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THYROID

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Title: THYROID


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THYROID PARATHYROID
  • COLIN G. THOMAS, JR., MD

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The Thyroid Gland
  • 130-201 Galen
  • 1543 Vesalius
  • Wharton Oblong Shield
  • Gull Adult Cretinism
  • Murray Liquor Thyroidei
  • Kocher Nobel Prize
  • Kendall Isolation of thyroxine
  • 1951 Pitt-Rivers-isolation of T3

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Historical Aspects of Goiter200 BC
  • Atharva Veda (Hindu) exorcism of goiter

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1271
  • Marco Polo They are in general afflicted with
    tumors in the throat occasioned by the nature of
    the water which they drink.

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Incidence of Thyroid Disorders in
Connecticut(Annual physical Examination, 1544
Patients One Year)
  • Simple goiter 29 1.88
  • Graves disease 15 0.97
  • Iatrogenic hyperthyroidism 2 0.10
  • Hot nodule 9 0.58
  • Multinodular goiter 13 0.84
  • Thyroiditis 8 0.51
  • Single cold nodule 8 0.51
  • Hypothyroidism 6 0.39
  • Cancer 0 0.00
  • Total 90 5.78

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Nodular Goiter
  • Prevalence Rate .08/yr
  • Clinical incidence- Adults 4-7
  • Females gt Males
  • Incidence with ionizing radiation 20-30
  • Autopsy incidence 50
  • Occult cancer (Autopsy) 4-28

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Cancer Incidence and DeathsEstimated- U.S. 2005
  • Organ System New Cases Deaths
  • Lung 172,570 163,510
  • Colon 104,950 56,290
  • Rectum 42,000 7,000
  • Pancreas 32,180 31,800
  • Breast 212,930 40,870
  • Stomach 24,000 14,000
  • Thyroid 25,690 1,490
  • Prostate 232,090
    30,050

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Thyroid Cancer
  • 1985 1994 1998
  • New Cases 10,000 13,900 17,200 (? 72)
  • Deaths 1,100 1,120 1,200 (?8)
  • American Cancer Society 1998

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Evaluations ofNodular Thyroid Disease
  • History- symptoms, duration, familial
  • Physical findings, i.e. topography, firmness,
    surface, lymphadenopathy
  • Thyroid functions tests- TFT (s) - TSH

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Diagnostic Studies- Thyroid Cancer
  • Fine Needle Aspiration- Establishes Cytologic
    Diagnosis
  • Thyroid function tests (TSH- 1st in
    Thyroiditis)
  • Technetium Scan- reflects trapping function,
    hot nodule
  • Ultrasonography- reflects volume, composition,
    occult nodules

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Thyroid Cancer- Diagnosis
  • Cytology
  • Scans
  • Technetium
  • Radioiodine
  • Sestamibi
  • MR/CT/PET
  • Ultrasound
  • Frozen Sections
  • Fixed Sections

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Thyroid Cancers
  • Papillary 80
  • Follicular 11
  • Hürthle 3
  • Medullary 4
  • Anaplastic 2
  • National Cancer Data Base
  • 31,513 patients (1985-1995)

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Biological Characterstics
  • Thyrotropin Receptor-
  • Adenylate Cyclase Systems
  • Iodine Trapping/Organification
  • Thyroglobin Production

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Thyroid CancerA Spectrum of Neoplasms
  • Surgical Treatment Reflect Biological
    Characteristics

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Papillary Carcinoma
  • Ames (Age, Distant Metastases, Extent, Size)
  • 89- Low risk Mortality 1.8 and
  • 11 High Risk, Mortality 46

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Adjuvant Therapy
  • Thyroxine ? TSH Suppression
  • Radiodiodine (Ablation/Rx)
  • Thyroxine ? ? TSH ?
  • Recombinant TSH
  • External Radiation (?)
  • Chemotherapy (?)

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On a New Gland in Man and Several Mammals
  • Ivar SandstrOm
  • About three years ago (1877) I found on the
    thyroid gland of a dog a small organ, hardly as
    big as a hemp seed, which was enclosed in the
    same connective tissue capsule as the thyroid,
    but could be distinguished there from by a
    lighter color. A superficial examination
    revealed an organ of totally different than that
    of the thyroid and with a very rich versatility.

