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Endocrinology - Archer USMLE step 3
 

Endocrinology - Archer USMLE step 3

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Archer USMLE step 3 Endocrinology lecture notes. These lecture notes are samples and are intended for use with Archer video lectures. For video lectures, please log in at ...

Archer USMLE step 3 Endocrinology lecture notes. These lecture notes are samples and are intended for use with Archer video lectures. For video lectures, please log in at http://www.ccsworkshop.com/Pay_Per_View.html

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    Endocrinology - Archer USMLE step 3 Endocrinology - Archer USMLE step 3 Presentation Transcript

    • ENDOCRINOLOGY Archer Online USMLE Reviews www.ccsworkshop.com All rights reserved Archer Slides are intended for use with Archer USMLE step 3 video lectures. Hence, most slides are very brief summaries of the concepts which will be addressed in a detailed way with focus on High-yield concepts in the Video lectures. These slides are only SAMPLES
    • Thyroid Disorders Thyrotoxicosis Subacute Thyroiditis Thyroid Function Tests Hashimatos Thyroiditis Hypothyroidism Thyrotoxic periodic paralysis Thyroid Nodule and Approach Thyroid Cancer
    • Thyroid Diagnostic Studies
      • Thyroid Function Tests : TSH, Total T4, Free T4, T3 levels.
      • Thyroid Binding Globulin
      • Thyroid Uptake Scan – Radio active iodine uptake scan ( RAIU scan)
      • Antibodies : Thyroid stimulating immunoglobulins, Anti-microsomal antibodies, Anti-thyroid peroxidase antibodies
      • Thyroid ultrasound
      • Thyroid Biopsy, FNAC
    • TSH
      • Obtain screening TSH in patients with conditions that may be explained by or worsened by hyperthyroidism :
      • Unexplained weight loss
      • Anxiety or sleep disturbance
      • Tachycardia, including supraventricular tachycardia and new onset atrial fibrillation
      • Osteoporosis ( always suspect and rule out hyperthyroidism especially when osteoporosis is worsening despite adequate therapy in the elderly)
    • TSH
      • Obtain screening TSH in patients with conditions that may be explained by or worsened by hypothyroidism :
      • History of thyroid disease
      • Autoimmune disease (R/O co-existent hashimatos)
      • Unexplained depression
      • Cognitive dysfunction ( dementia, delirium)
      • Hypercholesterolemia ( can be secondary to hyopthyroidism or can be worsended by it)
      • Unexplained constipation
      • Screen in early pregnancy
    • TSH
      • Preferred Screening test for suspected HYPO/HYPER Thyroidism
      • Preferred Follow-up test for patients receiving therapy for either hypo or hyperthyrodism or pts who had thyroid cancer therapy
      • If TSH High  possible Primary hypothyroidism or rarely, secondary hyperthyroidism
      • If TSH low  possible Primary hyperthyroidism or rarely, secondary hypothyroidism
      • If TSH low in pt on treatment for hypothyroidism  reduce dose of levothyroxine. ( usually in increments of 25mcg each time)
      • If TSH high in a pt on treatment for hypothyroidism  Increase dose of levothyroxine. ( usually in increments of 25mcg each time)
      • If TSH low in pt on treatment for hyperthyroidism  Increase dose of Propylthiouracil/ Methimazole ( or may indicate inadequate therapy)
      • If TSH high in a pt on treatment for hyperthyroidism  Reduce dose of Propylthiouracil/ Methimazole ( Indicates excess antithyroid therapy.
      • If Radioiodine therapy was chosen, then aim is to make the pt Hypothyroid in order to achieve good cure rates in Graves thyrotoxicosis  in that case, you need to start levothyroxine post radioiodine therapy or post surgically)
    • TFTs – Further Approach Obtain Total and Free T4 levels, ONCE TSH comes abnormal
    • TFTs – Further Approach
      • If TSH high but Free T4 low  primary hypothyroidism
        • Usually Hashimatos thyroiditis.
        • In countries where Iodine deficiency is a problem, this could be due to endemic goiter. (urine iodine low)
        • Iatrogenic Hypothyroidism due to Thyroidectomy or Radioiodine therapy
        • Drug induced  Amiodarone, Lithium, Iodine {excess iodine immediately inhibits both new hormone synthesis (by blocking organification, known as the Wolf - Chaikoff effect ) and the release of thyroid hormone. It also decreases gland size and vascularity. This effect is transient, however, lasting approximately 1-3 weeks}, Interferon, Thionamides
        • Late phase of Post-partum thyroiditis, Subacute thyroiditis, silent thyroiditis
    • TFTs – Further Approach
      • If TSH High but Free T4 also high  secondary Hyperthyroidism ( pituitary adenomas) - rare
      •  Get a Pituitary MRI
    • TFTs – Further Approach
      • If TSH high but Free T4 normal  Subclinical Hypothyroidism
      • Subclinical Hypothyroidism :
        • Treatment recommended only :
          • If clinical symptoms are present
          • If hyperlipidemia (high LDL)
          • If patient has goiter or
          • If TSH > 10mU/l , For TSH between 5 to 10  obtain TPO antibodies and consider treatment if TPO antibodies high)  In cases of subclinical hypothyroidism, presence of anti-TPO antibodies predicts progression to overt Hypothyroidism ( Hashimato’s)
    • TFTs – Further Approach
      • If TSH low but Free T4 high  primary hyperthyroidism
        • Usually Graves Thyrotoxicosis ( Thyroid scan – homogenous, diffuse uptake)
        • Toxic Multinodular Goiter ( Thyroid scan – Heterogenous)
        • Toxic Solitary Adenoma
        • Early phase of Subacute Thyroiditis/ Silent Thyroiditis ( No Uptake on Thyroid scan)
        • Post-partum Thyroiditis ( painless, may be followed by hypothyroid phase)
        • Iatrogenic Hyperthyroidism due to excess levothyroxine therapy in a hypothyroid patient
        • Surreptious intake of Thyroid hormones
        • Struma Ovarii ( Increased pelvic uptake on whole body iodine scan)
        • Gestational Thyrotoxicosis ( Increased HCG is responsible, Nuclear imaging contraindicated here)
        • Amiodarone induced ( two types of thyrotoxicosis)
    • TFTs – Further Approach
      • If TSH low but Free T4 also low  secondary Hypothyroidism  ( pituitary adenomas causing compression, craniopharyngioma)  clues are headaches, visual field deficits, ophthalmoplegia), pituitary/ hypothalamic surgery, pituitary/ hypothalamic infection/ infarction  Next step, get a Pituitary MRI
    • TFTs – Futher Approach
      • If TSH low but Free T4 normal  get T3 level.
