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TitleThyroid Disorders Basic Science and Clinical Practice
TagsThyroid Stimulating Hormone Thyroid Hypothyroidism Hyperthyroidism Thyroid Disease
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Table of Contents
                            Preface
Acknowledgments
Editors
Contents
Contributors
Part I: Fundamental Concepts
	1: Thyroid: A General Overview
		Introduction
		Thyroid Gland: Basic Structure
		Thyroid Dysfunction: Distribution and Burden
		Classification of Thyroid Dysfunction
		Thyroid Dysfunction and Health Issues
		Screening for Thyroid Disorders
		Accuracy of Screening Tests
		The USPSTF: Summary of Recommendation
		Recommendations of Other Authorities
		Conclusion
		References
	2: Functions of Thyroid Hormones
		Introduction
		Thyroid Hormone Synthesis
			Steps Involved in Synthesis of Thyroid Hormones
			Role of Iodine in Thyroid Hormone Synthesis and Function
				Wolff- Chiakoff Effect
			Central Regulation of Thyroid Hormone Synthesis: The ‘Hypothalamic –Pituitary- Thyroid Axis’
				Production of TRH
				Hypophysiotropic and Non-­hypophysiotropic Neurons
				Role of Autonomic Nervous System in Regulation of Thyroid Function
				Inactivation of Secreted TRH
				Negative Feedback Regulation of Hypophysiotropic TRH Neurons
				Deiodinases and Their Role in Negative Feedback Regulation
			Role of Thyroid Hormone Transporters in Secretion of Ths
		Thyroid Hormones- Mechanism of Action
			Genomic Pathways
			Non-genomic Pathways
		Thyroid Hormone Functions
			Role in Brain Development
			Effect on Myocardium
			Effect on Bone
			Effect on Adipose Tissue
			Effect on Liver
			Effect on Pituitary
			Effect on Fetal Growth and Maturation
				Effect on Growth
				Effect on Fetal Metabolism (Oxygen (O2) Consumption)
				Effect on Fetal Tissue Maturation
				Effect on Lung Maturation
				Effect on Fetal Heart and Cardiovascular System
			Other Important Effects
		Conclusion
		References
	3: Iodine and the Thyroid
		Introduction
		Epidemiology
		Definition of IDD and Its Impact on Health and on the Population
		Iodine Chemistry
		Iodine Ecology and Cycle
		Food Sources of Iodine
		Iodine Metabolism
		Toxic Effects of Iodine Excess
		Diagnosis of Iodine Deficiency
		IDD Prevention and Treatment
		Impact of Iodine Supplementation in Deficient Populations
		Conclusion
		References
	4: The Role of Thyroid Hormones in Neural Development
		Introduction
		Thyroid Hormone Synthesis and Secretion
		Thyroid Hormone Transport, Uptake and Metabolism
		Disruption of Brain Development by Thyroid Hormone Depletion
		Effects of Thyroid Hormones on Neural Cell Proliferation and Differentiation
		Non-genomic and Mitochondrial Effects of Thyroid Hormones
		Conclusion
		References
	5: Autoimmune Thyroid Disease (Flajani-Parry-Graves-von Basedow Disease): Etiopathogenesis, Clinical Manifestations and Diagnosis
		Introduction
		Background and History
		Epidemiology
		Genetics and Etiopathogenesis
		Clinical Manifestations
		Clinical Diagnosis
		Laboratory Diagnosis
		Imaging Diagnosis
		Histopathological Diagnosis
		Conclusions
		Bibliography
Part II: Thyroid Dysfunction and Clinical Application
	6: Thyroiditis
		Introduction
		Thyroiditis Without Thyroid Pain and Tenderness
			Hashimoto’s Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Painless Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Postpartum Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Amiodarone-Associated Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Thyroiditis Induced by Other Drugs
			Lithium
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features, Diagnostic Evaluation and Differential Diagnosis
				Treatment
			Interferon-alpha
