1 What are the thyroid’s landmarks?

They are the laryngeal prominence and cricoid cartilage. Start your exam by identifying the hyoid bone, a horseshoe mobile structure just under the mandible, so called because of its “upsilon” like shape. Immediately below it, you will find the thyroid cartilage, which can be readily identified by its V shape, the midline notch on the superior edge (laryngeal prominence), and its being the most prominent structure in the anterior neck (Adam’s apple). Just below it, separated by a little gap (the cricothyroid recess), is the horizontal ring of the cricoid cartilage. The thyroid isthmus lies immediately below, 4   cm from the laryngeal prominence. It connects the two lateral lobes of the gland by crossing the trachea over the second, third, and sometimes even the fourth ring. Note that while the distance between isthmus and landmarks (cricoid cartilage and laryngeal prominence) is constant in all individuals, the distance between laryngeal prominence and suprasternal notch is variable. This may result in glands that are either low lying or high lying in the neck (see Fig. 8-1).

Figure 8-1 Surface anatomy of the anterior neck.

2 Where are the thyroid lobes in relation to other neck structures?

The lateral lobes fan out from the midline isthmus just below the cricoid cartilage, curve posteriorly around the sides of trachea and esophagus, and then ascend backwards and upward like the two branches of a V (Fig. 8-2). Each lobe is 3–5   cm long, so that the lower margin reaches down to 2   cm above the clavicle (and fifth to sixth tracheal ring), whereas the upper margin extends instead upward to the middle of the thyroid cartilage. Except for its isthmus, the thyroid is covered by thin, strap-like muscles, of which only the sternocleidomastoid muscles (SCMs) are visible. Since the fascial envelope of the gland is continuous with the pretracheal fascia of both the hyoid and cricoid, the isthmus will ascend and descend with the larynx upon swallowing. This is important because it helps in distinguishing the thyroid from other neck structures.

Figure 8-2 Midline structures of the anterior neck.

3 What is the pyramidal lobe?

An upward extension of one of the lobes, usually the left, present in up to 50% of autopsies. Rarely palpable in the normal-sized gland, it is detectable in 10–15% of nontoxic goiters.

4 What is the best way to Inspect the thyroid?

By having the patient either stand or sit, with the head slightly tipped backward (around 10 degrees), and the cervical muscles as relaxed as possible. Neck extension is beneficial for two reasons:

Once the patient is well positioned, inspect the midline, 2–3   cm above the clavicles. Look within the SCMs for the inferior margins of the thyroid lobes, and then locate the isthmus (just below the cricoid cartilage). Finally, inspect the superior margins of the lobes (which should barely touch the sides of the thyroid cartilage). Look also for any possible pyramidal lobe. Use cross-illumination with a penlight to better accentuate shadows and nodules. Observing the gland from the side also may help detect possible protrusions. Note that unless a goiter is present, there should be no bulging between cricoid cartilage and suprasternal notch. Hence, a goiter is effectively ruled out if the gland is not visible on lateral view of an extended neck. Once inspection is complete, assess the associated venous structures of the neck, and record any possible abnormality (Figs. 8-3 and 8-4).

Figure 8-3 Nodule in the left lobe of the thyroid.

Figure 8-4 Accentuation of the thyroid nodule with lateral flexion.

5 How helpful is swallowing during inspection or palpation?

Quite helpful. According to some authors, it may raise the sensitivity of inspection to that of inspection and palpation combined. Although its role has not been formally studied, most skilled examiners do ask patients to swallow during inspection (and even palpation) for the following reasons:

6 Should the patient be given a glass of water?

Probably yes, since the extent to which laryngeal and thyroid structures move upward is proportional to the amount of swallowed bolus. Give patients a glass of water and ask them to hold a sip in their mouth until given the command to swallow. Repeat as needed.

7 How much information can be gained by inspection?

Quite a bit, thanks to the gland’s superficial position in the anterior neck. Inspection can tell us about location, size, shape, symmetry, and surface. It also can teach us about mobility with swallowing, thus distinguishing the thyroid from other neck structures.

8 What is Marañón’s sign?

It is the red (and at times itchy) skin overlying the thyroid of Graves’ patients. It was first described by the Spanish endocrinologist, Gregorio Marañón (1887–1960).

