ENDOCRINOLOGY-THYROID DISORDER

THYROID-GENERALITIES Main secretory hormone T4; T3 more

potent Free hormone only active 1.FT4

2.FT3(#2) TSH is the best initial test for

diagnosis(#1) TBG (#3)( increase=endogenous T4) Antimicrosomal antibody Radioactive iodine uptake scan(RAIS)-

check functional status of thyroid

THYROID-GENERALITIES Total T3,T4 are not always accurate:1. Increase TBG level:- Pregnancy- OCP2. Decrease TBG level:-nephrotic syndrome-liver ds

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?

1. Creatinine kinase 2. Calcium, magnesium, phosphorus levels 3. Liver function tests 4. Thyroid stimulating hormone 5. Lead level

PREFERRED RESPONSE ▼ 4 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.

The diagnosis of hyperthyroidism in the elderly patient requires a high index of suspicion, as the disease does not always present with the classic symptoms of hyperthyroidism, such as heat intolerance, weight loss, and hyperactivity. In elderly patients, the most common presenting symptoms are cardiac, specifically atrial fibrillation, congestive heart failure, and angina. Furthermore, these symptoms can be confused with primary cardiac pathology or masked by home medications (i.e. beta-blockers). Apathetic thyrotoxicosis manifests with apathy, weakness, depression, and lethargy.

In their review, Espino et al. discuss the work-up of altered mental status in the elderly patient. They recommend first distinguishing delirium from dementia or depression based on the patient's history and exam. A Mini-Mental State Exam may be helpful in determining the degree of impairment (Illustration A). Treatment is based on the underlying cause.

In a case series of three patients presenting with apathetic thyrotoxicosis, Arnold et al. report presenting symptoms of anorexia, gradual weight loss, restlessness, lethargy, weakness, dyspnea on exertion, depression, irritability, forgetfulness, anhedonia, CHF, dry skin, pedal edema, and polymyalgia. The three patients in this case series were female age 59-62 years old.

Figure A shows an EKG of a patient in atrial fibrillation. Illustration A shows a Mini-Mental State Examination. The test is comprised of 30 points

assessing for attention, memory, language, orientation, and registration. A score below 24 is considered abnormal.

Incorrect Answers: Answer 1: A creatinine kinase level may be useful in a

patient who was found down for a prolonged or undetermined amount of time.

Answer 2: Although hypocalcemia can result in altered mental status, in a patient with new onset atrial fibrillation without complaint of abdominal pain, tetany, or muscle cramps, hyperthyroidism should be ruled out first.

Answer 3: Liver function tests (LFTs) should be obtained in a patient with known or suspected liver disease where hepatic encephalopathy is suspected. Hepatic encephalopathy presents with new-onset dementia, seizures, coma, and asterixis.

Answer 5: A lead level should be obtained in a patient presenting with anemia, abdominal colic, and encephalopathy.

QUESTION

1

2

3

ANSWER

THYROID GLAND-HYPERTHYROIDISM Graves ds(MC) Toxic multinodular goiter Subacute thyroiditis Extrathyroid source-thyrotoxicosis factitious-stroma ovarii Excess TSH (rare)

HYPERTHYROIDISM

RAI UPTAKE SCAN

GRAVES DS Hyperthyroidism + diffuse goiter +

exophthalmus + Dermatopathy Women(4th decade) Autoantibody (Thyroid stimulating Ig) Ass with other Autoimmune disorders:-pernicious anemia-myasthenia-diabetes

GRAVES DS Most common cause of hyperthyroidism An autoimmune disease with stimulating anti-TSH receptor

antibodies a type II hypersensitivity anti-microsomal, anti-thyroglobulin antibodies also present Female dominant HLA-B8, Dr3 association Often incited during stress e.g. childbirth, infection, steroid

withdrawalPhysical exam symmetrical, non-tender thyroid enlargement ophthalmopathy (proptosis, exophthalmos) due to

glycosaminoglycan deposition pretibial myxedema digital swelling Serology ↑ total serum T4 ↑ free T4 ↓ serum TSH diffusely ↑ 123I uptake

Treatment Medical β-blockers thionamides result in reduced hormone synthesis PTU and methimazole 131I ablation hypothyroidism may result May cause transient worsening of exophtalmos or

hyperthyroid symptoms due to release of thyroid hormone with thyroid cell destruction

Prevention: pretreatment with glucocorticoids

Prognosis, Prevention, and Comlications

Stress-induced catecholamine surge may be fatal by arrhythmia

Pregnancy complications anti-TSH receptor antibodies may cross placenta and produce hyperthryoidism in the fetus

GRAVES DISEASE

HYPERTRHYROIDISM PRESENTATION Nervous system(yonger) Inability to sleep,tremor Diarrhea,sweat Heat intolerance Weight loss(despite increase appetite) Dypnea,palpitation,angina,cardiac

failure,myopathy(old pt) Pretibial myxedema Palmar erythema Menstrual irregularity Osteoporosis,hypercalcemia

PRETIBIAL MYXEDEMA

DIAGNOSIS Thyroid studies(#1)-suppress TSH-serum FT3,4 elevated RAI uptake(diffuse uptake) dy/dx solitary

uptake=toxic nodular goiter Thyroid stimulating Ig (TSI) (usually not

needed)

