Radionuclide methods in endocrinology

Otto Lang, MD; Helena Balon, MD

Dept Nucl Med

Charles Univ

3rd School of Medicine

Prague

material for medical students

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

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

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)

Thyroid follicles

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)

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

Thyroid gland - physiology

Normal scan of thyroid gland

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

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)

Graves – Basedow diseaseDiffuse Nodular

Post strumectomy

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

Autonomous adenoma

Initial scan - euthyreosis Repeat scan - hyperhyreosis

Toxic goitre

Before treatment After tx with I-131

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

Thyroiditis

Right lobe involved Left lobe involved

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)

Hashimoto´s thyroiditis

Tc-99m pertechnetate Ga-67 citrate

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

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

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

Methods

• In vitro– RIA of hormones level (T3, T4, TSH))

• In vivo– Non-imaging

• Radio-iodine uptake test

• Perchlorate test

– Imaging • Scintigraphy

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

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)

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)

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)

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

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

“Cold” nodule

Tc-99m pertechnetate

“Hot” nodule

TSH = 1.2

Subacute thyroiditis

Tc-99m pertechnetate

Hashimoto’s thyroiditis

TSH = 4.1

Tc-99m pertechnetate

Graves’ disease

TSH=0.02, FTI=8.9

Tc-99m pertechnetate

Perchlorate test - scheme

Perchlorate testPositive

Tc-99m I-123 test

Negative

Tc-99m

I-123 test

quantification

Tc-99m quantification test

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

Normal scan with I-131

Follicular carcinoma of thyroid gland

Multiple matastases

Follicular carcinoma of thyroid gland

Lung and scull meta Effect of therapy with I-131

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

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

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

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

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

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

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

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

Parathyroid gland

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)

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)

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)

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

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

Subtraction technique

Normal finding

Subtraction technique

Autonomous adenoma

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

Adrenals - medulla

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

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

Image with I-123 MIBG

Normal finding

Pheochromocytoma I-131

Before therapy

Post therapy

Pheochromocytoma I-123