1. Disorders of the Thyroid Gland Clinical Medicine I Elizabeth Bunting, MS, PA-C March 21, 2011
2. Objectives Describe the anatomy of the thyroid gland, with regard to its relationship to: Other structures in the neck The parathyroid glands The major vessels Embryologic development Describe the regulation of thyroid metabolism, particularly: The role of the thyroid gland in the hypothalamus-anterior pituitary-thyroid axis The role of iodine within the gland in controlling thyroid function
3. Objectives Discuss the synthesis and secretion of thyroid hormone, describing: The two principal thyroid hormones secreted Their relative utilization within the body How they are chemically related Describe the action of the hormones, particularly: The location of the receptors for thyroxine and triiodothyronine and their function The hormonal effect on cellular metabolism and development Define hyperthyroidism, list and describe the: Associated pathophysiology Common clinical presentations Significant historical and physical exam findings Diagnostic tests Management
4. Objectives Define thyrotoxicosis, and describe its pathophysiology, clinical presentation, diagnostic work-up and management. Define hypothyroidism, list and describe the: Associated pathophysiology Common presentations Significant historical and physical exam findings Diagnostic tests Management Define myxedema and myxedema coma, and describe their pathologic process, clinical presentation, diagnostic work-up and management. Identify the different forms of thyroiditis and their distinguishing features and management
5. Objectives Describe the various therapies, such as: Use of surgery, radioactive iodine, or anti-thyroid drugs for hyperfunction Use of thyroid hormone for hypofunction List and describe the types of thyroid cancer. Explain the signs and symptoms, pathophysiology and epidemiology of thyroid cancer. Discuss the diagnostic work-up and management of thyroid cancer. Discuss the prognosis for each of the major types of thyroid cancer.
10. Thyroid Physiology Makes Thyrotropin Releasing Horomone (TRH) Hypothalmus Anterior Pituitary Makes Thyroid Stimulating Hormone (TSH) Makes T3(Triiodothyronine) & T4 (Thyroxine) Thyroid Gland
11. Thyroid Produces two related hormones T3 – triiodothyronine T4 – thyroxine These hormones play a critical role in Thermogenic homeostasis in adults Metabolic homeostasis in adults Cell differentiation during development
12. Regulation of the Thyroid Axis TSH is the most useful physiologic marker of thyroid hormone action T3 and T4 are the dominant regulators of TSH production TSH is released in a pulsatile manner and exhibits a diurnal rhythm Highest levels at night
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15. Deficiency is prevalent in many mountainous regions globally and if present, may lead to goiter
22. Removal of one of the iodine atoms leads to production of the potent hormone triiodothyronine (T3)T4 may be thought of as a precursor for the more potent T3 T4 is converted to T3 in the peripheral tissues
43. Hypothyroidism Insufficiency in the amount of thyroid hormone in the body PRIMARY HYPOTHYROIDISM: thyroid gland failure despite proper stimulation from the pituitary SECONDARY HYPOTHYROIDISM: failure of the pituitary to produce TSH to stimulate the thyroid gland TERTIARY HYPOTHYROIDISM: failure of the hypothalamus
44. Primary Hypothyroidism General Considerations Common: affects 1% of the general population and 5% over the age of 60 Women > men 4:1 ratio Mean age at diagnosis is 60 years Prevalence increases with age Thyroid hormone deficiency affects almost all body functions
51. treatment of hyperthyroidismTrauma to thyroid/pituitary/hypothalamus Radiation exposure Severe infection Neoplasia (pituitary tumor) Drugs – glucocorticoids, phenobarbital, phenytoin, salicylates (large doses), fluorouracil, androgens, amiodarone, interferon
52. Primary Hypothyroidism Symptoms Common manifestations Weight gain Fatigue, lethargy Depression Weakness Dyspnea on Exertion Arthralgias/myalgias Muscle cramps Paresthesias Cold intolerance Constipation Dry skin, brittle hair and nails Headache Carpal Tunnel Syndrome Menorrhagia
