Endocrine: Thyroid

§  Ionized salt

§  Seafood

§  Dairy products

§  Meat

§  Vegetables

§  Eggs

Na+/I- active symporter

thyroid peroxidase (TPO)

monoiodotyrosine (MIT)

and

diiodotyrosine (DIT)

MIT + DIT

DIT + DIT

inc. MIT:DIT ratio

inc. T3:T4 ratio

inc. serum TSH

inc. T3, T4 & iodotyrosines

inhibited by excess iodine and lithium

Recycled

§  Thyroxine-binding globulin (TBG)

§  Thyroxine-binding prealbumin (TBPA)

§  Albumin


T3 and T4 >99% bound (esp. T4)

80 µg from thyroid

100% secreted from thyroid

t_1/2 7 days

low activity

0.04% unbound

30 µg from thyroid

20% secreted from thyroid

t_1/2 1 days

high activity

0.04% unbound

released from hypothalamus

• stims synth and release of TSH & prolactin
•      
• secretion stim'ed by dec T3 or T4
•      
• blocked by inc T3 or T4

Released from the pituitary

Synth controlled by T3 or T4 and TRH level

• somatostatin
• dopamine
• dopamine agonists
• steroids

in peripheral tissues

5’ deiodinase

o   Recommended for initial eval

o   Most sensitive for hyper, hypo, and replacement therapy

o   Total free and bound T4

o   Specific and sensitive test if no alterations in TBG

o   Total free and bound T3

o   Detects early hyper and T3 toxicosis

o Direct measurement of free thyroxine

• o “Gold standard” is by the equilibrium
• dialysis technique

o Calculated free thyroxine index

• o Compensates for alterations in TBG by
• using T3 resin-uptake

o Not valid in pts w/euthyroid sick syndrome

o Radioactive Iodine Uptake (I123 or I131)

o no correlation to hormone synth

o Falsely decreased w/ excess iodide intake

o Elevated in hyperthyroidism

o  Trace dose of I123 or I131 prior to scan

o assess gland size, shape, and tissue activity

o Can detect “hot” or “cold” areas in nodular disease

dec circulating thyroid hormone conc

slowing down of metabolic process

Hashimoto’s (autoimmune) most common

goitrous enlargement = mild hypothyroidism

atrophy = more severe hormone deficiency

antibodies v. thyroid peroxidase and thyroglobulin

post radiation/surgery

3-12 months after ¹³¹I 

1 month following surgery

Iodine deficiency/excess

Enzyme defects

Thyroid hypoplasia

Much less common

• Pituitary disease
• Hypothalamic disease

­high TSH

low T4

normal to low TSH

low T4

high TSH

normal T4

normal thyroid hormone concentrations

symptomatic relief

prevent neurological deficits in newborns

avoid overtreatment

should imp. QoL

decreases atherosclerotic risk (LDL)

decreases risk of complications

Synthetic T4 (converted to T3)

DOC

t_1/2 7 days

F = 40-80%

Highly protein bound

Untreated thyrotoxicosis

Acute MI

Untreated adrenal insufficiency

NTI

Elderly

CV disease

Mucosal disease

• Impaired GI absorption:
•      cholestyramine
•      calcium carbonate
•      sucralfate
•      aluminum hydroxide
•      ferrous sulfate
•      dietary fiber supplements

• Increased non-deiodinative T4 clearance:
•      carbamazepine
•      phenytoin

T4 -> T3 blockade: amiodarone

Category A

Minimal excretion in human milk

over replacement S/Sx

PO:IV 1.33:1

200 & 500 mcg IV vials

25 - 300 mcg PO tabs

Maintenance usu. ~125 mcg/day

Initiate @ 50 mcg/day (25 mcg in elderly)

Increase 25-50 mcg q6-8wks based on TSH

estimate @ 1.6 mcg/kg/day

empty stomach (seperate from other meds 1hr)

do not sub brands w/o MD approval

S/Sx of overtreatment

Imp. in 2-3wks

Resolution over months

4:1 ratio of T4:T3 (mimics normal ratio)

expensive

lack of Tx rationale

Extracted from hog, beef, or sheep

Use is rare and unwarranted

Unpredictable tablet conc.

