Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Thyrotoxicosis:
  • Is the common feature of both:
    • Toxic nodular goiter (TNG) and Graves’ disease
  • It may be clinical or subclinical:
    • Subclinical hyperthyroidism:
      • Presents few, if any, mild symptoms ;
        • In the presence of a suppressed TSH with normal free thyroid hormones (T3 and T4)
  • Early in Graves’ disease:
    • Hyperthyroidism may be from:
      • Preferential T3 secretion:
        • So-called T3 toxicosis
• History and Physical Examination:
  • The clinical presentation ranges from:
    • No symptoms and a suppressed sensitive serum TSH level to overt or obvious clinical hyperthyroidism:
      • The latter includes symptoms associated with:
        • Increased adrenergic tone and resting energy expenditure and other hormonal effects
        • Features related to increased adrenergic tone include:
          • Nervousness
          • Tremor
          • Increased frequency of defecation
          • Palpitations
          • Diaphoresis
          • Irritability
          • Insomnia
          • Headaches
          • Lid retraction and lid lag
          • Muscle weakness
          • Tachycardia
          • Hyperreflexia, and widened pulse pressure
        • Those related to increased energy expenditure include:
          • Heat intolerance
          • Unintentional weight loss without anorexia
          • Warm, moist skin
      • In elderly subjects, the presentation may be subtle, with:
        • Atrial fibrillation
        • Weight loss
        • Weakness
        • Depression
    • Goiter may be detected in patients with either TNG or Graves’ disease:
      • Nodular irregularity is characteristic of TNG:
        • Whereas Graves’ disease is more typically:
          • Diffuse, soft, and rubbery and may have an overlying thyroid region bruit
  • Patients with Graves’ disease often have a:
    • Goiter:
      • Diffuse, soft, and rubbery:
        • May have an overlying thyroid region bruit
    • May present with hyperthyroidism alone, or
    • May have one or more extra-thyroidal manifestations
  • Clinically apparent eye disease may occur in up to a third of patients with Graves’ disease:
    • But orbital CT may detect changes in a majority of patients
    • Signs of eye disease include:
      • Proptosis or exophthalmos
      • Lid lag and retraction
      • Impaired extraocular muscle function
    • Eye symptoms and signs generally begin about six months before or after the diagnosis of Graves’ disease:
      • It is generally uncommon for eye involvement to develop after the thyroid disease has been successfully treated:
        • There is great variability, however, and in some patients with eye involvement, hyperthyroidism may never develop
      • The severity of eye involvement is not related to the severity of hyperthyroidism
      • Early signs of eye involvement may be:
        • Red or inflamed eyes
      • Ultimately, proptosis may develop from the inflammation of retro-orbital tissues
      • Diminished or double vision is a rare problem:
        • That usually occurs later
      • It is not well known why, but problems with the eyes occur much more often in people with Graves’ disease who smoke cigarettes than in those who do not smoke
  • Other features of Graves’ disease include:
    • Onycholysis, acropachy, and pretibial myxedema
    • Pretibial myxedema:
      • Is a rare, reddish lumpy thickening of the skin of the shins
      • This skin condition is usually painless and is not serious
      • Like the eye disorders of Graves’ disease, the skin manifestation does not necessarily begin precisely when hyperthyroidism starts
      • Its severity is not related to the level of thyroid hormones
      • It is not known why this problem is usually limited to the lower leg or why so few people have it
  • Occasionally symptoms related to the mass effect of a large goiter may occur:
    • Very large goiter may extend retrosternally or substernally, resulting in symptoms and signs of tracheoesophageal pressure:
      • These may include:
        • Dysphagia
        • Cough
        • Choking sensation
        • Stridor:
          • Particularly if severe tracheal narrowing exists
        • The development of facial plethora, cyanosis, and distention of neck veins:
          • With raising both arms simultaneouslymay result from deep goiter compression of the structures located within the bony confines of the thoracic inlet (Pemberton sign)

#Arrangoiz #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #ThyroidExpert #SurgicalOncologist #EndocrineSurgery #MountSinaiMedicalCenter #Miami #ThyroidNodule #ToxicNodularGoiter #TNG #MultinodularGoiter #GravesDisease #Hyperthyroidism #Goiter

Did you know? 🤔
The major horn of the hyoid bone is a useful repair in lateral neck surgeries.
Its highlight allows us to specify the location:

• towards the upper: of the hypoglossal nerve next to the ranine veins and of the lingual artery (in the triangle of Beclard).
• downwards: from the nerve and the superior laryngeal vessels (in the Portmann quadrilateral).