9 What are the goals of palpation?

To confirm size, location, shape, symmetry, and mobility of the gland—all previously identified through inspection. Palpation also can assess texture and consistency as well as fluctuance or tenderness—focal or diffuse. A hard thyroid, for example, suggests cancer, whereas a rubbery one is typical of Hashimoto’s disease. Palpation also can identify a solitary nodule or the multiple bumps of a multinodular goiter. It can detect the diffuse, fine, and rounded protuberances of Graves’ disease, whose gland is as bosselated as a raspberry. In these patients, a diffusely enlarged and soft goiter (i.e., one with the consistency of surrounding tissues) suggests a hypervascular Graves’ thyroid, whereas a firm goiter argues instead for an infiltrated gland, as in the later phases of the disease. Finally, tenderness in a firm and diffusely nodular gland argues for subacute thyroiditis, whereas tracheal deviation and cervical adenopathy suggest cancer.

10 What does the normal gland feel like?

Like the meat of an almond. In fact, each lobe is the size of a whole almond, no larger than the distal phalanx of the thumb (“rule of thumb”).

11 Should a normal thyroid be palpable?

Not necessarily. Glands of 15–20   gm (upper limit of normal) are barely palpable, whereas smaller ones (10–15   gm) are almost never detectable. Since thyroid size in a population is largely determined by dietary iodine supply, glands tend to be larger in deficient areas. Iodine supplementation has lately reduced the upper limit of normal from 35 to 20   gm in the United States, even though it remains 35 in iodine-deficient regions. This means that even a palpable thyroid may be “normal” in some parts of the world.

12 What is the average size of the gland?

Lobes are 2   cm wide, 4–5   cm high, and 2.5   cm deep. The isthmus is 1.25–2   cm wide (and high) and <0.6   cm deep. Weight is 10–20   gm, and volume <20   mL. Still, it is more convenient (for both physician and patients) to categorize thyroids as normal and palpable or normal and nonpalpable. Experienced examiners can easily palpate small goiters of up to 1.5 times normal (25–30   gm). In fact, in some iodine-deficient regions, glands of this sort may be considered nongoitrous. Thyroids weighing 40   gm (i.e., twice normal) are usually large enough to be appreciated even by a first-year student.

13 How do you palpate a thyroid?

Unlike inspection, palpation comes in many forms, including bimanual or single hand and anterior or posterior. None has been shown to be better.

Figure 8-5 Thyroid palpation, posterior bimanual approach.

Figure 8-6 Thyroid palpation of contralateral lobe, posterior approach.

Figure 8-7 A and B, Thyroid palpation, anterior approach.

14 What are the normal variants in size and location?

15 What other aspects of the general exam should be emphasized?

If you suspect an autoimmune disorder (such as Graves’), search for extrathyroidal signs—especially in the eyes and integument (nails and skin). Search also for findings of dysthyroidism.

16 What additional aspects of the neck exam are important in thyroid evaluation?

17 What are the potential complications of a large goiter?

Mostly obstructive, with impaired venous return (facial plethora) and a compression of the esophagus and trachea that may result in dysphagia and dyspnea. Stridor occurs in 10% of substernal goiters; tracheal deviation in one third. Although Graves’ glands may be up to two times normal (i.e., 40   gm), multinodular goiters are usually the most prominent offenders. When a large mediastinal or substernal thyroid obstructs the superior vena cava, there will be venous engorgement over the anterior chest and neck and possible impairment of cerebral venous return (Fig. 8-8). If reversible, all these findings can be unmasked by the Pemberton’s maneuver.

Figure 8-8 A and B, Superior vena cava syndrome.

18 What is the Pemberton’s maneuver?

A reversible superior vena cava (SVC) obstruction caused by a substernal goiter being “lifted” into the thoracic inlet as a result of arm raising. This makes the goiter behave like a “thyroid cork,” blocking the inlet and thus preventing venous return. To carry out the maneuver, ask the patient to elevate the arms above the level of the head, as if surrendering (“elevat[ing] both arms until they touch the sides of the head,” in Pemberton’s words). If the sign is present, “after a minute or so, congestion of the face, some cyanosis, and lastly distress become apparent.” In fact, the test is considered positive when the patient experiences either facial plethora (blue or pink suffusion of the neck and/or face due to venous stasis) or head congestion, dizziness, and stuffiness. If severe, the “thyroid cork” may even cause dyspnea and hypotension. The test is negative if nothing happens after 3 minutes of arm elevation (Fig. 8-9).

