Transcript
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S3 - Lec 10: Thyroid, Parathyroid, and Adrenals
N i n a I a n J o h n G R a c h e l
a r k J o c e l l e J u n j u
n G i e n a h J h o K a t h A y n z J e G l a d N i c k i e R i c o T i t s e r D a d a n g N i ň a A r l e n e V i v s P a u l F . R i c o F . R e n
a i R e v s
a v i s J e p a y Y a n a
a y i S e r g e H u n g T o p e A g n e s B i e n
THYROID GLAND
HISTORY
1200’s AD
- Advancements in goiter procedures included applying hot irons
through the skin and slowly withdrawing them at right angles. The
remaining mass of pedicled tissue is excised
- Patients were tied to the table and held down to prevent unwanted
movements
- Most died from hemorrhage or sepsis
1646 AD
- Willhelm Fabricus performed a thyroidectomy with standard
surgical scalpels
- The 10 y/o girl died, and he was imprisoned
1808 AD
- Guillaume Dupuytrem performed a total thyroidectomy
- The patient died postoperatively of ―shock‖
- Condemned for years as heroic and butchery
1850- French Academy of Medicine proscribed any thyroid surgery
Mid-1800’s- only 106 documented thyroidectomies
- Mortality 40%: exsanguination and sepsis
1842- Crawford Long uses ether anesthesia
1867- Lister describes antisepsis (lancet)
1874- Pean- invents hemostat
1883- Neuber- Cap and gown (asepsis)
1870’s-80’s- Billroth- merges a leader in thyroid surgery (Vienna) - Mortality-8%
- Shows need for RLN preservation
- Defines need for parathyroid preservation (von Eiselberg)
- Emphasis on speed
1883- Kocher’s performs a retrospective review
- 5000 career thyroidectomies
- Mortality rates decreased
40% in 1850 (pre-Kocher and Billroth)
12.6% in 1870’s (Kocher begins practice)
0.2% in 1898 (end of Kocher’s career)
- Many patients developed cretinism or myxedema
- “cachexia strumipriva‖ to describe this condition
Kocher emerges as leader in thyroid surgery (Bern)
- Mortality:
1889-2.4%
1900- 0.18%
- Emphasis on meticulous technique
In 1909 Kocher was awarded the Nobel Prize for medicine in
recognition ―for his works on the physiology, pathology, and surgery of
the thyroid gland.‖
THYROID DEVELOPMENT
outpouching of the primitive foregut around the third week of gestatio
Foramen cecum - site of origin of thyroglossal duct between floor o
bronchial arches 1 and 2. A depression of the posterior tongue
Thyroglossal duct - endodermal down growth of thyroid epithelium
from it. Developing tissue invades hypobronchial mesenchyme which
gives capsule and septa
Sites of thyroglossal cysts - (move up with protrusion of tongue
remnant thyroid tissues (lingual thyroid), fistulae, sinuses and
pyramidal lobe
Retrosternal thyroid- if developing process goes too far
The ultimobronchial bodies (5th pouch) give ―C‖ cells
Descent of the thyroid gland
o Initial descent starts anterior to the pharyngeal gut
o Thyroid still connected to the tongue via the thyroglossal duct
o Later- tubular duct solidifies then obliterates entirely (during
gestational weeks 7-10)
o Foramen cecum- opening of the thyroglossal duct into the
tongue
o Pyramidal lobe
- In up to 50% people
- Persistence of the inferior end of the thyroglossal duct (failure t
obliterate)
- May be attached to the hyoid bone (~thyroglossal duct cyst) or
may be incorporated into a thyroglossal duct cyst.
o Further descent- ant (ventral) to the hyoid bone and laryngeal
cartilage
o During descent- thyroid forms its mature shape: median isthmuconnecting 2 lateral lobes
o Descent complete at 7th gestational week
DEVELOPMENTAL ABNORMALITIES
Thyroglossal duct cyst
- most commonly encountered congenital cervical anomalies
- failure of the duct to disappears by the eighth week of gestation
- 1% TDC contains cancer (papillary 85%)
- Lined by PCCE
- Duct failure to atrophy
- Can form a sinus
- Rx- ―sistrunk‖ procedure (en bloc cystectomy and excision of thcentral hyoid bone to minimize recurrence)
Ectopic thyroid
- Can occur anywhere along the path of descent
- Most common at the base of the tongue ―lingual thyroid‖
Lingual thyroid
- failure of the median thyroid anlage to descend normally
- Many of these patients develop hypothyroidism (evaluate px fo
surg)
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- Rx- exogenous thyroid hormone & radioactive I ablation followed
by hormone replacement
Pyramidal Lobe
- Persistent structure connected at the distal thyroid projecting up
from the isthmus, lying just to the left or right of the midline
- Palpable in thyroid hypertrophy
Accessory thyroid- From remnants of thyroglossal duct
- May be functional but insufficient for normal function of thyroid
Thyreos - ―shield‖-convex anteriorly and concave posteriorly
Pseudolobulation - fibrous capsule with septae
Right and left lobe connected by isthmus
Brownish red, highly vascular gland
Location: ant neck at C5-T1, overlays 2nd-4th tracheal rings
Avg width: 12-15 mm (each lobe)
Avg height: 50-60 mm long
Avg weight: 20-30g in adults (slightly more in women)
A. Enlarges during menstruation and pregnancy
Pyramidal lobe
- Often ascends from the isthmus or the adjacent part of either
lobe (usually L) up to the hyoid bone
- May be attached by a fibrous/fibromuscular band ―levator‖ of
the thyroid gland
Relations with strap muscles
- Lateral - sternothyroid
- Anterior - omohyoid, sternohyoid
- Inferior - SCM (lower portion)
Vascular anatomy
A. Arterial
Superior and inferior thyroid anterior (occ thyroidea ima)
++collateral anastomoses (ipsi and contralaterally)
Thyroidea ima (when present) originates from the aortic arch o
innominate artery, enters the thyroid at inferior border of
isthmus
1. Superior Thyroid artery
First ant branch of ECA
Descends laterally to the larynx under the omohyoid and
sternohyoid muscles
Runs superficially on the ant border of the lateral lobe, sending a
branch deep into the gland before curving toward the isthmus
where it anastomoses with the contralateral artery
Relationship with SLN:
- Cephalad to the superior pole, ext branch of SLN runs with
STA before turning medially supply cricothyroid muscle
- Careful with ligating artery
2. Inferior Thyroid artery SCA thyrocervical trunk ITA
ITA ascends vertically and then curves medially to enter the
tracheoesophageal groove (posterior to carotid sheath)
Branches penetrate the posterior aspect of the lateral lobe
Relationship with RLN:
- RLN ascends in the TE groove and enter the larynx betwee
the inferior cornu of the thyroid cartilage and the arch of the
cricoid
- RLN can be found after it emerges from the superior
thoracic outlet
Sup: thyroid lobe
Lat: CCA
Med: trachea- Relationship bet RLN and ITA highly variable (Redd, 1943-
described 28 variations)
Ex:
Deep to ITA (40%)
Superficial (20%)
b/w braches of artery (35%)
- also only 17% of the time is the nerve/artery relationship th
same on both sides
- at the level ITA- extralaryngeal branches RLN present 5% o
the time
B. Venous
3 pairs of veins:
1) STV- asc along STA and becomes tributary of IJV
2) MTV- directly lateral IJV
3) ITV (variable)
- R- passes ant to the innominate artery R BCV or ant
trachea L BCV
- L- drainage L BCV
- Both inferior veins form a common trunk ―thyroid ima
vein‖ empties into L BCV
C. Lymphatics
- Extensive, mutlidirectional flow
- Periglandular prelaryngeal (Delphian)
pretracheal paratracheal (along RLN)
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brachiocephalic (sup mediastinum) deep cervical
thoracic duct
- ND: regional metastasis of thyroid carcinoma are superior
and lateral, along IJV ie: invasion of the pretracheal and
paratracheal LNs and obstruction of normal lymph flow.
