THYROID & PARATHYROID
COLIN G. THOMAS, JR., MD
The Thyroid Gland
130-201
1543
1656
1873
1889
1909
1915
1951
Galen
Vesalius
Wharton “Oblong Shield”
Gull – “Adult Cretinism”
Murray “Liquor Thyroidei”
Kocher – Nobel Prize
Kendall –Isolation of thyroxine
Pitt-Rivers-isolation of T3
Historical Aspects of Goiter
200 BC
Atharva Veda (Hindu): exorcism of goiter
1271
Marco Polo: “They are in general afflicted
with tumors in the throat occasioned by
the nature of the water which they drink.”
Incidence of Thyroid Disorders in Connecticut
(Annual physical Examination, 1544 Patients – One Year)
Simple goiter
Graves’ disease
Iatrogenic hyperthyroidism
Hot nodule
Multinodular goiter
Thyroiditis
Single cold nodule
Hypothyroidism
Cancer
Total
#
29
15
2
9
13
8
8
6
0
90
%
1.88
0.97
0.10
0.58
0.84
0.51
0.51
0.39
0.00
5.78
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%
Cancer Incidence and Deaths
Estimated- U.S. 2005
Organ System
Lung
Colon
Rectum
Pancreas
Breast
Stomach
Thyroid
Prostate
New Cases
172,570
104,950
42,000
32,180
212,930
24,000
25,690
232,090
Deaths
163,510
56,290
7,000
31,800
40,870
14,000
1,490
30,050
Thyroid Cancer
1985
1994
New Cases 10,000
13,900
17,200 (↑ 72%)
1,120
1,200 (↑8%)
Deaths
1,100
American Cancer Society 1998
1998
Evaluations of
Nodular Thyroid Disease
• History- symptoms, duration, familial
• Physical findings, i.e. topography,
firmness, surface, lymphadenopathy
• Thyroid functions tests- TFT (s) - TSH
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
Thyroid Cancer- Diagnosis
• Cytology
• Scans
– Technetium
– Radioiodine
– Sestamibi
– MR/CT/PET
• Ultrasound
• Frozen Sections
• Fixed Sections
Thyroid Cancers*
Papillary
Follicular
Hürthle
Medullary
Anaplastic
*National Cancer Data Base
31,513 patients (1985-1995)
80%
11%
3%
4%
2%
Biological Characterstics
• Thyrotropin Receptor– Adenylate Cyclase Systems
• Iodine Trapping/Organification
• Thyroglobin Production
Thyroid Cancer
A Spectrum of Neoplasms
Surgical Treatment: Reflect Biological
Characteristics
Papillary Carcinoma
• Ames (Age, Distant Metastases, Extent,
Size)
• 89%- Low risk; Mortality 1.8% and
• 11% High Risk, Mortality 46%
Adjuvant Therapy
Thyroxine → TSH Suppression
Radiodiodine (Ablation/Rx)
Thyroxine ↓ → TSH ↑
Recombinant TSH
External Radiation (?)
Chemotherapy (?)
On a New Gland in Man and
Several Mammals
Ivar SandstrŐm
“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.”
Ivar SandstrŐm
“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.”
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
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.”
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
Albert Jähne
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
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 ↓
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
Captain Charles Martell (1889-1932)
1926
1926
1932
1932
1932
1932
“Hyperparathyroidism” suggested by Dr.
Dubois, Bellvue Hospital
May and June- Two normally parathyroid
glands removed by Dr. E.P. Richardson, MGH
(March) Neck exploration- Dr. Russell
Patterson, New York
Three neck explorations- Drs. Oliver Cope and
E. D. Churchill, MGH
(November) Mediastinal parathyroid adenoma
partially excised- Dr. E. D. Churchill, MGH
Death from tetany
1932 _____ ______ (J. Morelle) Louvain
Diagnosis by Serendipity
Primary Hyperparathyroidism
Abnormal relationship between calcium and
PTH levels with changes in parathyroid
mass and calcium setpoints.
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
Hyperparathyroidism
(Classification)
I.
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
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)
Table 1. Symptoms and Signs of
Hypercalcemia*
Percent
Symptoms
Fatigue
Mental status change
Depression
Gastrointestinal
Signs
Cardiovascular
Nephrolithiasis
Bone disease
Pancreatitis
Asymptomatic
28
24
12
24
14
28
47
2
11
*Many patients had more then one symptom or sign.
Udelsman –Ann. Surg 2001; 113: 59-66
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
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.)
Evaluation of 1°
Hyperparathyroidism
• SERUM ELECTROLYTES
• BUN, CREATININE
• iPTH
•
•
•
•
Alkaline Phosphatase
Bone Density Studies
Urinary Calcium
Localization Procedures
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?
Table 1. Comparison of Old and New Criteria
for Parathyroid Surgery in Patients with
Asymptomatic Primary Hyperparathyroidism.*
Variable
1990 Guidelines
2002 Guidelines
Serum calcium
Concentration
1.0-1.6 mg/dl above
upper limit of
normal
1.0 mg/ dl of upper
limit of normal
>400 mg
>400 mg
30%
30%
Z score below -2.0 in the
forearm
T score below -2.5 at any
site
<50 yr
<50 yr
24- Hr urinary
Calcium excretion
Reduction in
Creatinine clearance
Bone mineral
Density
Age
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
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
Parathyroid ImagingLocalization
•
•
•
•
•
•
•
Experienced Surgeon
Ultrasound
Scintigraphy (sestamibi:technetium99m)
Venous sampling (qPTH – pre-intraoperative)
Computerized tomography
Magnetic resonance imaging
Angiography (selective digital subtraction
angiography)
• Fine needle aspiration: cytology/iPTH
End Stage Renal Disease
• Eu- hypercalcemia
• Hyperphosphatemia
• ↑ alkaline phosphatase
• ↑ iPTH
• Osteodystrophy
Renal Osteodystrophy
Indications for Parathyroidectomy
• Bone pain
• Proximal myopathy
• Persistent hypercalcemia
• Calcinosis – unresponsive to Rx
• Calciphylaxis