      • If T3 high  T3 toxicosis.
      • If T3 normal  Subclinical Hyperthyroidism  Get an RAIU scan to see if this is Graves or a Toxic adenoma .
        • Subclinical hyperthyroidism can be just followed if no clinical symptoms and if there is no significant reason to treat.
        • Treatment of subclinical hyperthyroidism is recommended
          • in cases of osteoporosis ( Thyroxine increases bone resorption)
          • In atrial fibrillation
          • in elderly due to risk of atrial fibrillation and osteoporosis.
          • (If Graves, thionamide or I131. If Toxic adenoma, I131 is preferred.)
    • TFTs
      • Remember any combinations of TSH/Free T4 can occur in severe nonthyroidal illness depending on the phase of the illness ( critical phase, recovery phase)  Euthyroid sick syndrome . Some combinations
      •  low TSH, Normal free T4 ( may look like subclinical hyperthyroidism)
      •  High TSH, Normal free T4 ( recovery phase, may look like subclinical hypothyroidism)
      • Your clue to answer questions in such situations is the history recent or ongoing critical illness.
    • Thyrotoxicosis Important topics: Graves disease Subacute thyroiditis Post partum thyroiditis Amiodarone induced
    •  
    • Classification of Thyrotoxicosis based on RAIU Scan High RAIU Low RAIU Graves' disease Subacute thyroiditis Toxic multinodular goiter* Painless thyroiditis (includes postpartum thyroiditis) Toxic adenoma* Chronic thyroiditis with transient thyrotoxicosis HCG-mediated (choriocarcinoma) Iatrogenic/surreptitious thyroid hormone TSH-secreting pituitary tumor Metastatic functional follicular thyroid cancer (after thyroidectomy) Amiodarone-induced thyroiditis Struma ovarii (uptake in pelvis)
    • Grave’s Disease
      • Features : Diffuse Goiter, Ophthalmopathy ( proptosis, extraocular muscle paralysis, peri-orbital edema are specific. Lid-lag and stare can occur with any hyperthyroidism ) and Dermopathy (pre-tibial myxedema) .
      • Diagnosis : clinical features of hyperthyroidism ( palpitations, sweating, diarrhea, anxiety, tremor, hairloss, weightloss, menorrhagia) + diffuse goiter, thyroid bruit/thrill can be heard due to hyperdynamic circulation and increased thyroid vascularity.
            • Pain usually absent in thyroid ( PAIN may be present in subacute thyroiditis)
            • Always r/o subacute thyroiditis in differential
            • Obtain RAIU scan  Graves shows homogeneous uptake where as no uptake in subacute thyroiditis/ Surreptious intake of LT4. { Measure serum thyroglobulin and ESR to distinguish subacute thyroiditis (elevated thyroglobulin and ESR) from surreptitious thyroid hormone ingestion (suppressed thyroglobulin, normal ESR)}. Painless thyroiditis has elevated thyroglobulin but normal ESR.
            • TSH low, Free T4 high.
            • Antibodies present  Thyroid stimulating antibodies ( TSIgs) are high and are responsible for goiter and hyperthyroidism. Anti-TSH antibodies, Anti-TPO antibodies.
            • Can be associated with other autoimmune diseases  Vitilgo, pernicious anemia
    • Treatment Options
      • Treatment options in Hyperthyroidism :
      •  Medications ( Antithyroid drugs - PTU, Thionamides i.e; methimizole ) , B-Blockers ( propranolol, atenolol) for symptoms. ( propranolol preferred because it can block T4 to T3 conversion in high doses)
      •  Raioactive iodine therapy (131 I)
      •  Surgery ( Thyroidectomy)
      • Consider the following when selecting treatment for thyrotoxicosis:
          • Patient preference
          • Patient's age and comorbidities
          • Severity of thyrotoxicosis
          • Goiter size
          • Presence of ophthalmopathy (in Graves' disease patients)
    • Treatment for Thyrotoxicosis Due to Overproduction of Thyroid Hormone Modality Advantages Disadvantages Antithyroid drug therapy Least invasive Least costly Lower risk of permanent hypothyroidism Potential beneficial immunomodulatory effects Adverse drug effects Low permanent remission rate (approximately 33%-50%) Radioiodine Moderately fast reduction in thyroid hormone levels Less invasive than surgery Permanent hypothyroidism likely Requires delay in pregnancy (6-12 months) and breastfeeding May precipitate new or worsened ophthalmopathy Slight risk of thyroid storm after treatment ( in severe Hyperthyroidism, use pre-treatment) Thyroidectomy Rapid reduction in thyroid hormone levels Allows concurrent removal of suspicious nodules (if present) Allows reduction in size of large goiters Most invasive Most costly Permanent scar Permanent hypothyroidism likely Potential injury to parathyroids and recurrent laryngeal nerve
    • Anti-thyroid drug therapy
      • Propyl thiouracil :
            • Typical starting dose 100mg tid
            • Will need to discontinue 2 weeks prior to Radioiodine therapy because it can lead to failure of the therapy as it inhibits roadioiodine uptake by thyroid. ( REMEMBER METHIMIZOLE WILL NOT MUCH AFFECT RADIOIODINE UPTAKE – So, it is the preferred therapy to start if I131 therapy is planned but stop it 3 days prior to I131)
            • LESS POTENT than Methimizole.
