
were diagnosed with thyroid carcinoma between 1991 and 2005. The study demonstrated
that PTC was the most common type of thyroid cancer with an incidence of 84%.[[10]]
Patients with differentiated thyroid cancer are often managed according to the 2015
revised American Thyroid Association guidelines. The initial management of differentiated
thyroid cancer includes staging the cancer, risk assessment, surgical interventions
such as partial thyroidectomy, total thyroidectomy, and completion thyroidectomy.
Furthermore, radioactive iodine (RAI) I131 and thyrotropin suppression therapy such
as thyroxine can be used in some cases of thyroid cancer. Long-term management of
patients with differentiated thyroid cancer focuses on the identification and prevention
of recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy,
and targeted therapy.[[11]],[[12]]
The aim of this study is to evaluate the histological, epidemiologic, and surgical
factors of thyroid cancer patients who underwent thyroidectomy at Cleveland Clinic
Abu Dhabi in the UAE.
Materials and Methods
All cases of thyroid carcinoma surgically managed between July 2015 and July 2017
at Cleveland Clinic Abu Dhabi were included in this study. Institutional Review Board
approval was obtained, and data were stored in an excel file on a password protected
work computer. Cases were identified by searching all CPT codes for thyroidectomy.
Those patient charts were reviewed and all patients with thyroid cancer were included.
The electronic medical records (EPIC database) of study patients were retrospectively
reviewed to gather information such as patient demographics, types of procedure performed,
and use of RAI. The histopathological features of the tumor including the size, subtype,
focality, and extra thyroidal extension were also collected. All the surgical pathology
was performed and reviewed in the Cleveland Clinic Abu Dhabi Pathology Department
and was staged based on the College of American Pathologists Protocol for Carcinomas
of Thyroid Gland (American Joint Committee on Cancer, 7th edition, 2010).
RAI was not available in our facility during the study period. However, cases that
were recommended RAI for further management received a referral to an outside facility
to receive their treatment. Those patients who received this therapy were tracked
and followed up at our institution. Basic statistical analysis using Microsoft excel
was used to determine the required parameters such as mean and median.
Results
Two hundred and fourteen patients underwent thyroidectomy at our institution during
the study period. Of these, 100 patients were noted to have thyroid carcinoma on final
histopathology. These 100 patients were included in our study. Age of the patients
ranged from 14 to 81 years, with median age of 38 and mean age of 39.6. At the time
of diagnosis, 71/100 (71%) patients were younger than 45 years of age. The overall
female to male ratio was 5.25: 1 with 84 females (84%) and 16 males (16%). There was
a wide range of ethnicities of patients. Eighty-eight patients (88%) were from the
Arabian Gulf states while 12 patients (12%) were from non-Gulf states. The female
to male ratio in the patients from the Gulf was 5.8:1, in comparison to 3:1 in patients
not from the Gulf [[Table 1]].
Table 1: Patient demographics
Thirty-two percent of the total patients had one or more comorbidity while 15% demonstrated
multiple comorbidities. The most common comorbidity demonstrated was hypertension
(19%). Other medical conditions investigated were diabetes mellitus, dyslipidemia,
and asthma (13%, 18%, and 8% respectively). Sixty-eight percent of patients had preoperative
Vitamin D deficiency.
Surgical procedures performed at our facility included total thyroidectomy, hemithyroidectomy,
and completion thyroidectomy [[Table 1]]. The total number of procedures performed during this period was 107 on the 100
patients. Seven patients had initial hemithyroidectomy in our institution followed
by completion thyroidectomy due to malignancy found on surgical pathology. Two patients
underwent completion thyroidectomy following initial surgery at an outside facility.
The most common procedure performed was total thyroidectomy (75.7%) followed by hemithyroidectomy
(15.9%). There were 17 patients who had positive lymph nodes and 13 patients required
formal lymph node dissection with total thyroidectomy. None of the patients in this
study had distant metastases. Following surgical management, 32% of patients received
RAI. An additional 5% were advised to receive RAI but were either lost to follow-up
or declined.
PTC was the most common pathological subtype (89%). This was followed by FTC (9%).
Only 1 case of mixed papillary and follicular and 1 case of Hurthle cell carcinoma
were present. Seventeen cases (17%) showed extrathyroidal extension, 10 cases (10%)
showed angioinvasion, and 6 cases (6%) showed lymphatic invasion. The majority of
tumors demonstrated unifocality (59%), while 41% were multifocal. Tumor size ranged
from 0.16 cm to 8 cm with a median size of the largest tumor in each patient of 1.6
cm [[Table 2]]. The length of patient follow-up ranged from 0.3 months to 54.2 months. The median
follow-up of patients was 32.9 months with mean follow-up of 30.6 months. During this
period of follow-up, there were no patients found to have histologically confirmed
recurrence. There was one patient who travelled outside the country after the first
operation and was noted to have nodal disease on postoperative imaging so underwent
neck dissection and RAI ablation. Another patient developed a small suspicious area
of tissue near thyroid resection bed noted on whole body thyroid scan about a year
after surgery; but, this was just monitored. None of the patients developed distant
metastatic disease.
Table 2: Pathologic tumor types and characteristics
The postoperative complication rate in our study was 25% overall, with transient hypocalcemia
being the most common complication in 22 cases (22%). Other complications included
2 cases of transient voice change, as well as tachycardia, lymph leak, and hematoma
requiring operative intervention in single cases each [[Table 3]]. All the complications occurred in patients who underwent either total thyroidectomy
or completion thyroidectomy. Patients who underwent hemithyroidectomy demonstrated
no complications postoperatively.