- Regional lymph nodes include pretracheal, paratracheal,
perithyroidal, recurrent laryngeal nerve, superior
mediastinal, retropharyngeal, esophageal, and upper,
middle, and lower jugular chain nodes. Classified intoseven levels
Innervation
A. Principally from ANS
Parasympathetic fibers- from vagus
Sympathetic fibers- from superior, middle and inferior ganglia of
the sympathetic trunk
B. Enter the glans along with the blood vessels
C. Recurrent layngeal nerve
Innervates all larynx except cricothyroid
Closely associated with ITA
NB: ―non recurrent LN’ ~5/1000 pt’s on R side
- When retroesophageal R SCA from dorsal aortic arch
- NRLN- branches fr X at ~ cricoid cartilage
- Directly enters the larynx without looping around SC
- L sided- only when R aortic arch and ligamentum
arteriosum concurrent with L retroesophageal subclavian
artery
Histology
Under middle layer of deep cervical fascia (pretracheal) thyroid
inner true capsule thin and closely adherent to the gland
Capsule extensions within the gland form septae, dividing it into lobes
and lobules
Lobules are composed of follicles= structural units of the gland
layer epithelium enclosing a colloid-filled cavity
Colloid (pink on H&E stain) contains an iodinated glycoprotein,
iodothyroglobulin (precursor of thyroid hormones)
Follicles= variable size
Surrounded by dense plexuses of fenestrated capillaries, lymphatic
vessels, and sympathetic nerves
Epithelial cells= 2 types
Principal (ie follicular)- formation of colloid (iodothyroglobulin)
Parafollicular (ie C cells- clear, light), lie adjacent to the follicles withi
the basal lamina produce calcitonin
THYROID PHYSIOLOGY
Production of T3 and T4- iodine dependent process
Three sequential steps:
- Active transport of iodide to the gland
- Organification of iodide with thyrosine—MIT and DIT
- Coupling of hormonally inactive MIT and DIT to form the
physiologically effective iodothyroninines, T3 and T4
Thyroid hormone synthesis
- Iodide trapping
- Oxidation of iodide and iodination of thyroglobulin
- Coupling of iodotyrosine molecules within thyroglobulin
(formation of T3 and T4)
- Proteolysis of thyroglobulin
- Deiodination of iodotyrosines
- Intrathyroidal deiodination of T3 and T4
Wolff-Chaikoff Effect
- Increasing dose of I - increase hormone synthesis initially
- Higher doses cause cessation of hormone formation
- This effect is countered by iodide leak f rom normal thyroid tissu
- Patients with autoimmune thyroiditis may fail to adapt and
become hypothyroid
Jod-Basedow Effect
- Opposite of Wolff-Chaikoff effect
- Excessive iodide loads induce hyperthyroidism
- Observed in hyperthyroid disease processes
Grave’s disease
Toxic multinodular goiter
Toxic adenoma
- This effect may lead to symptomatic thyrotoxicosis in patients
who receive large iodine doses from
Dietary changes
Contrast administration
Iodine containing meds (Amiodarone)
TSH
- Produced by adenohypophysis thyrotrops
- Up-regulated by TRH
- Down-regulated by T3 and T4
- Travels through portal venous system to cavernous sinus, body
- Stimulates several processes
Iodine uptake
Coloid endocytosis
Growth of thyroid gland
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Thyroid hormone
- Majority of circulating hormone is T4
98.5% T4
1.5 % t3
- Total hormone load is influenced by serum binding proteins
Albumin 15%
Thyroid binding globulin 70%
Transthyretin 10%
- Regulation is based on the free component of thyroid hormone
EVALUATION
Thyroid evaluation
1. History and PE
2. TRH
3. TSH (N= .5-5 U/ml)
4. Total T3 (1.5-3.5 nmol/L), T4 (55-150 nmol/L)
5. Free T3 (3-9 pmol/L),T4 (12-28 pmol/L)
6. Thyroglobulin
7. Antibodies: antiTg, Anti-TPO, TSI
History- Age
- Gender
- Exposure to radiation
- s/sx of hyper/hypothyroidism
- rapid change in size
with pain may indicated hemorrhage into nodule
without pain may be a bad sign
Physical exam
- Suggestive of malignancy:
Fixation
Adenopathy
Fixed cord
Induration
Stridor
- Not very sensitive/specific
Workup
- CT scan/ MRI
- TFTs
TSH is the screening test of choice for thyroid function (nml
0.3-5 mU/L)
Unbound, free portion of t4 is indicative of thyroid status Previously, estimate of FT4 was determined by means of
T3 resin uptake (total T4x CRU free thyroxin level)
Free t4 assay is currently preferred
(see diagram at the back)
- Plain films
Not routinely ordered
May show:
Tracheal deviation
Pulmonary metastasis
Calcifications (suggest papillary or medullary
- Ultrasonography
Thyroid vs non-thyroid
Good screen for thyroid presence in children
Cystic vs solid
Localization for FNA or injection
Serial exam of nodule size
2-3 mm lower end
May distinguish solitary nodule from multinodular goiter
Dominant nodule risks no different
Findings suggestive of malignancy
Presence of halo
Irregular border
Presence of cystic components
Presence of calcifications
Heterogenous echo patterns
Extrathyroidal extension
No findings are definitive
- Nuclear Medicine
Concept
Uses
Metabolic studies
Imaging
Iodine is taken up by gland and organified
Technetium trapped but not organified
Usually only for papillary and follicular
Rectilinear scanner (historical interest) vs. Scintillation
camera
Radioisotopes
I-131
I-123
I-125 Tc-99m
Thallium-201
Gallium 67
RAIU
Scintillation counter measures radioactivity after I-123
admin
Uptake varies greatly by iodine status
- Indigenous diet (normal uptake 10% vs 90%)
- Amiodarone, contrast study, topical betadine
o Elevated RAIU with hyperthyroid symptoms
- Graves’
- Toxic goiter o Low RAIU with hyperthyroid symptoms
- Thyroiditis (subacute, active Hashimoto’s)
- Hormone ingestions (thyrotoxicosis facada,
Hamburger Thyrotoxicosis)
- Excess I- intake in Graves’ (Jod-Badesdow
Effect)
- Ectopic thyroid CA (Struma ovarii)
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- Fine Needle Aspiration Biopsy
o Emerged in 1970’s- has become standard first-line test
of diagnosis
o Concept
o Results comparable to large-needle biopsy, less
complications
o Safe, efficacious, cost-effective
o
Allow pre-op diagnosis and therefore planning o Some use for sclerosing nodules
o Results:
- Benign
- Malignant
- Suspicious/indeterminate
- Insufficient/inadequate
o Technique
- 25-gauge needle
- Multiple passes
- Ideally from periphery of lesion
- Re-aspirate after fluid is drawn
- Immediately smeared and fixed
- Papanicolaou stain commono Problems:
- Sampling error
Small (<1cm)
Large (>4 cm)
- Hashimoto’s vs lymphoma
- Follicular neoplasm
- Fluid-only cysts
- Somewhat dependent on skill of cytopathologist
MOST COMMON TYPES OF THYROID DISEASE
1) Hyperthyroidism refers to overactivity of the thyroid gland leading to excessive
synthesis of thyroid hormones and accelerated metabolism in
the peripheral tissues. The secretion of thyroid hormone is no
longer under the regulatory control of the hypothalamic-pituitary
center.