            • Preferred drug in severe Hyperthyroidism because it can block T4 to T3 Conversion ( this effect not seen with methimazole)
            • Side effects : Rash, Agranulocytosis, Hepatocellular necrosis
            • Safe in pregnancy ( as it highly binds to plasma protein and very little crosses placenta. There is NO risk of Aplasia Cutis). However, Fetal hypothyroidism can occur in high doses due to transplacetal passage.
            • MONITOR LFTS AND CBC  If pts have sorethroat/ infection etc suggesting possibility of agaranulocytosis d/c PTU and get a blood count
    • Anti-thyroid drug therapy
      • Methimizole :
            • More potent than PTU
            • Typical starting dose is 30mg/d – preferred drug for most patients because single daily dose (except for patients with allergy to methimazole, who are pregnant, or have severe thyrotoxicosis or thyroid storm)
            • Contraindicated in pregnancy due to risk of Aplasia cutis and higher transplacental spread than PTU.
            • Not preferred in breast feeding ( PTU is preferred in breast feeding)
            • Side effects : Rash, Agranulocytosis, cholestatic jaundice
            • Good for pre-treatment prior to I-131 therapy. ( pre-treatment is used to normalize thyroid function before the administration of radioiodine and to attenuate potential exacerbations following ablative radioiodine therapy.  recommended for the elderly and those with underlying cardiac disease, who may be more vulnerable to worsening thyrotoxicosis during I 131 therapy.). Stop pre-treatment with methimazole 3 days prior to I131 to prevent treatment failure. Restart 3 days after giving I131 ( I131 takes 12 to 15 weeks to correct hyperthyroidism – monitor free T4 after I131 Therapy)
            • PTU is preferred over methimizole in severe hyperthyroidism.
      • IF USING ANTITHYROID THERAPY as sole primary therapy use for at least 12-18 months before tapering.
      • When started, Thionamides can correct hyperthyroidism in about 4 to 8 weeks ( response expected in 4 to 8 wks)
    • Antithyroid drug therapy
      • For Grave’s disease patient getting only anti thyroid drug therapy, factors favoring remission are :
          • - Small goiter - Low T3/T4 ratio - Mild thyrotoxicosis - Negative TSH-receptor antibody titers after treatment - No prior relapse
      • So, antithyroid drug therapy can be a preferred modaility in these scenarios.
    • Aplasia Cutis
      • Absence of skin in the newborn
      • Can occur with Methimizole use during pregnancy.
      • PIC : Aplasia Cutis of scalp
    • Radioiodine therapy
      • Select a dose of radioiodine based on the size of the patient's goiter and the result of the RAIU test.
      • Do not use radioactive iodine in patients who are pregnant (absolute contraindication) or breastfeeding.
      • Pregnancy should be delayed four to six months after radioiodine therapy.
      • Radioiodine is better avoided in patients with Graves' ophthalmopathy.
      • ( may cause worsening of ophthalmopathy)
      • After Radioiodine therapy
        • mother should stay away from children at least for 7 days ( Mother need to Arrange for a care taker for baby).
        • A I131 recepient must avoid contact with pregnant women, avoid sexual contact for one week after the therapy
    • Radioiodine Therapy – Follow Up
      • Hypothyroidism is inevitable in most cases. The risk of Hypothyroidism depends on the dose of I131.
      • About 2/3 of the patients develop hypothyroidism in the first year after I131. Even if they do not develop hypothyroidism in the first year, the TSH should be followed every 6 months forever after I131 therapy since the risk of developing hypothyroidism persists for lifetime
      • Get free T4 in the early period after I131 therapy not TSH. TSH can be misleading in that it can remain low for about 4 to 6 weeks even when patient’s free T4 returns to normal and patient is clinically euthyroid.
      • I131 typically takes 12 to 15 weeks to correct hyperthyroidism. So, thionamide has to be restarted 3 days after I131 and Free T4 and TSH carefully monitored. Once there is evidence of euthyroid state, taper and stop thionamide. Follow TSH, if hypothyroidism sets in  start Levothyroxine)
      • Start Levothyroxine after getting TSH level and Free T4 if the levels are consistent with hypothyroidism .
    • Surgery
      • Especially preferred in :
            • Goiter causing obstructive symptoms
            • Pregnant women allergic to PTU or develop agranulocytosis on PTU ( Radio iodine is not an option in pregnancy)
            • Intolerance to thionamides; refusal to take antithyroid drugs or radioactive iodine
            • Recurrence after a trial of thionamide therapy for Graves’ disease
            • Large MULTI-NODULAR goiter
            • Suspicion of malignancy.
      • Patients should be made euthyroid with thionamide therapy prior to elective surgery. Once a euthyroid state is achieved, oral iodine is given 7 to 10 days preoperatively to reduce the vascularity of the gland  then total/ subtotal thyroidectomy.
      • Complications : Hypothyroidism inevitable, Recurrent laryngeal nerve palsy (1%) , Permanent hypoparathyroidism ( 1% risk) and 1% risk of recurrent hyperthyroidism
      • Admit pts to ICU for 24 hrs s/p surgery  Monitor calcium level q6hrs in patents s/p thyroid surgery and replete calcium aggressively if <7mg%
    • Follow-up
      • In pts on long term antithyroid drug therapy
        • Monitor for adverse effects of antithyroid drugs such as rash, hepatic dysfunction, and agranulocytosis.
        • Repeat thyroid function tests every 3 to 6 months for the first year and then every 6 to 12 months after attaining normal FT4 and TSH levels.
      • Follow serum FT4 and TSH levels at 4-week intervals to ensure adequate replacement therapy ( for hypothyroidism) immediately after radioiodine therapy.
    • Q1
      • A 58-year-old woman has anxiety, tremors, excessive sweating, palpitations, and insomnia of approximately 1 month’s duration. Her medical history is unremarkable. She has had no recent pregnancies or miscarriages. She has a modest, nontender goiter and no exophthalmos. She takes no medications and has had no recent radiologic procedures. The
      • 24-hour radioactive iodine uptake is 10% (normal, 20% to 35%).
