Thyroid and Parathyroid

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  • 1. THYROID & PARATHYROID COLIN G. THOMAS, JR., MD
  • 2. 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
  • 3. Historical Aspects of Goiter 200 BC
    • Atharva Veda (Hindu): exorcism of goiter
  • 4. 1271
    • Marco Polo: “They are in general afflicted with tumors in the throat occasioned by the nature of the water which they drink.”
  • 5.  
  • 6. 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
  • 7. Nodular Goiter
    • Prevalence Rate: .08%/yr
    • Clinical incidence- Adults: 4-7%
      • Females > Males
    • Incidence with ionizing radiation: 20-30%
    • Autopsy incidence: 50%
    • Occult cancer (Autopsy): 4-28%
  • 8.  
  • 9. Cancer Incidence and Deaths Estimated- 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
  • 10. 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
  • 11.  
  • 12.  
  • 13. Evaluations of Nodular Thyroid Disease
    • History- symptoms, duration, familial
    • Physical findings, i.e. topography, firmness, surface, lymphadenopathy
    • Thyroid functions tests- TFT (s) - TSH
  • 14.  
  • 15.  
  • 16.  
  • 17. Diagnostic Studies- Thyroid Cancer
    • Fine Needle Aspiration- Establishes Cytologic Diagnosis
    • Thyroid function tests (TSH- 1 st in Thyroiditis)
    • Technetium Scan- reflects trapping function, “hot nodule”
    • Ultrasonography- reflects volume, composition, occult nodules
  • 18.  
  • 19.  
  • 20.  
  • 21.  
  • 22.  
  • 23.  
  • 24.  
  • 25.  
  • 26. Thyroid Cancer- Diagnosis
    • Cytology
    • Scans
      • Technetium
      • Radioiodine
      • Sestamibi
      • MR/CT/PET
    • Ultrasound
    • Frozen Sections
    • Fixed Sections
  • 27. Thyroid Cancers*
    • Papillary 80%
    • Follicular 11%
    • H ürthle 3%
    • Medullary 4%
    • Anaplastic 2%
    • *National Cancer Data Base
    • 31,513 patients (1985-1995)
  • 28. Biological Characterstics
    • Thyrotropin Receptor-
      • Adenylate Cyclase Systems
    • Iodine Trapping/Organification
    • Thyroglobin Production
  • 29. Thyroid Cancer A Spectrum of Neoplasms
    • Surgical Treatment: Reflect Biological Characteristics
  • 30.  
  • 31. Papillary Carcinoma
    • Ames (Age, Distant Metastases, Extent, Size)
    • 89%- Low risk; Mortality 1.8% and
    • 11% High Risk, Mortality 46%
  • 32.  
  • 33.  
  • 34.  
  • 35.  
  • 36. Adjuvant Therapy
    • Thyroxine -> TSH Suppression
    • Radiodiodine (Ablation/Rx)
    • Thyroxine ↓ -> TSH ↑
    • Recombinant TSH
    • External Radiation (?)
    • Chemotherapy (?)
  • 37.  
  • 38.  
  • 39.  
  • 40.  
  • 41.  
  • 42.  
  • 43.  
  • 44.  
  • 45. On a New Gland in Man and Several Mammals
    • Ivar Sandstr Ő m
    • “ 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.”
  • 46. Ivar Sandstr Ő m
    • “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.”
  • 47. 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
  • 48. 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.”
  • 49. 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 Recklinghausen’s Disease
  • 50. Albert J ä hne RX: Von Recklinghausen’s 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
  • 51.  
  • 52. 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 ↓
  • 53. 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
  • 54.  
  • 55. 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
  • 56. 1932 _____ ______ (J. Morelle) Louvain
    • Diagnosis by Serendipity
  • 57. Primary Hyperparathyroidism
    • Abnormal relationship between calcium and
    • PTH levels with changes in parathyroid
    • mass and calcium setpoints.
  • 58.  
  • 59. Hyperparathyroidism
    • Incidence 1:700 (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
  • 60. 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
  • 61. 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 α )
          • Lymphotoxin (Tumor Necrosis Factor β )
  • 62.  
  • 63. 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
  • 64. 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
  • 65. 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., 197:135, 1983.)
  • 66. Evaluation of 1 ° Hyperparathyroidism
    • SERUM ELECTROLYTES
    • BUN, CREATININE
    • iPTH
    • Alkaline Phosphatase
    • Bone Density Studies
    • Urinary Calcium
    • Localization Procedures
  • 67.  
  • 68.  
  • 69.  
  • 70.  
  • 71.  
  • 72. 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?
  • 73. 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 >400 mg >400 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 <50 yr <50 yr
  • 74. Parathyroidectomy Indications
    • Symptomatic Patients
    • Asymptomatic Patients
        • Calcium ≥ 11 mgms. % ( 1 mg > Normal )
        • Not Amenable to Surveillance
        • Decreasing Bone Density, Osteopenia Hypertension, Hypercalciuria Decreasing Renal Function
  • 75. 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
  • 76. Parathyroid Imaging- Localization
    • Experienced Surgeon
    • Ultrasound
    • Scintigraphy (sestamibi:technetium 99m )
    • Venous sampling (qPTH – pre-intraoperative)
    • Computerized tomography
    • Magnetic resonance imaging
    • Angiography (selective digital subtraction angiography)
    • Fine needle aspiration: cytology/iPTH
  • 77.  
  • 78.  
  • 79.  
  • 80. End Stage Renal Disease
    • Eu- hypercalcemia
    • Hyperphosphatemia
    • ↑ alkaline phosphatase
    • ↑ iPTH
    • Osteodystrophy
  • 81. Renal Osteodystrophy Indications for Parathyroidectomy
    • Bone pain
    • Proximal myopathy
    • Persistent hypercalcemia
    • Calcinosis – unresponsive to Rx
    • Calciphylaxis
  • 82.