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Ivar SandstrOm
  • So much the greater was my astonishment
    therefore when in the first individual (patient)
    examined I found on both sides at the inferior
    border of the thyroid gland an organ of the size
    of a small pea, which judging from its exterior
    did not appear to be a lymph gland nor an
    accessory thyroid gland and upon histological
    examination showed a rather peculiar structure.

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Herr Bleich, 40, Male, Mason
  • April 1888 Fall, ? Femoral neck fracture
  • August 1888 Fall, Clavicle fracture
  • Hospitalized- Fracture of femur
    in bed.
  • July 1889 Bending of bones, bone pain
  • October 1889 Marasmus- Death

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Herr Bleich Autopsy(Pathological Institute of
Strassburg)
  • 1889 Von Recklinghausen
  • Skeletal Findings Widespread fibrosis, cysts,
    brown (giant cell) tumors
  • 1933 Jung
  • Above the left Thyroid gland, a lymph gland,
    red-brown in color is present.

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Albert ____ 38, Male, Street Car Conductor
  • Chicken pox 5, Measles 6, Syphilis 19,
    Tuberculosis
  • 1921- Pain legs, hips, tiredness-pensioned
  • 1923- X-Rays Bone cysts
  • 1924- Diagnosis Von Recklinghausens Disease

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Albert JähneRX Von Recklinghausens Disease
  • 1924 Parathyroid Extract from animals,
  • Parathyroid Transplantation (MANDL)
  • 1925 Jellyfish stage Parathyroid tumor removed
    92.5 X 1.5 X 1.2 cm.) July 20
  • 1932 Recurrence Two normal glands removed
  • 1936 Death No tumor at autopsy

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Elva Dawkins
  • February 1928
  • Fractured left humerus, tumor of maxilla,
    benign giant cell sarcoma- left ulna
  • Dixon (student) studying nerve- muscle
    preparation
  • Calcium 16 mgs. , phosphorus- 1.4 mgs.
  • Walnut sized mass left lobe of thyroid
  • July 1929, Paraparesis, UTI, renal function ?

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Hyperparathyroidism
  • Rarefaction of bone
  • Multiple cystic bone tumors, giant cell sarcoma
  • Muscular weakness and hypotonia
  • Abnormal excretion of calcium and formation of
    calcium stones
  • Abnormally high serum calcium

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Captain Charles Martell (1889-1932)
  • 1926 Hyperparathyroidism suggested by Dr.
    Dubois, Bellvue Hospital
  • 1926 May and June- Two normally parathyroid
    glands removed by Dr. E.P. Richardson, MGH
  • 1932 (March) Neck exploration- Dr. Russell
    Patterson, New York
  • 1932 Three neck explorations- Drs. Oliver Cope
    and E. D. Churchill, MGH
  • 1932 (November) Mediastinal parathyroid adenoma
    partially excised- Dr. E. D. Churchill, MGH
  • 1932 Death from tetany

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1932 _____ ______ (J. Morelle) Louvain
  • Diagnosis by Serendipity

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Primary Hyperparathyroidism
  • Abnormal relationship between calcium and
  • PTH levels with changes in parathyroid
  • mass and calcium setpoints.

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Hyperparathyroidism
  • Incidence 1700 (0.14)
  • Most common cause of Hypercalcemia in
    non-hospitalized patients
  • Female greater than male
  • Most common in peri/post menapausal female
  • Rare in children

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Hyperparathyroidism(Classification)
  • 1 HPT- Idiopathic inappropriate secretion
    of PTH
  • II. 2 HPT- Hypersecretion of PTH 2 to ?
    Ca
  • III. 3 HPT- Autonomous hypersecretion of
    PTH/2 HPT

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Hyperparathyroidism(Classification)
  • IV. Ectopic Hyperparathyroidism
  • (Humoral Hypercalcemia of Cancer)
  • Pseudo Hyperparathyroidism
  • (Bone Resorption via Local Mechanism)
  • Prostaglandinis E
  • Cytokines (Osteoclast Activating Factor)
  • Interleukin-1
  • Cachectin (Tumor Necrosis Factor a)
  • Lymphotoxin (Tumor Necrosis Factor ß)