Differential Diagnosis of Hyperthyroidism
Increased hormone synthesis (increasedRAIU)
Release of preformedhormone (decreased RAIU)
Graves' disease (diffuse toxic goiter) Thyroiditis—acute phase of Hashimoto's thyroiditis,subacute thyroiditis
Toxic multinodular goiter Factitious (iatrogenic)thyrotoxicosis
Plummer's disease (toxic adenoma) "Hamburger thyrotoxicosis"
Drug induced—amiodarone, iodine(Jodbasedow)
Thyroid cancer
Struma ovarii
Hydatidiform mole
TSH-secreting pituitary adenoma
TOXIC GOITER
Graves’ Disease
Clinical findings (pretibial myxedema, opthalmopathy)
Anti-TSH receptor Ab
High RAUI
Thyroiditis
- Clinical findings (painful thyroid in subacute thyroiditis)- Low RAUI
Recent Iodine Admin
- Amiodarone
- IV conrast
- Change in diet
FNA evaluation
- Not indicated in hyperthyroid nodules due to low
incidence of malignancy
- FNA of hyperthyroid nodules can mimic follicular
neoplasms
Risks of hyperthyroidism
- Atrial fibrillation
- Congestive heart failure
- Loss of bone mineral density
- Risks exist for both clinical or subclinical disease
Toxic goiter
Toxicity is usually londstanding
Acute toxicity may occur in hyperthyroid states (Jod-Basedow
effect) with
- Relocation to I replete area- Contrast admin
- Amiodarone (37% I)
Treatment for Toxic MNG
- Anti-thyroid drugs
May require prolonged tx
- Radioiodine
Primary tx for toxic MNG
Large I-131 dose required due to gland size
Goiter size reductions by 40% within 1 yr
Risk of hypothyroidism 11%-24%
May require second dose
- Surgery
Used for compressive symptoms
Hypothyroidism occurs in up to 70% of subtotal
thyroidectomy pts
Pre-surgical stabilization with thionamide meds
Avoid SSKI due to rick for acute toxic symptoms
Graves Disease Tx
B-blockers for symptoms
Anti-thyroid meds
- May re-establish euthyroidism in 6-8 weeks
- 40-60% incidence of disease remission
-
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Radioiodine ablation
- 10% incidence of hypothyriodism at 1 yr
- 55-75% incidence of hypo at 10 yrs
- Avoid RAI in children and pregnancy
Surgery
- Large goiters not amenable to RAI
- Compressive symptoms
- Children, pregnancy
- 50-60% incidence of hypothyroidism
Toxic Ademona
Thyrotoxicosis
- Hyperfunctioning nodules <2 cm rarely lead to
thyrotoxicosis
- Most nodules leading to thyrotoxicosis are >3cm
Tx indications
- Post-menopausal female due to increased bone loss
- Patients over 60 due to high risk of atrial fibrillation
- Adenomas greater than 3 cm
Tx- Antithyroid meds
Not used due to complicationsof long-term tx
- Radiodiodine
Cure rate >80% (20 mCi I-131)
Hypothyroidism risk 5%-10%
Second dose of I-131 needed in 10% to 20%
Patients who are symptomatically toxic may require
control with thionamide meds before RAI to reduce
risk of worsening toxicity
- Surgery
Preferred for children and adolescents
Preferred for very large nodules when high I-131
doses needed Low risk of hypothyroidism
- Ethanol injection
Rarely done in US
May achieve cure in 80%
2) HYPOTHYROIDISM
Types of hypothyroidism
o Primary- thyroid gland failure
o Secondary- pituitary failure
o Tertiary- hypothalamic failure
o Peripheral resistance
S/Sx of Hypothyroidism (SLUGGISH)
o S-leepiness, fatigue, Lethargy
o L-oss of memory, trouble concentrating
o U-nusually dry, coarse skin
o G-oiter (enlarged thyroid)
o G-radual personality change, depression
o I-ncrease in wgt, bloating or puffiness (edema)
o S- ensitivity to cold
o H-air loss, sparseness of hair
Cause is determined by geography
o Hashimoto’s in industrialized countries
o May be due to iodine excess in some coastal areas
Dx
o Los FT4, high TSH (primary, check for Ab)
o Low FT4, low TSH (secondary or tertiary, TR stimulation test, MR
Txo Levothyroxine (T4) due to longer half-life
o Tx prevents bone loss, cardiomyopathy, myxedema
Hypothyroidism causes
o Agenesis
o Thyroid destruction
Hashimoto’s thyroiditis
Surgery
I-131 ablation
Infiltrative disease
Post-laryngectomy
o Inhibition of function
Iodine deficiency Iodine admin
Anti-thyroid med (PTU, Methimazole, Lithium, Interferon)
Inherited defects
o Transient
Postpartum
Thyroiditis
3) HASHIMOTO’S (CHRONIC, LYMPHOCYTIC)
Most common cause of hypothyroidism
Result of anti-bodies to TPO, TBG
Commonly presents in females 30-50 yrs
Usually non-tender and asymptomatic
Lab values
o High TSH
o Low T4
o Anti-TPO Ab
o Anti-TBG Ab
Tx: levothyroxine
4) HASHIMOTO’S THYROIDITIS
Most common cause of goiter and hypothyroidism
Physical
o Painless, diffuse goiter
Lab studies
o Hypothyroidism
o Anti-TPO Ab (90%)
o Anti thyroglobulin Ab (20-50%)
o Acute hyperthyroidism (5%)
Tx
o Levothyroxine if hypothyroid
o Triiodothyronine (for myxedema)
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o Thyroid suppression (levothyroxine) to decrease goiter
size
Contraindications
Stop if no resolution noted
o Sugery for compression or pain
5) SILENT THYROIDITIS (POST-PARTUM THYROIDITIS)
Silent thyroiditis is termed post-partum thyroiditis if it occurs withinone year of delivery
Clinical
o Hyperthyroid symptoms at presentation
o Progression to euthyroidism followed by
hypothyroidism for up to 1 yr
o Hypothyroidism generally resolves
Dx
o May be confused with post-partum Graves’ relapse
Tx
o B-blockers during toxic phase
o No anti-thyroid med indicated
o Iopanoic acid (Telopaque) for severe hyperthyroidism
o Thyroid hormone during hypothyroid phase. Mustwithdraw in 6 mos to check for resolution
6) SUBACUTE THYROIDITIS (DEQUERVAIN’S GRANULOMATOUS)
Most commone cause of painful thyroiditis
Often follows URI
