Imaging in Endocrinology

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Library of Congress Cataloging-in-Publication Data

Pozzilli, Paolo, author.

Imaging in endocrinology / Paolo Pozzilli, Andrea Lenzi, Bart L. Clarke, William

F. Young Jr.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-470-65627-3 (cloth : alk. paper) – ISBN 978-1-118-74907-4 (epub) – ISBN

978-1-118-74908-1 – ISBN 978-1-118-74930-2 (emobi) – ISBN 978-1-118-74931-9 (epdf)

I. Lenzi, Andrea, author. II. Clarke, Bart, author. III. Young, William F., Jr., 1951- author. IV.

Title.

[DNLM: 1. Endocrine System Diseases–Atlases. 2. Diagnostic Imaging–methods–Atlases.

3. Metabolic Diseases–Atlases. WK 17]

RC649

616.40022′3–dc23

2013029209

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover images: © the authors

Cover designer: Visual Philosophy, Ltd., Oxford

About the Companion Website

This book is accompanied by a companion website: www.wiley.com\go\Pozzilli\endocrinemetabolicdisease

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Powerpoints of all figures from the book for downloading

Preface

No medical discipline requires such a precise phenotypic classification and careful consideration of the image as does endocrinology. Indeed, it is from observation that the endocrinologist extrapolates the elements upon which he or she bases clinical reasoning in the identification of a medical condition.

This atlas aims to be a valuable guide in endocrine diagnosis – suitable for both specialists and physicians in training, as well as physicians in other disciplines with an interest in endocrine disorders. Using the image as a unifying theme, we address the most salient themes of the science of endocrinology – including thyroid, pituitary, adrenal, endocrine pancreas, bone and mineral metabolism, and gonads. Each section provides iconographic support for the pathologies examined.

The universal character of this atlas guarantees a high standard of quality. The work was carried out in both Italy and the USA and has the added benefit of combining the rigor and scientific integrity belonging to the cradle of modern endocrinology (Rome) and the clinical resources of a major quaternary endocrine referral center (Mayo Clinic).

We would like to express our gratitude to all those who collaborated on this project. Their passion and enthusiasm toward the completion of this work has been exceptional. Without their hard work and dedication, this publication would have not seen the light.

We would also like to thank Wiley and its editors, who have demonstrated, once again, the high level of professionalism and special attention to detail needed to successfully bring to fruition this type of publication. We hope you enjoy consulting the Atlas.

Paolo Pozzilli, Andrea Lenzi, Bart L Clarke

and William F Young Jr

July 2013

Collaborators

Giusy Beretta

(collaborator for Thyroid and Pancreas chapters)

Senior Investigator

Dept of Endocrinology and Diabetes

University Campus Bio-Medico

Rome, Italy

Daniele Gianfrilli

(collaborator for Gonads and Mucocutaneous Manifestations of Endocrine Disorders chapters)

Senior Investigator in Endocrinology

Dept of Experimental Medicine

Section of Medical Pathophysiology, Food Science, and Endocrinology

Sapienza University of Rome

Rome, Italy

Elisa Giannetta

(collaborator for Gonads and Mucocutaneous Manifestations of Endocrine Disorders chapters)

Senior Investigator in Endocrinology

Dept of Experimental Medicine

Section of Medical Pathophysiology, Food Science, and Endocrinology

Sapienza University of Rome

Rome, Italy

Andrea M. Isidori

(collaborator for Gonads and Mucocutaneous Manifestations of Endocrine Disorders chapters)

Assistant Professor of Endocrinology

Dept of Experimental Medicine

Section of Medical Pathophysiology, Food Science, and Endocrinology

Sapienza University of Rome

Rome, Italy

Angelo Lauria

(collaborator for Thyroid and Pancreas chapters)

Senior Investigator

Dept of Endocrinology and Diabetes

University Campus Bio-Medico

Rome, Italy

Andrea Palermo

(collaborator for Thyroid and Pancreas chapters)