HYPERTHYROIDISM MANAGEMENT

Treatment of Acute Hyperthyroidism and "Thyroid Storm"1. Propranolol: blocks target organ effect, inhibits peripheral conversion of T4T32. Thiourea drugs (methimazole and propylthiouracil) : blocks hormone production(PTU safer in pregnancy)3. Iodinated contrast material (iopanoic acid and ipodate): blocks the peripheral conversion of T4 to the more active T3; also blocks the release of existing hormone4. Steroids (hydrocortisone)5. Radioactive iodine: ablates the gland for a permanent cure

TIPS IN USING DRUG Thiourea drug may cause

neutropenia(agranulocytosis)stop and change medication immediately

Long term treatment:-RAI ablationfollow them twice a year prevent them getting hypothyroidism-Thyroidectomy (rarely)-->reserve and use in pregnancy because we cant use RAI ablation in pregnancy PregnancyMethimazole is

contraindicated.

GRAVES OPHTHALMOPATHY

Steroids are the best initial therapy. Radiation is used in those not responding to steroids. Severe cases may need decompressive surgery

TOXIC MULTINODULAR GOITER Non-autoimmune Consequences of simple goiter Nodular goiter on examination Disease of the elderly Presentation-Arrthymia, CHF(cardiac manifestation) No opthalmopathy Treatment: radioactive iodine

THYROID STORM Extreme form of thyrotoxicosis Precipitated by stress,surgery or trauma Manifestation:-High fever + cardiac manifestation -hypotension,CHF-delirium,coma

HYPOTHYROIDISM-ETIOLOGY Primary(95%)1. Chronic thyroiditis(hashimato)2. Post-ablative surgery,RAI3. Drugs: lithium,amiodarone4. Heritable biosynthethic

defect(enzymatic deficiency)(rare)5. Iodine deficiency Suprathyroid cause: pituitary induces

(secondary) or hypothalamic induced(tertiary)

HYPOTHYROIDISM PRESENTATION Acromegaly Bilateral carpal tunnel syndrome Cold intolerance Pseudodementia Increase weight Dry hair and skin Hoarse voice Slow deep tendion reflex Elevated cholesterol

HYPOTHYROIDISM IN KIDS

Cretinism(in newborn) and juvenile hypothyroidism.

Persistent physiology jaundice,hoarse cry,constipation,somnolence and feeding problem.

In later months,delayed mile-stones and dwarfism, coarse features, protruding tongue, broad flat nose, widely set eyes, sparse hair, dry skin ,protuberant abdomen, potbelly with umbilical hernia, impaired mental development, retarded bone age, and delayed dentition.

HYPOTHYRODISM DIAGNOSIS

HYPOTHYROIDISM MANAGMENT Restore metabolic state Levothyroxine (T4) administered with

monitoring of TSH/T3 level (it takes 6 weeks to stabilize after dosing changes).

If there is a strong suspicion of suprethyroid hypothyroidism/hypothalamic /pituitary origin given hydrocortisone first then replace thyroid hormone

MYXEDEMA COMA- SIGN AND SYMPTOM

Older age presenting as: Mental confusion Hypothermia Bradycardia Hyponatremia Hypoglycemia Hypercapnia Leukocytopenia Decrease hematocrit increaseCPK Decrease EKG voltage

THYROIDITISDefine:Inflammation of thyroid Subacute thyroiditis Hashimato thyroiditis Lymphocytic thyroiditis Reidel thyroiditis

SUBACUTE THYROIDITIS Granulomatous,giant cell,or the Quervan thyroiditis Viral origin and follows upper respiratory infection

symptoms include:-malaise,fever,pain over thyroid,and pain refer to lower jaw,ears,neck and arms. Thyroid gland is enlarged and firm Lab test:1.Increase ESR2.Initial increase T3 and T4 follow by hyopthyroidism3. decrease RAI uptake Rx: symptomatic NSAIDs,prednisone and propanolol. May smolder for months but eventually wil lreturn to

normal function

A 34-year-old woman presents with a pain in the neck when with a mass. These symptoms started following a viral upper respiratory infection she had last week. On exam her thyroid is enlarged and tender to palpation. A biopsy is shown. (subacute granulomatous thyroiditis)

QUESTION 127year old woman comes to your office for “throat pain” for 1week and palpitation. She had no prior hx . Not taking any medication. BP 142/92,PP:112. Oropharynx normal ; thyroid painful and diffusely enlarged. TSH < 0.01 T4 : 14.4 (increase) RAI uptake scan 3%(low) What would be the next most appropriate test? Treatment?

ANSWER FOR QUESTION 1 Subacute Thyroiditis. Check ESR Treatment : only symptomatic treatment

(pain)

QUESTION 232yo man admitted to ICU with delirium is treated with presumed sepsis.Thyroid hormone drawn on the day of admission show a very low FT3. The TSH is normal.There is concern about myxedema coma given that he had 2 history of “thyroid nodule”.What is the most likely diagnosis.

ANSWER 2=EUTHYROID SICK SYNDROME

Apparent alterations thyroid hormone level with normal thyroid gland funciton peripheral activity of outer ring deiodinase is ↓ normally converts T4 to T3 peripheral activity of inner ring deiodinase is ↑ normally converts T4 to

reverse T3 Associated with cancer cardiac disease (MI, CHF) CRF sepsis Serology ↓ total serum T4/T3 ↓ serum TSH ↑ reverse T3 Management Treat and manage primary underlying illness Likely no need to start thyroid hormone replacement (controversial) Recheck thyroid function studies after illness has resolved.

