Parathyroid Imaging A Guide to Parathyroid Surgery
Primary Hyperparathyroidism (PHPT) 3 rd most common endocrine disorder after diabetes and hyperthyroidism Prevalence in women 2% Often discovered in asymptomatic pts because of elevation of serum calcium Dx: associated with elevated serum calcium and elevated PTH PTH may be normal but inappropriate to hypercalcemia Familial hypercalciuric hypercalcemia pts are not surgical candidates
Hyperparathyroidism: Symptoms Fragile bones that easily fracture (osteoporosis) Renal stones Increased frequency of urination Unexplained abdominal pain Fatigue out of proportion to task Depression Forgetfulness Bone and joint pain Frequent complaints of illness with no apparent cause GI complaints (nausea, vomiting or loss of appetite)
Parathyroid Hormone
Parathyroid Hormone (PTH) Secreted by the chief cells of the parathyroid gland as an 84 amino acid polypeptide Increases blood concentration of ionic calcium
Parathyroid Hormone (PTH) Acts on parathyroid hormone 1 receptor in bone and kidney Acts on parathyroid hormone 2 receptor in the CNS,pancreas, testes and placenta Half-life of 4 minutes
Regulation of PTH Secretion Controlled by serum calcium through negative feedback Calcium-sensing receptors on parathyroid cells activated when calcium is elevated Additional calcium receptors found in brain, heart, skin, stomach and other tissues. High calcium levels inhibits secretion of preformed PTH from storage granules in the parathyroid gland
Stimulators of PTH Secretion Decreased serum calcium Mild decreases in serum Magnesium Increase in serum phosphate Calcium phosphate complex reduces available calcium for receptors resulting in increased PTH secretion
Inhibitors of PTH Secretion Increased serum Calcium Severe decreases in Magnesium May produce symptoms of hypoparathyroidism Calcitriol Hormonally active metabolite of Vitamin D Increases the level of calcium in the blood by increasing GI absorption Possibly increases release of bone calcium
Indications for Parathyroid Surgery * Only curative treatment for PHPT Indicated in any patient < 50 with serum calcium >0.25 mmol/l(>1mg/dl) above upper limit of normal 24hr-urine calcium >10 mmol Creatinine clearance < 60ml/min * Bilezikian, JP, et al. Guidelines for the management J Clin Endocrinol Metab 99:3561-3569, 2014
Indications for Parathyroid Surgery * Increased stone risk (evidence of stone on imaging) Osteoporosis Vertebral fracture on imaging * Bilezikian, JP, et al. Guidelines for the management J Clin Endocrinol Metab 99:3561-3569, 2014
Rationale for Preoperative Parathyroid Imaging Planning Surgical Strategy Limited exploration vs bilateral Determination of ectopic parathyroid tissue Evaluate recurrent disease Persistent elevation of PTH as high as 20% * Not an initial diagnostic test PTH, Serum Calcium to evaluate patient s signs and symptoms * Bergenfelz, AO, et al. Results of surgery.arch Surg 396:83-90, 2011
Normal Parathyroid
Ectopic Parathyroid
Ectopic Parathyroid Incidence of ectopic parathyroid glands approximately 6-16% * Single parathyroid adenoma most frequent Multi-Glandular Disease (MGD) 2-3 adenomas or MGD hyperplasia in 15-20% of cases Parathyroid Carcinoma (less than 1%) * Phitayakorn, R., et al. Incidence and location of ectopic.. Am J Surg 191:418-423, 2006
Ectopic Parathyroid MGD sporadic or hereditary Isolated familial PHPT MEN-1, MEN-2A, MEN-4 Parathyroid involvement MEN-1 = 95% Suspect MGD in pts with neck radiation or Lithium exposure 5 th parathyroid in 10-15% of normal subjects As many as 2% of subjects require thoracic surgery instead of cervical surgery* * Phitayakorn, R., et al. Incidence and location of ectopic.. Am J Surg 191:418-423, 2006
Parathyroid Imaging Methods Ultrasound Planar imaging with parallel hole collimator Early and delayed views (3 hours) Pinhole collimator Dual isotope planar/pinhole Dual isotope with subtraction SPECT SPECT/CT
Parathyroid Imaging Methods Non-invasive No radiation Cost effective Operator dependent Ultrasound Sensitivity and specificity variable Comparison with MIBI difficult and dependent on techniques used MIBI superior for localizing ectopic parathyroid
Radiopharmaceuticals in PHPT Imaging Thallium-201 Potassium Analog Tc-99m MIBI Mitochondrial seeking agent Tc-99m Pertechnetate Thyroid gland imaging I-123 Thyroid gland imaging
