Scintigraphic manifistation of thyrotoxicosis

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Scintigraphic Manifestations of

ThyrotoxicosisDr. Ahmed Abdo Harwn

هارون. عبدالله عبده أحمد دNuclear Medicine Consultant

1 December 2011Scintigraphic manifistations of thyrotoxicosis –

Dr.Ahmed Harwn

Scintigraphic manifistations of thyrotoxicosis – Dr.Ahmed Harwn

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LEARNING OBJECTIVES

Review the thyroid physiology and iodin metabolism

Discuss the distinction between thyrotoxicosis and hyperthyroidism.

Identify the thyroid uptake and Scintigraphy findings in both the common and uncommon causes of thyrotoxicosis.

Describe the therapeutic approach for the patient with thyrotoxicosis.

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• is the functional unit composed of thyroid follicular cells (Thyrocyts) that surround secreted colloid.

Follicle

• polarized—the basolateral surface is apposed to the bloodstream and an apical surface faces the follicular lumen.

The follicular cell

Thyroid physiology

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Thyroid physiology

Thyroid hormone level is monitored by:

• hypothalamic supraoptic nuclei• thyrotrophs of the anterior pituitary gland.

Reduced levels of thyroid hormone:

• increase basal TSH production• enhance TRH-mediated stimulation of

TSH

TSH-R stimulate adenylate cyclase and activate cAMP cascade.

• This stimulate NIS to trap iodide• Stimulate producing thyroglobulin• Stimulate hormone synthesis• Stimulate release of thyroid hormones.

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Thyroid physiology

High thyroid hormone

• Suppress TSH gene expression secretion • Inhibit TRH stimulation of TSH

Thyroid hormones return to its normal level

The thyroid axis is a classic example of an endocrine feedback loop.

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Iodine metabolism

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Deficiency:Goiter

• Children-diffuse goiters, • Adults-nodular goiters.

Hypothyroidism.

Critinism: most extreme manifestation of IDD

Decreased fertility rate

increased infant mortality

Mental retardation:

•Worldwide, iodine deficiency is the leading cause of preventable mental retardation , low IQ , and poor mental and psychomotor development (predominantly in language and memory skills). •Reduction in IQ in affected youth from regions of severe and mild iodine deficiency.•exaggerated in the setting of concomitant deficiencies of selenium or vitamin A.

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Daily allownce

Normal daily Dietary intake:The US Institute of Medicine (IOM) recommended dietary allowance (RDA)

• 150 mcg/d of iodine for adults and adolescents,• 220 mcg/d for pregnant women, • 290 mcg/d for lactating women, • 90-120 mcg/d for children aged 1-11 years. • The adequate intake for infants is 110-130 mcg/d.

Absorption: GI

• 100% regardless of the plasma level

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Excretion:

• Kidneys: 80% of daily intake• 24-hour urine collection• a median of 50-100 mcg of iodine per liter is consistent with mild iodine

deficiency, • 20-49 mcg of iodine per liter is consistent with moderate deficiency, • and less than 20 mcg of iodine per liter is consistent with severe

deficiency.• Fecal loss 15 μg/day• Minimal amount in sweat.

1 December 2011Scintigraphic manifistations of thyrotoxicosis –

Dr.Ahmed Harwn


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Iodine Sources

• Drinking water • Dairy products• Sea food• Kelp

Natural source:

• Bread (150 microgram per slice)• Cooking oil• Table salt (30 mcg / gram salt)

Supplement in

• Vitamin preparation• Cough medications• Amiodaron

medications:

Red food coloring

• 100ml contains : 30, 000, 000 μg of iodine = 100, 000 times the normal daily dietary intake.

Radiographic contrast

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Iodide pools:

Intra-thyroidal organic iodine pool:• Greatest = 6000 μg iodine.

Extra-thyroidal organic iodine pool:• ( thyroid hormones in circulation) = 500 µg

Inorganic free iodide pool:• in circulation =375 µg• 300 µg from daily intake• 60 µg from deiodination of thyroid hormones • 10 µg thyroid iodide leakage

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Excess amount of Iodide in Normal person.