📚References:
1- Major horn (horn) of the hyoid bone.
2- Hypoglossal nerve.
3- Lingual artery: 3a -in the area of the triangle of Beclard, behind the hyoglossus muscle. 3b- in the area of the Pirogoff triangle, behind the mylohyoid and hyoglossus muscle.
4- Anterior belly of the digastric muscle.
5- Superior laryngeal nerve.
6- Mylohyoid muscle (in submental triangle).
7- Posterior belly of the digastric muscle.
8- Minor horn (horn) of the hyoid bone.
9- Body of the hyoid bone.
10- Cranial insertion of the omohyoid muscle.
11- Thyrohyoid muscle.
12- Sternocleidohyoid muscle.
13- Lateral thyroid ligament.
14- Portmann quadrilateral.
15- Upper horn of the thyroid cartilage.
16- Trunk of the superior thyroid artery and superior laryngeal artery.
17- Primitive carotid artery.
18- Internal jugular vein.
19- Projection of the imaginary “safety” line in the Sistrunk operation.
20- Stylohyoid muscle.
21- Fascial sling of the intermediate tendon of the digastric muscle.

• Hyperthyroidism in the United States:
  • Occurs in 0.05% to 1.3% of the general population:
    • With the majority of cases consisting of subclinical disease
  • The prevalence of hyperthyroidism:
    • Is approximately 5 to 10 times less than that of hypothyroidism
    • White and Hispanic populations in the United States:
      • Have a slightly higher prevalence of hyperthyroidism than black populations
• TNG:
  • Is the most frequent cause of thyrotoxicosis:
    • In the elderly
  • It accounts for about 5% to 15% of patients with endogenous hyperthyroidism:
    • But the proportion is:
      • Higher in iodine-deficient geographic regions
  • Changes in the iodine content of salt and in the iodine supplementation of water have been linked to changes in the incidence of TNG:
    • In Switzerland in 1980 and in Spain in 1994:
      • The iodine content of salt was increased, and this was associated with a transient increased incidence of thyrotoxicosis followed by decreased incidence:
        • Mainly the result of reduced TNG incidence
• Graves Disease:
  • Being the most common cause of thyrotoxicosis in all age groups
  • Graves’ disease accounts for 70% to 80% of endogenous hyperthyroidism
  • The incidence of Graves’ disease is five times higher in females than in males:
    • Occurring generally during women’s reproductive years:
      • Although it may occur at any age

#Arrangoiz #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #ThyroidExpert #SurgicalOncologist #EndocrineSurgery #MountSinaiMedical Center #Miami #ThyroidNodule #ToxicNodularGoiter #TNG #MultinodularGoiter #GravesDisease #Hyperthyroidism #Goiter

• In the absence of extra-thyroidal symptoms or diffuse goiter, measurement of thyrotropin-receptor antibodies is performed and has a sensitivity and specificity of over 99%

#Arrangoiz #ThyroidSurgeon #ThyroidExpert #CancerSurgeon #HeadandNeckSurgeon #Hyperthyroidism #GravesDisease #EndocrineSurgery #Miami #Mexico #MountSinaiMedicalCenter

• Hyperthyroidism refers to thyrotoxicosis:
  • Caused by the overproduction of the thyroid hormones:
    • Thyroxine (T4) and triiodothyronine (T3)
• The most common type of thyrotoxicosis encountered in the United States and worldwide:
  • Is Graves’ disease
• Toxic nodular goiter (TNG):
  • Is the second most common type of thyrotoxicosis
• Goiter:
  • Is enlargement of the thyroid gland:
    • That is commonly encountered in clinical endocrine practice
  • It may be classified as:
    • Diffuse or
    • Nodular
      • May be either:
        • Non-toxic or
        • Toxic
  • Nodular goiter may include:
    • Multiple nodules:
      • Multi-nodular goiter (MNG)or
    • A single nodule
  • Regardless of different possible mechanisms of development:
    • Diffuse thyroid enlargement eventually evolves into a nodular stage
• A TNG is a thyroid gland that contains:
  • Autonomously functioning thyroid nodule(s):
    • With resulting hyperthyroidism
  • Also called Plummer’s disease:
    • TNG was first described by Henry Plummer at Mayo Clinic in 1913
  • TNG is the second most common cause of hyperthyroidism in the Western world, after Graves disease:
    • In elderly individuals and in geographic areas of endemic iodine deficiency:
      • TNG is the most common cause of hyperthyroidism
• Graves’ disease:
  • Is the most common type of thyrotoxicosis encountered in the industrialized world
  • Graves’, disease owes its name to an:
    •  Irish doctor, Robert James Graves’ who described the first case of goiter with exophthalmos in 1835
  • Patients with Graves’ disease usually have:
    • Diffuse, nontender, symmetric enlargement of the thyroid gland

#Arrangoiz #ThyroidExpert #ThyroidSurgeon #CancerSurgeon #EndocrineSurgery #Miami #MountSinaiMedicalCenter #Hyperthyroidism #Goiter #ThyroidNodules #HeadandNeckSurgeon #MulitnodularGoiter #MNG #PlummerDisease #ToxicNodularGoiter #TNG #Mexico