A 73-year-old female with a history of COPD and hypertension presents to the emergency room with a primary complaint of altered mental status. Her husband reports that the patient was suffering from worsening fatigue and a productive cough over the last several days. Chest radiographs in the emergency department suggest a diagnosis of pneumonia. Blood cultures are obtained and ultimately grow S. pneumoniae. The patient is admitted to the ICU for management of pneumonia and sepsis. During the course of her admission, thyroid function studies are ordered and show decreased levels of total serum T3 and T4, high-normal TSH, and increased levels of reverse T3. Which of the following is the most appropriate next step in management of this patient's abnormal thyroid function test results?

QUESTIONA. Initiate thyroxineB. Radioactive iodine thyroid uptake testC. Thyroid ultrasoundD. Fine needle aspiration thyroid biopsyE. Continue to monitor patient and recheck thyroid function after illness resolves

CORRECT ANSWER=E This patient with pneumonia and sepsis as well as decreased levels of thyroid

hormones is suffering from euthyroid sick syndrome. Management of euthyroid sick syndrome entails treatment of the primary underlying disease and rechecking thyroid function after resolution of the illness.

Euthyroid sick syndrome is characterized by abnormal thyroid function tests concurrent with non-thyroid illness. Specifically, there are increased levels of reverse T3 and decreased levels of total T3. The effect on total T4 and TSH is more variable and less predictable. Euthyroid sick syndrome may present in the setting of underlying malignancy, cardiac disease such as myocardial infarction or congestive heart failure, renal failure, or sepsis.

Pittman reviews the evaluation and management of patients with abnormal thyroid function tests. Patients who are critically ill may have a wide array of abnormal thyroid function tests secondary to sick euthyroid syndrome. For the majority of patients, these abnormal results are due to the underlying disease and NOT a primary thyroid disorder. Management includes, first and foremost, addressing the underlying illness, with repeat thyroid function testing after recovery.

McIver and Gorman review euthyroid sick syndrome. The thyroid hormone abnormalities seen are likely due to cytokines or other inflammatory mediators acting on the hypothalamus, pituitary, and/or thyroid gland. The degree of thyroid hormone disturbance has been shown to correlate with the severity of illness; lower levels of thyroid hormones may predict a poorer prognosis. The use of thyroid hormone replacement therapy in euthyroid sick syndrome remains controversial.

INCORRECT ANSWERS:

Answer A: There are no prospective studies available that demonstrate the efficacy or utility of thyroid replacement therapy for euthyroid sick syndrome. Thyroid function abnormalities are typically reversible with treatment and resolution of the underlying causative illness.

Answers B,C: Imaging studies such as thyroid ultrasound or radioactive thyroid uptake test are not necessary in euthyroid sick syndrome.

Answer D: Thyroid biopsy is utilized to rule out thyroid cancer and diagnose thyroid nodules identified on imaging studies; it has no utility in euthyroid sick syndrome.

A 27-year-old female presents to the emergency room with palpitations. Vitals are stable with the exception of tachycardia. On physical examination, she appears gaunt but has no goiter or proptosis. Serum thyroglobulin and TSH are low. T3 is elevated. A radioactive iodine study is performed which shows low uptake in the thyroid gland. What is the most likely diagnosis? Topic Review Topic

1. Graves' disease 2. Toxic multinodular goiter 3. Factitious thyrotoxicosis 4. Papillary thyroid carcinoma 5. Iatrogenic hypothyroidism

PREFERRED RESPONSE ▼ 3 This patient has signs and symptoms of hyperthyroidism. Low

uptake of radioactive iodine in conjunction with a low TSH and thyroglobulin are characteristic of excessive doses of levothyroxine (or factitious thyrotoxicosis).

Patients with factitious thyrotoxicosis have signs and symptoms of thyrotoxicosis without goiter or exophthalmos. Consider this diagnosis in a patient who has access to levothyroxine such as a nurse or a pharmacist. Recall the other common causes of hyperthyroidism: Graves' disease (diffuse toxic goiter), Plummer's disease (multinodular toxic goiter), toxic thyroid adenoma, Hashimoto's thyroiditis (which may cause transient hyperthyroidism before causing hypothyroidism), postpartum thyroiditis, and iodine induced hyperthyroidism. All these patients may present with the classic clinical features including nervousness, hand tremor, sweating, weight loss, diarrhea, and palpitations. Treatment may be pharmacologic via thionamides such as PTU and methimazole, or may consist of radioactive iodine 131, and even surgical subtotal thyroidectomy.

incorrect Answers: Answer 1: In Graves' disease, the patient would have

a goiter and the radioiodide scan would show diffuse uptake.

Answer 2: In toxic multinodular goiter (Plummer's disease), there would be patchy uptake on the thyroid scan. This form of hyperthyroidism is also more common in elderly patients.

Answer 4: Thyroid carcinomas are usually non-functioning nodules.

Answer 5: This patient's symptoms are indicative of hyperthyroidism, not hypothyroidism. Iatrogenic hypothyroidism occurs after radioiodine therapy, thyroidectomy, or may occur with certain medications such as Lithium.