      • Laboratory Studies
      • Erythrocyte sedimentation rate 8 mm/h
      • Free thyroxine 3.5 ng/dL
      • Thyroid-stimulating hormone < 0.01 μU/mL
      • Thyroglobulin 45 ng/mL (normal, 2 to 20 ng/mL) ( do not confuse thyroglobulin with thyroid binding globulin – thyroglobulin is the one present in the thyroid follicles and is released out and elevated whenever there is “thyroidITIS”
      • Antithyroperoxidase 26 (normal, <2 μU/mL)
      • What is the most likely diagnosis?
      • ( A ) Struma ovarii
      • ( B ) Recent imaging study with an iodinated contrast
      • ( C ) Subacute thyroiditis
      • ( D ) Surreptitious use of thyroid hormones
      • ( E ) Painless/silent thyroiditis
      • (F) Use of Amiodarone
    • Q2
      • A 58-year-old woman presents to your office with increasing fatigue, memory loss, and depression for the past one year. Her history is significant for hypertension and she takes enalapril for it. Her family history reveals a brother who takes a medication for his thyroid. On physical examination, she is 168 cm (66 in) tall and weighs 73 kg (162 lb). Blood pressure is 152/88 mm Hg and heart rate is 86/min. HEENT exam is nornal without any thyroid enlargement.
      • Laboratory Studies
      • Hematocrit 46%
      • Plasma glucose 82 mg/dL
      • Total cholesterol 255 mg/dL
      • High-density lipoprotein cholesterol 49 mg/dL
      • Low-density lipoprotein cholesterol 187 mg/dL
      • Thyroid-stimulating hormone 12.2 μU/mL
      • A free thyroxine level of 0.9 ng/dL.
      • Which of the following statements is correct about levothyroxine replacement therapy for this patient?
      • ( A ) Her LDL will decrease.
      • ( B ) There will be no improvement in her symptoms.
      • ( C ) She is likely to lose weight.
      • ( D ) She will be at an increased risk of atrial fibrillation
      • ( E ) she will have an increased risk of osteoporosis
    • ANS.A
      • This patient has subclinical hypothyroidism. Rx is recommended if serum TSH levels greater than 10 μU/mL. Also, Rx is recommended in patients having symptoms and effects of hypothyroidism like hyperlipidemia In such cases, levothyroxine therapy reduces LDL cholesterol levels and improves symptoms.
    • Q3
      • A 50 y/o HIV +ve man with a CD4 count of 200 prrsents with complaints of fatigue, weightloss and dry cough. Cough has been for past 2 days and has high grade fever. No chest pain but he is visibly short of breath. His ABGs revealed hypoxemic respiratory failure with a po2 of 45. He is started on Bactrim IV and steroids.
      • Laboratory Studies reveal
      • Free thyroxine 0.9 ng/dL
      • Triiodothyronine 22 ng/dL
      • Thyroid-stimulating hormone 0.3 μU/mL
      • Which of the following statements about this patient’s condition is true?
      • ( A ) Perform a radioactive iodine uptake test
      • ( B ) Using T3 treatment will improve his condition and prognosis.
      • ( C ) The lab abnormalities are due to decreased peripheral conversion of thyroxine to triiodothyronine
      • ( D ) Serum thyroid binding globulin is increased
      • ( E ) Pituitary MRI should be obtained
    • Euthyroid Sick Syndrome
    • Euthyroid Sick Syndrome
      • Euthyroid sick syndrome is seen in acutely and critically ill patients.
      • Occurs due to alterations in the levels of circulating thyroid hormones that can occur in severe nonthyroidal illnesses.
      • Features: low T3, high reverse t3 normal T4, and low TSH levels. TSH starts elevating to hypothyroid levels during “recovery” phase of non thyroidal illness and returns to normal with complete recovery. But many combinations can occur
    • Q4
      • A 32-year-old woman is evaluated for recent onset of fatigue, palpitations, profuse sweating, and emotional lability. She gave birth to her second child 8 weeks ago and is not breast feeding. On physical examination, her pulse rate is 100/min, and she has mild lid lag, a fine hand tremor, and a slightly enlarged, nontender thyroid gland. Radioactive iodine uptake is less than 1% at 4 and 24 hours (normal, 20% to 35%). Laboratory test results include a serum thyroid-stimulating hormone level of less than 0.03 μU/mL and a free thyroxine level of 3.8 ng/dL.
      • Which of the following is the optimal treatment for this patient?
      • ( A ) Antithyroid drugs
      • ( B ) Radioactive iodine
      • ( C ) Thyroidectomy
      • ( D ) Prednisone
      • ( E ) ß-blockers
    • Key Point
      • Women presenting with thyrotoxicosis are treated with beta blockers to decrease palpitations tremors..
      • Antithyroid medications are not used in the thyrotoxic phase as since thyroid is not overactive.
      • Post partum thyroiditis may be followed by a hypothyroid phase ( due to destruction – which may start 4-8 months post-partum and may last 9-12 months) - treated with thyroid hormone replacement  which should be later tapered off  It is always important to monitor and taper off thyroid hormone after postpartum thyroiditis, since 80% of patients will regain normal thyroid function and not require chronic therapy.
    • IMP! – AIT
      • This condition occurs in up to 10% of patients who use amiodarone, which has a very high iodine content. Two subtypes occur: type 1 AIT is caused by iodine overload and occurs primarily in patients with underlying goiters; type 2 AIT is caused by drug-induced thyroid follicular damage (thyroiditis).
      • Both types are associated with a low 24-hour radioactive iodine uptake. No tests reliably distinguish between the two subtypes, although an underlying goiter and detectable radioactive iodine uptake are more common in type 1
      • AIT. Treatment of type 1 AIT consists of administering thionamides, with or without potassium perchlorate
      • Type 2 AIT may respond to corticosteroid therapy.
      • Patients who do not respond to this treatment may require plasmapheresis, dialysis, or thyroidectomy.
      • A 70-year-old man is evaluated because of a 1-year history of progressive weakness, weight loss, and hand tremors. For nearly 3 years, he has been treated with amiodarone for paroxysmal atrial flutter. He has no goiter and no history of thyroid disease. Thyroid scan shows scant, patchy tracer uptake. The 24-hour radioactive iodine uptake is 2.7% at 6 hours and 4.1% at 24 hours (normal, 20% to 35%). The serum thyroid-stimulating hormone level is <0.01 μU/mL and the serum free thyroxine level is 3.8 ng/dL.
