25. Thyroid, Parathyroid, and Adrenal

8/8/2019 25. Thyroid, Parathyroid, and Adrenal

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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



Page 10 of 1

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



Page 13 of 1

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



Page 14 of 1

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



Page 15 of 1

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



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)

Documents

25. Thyroid, Parathyroid, and Adrenal