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Table 1. Symptoms and Signs of Hypercalcemia
  • Percent
  • Symptoms
  • Fatigue 28
  • Mental status change 24
  • Depression 12
  • Gastrointestinal 24
  • Signs
  • Cardiovascular 14
  • Nephrolithiasis 28
  • Bone disease 47
  • Pancreatitis 2
  • Asymptomatic 11
  • Many patients had more then one symptom or sign.
  • Udelsman Ann. Surg 2001 113 59-66

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Clinical Manifestations of Hyperparathyroidism
  • Renal
  • Hypercalciuria, negative calcium balance
  • Renal parenchymal calcification nephrocalcinosis
  • Obstructive uropathy nephrolithiasis
  • Skeletal
  • Increased bone resoption (also increased
    formation)
  • Greater loss of cortical than trabecular bone
  • Brown tumors presenting as lytic lesions
    (uncommon)
  • Gastrointestinal
  • Anorexia, nausea, vomiting, weight loss,
    constipation
  • Pancreatitis
  • Neuromuscular
  • CNS depression lethargy, coma
  • Muscle weakness, hyporeflexia
  • Peripheral neuropathy axonopathy

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Hyperparathyroidism in the Elderly ( 65)
  • Incidence 1.5
  • 40 - Hypercalcemia A Serendipitous Finding
  • Neuromuscular Symptoms
  • Easy Fatigability
  • Emotional Instability
  • Anorexia
  • Sudden Accentuated Aging
  • ? Intellectual Capacity
  • Lack of Initiative
  • (From Tibblin, et. al. Ann. Of Surg., 197135,
    1983.)

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Evaluation of 1 Hyperparathyroidism
  • SERUM ELECTROLYTES
  • BUN, CREATININE
  • iPTH
  • Alkaline Phosphatase
  • Bone Density Studies
  • Urinary Calcium
  • Localization Procedures

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Asymptomatic Hyperthyroidism
  • Natural History Unknown
  • Rapid Progression to Severe Disease Rare
  • 20 Develop Complications in Ten Years
  • Accelerated Bone Loss Mental Function/Well
    Being Compromised?

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Table 1. Comparison of Old and New Criteria for
Parathyroid Surgery in Patients with Asymptomatic
Primary Hyperparathyroidism.
  • Variable 1990 Guidelines 2002 Guidelines
  • Serum calcium 1.0-1.6 mg/dl above 1.0 mg/ dl of
    upper
  • Concentration upper limit of limit of normal
  • normal
  • 24- Hr urinary gt400 mg gt400 mg
  • Calcium excretion
  • Reduction in 30 30
  • Creatinine clearance
  • Bone mineral Z score below -2.0 in the T score
    below -2.5 at any
  • Density forearm site
  • Age lt50 yr lt50 yr

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Parathyroidectomy Indications
  • Symptomatic Patients
  • Asymptomatic Patients
  • Calcium 11 mgms. ( 1 mg gt Normal )
  • Not Amenable to Surveillance
  • Decreasing Bone Density, Osteopenia Hypertension,
    Hypercalciuria Decreasing Renal Function

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Effects of Successful Surgery on Problems
Associated with Hyperparathyroidism
  • Osteopenia Increased bone mineral density in
    spin and hip ( 10-15 within 1-2 yrs)
  • Hypercalciuria and nephrolithiasis are
    significantly reduced
  • Neuromuscular symptoms frequently improve
  • - Objective improvements documented in motor
    strength and fine motor control but not sensory
    function
  • Some aspects of psychiatric morbidity are
    subjectively improved
  • - Improved subjective scores of fatigue,
    depression, irritability, sleep disturbance and
    lack of concentration
  • - No changes in cognitive function or anxiety
    scores
  • Pre-existing hypertension is generally not
    improved but LVH may regress

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Parathyroid Imaging- Localization
  • Experienced Surgeon
  • Ultrasound
  • Scintigraphy (sestamibitechnetium99m)
  • Venous sampling (qPTH pre-intraoperative)
  • Computerized tomography
  • Magnetic resonance imaging
  • Angiography (selective digital subtraction
    angiography)
  • Fine needle aspiration cytology/iPTH

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End Stage Renal Disease
  • Eu- hypercalcemia
  • Hyperphosphatemia
  • ? alkaline phosphatase
  • ? iPTH
  • Osteodystrophy

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Renal OsteodystrophyIndications for
Parathyroidectomy
  • Bone pain
  • Proximal myopathy
  • Persistent hypercalcemia
  • Calcinosis unresponsive to Rx
  • Calciphylaxis

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