• Clin Thyroidol 2022;34:78–80.
• Background:
  • Several studies have reported that microscopic extrathyroidal extension (m-ETE) does not increase disease-related mortality in patients with papillary thyroid cancer (PTC); however, the literature is scarce with regard to the impact of macroscopic (gross) extrathyroidal extension invading only strap muscles (T3b-ETE) on outcomes that are important to patients
  • This study was performed to evaluate the association between T3b-ETE tumors and disease-specific survival (DSS) in patients with PTC
• Methods:
  • This hospital-based single-institution study included adults who underwent initial surgery for PTC, with or without local or distant metastasis, between 1986 and 2015
  • The cohort was classified into three groups:
    • Mo macro-ETE:
      • No gross intra-operative evidence of extrathyroidal extension
    • T3b-ETE:
      • Gross intraoperative evidence of extra-thyroidal extension invading only strap muscles
    • T4-ETE:
      • Gross intraoperative evidence of extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, recurrent laryngeal nerve, prevertebral fascia, or carotid artery/mediastinal vessels
  • A Cox proportional-hazards model was used to investigate the association of ETE categories and 10-year disease-specific survival (DSS, defined as the interval between initial surgery and last appointment or death with evidence of local or distant disease)
  • This model was adjusted for pathologic nodal stage, distant metastasis stage, and age
  • A subgroup analysis by age (< 55 vs. ≥ 55 years) was planned
• Results:
  • A total of 5880 patients with a median follow-up of 64 months were included
  • Most were female (72.2%), were < 55 years of age (68.2%); had a tumor size between 0 and 4 cm (94.6%); were classified as T1 (71.3%), N0/Nx (68.1%), and M0 (98.9%); had ATA intermediate-risk disease (37.6%); and had AJCC stage I disease (89.4%)
  • Overall, 5485 patients had macro-ETE (93.3%), 179 had T3b-ETE (3.0%), and 216 had T4-ETE (3.7%)
  • In the overall adjusted multivariate analysis and compared with the no macro-ETE group, the T3b-ETE group had a similar risk of DSS (HR, 2.11; 95% CI, 0.72–6.15) and the T4-ETE group had a higher risk of DSS (HR, 5.22; 95% CI, 2.90–9.40)
  • In the subgroup analysis, patients ≥ 55 years of age with T3b-ETE had a higher risk of DSS as compared with patients with no macro-ETE (HR, 3.29; 95% CI, 1.07–10.08), similar to the higher risk also seen in the T4-ETE group (HR, 9.39; 95% CI, 4.68–18.81)
  • There were 26 patients with residual disease after initial surgery (none from the T3b-ETE group), and there were only 60 DSS events
• Conclusions:
  • Macroscopic extrathyroidal extension invading only the strap muscles (T3b-ETE) increases disease-specific death in patients with PTC who are ≥55 years of age, as compared with patients with no macro-ET
• This retrospective study found no increased disease-specific mortality in patients with T3b-ETE overall and increased disease-specific mortality only in those ≥55 years
• The strength of the Harries et al. study is the meticulous record review and histologic confirmation of the intraoperative T3b-ETE findings
• Nevertheless, the small number of DDS events limited the analysis of other prognostic factors in the multivariate model, including the tumor size and impact of postoperative radioactive iodine ablation
• The literature about the impact of extrathyroidal extension (ETE) on disease outcomes provides inconsistent conclusions
• Factors contributing to different findings are the lack of a standard definition and reporting of ETE
• For instance, some studies defined ETE and its severity by the direction of invasion (perithyroid tissue, strap muscle, and beyond strap muscle), while others defined ETE based on pathology reports and operative findings
• Therefore, it is expected that different definitions of the disease may lead to different outcomes and conclusions
• Macroscopic ETE is defined as an operative or gross examination finding noted when cancer extends out of the thyroid into adjacent structures
• In contrast, microscopic ETE is defined as when the tumor invasion is observed under a microscope
• It is expected that all macroscopic ETE will have evidence of microscopic ETE
• These definitions imply that clinicians taking care of patients with thyroid cancer should carefully review the pathological report and the operative report to classify ETE correctly
• We have also found that frequent communication with our surgical colleagues can help clarify the operative and histopathologic findings
• Future studies using standardized definitions will elucidate the impact of macroscopic disease on recurrence and mortality in PTC
• In the meantime, we agree with the authors of this study that it is prudent to consider T3b-ETE as a prognostic adverse risk factor between microscopic ETE and macroscopic ETE with invasion into adjacent tissues

#Arrangoiz #ThyroidSurgeon #ThyroidExpert #HeadandNeckSurgeon #CancerSurgeon #PapillaryThyroidCancer #ExtrathyroidExtension #Miami #Mexico #MountSinai #EndocrineSurgery #SurgicalOncology #Surgeon #Teacher