Thyroid hormones level rises initially.

Intrathyroidal iodide level increases

Excess amount of Iodide

Soon return to normal through an escape phenomenon.

The hormone level goes down below the normal level

Inhibit thyroid hormone formation (Wolff-Chaikoff effect)

Intrathyroidal iodide reaches critical level

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Excess Iodide in abnormal situation

Thyrotoxicosis (iodide-induced)

(Jod-Basedow phenomenon)

No ((Wolff-Chaikoff effect)

Increased thyroid hormone levels

Excess amount of iodide

Iodine deficient areas

Patients with MNG

Hypothyroidism (iodide-induced)

No escape phenomenon

The hormone level goes down below the normal level

(Wolff-Chaikoff effect)

Increased thyroid hormone levels

Excess amount of iodide

in chronic inflammation like Hashimot;s thyroiditis

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Thyroid Hormone synthesis

Iodide trapping• Stimulated by TSH, TSI• Inhibited by competition

from large molecules Like TcO4

- , • Blocked by exogenous

Thyroxin • loss of iodide trapping

function in thyroid cancer associated with failure of radioiodine treatment.

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Organification (Oxidative iodination) & iodination• MIT or DIT• Stimulated by TSH• Inhibited by methimazole, PTU,

lithium, excess iodide.


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Coupling of iodo-tyrosine


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Release. (last come , first served)

stimulated by TSH

inhibited by lithium, excess iodide.

90% of the released thyroid hormone is in the form of T4, and 10% in the form of T3.

The great majority of T3 (80-90%) is produced by the peripheral conversion of T4.

The metabolic activity of thyroid hormone is determined by the amount of free T3 and free T4.


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Thyroid hormone actionRegulate the body’s metabolism and heat production.

Increases tissue O2 consumption

Increases glucose use

Increases lipolysis

Increases urinary nitrogen excretion

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Signs and symptoms


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Thyrotoxicosis

• Clinical syndrome of increased systemic metabolism that results when the serum concentrations of free thyroxin, free triiodothyronine, or both are elevated

Hyperthyroidism

• Overactivity of the thyroid gland with a resultant increase in thyroid hormone synthesis and release into the systemic circulation

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Classification of thyrotoxicosis

Increased thyroid function• Graves disease• Marine-Lenhart syndrome, • toxic autonomous nodule,• toxic multinodular goiter)

Thyroid inflammation

• subacute thyroiditis• silent thyroiditis, • Post partum thyroiditis

Iodine-induced hyperthyroidism.

• Factitious Hyperthyroidism,• Metastatic thyroid cancer,• Toxic struma ovarii

Thyrotoxicosis of Extrathyroidal Origin

Thyrotropin-induced hyperthyroidism (pituitary adenoma).

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Graves Disease (diffuse toxic goiter)

History:

• 24-year-old woman.

Laboratory:

• T4 = 16.7 μg/dL, • T3 = 311 ng/dL, • TSH < 0.01 μIU/mL.• 24-hour RAIU was 84%.

Findings:• Enlarged gland.• The target-to-background activity is

increased t• appearance of the pyramidal lobe (large

arrow).

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PATH PHYSIOLOGY:

• most common cause of thyrotoxicosis• an autoimmune disorder characterized by the presence of Thyroid

Stimulating Immunoglobulin (TSI) or Thyroid-Stimulating Antibody (TSAb).

• TSI is found in 90 to 95% of cases of Graves disease.

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The RAIU

• usually elevated at 24 hours. • Occasionally, normal in rapid iodine turnover, in severe cases. (4hrs is

useful)

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Therapy

Antithyroid medication:

• Normal sized gland• mild severity.