53. Primary Hypothyroidism Symptoms Less common Decreased appetite and weight loss hoarseness Decreased sense of taste and smell Deminished auditory acuity Signs Bradycardia Diastolic hypertension Thin, brittle nails, hair Peripheral edema Puffy face and eyelids (myxedema) Skin pallor or yellowing (carotenemia) Delayed DTR Goiter
54. Primary Hypothyroidism Diagnostic findings TSH Free T4 Treatment Treat the underlying cause if possible Thyroid replacement with T4 Levothyroxine (Synthroid) Adults <60 years without evidence of heart disease Start with 25-75 μg qd Repeat TSH in 6 weeks Adjust dosage by 25 μg every 1-3 weeks based on TSH Goal – symptom relief and TSH in lower half of reference range
55. Primary Hypothyroidism Treatment Adults >60 years or patients with known cardiac disease Start with 25-50 μg qd Medication increases cardiac contractility and oxygen demand and don’t want to precipitate an MI Repeat TSH in 6 weeks Adjust dosage by 25 μg every 1-3 weeks based on TSH Goal – symptom relief and TSH in lower half of reference range
56. Primary Hypothyroidism Treatment Average daily replacement dose is usually 1.7μg/kg body weight (typically 100-150 μg) Once full replacement is achieved and TSH levels are stable you can extend f/u visits to 6 months and then yearly Take Levothyroxine (Synthroid) at least 4 hours between antacids, vitamins, seizure meds, food, lovastatin, sertraline – these medications affect T4 absorption or clearance
68. Myxedema Treatment High mortality rate even with treatment Thyroid hormone replacement (initially IV then switch to oral) Levothyroxine 500μg IV bolus Continue orally at 50-100 μg/day
69. Myxedema Coma Medical emergency Often induced by underlying infection: cardiac, respiratory, or CNS system illness, cold exposure or drug use Multiple organ abnormalities and progressive mental deterioration Very rare, but has high mortality rate Most commonly results from stressful situations (e.g. trauma, surgery, burns, infection) Can occur because of coexisting disease states (e.g. diabetes, MI, fluid and electrolyte abnormalities) Can be precipitated by certain medications
70. Myxedema Coma Treatment IV thyroid hormone replacement Treat underlying infection, if present Monitor TSH Monitor glucose and sodium levels Warming if hypothermia (blankets only) Prognosis Mortality rate of 30 – 60% Poor prognosis if advanced age, bradycardia and persistent hypothermia
71. Cretinism Congenital hypothyroidism Etiology 1 in 4000 live births Pathology Hypoplasia or aplasia of the thyroid gland OR failure of the gland to migrate into normal anatomic location OR ineffective hormone due to enzyme deficiency
72. Cretinism Clinical features Sluggishness Pale, gray, cool or mottled skin Nonpitting myxedema Constipation Large tongue Poor muscle tone Mental retardation Dry, brittle hair
73. Cretinism Diagnostic studies Low T4 Elevated TSH Delayed skeletal maturation on x-rays Treatment – thyroid hormone replacement Prevention Neonatal screening within 60 days of birth Improved prognosis with therapy started in first 2 months of life
75. Hyperthyroidism Etiology Grave’s disease – most common Toxic multinodular goiter and thyroid adenomas Subacute (de Quervain) Thyroiditis Exogenous thyroid hormone Struma Ovarii (ovarian teratoma) No goiter Pituitary tumor secreting TSH Secondary hyperthyroidism Normal or increased TSH with diffuse goiter and elevated T4 Medication induced Amioderone
76. Grave’s disease Epidemiology Accounts for 60-80% of thyrotoxicosis Females > males at 8:1 Typically occurs between ages 20-40 Pathology Grave’s disease is an autoimmune disorder Involves the formation of autoantibodies that bind to the TSH receptors in the thyroid and stimulate gland hyperfunction Characterized by an increase synthesis and release of thyroid hormones Gland is typically enlarged Familial tendency (HLA-B8 and HLA-DR3)
77. Grave’s disease Symptoms Descending order of frequency Hyperactivity, irritability, dysphoria Heat intolerance, increased sweating Palpitations Fatigue, weakness Weight loss (increased appetite) Diarrhea Polyuria Oligomenorrhea, loss of libido
