Thyroid Disorders

Tapan A. Patel

Cuong Nguyen

Mona Jamaldinian

Thyroid Gland Second largest endocrine gland in body Small butterfly shaped gland located at

base of neck below the sternocleidomastoid muscles

Thyroid is controlled

by the hypothalmus

and pituitary

Functions Stimulates & maintains metabolic processes

Produces thyroid hormones T3-triiodothyronine and T4-thyroxine

These hormones regulate metabolism & affect the growth and function of other systems in the body

Secretes calcitonin to lower serum calcium levels

Parathyroid gland secretes PTH to raise serum calcium levels

Functions Metabolic stimulants of:

Neural and skeletal development Oxygen consumption at rest Stimulating bone turnover by increasing formation and

resorption Promoting chronitropic and ionotropic effects Increasing number of catecholamine receptors in heart Increasing production of RBC Altering the metabolism of carbs, fats, and protein

Hormones: T3 & T4

T3 (Triiodothyronine) & T4 (TetraiodothyronineStored in Follicles (round sacs) in the thyroid

filled with thyroglobulin, a thyroid protein. Dietary iodine enters follicles where they are

stored as T3 and T4

T4 is converted to T3 by peripheral organs such as kidney, liver, and spleen

T3 is 10x more active than T 4

Hormones: T4 to T3

Only 20% of total T3 is secreted by thyroid Majority is formed from catalysis of T4 by 5’-

iodthryonine deiodinase (highest activity in liver and kidney)

Hormones: T4 T4-thyroxine contains 4 iodine atoms It is a slow-acting pre-hormone T4 takes 4 days to peak in blood

Half-life 7 days Overall effects take 6 weeks T3 is the active and faster-acting hormone The immediate effects of T3 last 1-2 days

Half-life 1.5 days

Iodine Dietary Iodide is removed from the bloodstream by

means of an active pump The pump can concentrate iodide in the follicular

sacs at 350x greater than the blood concentration Oxidation of iodide by thyroid peroxidase converts

iodide iodine Peripheral de-iodination of T4 to T3 is regulated by

many factors including health, nutritional status, and other hormones

Hormones- TSH TSH

TSH is a pituitary hormone Controlled by TRH-thyrotropin releasing hormone from

hypothalamusFunctions to stimulate thyroid hormone production

May enlarge thyroid (goiter) when under producing

Labs: High TSH indicates low thyroid hormone= hypo Low TSH indicates high thyroid hormone = hyper

Hormones-Calcitonin & PTH

Produced by thyroid to regulate serum calcium levels

Calcitonin stimulates movement of calcium into bone

Parathyroid hormone (PTH) opposite effect of calcitonin

Negative Feedback System

TRH

T3 & T4 Thyroid

TSH

The disruption of any of these mechanisms can cause abnormal levels of T3 and T4 leading to thyroid disease

Diseases Hypothyroidism-Under Activity Prevalence

Affects 5-17% of population Females> Males Higher in >60 years old

Types Hashimoto’s thyroiditis Ord’s thyroiditis Postoperative hypothyroidism Postpartum hypothyroidism Iatrogenic hypothyroidism

Diseases Hyperthyroidism- Over activity Prevalence

Affect 5-17% of population Females> Males More common in younger persons

Types Thyroid storm Graves disease Toxic thyroid nodule Plummers disease Hashitoxicosis De Quervain thryoiditis Iatrogenic hyperthyroidism

Labs

Thyroid Function Test

Measurement Normal Range

Total T4 (TT4) Bound & Free T4 4.5-12.5mg/dL

Free T4 (FT4) Free T4 0.8-1.5 ng/dL

Total T3 (TT3) Bound & Free T3 80-220ng/dL

T3 Resin Uptake Binding capacity of TBG

22-34%

TSH Thyroid stimulating hormone

0.25-6.7U/mL

Total(T3) Bound & Free T3 80-220ng/dL

Labs

HyperthyroidismFT4 TSH

HypothyroidismFT4 TSH

Hyperthyroidism-Types

Graves diseaseMost common form (70-80%)

Autoimmune disorder in which thyroid-stimulating antibodies are circulating in blood. These bind to thyroid cells and activate cells in the same manner as TSH.

7 times greater in womenPeak onset is 20-30’s

Hyperthyroidism-Types

Can be caused by:Toxic multinodular goiterSolitary toxic noduleThyroiditisDrug-induced thryotoxicosisPituitary or trophoblastic tumors

Hyperthyroidism-Symptoms

Weight loss Tachycardia Bulging eyes Nervous/Anxious Insomnia Intolerant of heat Goiter

Goiter A diet deficient in

iodine Increase in thyroid

stimulating hormone (TSH) in response to a defect in normal hormone synthesis within the thyroid gland.

