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Thyroid Thyroid DisordersDisorders

ThyrotoxicosisThyrotoxicosisSubacute ThyroiditisSubacute Thyroiditis

Thyroid Function TestsThyroid Function TestsHashimatos ThyroiditisHashimatos Thyroiditis

HypothyroidismHypothyroidismThyrotoxic periodic paralysisThyrotoxic periodic paralysisThyroid Nodule and ApproachThyroid Nodule and Approach

Thyroid CancerThyroid Cancer

Thyroid Diagnostic Thyroid Diagnostic StudiesStudies

Thyroid Function Tests : TSH, Total T4, Thyroid Function Tests : TSH, Total T4, Free T4, T3 levels.Free T4, T3 levels.

Thyroid Binding GlobulinThyroid Binding Globulin Thyroid Uptake Scan – Radio active iodine Thyroid Uptake Scan – Radio active iodine

uptake scan ( RAIU scan)uptake scan ( RAIU scan) Antibodies : Thyroid stimulating Antibodies : Thyroid stimulating

immunoglobulins, Anti-microsomal immunoglobulins, Anti-microsomal antibodies, Anti-thyroid peroxidase antibodies, Anti-thyroid peroxidase antibodiesantibodies

Thyroid ultrasoundThyroid ultrasound Thyroid Biopsy, FNACThyroid Biopsy, FNAC

TSHTSH Preferred Screening test for suspected HYPO/HYPER ThyroidismPreferred Screening test for suspected HYPO/HYPER Thyroidism Preferred Follow-up test for patients receiving therapy for either Preferred Follow-up test for patients receiving therapy for either

hypo or hyperthyrodism or pts who had thyroid cancer therapyhypo or hyperthyrodism or pts who had thyroid cancer therapy If TSH High If TSH High possible Primary hypothyroidism or rarely, possible Primary hypothyroidism or rarely,

secondary hyperthyroidismsecondary hyperthyroidism If TSH low If TSH low possible Primary hyperthyroidism or rarely, possible Primary hyperthyroidism or rarely,

secondary hypothyroidismsecondary hypothyroidism If TSH low in pt on treatment for hypothyroidism If TSH low in pt on treatment for hypothyroidism reduce dose reduce dose

of levothyroxine. ( usually in increments of 25mcg each time)of levothyroxine. ( usually in increments of 25mcg each time) If TSH high in a pt on treatment for hypothyroidism If TSH high in a pt on treatment for hypothyroidism Increase Increase

dose of levothyroxine. ( usually in increments of 25mcg each dose of levothyroxine. ( usually in increments of 25mcg each time)time)

If TSH low in pt on treatment for hyperthyroidism If TSH low in pt on treatment for hyperthyroidism Increase Increase dose of Propylthiouracil/ Methimazole ( or may indicate dose of Propylthiouracil/ Methimazole ( or may indicate inadequate therapy)inadequate therapy)

If TSH high in a pt on treatment for hyperthyroidism If TSH high in a pt on treatment for hyperthyroidism Reduce Reduce dose of Propylthiouracil/ Methimazole ( Indicates excess dose of Propylthiouracil/ Methimazole ( Indicates excess antithyroid therapy. antithyroid therapy.

If Radioiodine therapy was chosen, then aim is to make the pt If Radioiodine therapy was chosen, then aim is to make the pt Hypothyroid in order to achieve good cure rates in Graves Hypothyroid in order to achieve good cure rates in Graves thyrotoxicosis thyrotoxicosis in that case, you need to start levothyroxine in that case, you need to start levothyroxine post radioiodine therapy or post surgically)post radioiodine therapy or post surgically)

TSHTSHObtain screening TSH in patients with Obtain screening TSH in patients with

conditions that may be explained by conditions that may be explained by or aggravated by hyperthyroidism : or aggravated by hyperthyroidism :

Unexplained weight loss Unexplained weight loss Anxiety or sleep disturbance Anxiety or sleep disturbance Tachycardia, including Tachycardia, including

supraventricular tachycardia and new supraventricular tachycardia and new onset atrial fibrillation onset atrial fibrillation

Osteoporosis Osteoporosis

TSHTSH

Obtain screening TSH in patients with Obtain screening TSH in patients with conditions that may be explained by or conditions that may be explained by or aggravated by hypothyroidism :aggravated by hypothyroidism :

History of thyroid diseaseHistory of thyroid disease Autoimmune disease (R/O co-existent Autoimmune disease (R/O co-existent

hashimatos)hashimatos) Unexplained depression Unexplained depression Cognitive dysfunction ( dementia, delirium)Cognitive dysfunction ( dementia, delirium) HypercholesterolemiaHypercholesterolemia Unexplained constipationUnexplained constipation

Screen in early pregnancyScreen in early pregnancy

Other TFTsOther TFTs Obtain Total and Free T4 levels, ONCE TSH comes Obtain Total and Free T4 levels, ONCE TSH comes

abnormalabnormal

If TSH high but Free T4 low If TSH high but Free T4 low primary hypothyroidism primary hypothyroidism Usually Hashimatos thyroiditis. Usually Hashimatos thyroiditis. In countries where Iodine deficiency is a problem, this could be In countries where Iodine deficiency is a problem, this could be

due to endemic goiter. (urine iodine low)due to endemic goiter. (urine iodine low) Iatrogenic Hypothyroidism due to Thyroidectomy or Radioiodine Iatrogenic Hypothyroidism due to Thyroidectomy or Radioiodine

therapy therapy Drug induced Drug induced Amiodarone, Lithium, Iodine {excess iodine Amiodarone, Lithium, Iodine {excess iodine

immediately inhibits both new hormone synthesis (by blocking immediately inhibits both new hormone synthesis (by blocking organification, known as the organification, known as the WolfWolf--ChaikoffChaikoff effecteffect) and the ) and the release of thyroid hormone. It also decreases gland size and release of thyroid hormone. It also decreases gland size and vascularity. This effect is transient, however, lasting vascularity. This effect is transient, however, lasting approximately 1-3 weeks}, Interferon, Thionamidesapproximately 1-3 weeks}, Interferon, Thionamides

Late phase of Post-partum thyroiditis, Subacute thyroiditis, silent Late phase of Post-partum thyroiditis, Subacute thyroiditis, silent thyroiditisthyroiditis

If TSH High but Free T4 also high If TSH High but Free T4 also high secondary secondary Hyperthyroidism ( pituitary adenomas) - rareHyperthyroidism ( pituitary adenomas) - rare

Other TFTsOther TFTs If TSH low but Free T4 high If TSH low but Free T4 high primary primary

hyperthyroidism hyperthyroidism Usually Graves Thyrotoxicosis ( Thyroid scan – Usually Graves Thyrotoxicosis ( Thyroid scan –

homogenous, diffuse uptake)homogenous, diffuse uptake) Toxic Multinodular Goiter ( Thyroid scan – Toxic Multinodular Goiter ( Thyroid scan –