• Clin Thyroidol 2022;34:75–77.
• Background:
  • The incidence of papillary thyroid cancer (PTC) is increasing at a rapid rate:
    • Probably related to thyroid nodules being detected incidentally by more frequent radiologic studies being performed, and
    • Also likely due to a change in the molecular oncogenes:
      • Driving its development and progression
  • The standard initial treatments include:
    • Thyroidectomy and, in some instances, radioactive iodine therapy
  • The factors that assist in the decision for a particular treatment are multiple, but include:
    • Patient age
    • Gender
    • Histologic characteristics
    • Findings on radiologic and nuclear medicine studies
    • Postoperative serum thyroglobulin levels
  • One particular histologic finding:
    • Minor extra-thyroidal invasion:
      • Has been controversial regarding its relevance to recurrence and prognosis
    • Diker-Cohen et al performed a meta-analysis and noted that:
      • Minimal extrathyroidal extension:
        • Did increase the risk of recurrence, but not of mortality
    • Castagna et al also reported:
      • An increased risk of recurrence in patients with minimal extrathyroidal extension when compared to intrathyroidal tumors
    • In contrast, Ahmaddy et al and Raruenrom et al:
      • Did not find that minimal extrathyroidal extension was associated with a worse prognosis
  • In the current study, Forleo et al have investigated this issue, adding further understanding to the interpretation of minimal extrathyroidal invasion in patients with PTC
• Methods:
  • The authors used the Italian Thyroid Cancer Observatory database to identify patients with PTC with minimal extrathyroidal extension and excluded patients who had local lymph node involvement with cancer
  • This database includes patient information prospectively collected from multiple medical centers
  • The authors identified 2,237 patients who fulfilled the study eligibility criteria and had at least 1 year of follow up
  • Multiple factors were evaluated, including the type of initial thyroid surgery, histologic variants of PTC, tumor diameter, risk stratification using the American Thyroid Association system, use and dose of radioactive iodine therapy and disease response
• Results:
  • There were 1831 patients (81.8%) who had an excellent response, 296 (13.2%) an indeterminate response, 55 (2.5%) a biochemically incomplete response, and 55 (2.5%) a structurally incomplete response
  • Detailed evaluation indicate that, as individual factors:
    • Minimal extrathyroidal extension, tumor size larger than 2 cm, aggressive PTC histology, and age at diagnosis:
      • Were not found to be associated with a worse initial therapy response:
        • However, the combination of:
          • Minimal extrathyroidal extension and tumor size greater than 2 cm:
            • Was associated with a significantly worse outcome
    • Radioactive iodine therapy did not appear to improve prognosis
• Conclusions:
  • Minimal extrathyroidal extension alone did not predict a worse prognosis in PTC patients who did not have cervical lymph node involvement in a large study cohort
  • However, it appears that the combination of tumor diameter larger than 2 cm and the presence of minimal extrathyroidal extension:
    • May help predict low-to-intermediate risk of recurrent or persistent disease
• This study by Forleo et al helps further our understanding of the possible role of minimal extrathyroidal extension in PTC in predicting recurrent or persistent disease
• The study has the attributes of analyzing a large group of patients, obtaining data from multiple medical centers at the time of initial surgery, of examining patients with no known cervical lymphadenopathy, and they used the ATA risk stratification system
• However, there are also several aspects that should also be noted
• There were multiple surgeons and pathologists, and there was not an independent pathologic review board that analyzed all of the samples
• The study analyzed only the response at 1 year, but is apparently monitoring these patients over a longer duration
• The definition of minimal extrathyroidal extension and its application in every case is not substantiated
• In summary, I think it clinically relevant that this analysis of a large cohort of PTC patients found that minimal extrathyroidal extension alone is not a significant risk factor for recurrence, but when it is combined with tumor size > 2 cm, there appears to be a higher risk of recurrence
• Radioactive iodine therapy did not seem to be beneficial, although there was a relatively low percentage of patients who received radioactive iodine and the statistical evaluation of this treatment was complex
• I think it reasonable to consider all relevant laboratory, histology, radiologic and clinical factors on an individual basis to help decide whether radioactive iodine therapy may be warranted
• In addition, performing a radioactive iodine scan with baseline and stimulated serum thyroglobulin levels may help in making this decision
• References
  • Diker-Cohen T, Hirsch D, Shimon I, Bachar G, Akirov A, Duskin-Bitan H, Robenshtok E 2018 Impact of minimal extra-thyroid extension in differentiated thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab 103:2100–2106.
  • Castagna MG, Forleo R, Maino F, Fralassi N, Barbato F, Palmitesta P, Pilli T, Capezzone M, Brilli L, Ciuoli C, Cantara S, Formichi C, Pacini F 2018 Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor. J Endocrinol Invest 41:1029–1035.