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features, Diagnostic Evaluation and Differential Diagnosis
				Treatment
			Interleukin-2
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features, Diagnostic Evaluation and Differential Diagnosis
				Treatment
			Tyrosine Kinase Inhibitors
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features, Diagnostic Evaluation, Differential Diagnosis
				Treatment
			Riedel’s Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Infiltrative Thyroid Disorders
		Thyroiditis with Thyroid Pain and Tenderness
			Subacute Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Suppurative Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Radiation-Induced Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
			Palpation or Trauma-Induced Thyroiditis
				Epidemiology
				Etiology and Pathogenesis
				Clinical Features
				Diagnostic Evaluation
				Differential Diagnosis
				Treatment
		Conclusion
		References
	7: Hypothyroidism
		Introduction
		Historical
		Definitions
		Epidemiology
		Etiology
			Primary Hypothyroidism
				Hashimoto’s Thyroiditis
				Iodine Deficiency
				Iodine Excess
				Iatrogenic
				Drugs
				Thyroid Infiltration and Infections
				Transient Hypothyroidism
				Primary Congenital Hypothyroidism
			Central Hypothyroidism
				Acquired Pituitary and Hypothalamic Disorders
				Central Congenital Hypothyroidism
				Drugs
			Other Disorders
				Resistance to Thyroid Hormone
				Consumptive Hypothyroidism
		Clinical Features
			Skin and Appendages
			Cardiovascular
			Respiratory
			Gastrointestinal
			Neurologic
			Musculoskeletal
			Renal
			Hematopoietic
			Endocrine
			Reproductive
			Energy Metabolism
		Course of the Disease
			Primary Hypothyroidism
			Central Hypothyroidism
			Hypothyroidism in Infants and Children
		Screening
			Congenital Hypothyroidism
			Acquired Hypothyroidism
		Diagnosis
		Differential Diagnosis
			Primary Hypothyroidism
			Central Hypothyroidism
		Treatment
			Primary Overt Hypothyroidism
				L-T4 Monotherapy
				Combination T4 and T3 Therapy
				L-T3 Monotherapy
				Desiccated Thyroid
				Compounded Thyroid Hormones
				Dietary Supplements, Nutraceuticals and Other Over-the-Counter Products
			Central Hypothyroidism
			Congenital Hypothyroidism
		Conclusion
		References
	8: Hyperthyroidism
		Introduction
		Etiology
			Graves Disease
				Epidemiology
				Pathophysiology and Genetic Interplay
				Other Associated Autoimmune Diseases
				Graves Ophthalmopathy
			Other Causes of Hyperthyroidism
				Toxic Multinodular Goiter (Plummer Disease)
				Toxic Adenoma
				Thyroiditis
				Drug-Induced Hyperthyroidism
				Tumors Induced Hyperthyroidism
				TSH-Secreting Pituitary Adenoma
				Hyperthyroidism Secondary to Thyroid Hormone Resistance
				Hyperthyroidism due to TSH-Receptor Mutations
		Clinical Features
			Features Related to Other Causes of Hyperthyroidism
			Apathetic Hyperthyroidism
		Diagnostic Modalities
			Hormonal Assays
			Antibodies
			Other Relevant Investigations
			Ultrasound
			Radioisotope Thyroid Scan
			Radioisotope Findings
			MRI/CT Scan
		Treatment
			Symptomatic Relief
			Diet and Activity
			Antithyroid Medications
			Adverse Effects of Thioamide Antithyroid Medications
			Radioactive Iodine 131 Ablation (RAI131)
			Other Less Commonly Used Antithyroid Medications
			Thyroidectomy
			Indications for Thyroidectomy
			Preparation for Thyroidectomy
			Adverse Effects of Thyroidectomy
				Postoperative Bleeding
				Infection
				Injury to the Recurrent Laryngeal Nerve
				Injury to the Superior Laryngeal Nerve
				Hypoparathyroidism
				Hypothyroidism
				Thyrotoxic Storm
			Follow up After Thyroid Surgery
			Cause-Specific Treatment
		Future Directions
		Conclusion