Senior Investigator

Dept of Endocrinology and Diabetes

University Campus Bio-Medico

Rome, Italy

Alberto Signore

(collaborator for Thyroid and Pancreas chapters)

Professor, Dept of Nuclear Medicine

Sapienza University II Medical Faculty

Rome, Italy; and

Dept of Nuclear Medicine

University of Groningen,

The Netherlands

1

Thyroid

Hashimoto’s thyroiditis (chronic autoimmune thyroiditis)

Definition and epidemiology

Hashimoto’s thyroiditis (HT), or chronic lymphocytic thyroiditis, is an autoimmune disease in which the thyroid gland is attacked by a variety of cell and antibody-mediated immune processes. The name Hashimoto’s thyroiditis is derived from the 1912 original report by Hashimoto describing patients with both goiter and intense lymphocytic infiltration of the thyroid (Figs 1.1 & 1.2) as struma lymphomatosa.

Hashimoto’s thyroiditis is the most common cause of primary hypothyroidism in iodine-sufficient areas of the world; it is among the most common causes of nonendemic goiter. On average 1.0–1.5/1000 people suffer from this disease. It occurs far more often in women than in men (incidence of 10 : 1 to 20 : 1, respectively), and it is most prevalent between 45 and 65 years of age. Occurrence in children is also uncommon, especially in populations where iodine is not a dietary scarcity.

Etiology and pathogenesis

Autoantibodies may be present against thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone (TSH) receptors, although a small percentage of patients may have none of these antibodies present. Antibody-dependent cell-mediated cytotoxicity is a substantial factor behind the apoptotic fallout of HT. Activation of cytotoxic T lymphocytes (CD8+ T cells) in response to cell-mediated immune response affected by helper T lymphocytes (CD4+ T cells) is central to thyrocyte destruction. Recruitment of macrophages is another effect of helper T-lymphocyte activation, with Th1-axis lymphocytes producing inflammatory cytokines within the thyroid tissue to further macrophage activation and migration into the thyroid gland for a direct effect. Infection, stress, sex steroids, pregnancy, iodine intake, and radiation exposure are known possible precipitating factors for HT. Fetal microchimerism within the maternal thyroid is also a possibility.

Signs and symptoms

Hashimoto’s thyroiditis very often results in hypothyroidism with bouts of hyperthyroidism. Symptoms of HT include weight gain, depression, mania, sensitivity to heat and cold, paresthesia, fatigue, panic attacks, bradycardia, tachycardia, high cholesterol, reactive hypoglycemia, constipation, migraine, muscle weakness, cramps, memory loss, infertility, hair loss, and myxedematous psychosis.

Diagnosis

Laboratory findings

Laboratory tests for HT include:

Antithyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs)

TSH, free thyroxine (FT4)

Total cholesterol, high density lipoprotein (HDL), and triglycerides

Imaging tests

Imaging tests for HT include:

Neck ultrasound (Fig. 1.3)

Computed tomography (CT) scan (rare)

⁹⁹mTcO4 thyroid scintigraphy (Fig. 1.4)

Treatment

In patients with primary hypothyroidism, the main treatment is levothyroxine.

Illustrations (Figs 1.1–1.4)

Figure 1.1 Cytology of thyroiditis. This figure shows rare and normal thyrocytes associated with numerous lymphocytes (Papanicolau, 10×).

Figure 1.2 Histology of thyroiditis. Hashimoto thyroiditis is characterized by Hürthle cells associated with follicular lymphoid structures (HE, 10×).

Figure 1.3 A 46-year-old woman with a recent episode of cervical tenderness and a familiar history of thyroid disease. The patient complained of fatigue and reported a weight gain of about 10 kg in the last 2 months. (a) Thyroid ultrasound – cross section. This ultrasound shows a thyroid with a slight increase in volume, globular shape, and homogeneous structure, and less echogenic than normal. (b) Thyroid ultrasound – longitudinal section. This ultrasound shows diffuse patchy hypoechoic lesions throughout the gland. This sonographic appearance is called a leopard skin pattern and is seen in lymphocytic infiltration of the thyroid in Hashimoto’s thyroiditis. The hypoechoic lesions within the thyroid are areas of lymphocytic infiltration of the thyroid tissue. C, carotid artery; H, hypoechoic lesions; P, thyroid parenchyma; T, trachea.