FNA may reveal multinucleated giant cells or granulomatous
change
Course
o Pain and thyrotoxicosis (3-6 wks)
o Asymptomatic euthyroidism
o Hypothyroid period (weeks to mos)
o Recovery (complete in 95% after 4-6 mos)
Dx
o Elevated ESR
o Anemia (normochromic, normocytic)
o Low TSH, Elevated T4>T3, low anti-TPO/Tgb
o Low RAI uptake (same as silent thyroiditis)
Tx
o NSAID’s and salicylates
o Oral steroids in severe cases
o B-blockers for symptoms of hyperthyroidism, iopanoic
acid for severe symptoms
o PTU not indicated sinced excess hormone results
from leak instead of hyperfunctiono Symptoms can recur requiring repeat tx
o Graves’ ds may occasionally develop as a late
sequellae
7) ACUTE(SUPPURATIVE) THYROIDITIS
Causes
o 68% Bacterial (S. aureus, S. pyogenes)
o 15% fungal
o 9% mycobacterial
May occur secondary to
o Pyriform sinus fistulae
o Pharyngeal space infections
o Persistent thyroglossal remnants
o Thyroid surgery wound infxn
More common in HIV
Dx
o Warm, tender, enlarged thyroid
o FNA to drain abscess, obtain culture
o RAU normal (vs dec in DeQuervain’s)
o CT or US if infected TGDC suspected Tx
o High mortality without prompt tx
o IV Antibiotics
Nafcillin/ Gentamycin ____cephin for
empiric therapy
o Search for pyriform fistulae (BA swallow, endoscopy)
o Recovery is usually complete
8) REIDEL’S THYROIDITIS
Rare disease involving fibrosis of the thyroid gland
Dx
o Thyroid Ab are present in 2/3o Painless goiter “woody”
o Open biopsy often needed
o Associated with focal sclerosis syndromes
(retroperitoneal, mediastinal, retroorbital, and
sclerosing cholangitis
Tx
o Resection for compressive symptoms
o Chemotherapy with tamoxifen, methotrexate or
steroids may be effective
o Thyroid hormone ony for symptoms of hypothyroidism
9) GOITER
Any enlargement of the thyroid gland
Endemic goiter
o Areas where>5 %6-12 yo have goiter
o Common in China and Central Africa
Sporadic Goiter
o Areas where <5% of children 6-12 yo have goiter
o Multinodular goiter in sporadic areas often denotes
presence of multiple nodules rather than gross gland
enlargement
Familial
Etiology of nontoxic goiter
o Endemic: iodine def, dietary goitrogens
o Meds: iodide, amiodarone, lithium, thyroiditis:
subacute, chronic
o Familial: hormone dysgenesis from enzyme defects,
resistance to thyroid hormone
o Neoplasm
10) SOLITARY THYROID NODULE (STN)
Thyroid Nodule
Nodules common, whereas cancer relatively uncommon
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Goal is to minimize ―unnecessary‖ surgery but not miss any
cancer
Epidemiology
Increases with age
Autopsy- 9th decade-80% women, 65%
men
Higher in women (1:2:1 4:3:1)
Estimated 5-15% of nodules are cancerous
Although cancer more common in women, a nodulein a man is more likely cancer
o Hot, Warm, Cold
Study 4457 pts with nodules
All scanned, all surgery
Results:
Cold 84% 16% cancer
Warm 10% 9% cancer
Hot 5.5% 4% cancer
o Hot nodules
Most authors feel that hot nodule in hyperthyroid pt
has low malignancy risk
Nodule in clinically hyperthyroid pt may be cold
nodule against background of Graves, so scan mayhelp
o Pregnancy increases risk
One study: u/s detection nodules-
9.4% nulliparous women
25%women previously pregnant
Attributed to increased renal iodide excretion and
basal metabolic rate
Rosen: nodules presenting during pregnancy
30 pts, 43% were cancer
HCG may be growth promoter (TSH-like
activity)
o Children
Nodule more likely to be cancer in adults
1950s: 70%
Current: approx 20%
10% thyroid cancer age <21
Thyroid cancer 1.5-2.0% all pediatric malignancies
More likely present with neck metastasis
Most common cause of lymphocytic thyroiditis
o Conclusion
Fine-needle aspiration initial test of choice
Role for TSH, ultrasound, nuclear scan
As always, knowledge of pathophysiology and
constant vigilance key to optimum patient care
11) THYROID CANCER
The most common endocrine malignancy
Among the 10 most common site of malignancy in the Phil
Characteristically slow-growing
Age is considered the most impt prognostic factors
Etiology
Irradiation in childhood (esp thymus, 20 yrs latent
period)
Familial (medullary ca assoc with inc calcitonin,
pheochromocytoma and mucosal neuromas
Endemic goiter (due to inc TSH, debated)
Pathology
From follicular cells- follicular, papillary or anaplast
Parafollicular cells-medullary- MEN II-A; MEN II-B
Lymphoma- rare
Metastatic- bronchogenic ca, hyperhephroma
Types of Thyroid Cancer
1) Papillary (80-85%)- develops from thyroid follicle cellsin 1 or both lobes; grows slowly but can spread
2) Follicular (5-10%)- common in countries with
insufficient iodine consumption; lymph node metastase
are uncommon
3) Medullary (5-10%)- develops from C cells, can spread
quickly; sporadic and familial types
4) Anaplastic (5%)- develops from existing papillary or
follicular cancers, aggressive, usually fatal
5) Lymphoma (5%)- develops from lymphocytes,
uncommon
Oncogenes and Tumor-Suppressor Genes Involved in Thyroid
Tumorigenesis Gene Function Tumor
Oncogenes
RET Membrane receptor withtyrosine kinase activity
Sporadic and familial MTC,PTC (RET/PTCrearrangements)
MET Same Overexpressed in PTC
TRK1 Same Activated in some PTC
TSH-R Linked to heterotrimeric Gprotein
Hyperfunctioning adenoma
Gs(gsp)
Signal transductionmolecule (GTP binding)
Hyperfunctioning adenoma,follicular adenoma
ras Signal-transductionprotein
Follicular adenoma andcarcinoma, PTC
PAX8/PPAR1 Oncoprotein Follicular adenoma, follicularcarcinoma
Tumor suppressors
p53 Cell-cycle regulator,arrests cells in G1,induces apoptosis