A 32-year-old woman presents to your office with a one month history of heat intolerance, racing heart, unintentional 4 pound weight loss, and sweating. On physical examination there is a non-tender enlarged thyroid without evidence of proptosis or exophthalmos. Lab tests return with increased total T4, decreased TSH, and increased free T4. A radioactive iodine uptake exam is ordered and the imaging is displayed in Figure A. What is the most appropriate definitive treatment option for this patient? Topic Review Topic

FIGURES: A

1. Watchful waiting for symptom progression or recession

2. Beta-blockade alone 3. Anti-thyroid medications alone 4. Radioactive iodine ablation alone 5. Radioactive iodine ablation and prophylactic

glucocorticoids

PREFERRED RESPONSE ▼ 4 DISCUSSION: The patient in the above vignette is experiencing symptoms

associated with Graves' disease. In the US, the definitive treatment for Graves' with mild or no ophthalmopathy is radioactive iodine ablation.

Graves' disease is an autoimmune disease in which thyroid stimulating immunoglobulins bind to TSH-receptors. There tends to be female predominance, and symptoms are often precipitated by stress (e.g. childbirth, infection). Graves' often presents with heat intolerance, tachycardia, sweating, and a non-tender thyroid enlargement. Some characteristic physical exam findings are demonstrated in Illustrations A-C. Radioactive iodine uptake scans will show diffuse uptake. Indications for radioactive iodine over antithyroid agents include a large thyroid gland, multiple symptoms of thyrotoxicosis, high levels of thyroxine, and high titers of TSI. Additionally, anti-thyroid medication use alone has been shown to result in a higher rate of relapse when compared with radioactive iodine ablation.

Reid et al. explore hyperthyroidism causes and treatment options. Graves' disease is the most common cause of hyperthyroidism. Graves' can be treated with radioactive iodine, anti-thyroid medications, or surgery, but in the US, radioactive iodine ablation is the treatment of choice in patients without contraindications. Of note, an infiltrative ophthalmopathy is noted in approximately 50% of these patients.

Marinò et al. report on the genetic and non-genetic factors of Graves'. Some of the environmental factors that have been shown to be associated with this pathology are female gender, periods of immune reconstitution, immune modulation, iodine, smoking, and physiologic stress. The major genes that have been found to predispose patients to Graves' disease are: HLA complex, CD40, CTLA-4, PTPN22, FCRL3, Thyroglobulin, & TSH-R. With further study, the goal is to establish a causal treatment pattern based on the defining etiology and genetics involved.

Incorrect Answers: Answer 1: Watchful waiting is not an appropriate

treatment option for an individual with symptomatic Graves' disease.

Answer 2: Beta-blockade alone would help with some of the hyper-sympathetic symptoms of Graves' disease (e.g. tachycardia), but is not considered a definitive treatment.

Answer 3: In the US, anti-thyroid mediations alone would not be considered an appropriate treatment option for a patient with Graves' disease and associated symptomatic tachycardia that could be treated with beta-blockers as well. When methimazole or propylthiouracil is used alone, there is an increased risk of relapse of hyperthyroidism at a later time.

Answer 5: Radioactive iodine ablation with prophylactic glucocorticoids would be an appropriate treatment option for someone with moderate to severe exophthalmos as thyroid destruction during ablation can cause worsening of symptoms.

PREFERRED RESPONSE ▼ 4 DISCUSSION: The therapy for Graves' disease with the best long-

term outcome is radioactive iodine therapy. Contraindications are pregnancy and severe ophthalmopathy.

Graves' disease (also known as diffuse toxic goiter) is the most common cause of hyperthyroidism, responsible for approximately 80% of all cases. It is an autoimmune disorder caused by the production of thyroid-stimulating antibody that bind to the TSH receptors on thyroid cells causing hormone synthesis. Treatment may include pharmacological therapy with propranolol for immediate control of symptoms as well as methimazole and propyltiouracil (PTU). However, the most successful therapy in the long term is radioactive iodine ablation therapy. This treatment is contraindicated in pregnant women in which PTU is preferred.

Recall the other common causes of hyperthyroidism: Plummer's disease, toxic thyroid adenoma, Hashimoto's thyroiditis, postpartum thyroiditis, iatrogenic hyperthyroidism, and iodine induced hyperthyoridism. All these patients may present with the classic clinical features including nervousness, hand tremor, sweating, weight loss, diarrhea, and palpitations. Treatment may be pharmacologic via thionamides such as PTU and methimazole, with radioactive iodine 131, or via surgical subtotal thyroidectomy.

Incorrect Answers: Answer 1: Levothyroxine is the treatment for

hypothyroidism but would make hyperthyroidism worse.

Answer 2: PTU is the therapeutic choice for a pregnant woman with Graves' but is inferior to radioactive iodine in the long term.

Answer 3: Methimazole is a pharmacologic option but it is not as effective as radioactive iodine in the long term. Notably, it is contraindicated in pregnancy.

Answer 5: Propranolol is good for immediate control of adrenergic symptoms but is not as efficacious as radioactive iodine in the long term.

A 45-year-old female presents to her primary care clinic with symptoms of palpitations, hyperhidrosis, tremor and general hyperactivity. A radioactive iodine update scan of this patient showing decreased thyroid uptake would effectively rule out which condition? Topic Review Topic

1. Subacute painless thyroiditis 2. Subacute granulomatous thyroiditis 3. Graves' disease 4. Iodine-induced thyroid toxicosis 5. Levothyroxineoverdose

REFERRED RESPONSE ▼ 3 DISCUSSION: The patient in this vignette most likely has

hyperthyroidism, as demonstrated by her symptoms of hypermetabolism. It is important to distinguish high and low uptake forms of hyperthyroidism, of which the only high uptake-form listed is Graves disease.