Figure 1.4 The same patient as in Fig. 1.3: ⁹⁹mTcO4 thyroid scintigraphy with iodine uptake curve. Iodine uptake was 2% at 4 hours (a) and 2% at 24 hours (b). The scan showed no uptake in the thyroid bed. The free triiodothyronine (FT3) and free thyroxine (FT4) levels were low with elevated thyroid stimulating hormone (TSH) and antibodies against thyroperoxidase (TPOAb) values. The patient started levothyroxine treatment.

Graves’ disease (Basedow’s disease)

Definition and epidemiology

Graves’ disease (GD) is an autoimmune disease representing the most common cause of hyperthyroidism (60–90% of all cases).

Graves’ disease has a powerful hereditary component, affecting up to 2% of the female population, and is between five and ten times more common in females than in males (incidence of 5 : 1 to 10 : 1, respectively). It is also the most common cause of severe hyperthyroidism, which is accompanied by extended clinical signs and symptoms and laboratory abnormalities compared with milder forms of hyperthyroidism. About 30–50% of patients with GD will also suffer from Graves’ ophthalmopathy, which is caused by inflammation of the eye muscles mediated by an inflammatory immune process.

Etiology and pathogenesis

Graves’ disease is an autoimmune disorder in which the body produces antibodies to the receptor for thyroid stimulating hormone (TSHrAb). (Antibodies to thyroglobulin and thyroperoxidase may also be produced.) TSHrAb bind to the thyroid stimulating hormone (TSH) receptors, which are located on cells producing thyroid hormone in the thyroid gland (follicular cells), and chronically stimulate them, resulting in an abnormally high production of triiodothyronine (T3) and thyroxine (T4). There are several factors that predispose to GD and Graves’ ophthalmopathy; in particular, genetic susceptibility, infection, smoking, pregnancy, iodine, and iodine-containing drugs.

Signs and symptoms

Signs and symptoms of GD all result from the direct and indirect effects of hyperthyroidism, with the main exceptions being Graves’ ophthalmopathy, goiter, and pretibial myxedema.

Diagnosis

Laboratory findings

Laboratory tests for GD include:

Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)

TSHrAb

Total cholesterol, high density lipoprotein (HDL), triglycerides

Imaging tests

Imaging tests for GD include:

Thyroid ultrasound (Fig. 1.5)

⁹⁹mTcO4 thyroid scintigraphy (Fig. 1.6)

Computed tomography (CT) neck scan

Orbital nuclear magnetic resonance (NMR)

Treatment

Treatment options for GD are:

Beta blockers (rapid amelioration of symptoms)

Thionamide

Radioiodine ablation

Surgery

Glucocorticoid (for Graves’ ophthalmopathy)

Orbital irradiation (for Graves’ ophthalmopathy)

Orbital decompression surgery (for Graves’ ophthalmopathy)

Illustrations (Figs 1.5 & 1.6)

Figure 1.5 A 32-year-old man presented with an unintentional 15 kg weight loss but with an otherwise normal physical examination. Laboratory studies revealed a suppressed thyroid stimulating hormone (TSH) concentration and an elevated thyroxine level, which are consistent with hyperthyroidism. Thyroid ultrasound – (a) cross section and (b) longitudinal section. These ultrasound/color Doppler images reveal markedly increased vascularity throughout the thyroid gland (thyroid hell). P, thyroid parenchyma; T, trachea.

Figure 1.6 Thyroid scan of the same patient from Figure 1.5 with ⁹⁹mTcO4. The thyroid scan with ⁹⁹mTcO4 before (a) and after (b) treatment with methimazole. Intense and homogeneous uptake of the radiopharmaceutical in both lobes of thyroid gland is seen before therapy. The post-therapy scan was performed 6 months after therapy and shows a reduction of thyroid size and uptake.