Dedifferentiated PTC, FTC,anaplastic cancers
p16 Cell-cycle regulator,
inhibits cyclin-dependentkinase
Thyroid cancer cell lines
PTEN Protein tyrosinephosphatase
Follicular adenoma andcarcinoma
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TNM CLASSIFICATION OF THYROID TUMORS
Papillary or Follicular Tumors
Stage TNM Younger than age 45 Years
I Any T, Any N, M0II Any T, Any N, M1
Age 45 Years and older I T1, N0, M0II T2, N0, M0III T3, N0, M0; T1-3, N1a, M0IVA T4a, N0-1a, M0; T1-4a, N1b, M0IVB T4b, Any N, M0IVC Any T, any N, M1
Medullary Thyroid Cancer Stage TNMI T1, N0, M0II T2-3, N0, M0III T1-3, N1a, M0IVA T4a, N0-1a, M0; T1-4a, N1b, M0IVB T4b, any N, M0IVC Any T, Any N, M1
Anaplastic Cancer Stage TNM
IVA T4a, Any N, M0IVB T4b, Any N, M0IVC Any T, Any M, M1
1) PAPILLARY THYROID CANCERS
Most common type
Makes up about 80% of all thyroid ca in the US
Females outnumber males 3:1
o Highest incidence in women in midlife
―Orphan Annie‖ nuclei
Psammoma bodies
Most common, well-differentiated, slow-growing, lymphatic
spread, good prognosis Characteristics
o Unencapsulated tumor nodule with ill-defined margins
o Tumor typically firm and solid
o May present as nodal enlargement
o Commonly metastasizes to neck and mediastinal lymph
nodes
40 to 60% in adults and 90% in children
o <5% pts have distant metastases at time of dx
Lung is most common site
2) FOLLICULAR THYROID CANCER
Second most common thyroic ca Solid invasive tumors, usually solitary and encapsulation
Usually stays in the thyroid gland, but can spread to the bones,
lungs, and CNS
Usually doesn’t spread to lymph nodes
Capsular invasion must be present
FNA inadequate for diagnosis
Well-differentiated, 2nd most common, more aggressive, vascular
invasion and spread
Dx and prognosis
o Most FTCs present as an asymptomatic neck mass
o If caught early, this type is often curable
Tumors >3cm has much higher mortality rate
Hurthle Cell Cancer
o A variant of follicular cancer that tends to be aggressive
o Represents about 3% to 5% of all types of thyroid cancers
o Prognosis:
May be benign or malignant, based on demonstratio
of vascular or capsular invasion
Malignancies tend to have a worse prognosis than
other follicular tumors and rarely respond to I -131therapy
Tend to be locally invasive
3) ANAPLASTIC THYROID CANCER
Extremely aggressive and exceptionally virulent
Composed of wholly or in part of undifferentiated cells
4) MEDULLARY THYROID CANCER
Tumor arising from calcitonin-secreting C-cells
Mortality rate 10% to 20% in 10 yrs
Types:
o 70-80% of cases are sporadic (median age =51 years)
o 20-30% are part of 3 familial autosomal dominantsyndromes (MEN-2A, MEN-2B, or familial non-MEN
medullary thyroid cancer [median age=21yrs])
Metastases
o Cervical lymph node metastases occur early
o Tumors >1.5 cm are likely to metastasize often to bone,
lungs, liver, and CNS
o Metastases usually contain calcitonin and stain for amyloid
5) PRIMARY THYROID LYMPHOMA
A rare type of thyroid cancer
o Affects fewer than 1 in 2 million people
o Constitutes 5% of thyroid malignancies
Characterisitics and dx
o Develops in setting of pre existing lymphocytic
thyroiditis
o Often diagnosed bec of airway obstruction symptoms
o Tumors are firm, fleshy, and usually pale
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Treatment of Thyroid Cancer with Radioactive Iodine
o Destroys remnants or normal thyroid tissue
o Destroys thyroid cancer cells
o Identifies distant metastases
o Maximizes sensitivity and specificity of serum
thyroglobulin
NORMAL THYROID CANCER PATIENTS
o Minimum LT4 to suppress TSH without thyrotoxicosis
STANDARD TREATMENT FOR THYROID CANCER
STANDARD TREATMENT OF THYROID CANCER
PHASES OF FOLLOW UP
TREATMENT OF THYROID CANCER SUMMARY
Papillary and follicular thyroid cancer
o Generally excellent prognosis
o Risk for recurrence for as long as 30 years
Initial management
o Surgery and radioactive iodine
o LT4 suppressive therapy
Follow-up
o PE
o Radioactive iodine scans
o Serum Tg
o TSH and T4
COMPLICATIONS of THYROID SURGERY
Wound- seroma, infxn, poor scar
Rare- injury to sympathetic trunk
Bleeding
Injury to RLN or SLN
Thyrotoxic storm
Hypothyroidism
Hypocalcemia-most common acute post-op complication
THYROID METASTASIS
Breast
Lung
Renal
GI
Melanoma
PARATHYROID
LOCATION
Most commonly found about the middle third of the thyroid lobe, atthe level of the cricothyroid junction, and near the point where therecurrent laryngeal nerve passes beneath the inferior pharyngealconstrictor to enter the larynx.
Inferior glands usually found near the lower pole of the thyroidlobe or below the lobe in the thyro-thymic ligament; commonly liebelow the inferior thyroid artery and anterior to the recurrentlaryngeal nerve
Carotid sheath
Retropharyngeal
Intrathyroid
Retroesophageal
Thymic (66%) Mediastinal
EMBRYOLOGY
Brachial arches and pharyngeal pouches form in the 4 th week
Arises from the 4th brachial pouch
Superior parathyroids : the 4th pharyngeal pouch with thyroid
Inferior parathyroids : 3rd pharyngeal pouch with thymus
MORPHOLOGIC CHARACTERISTICS OF PARATHYROID GLANDS
Shape –oval, bean, or teardrop appearance or flat shape when juxtaposed to thyroid gland
Color-yellowish brown to reddish brown in normal parathyroidglands and lighter gray tone in pathological states.
VASCULAR ANATOMY OF THE PARATHYROID GLANDS
Normal parathyroid glands most commonly are supplied by asingle dominant artery (80%)
The length of the dominant artery supplying glands vary from 1-40mm.