Figure 8-9 Pemberton’s sign. A 58-year-old woman with a 20-year history of goiter presented with a 2-month history of progressive dyspnea on exertion, occasional stridor, and a choking sensation while supine. She had previously been asymptomatic. A, Physical examination revealed a diffusely enlarged thyroid with no palpable nodules and undetectable lower poles. B, Within 30 seconds after raising both arms simultaneously (Pemberton’s maneuver), marked facial plethora (Pemberton’s sign) developed, indicating compression of the jugular veins. Serum thyrotropin and free thyroxine concentrations were normal. C, Computed tomography of the neck revealed a large goiter extending into the anterior superior mediastinum and causing compression and deviation of the trachea. The patient underwent thyroidectomy, and her symptoms resolved. Pathologic examination revealed a multinodular goiter.

(From Basaria R. Pemberton’s sign. N Engl J Med 350:1338, March 25, 2004, with permission.)

19 What is the significance of a positive Pemberton’s maneuver?

Facial plethora after arm raising (Pemberton’s sign) is diagnostic of increased pressure in the thoracic inlet. It is also prognostic, since these patients often have more severe disease, with airway compromise, reduced peak expiratory flow, and thrombosis of right subclavian and axillary veins. Hence, the maneuver should be used in all patients with:

Note that venous obstruction is not uncommon in substernal goiters, which present with distended neck and thoracic veins in 10–20% of the cases. Although rare, full-blown SVC syndrome also may occur. Still, many patients usually have few physical signs—with the possible exception of the inability to palpate the lower pole of the gland. This should serve as a clue to the presence of a substernal goiter. When in doubt, have the patient swallow, extend the neck, or carry out maneuvers that increase intrathoracic pressure—such as coughing or Valsalva’s or Pemberton’s.

20 Is Pemberton’s sign specific for a substernal goiter?

No, it may be encountered in other patients with reversible SVC syndrome because of lymphomas or upper mediastinal tumors. It also may occur in thoracic outlet obstruction.

21 Who was Pemberton?

Hugh Spear Pemberton (1890–1956) was a graduate of Liverpool University, and to Liverpool he returned after serving in WWI, practicing at Northern Hospital till his sudden death in January 1956 (just a year after retirement). An endocrinologist with an interest in diabetes, he also published on thyrotoxicosis, peripheral vascular disease, and hospital planning. The description of his homonymous sign appeared in a brief letter to The Lancet in 1946. Within 3 years the maneuver was on Bailey’s 1949 Demonstration of Physical Signs in Clinical Surgery, and then in most physical examination textbooks.

22 When should one auscultate the thyroid?

Whenever a goiter presents with signs of hyperthyroidism. A bruit reflects the gland’s increased vascularity—rare in simple thyrotoxicosis, but common in Graves’.

23 How do you distinguish a thyroid bruit from other neck sounds?

By location:

24 What is Berry’s sign?

An absent carotid pulse in patients whose cancer has invaded the vascular bundle. Always a sign of malignant thyromegaly.

25 Who was Berry?

Sir James Berry (1860–1946) was a Canadian surgeon who contributed extensively to the field of thyroid resection. During World War I, he also was a philanthropist, assembling with his first wife a medical team, and then traveling to Serbia. Captured by the Hungarians, he was forced to repatriate, but eventually returned to Eastern Europe to continue his humanitarian work. Berry died in 1946, at the age of 86.

26 How can one categorize thyroid abnormalities?

By assessing both physical findings and endocrine function (Table 8–1).

Table 8-1 Physical Findings and Disease Processes

27 What is the normal thyroid size?

“Normal” depends on iodine supply in the local diet. In the not-too-distant past, for example, thyroids became progressively larger as one ascended from the sea to the mountains. In fact, euthyroid goiters were so common in the Swiss and Italian Alps that they became part of the local folklore. For example, one of the most colorful of the Commedia dell’Arte masks was Gioppino, an Alpine mountaineer whose trademark sign was a gigantic goiter (Fig. 8-10). The very word cretin (in reference to endemic and congenital hypothyroidism) also has something to do with mountaineers and goiters. Sapira reminds us that some early Christians ran to the Pyrenees to escape persecution. They escaped successfully, but also acquired hypothyroidism, and the mental slowing associated with it. When traveling to different villages, they were easily recognized and immediately referred to as cretins (Chretien is French for Christian). Huge goiters still occur, but only in mountainous regions (like the Himalayas), where iodinated salt is not routinely instituted.

Figure 8-10 Goiter in the Commedia dell’Arte. The beginning of the 19th century saw the appearance of Gioppino in the Northern Italian area of Bergamo, even if little is known about its precise origins. The mask was first used onstage in 1820, by the puppeteer Battaglia, although many scholars believe it goes back even earlier, substantiating their claims with illustrations that clearly show its trademark three-hump goiter. Gioppino is a typical peasant character, full of common sense with a unique penchant for wine and good food. He invariably manages to get himself out of tricky situations by adhering to the popular motto: “big feet but a clever mind.” He sports a giant and trilobulated goiter (presumably euthyroid in function, since it has not slowed down its owner’s brain) and Horner’s syndrome (probably due to sympathetic compression by the goiter).