Thyroid Storm Life threatening syndrome Decompensated hyperthyroidism Symptoms

Hyperthyroid symptoms with agitation, confusion, delirium, psychosis

Gastrointestinal: Nausea/Vomiting, Abdominal pain

Tachycardia associated with CHF

Thyroid Storm Treatment Antithyroids

PTU 200-400mg po/NG q4-8h Methimazole 60-120mg/d PO/NG divided q6-8h

Potassium Iodide 2-5 drops PO/NG q6h Lugol Solution-Strong Iodine10 drops po TID Glucorticoids: block conversion of T4 to T3

Hydrocortisone succinate 100-200mg IV q6-8 Dexamethasone 2mg Po/IV q6-8h

BB Esmolol: 500mcg/kg/min Propranolol 20-80mg/dose PO/NG q4-6h

Hyperthyroidism-Treatment

Drug TherapyBeta blocker

Atenolol 50mg-100mg po daily Propranolol 20-40mg po TID

Antithyroids Methimazole 15-30mg po daily Propylthiouracil (PTU) 300mg TID

Hyperthyroid-Treatment

Procedural TherapyRadionuclide albation of thyroid glandTotal thyroidectomy

Methimazole

Methimazole prevents peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglubulin. Reduces T3 & T4 production.

Dosage15-30mg PO daily

Methimazole Adverse Effects

Skin rashLoss of tasteGI upsetDrowsinessDecreased Platelets

antagonistic properties of Methimazole

Methimazole

Drug Interactions:Discontinue before treatment with radioiodine;

affects uptakeAmiodarone: Increases T3 and T4 serum

levelsWarfarin: enhanced due to vitamin K

Propylthiouracil -PTU Thio-urea derivative Preferred agent in pregnant women DOC for severe thyrotoxicosis Dosage

Adults: 300-450mg/day divided q8h Severe cases: 600-1200mg/day Maintenance dose 100-150mg/day divided q 8-12 hours

Drug Interactions Similar to Methimazole

PTU

Adverse reactionsRash ItchingHivesAgranulocytosisVasculitis

Carbimazole-UK Pro-drug converted to active form -methimazole Dosage

15-40mg PO daily until normal function Reduce to 5-15mg po daily maintenance dose

Adverse EffectsBone marrow suppressionNeutropeniaAgranulocytosis

Sodium Iodide I-131 (Iodotope) Quickly absorbed and taken up by thyroid No other tissue capable of retaining radioactive

iodine therefore low adverse effects Dose

Adult 75-150mCi/g of thyroid x estimated thyroid gland size

24hour radioiodine uptakeDiscontinue antithyroid therapy 3-4days before

Hypothyroidism Types:

Primary hypothyroidism Most common cause Failure of thyroid gland Occurs primarily in women aged 30-50 years old

Chronic autoimmune thyroiditis or Hashimotos disease is the most common primary hypothyroidism AND hypothyroidism overall

Secondary HypothyroidismTertiary HypothyroidismOther causes

Hypothyroidism-Symptoms

Fatigue Weight Gain Depression Dry skin Bradycardia Constipation Intolerant to cold

Hashimoto’s Disease

Autoimmune disorder in which antibodies are directed against a thyroid sites to : Inhibit thyroid peroxidase Inhibit effects of TSHStimulate thyroid growth

Hypothyroidism-Primary Drug induced

Amiodarone, lithium, thiocyanates, phenylbutazone, sulfonylureas, PTU & methimazole

IatrogenicSurgical removal of the thyroid gland and

radiation treatment

Primary Hypothyroidism

Thyroid gland failureDecrease T3 & T4 Increase TRH due to negative feedback Increased TSH due to decreased TRH

Secondary Hypothyroid

Pituitary failure Insufficient TSH release as a result of:

Pituitary tumors Surgery Pituitary radiation Pituitary necrosis Autoimmune mechanisms

Tertiary Hypothyroidism

Hypothalamic Failure- very rare Insufficient TRH release as a result of:

Trauma IrradiationTumors

Hypothyroidism-Treatment Drug Therapy

Levothyroxine Sodium-DOC synthetic T4 Adults 1-1.5mgc/kg/day orally initially, adjust as needed. Average dose

1.6-1.8mcg/kg/day Pediatrics 1-1.5mgc/kg/day. Average 4 mcg/kg/day

Thyroid (Armour) 30mg PO daily, increase 15mg q 2-3 week

Liotrix (Thyrolar) synthetic combo T3 & T4 Thyrolar 1/2 (6.25/25mcg) start1 tab daily , increase PRN q 2-3 weeks.

L-triiodothyronine (Cytomel) synthetic T3 25mcg PO daily/ increase 12.5-25mcg daily every 1-2 weeks

Hypothyroidism-Treatment

Adverse EffectsMIOsteopeniaHA

ContraindicatedAcute MITreatment of obesityUncontrolled HTN

Monitoring

Obtain baseline FT4, TSH, LFT, CBCs before initiation of therapy

Repeat FT4 and TSH after 4-6 weeks on therapy and 4-6 weeks after adjustments

Once euthyroid state obtain thyroid function test after 3-6 months