• Clin Thyroidol 2022;34:59–62
• Background:
  • Graves’ disease (GD) is an autoimmune thyroid disorder that is the leading cause of hyperthyroidism
  • Understanding whether GD predisposes patients to thyroid cancer has been of interest for a long time
  • Previous research on the link between GD and the risk of concurrent thyroid cancer was based mostly on surgically treated GD patients, and the results were inconsistent
  • Furthermore, there are still controversies about the impact of GD on the clinical features and outcomes of thyroid cancer
  • Therefore, in the current study, Yoon and colleagues aimed to investigate the overall prevalence of thyroid cancer in patients with GD, as well as the clinicopathologic characteristics, prognosis, and predictive factors of its development
• Methods:
  • This retrospective multicenter study collected data on all patients with GD treated at three tertiary referral hospitals in South Korea between January 2010 and December 2019
  • During their follow-up for GD, all participants in the study underwent at least one high-resolution neck ultrasound
  • All included patients were followed-up for at least one year
  • Demographic information, status of GD, antithyroid medications for the treatment of GD, as well as clinicopathologic characteristics, surgical and postoperative management, and prevalence and clinical outcomes of concomitant thyroid cancer in patients with GD were described
  • In the subgroup analysis, patients were divided into nodular GD and non-nodular GD groups based on the presence of thyroid nodules other than the primary thyroid cancer lesion(s)
  • Clinicopathologic features and thyroid cancer prognosis were compared between the two subgroups
  • Using binary logistic-regression analysis, risk factors for thyroid cancer recurrence / persistence were further investigated
• Results:
  • The current study was composed of 15,159 patients with GD, including 262 (1.7%) with coexisting thyroid cancer
  • The majority of the patients (251 [95.8%]) had undergone cytologic assessment of thyroid tissue prior to surgery, while the remaining patients (11 [4.2%]) were diagnosed with occult thyroid cancer after thyroid surgery was performed for other indications, such as compression symptoms caused by a large goiter and / or uncontrolled hyperthyroidism
  • In 245 (93.5%) and 17 (6.5%) of the patients, total thyroidectomy and lobectomy, respectively, were performed
  • Micro–thyroid carcinomas were found in 182 GD patients (69.5%), which was comparable to the proportion of those in without GD (19,397 of 30,231 [64.2%])
  • The mean (±SD) age of patients with GD and coexisting thyroid cancer was 55.1±13.9 years
  • Active GD, defined as newly diagnosed GD or the use of anti-thyroid drugs, was found in 229 patients (87.4%)
  • Papillary thyroid cancer (PTC) accounted for nearly all (260 [99.2%]) of the histologic thyroid cancer subtypes
  • Extrathyroidal extension and lymph node metastases were identified in 65 (24.8%) and 89 (34.0%) of the patients, respectively
  • None of the patients had distant metastases
  • In 113 (43.1%) of the patients, radioiodine ablation was administered after surgery
  • There was no evidence of thyroid cancer in 242 (92.4%) of patients at a median follow-up of 59.1 months, while 20 (7.6%) had recurrent / persistent thyroid cancer
  • In the subgroup analysis, thyroid cancer patients with nodular GD were older (61.9±12.8 vs. 52.1±13.3 years, P = 0.001) and more were female (86.3% vs. 75.3%, P = 0.046) than those with non-nodular GD
  • There was no difference in thyroid cancer aggressiveness, according to preoperative cytologic and ultrasonographic assessments, between the groups
  • However, there was a substantial difference in the non-classic PTC subtypes between the two groups: patients in the nodular GD group had only follicular variant PTC, whereas the non-nodular GD group had seven patients with non–follicular variant, non-classic PTC subtypes
  • Although thyroid cancer recurrence was detected only in patients with non-nodular GD, the difference was not considered to be significant
  • Furthermore, multivariate analysis revealed that only lymph node metastasis (odd ratio, 4.359; 95% confidential interval, 1.267–14.944; P = 0.020) was independently associated with recurrent / persistent thyroid cancer
  • Conclusions:
  • This multicenter retrospective study of GD patients, including those without surgical intervention for GD, showed that the proportion of coexisting thyroid cancer was substantially lower than previously reported
