Radionuclide methods in endocrinology

1
Radionuclide methods in endocrinology
material for medical students

• Otto Lang, MD Helena Balon, MD
• Dept Nucl Med
• Charles Univ
• 3rd School of Medicine
• Prague

2
Endocrinology

• Key role of the thyroid gland
• Availability of I-131 (iodine is a part of T
  hormones) evolution of NM
• Diagnostic tool as well as therapy
• Beta radiation for therapy
• Parathyroid gland
• Adrenal
• Hormone-secreting tumors
• Diagnosis and therapy

3
Thyroid gland - anatomy

• Bilobe organ in the front of cricoid cartilage,
  butterfly-like shape on projection, isthmus
• Originated in the base of pharynx, migrates
  caudally functioning remnants (lobus
  pyramidalis), ectopia
• Not palpable, enlarged moves with swalloving
• Nodes appears with the age (degenerative),
  palpable always pathological

4
Thyroid gland - histology

• Basal functioning unit follicle
• Concavity with epithelial cells in the wall
• Creates, stores and releases T hormones
• Storage in the follicle colloid, hormones bind to
  TBG (thyroid-binding globulin)
• Parafollicular cells
• Calcitonin (calcium metabolism)

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Thyroid follicles
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Thyroid gland - physiology

• T hormones contain iodine
• Ingested in the upper intestin
• Trapped in the thyroid and highly concentrated
  (201)
• Oxidised and organified
• Binding to thyrosine on TBG inside follicular
  colloid
• Not-trapped iodine
• Temporarily accumulated by salivary and stomach
• Excreted by the kidneys
• Coupling of iodine-thyrosine to T3, T4
  (peroxidase)
• Storage of T hormones up to 10 mg on colloidal
  TBG
• Releasing to the blood by proteolysis of TBG (T4)

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Thyroid gland - physiology

• T hormones in plasma
• Bind to plasmatic TBG and prealbumin
• Free hormones only 0.1 (active)
• T4 prohormone, T3 active (cell nucleus)
• Function and grow controlled by TSH
• TSH produced by pituitary gland (hypophysis)
• Backward controll by T-hormones level
• TRH produced by hypothalamus, released TSH
• Autoregulation high iodine supress

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Thyroid gland - physiology
9
Normal scan of thyroid gland
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Thyroid gland - pathophysiology

• Thyreotoxicosis (hyperthyroidism) high level of
  T-hormones from different reasons
• Primary
• Graves-Basedow disease (GBD)
• Toxic goitre autonomous adenoma
• Secondary
• Overproduction of TSH
• Other causes

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Thyroid gland - pathophysiology

• Graves-Basedow disease
• Auto-immune disease with TSI antibody
• Thyroid stimulating imunoglobulin
• Stimulates grow, over-production and release of T
  hormones
• 50 of patients have exophtalmus
• Typical clinical picture, lab. tests confirm
• High level of T3, T4, low level of TSH, enlarged
  thyroid (nodules could be)

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Graves Basedow disease
Diffuse
Nodular
Post strumectomy
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Thyroid gland - pathophysiology

• Autonomous adenoma
• Toxic goitre
• Production of T hormones regardless to body need
  (out of regulation)
• Usually one adenoma
• It could be also in multinodular goitre
• Clinical picture the same as in GBD

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Autonomous adenoma
Initial scan - euthyreosis
Repeat scan - hyperhyreosis
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Toxic goitre
Before treatment
After tx with I-131
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Thyroid gland - pathophysiology

• Secondary thyreotoxicosis
• Pituitary adenoma
• Usually overfunction of other glands depending on
  pt
• Ectopic production of TSH-like hormone
• Chorio-carcinoma, molla hidatidosa
• Other causes of thyreotoxicosis
• Ectopic production of T-hormones (teratoma)
• Thyroiditis
• Transient (weeks), subsequent hypothyreoidism
  (all the cycle can repeat infective
  inflammation)
• Iatrogenic overdose of T-hormones

