Scintigraphy sorts FUNCTION, not benign-vs-malignant: a cold nodule is non-specific (mostly benign but cannot exclude cancer), so a focal FDG-avid or cold nodule needs ultrasound/FNA.
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¹²³I / ⁹⁹ᵐTc-pertechnetateRadioiodine
Mild · variable
Ranges from warm to cold; most palpable nodules are non-functioning ('cold')
¹⁸F-FDGFDG
Mild · variable
Usually low, but focal incidental FDG uptake is indeterminate
Why it looks this way
Benign follicular cells trap iodine/pertechnetate via NIS to a variable degree, and degenerating colloid nodules commonly lose trapping so appear 'cold'.
Interpretive pitfall
Incidental focal thyroid FDG uptake carries a genuine malignancy risk and must not be dismissed as benign.
Diffuse intense homogeneous uptake with HIGH RAIU = Graves — the key split is hyperthyroidism with high uptake (Graves, toxic nodular disease) versus low uptake (thyroiditis, exogenous/factitious).
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¹²³I / ⁹⁹ᵐTc-pertechnetateRadioiodine
Intense
Diffuse, homogeneous, intensely increased uptake with elevated RAIU
¹⁸F-FDGFDG
Moderate · variable
Diffuse mild-moderate uptake in the stimulated gland, typically incidental
Why it looks this way
TSH-receptor–stimulating antibodies cause diffuse hyperplasia and upregulate NIS throughout the gland, producing uniform high trapping and organification.
Interpretive pitfall
Diffuse thyroid FDG uptake on oncologic PET usually means autoimmune thyroid disease (Graves/Hashimoto), not malignancy.
Differential washout — the abnormal gland retains sestamibi on delayed imaging while thyroid washes out; ¹⁸F-fluorocholine PET is the most sensitive, particularly for multigland/ectopic glands.
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⁹⁹ᵐTc-sestamibi (dual-phase / SPECT/CT)Other
High
Retains tracer on delayed images relative to thyroid washout; SPECT/CT localizes
¹⁸F-fluorocholine PET/CTCholine
High
Most sensitive modality, especially multigland and ectopic disease
Taken up by thyroid only — subtracted to isolate the parathyroid focus
Why it looks this way
Hypercellular chief/oxyphil cells are mitochondria-rich, so the lipophilic cation sestamibi accumulates and is retained in mitochondria; choline uptake reflects membrane-phospholipid synthesis in proliferating parathyroid cells.
Interpretive pitfall
P-glycoprotein–mediated rapid washout and multigland disease cause sestamibi false-negatives; thyroid nodules also take up sestamibi and choline (false-positives).
Thyroid & parathyroid
Thyroiditis — Hashimoto and subacute (de Quervain)
Thyrotoxicosis with LOW radioiodine uptake indicates destructive/release thyroiditis rather than Graves — the single most useful RAIU discriminator.
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¹²³I / ⁹⁹ᵐTc-pertechnetateRadioiodine
None · variable
Low/absent uptake in the thyrotoxic (destructive) phase; patchy in chronic Hashimoto
¹⁸F-FDGFDG
Moderate · variable
Diffuse uptake in Hashimoto from lymphocytic infiltration
Why it looks this way
Follicular destruction releases preformed hormone while trapping fails (low RAIU); metabolically active lymphocytic infiltration in Hashimoto drives diffuse FDG uptake.
Interpretive pitfall
Hashimoto is the substrate for primary thyroid lymphoma and associates with papillary carcinoma — a dominant focal nodule/FDG focus on a Hashimoto background still needs evaluation.
Thyroid & parathyroid
Toxic (autonomously functioning) thyroid adenoma
Benign
¹²³I / ⁹⁹ᵐTc-pertechnetate · High¹⁸F-FDG · Mild
Key interpretation clue
A truly 'hot' (hyperfunctioning) nodule on RAI is almost always benign — the mirror image of the non-specific cold nodule.