  • The small proportion of thyroid cancer patients with concomitant GD had a generally favorable prognosis for their thyroid cancer, but those with lymph node metastases may need to be monitored more closely
• The possible association between thyroid cancer and autoimmune thyroid diseases, mainly GD and Hashimoto’s thyroiditis (HT):
  • Has been of considerable interest for a long time
• Although an underlying autoimmune pathology exists in both conditions, HT features chronic inflammatory infiltration in the thyroid gland, whereas GD involves the critical presence of thyroid stimulating antibody (TSAb)
• As growing evidence suggests that there is an increased risk of thyroid cancer in patients with HT, interest has also focused on the role of GD in the development and prognosis of thyroid cancer
• However, data from available studies have provided conflicting information
• A large-scale cohort study conducted in Taiwan has suggested a higher risk of thyroid cancer in GD patients:
  • In 5025 newly diagnosed GD patients, 52 thyroid cancer events were identified (1.0%), as compared with 20 events recorded in 20,100 non-GD subjects (0.1%)
  • However, there was little information on how these thyroid cancers were diagnosed
  • Given that patients with GD are more likely to undergo thyroid examination, including ultrasonography, than those without GD, we should not easily attribute a possible increased prevalence of thyroid cancers to GD per se, but rather to the attentive surveillance of the thyroid provided to GD patients
• The current study was based on all ultrasound-screened GD patients, including nonsurgically treated patients, in contrast to many previous studies in which only surgery-treated patients were included
• Hence, this study avoided selection bias generated from indications toward surgical management
• The rate of coexisting thyroid cancer in GD patients was higher than that in the above-mentioned Taiwan cohort (1.7% vs. 1.0%, P<0.001).;
  • Again, this suggests that routinely performing ultrasound screening leads to more cancer cases being found
• Although the authors could not directly compare the prevalence of thyroid cancer between GD patients and non-GD patients in their study, another population-based study performed at Health Promotion Center of Asan Medical Center, South Korea, provides some insight:
  • In 15,000 subjects who were ultrasound-screened and underwent fine-needle aspiration of suspicious thyroid nodules, 267 patients (1.8%) were identified with a coexisting thyroid cancer
  • Here, we notice that once ultrasound screening is uniformly applied on the population level, the prevalence of thyroid cancer in the general population and in GD patients is comparable
• Taken together, these studies suggest that GD may not increase the risk for thyroid cancer
• To avoid overdiagnosis of thyroid cancer, universal screening for thyroid cancer among GD patients should not be encouraged
• The current study also reported favorable thyroid cancer outcomes in patients with coexisting GD and thyroid cancer, although a comparison could not be made directly with non-GD patients
• There remain some questions to be answered;
  • First, in vitro studies have linked TSAb to mitogenic, antiapoptotic and angiogenic effects probably mediated through its binding to the TSH receptor and stimulation of various signaling pathways:
    • Would changing TSAb status over time (e.g., persistently high titers vs. rapidly declining titers) impact the clinical features and prognosis of thyroid cancer in GD patients differently?
  • Second, nearly 70% of the thyroid cancer patients found in this cohort had papillary microcarcinomas (<1 cm), which is the most indolent type of thyroid cancer:
    • Is it possible that the effects of GD on thyroid cancer outcomes might be more pronounced in more clinically relevant cases (i.e., larger or more aggressive thyroid cancers)?
    • This hypothesis is supported by a multicenter study in Italy, which indicated that GD was associated with a worse outcome of coexisting thyroid cancer only if the cancer was larger than 1 cm
  • Third, for patients with GD who have surgical indications, current American Thyroid Association guidelines recommend near-total or total thyroidectomy:
    • However, for GD patients whose thyroid function and TSAb titers are well controlled by antithyroid drugs, yet elect to have their coexisting low-risk PTC resected, what would be the optimal procedure to avoid overtreatment of these two diagnoses?
  • These important questions await further investigation

