Approach to the Patient with Subclinical Hyperthyroidism

JCEM 2007

Thyroid Nodule, AACE/AME/ETA 2010

Summary - Symptoms or Signs That Warrant Further Investigation:
• Prior head and neck irradiation
• Family history of MTC or MEN2
• Age <20 years or >70 years
• Male sex
• Growing nodule or nodule >10 mm
• Firm or hard consistency of nodule; ill-defined nodule margins on palpation
• Cervical adenopathy
• Fixed nodule on examination
• Dysphonia, dysphagia, and cough

Ultrasound is the first step in diagnosis: (Cancer is not less common in nodules <10 mm)
1) Microcalcifications: small intra-nodular punctate hyper-echoic spots with scanty posterior acoustic
shadowing (Specificity for cancer: 85-95%) (Sensitivity: 30-60%)
2) Irregular or micro-lobulated margins (Spec: 83.0% to 85.0%) (Sens: 55-75%)
3) Hypervascularity & chaotic arrangement of intra-nodular vascular images (Spec: 81%) (Sens: 74%)
(i.e. arteriovenous shunts and tortuosity of vessel course)
4) Degenerative changes and multiple fluid areas
5) Extracapsular growth: Extension of irregular hypo-echoic lesions beyond the thyroid capsule
(Invasion of pre-thyroid muscles, posterior extra-capsular growth, or infiltration of the recurrent
laryngeal nerve demand immediate cytologic assessment)
6) Complex or Cystic Lesions: Most complex thyroid nodules with a dominant fluid component are
benign. However, US-FNA should be done because papillary carcinomas can rarely be cystic.
7) Suspicious Cervical Adenopathy: Enlarged rounded lymph nodes with no hilum, but with cystic
changes, micro-calcifications, or chaotic hypervascularity are always biopsied.
Hypo-echoic appearance (a decreased echogenicity in comparison with the surrounding parenchyma,
similar to that of the cervical strap muscles) + one of the first 3 US findings above indicates a subset of
non-palpable thyroid nodules that are high risk for cancer

Additional suspicious criteria:
1) Rounded appearance
2) “More tall (anteroposterior) than wide (transverse)” shape of the nodule
3) “Marked hypo-echogenicity” of a solid lesion (hypo-echoic compared to the cervical muscles)
The presence of 2 suspicious criteria reliably identifies most neoplastic lesions (~90% of cases)
It is generally possible to restrict the number of US-FNA procedures to about a third of the
impalpable thyroid nodules.


American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules, 2010

Ultrasound of thyroid cancer, Cancer imaging, 2005

Equipment and technique

An advanced ultrasound machine with a high frequency transducer (7.5–12 MHz) is the basic equipment required. High frequency transducers allow superior near field resolution and form the basis of characterization of benign and malignant thyroid nodules. Colour flow applications are now standard, and a high sensitivity colour flow and power Doppler system is ideal. When using colour flow and power Doppler the machine should be calibrated to allow depiction of slow flowing vessels in the head and neck.

In evaluating the thyroid gland, scanning in the transverse and longitudinal planes is the most commonly used method. Adequate extension of the neck is required to ensure complete assessment of the inferior aspect of the thyroid gland, though this may be difficult in the elderly. Adjusting the depth and gain settings is essential to ensure the whole of both lobes and the superficial isthmus are fully assessed. To evaluate large goitres a lower frequency (5 MHz) transducer may be required to assess extension into the retroclavicular/retrosternal region.

Ultrasound examination of the thyroid must always include a detailed examination of the neck for any cervical lymphadenopathy. Metastatic cervical lymph nodes are frequently seen in thyroid cancers and may affect the surgical management and prognosis of patients.

Ultrasound features of thyroid nodules

The vast majority of thyroid nodules are benign, and the role of a radiologist in assessment of the thyroid gland is to differentiate a malignant thyroid nodule from the more commonly seen benign ones. It is therefore important to evaluate the sonographic features of thyroid nodules as these aid in their characterization.

Echogenicity

The incidence of malignancy is 4% when a solid thyroid nodule is hyperechoic. If the lesion is hypoechoic (Fig. 1), the incidence of malignancy rises to 26% [29]. However, hypoechogenicity alone is inaccurate in predicting malignancy, and if used as a sole predictive sign, it has a relatively poor specificity (49%) and positive predictive value (40%) [30].

Figure 1 Longitudinal grey scale sonogram shows a solid, hypoechoic thyroid nodule (arrows) with ill-defined margins anteriorly. Histology: papillary carcinoma.