Heterogenous)Heterogenous) Toxic Solitary Adenoma Toxic Solitary Adenoma Early phase of Subacute Thyroiditis/ Silent Thyroiditis Early phase of Subacute Thyroiditis/ Silent Thyroiditis

( No Uptake on Thyroid scan)( No Uptake on Thyroid scan) Post-partum Thyroiditis ( painless, may be followed by Post-partum Thyroiditis ( painless, may be followed by

hypothyroid phase)hypothyroid phase) Iatrogenic Hyperthyroidism due to excess Iatrogenic Hyperthyroidism due to excess

levothyroxine therapy in a hypothyroid patientlevothyroxine therapy in a hypothyroid patient Surreptious intake of Thyroid hormonesSurreptious intake of Thyroid hormones Struma OvariiStruma Ovarii ( Increased pelvic uptake on whole body ( Increased pelvic uptake on whole body

iodine scan)iodine scan) Gestational Thyrotoxicosis ( Increased HCG is Gestational Thyrotoxicosis ( Increased HCG is

responsible, Nuclear imaging contraindicated here)responsible, Nuclear imaging contraindicated here) Amiodarone induced ( two types of thyrotoxicosis)Amiodarone induced ( two types of thyrotoxicosis)

Other TFTsOther TFTs

If TSH low but Free T4 also low If TSH low but Free T4 also low secondary Hypothyroidism secondary Hypothyroidism ( pituitary adenomas causing ( pituitary adenomas causing compression, craniopharyngioma compression, craniopharyngioma clues are headaches, visual field clues are headaches, visual field deficits, ophthalmoplegia), pituitary/ deficits, ophthalmoplegia), pituitary/ hypothalamic surgery, pituitary/ hypothalamic surgery, pituitary/ hypothalamic infection/ infarctionhypothalamic infection/ infarction

Other TFTsOther TFTs If TSH low but Free T4 normal If TSH low but Free T4 normal get T3 get T3

level. If T3 high level. If T3 high T3 toxicosis. If T3 normal T3 toxicosis. If T3 normal subclinical Hyperthyroidism. subclinical Hyperthyroidism.

If TSH high but Free T4 normal If TSH high but Free T4 normal Sublinical Sublinical Hypothyroidism ( Treat only if symptoms are Hypothyroidism ( Treat only if symptoms are present or TSH > 10mU/l , For TSH between present or TSH > 10mU/l , For TSH between 5 to 10 5 to 10 consider Rx if TPO antibodies consider Rx if TPO antibodies high/ pt has goiter or high serum LDL) high/ pt has goiter or high serum LDL)

In cases of subclinical In cases of subclinical hypothyroidism, presence of anti-TPO hypothyroidism, presence of anti-TPO antibodies predicts progression to overt antibodies predicts progression to overt Hypothyroidism ( Hashimatos)Hypothyroidism ( Hashimatos)

Other TFTsOther TFTs

Remember any combinations of Remember any combinations of TSH/Free T4 can occur in severe TSH/Free T4 can occur in severe nonthyroidal illness depending on nonthyroidal illness depending on the phase of the illness ( critical the phase of the illness ( critical phase, recovery phase) phase, recovery phase) Euthyroid Euthyroid sick syndrome . Some combinations sick syndrome . Some combinations

low TSH, Normal free T4low TSH, Normal free T4

High TSH, Normal free T4High TSH, Normal free T4

ThyrotoxicosisThyrotoxicosis

Important topics: Important topics: Graves diseaseGraves disease

Subacute thyroiditisSubacute thyroiditisPost partum thyroiditisPost partum thyroiditisAmiodarone inducedAmiodarone 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 DiseaseGrave’s Disease Features : Diffuse Goiter, Ophthalmopathy ( proptosis, extraocular muscle Features : Diffuse Goiter, Ophthalmopathy ( proptosis, extraocular muscle

paralysis, peri-orbital edema are specific. Lid-lag and stare can occur with any paralysis, peri-orbital edema are specific. Lid-lag and stare can occur with any hyperthyroidism ) and Dermopathy (pre-tibial myxedema) .hyperthyroidism ) and Dermopathy (pre-tibial myxedema) .

Diagnosis : clinical features of hyperthyroidism ( palpitations, sweating, Diagnosis : clinical features of hyperthyroidism ( palpitations, sweating, diarrhea, anxiety, tremor, hairloss, weightloss, menorrhagia) + diffuse goiter, diarrhea, anxiety, tremor, hairloss, weightloss, menorrhagia) + diffuse goiter, thyroid bruit/thrill can be heard due to hyperdynamic circulation and thyroid bruit/thrill can be heard due to hyperdynamic circulation and increased thyroid vascularity.increased thyroid vascularity.

Pain usually absent in thyroid ( PAIN may be present in subacute Pain usually absent in thyroid ( PAIN may be present in subacute thyroiditis)thyroiditis)

Always r/o subacute thyroiditis in differentialAlways r/o subacute thyroiditis in differential

Obtain RAIU scan Obtain RAIU scan Graves shows homogeneous uptake where Graves shows homogeneous uptake where as no uptake in subacute thyroiditis/ Surreptious intake of LT4. as no uptake in subacute thyroiditis/ Surreptious intake of LT4. { Measure serum thyroglobulin and ESR to distinguish subacute { Measure serum thyroglobulin and ESR to distinguish subacute thyroiditis (elevated thyroglobulin and ESR) from surreptitious thyroiditis (elevated thyroglobulin and ESR) from surreptitious thyroid hormone ingestion (suppressed thyroglobulin, normal ESR)}. thyroid hormone ingestion (suppressed thyroglobulin, normal ESR)}. Painless thyroiditis has elevated thyroglobulin but normal ESR. Painless thyroiditis has elevated thyroglobulin but normal ESR.

TSH low, Free T4 high. TSH low, Free T4 high.

Antibodies present Antibodies present Thyroid stimulating antibodies ( TSIgs) are Thyroid stimulating antibodies ( TSIgs) are high and are responsible for goiter and hyperthyroidism. Anti-TSH high and are responsible for goiter and hyperthyroidism. Anti-TSH antibodies, Anti-TPO antibodies. antibodies, Anti-TPO antibodies.