      • Which of the following statements is true about the effects of amiodarone on this patient’s thyroid function?
      • ( A ) Amiodarone can cause thyrotoxicosis by producing iodine overload or thyroiditis.
      • ( B ) Amiodarone blocks peripheral thyroid hormone receptors.
      • ( C ) Amiodarone increases peripheral conversion of thyroxine to triiodothyronine.
      • ( D ) Amiodarone directly suppresses pituitary secretion of thyroid-stimulating hormone.
      • ( E ) Amiodarone increases serum thyroid hormone protein binding.
      • Two subtypes of amiodarone-induced thyrotoxicosis occur: type 1 is caused by iodine overload and occurs primarily in patients with underlying goiters; type 2 is caused by drug-induced thyroid follicular damage (thyroiditis).
    • Hypothyroidism
      • Important concepts:
      • Hashimato’s
      • Lithium induced
      • Myxedema coma
    • Hashimato’S Thyroiditis
      • Autoimmune thyroiditis associated with lymphocytic infiltration of thyroid gland.  causes gland disruption, initially may lead to hashitoxicosis and then hypothyroidism
      • Diagnosis : HIGH TSH, LOW FREE T4 and Elevated TPO antibodies/ anti microsomal antibodies.
      • TSIgs may be present too
      • Diffuse Goiter on physical exam.
      • Association with other autoimmune diseases must be kept in mind  pernicious anemia, addisons disease
      • Can be associated with B cell lymphomas
    • Treating Hypothyroidism
      • Levothyroxine (LT4) drug of choice.
      • In young patients  start initial full replacement dose calculated as 1.6 µg/kg/d. ( 70kg man – 112mcg/d)
      • In obese patients  calculate the initial dose using ideal body weight  of course , you can follow-up serum TSH 6-8 weeks later and titrate the dose.
      • In elderly patients > 60 yrs of age  start at dose 25 to 50 mcg and titrate every 6-8 wks untill TSH comes to desired range.
      • In those with KNOWN CAD/ hx of CHF and arrhythmias  Start at 12.5 mcg to 25 mcg dose and then titrate every 6-8 wks untill TSH comes to desired range.
      • Ideal Body Weight (men) = 50 + 2.3 ( Height(in) - 60 )
      • Ideal Body Weight (women) = 45.5 + 2.3 ( Height(in) - 60 )
    • Follow up – Treatment adequacy
      • TSH is used to follow up treatment adequacy
      • Levothyroxine has a t 1/2 of 7days. It takes a drug four to five t1/2s to reach steady state  which means DO NOT INCREASE LT4 dose prior to 4 to 6 weeks if pt is not symptomatic.
      • TSH level should be obtained at 6 – 8 weeks after starting therapy  because it takes this time for raised to TSH to normalize and also this is the time at which you can properly assess adequacy of LT4 therapy because LT4 reaches steady state around this time.
    • Follow up – Treatment adequacy
      • Use TSH levels as the guide to thyroid hormone dosage requirements.
      • Once treatment is started, monitor serum TSH levels every 6 to 8 weeks and adjust the LT4 dose until the TSH value is in the desired range.
      • Once TSH reaches desired range, recheck the TSH level 3 to 6 months later, and then if normal recheck annually.
      • If the TSH value is above the normal range, increase the LT4 dose by 12.5 to 25 µg/d and recheck in 6 to 8 weeks.
      • If the TSH value is low, decrease the LT4 dose by 12.5 to 25 µg/d and recheck in 6 to 8 weeks
    • Recognize Interactions!
      • Counsel patients to take levothyroxine at the same time each day and to avoid taking it within 4 hours of iron tablets, calcium supplements, antacids, and fiber supplements ( can reduce LT4 absorption)
    • Lithium Induced
      • Li Can cause hypothroidism
      • Rx  do not discontinue lithium, Start levothyroxine and continue lithium therapy.
    • Myxedema Coma
      • Severe hypothyroidism associated with altered mental status/ delirium/ coma.
      • Myxedema coma  usually found in elderly patients who have untreated or inadequately treated hypothyroidism and then develop a precipitating event. ( precipitating event for myxedema coma in a pt with untreated/inadequately treated hypothyroidism can be SEPSIS, Surgery, Trauma, GI bleeding, Stroke , MI, CHF, Sedative use)
      • So, always evaluate the pt for precipitating factor also  treat both myxedema coma as well as precipitant.
    • Myxedema coma
      • Admit to ICU for careful monitoring and appropriate treatment.
      • Get Endocrine consult always.
      • Obtain blood cultures, CT head, cardiac enzymes, EKG, CHEM 18, CBC R/o preciptating factors
      • TSH, FREE T4
      • RX :
          • Vital support : intubation if prolonged coma for airway protection, IV fluids, hypothermia blanket.
          • Levothyroxine intravenosly (500 µg, then 50-100 µg/d for myxedema coma, for npo pts 80% of oral dose ) + hydrocortosine 100 q8hrs x 2days to address possible decreased adrenal reserve in myxedema .
          • Also can use combination of LT4+LT3 for rapid T4 and T3 repletion in myxedema coma
          • Look for and treat any precipitating factor
    • Thyroid Nodule Approach
    • Approach – Palpable Thyroid Nodule
      • If thyroid nodule palpable
            • Get TSH First.
            • If High TSH – suggests cold nodule/ Hashimatos  Get FNAC ( some recommend ultrasound as next step here because hashimatos may have benign nodularity that regress with therapy and ultrasound will help to see if there are suspicious features. If U/S suspicious, then FNAC is recommended. This may be optimal approach because hurthle cells of hashimatos may cause false positives on cytology if the FNAC is obtained from such benign nodule). Treat with levothyroxine if overt hypothyroidism or subclinical hypothyroidism that warrants treatment.
