ENDOCRINOLOGYBOARD REVIEW

THYROID DISORDERSHenri Godbold, MD

General- Thyroid produces two related hormones

thyroxine(T4) and triidothyronine (T3)- Function is through nuclear receptors playing a

role in cell differentiation- Maintains thermogensis, and metabolic

homeostasis- Disorders result from autoimmune processes that

either stimulate overproduction of hormones (thyrotoxicosis) or glandular destruction and hormone deficiency (hypothyroidism)

- Benign nodules and various forms of thyroid cancers

Anatomy- Located anterior to trachea consist two lobes-  Weighs 12-20gm soft and highly vascular a

posterior region gland contain four parathyroid gland that produce parathyroid hormone

- Lateral borders of the gland is transversed by the recurrent laryngeal nerves

- Develops from the floor of the primitive pharynx third week of gestation migrates from the foramen cecum, at the base of tongue along the thyroglossal duct to neck

- Hormonal synthesis usually begin at about 11 weeks’ gestation

Thyroid Physiology- Thyroid releases (2) forms of hormones - Thyroxine (T4) and triiodothyroxine (T3) ratio

14:1 - T3 is 80% derived from peripheral tissue- T4 all within the thyroid gland- T3 is produced from T4 in liver, kidneys,

pituitary gland and CNS- T3 is the physiologically active in almost all

tissue binding to specific nuclear receptors regulating the transcription of thyroid hormone dependent genes

 

Drugs decreasing Peripheral conversion of T4 to T3

       Propranolol        Corticosteroids        Propylthiouracil (PTU)        Amiodarone

 

SYNTHESIS AND RELEASE

- TSH controls release under the influence TRH from the hypothalamus- TSH stimulate thyrocyte function resulting in iodide uptake actively on the basal surface of the thyroid follicle cell- Iodide undergoes oxidation to iodine which iodinates tyrosine residues catalyzed by peroxidase - Thyroglobulin coupling occurs to form mono-

and diiodotyrosine (MIT and DIT- Two DITs coupling = T4- One DIT and one MIT combine =T3- If iodine scarce, the production of T3 is increase - Activity is dictated by # iodines attached to tyrosine molecules and location

 

Secretion Degradation process with endocytosis of the follicular

colloid containing MIT, T3, T4, DIT attached to thyroglobulin undergoes fusion

with lyosome resulting in proteolysis release Deiodination occurs with the recycling iodide and

secretion of T3 and T4 Circulating thyroid hormones are more than 99%

protein bound, are thyroxine-binding globulin, albumin, and transthyretin.

80% of circulating T3 is derived from the conversion of T4 outside the thyroid

Serum half-life of T3 is much shorter than that T4 (1day vs 8days)

Storage- Iodine as iodinated tyrosine of

thyroglobins 8000 micrograms total

- T4 and T3 represent 600 micrograms

each

- Enough hormone is stored in the

follicular colloid to last 2-3 months 

Overveiw of Thyroid Fx Workup

1st Test 2nd Test 3rd Test

TSH FT4-I,

FT4

Clinical Status

HIGH Low Prim hypothyr’ism N/A

Normal Subclinical hypothy’ism TRH to confirm

High Pituitary hyperthyr’ism N/A

LOW High Thyrotoxicosis RAIU

Normal Subclinical hypothyr’ism TRH to confirm

Low Pituitary hyperthyr’ism N/A

Measurement RAIU

Levels Specific disorders

High Hyperfunction (Graves’, multinodule goiter, toxic solitary nodule, hCG secreting tumor)

Normal Euthyroid

Low Thyroiditis, severe iodine excess, amiodarone induced thyrotoxicosis

Drugs and condition that affect thyroid Function Tests

Increase

TBG

Decrease TBG Block peripheral conversion of T4 to T3

Blocks thyroidal release T4 and T3

Estrogen

OCT,

pregnancy

Tamoxifen

Clofibarate

Narcotics

Hepatitis

Bililary cirrhosis

Androgens

Gluccorticoid

Nephrotic syn

Propranolol

Glucorticoid

PTU

Amiodarone

Lithium

Iodine

Thyroid PathologyA. Thyroid Gland

1. Multinodular goiter (nontoxic goiter) Presentation

i. Females > males

ii. Frequently asymptornatic

iii. Typically euthyroid

iv. Goiter

v. Plummer's syndrome:development of

hyperthyroidism (toxic multinodular Goiter)

late in course

B. GROSS

enlarged thyroid gland with multiple colloid nodules

C. MICROSCOPIC

i. Nodules of varying sizes composed of colloid follicles

ii. Calcification, hemorrhage, cystic degeneration, and fibrosis

D. LAB: normal T4, T3, and TSH

B Hyperthyroidism1. General features of hyperthyroidism I

a. Clinical features

i. Tachycardia and palpitations

ii. Nervousness and diaphoresis

iii. Heat intolerance

iv. Weakness and tremors

v. Diarrhea

vi. Weight loss despite a good appetite

b. Labs

i. Elevated free T4 ii. Primary hyperthyroidism: decreased

TSH

Graves'disease

a. Definition: autoimmune diseases characterized by production of IgG autoantibodies to the TSH receptor