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¹²³I / ⁹⁹ᵐTc-pertechnetateRadioiodine
High
Focal 'hot' nodule with suppression of the surrounding and contralateral gland
¹⁸F-FDGFDG
Mild
Characteristically low — hyperfunctioning nodules are almost always benign
Why it looks this way
Activating TSH-receptor or Gsα (GNAS) mutations drive constitutive NIS-mediated trapping and organification independent of TSH, suppressing the rest of the gland.
Interpretive pitfall
A discordant nodule (warm on pertechnetate = trapping, but cold on radioiodine = no organification) can rarely harbour malignancy; pertechnetate reflects trapping only.
Thyroid & parathyroid
Anaplastic thyroid carcinoma and primary thyroid lymphoma
Malignant
¹⁸F-FDG · Intense¹²³I / ¹³¹I (RAI) · None
Key interpretation clue
A rapidly growing, intensely FDG-avid but radioiodine-COLD thyroid mass is anaplastic carcinoma or lymphoma — the dedifferentiated end of the spectrum; lymphoma (often on a Hashimoto background) is chemo/radiosensitive, so urgent tissue diagnosis is critical.
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¹⁸F-FDGFDG
Intense
Intensely avid, rapidly enlarging mass; used for staging and response
¹²³I / ¹³¹I (RAI)Radioiodine
None
Photopenic/cold — no NIS expression, no role for radioiodine therapy
Why it looks this way
Undifferentiated anaplastic cells and lymphoma are highly glycolytic (GLUT overexpression) yet have lost follicular differentiation and NIS, so they neither trap iodine nor respond to RAI.
Interpretive pitfall
Intense FDG uptake is non-specific — anaplastic carcinoma, lymphoma and florid Hashimoto/inflammation overlap, so biopsy, not PET intensity, makes the diagnosis.
Hürthle cell carcinoma is the classic 'iodine-negative, FDG-positive' differentiated cancer — do not rely on RAI; stage and follow with FDG PET.
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¹²³I / ¹³¹I (RAI)Radioiodine
Moderate · variable
Follicular carcinoma is often iodine-avid (esp. metastases); Hürthle/oncocytic is frequently NON-avid
¹⁸F-FDGFDG
High · variable
Workhorse when RAI-negative; Hürthle and dedifferentiated follicular disease are FDG-avid
Why it looks this way
Follicular carcinoma retains variable NIS, whereas oncocytic (Hürthle) cells are mitochondria-rich, highly glycolytic and typically NIS-poor — low iodine trapping but high glucose metabolism.
Interpretive pitfall
Mitochondria-rich Hürthle cells can show sestamibi uptake; follicular adenoma vs carcinoma cannot be separated by scintigraphy (diagnosis rests on histologic capsular/vascular invasion).
MTC does NOT concentrate radioiodine — image it as a neuroendocrine tumour (F-DOPA first-line with elevated calcitonin; FDG for aggressive/CEA-driven disease; DOTATATE mainly to assess PRRT eligibility); biomarkers guide tracer choice.
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¹⁸F-DOPAAmino-acid PET
High
First-choice per guidelines, especially with elevated calcitonin; reflects amine-precursor uptake/decarboxylation
Avid in higher-grade disease with rising CEA and short calcitonin doubling time
¹²³I / ¹³¹I (RAI)Radioiodine
None
No uptake — C-cell origin lacks NIS
Why it looks this way
Parafollicular C cells are neuroendocrine (APUD): they express amine-precursor machinery (F-DOPA) and somatostatin receptors (DOTATATE) but are not follicular and lack NIS.
Interpretive pitfall
A normal radioiodine/pertechnetate scan does not exclude MTC, and heterogeneous expression means tracers are complementary, not interchangeable.
The 'flip-flop' phenomenon — iodine-avid and FDG-negative when differentiated, iodine-negative and FDG-avid when dedifferentiated; FDG-avid disease carries a worse prognosis and is not RAI-treatable.