            • If TSH normal – suggests cold nodule - get FNAC next
            • If TSH low - suggests Hot nodule ( toxic adenoma) but not confirmative (What if there is GRAVES in the surrounding tissue and this is a cold nodule?)  so, next step get RAIU scan  if COLD nodule, get FNAC. If RAIU scan shows Hot nodule treat with I131 ( if there is overt hyperthyroidism from this toxic adenoma) or just observation.
      • Cold nodules are more likely to be malignant when compared to hot nodules ( hot/ functioning nodule virtually rules out malignancy)
      • A negative FNAC does not rule out cancer completely. So, if clinical suspicion for cancer is high  consider surgical excision of the entire nodule. ( especially, when histology revealed follicular adenoma – remember, a negative FNAC from one area may not rule out possibility of follicular carcinoma in follicular adenoma )
    • Approach – Thyroid Incidentalomas
      • Thyroid Incidentalomas – These are those nodules ( not the palpable ones) detected on ultrasound such as ultrasound done for other palpable thyroid abnormalities, during carotid artery imaging or ultrasound done for hyperparathyroidism).
      • FNAC indicated if
            • Nodule > 10 mm in diameter.
            • On ultrasound, if nodule has suspicious features of malignancy  hypoechoic, microcalcifications, irregular shape, blurred margin or increased vascularity
            • If there are risk factors for thyroid cancer ( family history, childhood neck irradiation)
    • After FNAC - Further Approach
      • If FNAC is benign
            • Cystic nodule – use percutaneous Ethanol injection to get rid of nodule
            • Solid Nodule – use suppressive therapy with levothyroxine if there are no contraindications ( Heart disease, old age). Suppressive therapy with LT4 aims to reduce TSH and there by, regress the nodule
      • If FNAC is malignant  SURGERY
      • If FNAC is follicular adenoma (benign)  get a thyroid scan if not already done  If this is hot/functioning nodule, it rules out malignancy – so, follow-up. If this is a cold nodule, a negative FNAC from one area may not rule out possibility of follicular carcinoma in follicular adenoma – so, do Surgical excision of the entire nodule
      • (sub-total thyroidectomy) in those cases.
      • If FNAC is non-diagnostic  repeat FNAC
    • Guidelines ( Source: NEJM)
    • Thyroid Cancer - Prevalence
      • Prevalence of thyroid cancer is higher in the following groups and hence, high clinical suspicion should be maintained if you find a thyroid nodule in these groups ( i.e; warrants further evaluation of the nodule):
        • Children
        • Adults less than 30 yrs or above 60 yrs of age
        • History of head and neck radiation (eg: Hodgkins )
        • Family history of thyroid cancer
    • Radiation Exposure – Follow up for detecting thyroid cancer
      • Guidelines are not clear.
      • The incidence of thyroid cancer after radiation exposure is high for about four decades after exposure and then it declines.
      • If there is a history of significant radiation exposure such as ( therapeutic external beam radiation therapy in children, survivors of Japan atomic bombing, exposure during chernobyl nuclear incident), physical examination by thyroid palpation and ultrasound should be obtained every three years to detect any nodules.
      • If there is a palpable nodule in these patients, ultrasound must still be obtained to detect any non palpable nodules ( because multiple nodules are a common finding in radiation exposed patients)
      • All palpable nodules and suspicious nodules on ultrasound, must undergo FNAC.
    • Pheochromocytoma
    • Pheochromocytoma
      • Consider evaluating for Pheochromocytoma in patients with:
      • Refractory hypertension
      • Hypertension, accompanied by hyperadrenergic spells with:
        • Nonexertional palpitations
        • Diaphoresis
        • Headache
        • Tremor
        • Pallor
      • Family history of familial pheochromocytoma
      • A genetic syndrome that increases the risk of pheochromocytoma, such as:
        • Multiple endocrine neoplasia type 2
        • von Hippel-Lindau disease - RCC
        • Neurofibromatosis type 1
      • History of gastric stromal tumor or pulmonary chondromas (Carney triad)
      • An incidentally discovered adrenal mass ( Adrenal Incidentalomas)
    • Pheochromocytoma
      • Episodic Hypertension is charecterestic but ORTHOSTATIC HYPOTENSION can be seen.
      • Pheochromocytomas are 10% tumors  10% malignant, 10% bilateral and 10% familial.
    • Pheochromocytoma - Diagnosis
      • Best diagnostic test and high specificity (99%)  24 hr Urinary Metanephrines ( metanephrines or normetanephrines above the upper limit of normal in a patient not taking an interfering medication and not physically stressed is consistent with pheochromocytoma )
      • Plasma Metanephrines can be used if 24 hr unrine collection is not possible –specificity (88%) lower than 24 hr urine metanephrines
      • Obtain CT Abdomen to r/o Adrenal mass only if biochemical tests are positive. Very sensitive (96%) for pheochromocytoma ( adrenal mass) but low specificity due to high prevalence of adrenal incidentalomas.
      • MIBG scan  Very specific for pheochromocytoma . Sensitivity lower than CT scan. (Sensitivity only 80% and specificity 100%) MIBG (Metaiodobenzylguanidine) scan is the best test if looking for extra adrenal pheochromocytomas
      • Other tests – Plasma catecholamines, Urine VMA
    • False + ves
      • Medications and activities that may increase measured levels of catecholamines and metabolites ( False +ves for Metanephrines/ VMA)
      • Tricyclic antidepressants
      • Labetalol
      • Levodopa
      • Drugs containing catecholamines (e.g., decongestants)
      • Amphetamines
      • Buspirone (and most psychoactive agents)
      • Sotalol
      • Withdrawal from clonidine hydrochloride and other drugs
      • Ethanol
      • Acetaminophen and phenoxybenzamine (fractionated plasma metanephrines)
      • Physical stress (e.g., stroke, obstructive sleep apnea)
    • Treatment
      • Acute Hypertensive crises  use IV Phentolamine, Sodium nitroprusside or Nicardipine .
      • Definitive treatment is SURGERY. Send for histopath to r/o malignancy.