I-131 therapy

• modality of choice except in• pregnant • Lactating • severe ophthalmopathy

Surgery: Thyroidectomy

• in marked thyromegaly with tracheal compression

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Marine-Lenhart Syndrome

History:


Laboratory values:

• free T4 = 2.9 ng/dL, • T3 = 181 ng/dL, • TSH < 0.01 μIU/mL.

Scan:

• enlarged thyroid• diffusely increased radiotracer trapping, as

in Graves disease per se. • However, within the gland are distinct cold

nodules .1 December 2011


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Marine-Lenhart SyndromeGraves disease

• coexists with TSH-dependent cold thyroid nodules

Other names:

• Graves disease coexistent with a multinodular goiter. • Nodular Graves disease.

The RAIU

• Elevated.

Therapy:

• Further evaluation for the cold nodules.

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Toxic Autonomous Nodule (toxic adenoma)

History:

• 49-year-old woman

LAB:

• T4 = 15.1 μg/dL, • T3 = 304 ng/dL, • TSH < 0.01 μIU/mL• The 24-hour RAIU was elevated (46%).

Scan :• hot nodule occupies most or all of the right thyroid lobe with near-total suppression of the left lobe .

• The background activity is diminished to such an extent that the salivary glands are barely visualized.

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Toxic Autonomous Nodule (toxic adenoma)

Mechanism of formation:

• TSH receptors on the adenoma surface undergo gene mutation, resulting in their continuous activation

The RAIU

• mildly to moderately elevated or occasionally is in the upper range of normal.

Therapy:

• I-131 is the preferred therapy • surgical removal of the toxic nodule.

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Toxic Multinodular Goiter

History:

• 71-year-old man with anxiety and weight loss.

Laboratory values:• T4 = 12.1 μg/dL, • T3 = 299 ng/dL, • TSH < 0.01 μIU/mL• The RAIU was 17% at 6 hours and 37% at 24

hours. Scan:

• enlarged thyroid with overall nonuniform uptake.

• Areas of both increased and decreased activity are scattered throughout the gland

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Clinical diagnosis

• on palpation and diagnostic imaging of multiple (ie, two or more) nodules in the thyroid.

• The thyroid hormone levels are mildly elevated and the TSH level is suppressed

Scintigraphy :

• heterogeneous appearance• Functioning (hot) nodules scattered within

suppressed extranodular thyroid tissue.

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The RAIU:

• normal or slightly elevated.

Therapy:

• I-131 is most frequently used• Surgical

• very large goiter, with airway compression• substernal extension of the goiter

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Subacute thyroiditis

History:• 32-year-old woman with relatively rapid onset of

palpitations, insomnia, anxiety, neck pain, and mood swings, all of which were preceded by an upper respiratory tract infection.

Physical examination:

• neck tenderness.

Laboratory values:• Free T4 = 2.5 ng/dL, • free T3 = 640 ng/L, • TSH < 0.01 μIU/mL. • The 24-hour RAIU was 0.5%. Scan:

• minimal thyroid activity (arrow) only slightly higher than background activity.

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Subacute thyroiditis• subacute granulomatous

thyroiditis• giant cell thyroiditis, • de Quervain thyroiditis

Other names:

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Subacute thyroiditis

• very low since the affected thyroid is unable to transport or organify iodine.

RAIU

• no or minimal activity within the gland

Scintigrahy:

• Supportive: Salicylates and other nonsteroidal anti-inflammatory.

• steroids are the most effective therapy.

Treatment:

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Silent Thyroiditis

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History:

• 28-year-old woman. Thyrotoxic• No neck tenderness.

Laboratory values:

• T4 = 21 μg/dL, • T3 = 289 ng/dL, • TSH < 0.02 μIU/mL. • The 24-hour RAIU was 0.6%.

Scan:• barely visible thyroid • prominent salivary glands• a large-core needle biopsy was

performed, which demonstrated lymphocytic infiltrations within the thyroid parenchyma.