		References
	9: Autoimmune Thyroid Disease (Flajani-Parry-Graves-von Basedow Disease): An Overview of Treatment
		Introduction
		Anti-thyroid Medications
			Doses and Follow-up Regimes
			Adverse Reactions
		Radioactive Iodine Treatment
			I-131 Adverse Effects and Risk of Malignancy
		Surgical Treatment for GD
		Special Conditions
			Pregnancy
			Graves’ Eye Disease
			Pretibial Myxedema
		Conclusions
		Bibliography
	10: Subclinical Hyperthyroidism
		Introduction
			Causes
			Exogenous Subclinical Hyperthyroidism
			Endogenous Subclinical Hyperthyroidism
		Epidemiology and Natural History
		Clinical Findings
			Cardiovascular Mortality Risk
			Atrial Fibrillation
			Coronary Heart Disease, Heart Failure, and Other Cardiac Factors
			Cardiovascular Mortality
			Bone and Mineral Metabolism
			Dementia Cognitive Function
			Quality of Life
		Evaluation
		Diagnosis
		Pregnancy
		Screening Guidelines
		Management
			Patients on T4 for the Treatment of Hypothyroidism
			Patients on Suppressive Levothyroxine Therapy
			Endogenous Subclinical Hyperthyroidism
			Patients at High Risk for Complications
			Patients at Low Risk for Complications
			Treatment Options
		Conclusion
		References
	11: Subclinical Hypothyroidism
		Introduction
		Epidemiology
		Etiology
		Screening for Subclinical Hypothyroidism
		Diagnosis
		What Is the Upper Limit of Normal for the Serum TSH Level?
		Differential Diagnosis
		Evaluation
		Consequences of Subclinical Hypothyroidism
			Systemic Symptoms of Hypothyroidism
			Progression to Overt Hypothyroidism
			Cardiovascular Disease
			Cardiovascular Mortality
			Non-alcoholic Fatty Liver Disease
			Neuropsychiatric Symptoms
			Neuromuscular Dysfunction
			Potential Consequences
			Pregnancy
		Effects of Thyroid Hormone Replacement
			Hypothyroid Signs and Symptoms
			Cardiovascular Disease
			Serum Lipid and Apoprotein Concentrations
			Other Benefits
		Management of Subclinical Hypothyroidism
			Serum TSH Concentration of 3–5 mlu/l
			Serum TSH Concentration of 5.1–10 mlu/l
			Serum TSH Concentration Greater Than 10 mlu/l
			Candidates for T4 Replacement
			Thyroid Peroxidase Antibodies
			Arguments for Treatment
			Arguments Against Treatment
			Goals of Treatment
			Dose Modification Strategy
		Conclusion
		References
	12: Thyroid Emergencies
		True Thyroid Emergencies
			Thyroid Storm
				Pathophysiology
				Signs/Symptoms
				Establishing Diagnosis
				Scoring System
				Treatment
				Do and Don’ts/Things Not to Be Missed
				Follow Up of Patients
			Myxedema Coma
				Pathophysiology
				Establishing Diagnosis
				Signs/Symptoms
				Treatment
				Do and Don’t/What Not to Miss
				Follow Up of Patients
		Thyroid Dysfunction Requiring Urgent Measures
			Thyroid Dysfunction During Pregnancy
				Hyperthyroidism
				Hypothyroidism
			Neurological Presentation of Thyroid Disease
				Cognitive Disorders and Seizures
			Neuromuscular Emergencies
			Cardiovascular Emergencies
		Medication Exposure and Thyroid Emergencies
			Acute Iodine Exposure: Jod-Basedow Phenomenon/Wolff-Chaikoff Effect
			Lithium Intoxication
			Amiodarone-Induced Thyroid Emergencies
			Post RAI
			Thyroxine Overdose
		Conclusion
		References
	13: Thyroid Nodule
		Introduction
			Epidemiology
			Clinical Problem
		Clinical Evaluation
			History
			Physical Examination
				High Suspicion for Malignancy
				Moderate Suspicion for Malignancy
		Investigations
			Indications for Evaluation [22]
		Biochemical Tests
			Serum TSH
			Serum Thyroglobulin
			Serum Calcitonin
		Imaging
			Radionuclide Scanning
				Thyroid Ultrasound
			Other Imaging Studies
			Fine Needle Aspiration
		Treatment
		Overview of Treatment Options for Solitary Thyroid Nodules
			Surgery
			Radio-Iodine