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Thyroiditis
Right lobe involved
Left lobe involved
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Thyroid gland - pathophysiology

• Hypothyroidism low level of T-hormones
• Primary
• 95 of hypothyroidism, atypical clinical picture
  lab. diagnosis is essential (high TSH)
• Hashimotos goitre (chronic autoimmune) the
  most frequent
• Iatrogenic
• Post strumectomy clinically discrete, lab.
  follow-up essential
• Post drugs - Amiodaron
• Secondary
• Non-production of TSH (pituitary destruction)

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Hashimotos thyroiditis
Tc-99m pertechnetate
Ga-67 citrate
20
Thyroid gland - carcinoma

• 90 well differentiated (accumulates iodine)
• 80-90 papillary
• Two-fold more frequent in female, meta by
  lymfatic
• 10-20 follicular
• Without gender preferention, meta hematogenous
  (lungs, bone, liver, brain)
• Good prognosis 5y survival 95 pts
• 5 non-differentiated (anaplastic)
• Mainly in elderly, poor prognosis
• 5 medullary
• Calcitonin production

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Radiopharmaceuticals

• Tc-99m pertechnetate
• Trapped but non-organified fast release
• E140 keV, T/26 hours
• I-123
• Optimal for diagnosis pure gamma emitter
• E159 keV, T/213 hours
• I-131
• Used for therapy (beta radiation)
• Egama364 keV, T/28 days

22
Thyroid gland - physiology comparison of
radiopharm. (Tc vs I)
23
Methods

• In vitro
• RIA of hormones level (T3, T4, TSH))
• In vivo
• Non-imaging
• Radio-iodine uptake test
• Perchlorate test
• Imaging
• Scintigraphy

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Methods

• Radio-iodine uptake test
• The only indication before therapy to calculate
  appropriate dose
• 0.4 to 0.7 MBq of I-131 orally, measurement over
  thyroid at 4, 6 and 24 hours
• Normal limits
• 6-18 at 4-6 h, 10-30 at 24 h
• Influencing issues
• Low accumulation
• High I diet, renal failure, drugs, contrast media
• High accumulation
• Low iodine diet

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Methods

• Radio-iodine uptake test
• Increased accumulation
• Thyreotoxicosis primary as well as secondary (it
  could be normal multinodular goiter), other
  pathol.
• Decreased accumulation
• Inadequate diagnostic test
• Perchlorate test
• Perchlorate administrationi iodine release
• Diagnosis of iodine binding disorders (Hashimoto)

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Methods

• Imaging (scintigraphy)
• Radiopharmaceuticals
• Tc-99m (cheap, available), I-123 (expensive,
  ideal), I-131 for carcinomas
• Indications
• Diff dg diffuse toxic goiter vs toxic adenoma
• Function assessment of palpable nodules
• Ectopic tissue
• Organification disorders (perchlorate test)

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Methods

• Thyroid imaging process
• Tc-99m 100 150 MBq i.v.
• Images 20 min post injection, supine, pin-hole
  collimator, do not swallow
• I-123 10 20 MBq p.o.
• Patient fasting
• Images by the same waybut later (4 or 24 h post
  injection)

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Methods

• Images interpretation
• Normal finding
• Butterfly shape (many variations) 2x5 cm,
  homogenous distribution of activity, above
  jugulum
• Pathology
• Magnitude enlarged, remnants post thyroidectomy
• Accumulation
• Diffuse increase or decrease
• Focal increase or decrease
• nodules warm, hot, cold

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Methods

• Thyriod imaging interpretation
• Cold nodules
• Non-specific finding (cyst, adenoma)
• Risk of carcinoma 15-20 (more in children, post
  I131 therapy up to 40) biopsy essential
• Hot nodules
• Mostly benign, about 50 autonomous
• Multinodular goitre
• Enlarged, different types of nodules, cause
  swallowing disorders, frequent in middle-aged
  women
• Diffuse toxic goitre
• Enlarged, increased accumulation, lobus
  pyramidalis

