Hyperthyroidism

Hyperthyroidism and Myopathy

excess thyroxine eventually leads to a degradation (atrophy) of muscle tissue Physical acts such as lifting objects and climbing stairs may become increasingly difficult.

http://www.bio.davidson.edu/courses/immunology/students/spring2003/breedlove/gravesdisease.html

http://www.bio.davidson.edu/courses/immunology/students/spring2003/breedlove/gravesdisease.html

http://www.usmle-forums.com/usmle-step-1-bits-pieces/1011-radioactive-iodine-uptake-thyroid-diseases.html

http://www.usmle-forums.com/usmle-step-1-bits-pieces/1011-radioactive-iodine-uptake-thyroid-diseases.html

Stress and Grave's Disease

often incited during stress e.g. childbirth, infection, and steroid withdrawal

Are there any symptoms that may worsen after treatment of Grave's Disease? If so which one

opthalmopathy why?? look at the link on usmle forum*****

Grave's Ophthalmopathy is more common in which group of people?

Smokers

Grave's Disease

* *Most frequently seen in women (20-40 = peak age) *Associated with HLA-DR3 and HLA-B8. *Associated with other autoimmune diseases (i.e T1DM, Pernicious Anemia, Sjogren's, **Commonly triggered by stress, infection, and pregnancy* * **Smoking causes increased risk of disease and makes the ophthalmopathy worse* * * *Also antibodies to thyroid peroxidase and thyroglobulin, which are also present in Hashimoto thyroiditis *

A 65-year-old woman has a 6-month history of progressive irritability, palpitations, heat intolerance, frequent bowel movements, and a 6.8-kg (15-lb) weight loss. She has had a neck mass for more than 10 years. 131I scan shows an enlarged thyroid gland with multiple areas of increased and decreased uptake. Which of the following is the most likely diagnosis? (A) Defect in thyroxine (T4) biosynthesis (B) Graves' disease (C) Multinodular goiter (D) Riedel's thyroiditis (E) Thyroid carcinoma (F) Thyroiditis (G) Toxic adenoma (H) Triiodothyronine (T3) thyrotoxicosis

(C) Multinodular goiter

Thyroid Storm

* * * * * * * *

Describe the Histological findings of Grave's Disease

*Diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells results in abundant tall columnar cells lining the follicles *These enlarged epithelial cells project into the lumen and resorb the colloid resulting in the scalloped appearance *Lymphocytic infiltrate leads to germinal centers in the thyroid (more commonly seen in Hashimoto thyroiditis). Germinal centers are found in normal lymph nodes and should NOT be in the thyroid.

Pretibial myxedema

*Infiltrative dermopathy of the shins which produces scaly thickening and has an orange-peel texture; dough like consistency of skin *Only present in 1-2% of cases *NONpitting edema *Pathogenesis is similar to that of grave's ophthalmopathy *Occurs as a result of the deposition of interstitial GAGS (i.e hyaluronic acid)in the dermis and subcutis *Fibroblasts in this area also have thyroid hormone receptors and activation leads to deposition of Glycosaminoglycans

Thyroid Acropachy

*Rare manifestation of autoimmune hyperthryoidism that is unique to Grave's Disease *Usually appears in combination with exopthalmos and pretibial myxedema *Nails separate from nail bed (lifted up) *Digital swelling and clubbing of fingers *Periosteal bone formation typically in the fingers and toes

Describe the pathophysiology behind the development of Exophthalmos in Grave's Ophthalmopathy

*TSH receptor is highly by retro-orbital fibroblasts *Activation of these fibroblasts results in increased production and accumulation of hydrophilic GAGs (mainly hyaluronic acid) *The accumulation of GAG causes a change in osmotic pressure, which in turn leads to a fluid accumulation and an increase in pressure within the orbit *Furthermore, activation of the TSH receptor also increases adipocyte formation *These changes (increased volume of extraocular muscles, retroorbital connective tissues, and increased adipocyte tissue) displace the eyeball forward

37 year old primigravid woman at 25 weeks gestation is brought to the emergency department by her husband because of confusion for 12 hours. She also has had progressive fever and intermittent nausea and vomiting over the past 2 weeks. She has not had any contractions but has noted decreased fetal movement. Her preg had been uncomplicated. Family history of HTN, T1DM, seizure disorder Vitals - temp 101.9, pulse 168/min, BP 187/84 Examination - mildly enlarged thyroid. Lungs- clear CVS - 3/6 systolic ejection murmur Abd - Uterus 25 weeks gest; no tenderness FHR - 182/min Labs: Hb:9.9 platelet = 282,000 Na = 134 cl - 94 k - 2.9 Glucose - 102 Urea nitrogen - 62 TSH - 0.01 AST = 33 LDH - 112 Uric acid - 5.4 What is the diagnosis? 1. Acute Tubular Necrosis 2. Chronic pyelonephritis 3. Coarctation of aorta 4. Eclampsia 5. Essential HTN 6. Gest trophoblastic disease 7. Malignant HTN 8. Preclampsia 9. Superimposed Preclampsia 10. Pheochromocytoma 11. Primary aldosteronism 12. SLE 12. Thyroid Storm