Can be associated with other autoimmune diseases Can be associated with other autoimmune diseases Vitilgo, Vitilgo, pernicious anemiapernicious anemia

Treatment OptionsTreatment Options Treatment options in Hyperthyroidism :Treatment options in Hyperthyroidism : Medications ( Antithyroid drugs - PTU, Medications ( Antithyroid drugs - PTU,

Thionamides i.e; methimizole ) , B-Blockers Thionamides i.e; methimizole ) , B-Blockers ( propranolol, atenolol) for symptoms. ( propranolol, atenolol) for symptoms. ( propranolol preferred because it can block T4 ( propranolol preferred because it can block T4 to T3 conversion in high doses)to T3 conversion in high doses)

Raioactive iodine therapy (131 I) Raioactive iodine therapy (131 I) Surgery ( Thyroidectomy) Surgery ( Thyroidectomy) Consider the following when selecting treatment Consider the following when selecting treatment

for thyrotoxicosis: for thyrotoxicosis: Patient preference Patient preference Patient's age and comorbidities Patient's age and comorbidities Severity of thyrotoxicosis Severity of thyrotoxicosis Goiter size Goiter size Presence of ophthalmopathy (in Graves' disease patients) Presence of ophthalmopathy (in Graves' disease patients)

Treatment for Thyrotoxicosis Due to Overproduction of Thyroid Hormone

Modality Advantages Disadvantages

Antithyroid drug therapy

Least invasiveLeast costlyLower risk of permanent hypothyroidismPotential beneficial immunomodulatory effects

Adverse drug effectsLow permanent remission rate (approximately 33%-50%)

Radioiodine Moderately fast reduction in thyroid hormone levelsLess invasive than surgery

Permanent hypothyroidism likelyRequires delay in pregnancy (6-12 months) and breastfeedingMay precipitate new or worsened ophthalmopathySlight risk of thyroid storm after treatment ( in severe Hyperthyroidism, use pre-treatment)

Thyroidectomy

Rapid reduction in thyroid hormone levelsAllows concurrent removal of suspicious nodules (if present) Allows reduction in size of large goiters

Most invasiveMost costlyPermanent scarPermanent hypothyroidism likelyPotential injury to parathyroids and recurrent laryngeal nerve

Anti-thyroid drug therapyAnti-thyroid drug therapy Propyl thiouracil : Propyl thiouracil :

Typical starting dose 100mg tidTypical starting dose 100mg tid Will need to discontinue 2 weeks prior to Radioiodine therapy Will need to discontinue 2 weeks prior to Radioiodine therapy

because it can lead to failure of the therapy as it inhibits because it can lead to failure of the therapy as it inhibits roadioiodine uptake by thyroid. ( REMEMBER roadioiodine uptake by thyroid. ( REMEMBER METHIMIZOLE WILL NOT AFFECT RADIOIODINE THERAPY METHIMIZOLE WILL NOT AFFECT RADIOIODINE THERAPY – So, it is the preferred therapy to start if I131 therapy is – So, it is the preferred therapy to start if I131 therapy is planned)planned)

LESS POTENT than Methimizole.LESS POTENT than Methimizole. Preferred drug in severe Hyperthyroidism because it can Preferred drug in severe Hyperthyroidism because it can

block T4 to T3 Conversionblock T4 to T3 Conversion ( this effect not seen with ( this effect not seen with methimazole)methimazole)

Side effects : Rash, Agranulocytosis, Hepatocellular necrosisSide effects : Rash, Agranulocytosis, Hepatocellular necrosis Safe in pregnancy ( as it highly binds to plasma protein and Safe in pregnancy ( as it highly binds to plasma protein and

very little crosses placenta. There is NO risk of Aplasia Cutis). very little crosses placenta. There is NO risk of Aplasia Cutis). However, Fetal hypothyroidism can occur in high doses due to However, Fetal hypothyroidism can occur in high doses due to transplacetal passage.transplacetal passage.

MONITOR LFTS AND CBC MONITOR LFTS AND CBC If pts have sorethroat/ infection If pts have sorethroat/ infection etc suggesting possibility of agaranulocytosis d/c PTU and get etc suggesting possibility of agaranulocytosis d/c PTU and get a blood counta blood count

Anti-thyroid drug therapyAnti-thyroid drug therapy Methimizole : Methimizole :

More potent than PTUMore potent than PTU Typical starting dose is 30mg/d – preferred drug for Typical starting dose is 30mg/d – preferred drug for

most patients because single daily dose (except for most patients because single daily dose (except for patients with allergy to methimazole, who are pregnant, patients with allergy to methimazole, who are pregnant, or have severe thyrotoxicosis or thyroid storm) or have severe thyrotoxicosis or thyroid storm)

Contraindicated in pregnancy due to risk of Contraindicated in pregnancy due to risk of Aplasia Aplasia cutiscutis and higher transplacental spread than PTU. and higher transplacental spread than PTU.

Not preferred in breast feeding ( PTU is preferred in Not preferred in breast feeding ( PTU is preferred in breast feeding)breast feeding)

Side effects : Rash, Agranulocytosis, cholestatic jaundiceSide effects : Rash, Agranulocytosis, cholestatic jaundice Good for pre-treatment prior to I-131 therapy. ( pre-Good for pre-treatment prior to I-131 therapy. ( pre-

treatment is used to normalize thyroid function before treatment is used to normalize thyroid function before the administration of radioiodine and to attenuate the administration of radioiodine and to attenuate potential exacerbations following ablative radioiodine potential exacerbations following ablative radioiodine therapy. therapy. recommended for the elderly and those with recommended for the elderly and those with underlying cardiac disease, who may be more vulnerable underlying cardiac disease, who may be more vulnerable to worsening thyrotoxicosis during I 131 therapy.to worsening thyrotoxicosis during I 131 therapy.

PTU is preferred over methimizole in severe PTU is preferred over methimizole in severe hyperthyroidism.hyperthyroidism.

IF USING ANTITHYROID THERAPY as sole IF USING ANTITHYROID THERAPY as sole primary therapy use for at least 12-18 primary therapy use for at least 12-18 months before tapering. months before tapering.

Antithyroid drug therapyAntithyroid drug therapy For Grave’s disease patient getting For Grave’s disease patient getting

only anti thyroid drug therapy, only anti thyroid drug therapy, factors favoring remission are : factors favoring remission are :

- - Small goiterSmall goiter- Low T3/T4 ratio- Low T3/T4 ratio- Mild thyrotoxicosis- Mild thyrotoxicosis- Negative TSH-receptor antibody titers - Negative TSH-receptor antibody titers after treatmentafter treatment- No prior relapse - No prior relapse

So, antithyroid drug therapy can So, antithyroid drug therapy can be a preferred modaility in these be a preferred modaility in these scenarios.scenarios.

Aplasia CutisAplasia Cutis Absence of skin in the newbornAbsence of skin in the newborn Can occur with Methimizole use Can occur with Methimizole use

during pregnancy.during pregnancy. PIC : Aplasia Cutis of scalpPIC : Aplasia Cutis of scalp

Radioiodine therapyRadioiodine therapy Select a dose of radioiodine based on the size Select a dose of radioiodine based on the size

of the patient's goiter and the result of the of the patient's goiter and the result of the RAIU test. RAIU test.

Do not use radioactive iodine in patients who Do not use radioactive iodine in patients who are pregnant or breastfeeding. are pregnant or breastfeeding.

