10/17/16

1

Thyroid Disorders Lubna Mirza, MD

Norman Endocrinology Associates10/2016

Introduction: The importance of thyroid hormone for normal growth

and development

Outline- Hypothyroidism • Case 1• Pathophysiology• Diagnosis• Treatment • Hypothyoridism during pregnancy

10/17/16

2

Case 1

• Cc: – Hypothyroidism

• HPI:– 68 year old woman with Hypothyroidism– Taking 100mcg po daily levothyroxine– c/o Anorexia, weight loss and vomiting for a

year

History• PMHx:

– HTN– Hypothyroidism

• Family history:– Daughters and sister have thyroid disease

• Social history: – Widow lives at home by herself– Former smoker

Medications• HTN:

– Amlodipine 10mg po daily– Hydrochlorothiazide 25mg po daily

• Hypothyroidism– Levothyroxine 100mcg po daily

• Allergies: – NKDA

10/17/16

3

Physical Examination• VS: 128/76mmHg, HR 80, RR 16, T 98.6F, Wt

101.6 pounds, Ht 66 inches, BMI 16.40• Gen: Thin small woman• HEENT: AT, NC, AI, PEARL• NECK: Supple, No thyromegaly, No

lymphadenopathy• CHEST: CTAB• CVS: RRR, S1, S2, No m, r, g• ABD: Soft, NT, ND, BS+• EXT: No e/c/c• NEURO: DTR 2+ SKIN: No rash

Assessment and Plan

• Hypothyroidism: Check TSH today and adjust levothyroxine accordingly

• Celiac disease: She is thin with several GI symptoms. May not be absorbing thyroxine. Screen for Celiac disease

Labs

• TSH 10 Reference range 0.4-4.0• Transglutaminase autoantibodies (tTGA)• 77 U/ml Reference range <4• CBC, CMP and Iron studies returned in

normal reference range

10/17/16

4

Plan

• Follow gluten free diet• Increase levothyroxine to 125mcg po daily

Follow up• 3 months later

– TSH is 0.45 (0.4-4.0)– Weight 107 pounds– Nausea and vomiting has stopped– Patient gained 6 pounds

• Recommendations:– Continue to follow gluten free diet– Cut back on levothyroxine to 112mcg po daily

Lessons to take home!• In the presence of one Autoimmune disease,

expect to find others!• Some examples of Autoimmune diseases

– Hashimoto’s thyroiditis– Type 1 Diabetes– Addison’s disease– Premature ovarian failure– Autoimmune Hepatitis– Pernicious anemia– Vitiligo

10/17/16

5

Outline • Case 1 • Pathophysiology• Diagnosis• Treatment • Hypothyoridism during pregnancy

Outline • Case 1• Pathophysiology• Diagnosis• Treatment • Hypothyoridism during pregnancy

Embryology

10/17/16

6

Anatomy

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html

THYROID GLAND HISTOLOGY

O OH

I

I

IIOH

O

NH2

Thyroxine (T4)

O OH

I

I

IOH

O

NH2

3,5,3’-Triiodothyronine (T3)

THYROID HORMONES

10/17/16

7

FEEDBACK REGULATIONTHE HYPOTHALAMIC-PITUITARY-THYROID AXIS

HM Goodman, BASIC MEDICAL ENDOCRINOLOGY 3rd Ed.

– –

+

Iodine Transport and Thyroid Hormone Synthesis

THYROID HORMONES IN THE BLOOD

• Approximately 99.98% of T4 is bound to 3 serum proteins:– Thyroid binding globulin (TBG) ~75%– Thyroid binding prealbumin (TBPA or

transthyretin) 15-20%– Albumin ~5-10%

• Only ~0.02% of the total T4 in blood is unbound or free

• Only ~0.4% of total T3 in blood is free

10/17/16

8

THYROID HORMONE DEIODINASES

• Three deiodinases (D1, D2 & D3) catalyze the generation and/disposal of bioactive thyroid hormone

• D1 & D2 “bioactivate” thyroid hormone by removing a single “outer-ring” iodine atom

• D3 “inactivates” thyroid hormone by removing a single “inner-ring”iodine atom

BASICS OF THYROID HORMONEACTION IN THE CELL

SPECIFIC ACTIONS OF THYROID HORMONE: METABOLIC

• Metabolic actions:– Regulation of Basal Metabolic Rate (BMR)– Increases oxygen consumption in most target

tissues• Permissive actions:

– Increases sensitivity of target tissues to catecholamines, thereby elevating lipolysis, glycogenolysis, and gluconeogenesis.