b. Clinical features

i. Females > males; age 20‑40

ii. Hyperthyroidism

iii. Diffuse goiter

iv. Ophthalmopathy: exophthalmus

v. Dermopathy: pretibial myxcdema

c. Micro: hyperplastic follicles with scalloped

colloid

Other causes of hyperthyroidism

a. Toxic multinodular goiter

b. Toxic adenoma: functioning adenoma

producing thyroid hormone

c. Hashimoto’s and subacute thyroiditis

(transient hyperthyroidism)

Juvenile Graves Disease Diffuse hyperplasia Most common cause of thyrotoxicosis in children and

adolescents Clinical manifestation - muscle weakness - behavior problems - anxiety - cardiomegaly - palpitations - tachycardia - appetite - widen pulse pressure - Tremor - Emotional liability - rapid DTR time - Excessive perspiration Opthalmopathy, dermopathy, pretibial myxedema rare in children

Test: TSH suppressed and serum T4 high Treatment:

a. Blunting toxic effects circulating T3/T4 b. Stop further increase in production

B-blockers prior to Sx intervention RAI rarely used in children and adolescences

potential risk leukemia, thyroid Ca, and genetic disorder.

Medical management: PTU and methimazolemechanism: Both inhibit the coupling of

iodotyrosines, oxidation and binding of iodide

PTU 5-10mg/kg PO div q8hr Methimazole 0.2 mg/kg PO daily Once gland cools off and decrease in size

tapper drugs Give synthetic T4 once euthyroid adjust to

maintain a euthyroid status

Neonatal Thyrotoxicosis Due to TSH-receptor stimulating antibodies(TSH) Transmitted transplacentally in mother with inactive or active Graves or Hashimoto thyroiditis Presentation: newborn irritability, flushing, tachycardia,

HTN, thyromegaly High total T4, FT4, T3 postnatal blood, low TSH

Treatment: a. sedative and digitalis if neededb. Iodidec. Lugol (5% iodine and 10% K iodine) d. Methimazole

Hypothyroidisma. Clinical features

i. Fatigueii. Sensitivity to cold temperatures

iii. Decreased cardiac output iv. Myxedema:

- Facial and periorbital edema - Peripheral edema of the hands

and feet

- Deep voice - Macroglossia

v. Constipationvi. Anovulatory cycles

b. Labi. Decrease Free T4

ii. Primary hypothyroidism: elevated TSH

Iatrogenic hypothyroidism Most common cause of hypothyroids in US Secondary to thyroidectomy or RAI rx Rx: Levothyroxine 12.5-50mcg PO qd adjusting

dose by 12.5-25mcg/d q4-8wks

Congential Hypothyroidism(cretinism)a. Etiology

i. Endemic region: iodine deficiency during intrauterine and

neonatal life ( worldwide)

ii. Non endemic regions: thyroid dysgenesis

b. Presentation

i. Failure to thrive

ii. Stunted bone growth and dwarfism

-Commonly absent distal femoral epiphysis

iii. Spasticity and motor incoordination

iv. Mental retardation

v. Goiter (endemic cretinism)

‑ Endemic goiter

a. Uncommon in the US

b. Etiology: dietary deficiency of iodine

Clinical Manifestation congenital Hypothyroidism

Occurs in 1/4000 Worldwide Most infant are asymptomatic at birth because of

transplacental passage of T4 (usu 3rd day of life) Most common cause is thyroid dysgenesis Presentation: hypoglycemia, jaundice micropenis, midline facial anomalies, enlarge posterior fontanelle, macroglossiaRx: Initial dose: Sodium L-tyroxine 10-15 microgrms/kg/day( should not be mixed soy protien or iron) Then, 4 micrgms/kg/day

Thyroiditis1. Hashimoto's thyroiditis a. Definition: chronic autoimmune disease characterized by

immune destruction of the thyroid gland and hypothyroidismb. Most common noniatrogenic cause of hypothyroidism and Goiter in children > 6yo and adults in US

c. Clinical presentationi. Females > males; age 40‑65ii. Painless goiteriii. Hypothyroidiv. Initial inflammation may cause transient hyperthyroidism.

d. Gross: pale enlarge gland e. Micro:

i. Lymphocytic inflammation with germinal centers ii. Epithelial "Harthle cell" changes

f. May be associated with other autoimmune diseases (SLE, RA, SS [Sjogren's syndrome], etc.)