There are several types of thyroiditis, one form of which is subacute granulomatous thyroiditis. This condition can present initially with either hypo or hyperthyroidism. In the case of initial hyperthyroidism, the destruction of the thyroid gland causes a release of previously synthesized thyroid hormone but will ultimately convert to a hypothyroid state as these stores are consumed but not replaced. It is important to note that the initial hyperthyroidism may progress to thyroid storm, which may be fatal. Subacute granulomatous thyroiditis can also initially present as a hypothyroid state usually following a viral illness, and in these cases is usually self-limited.

) 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?

FIGURES: A

1. Agranulocytosis 2. Increased total cancer mortality 3. Hyperthyroidism 4. Hypothyroidism 5. Hypoparathyroidism

PREFERRED RESPONSE ▼ 4 DISCUSSION: The clinical presentation is

consistent with Graves' disease. Hypothyroidism (due to radiation thyroiditis) may occur in the treatment of Graves' disease with I-131 radioiodine therapy.

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.

Incorrect Answers:Answer 1: Agranulocytosis is the most feared complication of the anti-thyroid drugs propylthiouracil and methimazole.Answer 2: Ron et al., in a study of over 35,000 patients, found no increased risk of total cancer mortality following I-131 treatment. There may be a slightly elevated risk of thyroid cancer mortality following I-131 treatment, but underlying thyroid disease appears to play a role.Answer 3: While possible if insufficient dose of I-131 is given, hypothyroidism is much more common. Answer 5: Hypoparathyroidism occurs if the parathyroid glands are incidentally removed during total thyroidectomy.

A 69-year-old man presents to the general medical clinic with palpitations. He has a history of an endocrine disorder that he reports has caused him to have chronic diarrhea and weight loss. His vital signs are temperature 37 degrees Celsius, blood pressure 130/85, heart rate 141, and respiratory rate of 18 with an oxygen saturation of 99% on room air. His pulse is irregular on physical examination. He is mentating normally and is in no acute distress. His exam is also notable for hyperreflexia and enlargement around his neck. An EKG reveals the following in figure A. What would be the next best step in management of this patient's chief complaint? Topic Review Topic

FIGURES: A

1. Emergent cardioversion 2. Administration of propranolol 3. Administration of amiodarone 4. Iodine 131 ablation 5. Administration of methimazole

PREFERRED RESPONSE ▼ 2 DISCUSSION: In a patient with atrial fibrillation or tachycardia

secondary to hyperthyroidism, the initial appropriate treatment is a beta blocker if that patient is stable.

Atrial fibrillation occurs when conduction in the atria fires in a continuous chaotic pattern resulting in an irregular, rapid ventricular rate. There are multiple causes including coronary artery disease, myocardial infarction, hypertension, mitral valve disease, pericarditis, pulmonary disease, alcohol intake, and stress. Another cause is hyperthyroidism. Clinically patients present with palpitations, dizziness, angina, and an irregular pulse. On EKG, the clinician should look for irregular RR intervals and tachycardia. Treatment depends on whether the patient is stable or unstable. In the unstable patient, immediate electrical cardioversion to sinus rhythm is indicated. In a stable patient, treatment focuses on rate control (target 60-100) with beta blockers or calcium channel blockers. After rate is controlled, rhythm can be addressed with cardioversion.

Image A depicts the classic irregularly irregular tachycardia indicative of atrial fibrillation. Note the absence of P waves.

Incorrect Answers: Answer 1: Emergent cardioversion is indicated in

management of atrial fibrillation when the patient is not stable. However, this patient is stable and could be treated with a beta blocker.

Answer 3: Administration of amiodarone is used in the treatment of post myocardial infarction arrhythmias such as ventricular tachycardia but would not be indicated in this case.

Answers 4 and 5: These are potential options in the management of Grave's hyperthyroidism but would not immediately address the patient's chief complaint which is palpitations secondary to atrial fibrillation and tachycardia.

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

PREFERRED RESPONSE ▼ 4 DISCUSSION: 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.

Graves' disease is the most common cause of hyperthyroidism. This condition is an autoimmune disorder with stimulating anti-TSH receptor antibodies (type II hypersensitivity). Anti-microsomal and anti-thyroglobulin antibodies are also present. Graves' disease is a female dominant disorder and has associations with HLA-B8 and DR3. Thyrotoxicosis is most often incited during stress (e.g. childbirth, infection, or steroid withdrawal). Fetal hyperthyroidism can present with low birth weight, microcephaly, warm wet skin, dysphagia, irritability, increased appetite with poor weight gain, exophthalmos, and diffuse goiter.

Bishnoi and Sachmechi discuss hyperthyroid disease management during pregnancy. Thyroid-stimulating hormone (TSH) is induced in normal pregnancy; however, in patients who are already hyperthyroid this may result in thyrotoxicosis leading to abortion, stillbirth, neonatal death, and low birth weight. They report that the main cause of thyrotoxicosis in pregnancy is Graves' disease, which may be treated with antithyroid drugs or surgery. Importantly, many thyroid conditions and treatments may directly affect the fetus, such as autoimmune postpartum thyroiditis.

