NUCLEAR ENDOCRINOLOGY Prof. Dr. Haluk B. Sayman

THYROİD Embryology Derived from median primordium which is developed from two lateral primordia in 1st maternal month. It has two lobes connected with thyroglossal duct and located in front of pharynx. At the end of 7th week these lobes migrate to both sides of trachea. The lower part of thyroglossal duct makes pyramidal lobe. By the end of 3rd month it concentrates colloidal material. Within 10.5 weeks it concentrates iodine and starts hormon synthesis.

Thyroid consists of two lobes and an isthmus connecting them. It is located in front of neck at the level of 2. and 3. trachea cartilage. It weighs gr. Each lobe cm in height and cm in width, isthmus is 2 cm wide and 0.5 cm thick. Superior thyroid arteries branches from external carotis, inferior thyroid arteries from the thyroservical branch of subclavian artery. It has superior, middle and inferior veins. RecLN is close to inferior SupLN is to superior arteries. THYROID Anatomy

THYROID Physiology Thyroid gland produces T4 and T3 hormones in the follicule cells after organifying the iodine trapped inside the colloid by peroxidase and binding it with the thyrosin molecule linked with thyroglobulin. These hormones are released from the thyroglobulin by proteolysis and secreted to the blood by TSH. In the body, T4 is converted into T3 by 5´deiodinase enzyme. Calcitonin is secreted by parafollicular ‘C’ cells into the serum depending on the calcium levels.

THYROID Diseases Thyroid diseases are very frequent in our country and for the first diagnosis, in-vitro laboratory tests with scintigraphy and ultrasonography are used. Thyroid Diseases in general: Simple Goiter Nodular Goiter Hypothyroidism or Hyperthyroidism Thyroiditis Malignant Thyroid Diseases

In-vitro thyroid function tests T4, T3 or fT4, fT3: Lately radioimmunoassay, presently ELISA or chemiluminescent methods are used to measure these. Increase in hyperthyroidism, decrease in hypothyroidism or thyroiditis. TSH: Increases or decreases by the negative feedback of thyroid hormons on hypophysis. Increases in hypothyroidism, decreases in hyperthyroidism. Thyroglobulin: Helps to differentiate Thyrotoxicosis factitia and thyrotoxicosis from thyroiditis. Actually, used in the follow-up of well differentiated thyroid cancers after postoperative radioiodine ablation. Increases in case of metastasis. Calcitonin: Secreted by parafolicular C-cells. Used for the diagnosis of C-cell hyperplasia or medullary thyroid carcinoma. Pentagastrin or pentagastrin-Ca provocation increases its sensitivity. Thyroid antibodies: TT, TM, TPO, TSH receptor antibodies increase in autoimmune thyroid diseases (Hashimoto, Graves’).

THYROID imaging Radiography Scintigraphy-Planar, SPECT, PET Ultrasonography Computerized Tomography Magnetic Resonance Imaging X-ray Florescence scanning

RADIOLOGY Simple radiography can detect a space occupying thyroid mass with incidental calcifications. A chest X-ray, ordered for another indication can show a soft tissue density or a thyroid hyperplasia shifting trachea off the midline.

THYROID Scintigraphy Tc-99m pertechnetate is the most widely used radionuclide. Tc-99m, is captured like iodine molecule but is not organified. I-123, on the other hand, is both captured and organified to show total function. But since it is a cyclotron product, it is expensive and short lived. I-131 is usually spared for metastatic disease screening for its high radiation dose and inferior image quality. 20 min. after iv injection of 5 mCi Tc-99m, anterior and both anterior oblique images are acquired for counts, preferably with pin-hole collimator. Sternal notch is marked with a radioactive marker.

THYROID Scintigraphy Both lobes are visualised as V-shaped elipsoid bodies connected with a thin isthmus in normal scan. Salivary glands, oral mucosa and esophagus may be seen in the neighbourhood. Right lobe is somewhat larger than the left. In 10% of the patients pyramidal lobe may be present. ANTERIOR R ANT. OBLİQUE L ANT. OBLİQUE

THYROID Scintigraphy The size and activity uptake of thyroid increase homogenously in hyperthyroidism and Basedow Graves’ disease and pyramidal lobe becomes prominent. EXOPHTALMIA Normal Enlarged RAO LAO ANT

THYROID Scintigraphy The activity uptake decreases with variable sizes in hypothyroidism and thyroiditis.

THYROID Scintigraphy Consuming external thyroid hormone, iodine or radiological contrast media decrease the uptake.

THYROID Scintigraphy While uptake increases in a toxic nodule, it decreases in the surrounding tissue due to suppression. Hypoactive nodules has lower uptake in comparison with its surrounding and has an increased malignancy rate.

THYROID Scintigraphy In well differentiated thyroid cancers (DTC) Tl- 201 or Tc-99m MIBI uptake is more than normal tissue. The recurrence and metastasis of DTC is screened by periodical I-131 or I-123 whole- body scintigraphies. Medullary thyroid cancers may have I-131 MIBG, Tc-99m (V) DMSA or In-111 Octreotide uptakes. Anaplastic and low differentiated cancers have no Tc-99m or radioiodine uptakes.