12. Thyroid Storm BUN greater than 20..so cant be acute tubular necrosis no flank pain ...cant be chronic pyelonephritis no radio femoral BP diff...cant be coarctation no convulsions...cant be eclampsia no hx of prior hypertension "preg has been uncomplicated...cant be essential htn no hx suggestive of GTD not malignant Htn no proteinuria given...so cant make a diagnosis of preeclampsia no hx suggestive of pheopchromocytoma sodium value doesnt support hyperaldosteronism no hx suggestive of SLE finally...TSH is low, enlarged thyroid...hence ans is thyroid storm

A 61-year-old man presents to the emergency room complaining a racing heart, sweats, and diarrhea for 2 weeks. Review of systems is positive for unintentional weight loss of 10 pounds in 1 month. Serum TSH is found to be 0.02 mIU/L (normal 0.5 - 5.0 mIU/L). The patient is shown in Figure A. If the patient is treated with I-131 radioiodine therapy, which of the following is the most likely complication? 1. Agranulocytosis 2. Increased total cancer mortality 3. Hyperthyroidism 4. Hypothyroidism 5. Hypoparathyroidism

4. Hypothyroidism In Graves' disease, the entire thyroid gland is hyperfunctional. Uptake of the radioactive isotope of iodine throughout the gland results in effective ablation but may destroy too much thyroid tissue, resulting in a hypothyroid state. More than 75% of patients become hypothyroid following radioactive iodine thyroid ablation.

A 36-year-old G1P0 female presents to labor and delivery in the 38th week of her pregnancy and undergoes an uncomplicated spontaneous vaginal delivery. Shortly after birth, the child is noted to have dysphagia, irritability, frequent stooling, and increased appetite. The mother notes no history of drug or medication use during the pregnancy. The newborn's CBC is within normal limits. Thyroid studies reveal an increased free T4 in the newborn. Which of the following is the most likely the cause of this infant's presentation? 1. Initial presentation of DiGeorge syndrome 2. Intrauterine toxoplasmosis infection 3. Maternal iodine deficiency 4. Maternal history of Graves' disease treated with radioactive thyroid ablation 10 years ago 5. Maternal history of Hashimoto's thyroiditis

4. Maternal history of Graves' disease treated with radioactive thyroid ablation 10 years ago Pregnant mothers with Graves' disease, even after being treated surgically with thyroidectomy, can have persistent levels of thyroid stimulating immunoglobulin that can cross the placenta and cause thyrotoxicosis in the newborn, as seen in this vignette.

A 32-year-old woman with Graves' disease is undergoing treatment with radioactive iodine. Her initial presentation consisted of symptoms of sweating, weight-loss, and intermittent palpitations along with a physical examination significant for mild-to-moderate exophthalmos. After completing one week of radioactive iodine therapy, she reports worsening of her proptosis, with increased pain and worsened periorbital edema. Which of the following could have prevented the worsening of this patient's exophthalmos? 1. Giving a larger dose of radioiodine therapy 2. Initiation of beta-blocker at time of radioiodine therapy 3. Begin methimazole concurrent with initiating radioiodine therapy 4. Pre-treatment with prednisone prior to initiating radioiodine therapy 5. This is an expected outcome from radioactive iodine therapy, no preventive options are available

4. Pre-treatment with prednisone prior to initiating radioiodine therapy This patient's Graves' ophthalmopathy was worsened by the initiation of radioactive iodine. Pretreatment with glucocorticoids, such as prednisone, may prevent this adverse effect. Worsening of exophthalmos is due to the release of excess thyroid hormone during the destruction of thyroid cells by the radioactive iodine. Administration of radioactive iodine may also precipitate a thyroid storm through an identical mechanism. Preventive administration of steroids for several months (2-3) followed by a brief taper prior to initiating radioiodine therapy is recommended for patients with mild, moderate, or progressive ophthalmopathy. Patients without obvious ophthalmopathy initially are at a much lower risk of exacerbation with the start of radioactive iodine treatment.