10/17/16

9

• Development:– Critical for normal development of the skeletal system

and musculature– Essential for normal brain development and regulates

synaptogenesis, neuronal integration, myelination and cell migration

– Cretinism is the term for the constellation of defects resulting from untreated neonatal hypothyroidism

SPECIFIC ACTIONS OF THYROID HORMONE

Causes of Hypothyroidism

• Autoimmune 85%• Treatment of hyperthyroidism• Surgery• Radiation• Medications• Congenital• Iodine deficiency• Pituitary disorder

Risk Factors for Hypothyroidism• Are a woman older than age 60• Have an autoimmune disease• Have a close relative, such as a parent or

grandparent, with an autoimmune disease• Have been treated with radioactive iodine or anti-

thyroid medications• Received radiation to your neck or upper chest• Have had thyroid surgery (partial thyroidectomy)• Have been pregnant or delivered a baby within the

past six months

10/17/16

10

Signs and Symptoms of Hypothyroidism

• Fatigue• Increased sensitivity to cold• Constipation• Dry skin• Unexplained weight gain• Puffy face• Hoarseness• Muscle weakness• Elevated blood cholesterol level• Muscle aches, tenderness and stiffness• Heavier than normal or irregular menstrual periods• Thinning hair• Slowed heart rate• Depression• Impaired memory

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

EXAMPLES OF THYROID DISEASES

1° Hypothyroidism Hyperthyroidism

EXAMPLES OF THYROID DISEASES

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

Congenital HypothyroidismJuvenile Hypothyroidism

10/17/16

11

Outline • Case 1 • Pathophysiology• Diagnosis• Treatment • Hypothyoridism during pregnancy

Diagnosis

• Check TSH when you suspect hypothyroidism

• Normal reference range:– For general population

• 0.4-4.0

– For young women in childbearing age • 0.4-2.5

Outline • Case 1• Pathophysiology• Diagnosis• Treatment • Hypothyoridism during pregnancy

10/17/16

12

Treatment

• Replace what’s missing– Levothyroxine 1.5 to 1.7mcg oral daily per

kilogram of ideal body weight• Special Instructions:

– Take early in am before eating breakfast on empty stomach

– Not combined with any other meds especially calcium or iron

Outline • Case 1 • Pathophysiology• Diagnosis• Treatment • Hypothyoridism during pregnancy

TSH during Pregnancy

10/17/16

13

Hypothyroidism During Pregnancy

• Associated with maternal and fetal complications

• Levothyroxine is the treatment of choice• Dessicated thyroid or T3 is not

recommended• Hypothyroid women on treatment should

increase leovothyroxine dose by 25-30%• Iodine intake 250micrograms/day during

pregnancy and lactation

TSH during Pregnancy

• American Thyroid Association guidelines:– Normal range for TSH– In the first trimester 0.1 to 2.5 mIU/L– Second trimester 0.2 to 3.0 mIU/L– Third trimester 0.3 to 3.0 mIU/L

Take Home Points –Hypothyroidism

• Thyroid hormone is important for normal growth and development

• Screen and treat appropriate patients• Universal screening is recommended for

neonates• TSH goals are different

10/17/16

14

Hyperthyroidism

Introduction• What is Hyperthyroidism?

– “Hyperthyroidism” refers to over-activity of the thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues

– The secretion of thyroid hormone is no longer under the regulatory control of the hypothalamic-pituitary center

Outline- Hyperthyroidism

– Case– Epidemiology– Pathophysiology– Signs and symptoms – Diagnosis– Treatment– Clinical outcomes of under-treatment– Conclusions

10/17/16

15

Case1

• 33 year old white man referred to Endo service for thyroid disease

• Was in usual state of health until 3 years ago• Developed nausea, heat intolerance, nervousness, fast

heart beat, muscle weakness, weight loss, fatigue and enlarging eyes with blurred vision

• Labs: TSH <0.1 (0.4-4.0), Free T4 4.8 (0.6-1.6), Thyroperoxidase antibodies 261 (<9)

• Atenolol 50mg po daily started that made him feel better

History

• PMHx:– Acne

• FMHx: – Sister developed hyperthyroidism while he was

being treated• SHx:

– Lives at home with wife and a baby– No smoking– No drugs– Works as a machinist

PhysicalExamination• VS: 128/81, HR 88, Temp 98.9F, Wt 159, Ht 71, BMI 22.17• GEN: Anxious appearing thin man with tremors• HEENT: + Exophthalmos, No chemosis, eye movements

intact• NECK: Moderate thyromegaly with bruit• CHEST: CTAB• CVS: Tachycardia, S1, S2, no murmurs• ABD: Soft, NT, ND, BS+• EXT: No edema, cyanosis or clubbing• NEURO: DTR 2+ SKIN: Smooth, warm