ITA is dominant blood supply to both superior and inferior parathyroid glands most of the time.
pituitaryTSH
thyroidT4
total
thyroidectomy
RAI ablation
Supression therapy
whole body scan Tg
assay (after 1 yr)
Phase 1Determine extent of disease
Treat detectable disease
Initial surgery RAI ablation
Phase 2No detectable disease At risk for recurrence
Whole body scanStimulated Tg
Phase 3Long-term disease-free survivor Low risk for recurrence
Suppressed Tg assayTSH assayT4 assayNeck examination
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HISTOLOGY
50/50 parenchymal cells, stromal fat
Chief cells : secrete PTH
Waterclear cells
Oxyphil cells
CALCIUM
50% of the serum calcium is in the ionized form 40% bound to albumin
10% organic anions such as phosphate and citrate
Total serum calcium levels range from 8.5 to 10.5 mg/dL
Ionized calcium levels range from 4.4 to 5.2 mg/dL
PARATHYROID HORMONE
Synthesized in chief cells as large precursor-pre-prothyroidhormone
Cleaved intracellularly into proparathyroid hormone then to final84 AAPTH
PTH then metabolized by liver into hormonally active N-term andinactive C-term
CALCITONIN
Produced by thyroid C cells
Functions as an antihypercalcemic hormone
Increases phosphate excretion at the kidney
Useful as a marker of medullary thyroid cancer
Use in treating acute hypercalcemic crisis
VITAMIN D
Vitamin D family comprises of several different compounds, allhaving similar functions.
Most important is vit. D3 (cholecalciferol)
Derived from irradiation of 7-dehydrocholesterol in skin by UV
rays Causes Ca absorption from intestinal tract
Active form of this hormone is 1,25-dihydroxycholecalciferol(calcitriol)
The main effect of calcitriol is to increase intestinal absorption of Ca
HYPERPARATHYROIDISM
PRIMARY HYPERPARATHYROID
Normal feedback of Ca disturbed, causing increasedproduction of PTH
PTH: normal
Ca2+: high
Adenoma (80%) Multiple ademoma/hyperplasia (15-20%)
Carcinoma (1%)
Biochemical Features of Primary Hyperparathyroidism
Serum Tests Alteration
Calcium Increased, except in normocalcemic primaryhyperparathyroidism
Intact PTH Increased or inappropriately high
Chloride Increased or high normal
Phosphate Decreased or low normal
Serum Tests Alteration
Chloride:phosphate ratio Increased (usually >33)
Magnesium Unchanged or decreased (in patients withosteitis fibrosa cystica)
Uric acid Normal or increased
Alkaline phosphatase Normal or increased (in the presence of bondisease)
Acid –base status Mild hyperchloremic metabolic acidosis
Calcium:creatinineclearance ratio
>0.02 (vs. <0.01 in BFHH)
1,25-dihydroxy vitamin D Normal or increased
Urine Tests
24-Hour urinary calcium Normal or increased
SECONDARY HYPERTHYROIDISM
Defect in mineral homeostasis leading to a compensatoincrease in parathyroid gland fuction
PTH: appropriate
Ca2+: low
Chronic renal failure Vitamin D deficiency
TERTIARY HYPERPARATHYROIDISM
After prolonged compensatory stimulation, hyperplasticgland develops autonomous function
Continued excess PTH secretion following prolongedsecondary hyperparathyroidism
After kidney transplant
SIGNS/ SYMPTOMS
Asymptomatic (mild, <2.99)
―bones, stones, abdominal groans, psychic moans, musclefatigue
Bones Bones pain, arthralgiaRenal Stones, polyuriaG.I. Pain, duodenal ulcer, pancreatitisNeuro Depression, apathyMuscular Fatigue, chondrocalcinosis adn
pseudogout
PHYSICAL EXAMINATION 1. Usually nor helpful in diagnosis2. If a mass is palpable,suspect thyroid pathology or parathyroid
carcinoma- Band Keratopathy
Differential Diagnosis of Hypercalcemia
Hyperparathyroidism
Malignancy—hematologic (multiple myeloma), solid tumors (caused byPTHrP)
Endocrine diseases—hyperthyroidism, addisonian crisis, VIPoma
Granulomatous diseases—sarcoidosis, tuberculosis, berylliosis,histoplasmosis
Milk –alkali syndrome
Drugs—thiazide diuretics, lithium, vitamin A or D intoxication
Benign familial hypocalciuric hypercalcemia
Paget's disease
Immobilization
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DIAGNOSIS
Parathyroid Localization Studies
Study Advantages Disadvantages
Preoperative,noninvasive
99mTechnetium-
sestamibi scan
Allows planar and 3D
SPECT imaging
False-positive tests because
of thyroid nodules,lymphadenopathy; false-negative study more commonwith multiple abnormalparathyroids
Ultrasound Identification of juxta-and intrathyroidaltumors; relativelyinexpensive
False-positive results becauseof thyroid nodules, lymphnodes, esophageal lesions;false-negatives result fromsubsternal, ectopic, andundescended tumors
CT scan Localization of ectopic(mediastinal) glands
Not useful for juxta- or intrathyroidal glands; false-positives from lymph nodes;
relatively high cost; radiationexposure; requiresintravenous contrast;interference from shouldersand metallic clips
MRI scan Localization of ectopictumors; no radiationexposure; nointravenous contrast;no metal clip artifact;
Expensive; false-positivesfrom lymph nodes and thyroidnodules; cannot be used inclaustrophobic patients
Preoperative,invasive
FNA biopsy Helpful for
distinguishingparathyroid tumor fromlymphadenopathy
Experienced cytologist
needed
Angiogram Provides a road mapfor selective venoussampling; treatment of mediastinal tumors byembolization
Expensive; experiencedradiologist needed; neurologiccomplications
Venoussampling
Useful to lateralizetumor in equivocalcases
Expensive; experiencedradiologist needed
Intraoperative
PTH assay Immediate confirmation
of tumor removal
Expensive
RADIOLOGIC TEST
Hand and skull x-rays
Bone mineral density
Abdominal ultrasound – for renal stones(Table 37-11; indications for parathyroidectomy in patients withasymptomatic primary HPT)
SESTAMIBI-TECHNETIUM 99M SCINTOGRAPHY
Sestamibi taken up mitochondria of parathyroid cells greater thasurrounding parenchyma
Inject 20-25 millicuries of technetium-99m sestamibi. Imagesobtained at 10-15 minutes then 2-3 hours after the injection
Late phase preferable for detecting parathyroid adenomas, asthryroid nodules clear uptake faster than do parathyroidneoplasms
Sensitivity (solitary adenoma) ~ 100%, specificity ~90%. False positive:
1. Solid thyroid nodules (adenomas)2. Hurthle cell carcinoma3. Malignant thyroid lymph node metastases4. No false-positive with cystic lesions of the thyroid
gland
WHO SHOULD HAVE SURGERY?