Margins

A malignant thyroid nodule tends to have ill-defined margins on ultrasound (Fig. 1). A peripheral halo of decreased echogenicity is seen around hypoechoic and isoechoic nodules and is caused by either the capsule of the nodule or compressed thyroid tissue and vessels [31]. The absence of a halo has a specificity of 77% and sensitivity of 67% in predicting malignancy [32].

Calcification

Fine punctate calcification (Fig. 2) due to calcified psammoma bodies within the nodule is seen in papillary carcinoma in 25%–40% of cases [16]. If used as the sole predictive sign of malignancy, microcalcification is the most reliable one with an accuracy of 76%, specificity of 93% and a positive predictive value of 70% [30]. Coarse, dysmorphic or curvilinear calcifications commonly indicate benignity (Fig. 3).

Figure 2 Longitudinal grey scale sonogram shows characteristic punctate calcification (arrowheads) within an ill-defined solid hypoechoic thyroid nodule (arrows) which is highly suggestive of papillary carcinoma.

Figure 3 Longitudinal grey scale sonogram shows coarse calcifications (arrows) with dense shadowing within a thyroid nodule suggestive of benign calcification.

Comet tail sign

The presence of a comet tail (Fig. 4) sign in a thyroid nodule indicates the presence of colloid within a benign colloid nodule [33] and is a strong predictor of benignity.

Figure 4 Transverse grey scale sonogram shows the presence of comet-tail artifacts (arrowheads) within a predominantly cystic thyroid nodule (arrows). Features are of a benign colloid nodule. Curved arrow identifies the internal jugular vein and asterisk marks (more ...)

Solid/cystic

It is generally believed that thyroid nodules with large cystic components are usually benign nodules that have undergone cystic degeneration or haemorrhage (Fig. 5). However, papillary carcinoma occasionally demonstrates a cystic component and may mimic a benign nodule, though the presence of punctate calcification within the solid component helps in its identification (Fig. 6).

Figure 5 Longitudinal grey scale sonogram shows a well-defined heterogeneous thyroid nodule (arrows) with a large cystic component (arrowheads) and septation (open arrows). Features are compatible with a benign hyperplastic nodule.

Figure 6 Transverse grey scale sonogram shows a cystic component (open arrows) within a papillary carcinoma (arrows) of the thyroid. The presence of punctate calcification (arrowheads) identifies its malignant nature.

Multinodularity

It is a myth that multinodularity implies benignity, as approximately 10%–20% of papillary carcinomas may be multicentric [31, 34]. In those with true solitary nodules confirmed at surgery the risk of cancer is the same as in those with multinodular goitres [35]. Therefore against a background of multinodular changes, extra caution should be taken not to miss a suspicious nodule.

Colour flow patterns

In general there are three patterns of vascular distribution within a thyroid nodule [36]:

• –Type I: complete absence of flow signal within the nodule
• –Type II: exclusive perinodular flow signals
• –Type III: intranodular flow with multiple vascular poles chaotically arranged, with or without significant perinodular vessels.

Type III pattern is generally associated with malignancy. Types I and II are more commonly seen in benign hyperplastic nodules [36, 37]. Unfortunately if used as the sole predictor of malignancy, colour flow characteristics are not accurate [32], and have to be used in combination with other features seen on grey scale ultrasound.

It is well recognized that the predictive ability of ultrasound for malignancy is effective only when multiple signs are present in the same nodule. Although their predictive value increases in summation, it is at the cost of sensitivity [32].

Ultrasound of thyroid cancer

Thyroid nodule

THYROID NODULE GUIDELINES, American thyroid association, 2009

AACE/AME/ETA, 2010

Cutt off points of waist circumference for defining abdomnial obesity in the Korean population, 2006 대한비만학회지

Background: Recently, the International Diabetes Federation (IDF) consensus proposed a new definition for diagnosing metabolic syndrome. Ethnic-specific waist circumference (WC) cut-off points have been incorporated into the definition. Therefore, the study of the WC cut-off points for defining abdominal obesity in Koreans was performed by the Korean Society of the Study of Obesity.

Methods: The data used for analysis was from the Korean National Health and Nutritional Examination Survey (KNHANES) performed in 1998 (involved 6562 participants), which is representative of nutritional health research in Korea. The 2005 International Diabetes Federation definition of the metabolic syndrome was applied. The reasonable cut-off points of WC for abdominal obesity in Koreans were set based on Receiver Operating Characteristics (ROC) curve, odds ratio and prevalence of abdominal obesity in the study population.