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Cold nodule
Tc-99m pertechnetate
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Hot nodule
TSH 1.2
32
Subacute thyroiditis
Tc-99m pertechnetate
33
Hashimotos thyroiditis
Tc-99m pertechnetate
TSH 4.1
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Graves disease
Tc-99m pertechnetate
TSH0.02, FTI8.9
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Perchlorate test - scheme
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Perchlorate test
Negative
Positive
quantification
Tc-99m
test
Tc-99m
I-123
I-123
test
Tc-99m
quantification
test
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Methods

• Thyroid carcinoma imaging
• Post strumectomy
• 1 to 3 months post surgery, substitution therapy
  must be withheld (to increase TSH)
• 100 to 200 MBq I-131, WB study, images 3-5 days
  later
• Post I-131 therapy
• Seeking for metastases
• WB study post therapeutical dose of I-131
  administration
• Imaging the same as above
• Untill negative for two consecutive years

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Normal scan with I-131
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Follicular carcinoma of thyroid gland
Multiple matastases
40
Follicular carcinoma of thyroid gland
Lung and scull meta
Effect of therapy with I-131
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Methods

• Pregnancy and breast-feeding
• All radiopharmaceuticals freely cross placenta,
  fetal thyroid accumulates iodine from the 12th
  week carefull indication
• I-131 contra-indicated
• All radiopharmaceuticals freely pass to milk
  breast feeding must be interrupted
• Tc-99m for 12 to 24 hours
• I-123 for 2 to 3 days
• I-131 gt 70 kBq must be stopped

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I-131 therapy

• Principle
• Tissue destruction by beta radiation
• Effect appears after weeks or months
• Contra-indicated at pregnancy
• Pregnancy not sooner than 6 months post therapy
• Indications
• Thyrotoxicosis
• Remnants of thyroid post surgery
• Therapy of metastases which accumulate iodine
• In Czech only for inpatients

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I-131 therapy - thyrotoxicosis

• Therapeutical strategy
• Antithyroid drugs surgery radioiodine I-131
• Radioiodine
• Low doses
• Eliminates thyroid function during one year
• High doses
• Eliminates tharoid function asap (weeks)
• Hypothyroidism follows always substitution!
• Clinical symptoms not serious
• Lab controls are essentials

44
I-131 therapy - thyrotoxicosis

• Factors influencing dose
• Thyroid mass, nodularity, accumulation test
• Activity administered
• 100 to 200 MBq diffuse, 300 to 800 nodular
• Patient fasting, could repeat after 3-6 months
• Severe symptoms antithyroid drugs,
  beta-blockers
• Symptoms post therapy (within 10 days)
• Sore throat, dysphagia drink enough,
  corticosteroids
• Therapeutical effect
• Could be expected after 3 to 6 weeks, could be
  repeated

45
I-131 therapy - carcinoma

• High doses
• 1 to 8 GBq
• Follow-up scan 1 year later
• Substitution should be withdrawn (increase TSH)
• T4 for 4 to 6 weeks
• T3 for 2 weeks
• Metastases
• 4 to 8 GBq
• Could be repeated one year later up to ten-times
• Symptoms post therapy see thyrotoxicosis

46
I-131 therapy - requirements

• Single-bed rooms with toilet and shower
• Confined to the room for several days
• Visits only on according to dose
• Visitors should remain 2 m from the pt
• To douche every day
• To flush toilet several times after each use
• Use only disposable plates and cups and other
  disposables
• Washing up separately

47
I-131 therapy - requirements

• Urine, feces, and vomitus should be stored
• Special container, disposed of after decay
• Minimal required nursing time near the patient
• Room door labeled with radioactivity symbol
• Staff thyroid burden should be monitored
• Died pt must be buried into the grave