Unpredictable pt response

no brand bioequivalence

may be antigenic

Treatment is usually lifelong

TSH q6-8 weeks until euthyroid then annually

FT4 can determine adherence or malabsorption

TSH no goodw/ 2^o hypo (monitor T4)

TSH treatment goal: 0.5-2.5

symptoms may be absent or non-specific

• controversy over treating
•       guidelines recommend only if symptomatic

inc rate of still-birth & lower psych scores

necessary for fetal growth

fetus can't make own fro first 2 months

Levothyroxine dose may inc 25-50%

TSH should be monitored

Initiate at lower starting dose (25 mcg/day)

Dosing requirements may decrease with age

End stage of uncontrolled hypothyroidism

Acute medical emergency (ICU)

Mortality of 60-70%

usu. require intubation and mech. vent.

w/ treatment  imp. expected w/in 24 hours

hypothermia

adv. stages of hypothyroid symptoms

delirium/coma

IV T4 300-500 mcg, then 75-100 mcg daily PO

Support: IV steroids, fluids (give with caution)

Euthyroid

OR

2^o Hypothyroidism

Hypothyroidism

Subclinical Hypothyroidism

Hyperthyroidism

T3-Thyrotoxicosis

Subclinical Hyperthyroidism

• Autoimmune
• Thyroid-stimulating antibodies (TSAb)
• Genetic link likely
• Any age

• Hyperthyroidism
• Diffuse thyroid enlargement,
• Exophtalamos,
• Pretibial myxedema,
• Thyroid acropachy
• Genetic link likely
• Any age

Release TSH w/o normal feedback loop

Autonomous thyroid nodule (independent of pituitary control)

“hot” nodules on radioiodine scan

• Insidiously onset (years)
• Usu. older pts w/ long-standing goiters

• self-limiting
• locally painful
• viral invasion of parenchyma
• unlikely to recur

• Reverse S/Sx and lab values
• Return TSH to normal range
• Avoid overcorrection (hypothyroidism)

• Init @ 30-60 mg/day in 3 div. doses
• Maintain @ 5-30 mg/day (taper @ 4-8wks)
• Tx is 12-24 months
• Max 120 mg/day

• Inhibits thyroid peroxidase
• (T4/T3 synthesis – coupling of MIT and DIT)

CI w/pregnancy or lactation

• Init @ 300-600 mg / day in 3-4 div. doses
• Maintain @ 50-300 mg in 2-3 div. doses (taper @ 4-8wks)
• Tx is 12-24 months
• Max 1200 mg/day

• Inhibits thyroid peroxidase
• (T4/T3 synthesis)

• Inhibits 5’ deiodinase
• (peripheral conversion of T4 to T3)

CI w/pregnancy

• Rapidly and completely absorbed from GI Actively concentrated in the thyroid
• Half-life: PTU 1 hour; MMI 5 hours
• Duration of action: PTU 6-10 hrs; MMI 24 hrs Clearance dec. in renal and hepatic disease

MMI 10-12 times more potent than PTU

Warfarin - clotting factors will have dec. metabolism --> dec. warfarin response

Minor: fever, rash, arthralgias, transient leucopenia

Major: agranulocytosis, hepatitis, vasculitis, lupus-like syndrome

Assume major reactions are cross-sensitive

• Baseline – leukocyte count (controversial)
• Labs – TSH, FT4, TT4 (once symptoms resolve monitor yearly)

ARs – weakness, fatigue, easy bruising/bleeding, urinary symptoms

• -> follicular necrosis
• pref. in Grave's pts
• 20% req.retreat in 6-12 months
• Avoid pregnancy for 6-12months (CI)
• Usu. hypothyroid in 4-12 months

d/t transient thyroid elevations pretreat elderly and cardiac pts w/MMI/PTU (controversial)

• exacerbates thyroid eye disease (exopthalmos)
• -inc. risk in smoker's
• -initiate glucocorticoids 4-7d post ¹³¹I dose and taper 2-3 months
• -Prednisone 0.4-0.5 mg/kg/day (or equivalent)

Pediatric pt w/ toxic rxn to antithyroid meds

Pregnant pt needing high dose PTU or w/ toxic rxn to PTU

Pt must be euthyroid before procedure

propranolol

Inhibit adrenergic effect

No significant antithyroid action

Calcium channel blocker

verapamil or diltiazem

alt if beta-blocker cannot be used

PTU preferred agent (highlt protein bound)

Use lowest possible dose

Inadequate Tx --> fetal tachycardia, severe growth restriction, premature birth, and 9-fold increased incidence of low birth weight

occurs d/t drug metabolism (iodine-induced)

treat w/ thioamides

• add lithium in severe cases
• (200-400 mg/day titrating to 0.6-1.2 mEq/L)

occurs d/t direct toxic effects (inflammation)

Prednisone 0.5-1.25 mg/kg/day; taper over 2-3 months

Usu. 40-60 mg/day

Pts w/ too much thyroid hormone supplementation

Decrease levothyroxine dose

Uncommon, life-threatening; Mortality of 20%

Precipitated by an ystressful illness

• high fever
• tachycardia
• tachypnea
• dehydration
• delirium
• CHF
• rapid aFib

• § PTU 600mg x1 dose, then 200-300mg q6h
• § Propranolol 40-80 mg q4-6h
• §  Iodide – SSKI 1-5 gtts PO TID
•           OR
•     Lugol’s soln 5-10 gtts PO TID in H2O/juice
• § Must wait 1 hour post PTU load

Fluids and electrolytes

Antibiotics if infectious etiology

Antipyretic – APAP only