Transcript ENDOCRINOLOGY BOARD REVIEW

ENDOCRINOLOGY
BOARD REVIEW
THYROID DISORDERS
Henri 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
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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 monoand 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
Secretion
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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
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
High
Thyrotoxicosis
RAIU
Normal
Subclinical hypothyr’ism
TRH to confirm
Low
Pituitary hyperthyr’ism
N/A
LOW
3rd Test
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 Pathology
A. 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 Hyperthyroidism
1. General features of hyperthyroidism
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
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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
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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:
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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 methimazole
mechanism: Both inhibit the coupling of
iodotyrosines, oxidation and
binding of iodide
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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
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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 needed
b. Iodide
c. Lugol (5% iodine and 10% K iodine)
d. Methimazole
Hypothyroidism
a. Clinical features
i. Fatigue
ii. 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. Constipation
vi.Anovulatory cycles
b. Lab
i. 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, macroglossia
Rx: Initial dose: Sodium L-tyroxine 10-15
microgrms/kg/day( should not be mixed soy
protien or iron) Then, 4 micrgms/kg/day
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Thyroiditis
1.
Hashimoto's thyroiditis
a. Definition: chronic autoimmune disease characterized by
immune destruction of the thyroid gland and hypothyroidism
b. Most common noniatrogenic cause of hypothyroidism and Goiter
in children > 6yo and adults in US
c. Clinical presentation
i. Females > males; age 40-65
ii. Painless goiter
iii. Hypothyroid
iv. 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 thyroiditis
a. 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 Neoplasia
Adenomas
a. Follicular adenomas are the most common
b. 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 bodies
iii. Characteristic nuclear features Clear "Orphan Annie eye" nuclei Nuclear grooves
Intranuclear cytoplasmic inclusions
c. 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 carcinoma
a. Accounts for 15% of malignant thyroid tumors
b. Females > males; age 40-60
c. 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 syndromes
 Treatment:
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 dysphagia
Rx: Well differentiated neoplasm should be excised
- TSH suppression
- RAI ablation
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Q1 An 18yo old boy presents with a 1 month history
of slowly enlarging neck mass. You palpate a 2cm 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 RAI
B. Obtain anteroposterior and lateral CXR
C. Perform needle bx of the neck
D. Perform total thyroidectomy
E. 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 antibodies
B. Needle bx of thyroid
C. Technetium thyroid scan
D. Thyroid-binding globulin levels
E. 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 levothyroxine
B. RAIU scan
C. Thyroid US
D. Observe patient
E. 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 hypothyroidism
E. 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