Incorrect Answers: Answer 1: Hypoparathyroidism, not

hyperthyroidism, is seen in DiGeorge syndrome. Answer 2: Intrauterine toxoplasmosis infection is

not associated with hyperthyroidism. Answer 3: Maternal iodine deficiency is associated

with hypothyroidism, not hyperthyroidism. Congenital hypothyroidism presents with poor feeding, lethargy, hypotonia, coarse facial features, large protruding tongue, and developmental delay at 6-12 weeks of life.

Answer 5: Maternal history of Hashimoto's thyroiditis is not associated with neonatal hyperthyroidism.

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? Topic Review Topic

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 availab

PREFERRED RESPONSE ▼ 4 DISCUSSION: 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.

Incorrect Answers: Answer 1: A larger dose of radioiodine could have led to

an even greater exacerbation of the patient's exophthalmos. A smaller dose could have mitigated the effect of the radioiodine.

Answer 2: Beta-blockers act to control the symptoms of hyperthyroidism, notably tachycardia and palpitations; initiating a beta-blocker would not be expected to decrease the risk or severity of the worsening of this patient's ophthalmopathy.

Answer 3: Antithyroid drugs should be stopped prior to initiating therapy with radioactive iodine.

Answer 5: Pretreatment with glucocorticoids has been shown to decrease the risk or extent of worsening exophthalmos after initiating radioactive iodine therapy.

A 33-year-old man is found to have lymphocytic infiltration of his extraocular muscles secondary to an autoimmune process. Fibroblasts in the orbits of his eyes are dysregulated and large amounts of glycosaminoglycans are deposited. Which of the following is most likely present in this patient? Topic Review Topic

1. Infection of the orbit 2. Decreased reabsorption of aqueous humor 3. Autoimmune destruction of the lacrimal glands 4. Anti-TSH receptor antibodies 5. Inflammation of the axial skeleton

PREFERRED RESPONSE ▼ 4 DISCUSSION: This patient's presentation is consistent with Graves' disease.

Graves' disease is an autoimmune disease characterized by stimulating anti-TSH receptor antibodies.

Graves' disease is the most common cause of hyperthyroidism. It presents with non-tender thyroid enlargement, exophthalmos, pretibial myxedema, and symptoms of hyperthyroidism. Exophthalmos occurs by autoimmune attack on the extracellular muscles by lymphocytes, and subsequent proliferation of fibroblasts with deposition of hyaluronic acid and glycosaminoglycans. Treatment is with beta-blockers, thionamides, or I-131 ablation.

Patel et al. discuss other autoimmune diseases with ocular manifestations including RA, JRA, Sjogrens, SLE, MS, GCA, and the seronegative spondyloarthropathies, whose "ocular symptoms may include dry or red eyes, foreign-body sensation, pruritus, photophobia, pain, visual changes, and even complete loss of vision."

Bahn discusses the pathophysiology of Graves' disease ophthalmopathy in NEJM: "orbital fibroblasts secrete large quantities of hyaluronan in response to various cytokines, and a subgroup of orbital fibroblasts can differentiate into mature adipocytes that have increased expression of thyrotropin receptor. These cellular changes lead to the characteristically enlarged eye muscles and expansion of orbital fat of patients with Graves' ophthalmopathy."

Incorrect Answers: Answer 1: Orbital cellulitis is an example of an infection

of the orbit. The question stem describes an autoimmune process, not an infectious one. Furthermore, exophthalmos is not usually seen in orbital cellulitis.

Answer 2: Decreased reabsorption of aqueous humor through the canal of Schlemm describes glaucoma. Glaucoma presents with insidious onset of peripheral vision loss (open-angle glaucoma) or acute onset of blurry vision (angle-closure glaucoma).

Answer 3: Autoimmune destruction of the lacrimal and salivary glands describes Sjogren's syndrome. Sjogren's syndrome presents with dry eyes and dry mouth.

Answer 5: Inflammation of the axial skeleton is one of the hallmarks of ankylosing spondylitis. Anklyosing spondylitis presents with insidious onset morning stiffness in the back.

A 53-year-old female presented to her primary care physician for an annual check-up. She does not smoke, use drugs, or consume alcohol. The patient currently takes no medications. Routine blood tests demonstrate a TSH level of 9.5 uU/mL (normal 0.35 to 5.0 uU/ml). Her T3/T4 levels are within normal limits. The initiation of treatment for hypothyroidism would be indicated for all EXCEPT which of the following findings? 1. Pretibial myxedema 2. Presence of antithyroid peroxidase (anti-TPO) antibodies 3. Hyperlipidemia 4. Constipation 5. Decreased sweating

PREFERRED RESPONSE ▼ 1 DISCUSSION: This patient’s elevated TSH level coupled with

normal T3/T4 levels indicates subclinical hypothyroidism. While patients with serum TSH levels greater than 10 uU/mL are generally treated with levothyroxine, asymptomatic patients with elevated TSH levels (but < 10) are not treated with thyroid supplementation. Pretibial myxedema is a symptom of clinically advanced HYPERthyroidism and does not warrant thyroid supplementation.