28 Which physical examination techniques can help establish thyroid size?

Still, little validation supports one method over another.

29 How precise are inspection and/or palpation in estimating thyroid size?

Quite precise. For interobserver variability, agreement among physicians in determining presence or absence of goiter (and in categorizing glandular size into one of three/four groups) is usually very good. The k for combined data from four studies is a respectable 0.77 (k ranges from +1.0 [two clinicians are in perfect agreement] through 0.0 [chance agreement] to −1.0 [two clinicians are in perfect disagreement]). Agreement is better among examiners with greater experience. It is also slightly better for palpation (k = 0.74) than inspection (k = 0.65). Data are good even for intraobserver variability. In this case, however, inspection (k = 0.73) seems to be slightly better than palpation (k = 0.65).

30 Why is estimating size clinically important?

Because in patients with suspected or known disease, size can:

For example, in patients presenting with symptoms of hyperthyroidism, an enlarged gland increases the likelihood of thyrotoxicosis, whereas a normal-sized gland makes anxiety more likely. Moreover, Graves’ disease patients presenting with a larger goiter are less likely to undergo immunologic remission during antithyroid therapy, thus favoring radioactive iodine (whose dose is also based on the size of the gland). Finally, evaluation of size can help monitor response to treatment. For example, shrinking of a large goiter after hormonal replacement suggests effective suppression.

31 What is a goiter?

From the Latin guttur (throat), this is a chronic enlargement of the gland (Fig. 8-11). Goiters occur endemically in iodine-deficient areas and sporadically elsewhere. As Sapira reminds us, the Latin for goiter is struma, a term still occasionally used, even though originally it did not indicate an enlarged thyroid, but instead a scrofula (i.e., the widening of the neck that makes the patient resemble a sow [scrofula in Latin]). Although this was mostly due to tuberculous lymphadenopathy, it eventually became linked to the thyroid after the Struma river of Bulgaria, an area of endemic goiter.

Figure 8-11 Euthyroid goiter in Nepalese woman.

32 What is the threshold for a goiter?

Some authors have suggested the “rule of thumb,” which defines as enlarged a lobe the size of the thumb’s distal phalanx. Alternatively, one could calculate the volume of each lobe by multiplying width by depth by length, and then multiplying the result by 2.

33 Are goiters neoplastic?

No. Cancers are usually nodular, even though at times they may be goitrous.

34 So what is the nature of goiters? Are they euthyroid?

Goiters are neither neoplastic nor inflammatory, but rather hypertrophic or degenerative. They do not reflect functional status either, since enlargements may occur in both euthyroid and dysthyroid states (either hypo- or hyper-). Overall, most goiters are euthyroid (80%); 10% are hypothyroid, and 10% hyperthyroid. Hence, they usually present as asymptomatic masses.

35 What are the three most common forms of a goiter?

Multinodular goiter, Hashimoto’s thyroiditis, and Graves’ disease. In euthyroid subjects, think of multinodular goiter and Hashimoto’s; in hypothyroid patients, think of Hashimoto’s; and in hyperthyroid patients, think of Graves’ and multinodular goiters (Graves’ also will have unique skin and eye manifestations).

36 What about subacute thyroidits?

It usually presents with tenderness, which can often mimic pharyngitis. Thyromegaly is otherwise modest (1.5–3 times normal). Note that the differential diagnosis of a painful and tender gland also should include spontaneous hemorrhage into a cyst or nodule.

37 Is goiter common in pregnancy?

No. Usually, there is a silent and postpartum thyroiditis that may manifest itself as goiter, although only half of the patients present as such (most are instead hyperthyroid). Otherwise, a true goiter is rather uncommon in pregnancy. Yet, mild hypertrophy is frequent, especially because of the changed hormonal milieu. In the past, this was even used as a “poor man’s” (or woman’s) pregnancy test. For example, overbearing Roman fathers used to keep a keen eye on their daughter’s neck by periodically measuring its circumference, so to detect, as early as feasible, any possible “loss of purity.”

38 What is the prevalence of goiter in iodine-replete countries?

Very low. If we define as “normal” a thyroid <10   gm (with an upper limit of 20), the prevalence of goiter in iodine-replete countries is about 2% in men and 10% in women.