NIH consensus statement 1991
All symptomatic
If assymptomatic1. Markedly elevated serum Ca2. H/o episodes of life-threatening hypercalcemia
3. Reduced renal function4. Kidney stone on radiograph5. Markedly elevated urinary Ca excretion6. Substantially reduced bone mass
PARATHYROIDECTOMY
Must find all four glands
Intraoperative frozen section, PTH measurement useful
If single gland enlarged, removal usually is curative
If multiple glands enlarged, removed. Normal just biopsied(hahahahah....barok yung pakakaphrase ng sentence.. yan talagnasa ppt ha)
if all 4 enlarged (generalized parathyroid hyperplasia) – subtotal
(3 ½ removed) can be implanted into forearm muscle
INDICATIONS FOR PARATHYROIDECTOMY IN PATIENTS WITHASYMPTOMATIC PRIMARY HPT
At initial evaluation:
Markedly increased serum calcium
Episode of life-threatening hypercalcemic episode
Reduced creatinine clearance
Kidney stones on abdominal x-rays
Markedly elevated 24-hour urinary calcium excretion (400 mg/d)
Substantially decreased bone mass
Age <50 years
Development of any of the following during follow-up:
Typical skeletal, renal, or gastrointestinal symptoms
Serum calcium >1 –1.6 mg/dL above upper normal range
A>30% decline in creatinine clearance
Urinary calcium >400 mg/d
Bone mass reduced to <2 SD below age-, gender-, and race-matched controlsUnwillingness or inability to undergo continued follow-up
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SUPERIOR PARATHYROID
easier to find
more consistent position
just on dorsal surface of upper thyroid
careful for superior thyroid artery and superior laryngeal nerve
INFERIOR PARATHYROID
less consistent location may be near thymus or inside thyroid
careful for recurrent laryngeal nerve between trachea/esophagus
inferior thryroid artery
STERNOTOMY
performed to locate a missing gland only after a complete searchhas been conducted in the neck
SUCCESS OF SURGERY
95% of cases cured at initial neck exploration
If failed initial procedure, can try to localize with radionuclide,detect with gamma probe
Sestamibi concentrates in parathyroid tissue
Increasingly used in initial operation
Limits dissection
Limits operative time
May need mediastinoscopy
POST OPERATIVE CARE
1. Airway management2. Hypocalcemia is common and occurs almost immediately
Monitor serum calcium
Symptoms – anxiety, hyperventilation, chvostek’s and
Trousseau’s signs, acral and sircumoral paresthesias Some advocate treating only symptomatic
hypocalcemia
Treat hypocalcemia with oral carbonate 1g PO q6h, or IV calcium gluconate for severe hypocalcemia (,7.0).
Vitamin D supplementation may be necessary for refractory hypocalcemia
3. Watch out for bleeding4. Infection
HYPERCALCEMIC CRISIS
Most patients with hyperparathyroidism chronically ill with renaland skeletal abnormalities
Rarely can become acutely ill
Rapidly developing weakness, N/V, weight loss, fatigue,drowsiness, confusion, azotemia
Uncontrolled PTH production, hyperCs, polyuria, dehydration,reduced renal function, worsening hyperCa
Definitive therapy: resection
Must reverse hyperCa first
Diuresis – saline hydration then Lasix to excrete Ca
Calcitonin – rapid effect, inhibits bone resorption
Steroids- take up to a week
Mithramycin – rapidly inhibiting bo0ne resorption
Medications Used to Treat Hypercalcemia
Medication Dosage andAdministration
Mechanism of Action
Side Effects
Bisphosphonates(pamidronate)
60 –90 mg IVover 4 –24hours
Inhibits osteoclasticbone resorption
May cause localpain and swelling,low-grade fever,lymphopenia,electrolyte
abnormalities
Calcitonin 4 IU/Kg SC/IM Inhibits osteoclastfunction, augmentsrenal calciumexcretion
Transient nauseaand vomiting,abdominal crampsflushing, and localskin reaction
Mithramycin(Plicamycin)
25 micro g/kgper day IV for 3 –4 days
Inhibits osteoclastRNA secretion
May cause renal,hepatic, andhematologiccomplications,nausea andvomiting
Gallium nitrate 200 mg/m2 BSA
per day IV for 5days
Reduces urinary
calcium excretion
Nephrotoxicity,
nausea, vomiting,hypotension,anemia,hypoPO4mia
Glucocorticoid Hydrocortisone100 mg IV q8h
Useful for hematologicmalignancies,sarcoidosis,vitamin Dintoxication,hyperthyroidism
Hypertension,hyperglycemia
HYPOPARATHYROIDISM
most common complication of total thyroidectomy
may be congenitally absent in the DiGeorge syndrome
Hyperparathyroidism in pregnant women can lead tohypoparathyroidism in neonates from suppression of fetalparathyroid tissue
Conditions Causing Hypocalcemia
Hypoparathyroidism
Surgical
Neonatal
Familial
Heavy metal deposition
Magnesium depletion
Resistance to the action of PTH
Pseudohypoparathyroidism
Renal failure
Medications—calcitonin, bisphosphonates,mithramycin
Failure of normal 1,25-dihydoxy vitamin Dproduction
Resistance to the action of 1,25-dihydroxyvitamin D
Acute complex formation or deposition of calcium
Acute hyperphosphatemia
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Acute pancreatitis
Massive blood transfusion (citrate overload)
"Hungry bones"
HYPOCALCEMIA Signs
1) Chvostek's sign - contraction of facial muscles elicited by
tapping on the facial nerve anterior to the ear
2)
Trousseau's sign -carpopedal spasm, elicited by occluding bloodflow to the forearm with a blood pressure cuff for 2 to 3 minutes
3) Tetany
THE ADRENALS
ANATOMY
The adrenal glands (also known as suprarenal glands) are pairedtriangular-shaped and orange colored endocrine glands andmeasures about 5x3x1 cm and weighs about 4-5gm locatedsuperiorly and medially to the kidneys at the level of the 11 th rib
Each adrenal glands consist of :
Adrenal medulla Secretes epinephrine (adrenalin) Norepinephrine (noradrenaline) Dopamine
Hormone Receptors and the Effects They Mediate
Receptor Tissue Function
a1 Blood vessels Contraction
Gut Decreased motility, increased sphincter tone
Pancreas Decreased insulin and glucagon release
Liver Glycogenolysis, gluconeogenesis
Eyes Pupil dilation
Uterus Contraction
Skin Sweating
Receptor Tissue Function
a2 Synapse(sympathetic)
Inhibits norepinephrine release
Platelet Aggregation
b1 Heart Chronotropic, inotropic
Adipose tissue Lipolysis
Gut Decreased motility, increased sphincter tone
Pancreas Increased insulin and glucagon release
b2 Blood vessels Vasodilation
Bronchioles Dilation
Uterus Relaxation