Epidemiology of Grave's Disease

7-10 times more common in women peak incidence is 3rd and 4th decade of life

Toxic multinodular goiter/ Plummer's Disease

A condition in which the thyroid gland contains multiple lumps (nodules) that are overactive and that produce excess thyroid hormones Represents a spectrum of disease ranging from a SINGLE hyperfunctioning nodule (TOXIC ADENOMA) within a multinodular thyroid to a gland with multiple areas of hyperfunction Second most common cause of hyperthyroidism usually thought to result from a hyperplastic response of the entire thyroid gland to a stimulus, such as IODINE DEFICIENCY commonly due to iodine deficiency INDEPENDENT OF TSH (usually due to a TSH receptor mutation)

A 51-year-old with Graves disease develops ulcerating pharyngitis after 6 months of propylthiouracil. What's the underlying cause of ulcerative pharyngeal disease? A) Agranulocytosis B) Leukocytoclastic vasculitis C) Thrombosis D) Thyroid necrosis E) Tumor necrosis factor-a blockade

A) Agranulocytosis

Which drugs should be avoided in treating hyperthyroidism during pregnancy?

Amiodarone Methimazole medications with large quantities of Iodine

Apathetic Thyrotoxicosis

Atypical presentation of hyperthyroidism in elderly patients characterized by apathy lethargy confusion depression weight loss may not have goiter Cardiac complications are the most common manifestations of hyperthyroidism in elderly. They are usually manifested as atrial arrhythmias (specifically atrial fibrillation), congestive heart failure, and angina. (Symptoms may be masked by treatment for coexisting diseases; for example, in a patient taking propranolol for hypertension or angina, hyperthyroid signs of tachycardia and tremulousness may be effectively masked. ) **** well recognised that the elderly may not manifest classical signs of thyrotoxicosis hence the name apathetic thyrotoxicosis. The cardinal features are apathy and depression, as opposed to hyperkinesis and mental alertness in the usual thyrotoxic patient

Scalloped appearance of Colloid in Grave's Disease

Colloid appears pale with scalloped (moth-eaten) margins due to increased colloid resorption by the enlarged follicular epithelial cells

Many times, Toxic multnodular goiters and Toxic adenomas can develop autonomously functioning nodules. When does this occur?

Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin, or thyroid-stimulating hormone (TSH)

In a patient with iodine-deficiency goiter who moves from an iodine-deficient area to an iodine-replete area, the occurrence of hyperthyroidism most likely represents which of the following A. Graves' disease B. Jod-Basedow phenomenon C. Choriocarcinoma D. Struma ovarii E. Toxic multinodular goiter

B

A female newborn is delivered at term to a 35-year-old primigravid woman. Pregnancy was complicated by untreated maternal Graves disease. Her respirations are 66/min. Physical examination shows stridor, nasal flaring, intercostal retractions, and an asymmetric neck mass. Which of the following is the most likely cause of the newborn's stridor? A) Cystic hygroma B) Enlarged thyroid gland C) Thyroglossal duct cyst D) Tracheomalacia E) Vascular ring

B) Enlarged thyroid gland TSH-receptor binding antibodies cross placenta and induce goiter development

The most frequent cause of thyrotoxicosis during pregnancy is: A: Hashimoto?s thyroiditis B: Grave's Disease C: Multinodular goiter D: Choriocarcinoma E: Hydatiform mole

B: Grave's Disease

increased levels of circulating thyroid hormone increases BMR and increases sympathetic nervous system activity. Differentiate the mechanism of the two

BMR increases via increased synthesis of Na/K/ATPase increased sympathetic activity via B1 adrenergic receptors

42 year old woman comes to the physician because of a 4 month history of fatigue, palpitations and anxiety. She has had 3 kg ( 7 lb) weight loss during this period. She has also noted heat intolerance and increasing frequency of bowel movements. She has a 10 year history of asthma well controlled with inhaled albuterol .Her temperature is 37 C ( 98.6 F ) , pulse is 110/min and regular and blood pressure is 150/70 mm Hg. Examination shows lid lag and exophthalmos. The thyroid gland is large and non-tender, a thyroid bruit is heard. Deep tendon reflexes are normal. Serum studies show and thyroid stimulating hormone concentration of less than 0.1 U/ml and thyroxine (T4) concentration of 16U/ml. A thyroid scan shows a diffuse increased uptake. Which of the following is the most appropriate initial step in management. A) Intravenous cortisol therapy B) Intravenous sodium iodide therapy C) Oral 131 therapy D) Oral propylthiouracil therapy E) Oral terazosin F) Subtotal thyroidectomy

D) Oral propylthiouracil therapy In thyrotoxicosis, initial therapy is giving anti thyroid drugs and propranolol to control symptoms and thyroid synthesis. If iodine is given initially, it may cause thyroid storm

