Thyroid Disease

Intern Conference

Normal Physiology
http://agrc.ucsf.edu/supplements/endocrine/15_hpt_axis.html

TSH stimulates secretion of T4 and T3 from thyroid Most serum T3 produced by deiodination of T4 Think of T3 as active hormone and T4 as prohormone Only small fraction total T4 and total T3 is unbound therefore free and active

TFTs
TSH is the screening test of choice for thyroid function (nml 0.3-5mU/L) Unbound, free portion of T4 is indicative of thyroid status Previously, estimate of FT4 was determined by means of T3 resin uptake (total T4 x T3RU ~ free thyroxine level) Free T4 assay is currently preferred

Screening
Screening at periodic health exam without signs/symptoms is controversial Universal screening is recommended for thyroid dysfxn in pregnant women or those hoping to become pregnant

Diagnostic Approach
low

TSH
nml ? Secondary (central) dz

high

Free T4
low high

Free T4
low nml

high

nml

1o Hypothyroid 2o Hypothyroid Subclinical 1o Hyperthyroid Hyperthyroid Subclinical Hypothyroid

2o Hyperthyroid Or Thyroid hormone resistance

diffuse homogeneous Graves Dz

RAIU
focal

None Serum Thyroglobulin low Thyrotoxicosis factitia Iodine load high Thyroiditis Struma ovarii

heterogeneous Toxic multinodular goiter Functioning Adenoma

Hypothyroidism
Slowing of metabolic processes
Sxs: Fatigue, weakness, cold intolerance, weight gain, cognitive dysfunction, mental retardation, constipation, growth failure Signs: Slow movement, slow speech, delayed relaxation of tendon reflexes, bradycardia

Accumulation of matrix substances

Sxs: Dry skin, hoarseness, edema Signs: Periorbital edema, puffy facies, loss of eyebrows, coarse skin, macroglossia

Other
Sxs: Decreased hearing, myalgia and paresthesia, depression, menorrhagia, pubertal delay Signs: Diastolic HTN, pleural and pericardial effusions, ascites, galactorrhea, hyperlipidemia, atherosclerosis

Hypothyroidism etiologies
Primary (90%)
Hashimotos thyroiditis
May be part of polyglandular autoimmune syndrome (Addisons, DM), incrd incidence of Sjogrens +Antithyroid peroxidase (anti-TPO) abs in >90%

Recovery after thyroiditis Iodine deficiency Surgical destruction, s/p radioactive iodine Amiodarone, lithium

Secondary
Hypothalamic or pituitary failure

Hypothyroidism treatment
Overt
Levothyroxine (1.5-1.7g/kg/day), recheck TSH q56wks and titrate until euthyroid Lower starting dose if at risk for ischemic heart disease (0.3-0.5g/kg/d)

Subclinical
Rx controversial
Follow expectantly or treat to improve mild sx Most initiate Rx if TSH>10mU/L, goiter, pregnancy or infertility Keep in mind risk of A. fib and accelerating osteoporosis with treatment

Hyperthyroidism
Sympathetic overactivity
Restlessness, sweating, tremor, moist warm skin, fine hair, tachycardia (A. fib), weight loss, increased stool frequency, menstrual irregularities, hyperreflexia, osteoporosis, lid lag

Hyperthyroidism etiologies
Graves Disease
+ thyroid antibodies
TSI, ANA

Classic manifestations
Goiter: diffuse, nontender, w/ thyroid bruit Ophthalmopathy: periorbital edema, proptosis, diplopia Pretibial myxedema

http://www.elp.manchester.ac.uk/pub_projects/2002/MNBY9APB/THETHYrOIDCLINICAL.htm

Hyperthyroidism etiologies
Thyroiditis
Thyrotoxic phase of subacute thyroiditis
Painful = viral, granulomatous, or de Quervains (fever, ESR, Rx = NSAIDs, steriods)

Hyperthyroidism etiologies
Others: Toxic adenomas (single or multinodular goiter) Rare functioning thyroid carcinoma TSH-secreting pituitary tumor Pituitary resistance to thyroid hormone Amiodarone, iodine-induced, thyrotoxicosis factitia, struma ovarii

Hyperthyroidismuptake
A. Normal B. Graves Dz C. Toxic Multinodular Goiter D. Toxic Adenoma E. Thyroiditis
http://embryology.med.unsw.edu.au/Notes/endocrine8.htm

Hyperthyroidism treatment
Beta-blockers: control sxs
Propranolol decr peripheral T4 -> T3 conversion

Graves Dz
PTU (safe in pregnancy) or methimazole
Rare side effect: agranulocytosis

Radioactive iodine
75% of treated pts become hypothyroid

Surgery
Usually reserved for obstructive goiter

Toxic Adenoma or TMNG

RAI or surgery

Sick Euthyroid Syndrome

TFT abnormalities in pts w/ severe nonthyroidal illness If thyroid dysfunction is suspected in critically ill patients, TSH alone is not reliable must measure all TFTs Replacement thyroxine not helpful or recommended for critically ill unless other s/s of hypothyroidism

Amiodarone and Thyroid Dz

Causes both hypothyroidism and hyperthyroidism
Hypothyroidism
Wolff-Chaikoff effect: iodine load decreases iodine uptake, organification, and release of T4 & T3 Inhibits coversion of T4 -> T3 Direct/immune-mediated thyroid destruction

Hyperthyroidism
Type 1 = underlying MNG or autonomous thyroid tissue Type 2 = destructive thyroiditis
Increased release of preformed T4 and T3 hyperthyroidism hypothyroidism recovery

Thyroid nodules
No difference in incidence of thyroid carcinoma between thyroids with single or multiple nodules
***Perform FNA/biopsy on all cold or non-specific thyroid nodules >1.0cm

Thyroid Nodulestypes
Thyroid adenoma ablate, resect, or med Rx Thyroid Carcinoma
Parafollicular (medullary)
Affects parafollicular C cells causing increased serum calcitonin 15% seen in MEN 2A (+ parathyroid hyperplasia, pheochromocytoma

Follicular
Papillary, Follicular, Anaplastic