Subacute thyroiditis (de Quervain’s thyroiditis)

Definition and epidemiology

Subacute thyroiditis (ST) is a subacute granulomatous thyroiditis that belongs to a group of thyroiditis conditions known as resolving thyroiditis. Other names for this disorder are de Quervain’s thyroiditis, subacute nonsuppurative thyroiditis, giant cell thyroiditis, and painful thyroiditis. It has an incidence of 12.1/100 000 per year with a higher incidence in females than in males (19.1 and 4.1/100 000 per year, respectively). It is most common in young adulthood (24/100 000 per year) and middle age (35/100 000 per year), and decreases with increased age.

Etiology and pathogenesis

Subacute thyroiditis is presumed to be caused by a viral infection or a postviral inflammatory process. The majority of patients have a history of an upper respiratory infection prior to the onset of thyroiditis (typically 2–8 weeks beforehand). The disease was thought to have a seasonal incidence (higher in the summer), and clusters of cases have been reported in association with Coxsackievirus, mumps, measles, adenovirus, and other viral infections. Thyroid autoimmunity does not appear to play a primary role in the disorder, but it is strongly associated with HLA-B35 in many ethnic groups. A unifying hypothesis might be that the disorder results from a common subclinical viral infection that provides an antigen, either of viral origin or resulting from virus-induced host tissue damage, that uniquely binds to HLA-B35 molecules on macrophages. The resulting antigen-HLA-B35 complex activates cytotoxic T lymphocytes that then damage thyroid follicular cells, since the cells have partial structural similarity with the infection-related antigen. Unlike autoimmune thyroid disease, however, the immune reaction is not self-perpetuating, so the process is limited. The resulting thyroid inflammation damages thyroid follicles and activates proteolysis of the thyroglobulin stored within the follicles. The result is an unregulated release of large amounts of thyroxine (T4) and triiodothyronine (T3) into the circulation resulting in clinical and biochemical hyperthyroidism.

Signs and symptoms

Subacute thyroiditis is a self-limiting thyroid condition associated with a triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function. In particular, ST may be responsible for 15–20% of patients with thyrotoxicosis and 10% of patients presenting with hypothyroidism. Pain is the main symptom and it may be limited to the thyroid region or it may radiate to the upper neck, jaw, throat, upper chest, or ears. It can be exacerbated by coughing or turning the head. Fever, fatigue, malaise, anorexia, and myalgia are common.

Diagnosis

Laboratory findings

Laboratory tests for ST include:

Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)

Erythrocyte sedimentation rate (ESR)

Polymerase chain reaction (PCR) for C-reactive protein

Hemochrome

Imaging tests

A neck ultrasound is needed (Fig. 1.7).

Treatment

Subacute thyroiditis is a self-limiting condition and so in most patients no specific therapy, such as antithyroid or thyroid hormone replacement therapy, is necessary. Treatment of patients with ST should be directed at providing relief for thyroid pain (e.g. prednisone) and tenderness, and ameliorating symptoms of hyperthyroidism (e.g. with a beta blocker such as propranolol).

Illustration (Fig. 1.7)

Figure 1.7 A 47-year-old woman presents with pain and tenderness on her right side due to a chronic goiter. Her erythrocyte sedimentation rate was elevated and her thyroid laboratory tests suggested subclinical hypothyroidism. Two weeks previously, she had a fever and now her ⁹⁹mTc pertechnetate uptake is markedly decreased. (a) Thyroid ultrasound – cross section (before treatment). Focal hypoechogenicity in the painful area with decreased vascular flow by Doppler scan. C, carotid artery; P, thyroid parenchyma. The patient’s clinical symptoms showed a dramatic response to glucocorticoid treatment. She became hypothyroid and began levothyroxine therapy. (b) Thyroid ultrasound – cross section (after treatment). The focal hypoechogenicity is reduced and the thyroid parenchyma has become more homogeneous. C, carotid artery; P, thyroid parenchyma.