Consider the use of concurrent corticosteroid Consider the use of concurrent corticosteroid therapy with radioiodine or avoidance of therapy with radioiodine or avoidance of radioiodine in patients with Graves' radioiodine in patients with Graves' ophthalmopathy. ( may cause worsening of ophthalmopathy. ( may cause worsening of ophthalmopathy)ophthalmopathy)

After Radioiodine therapy – mother should stay After Radioiodine therapy – mother should stay away from kids at least for 5 days ( Mother away from kids at least for 5 days ( Mother need to Arrange for a care taker for baby) need to Arrange for a care taker for baby)

Hypothyroidism is inevitable – start Synthroid Hypothyroidism is inevitable – start Synthroid after getting TSH level.after getting TSH level.

SurgerySurgery Especially preferred in : Especially preferred in :

Goiter causing obstructive symptoms Goiter causing obstructive symptoms Intolerance to thionamides; refusal to take antithyroid drugs or Intolerance to thionamides; refusal to take antithyroid drugs or

radioactive iodineradioactive iodine Recurrence after a trial of thionamide therapy for Graves’ diseaseRecurrence after a trial of thionamide therapy for Graves’ disease MULTI-NODULAR goiterMULTI-NODULAR goiter Suspicion of malignancy. Suspicion of malignancy.

Patients should be made euthyroid with thionamide Patients should be made euthyroid with thionamide therapy prior to elective surgery. Once a euthyroid therapy prior to elective surgery. Once a euthyroid state is achieved, oral iodine is given 7 to 10 days state is achieved, oral iodine is given 7 to 10 days preoperatively to reduce the vascularity of the gland preoperatively to reduce the vascularity of the gland then total/ subtotal thyroidectomy. then total/ subtotal thyroidectomy.

Complications : Hypothyroidism inevitable, Complications : Hypothyroidism inevitable, Recurrent laryngeal nerve palsy (1%) , Permanent Recurrent laryngeal nerve palsy (1%) , Permanent hypoparathyroidism ( 1% risk) and 1% risk of hypoparathyroidism ( 1% risk) and 1% risk of recurrent hyperthyroidismrecurrent hyperthyroidism

Admit pts to ICU for 24 hrs s/p surgery Admit pts to ICU for 24 hrs s/p surgery Monitor Monitor calcium level q6hrs in patents s/p thyroid surgery calcium level q6hrs in patents s/p thyroid surgery and replete calcium aggressively if <7mg%and replete calcium aggressively if <7mg%

Follow-upFollow-up

In pts on long term antithyroid drug therapy In pts on long term antithyroid drug therapy Monitor for adverse effects of antithyroid drugs Monitor for adverse effects of antithyroid drugs

such as rash, hepatic dysfunction, and such as rash, hepatic dysfunction, and agranulocytosis. agranulocytosis.

Repeat thyroid function tests every 3 to 6 months Repeat thyroid function tests every 3 to 6 months for the first year and then every 6 to 12 months for the first year and then every 6 to 12 months after attaining normal FT4 and TSH levels. after attaining normal FT4 and TSH levels.

Follow serum FT4 and TSH levels at 4-week Follow serum FT4 and TSH levels at 4-week intervals to ensure intervals to ensure adequate replacement adequate replacement therapytherapy ( for hypothyroidism) immediately ( for hypothyroidism) immediately after radioiodine therapy. after radioiodine therapy.

Q1Q1 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

Q2Q2 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.AANS.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.

Q3Q3

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 SyndromeEuthyroid Sick Syndrome

Euthyroid Sick SyndromeEuthyroid 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

Q4Q4 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 PointKey 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 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).

HypothyroidismHypothyroidism

Important concepts: Important concepts: Hashimato’sHashimato’s

Lithium inducedLithium inducedMyxedema comaMyxedema coma

Hashimato’S ThyroiditisHashimato’S Thyroiditis Autoimmune thyroiditis associated with Autoimmune thyroiditis associated with

lymphocytic infiltration of thyroid gland. lymphocytic infiltration of thyroid gland. causes gland disruption, initially may lead to causes gland disruption, initially may lead to hashitoxicosis and then hypothyroidismhashitoxicosis and then hypothyroidism

Diagnosis : HIGH TSH, LOW FREE T4 and Diagnosis : HIGH TSH, LOW FREE T4 and Elevated TPO antibodies/ anti microsomal Elevated TPO antibodies/ anti microsomal antibodies.antibodies.

TSIgs may be present tooTSIgs may be present too Diffuse Goiter on physical exam. Diffuse Goiter on physical exam. Association with other autoimmune diseases Association with other autoimmune diseases

must be kept in mind must be kept in mind pernicious anemia, pernicious anemia, addisons diseaseaddisons disease

Can be associated with B cell lymphomasCan be associated with B cell lymphomas

Treating HypothyroidismTreating Hypothyroidism Levothyroxine (LT4) drug of choice.Levothyroxine (LT4) drug of choice. In young patients In young patients start initial full replacement start initial full replacement

dose calculated as 1.6 µg/kg/d. ( 70kg man – dose calculated as 1.6 µg/kg/d. ( 70kg man – 112mcg/d)112mcg/d)

In obese patients In obese patients calculate the initial dose calculate the initial dose using ideal body weight using ideal body weight of course , you can of course , you can follow-up serum TSH 6-8 weeks later and titrate follow-up serum TSH 6-8 weeks later and titrate the dose. the dose.

In elderly patients > 60 yrs of age In elderly patients > 60 yrs of age start at start at dose 25 to 50 mcg and titrate every 6-8 wks dose 25 to 50 mcg and titrate every 6-8 wks untill TSH comes to desired range.untill TSH comes to desired range.

In those with In those with KNOWN CAD/ hx of CHFKNOWN CAD/ hx of CHF and and arrhythmias arrhythmias Start at 12.5 mcg to 25 mcg dose Start at 12.5 mcg to 25 mcg dose and then titrate every 6-8 wks untill TSH comes and then titrate every 6-8 wks untill TSH comes to desired range.to desired range.

IdealIdeal BodyBody WeightWeight (men) = 50 + (men) = 50 + 2.3 ( Height(in) - 60 )2.3 ( Height(in) - 60 )

IdealIdeal BodyBody WeightWeight (women) = 45.5 (women) = 45.5 + 2.3 ( Height(in) - 60 ) + 2.3 ( Height(in) - 60 )

Follow up – Treatment Follow up – Treatment adequacyadequacy

TSH is used to follow up treatment TSH is used to follow up treatment adequacyadequacy

Levothyroxine has a t 1/2 of 7days. It takes Levothyroxine has a t 1/2 of 7days. It takes a drug four to five t1/2s to reach steady a drug four to five t1/2s to reach steady state state which means DO NOT INCREASE which means DO NOT INCREASE LT4 dose prior to 4 to 6 weeks if pt is not LT4 dose prior to 4 to 6 weeks if pt is not symptomatic.symptomatic.