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Silent Thyroiditis

Other names:

• painless thyroiditis,• atypical thyroiditis,• subacute lymphocytic thyroiditis)

Cause:

• Autoimmune disease• The thyroid peroxidase antibody levels are elevated, as well as the thyroglobulin antibody titer. • An autoimmune response initiates an infiltration of lymphocytes, leading to disruption, with subsequent release of excess

thyroid hormone, • No neck pain or tenderness due to less follicular swelling compared with the giant cell infiltration and edema

characteristic of subacute thyroiditis.

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Self-limitingCourse:

Lasts from several weeks to several months

followed by a period of transient hypothyroidism,

which in turn is followed by complete recovery to the euthyroid state.

This disorder can recur at any time, and about 10% of patients will have recurrent episodes of thyroiditis.

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Silent Thyroiditis


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TFT:

• Serum T3 and T4 levels are high• TSH level is very low.

RAIU

• very low, as with subacute thyroiditis, secondary to cell damage.

Thyroid Abs

• The thyroid peroxidase antibody levels, and the thyroglobulin antibody are elevated

ESR is normal.

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Silent Thyroiditis


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minimal radiotracer concentration by the thyroid on scans because of the associated follicular cell damage

Acute phase:

the RAIU increases and the scan demonstrates diffusely increased activity “rebound” phenomenon. confusion with Graves disease

Recovery

phase

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Silent Thyroiditis


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Postpartum thyroiditisseen in

• 5 % of post-partum patients.

Pathophysiology:

• It is subtype of silent thyroiditis that appears 2 to 12 months after delivery (most commonly between 4 to 6 months).

The course of the disease :• similar to silent thyroiditis• thyrotoxicosis lasts 2 to 6 weeks and this is followed by• a period of hypothyroidism which also lasts 2 to 6 weeks.

Prognosis:

• 20-33% of patients with postpartum thyroiditis will become permanently hypothyroid.

Recurrence:

• The disorder tends to recur with multiple pregnancies

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Iodine-induced Hyperthyroidism (Jod-Basedow phenomenon).

History:

• 68-year-old man.• His history was significant for amiodarone therapy for intractable atrial fibrillation.

Laboratory values:

• free T4 = 1.7 ng/dL,• T3 = 351 ng/dL, • TSH = 0.05 μIU/mL. • The 24-hour RAIU was 2.7%.

Scan:

• decreased radiotracer trapping throughout the thyroid.

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Iodine-induced Hyperthyroidism (Jod-Basedow phenomenon).

Cause:• occurs insidiously when there is an excessive exposure to iodine in multinodular goiter,

in endemically iodine-deficient areas.• Does not occur in normal person due to protective mechanism Wolff-Chaikoff effect.

thyroid hormone levels:

• are elevated, • TSH level is suppressed,

RAIU

• low (The RAIU is inversely proportional to the iodine pool within the thyroid.)

Scintigraphy :

• diminished tracer concentration uniformly,

Treatment:• Antithyroid drugs in high doses, with or without potassium perchlorate, which blocks

further iodine uptake by the gland• If this regimen is unsuccessful, steroids are warranted

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History:

• 72-year-old male physician who was admitted to the hospital with multiple premature ventricular contractions.

thyroid function testing,

• free T4 = 5.5 ng/dL• T3 = 150 ng/dL, • TSH < 0.01 μIU/mL. • The I-123 RAIU at 24 hours was low (2%).

Scan:

• shows decreased activity throughout the thyroid.

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Factitious Hyperthyroidism

DDx

iodine-induced hyperthyroidism was not considered because there was no known previous iodine administration.

silent thyroiditis. The thyroid peroxidase Ant and antithyroid Ab are not elevated.

serum thyroglobulin level, which was undetectable; confirming the diagnosis of ?????????????

When confronted with this information, the patient admitted he was secretly taking L-thyroxine to “enhance sexual potency.”