			Percutaneous Ethanol Injection
			Levothyroxine
		Conclusion
		References
	14: Thyroid Cancer
		Introduction
		Calcification
		Differentiated Thyroid Cancers
			Papillary Cell Carcinoma
				Epidemiology
				Pathology
			Follicular Thyroid Carcinoma
				Epidemiology
				Pathology
				Molecular Biology of Differentiated Thyroid Cancer
				Diagnosis
				Investigations
				Treatment of Differentiated Thyroid Cancer
				Surgery
				Radioactive Iodine (RAI)
				TSH Suppression Therapy
				Long Term Management
				Treatment Options for Advanced DTC
				Novel Therapies
		Medullary Thyroid Cancer
			Epidemiology and Pathology
			Presentation and Diagnosis
			Treatment
		Anaplastic Thyroid Carcinoma
		Melignant Thyroid Lymphoma
		Conclusion
		References
	15: Thyroid Dysfunction and Mental Disorders
		Introduction
		Basic Concepts and Terminology
		Neurophysiology of Psychiatric Disorders
		Mood Disorders
		Antidepressant Effects on Thyroid Function
		Psychosis
		Cognitive Changes
		Anxiety Disorders
		Mechanism of Psychiatric Disorders Associated with Thyroid Dysfunction
		Psychiatric Management
		Outcome of Mental Disturbances
		Conclusion
		References
	16: Thyroid Dysfunction and Arrhythmias
		Introduction
		Genomic Action of Thyroid Hormone on Heart
		Non Genomic Action of Thyroid Hormone on Heart
			Electrophysiology and Mechanism of Action of T3 on the Atria
			Electrophysiology and Mechanism of Action of T3 on the Ventricles
		Relation Between Thyroid Hormone and Adrenergic System
		Mechanism Underlying the Effect of Thyroid Hormone (TH) on the Arrhythmogenesis
			Effects of Thyroid Hormones Excess on the Atrias
			Effects of Thyroid Hormones Excess on the Ventricles
		Supraventricular Arrhythmia
			Atrial Arrhythmia
				Hyperthyroidism
				Subclinical Hyperthyroidism and Atrial Fibrillation
				Hypothyroidism and Subclinical Hypothyroidism
				Euthyroid Range in Older Adults
				Should We Anticoagulate and Attempt Cardioversion in Those with AF?
				Arrhythmia and Amiodarone-Induced Hyperthyroidism
			Other Supraventricular Arrhythmia
		Ventricular Arrhythmia
			Hyperthyroidism
			Subclinical Hyperthyroidism
			Hypothyroidism
			Subclinical Hypothyroidism
		Conclusion
		References
Part III: Pregnancy and Thyroid Dysfunction
	17: Pregnancy and Hypothyroidism
		Introduction
			Physiologic Changes in Thyroid Function During Pregnancy
			Thyroid Function and the Fetus
			Subclinical Hypothyroidism During Pregnancy
			Thyroid Autoimmunity and Subclinical Hypothyroidism
			Hypothyroidism in Pregnancy
			Feto-maternal Risk
			Screening
		Diagnosis
			Indications for Thyroid Testing in Pregnancy [28]
		Treatment
			Thyroxine Replacement
			Iodine Replacement
			Monitoring Thyroid Status During Pregnancy
			Prognosis
			Preconception Counseling
		Conclusion
		References
	18: Pregnancy and Hyperthyroidism
		Introduction
		Clinical Features of Hyperthyroidism During Pregnancy
		Impact of Hyperthyroidism During Pregnancy
		Diagnosis of Hyperthyroidism During Pregnancy
		Establishing the Cause of Hyperthyroidism During Pregnancy
		Gestational Transient Thyrotoxicosis
		Graves’ Disease
			Pre-pregnancy Counseling
				Radioactive Iodine Ablation or Surgery
				Antithyroid Drugs [4, 6, 29]
				Incidence of Hyperthyroidism During Pregnancy
			Treating Graves’ Disease in Pregnancy
				Monitoring a Pregnant Woman on ATDs (Table 18.5)
				Natural Course of Graves’ Disease During Pregnancy
				Thyroidectomy for Graves’ Disease During Pregnancy
			Metarnal TRAb and Its Impact on the Fetus
			Fetal and Neonatal Hyperthyroidism
				Fetal Monitoring in a Woman with Graves’s Disease
			ATDs Use in Lactation
			Graves’ Disease in Post-partum Period
		Conclusion
		References
Index
                        