TSH level should be obtained at 6 – 8 TSH level should be obtained at 6 – 8 weeks after starting therapy weeks after starting therapy because it because it takes this time for raised to TSH to takes this time for raised to TSH to normalize and also this is the time at which normalize and also this is the time at which you can properly assess adequacy of LT4 you can properly assess adequacy of LT4 therapy because LT4 reaches steady state therapy because LT4 reaches steady state around this time.around this time.

Follow up – Treatment Follow up – Treatment adequacyadequacy

Use TSH levels as the guide to thyroid Use TSH levels as the guide to thyroid hormone dosage requirements. hormone dosage requirements.

Once treatment is started, monitor serum Once treatment is started, monitor serum TSH levels every 6 to 8 weeks and adjust the TSH levels every 6 to 8 weeks and adjust the LT4 dose until the TSH value is in the LT4 dose until the TSH value is in the desired range.desired range.

Once TSH reaches desired range, Once TSH reaches desired range, recheck the TSH level 3 to 6 months recheck the TSH level 3 to 6 months later, and then if normal recheck later, and then if normal recheck annually. annually.

If the TSH value is above the normal range, If the TSH value is above the normal range, increase the LT4 dose by 12.5 to 25 µg/d and increase the LT4 dose by 12.5 to 25 µg/d and recheck in 6 to 8 weeks. recheck in 6 to 8 weeks.

If the TSH value is low, If the TSH value is low, decrease the LT4 decrease the LT4 dose by 12.5 to 25 µg/d and recheck in 6 dose by 12.5 to 25 µg/d and recheck in 6 to 8 weeksto 8 weeks

Advise patients to take levothyroxine Advise patients to take levothyroxine at the same time each day and at the same time each day and to to avoid taking it within 4 hours of iron avoid taking it within 4 hours of iron tablets, calcium supplements, tablets, calcium supplements, antacids, and fiber supplements antacids, and fiber supplements ( can reduce LT4 absorption)( can reduce LT4 absorption)

Lithium InducedLithium Induced

Li Can cause hypothroidismLi Can cause hypothroidism

Rx Rx do not discontinue lithium, do not discontinue lithium, Start levothyroxine and continue Start levothyroxine and continue lithium therapy.lithium therapy.

Myxedema ComaMyxedema Coma Severe hypothyroidism associated with Severe hypothyroidism associated with

altered mental status/ delirium/ coma.altered mental status/ delirium/ coma. Myxedema coma Myxedema coma usually found in usually found in elderlyelderly

patients who have untreated or inadequately patients who have untreated or inadequately treated hypothyroidism and then develop a treated hypothyroidism and then develop a precipitating event. ( precipitating event for precipitating event. ( precipitating event for myxedema coma in a pt with myxedema coma in a pt with untreated/inadequately treated untreated/inadequately treated hypothyroidism can be SEPSIS, Surgery, hypothyroidism can be SEPSIS, Surgery, Trauma, GI bleeding, Trauma, GI bleeding, StrokeStroke, MI, CHF, , MI, CHF, Sedative use)Sedative use)

So, always evaluate the pt for precipitating So, always evaluate the pt for precipitating factor also factor also treat both myxedema coma as treat both myxedema coma as well as precipitant. well as precipitant.

Myxedema comaMyxedema coma Admit to ICU for careful monitoring and Admit to ICU for careful monitoring and

appropriate treatment. appropriate treatment. Get Endocrine consult always.Get Endocrine consult always. Obtain blood cultures, CT head, cardiac Obtain blood cultures, CT head, cardiac

enzymes, EKG, CHEM 18, CBC R/o enzymes, EKG, CHEM 18, CBC R/o preciptating factorspreciptating factors

TSH, FREE T4 TSH, FREE T4 RX : RX :

Vital support : intubation if prolonged coma for airway Vital support : intubation if prolonged coma for airway protection, IV fluids, hypothermia blanket.protection, IV fluids, hypothermia blanket.

Levothyroxine intravenosly (500 µg, then 50-100 µg/d for Levothyroxine intravenosly (500 µg, then 50-100 µg/d for myxedema coma, for npo pts 80% of oral dose ) + myxedema coma, for npo pts 80% of oral dose ) + hydrocortosine 100 q8hrs x 2days to address possible hydrocortosine 100 q8hrs x 2days to address possible decreased adrenal reserve in myxedemadecreased adrenal reserve in myxedema. .

Also can use combination of LT4+LT3 for rapid T4 and T3 Also can use combination of LT4+LT3 for rapid T4 and T3 repletion in myxedema comarepletion in myxedema coma

Look for and treat any precipitating factorLook for and treat any precipitating factor

Thyroid NoduleThyroid Nodule

ApproachApproach

ApproachApproach If thyroid nodule palpable If thyroid nodule palpable

GET TSH First.GET TSH First. If High TSH – suggests cold nodule. Get Thyroid Ultrasound to look for If High TSH – suggests cold nodule. Get Thyroid Ultrasound to look for

suspicious features. If no suspicious features, get free T4, TPO suspicious features. If no suspicious features, get free T4, TPO Antibodies and Rx as Hashimatos. If Suspicious features on ultrasound, Antibodies and Rx as Hashimatos. If Suspicious features on ultrasound, get FNACget FNAC

If TSH low – suggests Hot nodule ( toxic adenoma) but not confirmative If TSH low – suggests Hot nodule ( toxic adenoma) but not confirmative ( What if theres GRAVES and this is a cold nodule?) ( What if theres GRAVES and this is a cold nodule?) so, get RAIU so, get RAIU scan next scan next if COLD nodule get FNAC. If RAIU scan shows Hot nodule if COLD nodule get FNAC. If RAIU scan shows Hot nodule treat with I131 or follow up. treat with I131 or follow up.