THYROID Scintigraphy Normal Tc-99m MIBI scintigraphy has similarity with Tc- 99m and the uptake decreases with time. Tc-99m MIBI 10 min. MIBI 120 min.

THYROID Scintigraphy The MIBI uptake in malignant tumours with no Tc-99m or I-131 uptake does not decrease with time. Tc-99m I-131 MIBI 10 dk. MIBI 120 dk.

THYROID Scintigraphy Nodules without high malignancy risk does not have Tc-99m MIBI uptake or have rapid washout. MIBI 10 min. MIBI 120 min. MIBI 10 min. MIBI 120 min.

Whole-body Scintigraphy An I-131 whole body scan of a patient with differentiated thyroid cancer showing local recurrence during follow-up period, after therapy. ANTERIOR POSTERIOR

Whole-body Scintigraphy I-131 negative but In-111 octreotide positive whole-body scan in a patient with metastatic Hurthle cell thyroid cancer. I-131 In-111 ocreotide

Anatomical Imaging Methods CT USG MRI

Hybrid Imaging Methods The functional information is fuse with anatomical detail by PET-CT or SPECT-CT. This helps more precise lesion detection. It is indicated in the follow-up of those thyroid cancer patients with positive thyroglobulin levels but negative I-131 WB scans.

X-ray FLORECENCE SCANING Photons emited by Ameritium-241 source (γ ray) interact with the non- radioactive I-127 inside the thyroid cells and produce X-rays to record on films. Favorable in small children and pregnant ladies, since it does not need iv radioactivity injections.

THYROID Uptake Test A quantitative measure of thyroid function. It gives a percentage uptake of a standart radioiodine dose in a time constant. Measurements are made at 4 and 24 hours. It increases in hyperthyroidism, decreases in hypothyroidism and thyroiditis. Thyroid cpm (t)-Thigh cpm(t) Standart cpm(0) Uptake %: x x 100 Standart cpm(t) Glass cpm(0)

PARATHYROID Embryology Lower parathyroid glands arise from III. branchial sac, upper parathyroid glands arise from IV. branchial sac. Upper glands are usually located behind the upper poles of thyroid lobes. Although inferior glands are located nearby lower poles, they have frequent ectopic locations. Thymic or mediastinal ectopies may be seen.

PARATHYROID Anatomy and Physiology Normal parathyroid glands are 6 mm long, 3-4 mm wide and mm thick. There are 4 glands They are perfused by inferior thyroid arteries or by anastomoses between superior and inferior thyroid arteries. Parathyroid hormone regulates phosphate secretion and calcium reabsorption in kidneys, stimulates osteoclasts and increases calcium absorption in GIS. Larynx IV Parathyroids III Parathyroids

PARATHYROID Diseases Hyperparathyroidism Primary: The functional impairment of parathyroids Secondary: The reaction of parathyroids to chronic renal failure Tertiary: Autonomy of glands following secondary hyperparathyroidism

PARATHYROID Scintigraphy Technetium-Thallium subtraction scintigraphy: Thyroid captures both Tc an Tl. Parathyroid adenoma has only Tl uptake. First Tc-99m is injected and imaged. Then without moving patient under gamma camera Tl-201 is injected and imaged again. Images acquired on a computer are subtracted from each other and discrepant parathyroid uptake is detected.

PARATHYROID Scintigraphy Tc-99m MIBI scintigraphy: Used either instead of Tl-201 in subtraction scintigraphy or alone. If used alone, early images showing focal radionuclide uptake with retention on late images is characteristic with parathyroid adenoma. Same condition is true also for mediastinal ectopic glands. The retention of activity indicates ectopic parathyroid adenoma.

PARATHYROID Scintigraphy SPECT/CT: SPECT and CT images are recorded on the same equipment simultaneously. CT images are used for attenuation correction and detailed information for sectional anatomy. By this means the origin of Tc-99m MIBI accumulation is correctly identified.

ADRENAL GLANDS Adrenal Cortex scintigraphy: I-131 labeled cholesterol is used to show adrenal hyperplasia in Cushing syndrome or primary aldosteronism. Adrenal Medullary scintigraphy: I-123 or I-131 labeled MIBG (metaiodobenzylguanidine) is used for neuroblastoma ve pheochromacytoma.

ADRENAL GLANDS I-131 MIBG uptake on left adrenal pheochromocytoma mass.

ADRENAL GLANDS Neuroblastoma AP PA

ADRENAL GLANDS MRI and SPECT slices showing I-123 MIBG uptake on right adrenal neuroblastoma and its liver metastasis Low MIBG uptake in the heart is related with the increased metabolism of chatecholamins.

Therapy in Neuroendocrine Tumors High dose I-131 MIBG is administered to ablate MIBG receptor positive tumors. In-111 octreoscan is used to detect receptor positivity to apply somatostatin for treatment of carcinoid tumors.