Table 3: Postoperative complications (n=107)
Discussion
The current study describes the demographic and histological characteristics of patients
who underwent thyroidectomy for thyroid cancer at Cleveland Clinic Abu Dhabi in the
UAE between July 2015 and July 2017.
Our study included 100 patients diagnosed with thyroid cancer among whom 84% were
females. Over the past 4 decades in the US, 77,276 patients were diagnosed with thyroid
cancer with PTC being the most common subtype.[[13]] In Europe, specifically in Germany, 42,789 cases with thyroid cancer were reported;
68% and 32% of the cases were females and males, respectively.[[14]] In the Middle East region, 7670 thyroid cancer cases were reported in Saudi Arabia
with 6066 (79.1%) cases occurring in females while 1604 (20.9%) cases occurring in
males.[[15]]
PTC was the most common histological diagnosis. PTC is the most common subtype of
thyroid cancer in different countries around the world[[5]],[[15]],[[16]],[[17]] FTC was found to be the second most common subtype of thyroid cancer in the literature[[6]],[[16]],[[17]],[[18]] In our study, we did not demonstrate any anaplastic or MTC, while the incidence
in the literature is 1.44% and 1.4%, respectively.[[1]],[[3]] This could be explained by the small sample size of this study and the low rate
of incidence of these subtypes. Furthermore, our patient population included surgically
resectable tumors. Considering the aggressiveness of anaplastic carcinoma at presentation,
surgical resection is not always the primary management option so these tumors would
likely not be identified in the present study. PTC is traditionally seen in iodine-sufficient
countries, and a 2015 study done in the UAE showed the rate of PTC to be 84% in comparison
to our study which found PTC in 89%.[[10]]
The management of thyroid cancer differs among patients. In the present study, different
types of surgeries were performed on the patients. As mentioned in the results, 75.7%
of the patients had total thyroidectomy, 15.9% underwent hemithyroidectomy, and 8.4%
had completion thyroidectomy. Furthermore, 32% of patients received RAI treatment
after surgery. A study conducted in Saudi Arabia demonstrated that 600 patients who
had thyroid cancer between 2004 and 2005 underwent different types of treatments.
Ninety-three percent of cases had total or near-total thyroidectomy. RAI was given
to 82% of the cases. Seventeen patients did not undergo surgery due to different reasons
such as poor prognosis, old age, and different comorbidities.[[9]] In our study, only 15% of patients demonstrated comorbidities but were still considered
surgical candidates.
In the present study, tumor sizes ranged from 0.16 cm to 8 cm. There were 17 patients
who were noted to have positive lymph nodes. Of these patients, For patients who had
positive lymph nodes the median size of tumors was 2.2 cm. Eight of patients with
positive lymph nodes had tumors 2–4 cm in size (47%) and only one had a tumor >4 cm
(5.9%). The overall median size of the largest tumors in our patients was 1.6 cm.
Therefore, lymph node metastases occurred in about 47% of patients with tumors ≤2
cm. On median follow-up of 32.9 months, no confirmed local or distant recurrence was
noted in our patient cohort.
Complications of thyroidectomy are subdivided into early and late complications. Early
complications include hemorrhage, wound infection, voice changes, and vocal cord paralysis.
Hypothyroidism and permanent hypocalcemia are considered late complications. Weiss
et al.[[19]] found that hypocalcaemia accounted for 4.55% of postthyroidectomy complications
followed by hematoma (1.75%), vocal cord paralysis (1.1%), and voice changes (0.52%).
The complication rates in our study included hypocalcemia in 20.6% of cases, and hematoma
and transient voice change at rates of 0.9%. The cases of hypocalcemia were all transient
and no long-term hypocalcemia occurred in this patient cohort. Vitamin D deficiency
is commonly seen in our region, which has been mostly attributed to change in cultural
practices and traditional dress that limits exposure to sunlight. Sixty-eight percent
of our patient cohort had Vitamin D deficiency preoperatively that might have influenced
the higher rate of hypocalcaemia in our study. This association is confirmed by a
study done by Al-Khatib, et al. in Saudi Arabia that found severe Vitamin D deficiency
to be an independent predictor of postoperative hypocalcaemia after total thyroidectomy.[[20]]
In summary, thyroid carcinoma incidence is increasing worldwide with varying rates.
In addition to traditional risk factors, there are unique factors that influence the
rates and histopathology pattern in our patient population. These factors include
the rapid socioeconomic growth that was seen in our region that has led to the decrease
in iodine deficiency and therefore an increase in rates of PTC subtypes, which are
traditionally seen in iodine-sufficient regions. Other factors include the increased
exposure to radioactive material in the past few decades due to recent conflicts in
the region that have potentially influenced the overall rate of thyroid carcinoma.
The predominance of thyroid disease in females and younger patients (<45 years of
age) was displayed in our study which suggests that female gender and young age are
risk factors for thyroid cancer. Our study was a retrospective cohort study at a single
institution so may not completely reflect the characteristics of the wider population
in the region. However, due to the continuous growth and changing landscape in our
region, further studies are needed to demonstrate the influence of these changes on
our patient population.
Conclusion
In this study of thyroid cancer in the UAE, most patients had papillary thyroid carcinoma.
There was also a predominance of malignancy in females patients under the age of 45.
More studies are required to evaluate the epidemiology and characteristics of patients
with thyroid cancer in the Middle East region.