If TSH normal – get Ultrasound next. Do FNAC where indicated ( see If TSH normal – get Ultrasound next. Do FNAC where indicated ( see below)below)

FNAC indicated if FNAC indicated if Nodule > 10 mm in diameterNodule > 10 mm in diameter On ultrasound if nodule has suspicious features On ultrasound if nodule has suspicious features hypoechoic, hypoechoic,

microcalcifications, irregular shape, blurred margin or increased microcalcifications, irregular shape, blurred margin or increased vascularity vascularity

Cold nodules are more likely to be malignant when Cold nodules are more likely to be malignant when compared to hot nodules ( hot/ functioning nodule compared to hot nodules ( hot/ functioning nodule virtually rules out malignancy)virtually rules out malignancy)

A negative FNAC does not rule out cancer completely. A negative FNAC does not rule out cancer completely. So, if clinical suspicion for cancer is high So, if clinical suspicion for cancer is high consider consider surgical excision of the nodule. ( esply follicular surgical excision of the nodule. ( esply follicular adenoma)adenoma)

Further ApproachFurther Approach If FNAC is benign If FNAC is benign

Cystic nodule – use percutaneous Ethanol injection to get rid Cystic nodule – use percutaneous Ethanol injection to get rid of noduleof nodule

Solid Nodule – use suppressive therapy with levothyroxine if Solid Nodule – use suppressive therapy with levothyroxine if there are no contraindications ( Heart disease, old age). there are no contraindications ( Heart disease, old age). Suppressive therapy with LT4 aims to reduce TSH and there Suppressive therapy with LT4 aims to reduce TSH and there by, regress the noduleby, regress the nodule

If FNAC is malignant If FNAC is malignant SURGERY SURGERY If FNAC is follicular adenoma (benign) If FNAC is follicular adenoma (benign) get a get a

thyroid scan if not already done thyroid scan if not already done If this is If this is hot/functioning nodule, it rules out malignancy hot/functioning nodule, it rules out malignancy – so, follow-up. If this is a cold nodule, a – so, follow-up. If this is a cold nodule, a negative FNAC from one area may not rule out negative FNAC from one area may not rule out possibility of follicular carcinoma in follicular possibility of follicular carcinoma in follicular adenoma – so, do Surgery in those cases. adenoma – so, do Surgery in those cases.

If FNAC is non-diagnostic If FNAC is non-diagnostic repeat FNAC repeat FNAC

NEJM guidelinesNEJM guidelines

PheochromocytoPheochromocytomama

Pheochromocytoma Pheochromocytoma

Consider evaluating for Pheochromocytoma in patients with: Consider evaluating for Pheochromocytoma in patients with: Refractory hypertension Refractory hypertension Hypertension, accompanied by hyperadrenergic spells with: Hypertension, accompanied by hyperadrenergic spells with:

Nonexertional palpitations Nonexertional palpitations Diaphoresis Diaphoresis Headache Headache Tremor Tremor Pallor Pallor

Family history of familial pheochromocytoma Family history of familial pheochromocytoma A genetic syndrome that increases the risk of A genetic syndrome that increases the risk of

pheochromocytoma, such as: pheochromocytoma, such as: Multiple endocrine neoplasia type 2 Multiple endocrine neoplasia type 2 von Hippel-Lindau disease - RCCvon Hippel-Lindau disease - RCC Neurofibromatosis type 1 Neurofibromatosis type 1

History of gastric stromal tumor or pulmonary chondromas History of gastric stromal tumor or pulmonary chondromas (Carney triad) (Carney triad)

An incidentally discovered adrenal mass ( Adrenal An incidentally discovered adrenal mass ( Adrenal Incidentalomas)Incidentalomas)

PheochromocytomaPheochromocytoma

Episodic Hypertension is Episodic Hypertension is charecterestic but ORTHOSTATIC charecterestic but ORTHOSTATIC HYPOTENSION can be seen. HYPOTENSION can be seen.

Pheochromocytomas are 10% Pheochromocytomas are 10% tumors tumors 10% malignant, 10% 10% malignant, 10% bilateral and 10% familial.bilateral and 10% familial.

Pheochromocytoma - Pheochromocytoma - DiagnosisDiagnosis Best diagnostic test and high specificity (99%) Best diagnostic test and high specificity (99%) 24 hr 24 hr

Urinary Metanephrines ( metanephrines or Urinary Metanephrines ( metanephrines or normetanephrines above the upper limit of normal in a normetanephrines above the upper limit of normal in a patient not taking an interfering medication and not patient not taking an interfering medication and not physically stressed is consistent with physically stressed is consistent with pheochromocytoma )pheochromocytoma )

Plasma Metanephrines can be used if 24 hr unrine Plasma Metanephrines can be used if 24 hr unrine collection is not possible –specificity (88%) lower than collection is not possible –specificity (88%) lower than 24 hr urine metanephrines24 hr urine metanephrines

Obtain CT Abdomen to r/o Adrenal mass only if Obtain CT Abdomen to r/o Adrenal mass only if biochemical tests are positive. Very sensitive (96%) for biochemical tests are positive. Very sensitive (96%) for pheochromocytoma ( adrenal mass) but low specificity pheochromocytoma ( adrenal mass) but low specificity due to high prevalence of adrenal incidentalomas.due to high prevalence of adrenal incidentalomas.

MIBG scanMIBG scan Very specific for pheochromocytomaVery specific for pheochromocytoma. . Sensitivity lower than CT scan. (Sensitivity only 80% Sensitivity lower than CT scan. (Sensitivity only 80% and specificity 100%) MIBG (Metaiodobenzylguanidine) and specificity 100%) MIBG (Metaiodobenzylguanidine) scan is the best test if looking for extra adrenal scan is the best test if looking for extra adrenal pheochromocytomaspheochromocytomas

Other tests – Plasma catecholamines, Urine VMAOther tests – Plasma catecholamines, Urine VMA

False + ves False + ves Medications and activities that may increase Medications and activities that may increase

measured levels of catecholamines and metabolites measured levels of catecholamines and metabolites ( False +ves for Metanephrines/ VMA)( False +ves for Metanephrines/ VMA)

Tricyclic antidepressants Tricyclic antidepressants Labetalol Labetalol Levodopa Levodopa Drugs containing catecholamines (e.g., Drugs containing catecholamines (e.g.,

decongestants) decongestants) Amphetamines Amphetamines Buspirone (and most psychoactive agents) Buspirone (and most psychoactive agents) Sotalol Sotalol Withdrawal from clonidine hydrochloride and other Withdrawal from clonidine hydrochloride and other

drugs drugs Ethanol Ethanol Acetaminophen and phenoxybenzamine Acetaminophen and phenoxybenzamine

(fractionated plasma metanephrines) (fractionated plasma metanephrines) Physical stress (e.g., stroke, obstructive sleep Physical stress (e.g., stroke, obstructive sleep

apnea) apnea)

TreatmentTreatment Acute Hypertensive crises Acute Hypertensive crises use IV use IV

Phentolamine, Sodium nitroprusside or Phentolamine, Sodium nitroprusside or NicardipineNicardipine. .

Definitive treatment is SURGERY. Send for Definitive treatment is SURGERY. Send for histopath to r/o malignancy. histopath to r/o malignancy.

REMEMBER TO USE BOTH ALPHA AND BETA REMEMBER TO USE BOTH ALPHA AND BETA ADRENERGIC BLOCKING AGENTS PRIOR TO ADRENERGIC BLOCKING AGENTS PRIOR TO SURGERY – to prevent hypertensive crises SURGERY – to prevent hypertensive crises during surgery. ( use phenoxybenzamine + during surgery. ( use phenoxybenzamine + atenolol)atenolol)

Do not use non selective beta blocker without Do not use non selective beta blocker without alpha blocker ( eg: propranolol alone)alpha blocker ( eg: propranolol alone)

Understand that relatively short-acting, Understand that relatively short-acting, selective α1-adrenergic receptor blockers (e.g., selective α1-adrenergic receptor blockers (e.g., prazosin, terazosin, doxazosin) may be prazosin, terazosin, doxazosin) may be inadequate for preoperative drug preparation inadequate for preoperative drug preparation so phenoxybenzamine preferred for pre-op so phenoxybenzamine preferred for pre-op therapy as it is therapy as it is long acting.long acting.

