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 T3triiodothyronine 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 (Tetraiodothyronine Stored 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 5iodthryonine 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 hypothalamus Functions 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 TSH

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

T3 & T4

Thyroid

Diseases

Hypothyroidism-Under Activity Prevalence Affects 5-17% of population Females> Males Higher in >60 years old Types Hashimotos thyroiditis Ords 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
Total T4 (TT4) Free T4 (FT4) Total T3 (TT3) T3 Resin Uptake TSH Total(T3)

Measurement
Bound & Free T4 Free T4 Bound & Free T3 Binding capacity of TBG Thyroid stimulating hormone Bound & Free T3

Normal Range
4.5-12.5mg/dL 0.8-1.5 ng/dL 80-220ng/dL 22-34% 0.25-6.7U/mL 80-220ng/dL

Labs

Hyperthyroidism
FT4

TSH

Hypothyroidism
FT4

TSH

Hyperthyroidism-Types

Graves disease
Most

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.

times greater in women Peak onset is 20-30s

Hyperthyroidism-Types

Can be caused by:

Toxic

multinodular goiter Solitary toxic nodule Thyroiditis Drug-induced thryotoxicosis Pituitary 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 Therapy
Beta

blocker

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

Antithyroids

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

Hyperthyroid-Treatment

Procedural Therapy
Radionuclide

albation of thyroid gland Total thyroidectomy

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

15-30mg

PO daily

Methimazole

Adverse Effects
Skin

rash Loss of taste GI upset Drowsiness Decreased Platelets

antagonistic properties of Methimazole

Methimazole

Drug Interactions:
Discontinue

before treatment with radioiodine; affects uptake Amiodarone: Increases T3 and T4 serum levels Warfarin: 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 reactions
Rash Itching

Hives
Agranulocytosis Vasculitis

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 Effects
Bone

marrow suppression Neutropenia Agranulocytosis

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 uptake Discontinue 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

Hypothyroidism Tertiary Hypothyroidism Other causes

Hypothyroidism-Symptoms
Fatigue Weight Gain Depression Dry skin Bradycardia Constipation Intolerant to cold

Hashimotos Disease

Autoimmune disorder in which antibodies are directed against a thyroid sites to :

Inhibit

thyroid peroxidase Inhibit effects of TSH Stimulate thyroid growth

Hypothyroidism-Primary

Drug induced
Amiodarone,

lithium, thiocyanates, phenylbutazone, sulfonylureas, PTU & methimazole removal of the thyroid gland and radiation treatment

Iatrogenic
Surgical

Primary Hypothyroidism

Thyroid gland failure

Decrease

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 Irradiation Tumors

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 Effects
MI Osteopenia

HA

Contraindicated
Acute

MI Treatment of obesity Uncontrolled 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