* *
Parathyroid Adenoma Pertechnetate Planar MIBI Planar
Parathyroid Adenoma SPECT MIBI SPECT Pertechnetate SPECT
Parathyroid Adenoma 2.5 hours delay
MIBI early planar Thyroid Adenoma Thyroid Adenoma (concordant MIBI/Pertechnetate) MIBI SPECT Pertechnetate
Parathyroid Adenoma (Value of SPECT) MIBI planar Pertechnetate planar
Parathyroid Adenoma 3-hour delayed image
Parathyroid Adenoma Tc99m MIBI SPECT Pertechnetate SPECT
Parathyroid/Thyroid Adenoma Value of delayed imaging and SPECT MIBI early planar MIBI delayed planar
Parathyroid/Thyroid Adenoma Value of delayed imaging and SPECT MIBI SPECT Pertechnetate SPECT
Comparison of Tc-99m Sestamibi/Pertechnetate Planar & SPECT Imaging with Ultrasound: Advantage of Combined Studies Irina Lev, B.S Waxman, Alan D, M.D; Ih, Grace, B.S D'Agnolo, Alessandro, M.D; Thomson, Louise, M.D ; Adashek, Kenneth, M.D; Melany, Michelle, M.D Cedars Sinai Medical Center, Department of Imaging, Los Angeles, CA 90048 SNM National Meeting June 2010
MIBI/US FOR PARATHYROID ADENOMA : RESULTS TP FP TN FN Sens Acc PPV NM hyperplasia NM Adenoma NM Total N=127 U/S N=74 19 0 0 3 86% 86% 100% 101 0 0 4 96% 96% 100% 120 0 0 7 95% 95% 100% 69 1 0 5 93% 95% 99%
MIBI/US FOR PARATHYROID ADENOMA : RESULTS Adenoma sensitivity = 96% with a PPV = 100% FN adenoma sizes were 8,7,6,5 mm 2 were detected with U/S Hyperplasia sensitive = 86% PPV = 100%. U/S sensitivity = 93% PPV = 99% FN adenoma U/S sizes were 8,7,7,6,5 mm 4 of these were detected with MIBI There was only 1 pt that was (-)on both U/S and MIBI
ECTOPIC PARATHYROID Need for identification prior to surgical exploration MIBI/SPECT-CT best single test
Ectopic Parathyroid : MIBI vs US Incidence and Localization of Ectopic Parathyroid Adenomas in previously Unexplored Patients. Roy M, et al. World J Surg. 37:102-106, (2013)
Limited vs Bilateral National Trends in Parathyroid Surgery from 1998 to 2008: A Decade of Change. Greene AB, et al. J Am Coll Surg. Vol 209, No. 3, Sep 2009
Limited vs Bilateral National Trends in Parathyroid Surgery from 1998 to 2008: A Decade of Change. Greene AB, et al. J Am Coll Surg. Vol 209, No. 3, Sep 2009
Dual Isotope Subtraction Simultaneous co registration - Use I-123 Photo peak (159kEv) - Use Tc-99m photo peak (140kEv) Able to use planar and SPECT dual photo peak
EB - 64 YEAR OLD FEMALE
Dual Isotope Subtraction (Tc-99m I123) EB
EB Parathyroid Adenoma I-123 Subtraction from Tc-99m MIBI
77 year old female With elevated serum calcium and borderline elevation of PTH DG
DG
DG
DG I-123 Subtraction from Tc-99m MIBI
DG Parathyroid Adenoma I-123 Subtraction from Tc-99m MIBI
SPECT-CT High sensitivity Improved specificity Localization
40 YEAR OLD FEMALE WITH HYPERCALCEMIA -12.1 MG/DL (NORMAL 8.4-10.2) NECK ULTRASOUND = 1.7 cm hypoechoic nodule inferior to right thyroid lobe suspicious for an enlarged parathyroid. OH
OH
Parathyroid Adenoma EARLY 3 HOUR OH
OH Parathyroid Adenoma SPECT/CT
67 year old male with clinical suspicion of parathyroid adenoma. Serum Calcium 10.6 (H) (8.6-10.3 mg/dl). Parathyroid Hormone 78 (H) (14-64 pg/ml) U/S = MNG LE
67 year old male with clinical suspicion of parathyroid adenoma. LE
LE
PS 76 yo female with parathyroidectomy 11 years ago now with rising PTH and Calcium levels Parathyroid hormone 83.3 (H) (14-72 pg/ml). Calcium 11.4 (H) (8.4-10.2 mg/dl) Ultrasound demonstrates multi-nodular thyroid with no parathyroid adenoma located. CT negative for parathyroid adenoma
PS
Early 3hr- Delayed PS
Dx = TE Groove Parathyroid Adenoma Early MIBI PS
56 year old female Hx of total thyroidectomy and total parathyroidectomy for multinodular goiter and parathyroid hyperplasia right lower pole parathyroid was implanted in the patient's right forearm Patient has persistent elevation of parathyroid hormone. U/S negative EC
EC
EC Dx = L paratracheal PTA
EC Dx = L paratracheal PTA
EC Dx = L paratracheal PTA
EC Dx = L paratracheal PTA
EC Implanted Parathyroid Right Forearm
Summary Parathyroid imaging used for pre-surgical planning in pts with biochemical markers suggesting parathyroid adenoma or hyperplasia U/S mainly used as complimentary to MIBI Performs poorly in ectopic parathyroid Operator dependent MIBI/SPECT becoming standard of practice MIBI/SPECT-CT gives high sensitivity and specificity as well as location