Primary Primary HyperparathyroidHyperparathyroid

ismism-Parathyroid AdenomasParathyroid Adenomas

-Parathyroid hyperplasiaParathyroid hyperplasia

HypercalcemiaHypercalcemia EtiologyEtiology Clinical features : bones, moans, stones, groansClinical features : bones, moans, stones, groans Investigations: Ca, Phos, EKG, PTH, 24 hr Urinary calcium Investigations: Ca, Phos, EKG, PTH, 24 hr Urinary calcium

excretion or spot urine calcium/creatinine ratio ( R/o familial excretion or spot urine calcium/creatinine ratio ( R/o familial hypocalciuric hypercalcemia)hypocalciuric hypercalcemia)

Management:Management: Criteria for surgery in primary hyperparathyroidismCriteria for surgery in primary hyperparathyroidism Sestamibi scan only if surgery is planned/indicatedSestamibi scan only if surgery is planned/indicated Hypercalcemic crisis management – ivf + lasix after volume Hypercalcemic crisis management – ivf + lasix after volume

repletion onlyrepletion only Indications for corticosteroids : are useful for treating Indications for corticosteroids : are useful for treating

hypercalcemiahypercalcemia caused by vitamin D toxicity, certain caused by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, and other granulomatous diseases and other granulomatous diseases

Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium sensing (PTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease calcium. Also results in concomitant serum calcium decrease Indicated for Indicated for hypercalcemiahypercalcemia with parathyroid carcinoma. with parathyroid carcinoma.

Do not lower Calcium too much Do not lower Calcium too much Serum calcium reduction may Serum calcium reduction may cause lowered cause lowered seizure thresholdseizure threshold, paresthesia, myalgia, , paresthesia, myalgia, cramping, and tetany; cramping, and tetany;

Criteria for Surgery – Criteria for Surgery – Primary Primary

hyperparathyroidismhyperparathyroidism Serum total calcium level >12 mg per dL (3 mmol per Serum total calcium level >12 mg per dL (3 mmol per L) at any time L) at any time

Hyperparathyroid crisis (discrete episode of life-Hyperparathyroid crisis (discrete episode of life-threatening threatening hypercalcemiahypercalcemia) )

Marked hypercalciuria (urinary calcium excretion Marked hypercalciuria (urinary calcium excretion more than 400 mg per day) more than 400 mg per day)

Nephrolithiasis Nephrolithiasis Impaired renal function Impaired renal function Osteitis fibrosa cystica Osteitis fibrosa cystica Reduced cortical bone density (measure with dual x-Reduced cortical bone density (measure with dual x-

ray absorptiometry or similar technique) ray absorptiometry or similar technique) Bone mass more than two standard deviations below age-Bone mass more than two standard deviations below age-

matched controls (Z score less than 2) matched controls (Z score less than 2) Classic neuromuscular symptoms Classic neuromuscular symptoms Proximal muscle weakness and atrophy, Proximal muscle weakness and atrophy,

hyperreflexiahyperreflexia, and gait disturbance , and gait disturbance Age younger than 50Age 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

HyperprolactineHyperprolactinemiamia

-StressStress-Drugs (<100)Drugs (<100)

-Pituitary TumorsPituitary Tumors-Stalk effect Stalk effect

-HypothyroidismHypothyroidism

Remember!Remember!

““If suspecting Prolactin secreting If suspecting Prolactin secreting adenomas or while working up the adenomas or while working up the cause of hyperprolactinemia, the cause of hyperprolactinemia, the LEVEL OF PROLACTIN is the best LEVEL OF PROLACTIN is the best clue to the possible etiology of clue to the possible etiology of hyperprolatinemia” hyperprolatinemia”

Prolactin level usually less than 100 Prolactin level usually less than 100 with drugs or stress!with drugs or stress!

ProlactinomasProlactinomas Microademomas Microademomas prolactin levels usually > prolactin levels usually >

100100 Macroadenomas Macroadenomas Prolactin levels usually very Prolactin levels usually very

high 500 to 1000. Be aware of HOOK Effect.high 500 to 1000. Be aware of HOOK Effect. MRI is the next test if high prolactin level MRI is the next test if high prolactin level

encountered and cannot be explained by meds/ encountered and cannot be explained by meds/ stress. MRIs do not r/o small microadenomas stress. MRIs do not r/o small microadenomas (<3mm)(<3mm)

For microadenomas/ non invasive For microadenomas/ non invasive macroadenomas macroadenomas use Bromocriptine use Bromocriptine ( dopamine agonist) ( dopamine agonist) Consider surgery for Consider surgery for those patients not responding to or intolerant those patients not responding to or intolerant of dopamine agonists. of dopamine agonists.

If Prolactin Producing Macroadenomas with If Prolactin Producing Macroadenomas with mass effect mass effect Try bromocriptine first Try bromocriptine first if no if no response, Surgery ( trans sphenoidal resection)response, Surgery ( trans sphenoidal resection)

Pituitary AdenomasPituitary Adenomas In deciding how to approach INCIDENTALLY In deciding how to approach INCIDENTALLY

discovered pituitary tumors, first rule out Functiondiscovered pituitary tumors, first rule out Function R/O functioning adenomas first R/O functioning adenomas first prolactin level, prolactin level,

Dexamethasone suppression test, ACTH level, TSH Dexamethasone suppression test, ACTH level, TSH and and IGF 1IGF 1 level depending on the clinical features. level depending on the clinical features.

Except Prolactinomas, all other Except Prolactinomas, all other functioningfunctioning adenomas are treated primarily by surgeryadenomas are treated primarily by surgery

If Non functioning adenomas If Non functioning adenomas Surgery indicated Surgery indicated only if mass effects only if mass effects Visual field defects , Visual field defects , Headaches and Hypopituitarism Headaches and Hypopituitarism

Follow patients with non functioning Follow patients with non functioning microadenomas and small, noninvasive microadenomas and small, noninvasive macroadenomas with a 6-month MRI scan and macroadenomas with a 6-month MRI scan and yearly thereafter yearly thereafter If there is no evidence of If there is no evidence of enlargement after 3 to 5 years, then continue to enlargement after 3 to 5 years, then continue to follow patients clinically. 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

CARCINOIDCARCINOID-Flushing, diarrhea, wheezing are clinical Flushing, diarrhea, wheezing are clinical

featuresfeatures-Ileal carcinoids commonly metastisizes to Ileal carcinoids commonly metastisizes to

liverliver-Appendiceal carcinoids are most common.Appendiceal carcinoids are most common.