Document Text Contents
Page 1

Thyroid Disorders

Syed Khalid Imam
Shamim I. Ahmad
Editors

Basic Science
and Clinical Practice

123

Page 2

Thyroid Disorders

Page 163

152

Currently 27 families with a total of 152 affected
individuals with non-autoimmune familial hyper-
thyroidism have been reported . The hyperthy-
roidism is caused by monoallelic gain-of-function
germline mutations in the TSH receptor [ 46 , 47 ].

Affected individuals have a suppressed TSH
and elevated peripheral hormones in the absence
of TSH receptor-stimulating antibodies and TPO
antibodies. The family history is key in order to
demonstrate familial clustering suggestive for an
autosomal dominant disorder. Ultimately, the
diagnosis requires sequence analysis of the TSH
receptor gene in order to evaluate it for the pres-
ence of a monalllelic mutation.

Clinical Features

Generally, a constellation of information, includ-
ing the extent and duration of symptoms, past
medical history, and social and family history, in
addition to the information derived from physical
examination, help to guide the clinician to the
appropriate diagnosis.

The family history should include careful eval-
uation of the autoimmune disease, thyroid disease
and emigration from iodine-defi cient parts of the
world. Health care provider should also review a
complete list of medications and dietary supple-
ments. A number of compounds—including
expectorants, amiodarone, iodinated contrast
agents, and health food supplements containing
seaweed or thyroid gland extracts—contain large
amounts of iodine that can induce hyperthyroid-
ism in a patient with thyroid autonomy. Rarely,
iodine exposure can cause hyperthyroidism
in a patient with an apparently healthy thyroid.
Hyperthyroidism presents with multiple
symptoms that vary according to the age of the
patient, duration of illness, magnitude of hormone
excess, and presence of comorbid conditions.
Symptoms are related to the thyroid hormone’s
stimulation of catabolic enzymopathic activity
and catabolism, and enhancement of sensitivity to
catecholamines. Older patients often present with
a paucity of classic signs and symptoms, which
can make the diagnosis more diffi cult [ 41 , 48 ].

Hyperthyroidism leads to an apparent increase
in sympathetic nervous system. Younger patients

tend to exhibit symptoms of sympathetic activa-
tion, such as anxiety, hyperactivity, and tremor,
while older patients have more cardiovascular
symptoms, including dyspnea and atrial fi brilla-
tion with unexplained weight loss [ 37 , 49 ].

The clinical manifestations of hyperthyroid-
ism do not always correlate with the extent of the
biochemical abnormality.

Common symptoms of hyperthyroidism
include the following:

• Nervousness
• Insomnia
• Anxiety
• Increased perspiration
• Heat intolerance
• Hyperactivity
• Palpitations
• Weight loss despite increased appetite.
• Hyperdefecation
• Reduction in menstrual fl ow or

oligomenorrhea

Common signs of hyperthyroidism include
the following:

• Diffuse goiter/toxic nodule/multinodular
goiter

• Exophthalmos
• Tachycardia or atrial arrhythmia
• Systolic hypertension
• Warm, moist, smooth skin
• Lid lag
• Stare
• Hand tremor
• Proximal myopathy
• Brisk deep tendon refl exes

Features pathognomonic of Graves’ disease
include the following:

• Orbitopathy
• Thyroid bruit
• Pretibial myxedema
• Acropachy

Features of Graves Ophthalmopathy
Approximately 50 % of patients with Graves thy-

S.K. Imam

Page 164

153

rotoxicosis have mild thyroid ophthalmopathy.
Often, this is manifested only by periorbital
edema, but it also can include conjunctival edema
(chemosis), injection, poor lid closure, extraocu-
lar muscle dysfunction (diplopia), and Proptosis .
Evidence of thyroid eye disease and high thyroid
hormone levels confi rms the diagnosis of autoim-
mune Grave disease.

Graves Dermopathy In rare instances, Graves
disease affects the skin through deposition of gly-
cosaminoglycans in the dermis of the lower leg.
This causes nonpitting edema, which is usually
associated with erythema and thickening of the
skin, without pain or pruritus.