      • REMEMBER TO USE BOTH ALPHA AND BETA ADRENERGIC BLOCKING AGENTS PRIOR TO SURGERY – to prevent hypertensive crises during surgery. ( use phenoxybenzamine + atenolol)
      • Do not use non selective beta blocker without alpha blocker ( eg: propranolol alone)
      • Understand that relatively short-acting, selective α1-adrenergic receptor blockers (e.g., prazosin, terazosin, doxazosin) may be inadequate for preoperative drug preparation  so phenoxybenzamine preferred for pre-op therapy as it is long acting.
    • Primary Hyperparathyroidism
      • Parathyroid Adenomas
      • Parathyroid hyperplasia
    • Hypercalcemia
      • Etiology
      • Clinical features : bones, moans, stones, groans
      • Investigations: Ca, Phos, EKG, PTH, 24 hr Urinary calcium excretion or spot urine calcium/creatinine ratio ( R/o familial hypocalciuric hypercalcemia)
      • Management:
      • Criteria for surgery in primary hyperparathyroidism
      • Sestamibi scan only if surgery is planned/indicated
      • Hypercalcemic crisis management – ivf + lasix after volume repletion only
      • Indications for corticosteroids : are useful for treating hypercalcemia caused by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, and other granulomatous diseases
      • Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease  Indicated for hypercalcemia with parathyroid carcinoma.
      • Do not lower Calcium too much  Serum calcium reduction may cause lowered seizure threshold , paresthesia, myalgia, cramping, and tetany;
    • Criteria for Surgery – Primary hyperparathyroidism
      • Serum total calcium level >12 mg per dL (3 mmol per L) at any time
      • Hyperparathyroid crisis (discrete episode of life-threatening hypercalcemia )
      • Marked hypercalciuria (urinary calcium excretion more than 400 mg per day)
      • Nephrolithiasis
      • Impaired renal function
      • Osteitis fibrosa cystica
      • Reduced cortical bone density (measure with dual x-ray absorptiometry or similar technique)
        • Bone mass more than two standard deviations below age-matched controls (Z score less than 2)
      • Classic neuromuscular symptoms
      • Proximal muscle weakness and atrophy, hyperreflexia , and gait disturbance
      • Age younger than 50
      • A 66-year-old asymptomatic woman is evaluated for a serum calcium level of 11 mg/dL detected during a routine screening examination. Subsequently, the ionized calcium level is 5.7 mg/dL, and the intact parathyroid hormone level is elevated.
      • Which of the following is the most appropriate next step in the management of this patient?
      • ( A ) Parathyroidectomy
      • ( B ) Sestamibi scan of the parathyroid glands
      • ( C ) Creatinine clearance and 24-hour urine calcium excretion
      • ( D ) Chest radiograph
      • ( E ) Estrogen replacement therapy
    • Hyperprolactinemia
      • Stress
      • Drugs (<100)
      • Pituitary Tumors
      • Stalk effect
      • Hypothyroidism
    • Remember!
      • “ If suspecting Prolactin secreting adenomas or while working up the cause of hyperprolactinemia, the LEVEL OF PROLACTIN is the best clue to the possible etiology of hyperprolatinemia”
      • Prolactin level usually less than 100 with drugs or stress!
    • Prolactinomas
      • Microademomas  prolactin levels usually > 100
      • Macroadenomas  Prolactin levels usually very high 500 to 1000. Be aware of HOOK Effect.
      • MRI is the next test if high prolactin level encountered and cannot be explained by meds/ stress. MRIs do not r/o small microadenomas (<3mm)
      • For microadenomas/ non invasive macroadenomas  use Bromocriptine ( dopamine agonist)  Consider surgery for those patients not responding to or intolerant of dopamine agonists.
      • If Prolactin Producing Macroadenomas with mass effect  Try bromocriptine first  if no response, Surgery ( trans sphenoidal resection)
    • Pituitary Adenomas
      • In deciding how to approach INCIDENTALLY discovered pituitary tumors, first rule out Function
      • R/O functioning adenomas first  prolactin level, Dexamethasone suppression test, ACTH level, TSH and IGF 1 level depending on the clinical features.
      • Except Prolactinomas, all other functioning adenomas are treated primarily by surgery
      • If Non functioning adenomas  Surgery indicated only if mass effects  Visual field defects , Headaches and Hypopituitarism
      • Follow patients with non functioning microadenomas and small, noninvasive macroadenomas with a 6-month MRI scan and yearly thereafter  If there is no evidence of enlargement after 3 to 5 years, then continue to follow patients clinically.
      • A 25-year-old woman is evaluated because of a 9-month history of weight gain, fatigue, muscle weakness, and depression. She bruises and bleeds easily, and her menses have been irregular. Her medical history and family history are unremarkable. On physical examination, she is 157 cm (62 in) tall and weighs 74 kg (164 lb). Blood pressure is 160/95 mm Hg and pulse rate is 84/min. She has a rounded, plethoric face. Her supraclavicular fat pads are notably full, and she has a mildly enlarged dorsal fat pad (buffalo hump). She has several violaceous striae on the lower abdomen
      • and bruises on the left arm from recent blood testing.
      • Laboratory Studies
      • Urine cortisol 318 μg/24 h
      • Morning serum cortisol 28 μg/dL
      • Morning plasma adrenocorticotropic hormone 45 pg/mL
      • After administration of dexamethasone, 8 mg orally at bedtime, the morning serum cortisol level is 3 μg/dL. Findings on chest radiograph are normal.
      • Which of the following tests should be ordered next?
      • ( A ) Low-dose (1 mg) overnight dexamethasone suppression test
      • ( B ) Magnetic resonance imaging scan of the pituitary gland
      • ( C ) Computed tomography scan of the adrenal glands
      • ( D ) Computed tomography scan of the lungs
      • ( E ) Inferior petrosal sinus sampling
    • CARCINOID
      • Flushing, diarrhea, wheezing are clinical features
      • Ileal carcinoids commonly metastisizes to liver
      • Appendiceal carcinoids are most common.