g. Complication: increased risk of non‑Hodgkin‘ lymphoma (NHL) B‑cell lymphoma

2. Subacute thyroiditis a. Synonyms: De Quervain's thyroiditis, granulomatous thyroiditis b. Clinical features i. Second most common form of thyroiditis

ii. Females > males; age 30‑50 iii. Preceded by a viral illness iv. Tender, firm, enlarged thyroid gland v. May have transient hyperthyroidism

c. Micro: granulomatous thyroiditis d. Prognosis: typically the disease follows a self‑limited course e. Symptoms: control with analgesics, prednisone very severe

dx

Riedel's thyroiditisa. Definition: rare disease of unknown etiology characterized by

destruction of the thyroid gland by dense fibrosis and fibrosis of surrounding structures (trachea and esophagus)

b. Clinical features i. Females > males; middle age

ii. Irregular, hard thyroid that is adherent to adjacent structures

iii. May mimic carcinoma and present with stridor, dyspnea, or dysphagia

c. Micro i. Dense fibrous replacement of the thyroid gland

ii. Chronic inflammation d. Associated with retroperitoneal and mediastinal fibrosis

Thyroid NeoplasiaAdenomas

a. Follicular adenomas are the most commonb. Clinical features

i. Usually painless, solitary nodules In first 20 yrs life likely malignant than older person ii. "Cold nodule" on thyroid scans iii. May be functional and cause hyperthyroidism (toxic adenoma)

2. Papillary carcinoma a. Epidemiology

i. Account for 80% of malignant thyroid tumors

ii. Females > males; age 20‑50 iii. Risk factor: radiation exposure

b. Micro i. The tumor typically exhibits a papillary pattern.

ii. Occasional psammoma bodiesiii. Characteristic nuclear features Clear "Orphan Annie eye" nuclei Nuclear

grooves

Intranuclear cytoplasmic inclusionsc. Lymphatic spread to cervical nodes is common.d. Treatment

i. Resection is curative in most cases.ii. Radiotherapy with iodine 131 is effective for metastases.

e. Prognosis: excellent; 20‑year survival = 90%

Follicular carcinomaa. Accounts for 15% of malignant thyroid tumorsb. Females > males; age 40‑60c. Hematogenous metastasis to the bones or lungs is common.d. High mortality rate because most present with distant mets

Medullary carcinoma

a. Accounts for 5% of malignant thyroid tumors

b. Arises from C cells (parafollicular cells) and secretes

calcitonin

c. Micro: nests of polygonal cells in an amyloid stroma

d. Minority (25%) are associated with MEN 2 and MEN

3 syndromesTreatment: primarily surgical

- Advance disease external RT and chemo

Anaplastic carcinoma

a. Presentation i. Females > males; age > 60 ii. Firm, enlarging, bulky mass

iii. Dyspnea and dysphagia iv. Tendency for early widespread

metastasis and invasion of the trachea and esophagus b. Micro: undifferentiated, anaplastic, and pleornorphic cells c. Prognosis: very aggressive and rapidly

fatal

Diagnosis Fine needle aspirate vs. excision - Hx RT to neck or head - rapidly growing nodule - satellite LN and/or distant mets - Hoarseness or dysphagiaRx: Well differentiated neoplasm should be excised - TSH suppression - RAI ablation

Q1 An 18yo old boy presents with a 1 month history of slowly enlarging neck mass. You palpate a 2-cm mass in the superior lobe of the rt. thyroid with no lymphadenopathy.

Of the following, the BEST next step is to:A. Begin therapy with RAIB. Obtain anteroposterior and lateral CXRC. Perform needle bx of the neckD. Perform total thyroidectomyE. Prescribe oral cephalexin

Q2. 15yo female presents with an asymptomatic goiter. She has type 1 diabetes that was diagnosed at age 7 years

Of the following, study that is MOST likely to establish the diagnosis is

A. Measurement of antiperoxidase antibodiesB. Needle bx of thyroidC. Technetium thyroid scanD. Thyroid-binding globulin levelsE. US of the thyroid

Q3. 44yo male involved in a MVA unresponsive intubated in ICU with multiple orthropedic injuries. He is stabilized medically on day 2 undergoes open reduction and internal fixation of right femur and right humerus. After returning to the ICU, his TSH is 0.3mU/L and total T4 is normal. T3 is 0.6 micrograms/dl. What is the next appropriate step in the management of this patient?

A. Start levothyroxineB. RAIU scanC. Thyroid USD. Observe patientE. Initiate prednisone

Q4. Which of the following statements regarding hypothyroidism is true?

A. Hashimoto’s thyroiditis is the most common cause of hypothyroidism worldwide

B. The annual risk of developing overt clinical hypothyroidism from subclinical hypothyroidism in patients with positive thyroid peroxidase antibodies is 20%.

C. Hashimoto’s is characterized by marked infiltration of thyroid with activated T and B cells

D. Low TSH excludes the diagnosis of hypothyroidismE. Thyroid peroxidase antibodies are present in 50% of

patients with autoimmune hypothyroidism

References

American College of Physicians

MKSAP 13 MedStudy Pediatric Board Review Harrison’s Principle of Internal Medicine