39 Can goiters be easily differentiated from normal glands?

Yes. Normal thyroids are barely visible and only slightly palpable due to interference by various surrounding structures, especially the SCMs. Hence, the first sign of goiter is usually an increase in size of the lateral lobes, which become easily palpable. This is followed by a visible enlargement of the entire gland, first on lateral neck inspection and then on frontal view (with the neck extended). By the time the goiter is large enough to become palpable, it can be spotted from both front and sides.

40 So how can physical examination help identify a goiter?

Siminoski recommends the following strategy:

1. Examine the thyroid through inspection and palpation.

2. Categorize it as either normal or goitrous. If a goiter is present, subcategorize it as small (1–2 times normal) or large (>2 times normal).

3. If the goiter is small, consider the possibility of overestimation. Look for prominence in the neck profile and for visibility on frontal view while the neck is extended.

4. Finally, place the patient into one of the following three categories:

Goiter ruled-out (normal thyroid size, or gland not visible with neck extended)

Goiter ruled in (large goiter or lateral prominence >2   mm)

Inconclusive (all other findings)

41 What may lead to false-positive and false-negative results of goiter detection?

(a) False-positive thyroid enlargement (pseudogoiter)

1. Accentuated prominence of a palpable but in reality normal gland:

Thin patients whose thyroid is uniquely and misleadingly accessible.

Patients with long and curving neckline that makes the thyroid quite prominent in spite of its normal location and size. Such pseudogoiters have been dubbed the Modigliani syndrome, after the Italian artist’s penchant for long and lordotic necks. They are the most common cause of referral for possible goiter.

Patients whose thyroid is higher than usual in the neck. These account for 10% of all referrals. Important clues are a negative thumb sign and a laryngeal prominence that is more than 10   cm above the suprasternal notch.

2. The presence of a fat pad in the anterolateral neck (common in young women and obese patients). In contrast to the thyroid, the fat pad does not rise with swallowing.

3. Anterior neck masses. These can be easily differentiated from goiters by using swallowing. Branchial cleft cysts, cervical lymphadenopathy, and pharyngeal diverticula are all less likely to adhere to laryngeal structures, and thus will not rise with deglutition. Goiters instead will. One important exception is the thyroglossal duct cyst, which not only rises with swallowing, but also does so upon forced tongue protrusion (see Chapter 7, The Neck, questions 10–15).

(b) False-negative thyroid enlargement

42 What is the overall accuracy of physical examination in detecting a goiter?

Good. Combining data from nine separate studies, sensitivity is 70% and specificity 82%.

43 What is the clinical significance of a positive exam for goiter?

It depends. Goiters detected by inspection of the extended neck and palpation are unreliable. Conversely, goiters detected by inspection of the neck in normal position and palpation argue strongly in favor of thyromegaly (positive [likelihood ratio] LR = 26.3).

44 What is the significance of a negative exam?

Negative inspection, palpation, or a combination thereof does argue against the presence of goiter (LR of 0.4). Yet, it does not exclude it (see question 41). In fact, as many as half of all ultrasonically proven thyromegalies will remain undetected on exam.

45 What is the accuracy of physical examination in assessing thyroid size?

Quite good. The accuracy of exam in assigning thyroid size to the three categories of normal (0–20   gm), small goiter (1–2 times normal [i.e., 20–40   gm]), and large goiter (>2 times normal [i.e., >40   gm]) has positive likelihood ratios of 0.15, 1.9, and 25, respectively. Overall, glands that are 1–2 times normal tend to be overestimated in size, whereas glands that are 2.5 times normal tend to be underestimated.

46 Is the accuracy of detecting a goiter modified by the presence of thyroid nodules?

No, but it is increased by the examiner’s experience. As a result, senior physicians tend to have better accuracy than their more junior counterparts.

F. Thyroid Nodules

48 Why are nodules so commonly missed?

Same reasons as why goiters are missed: neck too short or thick, nodules too deep or small, and physicians too inept or cursory in their exams.

49 What is the average size of a palpable nodule?

3   cm. In fact, the larger the nodule, the more likely its detection (with <1   cm nodules being missed 90% of the time; <2   cm nodules 50% of the time).

50 Are thyroid nodules necessarily neoplastic?

No, only 5% are malignant. The rest are degenerative or adenomatous. Most are euthyroid.

51 And so, what is the significance of a thyroid nodule?

It should still be considered neoplastic until proven otherwise. Hence, it must be pursued with a fine needle aspirate. Ominous findings (such as vocal cord paralysis, cervical adenopathy, and fixation of the nodule to the surrounding tissues) argue in favor of malignancy, but are present in only one third of all thyroid cancers.