Avid when dedifferentiated/iodine-negative; used for Tg-positive, scan-negative disease
Why it looks this way
Differentiated follicular-derived cells retain NIS (iodine avidity); dedifferentiation (e.g. BRAF-V600E) downregulates NIS and upregulates GLUT/glycolysis, shifting the tumour to FDG avidity.
Interpretive pitfall
RAI imaging requires elevated TSH (withdrawal or rhTSH) and a low iodine load; physiologic salivary, bowel and bladder activity are normal and must not be called metastases.
Lung & mediastinum
Active granulomatous disease (tuberculoma / infectious granuloma)
Benign
¹⁸F-FDG · High · variable⁶⁸Ga-FAPI · Mild · variable
Key interpretation clue
The archetypal benign FDG false-positive — inflammation cannot be separated from cancer by avidity; a solitary FDG-avid nodule in a TB/fungal-endemic patient must be interpreted with morphology, calcification pattern and clinical context.
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¹⁸F-FDGFDG
High · variable
Active granulomas can be moderately-to-intensely avid, indistinguishable from malignancy on avidity alone; inactive/calcified granulomas are FDG-cold
⁶⁸Ga-FAPIFAPI
Mild · variable
Generally lower than in malignancy, potentially improving specificity, though inflammatory fibroblasts can still take up FAPI
Why it looks this way
Activated macrophages, epithelioid cells and giant cells in a granuloma are highly glycolytic and overexpress GLUT transporters, so FDG uptake reflects inflammatory metabolism rather than tumour.
Interpretive pitfall
A hypermetabolic solitary pulmonary nodule that is really a tuberculoma or histoplasmoma is the classic trap; benign calcification pattern on CT is the key clue.
Lung & mediastinum
Pulmonary hamartoma
Benign
¹⁸F-FDG · None
Key interpretation clue
CT clinches it — intralesional fat and 'popcorn' chondroid calcification in an FDG-cold nodule are diagnostic of hamartoma; imaging is confirmatory rather than needing FDG.
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¹⁸F-FDGFDG
None
Characteristically FDG-negative or minimally avid, consistent with an indolent benign lesion
Why it looks this way
Composed of mature cartilage, fat and connective tissue with negligible proliferation and low glucose metabolism, so it traps essentially no FDG.
Interpretive pitfall
Remember FDG-negativity alone is not proof of benignity (lepidic/mucinous cancers are also cold), so rely on the specific CT fat/calcification features, not the cold PET.
Lung & mediastinum
Sarcoid hilar/mediastinal lymphadenopathy
Benign
¹⁸F-FDG · High · variable⁶⁷Ga citrate · High
Key interpretation clue
Distribution over intensity distinguishes benign from malignant nodes — symmetric bilateral hilar 'lambda' (± lacrimal/parotid 'panda') uptake favours sarcoid, whereas asymmetric bulky avid nodes raise concern for lymphoma or metastatic cancer.
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¹⁸F-FDGFDG
High · variable
Active sarcoid nodes are often intensely avid in a symmetric bilateral hilar + right paratracheal (lambda) distribution; marks active inflammation and biopsy targets
⁶⁷Ga citrateGallium
High
Classic panda/lambda uptake pattern of active sarcoidosis (historical); largely superseded by FDG-PET
Why it looks this way
Non-caseating epithelioid granulomas packed with activated macrophages and lymphocytes are highly glycolytic, producing intense FDG uptake that mirrors disease activity rather than malignancy.
Interpretive pitfall
FDG-avid sarcoid nodes can perfectly mimic nodal metastases and cause overstaging of a known lung cancer; sarcoid-cancer coexistence means avid nodes still warrant tissue confirmation.
Practice and education only. Avidity is qualitative and pattern-based; correlate with the complete clinical picture and current guidance.