An 86-year-old female is brought to the emergency department from her nursing home facility. She has been more lethargic and less communicative over the past 3 days. The patient's only complaint is generalized weakness. Her past medical history is significant for mild dementia, well-controlled hypertension, and hyperlipidemia. Her medications include hydrochlorothiazide, losartan, and simvastatin. Triage vitals are T 99.0F, HR 104; RR 20; BP 120/86mmHg. EKG is shown in Figure A. Blood counts and metabolic panel are within normal limits. In addition to an infection work-up, which of the following would be the most useful to include in the evaluation of this patient? A) Creatinine Kinase B) Calcium, Magnesium, Phosphorous Levels C) Liver Function Tests D) Thyroid Stimulating Hormone E) Lead Level

D) Thyroid Stimulating Hormone In an elderly patient presenting with new-onset atrial fibrillation (EKG in Figure A) and hypoactive altered mental status, suspect apathetic thyrotoxicosis, an atypical presentation of hyperthyroidism. A thyroid simulating hormone level (TSH) is the most appropriate screening test for hyperthyroidism.

A 24-year-old Caucasian male comes to the outpatient clinic with complaints of heat intolerance and increased appetite. On examination, PR: 110/min and regular; Temperature: 37.2C(99F); RR: 14/min. Swelling is noted in the front of his neck, which moves with deglutition. Lab studies show: increased total T4; increased free T4; and decreased TSH. Radioactive iodine uptake is decreased. What is the most likely diagnosis? A. Multinodular goiter B. Toxic adenoma C. Graves disease D. Struma ovarii E. Thyroiditis

E. Thyroiditis

Example of hyperthyroidism with decreased uptake:

Factitious hyperthyroidism in which the exogenous T4 causes feedback inhibition on the TSH secretion. Any other exogenous thyroxine sources such as struma ovarii. Iodine induced thyroid toxicosis. Release of thyroid hormone by destructive process e.g. temporary hyperthyroidism seen in subacute thyroiditis. Toxic Nodular Adenoma, the nodule is active (causing hyperthyroidism) but the rest of the gland is with decreased uptake due to suppressed TSH.

What clinical features are unique to Grave's Disease?

Infiltrative Ophthalmopathy (50% of case) Pretibial myxedema (1-2%) Thyroid acropachy (1%) Thyroid bruit

Most common cause of hyperthyroidism?

Grave's Disease

Genetics of Grave's Disease

HLA-B8, -DR3 association increased concordance in twins tends to run in families

Jod-Basedow Effect

Iodine-induced hyperthyroidism, typically presenting in a patient with endemic goiter (due to iodine deficiency), who relocate to an iodine-abundant geographical area The Jod-Basedow effect does not occur in persons with normal thyroid glands who ingest extra iodine in any form

57yo M takes an angiotensin-converting enzyme (ACE) inhibitor for hypertension and has been advised to lose weight. Works as pharmacist. BP 152/94. Serum thyroid studies show TSH of 2, thyroxine (T4) of 18, and triiodothyronine (T3) concentration of 220.Radioactive thyroid scan shows decreased uptake and a small gland. Cause? - Exogenous administration of thyroid hormone

NBME s4 step 2 . find it

Toxic vs Non-Toxic Thyroid Goiter

Nontoxic means that the gland still depends on TSH Toxi means that the gland does not depend on TSH

Which is the drug of choice for treating hyperthyroidism in pregnancy

PTU Propylthiouracil (PTU) is the drug of choice for treating hyperthyroidism in pregnancy, as its transplacental effects on the fetus are less severe. PTU is cleared from the infant's system within a few days after birth

Hyperthyroidism is associated with _________ Increased/Decreased Cardiac Output

Patients with hyperthyroidism have an increase in cardiac output, due both to increased peripheral oxygen needs and increased cardiac contractility. Heart rate is increased, pulse pressure is widened, and peripheral vascular resistance is decreased

Toxic Adenoma

Single area of increase iodine uptake on scintigraphy

Describe the pathophysiology behind the development of Pretibial myxedema

Similar to Graves' ophthalmopathy, fibroblasts in the skin above the shins have TSH receptors, which are activated resulting in deposition of GAGS (i.e hyaluronic acid) in the dermis and subcutis

Hyperthyroidism increases the risk of miscarriage T/F?

T Hyperthyroidism must be controlled in pregnancy, as the risks of miscarriage and birth defects are much higher without treatment.

People with other autoimmune diseases have an increased chance of developing Graves' disease T/F?