52 What is hyperthyroidism?

A constellation of signs and symptoms due to increased blood levels of thyroid hormone.

53 How common is hyperthyroidism?

It affects 4% of women and 0.2% of men.

54 What are its most common causes?

In addition to excessive administration of thyroid supplement, causes are mostly three: Graves’ disease (60–90%), toxic nodular goiter, and thyroiditis (subacute, silent, or postpartum).

55 How does hyperthyroidism present?

56 What are the findings most suggestive of hyperthyroidism?

Lid retraction (LR = 31.5), lid lag (LR = 17.6), fine finger tremor (LR = 11.4), moist and warm skin (LR = 6.7), and tachycardia (LR = 4 .4). Findings more likely to rule out hyperthyroidism are normal thyroid size (LR = 0.1), heart rate <90/min (LR = 0.2), and no finger tremor (LR = 0.3). A cumulative score of 19 symptoms and signs (Wayne index) has an LR for hyperthyroidism of 18.2 (if >20) and of 0.1 (if <10). Older hyperthyroid patients exhibit more anorexia and atrial fibrillation, more frequent lack of goiter, and overall fewer signs, with tachycardia, fatigue, and weight loss in more than 50% of patients (and all three in 32%).

57 And so, how does hyperthyroidism present in the elderly?

Mostly with cardiac or neurologic manifestations, often subtle:

Hence, any older patient presenting with new-onset heart failure, atrial fibrillation, or depression should be thoroughly evaluated for hyperthyroidism.

58 What are the three major manifestations of Graves’ disease?

When all three are present, the diagnosis is rather simple. But since manifestations may follow an independent course, the diagnosis is often more challenging.

59 What is the frequency of Graves’ disease?

It depends on gender and age, being higher in women and in the third to fourth decade of life.

60 Who was Graves?

Robert Graves was an Irishman (born in Dublin in 1797) who studied and practiced in Ireland and England and eventually became a superb clinician and teacher with a sarcastic sense of humor. In addition to medicine and painting (his main hobby), he had a knack for languages (he once was jailed in Austria as a possible Prussian spy because the border guards did not believe that a foreigner could speak such good German) and was also a born leader. During a trip in the Mediterranean, for example, he once saved a ship and its mutinous crew by assuming command in the middle of a storm. Besides linking his name to the association of goiter and exophthalmos, Graves also reported scleroderma, angioneurotic edema, and the pin-sized pupils of pontine hemorrhage. Note that in German-speaking countries, Graves’ disease is still referred to as von Basedow’s disease, in honor of Karl A. von Basedow (1799–1854), the German physician who in 1840 described the triad of goiter, exophthalmos, and palpitations. This eventually became known as the Merseburg triad, after the German town where von Basedow practiced medicine.

61 What is the dermopathy of Graves?

It is the result of a local infiltrative process, present in 4% of cases and usually involving the shins (pretibial myxedema). Histologically, it is characterized by dermal thickening, with presence of lymphocytes, various inflammatory cells, and lots of mucopolysaccharides. Although hyperthyroid signs may also be present, pretibial myxedema (like the ocular involvement of Graves’, which is also infiltrative) is not due to hyperthyroidism. In fact, it is independent of, and unrelated to, the functional state of the gland. Hence, patients may be completely euthyroid, with an asymptomatic and diffusely bosselated goiter, and yet still carry the classical infiltrative manifestations of skin or eyes. Nonetheless, half of all dermopathy cases do coincide with the active state of Graves’ and thus are commonly associated with hyperthyroidism.

62 What does pretibial myxedema look like?

The most common presentation is a localized, nonpitting edema of the shins. The more classic examples are instead well-demarcated, raised, and bilateral pinkish/brownish nodules on the anterior aspects of the shins (Fig. 8-12). These lesions may progress into a plaque or be located elsewhere on the legs, although they rarely involve the feet. Finally, pretibial myxedema may be pruritic or hyperpigmented.

Figure 8-12 A-E, Examples of pretibial myxedema.

63 How do you distinguish pretibial myxedema from the myxedema of hypo-thyroidism?

Pretibial myxedema is localized, whereas the hypothyroid form is more generalized.

64 What is thyroid acropachy?

It is the clubbing plus new periosteal bone formation that can occur in 5% of Graves’ patients. Unlike the bony enlargement of pulmonary hypertrophic osteoarthropathy, thyroid periostitis occurs in the hands and feet, but not the long bones. It also is typically asymptomatic and painless. The cause is long-acting thyroid-stimulating hormone (LATS). Hence, it is absent in other causes of thyrotoxicosis.

