Parathyroid glands and parathyroid scintigraphy

Parathyroid gland anatomy

Usually 4 tiny glands (about 6x4x4 mm, 20-45 mg), one superior and one inferior on each side, partly embedded in the back of the lateral thyroid lobes; some people have 3 or 5+, and ectopic tissue can occur

Chief cells vs oxyphil cells

Chief cells are most abundant and make/release PTH; oxyphil cells are fewer, larger, and more mitochondria-rich, with an unknown normal role but can secrete excess PTH when abnormal

Why oxyphil content matters for imaging

Oxyphil-rich adenomas show avid sestamibi uptake and retention (more mitochondria) and are more likely to cause symptoms; chief-cell-dominant adenomas/hyperplasia show weaker sestamibi uptake and retention

Parathyroid development

Glands form in utero at week 6 as pouches at tongue level, then descend toward the neck with the thyroid; incomplete descent causes ectopic tissue at the tongue base or upper neck, excessive descent causes mediastinal/pericardiac tissue; inferior glands travel further and are more often ectopic, sometimes embedded in the thymus

Imaging field of view rationale

Must run from the top of the salivary glands to the level of the heart so ectopic parathyroid tissue is not missed

PTH regulation by calcium

Chief cells have calcium-sensing receptors; low Ca2+ triggers PTH release, high Ca2+ inhibits it (negative feedback); high Ca2+ also triggers calcitonin release from thyroid parafollicular cells, which opposes PTH

PTH vs calcitonin necessity

PTH is essential for life (no PTH causes tetany); a person can live without calcitonin

Normal serum calcium and PTH ranges

Serum calcium 2.1-2.6 mmol/L; PTH 1-7 pmol/L

PTH actions on bone, kidney, and gut

Bone - promotes osteoclast activity via osteoblast cytokines, releasing Ca2+ and phosphate; kidney - increases Ca2+ reabsorption, blocks phosphate reabsorption, promotes calcitriol formation; gut - via calcitriol, increases Ca2+ absorption from food; net effect is higher blood calcium and lower blood phosphate

Vitamin D activation pathway

Made in skin via UV, goes to the liver, then the kidney, where it becomes active calcitriol

Hypoparathyroidism

Very rare; most commonly caused by accidental removal or damage during thyroid surgery, also autoimmune or congenital; causes hypocalcaemia (nerve hyperexcitability, spasms, tetany, arrhythmias, osteopenia, potentially fatal respiratory dysfunction); treated with vitamin D analogues, calcium supplements, or synthetic PTH

Primary hyperparathyroidism

Serum Ca2+ high, phosphate low, PTH high; the gland itself is abnormal (adenoma, hyperplasia, carcinoma) and ignores feedback; nuclear medicine has a large localisation role

Secondary hyperparathyroidism

Serum Ca2+ low, phosphate variable (likely high in kidney disease), PTH high; healthy glands overwork to compensate for low Ca2+ (kidney failure, GI malabsorption, vitamin D deficiency); no role for nuclear medicine since glands aren't the problem and there's no surgery

Tertiary hyperparathyroidism

Serum Ca2+ high, phosphate variable, PTH high; chronic secondary disease leaves hyperplastic glands that no longer respond to feedback even once Ca2+ is restored; nuclear medicine has a smaller role (glands are small with fewer mitochondria)

Causes of primary hyperparathyroidism

Adenoma (about 85%, usually one gland, often oxyphil-rich); hyperplasia (under 15%, usually all 4 glands, mostly chief cells, genetic or tertiary-related); carcinoma (about 1%, invasive, often significant hypercalcaemia, looks like a solitary adenoma on scan)

Signs and symptoms of hypercalcaemia (mnemonic)

Stones (kidney stones, gallstones), thrones (frequent urination, thirst, dehydration, constipation), bones (pain from bone breakdown/osteoporosis), groans (muscle/bone pain, weakness), psychiatric overtones (confusion, depressed mood); also reduced neuron excitability, arrhythmias, hypertension, vessel/organ calcification

Surgical criteria and approach for hyperparathyroidism

Recommended if Ca2+ > 2.9 mmol/L, kidney/bone/organ damage, or age under 50; now typically a focused parathyroidectomy guided by imaging rather than the older bilateral neck exploration; for rare multi-gland disease, all glands and ectopic tissue are removed and a small fragment autotransplanted into a forearm muscle, with function returning in about 6 weeks

Medical management of hyperparathyroidism

Asymptomatic patients get regular blood tests and monitoring; cinacalcet (a calcimimetic) binds calcium-sensing receptors to lower PTH and Ca2+; bisphosphonates support bone health

Why nuclear medicine is used for parathyroid disease

Not diagnostic (diagnosis is biochemical) but localises hyperfunctioning gland(s) before a selective parathyroidectomy, showing number and site including ectopic positions

Imaging modality comparison

Ultrasound is cheap and radiation-free but weak for small/ectopic glands; 4D CT separates adenoma from thyroid/lymph nodes by HU differences but is insensitive for ectopic glands; nuclear medicine (scintigraphy) is best for adenomas (especially oxyphil-rich) and ectopic glands but poor for hyperplasia and lesions under 300 mg