Subclinical hypothyroidism is found in approximately 2% of the population, and may be found in as many as 20% of women over age 60. Indications for treatment of hypothyroidism with TSH levels below 10 uU/mL include the presence of anti-TPO antibodies, clinical symptoms of hypothyroidism, hyperlipidemia, and menstrual dysfunction. Subclinical hypothyroidism is otherwise not treated due to the risk of overtreatment with levothyroxine, which may cause atrial fibrillation and bone mineral loss.

A 40-year-old woman presents to her primary care physician for an annual check-up. She complains of intermittent fatigue. Laboratory tests are notable for the following: TSH, serum: 11.2 uU/mL (normal 0.5-5.0 uU/mL) Thyroxine (T4), serum: 9.8 ug/dL (normal 5-12 ug/dL) Which of the following other conditions, if present, would merit treatment with thyroxine? Topic Review Topic

1. Tender thyroid gland 2. High erythrocyte sedimentation rate (ESR) 3. Hypercholesterolemia 4. Proptosis 5. Hand tremor

PREFERRED RESPONSE ▼ 3 CORRECT DISCUSSION: The patient presents with elevated TSH

(normal range 0.5-5.0 uU/mL) and T4 levels within the normal reference range (5-12 ug/dL) consistent with subclinical hypothyroidism. Patients with subclinical hypothyroidism should be treated with thyroxine if hypercholesterolemia is present.

Subclinical hypothyroidism occurs in the early stages of thyroid function inadequacy. The hypothalamic-pituitary axis recognizes falling serum T4 levels and increases TSH function accordingly. Patients with the disease should be treated with thyroxine in the event of goiter, hypercholesterolemia, symptoms of hypothyroidism, or TSH levels > 20 uU/mL.

Incorrect Answers: Answers 1 and 2: Painful, tender thyroid

gland and high ESR are associated with hypothyroidism from subacute thyroiditis. Subacute thyroiditis is managed with NSAIDs and aspirin for mild symptoms and corticosteroids for severe pain.

Answer 4: Proptosis is a hallmark of Graves' disease.

Answer 5: Hand tremor is a symptom of hyperthyroidism

A 37-year-old female presents to a general medical clinic with muscle weakness. Review of systems also reveals fatigue and chronic constipation. Vital signs reveal HR 64, BP 110/80, RR 12 and T 36.4. Physical examination is notable for muscle weakness at the hips and shoulders. Initial laboratory testing reveals a normal erythrocyte sedimentation rate but an elevated creatine kinase. What is the next step in management? 1. Refer to a rheumatologist2. Send thyroid stimulating hormone and T43. Send rheumatoid factor4. Send ANA5. Send AM Cortisol

PREFERRED RESPONSE ▼ 2 This patient has symptoms suggestive of hypothyroidism and associated

myopathy. Evaluation of TSH and free T4 are the first step in evaluating for clinical hypothyroidism.

Myopathy can be caused by hypothyroidism. Because it is not an inflammatory-mediated myopathy, ESR should be normal, but CK will be elevated. Typically, other symptoms of hypothyroidism are present, such as fatigue, weight gain, and constipation. Other causes of myopathy include infectious myopathies, inflammatory myopathies such as dermatomyositis, inclusion body myopathies, and polymyositis, and drug induced myopathies (especially from statins).

Gaitonde et al. review hypothyroidism. Untreated hypothyroidism can contribute to hypertension, dyslipidemia, infertility, cognitive impairment, and neuromuscular dysfunction. The prevalence increases with age, and is higher in females than in males. Autoimmune thyroid disease is the most common etiology of hypothyroidism in the United States. The best laboratory assessment of thyroid function is a serum thyroid-stimulating hormone test.

Kaminsky et al. review hypothyroid myopathy. Hypothyroidism induces a metabolic myopathy, with a fall in energy production, especially mitochondrial metabolism. This is due to a global inhibition of the main oxidative pathways (substrate incorporation, substrate oxidation) and of the respiratory chain.

Incorrect Answers: Answer 1: Specialty referral in the setting of

hypothyroidism may include referral to an endocrinologist, but this is not appropriate at this time.

Answer 3: Rheumatoid Factor is a screening test for rheumatoid arthritis, but this patient's signs and symptoms are more indicative of hypothyroidism.

Answer 4: ANA is a high sensitivity, low specificity test for Lupus.

Answer 5: Morning cortisol would be appropriate if you suspected Cushing's Disease, but the history is more suggestive of hypothyroidism, which is also much more common among the general population.

A 31-year-old female with a past medical history of follicular thyroid cancer treated two years prior with a total thyroidectomy followed by radioactive iodine ablation presents to her gynecologist with questions relating to pregnancy. She and her partner are thinking about getting pregnant, but she is concerned about her thyroid replacement hormone, specifically the complications of being hypothyroid during pregnancy. She wants to know how her levothyroxine dosing should be handled prior to conception and during her pregnancy. Which of the following would be an appropriate response to this patient's concerns? Topic Review Topic

1. Your current dose will need to be increased before conception to reduce the potential fetal complications.

2. Your current dose will only need to be increased during pregnancy, not before.

3. Your current dose will only need to be increased before pregnancy, not during.

4. Your current dose will be sufficient for her and the fetus during pregnancy.

5. Your pregnancy is at increased risk of complications because of hypothyroidism regardless of the dose.

PREFERRED RESPONSE ▼ 2 DISCUSSION: In hypothyroidism during pregnancy,

the levothyroxine dose will only need to be increased during pregnancy, not before.