10/17/16

16

FurtherInvestigations• Repeat labs:

– Free T4 5.1ng/dl (0.6-2.00)– Free T3 18.16pg/ml (2.5-3.9)

• I 123 scan showed 73% uptake

http://www.nucmedtutorials.com/dwmolimaging/molimg2.html

I123UptakePatterns

http://www.nejm.org/doi/full/10.1056/NEJMct1007101

Treatment

• 19.8 millicuries of I 131 were given• The activity to be administered in I-131

therapy of benign thyroid disease is determined by– The radiation absorbed dose necessary to

cure the disease– The target mass and– The residence time of the I-131 in the target

volume

10/17/16

17

Next• TSH increased to 28 in 4 months• Patient was started on levothyroxine • Dose:

– 1.5-1.7mcg/kg of ideal body weight• Last seen in 07/12

– Dose increased to 175mcg po daily due to a TSH of 6.74mciu/ml (0.4-4.0)

– Directions: Take thyroid medicine early in am before eating breakfast on empty stomach not combined with any other medications especially calcium or iron

ClinicalStatistics

• Graves Disease is the most common cause of hyperthyroidism (60-80%) of all cases.

• Females are affected more frequently than men 10:1.5

• Monozygotic twins show 50% concordance rates

• Incidence peaks from ages 20-40

Outline

– Case– Pathophysiology– Signs and symptoms – Diagnosis– Treatment– Clinical outcomes of under-treatment– Conclusions

10/17/16

18

Pathophysiology

Cytotoxic T-lymphocyte antigen 4 (CTLA-4)

gene on Ch 2 is associated with Graves' disease (Weetman, 2000)

PathophysiologyofGravesDisease

http://www.bio.davidson.edu/Courses/Immunology/Students/Spring2003/Breedlove/GravesDisease.h

tml

Grave’sOphthalmopathy

10/17/16

19

Outline

– Case– Pathophysiology– Signs and symptoms – Diagnosis– Treatment– Clinical outcomes of under-treatment– Conclusions

SignsandSymptoms– Tremulousness or jitteriness– Exophthalmos – Weight loss despite excellent appetite – hypermetabolic state– Insomnia– Fatigue– Palpitations– Heat intolerance– Sweating– Diarrhea– Menstrual irregularities– Muscle weakness/wasting manifested as exercise intolerance or

difficulty climbing stairs– Eye symptoms, which may include pain or diplopia– Nervousness– Tachycardia– Goiter

Exopthalamos in Graves Disease

Lid Lag in Graves Disease

10/17/16

20

Outline

– Case– Pathophysiology– Signs and symptoms – Diagnosis– Treatment– Clinical outcomes of under-treatment– Conclusions

HowToDiagnoseHyperthyroidism

• TSH – expect this to be low• Free T4 – expect to be high• Nuclear thyroid scintigraphy iodine 123

uptake and scan – expect iodine uptake to increased

• Anti-thyroperoxidase antibody levels• TSH-receptor stimulating autoantibody

levels (TSI levels)

T4andTSHFineBalance

10/17/16

21

Outline

– Case– Pathophysiology– Signs and symptoms – Diagnosis– Treatment– Clinical outcomes of under-treatment– Conclusions

Treatments for Thyrotoxicosis

• Graves disease– Medical therapy

• Propylthiouracil• Methimazole• Propranolol

– Radioactive Iodine:• Ablation of the thyroid gland

with I 131 – Surgery:

• Thyroidectomy

TreatmentofOtherCausesofThyrotoxicosis

• Sub acute thyroiditis– NSAIDs– Steroids

• Iodine-induced hyperthyroidism– Stop Iodine

• Exogenous administration of T4– Reduce dose of thyroxine

10/17/16

22

ThyroidStorm(AnEmergency)

• High risk for mortality

• Classic Triad– Fever– Tachycardia– Central nervous

system dysfunction

BurchandWartofskyThyroidStormScoring

SystemScore >45 = Thyroid Storm

Score > 25 Impending Thyroid Storm

Score <25 Unlikely to represent Thyroid Storm

Ref: Burch, H. B. und L. Wartofsky (1993). "Life-Threatening Thyrotoxicosis. Thyrotoxic storm. " Endocrinology and Metabolism Clinics of North

America 22(2): 263-77

ThyroidStormManagement

• Treat precipitating cause • Supportive Care

– Fever• Cooling measures/Acetaminophen

• DO NOT USE ASPIRIN• Salicylates can decrease thyroid protein binding,

causing an increase in free thyroid hormone levels– Dehydration

• Intravenous fluids with dextrose

10/17/16

23

ThyroidStormManagement• Propranolol

– Will lower heart rate and blood pressure by beta blockade

– Block peripheral conversion of T4 to T3• Methimazole

– Blocks thyroid hormone production and release• Iodine drops

– Give after Methimazole to block thyroid hormone release

• Hydrocortisone– Blocks peripheral conversion of T4 to T3

HyperthyroidismDuringPregnancy

• Increased risk for maternal/fetal complications– Premature delivery– Placental abruption

