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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