Features Related to Other Causes
of Hyperthyroidism

Toxic adenomas present with signs and symp-
toms of hyperthyroidism and/or a thyroid nodule.
The signs and symptoms of thyrotoxicosis do not
differ from other etiologies. Features suggestive
for Graves’ disease such as endocrine ophthal-
mopathy, (pretibial) myxedema and acropachy
are missing. The onset of hyperthyroidism is
often insidious and more common in older
patients, who typically have larger adenomas.
Mechanical symptoms such as dysphagia or
hoarseness are uncommon. Autonomously func-
tioning nodules may remain stable in size, grow,
degenerate or become gradually toxic. In one
series, 10 % of patients followed for 6 years
became thyrotoxic [ 32 ]. Thyrotoxicosis may
develop independent of age, but is much more
common in nodules over 3 cm in diameter (up to
20 %).

Toxic Multinodular Goiter In addition to the
signs and symptoms associated with hyperthy-
roidism, patients with large toxic multinodular
goiters may also have dysphagia, shortness of
breath, stridor, or hoarseness.

Subacute thyroiditis often present with a his-
tory of a preceding respiratory tract infection
[ 50 ]. They may have fever, malaise, and soreness,

and the gland is exquisitely tender on palpation
and often displays a substantially increased
consistency.

Hydatiform Moles and Choriocarcinoma Most
women with hydatiform moles present with uter-
ine bleeding in the fi rst half of pregnancy. The
size of the uterus is large for the duration of ges-
tation [ 51 ].

Many women with molar pregnancies have
nausea and vomiting, some have pregnancy-
induced hypertension or pre-eclampsia. The
signs and symptoms of thyrotoxicosis are present
in some women, but they may be obscured
by toxemic signs. The characteristic features
belonging to Graves’ disease are missing.
Hyperthyroidism is usually not severe because of
a relatively short duration.

Women with choriocarcinomas present within
1 year after conception. The tumor may be con-
fi ned to the uterus, more frequently it is meta-
static to multiple organs such as the liver and
lungs. In men, choriocarcinomas of the testes is
often widely metastatic at initial presentation.
Gynecomastia is a common fi nding.

Struma Ovarii The clinical presentation may
include the fi nding of an abdominal mass, asci-
tes, pelvic pain, and, rarely, a pseudo-Meigs syn-
drome with pleural effusions. A subset of women
present with subclinical or overt thyrotoxicosis.
Goiter is only presented in patients with associ-
ated thyroid disease. For example, coexistence of
Graves’ disease and struma ovarii has been
reported [ 52 , 53 ].

Apathetic Hyperthyroidism

Hyperthyroidism in the elderly is a great mas-
querader, and even severe, life-threatening hyper-
thyroidism can easily be missed in patients older
than 60 years [ 54 ]. Not uncommonly, it appears in
an atypical manner, and the classic symptoms are
often absent. Graves disease and toxic multinodu-
lar goiter account for most cases in the elderly,
while as Solitary toxic adenomas are rare in elder
patients [ 55 – 58 ]. Again, like hypothyroidism, the

8 Hyperthyroidism

Page 326

319

lung maturation , 22
maturation , 21–22
myocardium , 19
neural development

brain development disruption , 52
metabolism , 51–52
on neural cell proliferation/differentiation , 52–54
non-genomic and mitochondrial effects , 54–55
synthesis and secretion , 50
transport , 51–52
uptake , 51–52

non-genomic pathways , 17
in pituitary , 21
replacement

benefi ts , 214
cardiovascular disease , 213–214
hypothyroid signs and symptoms , 213
serum lipid and apoprotein concentration , 214
serum TSH concentration , 214–215

structure of , 12
synthesis , 11–12

autonomic nervous system , 14–15
central regulation of , 13–14
deiodinases , 16
hypophysiotropic and non-hypophysiotropic

neurons , 14
hypophysiotropic TRH neurons , 15–16
iodine role in , 13
secreted TRH , 15
steps in , 12–13
transporters in secretion , 16
TRH production , 14
Wolff-Chiakoff effect , 13

Thyroiditis , 151, 187
amiodarone-associated , 96–97
classifi cation , 87–88, 108–109
Hashimoto’s (see Hashimoto’s thyroiditis (HT) )
interferon-induced , 98
interleukin-2 , 98–99
lithium , 97–98
lymphocytic and postpartum , 151
painless , 92–94
palpation , 107
postpartum , 94–96
radiation-induced , 106–107
Riedel’s , 99–101
subacute , 101–104, 151
suppurative , 104–106
with thyroid pain and tenderness , 101–107
trauma-induced , 107
without thyroid pain and tenderness , 88–101