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History:

• 53-year-old man with history of subtotal thyroidectomy for follicular thyroid cancer 5 years earlier. On suppressive dose of L-T4

• Presented with a mass compressing the lower thoracic spinal cord• Biopsy of the mass revealed metastatic follicular thyroid cancer.• In preparation for I-131 ablation, L-thyroxine therapy was stopped for 5

weeks. However, the thyrotoxic symptoms persisted;

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Lab:

• free T4 level was 2.6 ng/dL, • the free T3 level was 752 ng/L, • the TSH level was 0.02 μIU/mL.

Computed tomography (CT) of the chest

• a destructive mass in the right lung. • The diagnosis of thyrotoxicosis caused by metastatic follicular thyroid cancer was made.

I-131 ablation was then considered.

• Anterior Tl-201 whole-body image shows metastases in the right chest wall • thoracic spine.

Thallium-201 whole-body scanning was performed immediately before I-131 ablation.

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200 mCi (7,400 MBq) of I-131 was given as RAI treatment

• show thyroid bed uptake • right infraclavicular lymph node • chest wall metastasis • thoracic spine lesion

Postablation I-131 scan obtained 1 week


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Metastatic Thyroid Cancer

Rare to develop thyrotoxicosis.

• 131• ?? Surgery in single metastasis is causing the thyrotoxicosis,

pathogenesis is unknown, (thyroid-stimulating immunoglobulins)

The diagnosis: whole-body imaging or by postablation I-131 scanning.

Treatment:

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History:

• 81-year-old woman with thyrotoxicosis, ascites, and a pelvic mass.

Laboratory values:

• T4 = 13.7 μg/dL,• T3 = 200 ng/dL, • TSH < 0.01 μIU/mL.

pelvic CT.

• left ovarian mass

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Struma Ovarii

Tc-99m pertechnetate:

• decreased tracer activity in a small thyroid

The 24-hour RAIU

• 3%.

Pelvic scan was also performed.

• pelvic mass (arrowhead) displacing the bladder to the right (arrow).

I-123 scan for pelvis.

• Bottom left: I-123 image obtained after voiding shows the mass (arrow).

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Struma Ovarii

After surgery:

• Thyroid function soon returned to normal.

Two months later:

• 24-hour RAIU was 16%; • Tc-99m pertechnetate scanning shows normal

tracer concentration.

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Struma Ovariivery rare teratomatous ovarian tumour tumor that contains functioning thyroid tissue.• Serum T3 and T4 levels are elevated, • TSH level is suppressed. • RAIU is low

It is usually benign and is most commonly discovered by the pathologist when an ovarian tumor is removed

• faint visualization of the gland or nonvisulaization.

In a minority of cases, however, the tumor behaves autonomously and produces excess thyroid hormone.

Strong clinical suspicion for their diagnosis, comes from signs and symptoms relating to the abdomen or pelvis.

TFT:

Thyroid scan

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TSH-induced ThyrotoxicosisHistory:


Laboratory values:

• free T4 = 2.0 ng/dL,• T3 = 191 ng/dL, • TSH = 37.1 μIU/mL.

Tc-99m pertechnetate image:

• relatively high target-to-background activity

CT of the brain

• revealed a pituitary tumor. Upon removal of the tumor, the symptoms subsided and thyroid function returned to normal.

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ConclusionsThe patient with thyrotoxicosis is a diagnostic challenge to the clinician, symptoms can be mild to severe, signs can be subtle to obvious.

Signs and symptoms are identical regardless of the cause.

Cause must be determined for appropriate management and therapy.

The history and physical examination, along with thyroid function tests, enable correct interpretation of the thyroid scan and to make the diagnosis of thyrotoxicosis

RAIU and thyroid scintigraphy are useful in narrowing the differential diagnosis of Thyrotoxicosis

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References

Harrison's Principles of Internal Medicine, 18e

Nuclear Medicine 2e, Robert E. Henkin

Radiographics, “Scintigraphic manifestation of thyrotoxicosis” Charles M. Intenso et al

Iodine Deficiency Workup,

• Author: Stephanie L Lee, MD, PhD; Chief Editor and et al.

1 December 2011

Scintigraphic manifistation of thyrotoxicosis

Health & Medicine

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