      • If pt develops above symptoms on small doses of SSRIs  suspect Carcinoid syndrome
      • Screening test  Urine 5-HIAA
      • Confirmatory test – Octreotide Scan
      • Rx – medically, octreotide for symptoms
      • Surgery is definitive if no metastases
    • Hypoglycemia
      • Medication induced in Diabetics
      • Surreptious insulin/ sulfonyl urea abuse
      • Insulinoma
      • Treatment
    • INSULINOMA - Whipples Triad – the symptoms of hypoglycemia - C-peptide level.
      • A 38-year-old woman is evaluated while in a stuporous state. The patient is slender and nearly comatose. She responds minimally to a loud voice and sternal pain. On physical examination, the pulse rate is 110/min and blood pressure is 115/70 mm Hg. An accompanying friend informs you that the patient is a nurse and that she has had recent psychiatric problems. The blood glucose level is 14 mg/dL. Additional blood is drawn, and the patient is quickly resuscitated with intravenous glucose. A sulfonylurea screen is negative. Laboratory Studies
      • Serum calcium 9.5 mg/dL
      • Serum insulin 45 mU/mL
      • C-peptide 4.2 ng/mL (normal, 0.5 to 2.0 ng/mL)
      • Proinsulin 0.6 ng/mL (normal, 0 to 0.2 ng/mL)
      • Which of the following is the best explanation for these findings?
      • ( A ) Solitary insulin-producing pancreatic islet cell tumor
      • ( B ) Surreptitious insulin use
      • ( C ) Surreptitious metformin use
      • ( D ) Multiple endocrine neoplasia type 1
      • ( E ) Multiple endocrine neoplasia type 2A
      • The differential diagnosis of fasting hypoglycemia associated with hyperinsulinemia includes insulinoma, surreptitious insulin use, and oral sulfonylurea ingestion.
      • Surreptitious insulin use is associated with low serum C-peptide and proinsulin levels.
    • Glucagonoma Necrotizing migratory erythema Octreotide scan
    • Congenital Adrenal Hyperplasia
      • 21 Hydroxylase deficiency
      • Increased 17 hydroxy progesterone, increased adrenal androgens. Low cortisol
      • Ambiguous Genitilia in Congenital form
      • Needs Mineralocorticoid and Glucocorticoid replacement – prevent salt wasting and hypotension
      • Adult onset CAH is possible in mild deficiency – can be confused with PCOS
    • Polycystic Ovary Disease
    • Conns Syndrome
      • Primary Hyperaldosteronism – Hypertension, Hypokalemia and Alkalosis
      • PAC/ PRA ratio best screening test
      • CT scan to r/o adrenal mass after biochemical evidence.
      • Rx – medically with Spironolactone
      • Surgery if tumor > 4cm or suspicious features of adrenal cancer or if refractory HTN despite maximal medical therapy
    • Cushings Syndrome
      • Etiology :Adrenal Cushings
      • Pituitary Cushings
      • Ectopic Cushings ( Small cell ca)
      • Diagnosis : Overnight Low dose (1mg) dexamethasone suppression test, Urinary 24 hr free cortisol, High dose (8mg) dexamethasone suppression test, ACTH level.
      • CT abdomen if Adrenal cushing suspected
      • Pituitary MRI if Pituitary adenoma suspected
    • False +ve Low Dose dexamathasone test
      • Factors that can produce false-positive or false-negative dexamethasone suppression tests:
      • Alcohol, rifampin, phenytoin, and phenobarbital induce the cytochrome P450-related enzymes and enhance dexamethasone clearance  Cause False +ve
      • Hepatic failure retards dexamethasone clearance  cause false –ve.
      • In renal failure, serum cortisol may appear nonsuppressible by dexamethasone
      • Obesity and depression give false-positive results
      • Thiazolidinediones can give false-negative results
    • Addisons disease/ Adrenal insufficiency
      • Random cortisol level
      • Cosyntropin Stimulation test – 1hr and 24hr stimulation tests
      • Steroid replacement  HYDROCORTISOME 100 Q8hrs + Mineralocortcoid
    • Adrenal Incidentalomas
    • Work-up
      • In all Adrenal incidentalomas, R/o functioning adenomas first
          • Do Low dose dexamethasone test (1mg) and Plasma metanephrines in all patients
          • Do PAC/PRA only if HTN is present or if serum potassium is low.
      • If Functioning adenomas – Rx is usually surgery ( except in Conns Syndrome where medical Rx can be tried first)
    • Work-up
      • For non-functioning adenomas, further treatment depends on the size of adrenal mass.
        • < 4cm  low risk of cancer ( 2% risk) . Follow-up Ct scan at 6-12 months. If no change, no further follow up.
        • 4cm-6cm  6% risk of cancer  Adrenalectomy or a Follow-up CT Scan at 6months. If no growth, just follow clinically. ( no more imaging)
        • >6cm  high risk of malignancy (25% cases). Rx with adrenalectomy
      • After a fall while horseback riding, a 37-year-old woman is evaluated with an emergency CT scan of the abdomen. The CT scan shows no evidence of a ruptured spleen, but shows a 2.5-cm right adrenal mass. The patient’s medical history, including review of systems, is normal. Findings on physical examination, including blood pressure, are unremarkable. Plasma glucose level, serum electrolyte levels, and renal function are normal.
      • What is the most appropriate next step in the management of this patient?
      • ( A ) Surgical removal of the mass
      • ( B ) MRI of the adrenal glands
      • ( C ) Fine-needle aspiration biopsy of the mass under CT guidance
      • ( D ) Repeated CT scan in 3 to 6 months
      • ( E ) 24-Hour urinary catecholamines, metanephrine, and cortisol
      • 35-year-old man with a 10-year history of type 1 diabetes mellitus is evaluated because of recent onset of morning hyperglycemia. For the past 10 days, his morning blood glucose levels ranged from 220 to 300 mg/dL. He has also experienced nightmares recently.
      • Which of the following best explains this patient’s morning hyperglycemia?
      • ( A ) Diabetic nephropathy
      • ( B ) Undertreatment with insulin
      • ( C ) Overtreatment with insulin
      • ( D ) Diabetic neuropathy
    • KEY POINT SOMGYI EFFECT Nightmares are a clue and signifies a drop in blood glucose to low levels Next step  reduce the dose of pre-dinner insulin