78. Grave’s disease Signs Descending order of frequency Tachycardia; A fib in the elderly, PACs Tremor Goiter may be present (absence of goiter does not rule out hyperthyroidism) Skin warm, moist Muscle weakness, proximal myopathy Exophthalmos, proptosis, lid lag with downward gaze (von Graefe sign) or retraction (Dalrymaple sign), staring appearance (Kicher sign) Thyroid dermopathy – pretibialmyxedema Hyperreflexia Thyroid acropachy (digital clubbing) rare Hypokalemic periodic paralysis
79. Grave’s disease Diagnostic studies TSH T3 and T4 both total and free Anti-TPO positive in up to 80% TSH receptor antibody (TRaB) positive in 65% Imaging Thyroid RAI uptake and scan High in Grave’s Disease and toxic nodular goiter MRI of orbits if eye concerns
80. Grave’s disease Management Clinical features generally worsen without treatment Treat by reducing thyroid hormone synthesis, using antithyroid drugs –propylthiouracil (PTU), methimazole Reducing the amount of thyroid tissue with radioiodine treatment (RAI) Causes progressive destruction of thyroid cells Reducing the amount of thyroid tissue with thyroidectomy If not responding to medical treatment Large goiters Beta-blockers (propanolol) for symptoms during early treatment with antithyroid drugs and radioiodine tx
81. Thyroid Storm Rare Life-threatening emergency Exacerbation of hyperthyroidism/ thyrotoxicosis Usually precipitated by stress (surgery, infection, delivery, trauma) High mortality rate 30% even with treatment – cardiac failure, arrhythmia, or hyperthermia Pathology – same as hyperthyroidism with addition of stressor as above
82. Definitions Hypothyroidism: hypoactive thyroid gland Hyperthyroidism: hyperactive thyroid gland Thyrotoxicosis: excessive thyroid hormone Thyroid storm: the life threatening result of excessive thyroid hormone and physical stress Myxedema: Severe result of lack of thyroid hormone
83. Thyroid Storm Clinical features Exaggerated signs and symptoms of hyperthyroidism High fever Marked delirium Severe tachycardia Seizures Nausea, vomiting and diarrhea Dehydration Coma Jaundice Death
84. Thyroid Storm Diagnostic studies Highly elevated T3 and T4 EKG may show sinus tachycardia, a-fib or flutter Management Aggressive use of and large dose of propylthiouracil (PTU) Oral or IV Ipodate Sodium(decreases thyroid hormone production) with Iodide given 1 hour later as Lugol solution Propranolol given (cautiously if heart failure) Glucocorticoids (inhibits peripheral conversion of T4 to T3
85. Toxic Multinodular Goiter Multiple thyroid nodules that range in morphology from hypercellular regions to cystic areas filled with colloid Women > men Clinical presentation Subclinical hyperthyroidism or mild thyrotoxicosis Usually elderly A fib, tachycardia Nervousness, tremor Weight loss Recent exposure to iodine, from contrast dyes or other sources, may precipitate or exacerbate thyrotoxicosis
86. Toxic Multinodular Goiter Diagnostic testing T3 and T4 with T3 elevated to a higher degree TSH Thyroid scan shows heterogeneous uptake with multiple regions of increased and decreased uptake Treatment Management is challenging Antithyroid drugs in combination with beta blockers However this treatment often stimulates the growth of the goiter Radioiodine can be used to treat areas of autonomy Surgery provides definitive treatment
88. Thyroiditis Acute thyroiditis Rare Due to suppurative infection of the thyroid Typically occurs in children or young adults Signs and symptoms Thyroid pain often referred to throat or ears Small, tender goiter that may be asymmetric Fever, dysphagia and erythema over the thyroid Laboratory ESR WBC Normal thyroid function
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90. De Quervain’sThyroiditis AKA SubacuteThyroiditis, granulomatousthyroiditis, giant cell thyroiditis Etiology – probably viral, may be preceded by viral URI Symptoms can mimic pharyngitis Peak incidence occurs between 30-50 Women>men 3:1 ratio
91. De Quervain’sThyroiditis Pathology Enlargement and patchy inflammatory infiltrate of thyroid During initial phase of follicular destruction, there is release of thyroid hormones, leading to increased circulating T3 and T4 and suppression of TSH After several weeks, the thyroid is depleted of stored thyroid hormone and a phase of hypothyroidism typically occurs, with low free T3 and T4 and moderately increased TSH levels Finally thyroid hormone and TSH levels return to normal as disease subsides Thyrotoxicosis hypothyroidism NL thyroid function lasts several weeks lasts 4-6 months returns within 12 months (develops in 50%)