T! Conditions associated with Graves' disease include type 1 diabetes, rheumatoid arthritis, and vitiligo

Jod-Basedow Effect vs Wolff-Chaikoff effect

The Jod-Basedow effect DOES NOT OCCUR in persons with normal thyroids Wolff-Chaikoff effect happens in NORMAL persons AND in persons with thyroid disease, when comparatively large quantities of iodine or iodide are ingested.

Sequence of Events that cause Toxic multinodular goitre

The sequence of events leading to toxic multinodular goiter is as follows: 1. Iodine deficiency leading to decreased T4 production. 2. This induces thyroid cell hyperplasia to compensate for the low levels of T4. This accounts for the multinodular goitre appearance. 3. Increased thyroid cell replication predisposes to a risk of mutation in the TSH receptor. 4. If the mutated TSH receptor is constitutively active, it would then become 'toxic' and produces excess T3/T4 leading to hyperthyroidism.

Describe the treatment options for Grave's Disease

There are three treatment options for Graves' disease: antithyroid drugs (thioamides: PTU/Methimazole), radioiodine, or surgery *Some guidelines state to use the antithyroid drugs initially until the patient is euthyroid (prevents possibility of thyroid storm if radioiodine is given while patient is still hyperthyroid) *Then treat with Radioiodine/Surgery *Exception is in the patient with moderate to severe ophthalmopathy as Radioiodine can exacerbate this *Pretreatment with glucocorticoids, such as prednisone, may prevent this adverse effect *Radioiodine is contraindicated during pregnancy and lactation *Agranulocytosis may occur with PTU or Methimazole *Methimazole

Examples of hyperthyroidism with increased uptake:

Typically Grave's disease as the autoantibodies stimulate TSH receptor sensitivity enhancing the uptake. Secondary and tertiary hyperthyoroidism where the elevated TSH levels also stimulate the uptake. Toxic adenoma in which the overactive adenoma need to take Iodine to support the production of T4.

Hyperthyroidism and Osteoporosis

Thyroid hormone stimulates bone resorption, resulting in increased porosity of cortical bone and reduced volume of trabecular bone The increase in bone resorption may lead to an increase in serum calcium concentrations, thereby inhibiting parathyroid hormone secretion and the conversion of calcidiol (25-hydroxyvitamin D) to calcitriol (1,25-dihydroxyvitamin D). In addition, the metabolic clearance rate of calcitriol is increased. These changes can result in impaired calcium absorption and an increase in urinary calcium excretion. The net effect is osteoporosis and an increased fracture risk in patients with chronic hyperthyroidism

Grave's disease and hypocholesterolemia

Thyroid hormones: 1. Upregulate gene expression of LDL receptors. Therefore, more LDL receptors are produced and less LDL remains in the blood. This is the MAIN mechanism. 2. Stimulate both Lipoprotein lipase and Hepatic lipase 3. Stimulate cholesteryl ester transfer protein, an enzyme which transports cholesteryl esters from HDL to VLDL. VLDL is metabolized by lipoprotein lipase in adipose tissue and muscle. This promotes a lower blood cholesterol level. The opposite is true in HYPOthyroidism, which is characterized by HYPERcholesteroloemia.

Another term for hyperthyroidism?

Thyrotoxicosis

A classical clinical presentation for toxic MNG is

a hyperthyroid patient with a palpable nodular goiter or a thyroid ultrasound showing multiple nodules. The nodularity may only be appreciated on ultrasound. On thyroid scintigraphy, there are typically ONE OR MORE focal areas of increased radioiodine uptake

Wolff-Chaikoff effect

a reduction in thyroid hormone levels caused by ingestion of a large amount of iodine an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream happens in normal persons and in persons with thyroid disease persists longer in persons with thyroid disease

Risk factors for developing toxic multinodular goiter include

age above 60 being female commonly due to iodine deficiency so it may be seen in older populations of developing countries

Pathogenesis of Grave's Disease

an autoimmune disorder whereby the thyroid gland is overstimulated by antibodies directed to the thyroid-stimulating hormone (TSH) receptor on the thyroid follicular cells leads to increased PRODUCTION and increased RELASE of thyroid hormone

Symptoms of Hyperthyroidism

weight loss despite increased appetite heat intolerance and sweating tachycardia with increased cardiac output Arrythmia (eg. A fib) especially in the elderly Tremor, anxiety, insomnia, and heightened emotions staring gaze with lid lag diarrhea with malabsorption oligomenorrhea bone resorption with hypocalcemia decreased muscle mass with weakness HYPOcholesterolemia HYPERglycemia

Eye changes in Hyperthyroidism

wide-eyed stare, upper lid retraction, upper lid lag and sometimes proptosis (only in Graves disease)