• Use PTU in first trimester of pregnancy

• Aplasia cutis – Peptidase D

haploinsufficiency– Deletion in Chromosome

19

Outline

– Case– Pathophysiology– Signs and symptoms – Diagnosis– Treatment– Clinical outcomes of under-treatment– Conclusions

10/17/16

24

ClinicalOutcomesofInadequatelyTreatedHyperthyroidism

• Thyroid Storm– The mortality rate due to thyroid storm

ranges from 20 to 30% (1,2)• Hyperthyroidism/Subclinical

hyperthyroidism– Atrial fibrillation/Strokes– Osteoporosis/Fractures

[1] Jameson L, Weetman A. Disorders of the thyroid gland. In: Braunwald E, Fauci A,Kasper D, et al, editors. Harrison’s principles of internal medicine. 15th edition. New

York: McGraw-Hill; 2001. p. 2060–84.[2] Tietgens ST, Leinung MC. Thyroid storm. Med Clin North Am 1995;79:169–84.

Follow-upCare

• Patients who have been treated for hyperthyroidism need to be followed closely because they will develop HYPOthyroidism or recurrent hyperthyroidism

Conclusions

• Women are more likely to have Hyperthyroidism as compared to men

• Hyperthyroidism has several complications• Thyroid storm has high mortality• Prompt diagnosis and treatment can save lives• *Do not use Aspirin in Thyroid Storm• *Do not use propranolol in Asthma• *PTU only in the first trimester of pregnancy

10/17/16

25

Case2• 31 year old white woman seen in 2012 with a TSH of

0.006• Was in usual state of health until 2009• Developed goiter, hot flashes, bulging eyes, irregular

periods, uncontrollable mood swings, inability to sleep

• and choking• Started on methimazole 5mg po daily by other

physicians• Took medicine for ~4-6 months off and on

FurtherHistory

• PMHx: – Anemia– Headaches– Asthma

• FMHx: – Father- HTN, High Cholesterol– Mother- Diabetes– No family h/o thyroid disease

• SHx:– Lives at home with two kids– Husband is incarcerated for criminal activity– Smokes heavily 31 cigarettes per day for several years

AllergiesandMedications

• Allergies:– No known drug allergies

• Medications:– Methimazole 5mg po daily– Multivitamin one tablet daily– Atenolol 25mg po daily– Albuterol inhaler q 4 hours prn for

shortness of breath

10/17/16

26

PhysicalExamination

• VS: BP 132/76mmHg, HR 80, RR 24, Temp 99.2, Wt 127, Ht 60, BMI 24.88

• GEN: anxious, restless, nervous and temulous• HEENT: + lid lag and +exophthalmos• NECK: Large thyroid goiter with bruit present• CVS: RRR, S1, S2, no m, r or g• ABD: Soft, NT, ND, bowel sounds hyperactive• EXT: no e/c/c• NEURO: DTR 3+ bilateral• SKIN: warm, smooth

Labs:

• Free T4 2.56 (0.6-2.00)• Free T3 10.70 (2.5-3.9)

I123ScanResults• Findings:

– Right lobe of the thyroid measures 8.5 x 4.8 cm. No hot or cold nodules are seen.

– Left lobe of the thyroid measures 4.2 x 8.0 cm. No focal hot or cold nodules are seen.

– 24-hour uptake is estimated at 65.5% (10-30)

• Impression:– 1. Significantly elevated 24-hour uptake at 65.5% possibly secondary to

Graves' disease

– 2. Thyromegaly.

10/17/16

27

Furthercare• Advised to take

– 60mg po daily methimazole– Increase Atenolol to 50mg po daily– Take lugol iodide drops every 6 hours – Return in 4 weeks

• Four weeks Later– Free T4 4 (0.6-2.0)– Free T3 21 (2.5-3.9)– * Non-compliance– Free hormones increased to 5.8 and 29 in 2 months

I131TreatmentComplications

• Can exacerbate graves ophthalmopathy• Can precipitate thyroid storm with

inflammation of the thyroid gland

FurtherCare

• Admitted to the hospital• Methimazole 60mg po daily• Prednisone 20mg po daily• Lugol iodide 5% 3 drops qid• Atenolol 25mg po daily• Ambien 5mg po daily• Thyroidectomy in 5 days• Discharged home on 100mcg

po daily levothyroxine