Benign thyroid nodules

Definition and epidemiology

Thyroid nodules are the most common of thyroid diseases. They affect up to 5% of the general population and are more frequent in iodine deficient areas and in women (female to male ratio, 5 : 1). Thyroid nodules are mostly benign (adenoma, cysti, focal hyperplasia) and the incidence of malignant neoplasia is very low (4/100 000 per year).

Thyroid nodules are abnormal cell growths in the thyroid gland. The thyroid can be uninodular when a single nodule is present or multinodular when multiple nodules are present.

Thyroid nodules are mostly nonfunctioning but can be hyperfunctioning (toxic multinodular goiter, Plummer’s disease) leading to symptoms of hyperthyroidism.

Etiology and pathogenesis

The etiology of thyroid nodules is unknown. There are several factors that predispose to these nodules; in particular, genetic susceptibility, iodine deficiency, neck irradiation, and unknown environmental agents.

Signs and symptoms

Usually thyroid nodules are asymptomatic and they are occasionally discovered during physical examination or an ultrasound neck scan.

Signs and symptoms of large nodules or multinodular goiter mainly result from thyroid increased volume and neck compression. The signs and symptoms include:

Neck lump

Neck pain, dyspnea, dysphagia, dysphonia

Symptoms due to hyperthyroidism (in toxic multinodular goiter or Plummer’s adenoma)

Diagnosis

The gold standard for diagnosing thyroid nodules consists of both a neck ultrasound scan (evaluating nodules size and eventually suspicious features) and fine needle cytology (FNC) to diagnose malignant neoplasia.

Laboratory and cytology tests

The laboratory and cytology tests for thyroid nodules include:

Calcitonin (in nodules suspicious for medullary carcinoma)

Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)

Cytology (fine needle cytology)

Imaging tests

Imaging tests for thyroid nodules include:

Thyroid ultrasounds (Figs 1.8a, 1.9a & 1.10a): Relevant ultrasound scan features of thyroid nodules are: echostructure (solid, cystic, or mist nodules), echogenicity (ipo-, iso-, or anechogen nodules), vascular pattern, presence of microcalcifications (regular or irregular), and defined or undefined margins

Computed tomography (CT) neck scan (Fig. 1.11)

Neck X-ray

Scintigraphy thyroid scans (Figs 1.8b, 1.9b & 1.10b)

Treatment

Treatment options for thyroid nodules are:

Clinical and ultrasound scan follow-up

Surgery (for compressive symptoms, tracheal or neck vessel compression or dislocation, mediastinal thyroid)

Treatment of hyperthyroidism (toxic multinodular goiter, Plummer’s adenoma)

Illustrations (Figs 1.8–1.11)

Figure 1.8 A case of thyroid toxic adenoma. A 56-year-old female patient with symptoms of hyperthyroidism. Hormonal blood levels showed increased free triiodothyronine (FT3), free thyroxine (FT4), and suppressed thyroid stimulating hormone (TSH). (a) Thyroid ultrasound showed a hypoechoic solid nodule of 14 × 15 mm with intra- and perinodular vascularization in the lower third of the right thyroid lobe. (b) The thyroid morpho-functional study was performed with 50 μCi of ¹³¹I orally and 3 mCi of ⁹⁹mTcO4 intravenously to evaluate thyroid uptake of iodine and scintigraphic distribution of Tc, respectively. Thyroid uptake was 17% at 6 hours, 29% at 24 hours, and 22% at 48 hours (data relevant for dosimetric calculations). The thyroid scan confirmed the clinical suspicion of Plummer’s adenoma and showed complete functional inhibition of extranodular glandular tissue (inhibiting adenoma), which is the ideal condition for performing ¹³¹I therapy.

Figure 1.9 A case of single thyroid nodule. A 25-year-old patient with incidental ultrasound finding of a thyroid nodule in the left lobe. (a) Thyroid ultrasound shows a solid hypoechoic nodule, with microcalcifications. (b) Thyroid