92. De Quervain’sThyroiditis Clinical features Often complain of sore throat Exquisitely tender thyroid with small goiter (one or both lobes may be affected) Pain is often referred to jaw or ear Sometimes fever Malaise and URI symptoms may precede the thyroid-related features There may be signs of thyrotoxicosis or hypothyroidism, depending on the phase of the illness
93. De Quervain’sThyroiditis Diagnostic studies Lymphocytosis on CBC Elevated ESR Thyroid function tests evolve through 3 distinct phases over about 6 months Thyrotoxic phase - T3 and T4 elevated, TSH suppressed Hypothyroid phase Recovery phase Negative antibody tests Low thyroid radioiodine uptake (RAIU)
94. De Quervain’sThyroiditis Treatment ASA or NSAIDS typically sufficient to control symptoms May use beta blockers for symptoms during thyrotoxicosis phase Thyroid hormone during hypothyroid stage may be needed RAI can be used to cause prompt fall of T3 and improve thyrotoxic symptoms Monitor thyroid function every 2-4 weeks using TSH and free T4
95. Painless Thyroiditis Autoimmune thyroiditis Categories Sporadic Occurs in patients with underlying autoimmune thyroid disease Postpartum Occurs in 7.2% of women 3-6 months after pregnancy 3 times more common in women with type 1 diabetes 70% chance of recurrence with subsequent pregnancies
96. Painless Thyroiditis Clinical features Clinical course similar to subacute thyroiditis except there is little to no thyroid tenderness Thyrotoxicosis stage lasting 2-4 weeks followed by hypothyroid stage for 4-12 weeks, and then resolution Labs Positive anti-TPO Normal ESR Management Initial stage usually mild Can use propranolol for symptoms if needed Second stage – thyroxine replacement – use only for 6-9 months as recovery is the rule
97. Hashimoto’s Thyroiditis Chronic lymphocytic thyroiditis due to autoimmunity Epidemiology Women > men 6:1 ratio 14.3% of Caucasians 10.9% of Hispanics 5.3% of Blacks Mean age at diagnosis is 60 years Prevalence increases with age Tends to be familial
98. Hashimoto’s Thyroiditis Most common type of thyroid disorder in the US Pathology Immune mediated destruction of thyroid parenchyma B-lymphocytes invade the thyroid gland which leads to follicular atrophy and then fibrosis Initially may have hyperthyroidism due to passive release of stored thyroid hormone Detectable levels of anithyroid antibodies – anti-TPO or antithyroglobulin antibodies or both Only a small subset of individuals with elevated antithyroid antibody levels ever develop thyroid dysfunction Found in 3% of men and 13% of women
99. Hashimoto’s Thyroiditis May be associated with other autoimmune diseases Type I diabetes, Addison’s disease, pernicious anemia Signs and symptoms May be hyperthyroid, euthyroid or hypothyroid Thyroid gland may be diffusely enlarged (goiter), firm or rubbery, usually nontender Surface of thyroid may be irregular or nodular Slow progression to hypothyroidism over years Patients often present with signs and symptoms of hypothyroidism Dry skin, decreased sweating, thinning of skin, myxedema, puffy face and eyelids, nonpittingpretibial edema, dry/brittle hair, depression Thyroid is diffusely enlarged, firm, and finely nodular
100. Hashimoto’s Thyroiditis Diagnostic studies Thyroid function tests Hyperthyroid phase Free T4 levels higher than T3 due to it being the greater stored hormone Because T4 is less active than T3 the hyperthyroid symptoms are less severe than in other thyroiditis conditions TSH Hypothyroid state Free T4 TSH Positive antithyroid antibodies Anti-TPO in 90% Antithyroglobulin antibodies in 40%
101. Hashimoto’s Thyroiditis Imaging Ultrasound shows diffuse heterogeneous density and hyperechogenicity FNA for nodules Doppler may be needed to distinguish between Graves Disease and Hashimoto’s Treatment Thyroxine hormone replacement If hypothyroid Or if euthyroid with goiter present Will shrink the goiter by 30% in most cases over 6 months
