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)

5. Thyroid follicles

6. Thyroid gland - physiology
T hormones contain iodine
Ingested in the upper intestin
Trapped in the thyroid and highly concentrated (20:1)
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)

7. 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

8. Thyroid gland - physiology

9. Normal scan of thyroid gland

10. 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

11. 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)

12. Graves – Basedow disease
Diffuse
Nodular
Post strumectomy

13. 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

14. Autonomous adenoma Initial scan - euthyreosis
Repeat scan - hyperhyreosis

15. Toxic goitre
Before treatment
After tx with I-131

16. 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

17. Thyroiditis
Right lobe involved
Left lobe involved

18. Thyroid gland - pathophysiology
Hypothyroidism – low level of T-hormones
Primary
95% of hypothyroidism, atypical clinical picture – lab. diagnosis is essential (high TSH)
Hashimoto´s 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)

19. Hashimoto´s 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

21. Radiopharmaceuticals
Tc-99m pertechnetate
Trapped but non-organified – fast release
E=140 keV, T/2=6 hours
I-123
Optimal for diagnosis – pure gamma emitter
E=159 keV, T/2=13 hours
I-131
Used for therapy (beta radiation)
Egama=364 keV, T/2=8 days

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

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

24. 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

25. Methods Radio-iodine uptake test Perchlorate 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)

26. Methods Imaging (scintigraphy) Radiopharmaceuticals Indications
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)

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

28. Methods Images interpretation Normal finding Pathology
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

29. Methods Thyriod imaging – interpretation Cold nodules Hot 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

30. “Cold” nodule
Tc-99m pertechnetate

31. “Hot” nodule
TSH = 1.2

32. Subacute thyroiditis
Tc-99m pertechnetate

33. Hashimoto’s thyroiditis
Tc-99m pertechnetate
TSH = 4.1

34. Graves’ disease
Tc-99m pertechnetate
TSH=0.02, FTI=8.9

35. Perchlorate test - scheme

36. Perchlorate test Negative Positive quantification Tc-99m test Tc-99m

37. Methods Thyroid carcinoma imaging Post strumectomy Post I-131 therapy
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

38. Normal scan with I-131

39. Follicular carcinoma of thyroid gland
Multiple matastases

40. Follicular carcinoma of thyroid gland
Lung and scull meta
Effect of therapy with I-131

41. 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 > 70 kBq must be stopped

42. I-131 therapy Principle Indications In Czech only for inpatients
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

43. 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 Follow-up scan 1 year later
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

49. Parathyroid gland

50. Parathyroid gland Pathophysiology Hyperparathyroidism Primary
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)

51. Parathyroid gland Radiopharmaceuticals Tl-201 Tc-99m MIBI
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) Indications
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)

53. 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 Adenoma
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

55. Subtraction technique
Normal finding

56. Subtraction technique
Autonomous adenoma

57. 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

58. Adrenals - medulla

59. 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

60. 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

61. Image with I-123 MIBG
Normal finding

62. Pheochromocytoma I-131
Before therapy
Post therapy

63. Pheochromocytoma I-123