#Arrangoiz #ThyroidSurgeon #CancerSurgeon #HeadandNeckSurgeon #ThyroidExpert #EndocrineSurgery #PapillaryThyroidCancer #GravesDisease

• Clin Thyroidol 2022;34:71–74.
• Background:
  • In the period immediately following thyroidectomy for differentiated thyroid cancer, there is a need to determine the extent of persistent disease and the likelihood of cancer recurrence
  • Predicting the mortality from thyroid cancer is performed using the AJCC/UICC TNM system
  • In order to assess the risk for disease persistence and recurrence, the American Thyroid Association (ATA) guidelines for differentiated thyroid cancer use a variety of indicators that are determined primarily from the surgical pathology
  • In the initial postoperative assessment, the ATA guidelines state that postoperative thyroglobulin (Tg) values suggestive of distant metastases are considered high risk, though the levels that are useful to guide risk determination are not entirely clear
  • The current study is a single-center, retrospective analysis aimed at determining the prognostic significance of pre-ablation stimulated Tg (ps-Tg) levels on prediction of disease persistence / recurrence and its use as a component of the ATA risk-stratification system
• Methods:
  • Electronic records were collected from 2006 to 2018 at a tertiary care center in China
  • Patients were included in this analysis if they had undergone total thyroidectomy with postoperative radioactive iodine (RAI) ablation therapy and if their surgical pathology results were available
  • All patients were prepared for RAI using thyroid hormone withdrawal
  • Serum thyroid stimulating hormone (TSH), Tg, and thyroglobulin antibody (TgAb) levels were determined immediately prior to RAI administration
  • Patients with TgAb levels greater than 40 IU/ml were excluded
  • Patients were followed for an average of 5 years
  • The initial interaction was 6 to 12 months following RAI therapy
  • Patients with an excellent response to initial therapy (defined using criteria from the 2015 ATA differentiated thyroid cancer guidelines) were seen annually and followed with Tg measurements while taking levothyroxine (LT4) and with neck ultrasonography
  • Additional imaging studies were used if Tg levels were > 1 ng/ml
  • Anything other than an excellent response to initial therapy was counted as disease persistence
  • A receiver operating characteristic (ROC) curve was used to determine the most sensitive and specific levels of ps-Tg that predicted persistent/recurrent disease versus long-term remission
• Results:
  • Of the 2524 patients included in this analysis, over 26% were classified as high risk for recurrence by ATA criteria, indicating a cohort that included many patients with advanced disease
  • Of the 2524 patients, 69% were women and over 96% had classic variant papillary thyroid cancer (PTC)
  • The average primary tumor size was 1.4 cm, and 85% of patients had documented lymph node metastases
  • Approximately 85% of patients had an excellent response and 15% had persistent or recurrent disease at the end of the study
  • The median ps-Tg level was 2.42 ng/ml (1.87 for those with excellent response and 35.66 for those with persistent/recurrent disease). Based on ROC analysis, a ps-Tg level of 10.1 ng/ml correlated with a sensitivity of 76% and a specificity of 88%, yielding a positive predictive value (PPV) of 53% and a negative predictive value (NPV) of 95%. This NPV remained >90% in all ATA risk categories.When analyzed by ATA risk categories, a ps-Tg cutoff of 10.1 ng/ml was predictive of outcomes. When below this cutoff, the risk of persistent disease decreased from 9.9% to 4.1% in intermediate-risk patients and from 33.1% to 8.5% in high-risk patients. Similarly, a value above the cutoff significantly increased the risk of persistent/recurrent disease even in low-risk patients (3.5–26.7%). The risk increased in high-risk patients, from 33.1% to 69.5%.ConclusionsIn this retrospective institutional analysis, a single preablation stimulated Tg cutoff level of 10.1 ng/ml significantly improved the prediction of disease recurrence/persistence in differentiated thyroid cancer. The use of this cutoff significantly enhanced prediction when incorporated into the 2015 ATA risk stratification model for differentiated thyroid cancer.COMMENTARYAssessing the likelihood of disease persistence and recurrence is extremely important to patients and providers after a diagnosis of cancer. Notwithstand-ing a recent cancer diagnosis, there is a significant amount of anxiety for patients receiving RAI, as many of those selected to receive it typically have lymph node involvement or larger tumor sizes.Disease predictors lack predictive power in the immediate postoperative assessment of intermedi-ate- and high-risk scenarios based on the surgical pathology alone. Several studies have reported that delayed evaluation (i.e., up to a year following RAI ablation) utilizing biomarkers and neck ultrasonog-raphy have better prognostic capabilities (3-5). For a patient, waiting this long can be nerve-wracking. A test to improve the ability to predict recurrence earlier in the postoperative period is desirable.Often, we measure stimulated Tg prior to giving RAI, though there is no clear guidance as to the value above which higher risk for disease persistence is indicated. Moreover, where does this information fit in regard to what is already estimated based on the risk stratification from the 2015 ATA guide-lines? This study was based on a large sample size and used ROC curve analysis to identify 10.1 ng/ml as a preablation Tg level with an NPV of >90%. This study adds to the literature identifying a preablation stimulated Tg <10 ng/ml as a predictor of excellent response to initial treatment (i.e., surgery and RAI ablation) in intermediate- to high-risk patients (6). This is helpful, as prior studies have investigated lower-risk patients or used various Tg cutoff values (7-9). Additionally, the authors determined that the use of preablation Tg values helped to “refine” recurrence estimates within risk categories. Inter-THYROID CANCER Preablation Stimulated Thyroglobulin as a A l e x Te s s n owPredictor of Persistent/Recurrent Differentiated Thyroid Cancer