65 What other autoimmune findings can occur in Graves’ disease?

Premature graying, vitiligo, and hyperpigmentation.

66 What are the ocular manifestations of Graves’?

In addition to the nonspecific sympathetic manifestations of lid lag and lid retraction, Graves’ disease is associated with a unique infiltrative disease of the eyes, characterized by edema and lymphocytic penetration of ocular fat, connective tissue, and extraocular muscles. This may manifest with discomfort, a tearing/gritty sensation in the eyes, and diplopia. Eventually, congestion of multiple layers of the eyeball will cause proptosis of the involved eye (i.e., an abnormal forward protrusion of the eyeball from the orbit—more than 18   mm in extent) and ophthalmoplegia (see Figs. 8-13 and 8-14).

Figure 8-13 CT image of exophthalmos.

Figure 8-14 Gross pathology of exophthalmos.

67 Can proptosis be unilateral?

Yes, but rarely. Although Graves’ is the most common cause of proptosis in adults, this involves one eye in only 5% of the cases. Hence, unilateral proptosis should always be considered neoplastic (primary or metastatic) until proven otherwise.

68 How do you detect and assess the degree of proptosis?

The “poor man’s” test is to have the patient bend the head forward while you look down on the orbits and estimate the distance to the corneal surface. This usually allows you to assess whether the distance is indeed greater than normal. For a more accurate measurement, you can use a Hertel exophthalmometer (Fig. 8-15), a hand-held device designed to quantitate the distance between the lateral orbital rim and anterior corneal surface.

Figure 8-15 A and B, Hertel exophthalometer.

69 Does the degree of proptosis predict optic nerve involvement and loss of vision?

No. Only lid edema and extraocular motion defects predict involvement of the optic nerve and impending loss of vision.

70 What are the characteristics of Graves’ congestive ophthalmopathy?

It is characterized by the following (Fig. 8-16):

Figure 8-16 Congestive oculopathy.

71 What is ophthalmoplegia?

It is the inflammation, infiltration, engorgement, and paralysis of extraocular muscles in patients with Graves’ disease (often referred to as exophthalmic or congestive ophthalmoplegia). It preferentially affects the medial and inferior recti but may result in many extraocular motion defects and impairments, including muscle weakness and amblyopia, impaired upward gaze, impaired convergence, strabismus, visual field defects, and restriction of gaze and visual acuity. Described mostly in the past century by various German and Austrian physicians (plus a couple of Frenchmen, two Britons, a Swiss, and a Russian), these signs carry a plethora of eponyms. Note that lid retraction and lid lag can occur in any hyperthyroid patient, since they are caused by the sympathetic hyperactivity of the Mueller’s muscle (the same responsible for ptosis in Horner’s syndrome). Rosenbach’s sign is also the result of sympathetic hyperactivity. All other signs are instead typical of Graves’ infiltrative ophthalmopathy, occurring in 25–50% of patients (see Table 8-2).

Table 8-2 Thyrotoxicosis Eye Manifestations

* Nonspecific signs of hyperthyroidism. All others are typical of Graves’ ophthalmopathy.

72 What is onycholysis?

It is the partial separation of the nail plate from the nail bed at its more distal and lateral attachments (total separation is termed onychomadesis). Onycholysis is an uncommon finding of hyperthyroid states that typically involve the ring finger, wherein the free edge of the nail becomes undulated, upturned, and often so loose as to collect debris beneath it. Onycholysis can also involve all other fingernails. It is due to sympathetic overactivity and thus represents a nonspecific manifestation of hyperthyroidism. When associated with Graves’ disease, it is termed Plummer’s nails (Fig. 8-18). It can also occur with psoriasis, fungal nail infection (usually candidal), trauma, Raynaud’s disease, phototoxic reaction to tetracyclines, and constant wetting of the hands, as in dishwashers (see Chapter 3, The Skin, question 20).

Figure 8-18 Plummer’s nails (onycholysis).

73 Who was Plummer?

Henry Plummer was an American internist. Born in Hamilton, Minnesota, in 1874, he studied at Northwestern University and practiced at the Mayo Clinic from 1901 until his death in 1936. His creativity and innovation led him to redesign the medical records of Mayo and to develop the examination beds that are still commonly used throughout North America. Outside medicine, his interests included literature, music, and especially gardening. Plummer’s name also is linked to a thyroid nodule associated with hyperthyroidism but no ocular manifestations. The condition is sometimes called Plummer-Vinson adenoma in memory of Porter Vinson, a fellow in medicine at the Mayo Clinic and a junior associate of Plummer. This should not be confused with Plummer-Vinson syndrome (sideropenic dysphagia, iron deficiency anemia, dysphagia, esophageal web, and atrophic glossitis), which is not associated with onycholysis, but with the koilonychia of iron deficiency (see Chapter 3, The Skin, question 23).