The levothyroxine dose needs to be increased during pregnancy to maintain a euthyroid state as a result of the increase of thyroglobulin binding hormone in pregnancy which decreases the amount of circulating free T3/T4. Thyroid disease, if untreated during pregnancy, increases the risk of miscarriage, placental abruption, hypertensive disorders, and growth restriction. While this patient was well-informed, it is important for obstetricians to screen women at high risk, including those with a history of thyroid disease, type 1 diabetes mellitus, other autoimmune diseases, current or past use of thyroid therapy, or a family history of autoimmune thyroid disease.

You are working up a 6-week-old American infant in the pediatric clinic. He was born at term following an uncomplicated pregnancy and now lives with his parents in Massachusetts. However, his chart reveals an indirect hyperbilirubinemia present at birth. His mother reports poor feeding. On physical exam you note lethargy, hypotonia, a large, protruding tongue and coarse facial features. Which of the following is the most likely cause of this presentation? Topic Review Topic

1. Iodine deficiency 2. Thyroid dysgenesis 3. Rett syndrome 4. Trisomy 21 5. Toxoplasmosis

PREFERRED RESPONSE ▼ 2 DISCUSSION: The child in this vignette most likely has

cretinism caused by untreated congenital hypothyroidism as a result of thyroid dysgenesis, the most common cause of cretinism in the developed world.

Cretinism is a condition that develops in children who lack sufficient amounts of thyroid hormone. The classic presentation is a child who appears normal at birth (as there is maternal thyroid hormone present) but gradually develops lethargy, hypotonia, coarse facial features, and poor feeding over the next 6-12 weeks. Cretinism can also be caused by iodine deficiency, the most common cause in the developing world. Congenital hypothyroidism can be caused by agenesis of thyroid tissue or defects in the enzymes responsible for thyroid hormone production. T4 is crucial during the first two years of life for normal brain and bodily development.

Incorrect Answers Answer 1: While, iodine deficiency is the most

common cause of cretinism in the developing world, it is less common than congenital hypothyroidism due to thyroid agensis in the US.

Answer 3: Rett syndrome has normal development until 6-18 months with drooling, seizures, and decreased head circumference.

Answer 4: Down syndrome (trisomy 21), while a risk factor for Hashimoto throiditis, presents with macroglossia though would also have a flat facial profile prominent epicentral folds, and simian creases in hands.

Answer 5: Congenital toxoplasmosis presents with jaundice and hepatosplenomegaly but not the other signs.

THYROID NODULES AND CANCER These are incredibly common, and are palpable in as

much as 5% of women and 1% of men. Ninety-five percent are benign (adenoma, colloid nodule, cyst).

Thyroid nodules are rarely associated with clinically apparent hyperfunctioning or hypofunctioning.

Diagnostic Tests Thyroid nodules >1 em must be biopsied with a fine-

needle aspirate if there is normal thyroid function (T4/TSH). Nodules in those who are euthyroid should be biopsied. There is no need to ultrasound or do radionuclide scanning because these tests cannot exclude cancer.

When a patient has a nodule:1. Perform thyroid function tests (TSH and T4).2. If tests are normal, biopsy the gland.

A 46-year-old woman comes to the office because of a small mass she found onpalpation of her own thyroid. A small nodule is found in the thyroid. There is notenderness. She is otherwise asymptomatic and uses no medications.What is the most appropriate next step in the management of this patient?a. Fine-needle aspirationb. Radionuclide iodine uptake scanc. T4 and TSH levelsd. Thyroid ultrasounde. Surgical removal (excisional biopsy)

Answer: C. If the patient has a hyperfunctioning gland (i.e., the T4 is elevated or the TSH is decreased ), the patient does not need immediate biopsy. Malignancy is nothyperfunctioning. Ultrasound of thyroid is done to evaluate the size of the lesion, butdoes not change the need for either thyroid function testing or needle aspiration.

Thyroid carcinoma1. Workup of thyroid nodulesa. Thyroid nodules are usually benign and increase in frequency with age.b. Nodules should be evaluated with TSH levels, thyroid function tests, ultrasound(US), and fine needle aspiration (FNA) with biopsy.c. “Cold” nodules exhibit decreased radioactive iodide (I2) uptake (from decreasedmetabolic activity); “hot” nodules exhibit increased iodide uptake (from increasedmetabolic activity).d. Increased risk of malignancy 5 male, children, adults over age 60 years and underage 30 years, history of neck irradiation, poor iodide uptake on thyroid scan(cold nodule), solid nodule on USe. Malignant nodules can arise from a variety of thyroid cell types (see Table 5-7).

2. H/P nontender nodule in anterior neck, dysphagia, hoarseness; possible cervicallymphadenopathy3. Labs biopsy provides diagnosis; thyroid hormones normal or decreased4. Radiology US used to determine size and local extension; thyroid scan may differentiatehot from cold nodule (malignant nodules more likely to be cold)

5. Treatmenta. Benign small cystic nodules may be observed.b. Benign solid nodules are treated with surgery, radioablation, and postoperative levothyroxine to stop thyroid hormone overproduction and decrease risk of malignant conversion.c. Malignant tumors require surgical resection (lobectomy for nonanaplastic tumors,1 cm diameter, total thyroidectomy for larger tumors) and radioiodine ablation.d. Radiation therapy for tumors with local extension; chemotherapy for metastatic tumorse. Thyroid replacement (levothyroxine) needed after surgery