-If pt develops above symptoms on small If pt develops above symptoms on small doses of SSRIs doses of SSRIs suspect Carcinoid suspect Carcinoid

syndromesyndrome-Screening test Screening test Urine 5-HIAA Urine 5-HIAA

-Confirmatory test – Octreotide ScanConfirmatory test – Octreotide Scan-Rx – medically, octreotide for symptomsRx – medically, octreotide for symptoms

-Surgery is definitive if no metastasesSurgery is definitive if no metastases

HypoglycemiaHypoglycemia

Medication induced in Medication induced in DiabeticsDiabetics

Surreptious insulin/ sulfonyl Surreptious insulin/ sulfonyl urea abuseurea abuse

InsulinomaInsulinomaTreatmentTreatment

INSULINOMAINSULINOMA

- Whipples Triad – the - Whipples Triad – the symptoms of hypoglycemiasymptoms of hypoglycemia

- C-peptide level.- 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.

GlucagonomaGlucagonoma

Necrotizing migratory Necrotizing migratory erythemaerythema

Octreotide scanOctreotide scan

Congenital Congenital Adrenal Adrenal

HyperplasiaHyperplasia21 Hydroxylase deficiency21 Hydroxylase deficiencyIncreased 17 hydroxy progesterone,Increased 17 hydroxy progesterone, increased increased

adrenal androgens. Low cortisoladrenal androgens. Low cortisolAmbiguous Genitilia in Congenital formAmbiguous Genitilia in Congenital form

Needs Mineralocorticoid and Glucocorticoid Needs Mineralocorticoid and Glucocorticoid replacement – prevent salt wasting and replacement – prevent salt wasting and

hypotensionhypotensionAdult onset CAH is possible in mild deficiency – Adult onset CAH is possible in mild deficiency –

can be confused with PCOScan be confused with PCOS

Polycystic Ovary Polycystic Ovary DiseaseDisease

Conns SyndromeConns SyndromePrimary Hyperaldosteronism – Hypertension, Primary Hyperaldosteronism – Hypertension,

Hypokalemia and AlkalosisHypokalemia and AlkalosisPAC/ PRA ratio best screening testPAC/ PRA ratio best screening test

CT scan to r/o adrenal mass after biochemical CT scan to r/o adrenal mass after biochemical evidence.evidence.

Rx – medically with SpironolactoneRx – medically with SpironolactoneSurgery if tumor > 4cm or suspicious features Surgery if tumor > 4cm or suspicious features of adrenal cancer or if refractory HTN despite of adrenal cancer or if refractory HTN despite

maximal medical therapymaximal medical therapy

Cushings Cushings SyndromeSyndromeEtiology :Adrenal CushingsEtiology :Adrenal Cushings

Pituitary CushingsPituitary CushingsEctopic Cushings ( Small cell ca)Ectopic Cushings ( Small cell ca)

Diagnosis : Overnight Low dose (1mg) Diagnosis : Overnight Low dose (1mg) dexamethasone suppression test, Urinary dexamethasone suppression test, Urinary

24 hr free cortisol, High dose (8mg) 24 hr free cortisol, High dose (8mg) dexamethasone suppression test, ACTH dexamethasone suppression test, ACTH

level.level.CT abdomen if Adrenal cushing CT abdomen if Adrenal cushing

suspectedsuspectedPituitary MRI if Pituitary adenoma Pituitary MRI if Pituitary adenoma

suspected suspected

False +ve Low Dose False +ve Low Dose dexamathasone testdexamathasone test

Factors that can produce false-positive or false-Factors that can produce false-positive or false-negative dexamethasone suppression tests: negative dexamethasone suppression tests:

Alcohol, rifampin, phenytoin, and phenobarbital Alcohol, rifampin, phenytoin, and phenobarbital induce the cytochrome P450-related enzymes and induce the cytochrome P450-related enzymes and enhance dexamethasone clearance enhance dexamethasone clearance Cause False Cause False +ve+ve

Hepatic failure retards dexamethasone clearance Hepatic failure retards dexamethasone clearance cause false –ve. cause false –ve.

In renal failure, serum cortisol may appear In renal failure, serum cortisol may appear nonsuppressible by dexamethasone nonsuppressible by dexamethasone

Obesity and depression give false-positive results Obesity and depression give false-positive results Thiazolidinediones can give false-negative resultsThiazolidinediones can give false-negative results

Addisons disease/ Addisons disease/ Adrenal Adrenal

insufficiencyinsufficiency-Random cortisol levelRandom cortisol level

-Cosyntropin Stimulation test – Cosyntropin Stimulation test – 1hr and 24hr stimulation tests1hr and 24hr stimulation tests

-Steroid replacement Steroid replacement HYDROCORTISOME 100 Q8hrs + HYDROCORTISOME 100 Q8hrs +

Mineralocortcoid Mineralocortcoid

Adrenal Adrenal IncidentalomasIncidentalomas

Work-upWork-up

In all Adrenal incidentalomas, R/o In all Adrenal incidentalomas, R/o functioning adenomas first functioning adenomas first

Do Low dose dexamethasone test (1mg) and Do Low dose dexamethasone test (1mg) and Plasma metanephrines in all patientsPlasma metanephrines in all patients

Do PAC/PRA only if HTN is present or if Do PAC/PRA only if HTN is present or if serum potassium is low.serum potassium is low.

If Functioning adenomas – Rx is If Functioning adenomas – Rx is usually surgery ( except in Conns usually surgery ( except in Conns Syndrome where medical Rx can be Syndrome where medical Rx can be tried first)tried first)

Work-upWork-up For non-functioning adenomas, further For non-functioning adenomas, further

treatment depends on the size of adrenal treatment depends on the size of adrenal mass. mass. < 4cm < 4cm low risk of cancer ( 2% risk) . low risk of cancer ( 2% risk) .

Follow-up Ct scan at 6-12 months. If no Follow-up Ct scan at 6-12 months. If no change, no further follow up.change, no further follow up.

4cm-6cm 4cm-6cm 6% risk of cancer 6% risk of cancer Adrenalectomy or a Follow-up CT Scan at Adrenalectomy or a Follow-up CT Scan at 6months. If no growth, just follow clinically. 6months. If no growth, just follow clinically. ( no more imaging)( no more imaging)

>6cm >6cm high risk of malignancy (25% high risk of malignancy (25% cases). Rx with adrenalectomycases). 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 POINTKEY POINT

SOMGYI EFFECTSOMGYI EFFECT

Nightmares are a clue and Nightmares are a clue and signifies a drop in blood glucose signifies a drop in blood glucose

to low levels to low levels

Next step Next step reduce the dose of reduce the dose of pre-dinner insulinpre-dinner insulin