102. Riedel Thyroiditis AKA Invasive fibrous thyroiditis, Riedel struma, woody thyroiditis, ligneous thyroiditis, invasive thyroiditis Generally a manifestation of multifocal systemic fibrosis syndrome Causes hypothyroidism and sometimes hypoparathyroidism RARE Generally found in middle-aged or elderly women Signs and symptoms: Thyroid enlargement is asymmetrical and stony, hard and adherent to neck structures
103. Riedel Thyroiditis Signs and symptoms cont’d: Compression of the thyroid causes dysphagia, dyspnea, pain and hoarseness Fibrosis happens in other areas of the body as well Treatment Tamoxifen can provide remission in 3-6 months Short term corticosteroids can help with compression Surgical decompression may be needed
104. Thyroid Nodules Must consider cancer Pathology Adenomas, cysts, colloid nodules (most common nodules), localized thyroiditis, and cancer (mostly papillary and follicular) Clinical features Most are asymptomatic May have hyper- or hypothyroidism
105. Thyroid Nodules Clinical features Suspect cancer if rapid growth, fixed in place with no movement on swallowing, hx of neck radiation, male sex, extremes of age Diagnostic studies TSH and free T4 Fine needle aspiration and cytology Ultrasound
106. Thyroid Nodules Management MUST exclude malignancy Treatment according to specific diagnosis If malignant, surgery followed by thyroid radioiodine ablation
107. Thyroid Cancers Epidemiology Most common malignancy of the endocrine system Uncommon, diagnosed in less than 1% of the population Women > men 3:1 ratio Male sex associated with worse prognosis Incidence increases with age Classification Papillary carcinoma (most common) Follicular Medullary Anaplastic (most aggressive)
108. Thyroid Cancers Risk Factors of thyroid cancer in pt with a thyroid nodule History of head and neck irradiation Age <20 or >45 Bilateral disease Large nodule size, >4cm New or enlarging neck mass Male sex Nodule fixed to adjacent surfaces Genetic factors, especially medullary which has familial predisposition
109. Thyroid Cancers Signs and symptoms Palpable, firm, nontender nodule in the thyroid Most are asymptomatic Possible hoarseness Possible neck pain Possible cervical LAD Only 5% of palpable thyroid nodules are malignant Thyroid function tests are usually normal
110. Thyroid Cancers Diagnostic studies Serum calcitonin and CEA levels may be elevated in medullary cancer Usually seen as a “cold” nodule on radioactive iodine thyroid scan Ultrasound shows solid, well-formed nodule/s and can detect metastases in the neck FNA needed CT scan – used to detect metastases MRI and PET scans- distant mets
111. Thyroid Cancers Treatment Surgical excision with near-total thyroidectomy with post-surgical radioablation of the remnant thyroid tissue Most tumors are still TSH responsive, TSH suppression is a mainstay of treatment Goal is TSH range 01.-0.5 IU/L Chemo used if mets are present
112. Thyroid Cancers PapillaryFollicularMedullaryAnaplastic Incidence MOST 2nd MOST Uncommon LEAST COMMON COMMON COMMON Av. Age 42 50 50 57 Females 70% 72% 56% 2% Deaths 6% 24% 33% 98% I uptake + ++++ 0 0 Degree of + ++-+++ +-++++ ++++++++ Malignancy
114. References Jennifer Forbes, MHS, PA-C: many slides are hers from last year CMDT Harrison’s Principles of Internal Medicine Images: www.riversideonline.com/.../DS00396.cfm ehp.niehs.nih.gov/.../howdeshell-full.html healthfiles.net/disease/toxic-nodular-goiter/ www.missionfoto.com/images/fall03/goiter.html
Editor's Notes
Develops from the floor of the primitive pharynx during the 3rd week of gestation. The developing gland migrates along the thyroglossal duct to reach its final destination in the neck. This accounts for rare ectopic location of thyroid tissue at the base of the tongue. Also allows for thyroglossal duct cysts. Thyroid hormone synthesis begins around 11 weeks gestation.
Congenital hypothyroidism occurs in 1 in 4000 newborns and now a part of newborn screening in developed countries. Supplementation can prevent severe developmental abnormalities.
I disagree with dosing adjustments. I keep them on meds for 8 weeks, then recheck and titrate up from there every 6-8 weeks.