• Background:
  • Thyroid nodules and thyroid cancer are common clinical problems
  • The primary initial treatment of thyroid cancer is surgery:
    • Either thyroid lobectomy or total thyroidectomy
  • Experts have debated the extent of thyroid surgery and its impact on patient outcomes for many years
  • The 2015 ATA guidelines:
    • Endorsed thyroid lobectomy for low-risk differentiated thyroid cancers (DTCs):
      • Measuring 1 to 4 cm without extra-thyroidal extension (ETE) and clinical lymph node metastasis, in the absence of a family history of thyroid cancer and a personal history of radiation exposure to the head and neck
  • Subsequent literature has suggested that there has been a significant shift away from more extensive thyroid surgeries:
    • In managing benign and malignant thyroid disease
  • One study showed that the use of thyroid lobectomy in patients with thyroid cancer:
    • Increased from 17% in 2015 to 28% by the end of 2018
  • The current study was performed to further understand this surgical trend in patients with low-risk DTCs
• Methods:
  • This was a retrospective study of patients with well-differentiated thyroid cancer who underwent thyroid surgery at Memorial Sloan Kettering Cancer Center between 1986 and 2015
  • Patients were staged according to the American Joint Committee on Cancer 8th edition and classified as being at low, intermediate, or high risk for recurrence according to the 2015 ATA guidelines
  • The 2015 ATA dynamic risk-stratification system was used to assess the initial response to therapy within the first year
  • Patients with distant metastases; positive lymph nodes; stage T3, T4, or Tx; and ATA high risk of recurrence and who had undergone surgery other than total thyroidectomy (TT) or thyroid lobectomy (TL) were excluded
  • Propensity matching to create matched sets of TL and TT patients was used
  • Age, sex, histology, I-131 therapy, ATA risk, and pathologic T and N stage were used as propensity-matching criteria
  • Pearson’s test or Fisher’s exact test and the t-test were used to compare categorical and continuous variables, respectively
  • After propensity matching, multivariate analysis of the cohort using Cox proportional-hazards regression was performed
  • The primary outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS)
  • The Kaplan–Meier method was used to compare the primary outcome, and a log-rank test was used to compare the two groups
• Results:
  • A total of 3756 patients were included in the initial cohort (943 TL and 2813 TT)
  • The cohort used for analysis was then restricted to 1836 patients (918 patients in each group after propensity matching)
  • There were no differences in age, sex, histology, T stage, and ATA risk classification
  • The mean follow-up periods for TL and TT patients were 56.34 and 56.85 months, respectively
  • When comparing TL with TT, overall survival (10-year OS, 92.2% vs. 91.3%; P = 0.967), disease-specific survival (10-year DSS, 100% vs. 99.1%; P = 0.197), and recurrence-free survival (10-year RFS, 99.5% vs. 98.3%; P = 0.079) were not significantly different
  • Multivariate analysis showed that between variables of age, vascular invasion, microscopic ETE, margins, and extent of surgery, only age greater than 55 years was a predictor of OS (HR, 5.773; P<0.0001)
  • There were 67 and 45 deaths in the TL and TT groups, respectively:
    • Only 1 death was related to thyroid cancer, and it was in the TT group
  • There were 15 patients with recurrence, 10 (1.08%) in the TT group and 5 (0.05%) in the TL group
  • The median times from surgery to recurrence were 44.2 and 44.1 months for the TL and TT groups, respectively
  • There was no statistical difference between the two groups regarding the site of recurrence
• Conclusions:
  • Thyroid lobectomy is associated with mortality outcomes similar to those for total thyroidectomy in selected DTC patients with ATA low and intermediate risk for recurrence
  • It is reasonable to consider lobectomy in patients with:
    • Intrathyroidal DTCs less than 4 cm, no nodules in the contralateral lobe, and no suspicious lymph nodes on either preoperative imaging or intraoperative palpation
• Thyroid lobectomy is associated with fewer complications such as hypoparathyroidism, recurrent laryngeal nerve injury, and hypothyroidism
• However, the extent of thyroid surgery remains the subject of debate between experts despite the reported excellent outcomes in patients with low-risk thyroid cancers <4 cm treated with thyroid lobectomy
• This study also supports findings from these other studies in examining the extent of thyroid surgery on the long-term mortality outcomes of patients with low-risk thyroid cancer
• Also included in this study were 402 patients with ATA intermediate risk of recurrence:
  • There were 212 total thyroidectomies and 190 thyroid lobectomies, and no significant differences were identified between the two groups regarding overall survival, disease-specific survival, and recurrence-free survival
  • Because intermediate-risk features on histology are identified only postoperatively, these patients would usually be advised to undergo completion thyroidectomy
  • The likelihood of requiring completion thyroidectomy based on intermediate-risk disease has been reported to be around 30% to 60%
  • However, it has not been proven that completion thyroidectomy has a survival advantage over thyroid lobectomy in all patients with an intermediate risk of recurrence
• A study of 341 patients with papillary thyroid cancer (PTC) and intermediate risk of recurrence showed no benefit of total thyroidectomy in recurrence-free survival and disease-specific survival, as compared with thyroid lobectomy
• Another study of 129 patients with unilateral micro-PTC and ipsilateral lateral lymph node metastases without gross ETE showed non statistically significant recurrence-free survival between the group of patients treated with thyroid lobectomy plus lymph node dissection and that treated with total thyroidectomy plus lymph node dissection, with 60 months of follow-up
• The current study also concludes that thyroid lobectomy has an outcome equivalent to that for total thyroidectomy in selected patients with intermediate risk of recurrence
• Additional studies and long-term follow-up are warranted to examine the extent of thyroid surgery in thyroid cancer patients with an intermediate risk of recurrence
• It is essential to remember that many of these studies were carried out in a tertiary care center with experienced sonographers and experienced thyroid surgeons
• This recommendation may not translate to institutions where there is lower surgical volume and where radiologists may have less expertise in identifying suspicious findings related to thyroid cancer
• Patients’ preferences and financial status and ability to attend follow-up visits are also essential factors to consider
• Thus, the findings of this study are reassuring to show that selected patients even in this latter group (intermediate risk DTC patients) have similar long-term outcomes after thyroid lobectomy
• References
  • Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2016 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26:1–133.
  • Toumi A, DiGennaro C, Vahdat V, Jalali MS, Gazelle GS, Chhatwal J, Kelz RR, Lubitz CC 2021 Trends in thyroid surgery and guideline-concordant care in the United States, 2007-2018. Thyroid 31:941–949.
  • Matsuura D, Yuan A, Harries V, Shaha AR, Tuttle RM, Patel SG, Shah JP, Ganly I 2021 Surgical management of low-/intermediate-risk node negative thyroid cancer: A single-institution study using propensity matching analysis to compare thyroid lobectomy and total thyroidectomy. Thyroid 32:28-36.

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