Results: Using ROC analysis, the optimal WC to predict the risk factors of metabolic syndrome, such as high triglyceride levels, low levels of HDL-cholesterol, hypertension, and high glucose levels in Koreans, was 82~84 cm for men, and 79~82 cm for women. The odds ratio of having more than 2 metabolic abnormalities was about 5 in men with WC > 90 cm and in women with WC > 80 cm. WC in the 80th percentile in the Korean population is 90 cm and 86.5 cm for men and women, respectively.

Conclusions: The cut-off points of WC for abdominal obesity in Koreans are 90 cm for men and 85 cm for women, respectively. The cut-off points of waist circumference for defining abdominal obesity should be followed up by future additional studies and updated when new data becomes available.
Authorized only

Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005

This guideline is based on the evidence report and accompanying background papers developed by the Southern California Evidence-Based Practice Center. The American College of Physicians nominated this topic to the Agency for Healthcare Research and Quality Evidence-Based Practice Center program as part of a concerted effort to complement the guidelines of the U.S. Preventive Services Task Force. The College recommends that all clinicians refer to the Task Force recommendations as part of an overall strategy for managing overweight and obesity, which should always include appropriate diet and exercise for all patients who are overweight or obese. The intent of this guideline is to provide recommendations based on a review of the evidence on pharmacologic and surgical treatments of obesity. The target audience is all clinicians caring for obese patients, defined as a body mass index of 30 kg/m2 or greater. This guideline is not intended to be used by commercial weight loss centers or for direct-to-consumer marketing by manufacturers and does not apply to patients with body mass indices below 30 kg/m2.

Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005

Treatment of obesity, 2004 Finnish Medical Society Duodecim

Treatment of obesity, 2004 Finnish Medical Society Duodecim (revised 2007)

Obesity: Assessment and Management in Primary Care - June 1, 2001 - American Family Physician

Obesity: Assessment and Management in Primary Care - June 1, 2001 - American Family Physician

The Clinical/Practical Guide : Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, NIH

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report, 1998 NIH

The Practical Guide : Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, 2000 NIH

WHO | Obesity and overweight, 2005

Overweight and obesity lead to serious health consequences. Risk increases progressively as BMI increases. Raised body mass index is a major risk factor for chronic diseases such as:

•Cardiovascular disease (mainly heart disease and stroke) - already the world's number one cause of death, killing 17 million people each year.
•Diabetes – which has rapidly become a global epidemic. WHO projects that diabetes deaths will increase by more than 50% worldwide in the next 10 years.
•Musculoskeletal disorders – especially osteoarthritis.
•Some cancers (endometrial, breast, and colon).
Childhood obesity is associated with a higher chance of premature death and disability in adulthood.

WHO | Obesity and overweight

Diabetic Ketoacidosis: eMedicine Endocrinology

Diabetic Ketoacidosis: eMedicine Endocrinology

Grave's Disease, Review NEJM 2000

ROBERT Graves first identified the association of goiter, palpitations, and exophthalmos in 1835, although Caleb Parry had published details of a case 10 years earlier. The discovery of a thyroid-stimulating factor that was not thyrotropin in the serum of patients with Graves’hyperthyroidism was followed by the identification of this stimulator as an IgG antibody. It is now clear that Graves’hyperthyroidism is caused by these thyroid-stimulating
antibodies, which bind to and activate the thyrotropin receptor on thyroid cells. Graves’ disease also affects
the eyes (Graves’ ophthalmopathy) and the skin (localized dermopathy or myxedema), but the causes of these less common components of the disease are not known... Authorized only

Subclinical Hypothyroidism, Clinical Practice NEJM 2001

A 59-year-old woman is found to have a serum thyrotropin level of 7 mU per liter on routine screening. Her only symptoms are mild fatigue, which has been present for more than 10 years, and difficulty losing weight. The results of the physical examination are normal, except for the finding of a small, firm thyroid with a slightly irregular
surface. The serum cholesterol level is 220 mg per deciliter (5.69 mmol per liter), the low-density lipoprotein (LDL) cholesterol level is 140 mg per deciliter (3.62 mmol per liter), and a test for antibodies against thyroperoxidase is positive. Should treatment with thyroxine be initiated?... Authorized only

Antithyroid Drugs, Review NEJM 2005

Antithyroid drugs, which have been in use for more than half a century, remain cornerstones in the management of hyperthyroidism, especially for patients with Graves' disease. Surveys of thyroidologists from the early 1990s indicate that most practitioners consider antithyroid drugs the treatment of choice for most young people with Graves' disease, both in the United States and in the rest of the world.1,2 A substantial amount of new information, much of it evidence-based,3 has become available since the topic was last summarized in the Journal in 1984.4 The present review considers recent pharmacologic and clinical data related to the use . . . Authorized only