Adrenal cortex- produces 3 major hormones collectivelycalled corticosteroids
CORTICOSTEROID
Mineralocorticoidso aldosterone, 11-DOC, cortisol
Glucocorticoidso cortisolo regulated by ACTH secreted by the anterior pituitary,
which in turn, is under the control of corticotrophin-releasing hormone
Functions of Glucocorticoid Hormones
Function/System Effects
Glucosemetabolism
Increases hepatic glycogen deposition, andgluconeogenesis; decreases muscle glucose uptakeand metabolism
Protein metabolism Decreases muscle protein synthesis; increasedcatabolism
Fat metabolism Increases lipolysis in adipose tissue
Connective tissue Inhibition of fibroblasts, loss of collagen, thinning of skin, striae formation
Skeletal system Inhibits bone formation; increases osteoclast activity;potentiates the action of PTH
Immune system Increases circulation polymorphonuclear cells;decreases numbers of lymphocytes, monocytes andeosinophils; reduces migration of inflammatory cells tosites of injury
Cardiovascular
system
Increases cardiac output and peripheral vascular tone
Renal system Sodium retention, hypokalemia, hypertension viamineralocorticoid effect; increases glomerular filtrationvia glucocorticoid effects
Endocrine system Inhibits TSH synthesis and release, decreases TBGlevels, decreases conversion of T4 to T3
Sex hormoneo produced at zona fasciculata and reticularis from 17-
hydroxypregnenolone in response to ACTH stimulatioo dehydroepiandrosterone (DHEA) and its sulfated
counterpart (DHEAS), androstenedione, and smallamounts of testosterone and estrogen
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DISORDERS OF THE ADRENAL CORTEX
1. Hyperaldosteronism (Conn’s Syndrome) o SSx:
hypertension, which is longstanding, moderate tosevere, and may be difficult to control despitemultiple-drug therapy. Weakness, polydipsia,polyuria, nocturia, headaches, and fatigue
o Dx: Lab- Hypokalemia, Plasma aldosterone conc Radiologic-MRI & CT scan
o Tx: Adrenalectomy Preop- control hypokalemia (K sparing diuretic) &
HPN (Ca channel blocker & ACE inh) Postop- hypoaldosteronism (req
mineralocorticoid for 3 months)
2. Cushing’s Syndrome
Etiology of Cushing's Syndrome
ACTH-dependent (70%)
- Pituitary adenoma or Cushing's disease (70%)
- Ectopic ACTH production a (10%)
- Ectopic CRH production (<1%)
ACTH- independent (20 –30%)
- Adrenal adenoma (10 –15%)
- Adrenal carcinoma (5 –10%)
- Adrenal hyperplasia—pigmented micronodular cortical
- hyperplasia or gastric inhibitory peptide-sensitivemacronodular
- hyperplasia (5%)
Other
- Pseudo-Cushing's syndrome
- Iatrogenic—exogenous administration of steroids
o Dx: Lab- plasma cortisol, dexamethasone
suppression test, ACTH level & CRH test Rad- MRI & CT scan
o Tx: Unilateral laparoscopic adrenalectomy (TOC
adrenal adenoma) Transsphenoidal excision of pituitary adenoma Adrenalectomy- Postop: glucocorticoid administration to prevent
hypercoagulability after adrenalectomy
3. Adrenocortical cancer
o SSx: Functioning tumors=Cushing's syndrome+
virilizing features Nonfunctioning tumors =abdominal mass and
abdominal pain. Weight loss, anorexia, andnausea(rare)
o Dx: serum electrolyte level, CT scan, MRI
TNM Staging for Adrenocortical Cancer
Stage TNM Class
I T1, N0, M0
II T2, N0, M0
III T3, N0, M0
T1-2, N1, M0
IV T3-4, N1, M0
o Tx: adrenalectomy, mitotane, surgical debulking +systemic chemothera (for MDR tumor)
4. Sex Steroid Excesso Dx: plasma DHEA, urine 17-ketosteroidso Tx: adrenalectomy, Adrenolytic drugs (mitotane,
aminoglutethimide, & ketoconazole)
5. Congenital Adrenal Hyperplasiao group of disorders that result from deficiencies, or
complete absence, of enzymes involved in adrenalsteroidogenesis
o commonly due to 21-Hydroxylase def o Dx: karyotype analysis, palasma & urine steroids,
plama17-hydroxyprogesterone and progesteronelevels (inc in 21-hydroxylase def), 11-deoxycorticosterone and 11-deoxycortisol (inc in 11Bhydroxylase def), androgen & ketosteroid level
o Tx: cortisol & mineralocorticoid replacement, bilateralaparoscopic adrenalectomy (proposed)
DISORDERS OF THE ADRENAL MEDULLA
Pheochromocytomas (hereditary and malignant)o SSx: Triad (Headache, palpitations, and diaphoresis)o Dx:
Biochem-urinary cathecolamines &derivatives, VMA testing, chromogranin A(83%), plasma metanephrine(100%)
Rad: CT scan, MRI (pregnancy)o Tx: HPN & volume repletion control, adrenalectomy
Adrenal incidentalomao Dx: CT scan, FNAB
Differential Diagnosis of Adrenal Incidentaloma
Functioning Lesions Nonfunctioning Lesions
Benign Benign
Aldosteronoma Cortical adenoma
Cortisol-producing adenoma Myelolipoma
Sex-steroid-producingadenoma
Cyst
Pheochromocytoma Ganglioneuroma
Hemorrhage
Malignant Malignant
Adrenocortical cancer Metastasis
Malignantpheochromocytoma
o Tx: adrenalectomy, systemic chemotherapy
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Adrenal insufficiency
Etiology of Adrenal Insufficiency
Primary Secondary
Autoimmune (autoimmune polyglandular diseasetypes I and II)
Exogenousglucocorticoid therapy
Infectious: TB, fungi, CMV, HIV Bilateral adrenalectomy
Hemorrhage—spontaneous (Waterhouse-Friderichsen syndrome) and secondary to stress,trauma, infections, coagulopathy, or anticoagulants
Pituitary or hypothalamic tumors
Metastases Pituitary hemorrhage(postpartum Sheehan'ssyndrome)
Infiltrative disorders: amyloidosis,hemochromatosis
Transsphenoidalresection of pituitarytumor
Adrenoleukodystrophy
Congenital adrenal hyperplasia
Drugs: ketoconazole, metyrapone,aminoglutethemide, mitotane
o SSx: may mimic sepsis and presents with fever,
nausea, vomiting, lethargy, mild abdominalpain, or severe hypotension
fatigue, salt-craving, weight loss, nausea,vomiting, abdominal pain, and diarrhea(chronic & metastatic)
hyperpigmentation (inc MSH)
o Dx: ACTH level
Lab findings: hyponatremia, hyperkalemia,eosinophilia, mild azotemia, and fasting or reactive hypoglycaemia
o Tx: unlikely to survive =( , palliative
ADRENAL SURGERY
o Openo Anterior Approacho Posterior Approacho Lateral apperoach
o Laparoscopic o Lateral transabdominal approach
o Posterior retroperitoneal approach
o COMPLICATIONS OF ADRENAL SURGERY o Wound infectiono Urinary tract infectionso Deep vein thrombosiso Pneumoperitoneumo Nelson syndrome (complication of bilateral
adrenalectomy)
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