Thyroid nodule
biochemical tests , 244–245
clinical problem , 240
computed tomography , 245, 246
diagnostic algorithm , 242
epidemiology , 240
18FDG-PET imaging , 242, 246
fi ne needle aspiration , 246–248
history , 240–241

investigations , 241–244
levothyroxine , 249–250
magnetic resonance imaging , 245, 246
percutaneous ethanol injection , 249
physical examination , 241
radio-iodine , 249
radionuclide scanning , 245–246
surgery , 248–249
treatment , 248
ultrasonography , 245–246

Thyroid peroxidase antibodies (TPOAb) , 35, 89
subclinical hypothyroidism , 216–217

Thyroid-stimulating hormone (TSH) , 7, 12, 44
Thyroid-stimulating hormone receptor

(TSHR) , 12, 67–68, 151–152
Thyroid-stimulating hormone receptor antibodies

(TRAb) , 304
Thyroid-Stimulating Immunoglobulin (TSI) level , 155
Thyroid storm

diagnosis , 226
do and don’ts/things not to be missed , 227
follow up of patients , 227
pathophysiology , 225
scoring system , 226
signs/symptoms , 225–226
treatment , 226–227

Thyroid volume , 43–44
Thyrotoxicosis , 6, 147

apathetic , 267
signs and symptoms of , 153
treatment of , 148

Thyrotoxic storm , 162–163
Thyrotrophin-releasing hormone (TRH) , 50

hypophysiotropic neurons , 15–16
production , 14
secretion , 12, 15, 126
stimulation , 12

Thyroxine (T4) , 12–13, 274
administration , 187
candidates replacement , 215–216
hypothyroidism treatment , 195
overdose , 233–234
replacement, pregnancy , 293
tionamide therapy , 171

Thyroxine-binding globulin (TBG) , 154, 290, 299
defi ciency , 131
non-pregnancy due to , 299

Topolanski’s sign , 73
Torsade de pointes (TdP) , 282
Total thyroidectomy (TT) , 161, 174
Toxic adenoma (TA)

clinical features , 153
etiology , 150–151
fi ne needle aspiration , 156
radioisotope fi ndings , 156

Toxic multinodular goiter (TMNG)
clinical features , 153
etiology , 150
radioactive iodine therapy , 156, 160

Transient hypothyroidism , 121

Index

Page 327

320

Transplacental transfer , 51
Trauma-induced thyroiditis , 107
Triiodothyronine (T3) , 12–13, 274

on atria , 275
on ventricles , 275–276

TSH . See Thyroid-stimulating hormone (TSH)
TSH-secreting adenomas (TSHomas) , 151
TT . See Total thyroidectomy (TT)
Tumor Necrosis Factor (TNF) , 178
Tumors induced hyperthyroidism , 151
Type II autoimmune polyendocrine syndrome , 149
Tyrosine kinase inhibitor (TKI) , 99

U
Ultrasound (US)

amiodarone-associated thyroiditis , 96
DTC , 256
Graves’ disease , 78, 156
Graves’ opthalmopathy , 179–180
Hashimoto’s thyroiditis , 89
hyperthyroidism , 155–156
painless thyroiditis , 93
postpartum thyroiditis , 95
Riedel’s thyroiditis , 100

subacute thyroiditis , 102
suppurative thyroiditis , 106
thyroid nodule , 245–246

Uncoupling protein (UCP) synthesis , 20
United States Preventive Services task Force (USPSTF) ,

7
U.S. Preventive Services Task Force , 195

V
Ventricular arrhythmia , 282
Ventricular fi brillation (VF)

pathogenesis , 277–278
triiodothyronine on , 275–276

Von Graefe’s sign , 73

W
Wechsler Intelligence Scale for Children-Revised

(WISC-R) , 268
White adipose tissue (WAT) , 19–20
Wide Range Achievement Test-Revised

(WRAT-R) , 268
Wilder’s sign , 73

Wolff-Chaikoff effect , 13, 40, 41, 120, 232

Index

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