Tc-99m sestamibi properties

140 keV, 6-hour half-life, pure gamma emitter; lipophilic (diffuses passively across cell membranes); a cation drawn into the negatively charged mitochondrial interior and retained while that membrane potential is maintained; uptake depends on blood flow, cell density, and metabolic activity; excreted mainly via the hepatobiliary system

Sestamibi specificity

Non-specific — taken up by any mitochondria-rich tissue (muscle, liver, spleen, heart, thyroid, parathyroid, thyroid/parathyroid adenomas, and some cancers including lung, breast, oesophageal, bone, head and neck)

Why sestamibi imaging timing works

Parathyroid uptake peaks around 5 minutes but thyroid uptake is also high then; thyroid washout starts around 10 minutes with the biggest thyroid-to-parathyroid contrast at 10-15 minutes (early image); complete thyroid washout takes about 2-4 hours, so a delayed image shows mostly parathyroid tissue, which is retained longer especially in adenomas

Tc-99m tetrofosmin (Myoview)

Works similarly to sestamibi but washes out of the thyroid more slowly and costs more

Tc-99m pertechnetate as a subtraction tracer

An iodide look-alike entering thyroid follicular cells via the sodium/iodide symporter (NIS), trapped but not organified; maps thyroid only (NIS also exists in salivary glands, stomach, and lactating breast, but not parathyroid tissue); subtracting the pertechnetate (thyroid-only) image from the sestamibi (thyroid+parathyroid) image isolates hyperfunctioning parathyroid tissue

Patient preparation for sestamibi parathyroid scan

No special preparation required for sestamibi itself, though some departments stop calcimimetics, calcium supplements, and vitamin D for 1-4 weeks to improve sensitivity; if pertechnetate is used, prep as for a standard thyroid scan (including stopping thyroid medications, iodinated contrast, and iodine-containing supplements for set periods)

Common imaging set-up for parathyroid scintigraphy

Sestamibi dose 600-800 MBq IV, pertechnetate about 50 MBq; patient supine, arms down, neck extended; water given before imaging to clear salivary/oesophageal activity; LEHR collimator, high count rate, matrix 128 or 256, zoom 1; large-FOV anterior static image from the salivary glands to the heart

Dual-phase technique

Uses sestamibi only, relying on differential washout (thyroid clears, parathyroid tissue retains); technically simplest with one injection, but delayed imaging timing can miss the window (too early shows thyroid still, too late shows parathyroid washed out)

Dual-radiopharmaceutical (subtraction) technique

Uses pertechnetate plus sestamibi to directly subtract the thyroid-only image from the combined image; more accurate and sensitive, especially useful in thyroid disease, but is a longer procedure requiring the patient to stay still, and isn't useful after thyroidectomy or recent iodinated contrast

Dual-phase imaging steps

Inject 600-800 MBq sestamibi; early anterior static at 15 minutes; delayed static at 2-3 hours (closer to 2 hours if hyperplasia suspected); SPECT/CT early and/or delayed

Dual-radiopharmaceutical imaging steps

Inject about 50 MBq pertechnetate; static image at 10-20 minutes without moving the patient; inject 600-800 MBq sestamibi with the patient still under the camera; early static at 10-15 minutes, then delayed static at 2-3 hours; SPECT/CT as needed

Benefits and drawbacks of SPECT/CT for parathyroid imaging

Benefits include better detection of small/hyperplastic glands, more precise localisation, attenuation correction, and safer smaller-incision surgery; drawbacks are extra radiation dose, a longer scan, and possible patient intolerance (claustrophobia)

Interpreting a dual-phase scan

On early imaging, uptake occurs throughout the thyroid (can hide a parathyroid focus); on delayed imaging, thyroid activity washes out while a retained focal area suggests hyperfunctioning parathyroid tissue — though thyroid adenomas can also retain sestamibi, creating ambiguity

Interpreting a dual-radiopharmaceutical (subtraction) scan

Pertechnetate activity that persists on the sestamibi image indicates a thyroid adenoma; extra focal uptake on sestamibi absent on pertechnetate indicates abnormal parathyroid tissue, which should still be retained on delayed images; digital subtraction helps when the visual read is equivocal but requires the patient not to move

Causes of a false negative parathyroid scan

Hyperplastic glands (less uptake, thyroid-like washout), small lesions under 300 mg (poor sensitivity), adenomas with few oxyphil cells (less uptake/retention), and patient movement during subtraction

Causes of a false positive parathyroid scan

Thyroid lesions (e.g. adenoma) that also take up sestamibi, patient movement during subtraction, sestamibi-avid cancers (lung, breast, oesophageal, bone, head and neck), and parathyroid carcinoma mimicking a solitary adenoma

Radio-guided parathyroidectomy

A rare technique where a small sestamibi dose is given 2-3 hours before surgery so thyroid activity has washed out but parathyroid activity remains; a hand-held gamma probe in theatre locates and confirms removal of abnormal tissue, shortening surgery and helping locate ectopic tissue