48
Parathyroid gland

• Inside the thyroid, usually 4, 1x3x5 mm
• Ectopic neck, mediastinum can be multiple (up
  to 12 glands)
• Physiology
• Parathormone production (PTH)
• It mobilises bone calcium and increases calcium
  absorption in the bowel and kidneys if the blood
  calcium level is low
• It is a polypeptide, not stored, plasma half-life
  of active part 3-5 min, of non-active part
  several hours this is quantified as a measure
  of PTH production

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Parathyroid gland
50
Parathyroid gland

• Pathophysiology
• Hyperparathyroidism
• Primary idiopathic
• Secondary Ca depletion (chronic renal failure)
• Overproduction of PTH
• High plasma level of Ca and low of Phosphorus
• Calcification in kidneys (stones, inflammation,
  failure)
• Soft tissue calcification
• Morbus Recklinghausen osteomalatia, fractures,
  cysts
• Primary
• 85 only one autonomous adenoma, rarely more
• 1 to 3 carcinoma within MEN (multiple endcrn
  neo)

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Parathyroid gland

• Radiopharmaceuticals
• Tl-201
• Analogous to potassium, accumulates within
  thyroid as well as parathyroid subtraction
  imaging needed
• Tc-99m MIBI
• Similar pharmacokinetics subtraction also
  needed
• Nowadays two-phase (early and delayed) imaging is
  frequently used (prefered)

52
Parathyroid gland

• Imaging (scintigraphy)
• Normal glands is invisible (too small)
• Good results in adenomas above 500 mg weight
• Sensitivity 90
• Indications
• Localisation of adenoma before surgery
• To reduce operation time in risk pt
• Localisation of adenoma after unsucceful surgery
  (ectopic glands)

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Parathyroid gland

• Imaging technique
• The same images as in thyroid gland thorax
• Subtraction technique
• Imaging with Tl-201 (Tc-99m MIBI), then with
  Tc-99m (no pt moving) and images subtraction
• Two-phase imaging
• Images 5 to 10 minutes and 2 to 3 hours post
  radiopharmaceutical administration

54
Parathyroid gland

• Images interpretation
• Normal finding
• No activity
• Adenoma
• Hot nodule within thyroid post subtraction
  (delayed phase) or in mediastinum (ectopic)
• False positive finding
• Thyroid adenoma, pt movement (subtraction),
  lymphoma, sarkoidosis
• False negative finding
• Too small adenoma

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Subtraction technique
Normal finding
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Subtraction technique
Autonomous adenoma
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Adrenals - medulla

• Catecholamines (adrenalin) production
• Pheochromocytoma
• Instable hypertension, palpitations, flushes,
  headache, orthostatic hypotension
• It could be alone or in sympathetic ganglia
• Radiopharmaceuticals
• I-123 MIBG (metaiodobenzylguanidin) for diagnosis
  or I-131 MIBG for therapy
• Useful also for neuroblastomas and other tumors
  originated from neuroectoderma
• Carcionid, medullary carcinoma of the thyroid

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Adrenals - medulla
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Adrenals - medulla

• Imaging procedure using I-123 MIBG
• Precise biochemical diagnosis is essential
• Withdraw drugs 2 to 3 weeks before MIBG
  administration (reserpin, anti-depressives)
• WB images of head and body SPECT of suspected
  areas, all body in metastases
• Imaging 6 and 24 hours post administration
• Sufficient accumulation is the rational basis for
  I-131 MIBG therapy

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Adrenals - medulla

• Image interpretation of I-123 MIBG
• Normal finding
• Adrenals non-visible, physiologically salivary
  glands, liver, spleen, activity decreases with
  time
• Pheochromocytoma
• Focal intensive accumulation, increases with time
• Meta usually in lungs, bones, liver
• Neuroblastoma
• The most frequent extracranial tumor in children
• Early metastasizes into bone marrow
• Avid accumulation makes possible I-131 MIBG
  therapy

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Image with I-123 MIBG
Normal finding
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Pheochromocytoma I-131
Before therapy
Post therapy
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Pheochromocytoma I-123