74 What is hypothyroidism?

A constellation of signs and symptoms due to inadequate levels of thyroid hormone.

75 What is its frequency?

In countries that use iodine supplements, it affects 9% of women and 1% of men. The two most common causes are Hashimoto’s thyroiditis (two thirds of the cases) and radioiodine gland ablation (one third of the cases).

76 What is the value of physical exam in hypothyroidism?

It helps to separate patients with overt disease from those with the subclinical form, who have neither symptoms nor signs. It also helps to estimate pretest probability, prior to the inevitable hormonal measurement that remains the sine qua non for diagnosis.

77 How does hypothyroidism present?

With a reduced metabolic rate, tissue accumulation of mucopolysaccharides, and a series of neurologic/cardiovascular repercussions.

78 What are the manifestations of hypothyroidism?

See Table 8–3.

Table 8-3 Manifestations of Hypothyroidism

Skin and Soft Tissues	Neurologic Manifestations
Mostly due to accumulation of water-binding mucopolysaccharides (hence, the term myxedema)	Disinterested, complacent, lethargic
	Good muscle strength (but lethargic)
	Paresthesias
	Deafness
Coarse, dry, scaling, and cool skin (dryness from reduced sebum production, coolness from diminished blood flow)	Prolonged contraction and relaxation of the Achilles (“hung-up” reflex)—this can separate hypothyroid from euthyroid patients, but when assessed by the naked eye can be absent in three fourths of cases.
Sallow and yellowish color due to accumulation of carotenoids; in contrast to jaundice, also involves palms and soles	Hypothyroid speech (low-pitched, slow, and deep voice that has been compared to a 45 RPM record playing at 33 RPM); it can occur in up to 40% of patients and is due to accumulation of polysaccharides in the vocal cords.
Periorbital puffiness with facial edema
Doughy, nonedematous swelling
Thick nails
Coarse hair that breaks easily
Missing lateral eyebrow (Queen Anne’s sign). Present in one third of hypothyroid patients but also may occur in normal subjects; hence, of limited clinical value.
Cardiovascular Manifestations	Other Manifestations
Bradycardia	Goiter (more specific than sensitive: +LR, 2.8; −LR, 0.6)
	Weight gain—not as common as traditionally claimed, and in some studies not any more frequent in hypothyroid than euthyroid patients
	Constipation
	Menorrhagia

79 What is the clinical significance of hypothyroid findings?

They can only suggest the diagnosis, since confirmation of hypothyroidism depends exclusively on a highly sensitive thyroid-stimulating hormone (TSH) assay. Still, prevalence of symptoms and signs of overt hypothyroidism is remarkably different today from the old reports in the literature. To this end, Zulewski et al. have recently revisited the 1969 Billewicz index by quantifying each of its 14 signs and symptoms (Table 8–4) as +1 if present and 0 if absent. Using as gold standard modern thyroid function tests (absent in Billewicz’s time) they defined as hypothyroid patients with a cumulative score >5; as euthyroid those with score ≤2; and as intermediate (or borderline hypothyroid) those with scores 2–5. By doing so, they were able to identify 62% of overt hypothyroid and 24% of subclinical hypothyroid patients, as compared to 42% and 6%, respectively, when using Billewicz’s definition. As for hyperthyroidism, clinical scores of hypothyroidism may perform less well in the elderly. Overall, findings more strongly suggestive of hypothyroidism are: bradycardia (+LR = 3.88), abnormal ankle reflex (+LR = 3.41), and coarse skin (+LR = 2.3). Cool and dry skin also has high likelihood ratio. Still, no single finding, when absent, can effectively rule out hypothyroidism (−LR = 0.42–1.0). Even the combination of signs with the highest likelihood ratios (coarse skin, bradycardia, and delayed ankle reflex) is only modestly accurate (+LR = 3.75; −LR = 0.48).

Table 8-4 Frequency of Hypothyroid Signs and Symptoms in Patients and Controls

(Data from Zulewski H, Muller B, Exer P, et al: Estimation of tissue hypothyroidism by a new clinical score: Evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab 82:771–776, 1997.)

Acknowledgment

The author gratefully acknowledges the contributions of Janice Wood, MD, to this chapter in the first edition of Physical Diagnosis Secrets.