THE PARATHYROID GLAND

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					     THE PARATHYROID GLAND
THEORY AND NUCLEAR MEDICINE PRACTICE
             George N. Sfakianakis MD
       Professor of Radiology and Pediatrics
       Director, Division of Nuclear Medicine
                     UM/JMMC
                      Miami FL




                                                October 2009
           ENDONCRINE GLANDS
    RADIOISOTOPE IMAGING AND THERAPY
THYROID GLAND     TRAPPING MECHANISM : 99mTc-04Na (γ)
                  IODINATION: 123I (γ), 131I (β), 125I (Auger e-)
                  METABOLISM: 18FDG, 201TI (x), 99mTcMIBI (γ)

PARATHYROIDS      METABOLISM (K):       201TI(x), 99mTc-MIBI        (γ)

ADRENAL CORTEX    STEROIDOGENESIS:      131I(123I)   CHOLESTEROL

ADRENAL MEDULLA   NORADRENALIN SYNTHESIS:             131I(123I)   MIBG

PITUITARY GLAND   RECEPTORS: 18F-BROMOCTYPTINE
                             111In- 99mTc-OCTREOTIDE



RVH (RENIN)       ACE-INHIBITORS        99mTc-MAG
                                                       3/LASIX


SOMATOSTATIN RECEPTOR IMAGING:        111In-OCTREOTIDE
     PARATHYROID GLANDS




ANATOMY-EMBRYOLOGY-PHYSIOLOGY
LOCATION OF ORTHOTOPIC
AND ECTOPIC PARATHYROID
  GLANDS AND ADENOMAS
           HYPERPARATHYROIDISM




(1) PRIMARY: TUMORS (ADENOMAS-CARCINOMAS)
             HYPERPLASIA

(2) SECONDARY:   RENAL FAILURE => HYPERPLASIA
     PARATHYROID GLAND SCINTIGRAPHY




•   201Thallium+99mTc-Pertechnetate(TcPTC)


•   99mTc-SESTAMIBI+123INa   or TcPTC

•   99mTc-SESTAMIBI   30min+120min imaging

•   SPECT/CT (99mTc-SESTAMIBI 30min+2hr)
   PARATHYROID IMAGING
  RADIOPHARMACEUTICALS



Single Photon agents for Planar and SPECT


    201Thallium    99mTcSestamibi




        Tl +


        Tl
   PARATHYROID IMAGING
  RADIOPHARMACEUTICALS




           Mitochondria

 Pump




Thallium    Sestamibi
A patient is evaluated with clinical and laboratory finding
              suggesting hyperparathyroidism

   A Thallium / Technetium study is performed to see
                 parathyroid adenoma
              PARATHYROID ADENOMA (Primary)
        with Thallium-201 / Tc-99m Pertechnetate Subtraction

 Tl visualizes
                                                        Tc-PT visualizes
the Thyroid and
                                                        Only the Thyroid
the Parathyroid
   Adenoma

                        Thallium   Tc-Pertechnetate




     Subtraction Images
            show only
    the Parathyroid Adenoma


                                          Subtraction Images
           A patient is referred for parathyroid adenoma
   The patient had right hemi-thyroidectomy to remove (50% by
chance) an unidentified potentially orthotopic parathyroid adenoma
 The patient had a Thallium-201 / Tc-99m-Pertechnetate study now
  PARATHYROID ADENOMA (Primary)
               MEDIASTINAL

THALLIUM                        PERTECHNETATE



              Salivary glands

               Hemi-thyroid




     Mediastinal parathyroid adenoma
   Enters Sestamibi (MIBI)


Sestamibi has higher
   Sensitivity than Thallium
for Parathyroid adenomas

             but also

While Sestamibi is washed out
     from the thyroid gland
  it stays in the parathyroid


O’Docherty et al JNM 1992, 33:313-318
      EARLY AND LATE IMAGING WITH MIBI




PARATHYROID LESION: AREA OF PRESISTENT ACTIVITY


LOCALIZATION RATE 90% (19/21) FOR ADENOMA




Taillefere et al JNM 1992; 33:1801-1807
               (Surgical) Therapy of PTH-Adenomas
                       the Miami Approach

                      The effort of the surgeon:
Localization and Complete Excision of all Hyperfunctioning Tissue
          (this can be a difficult and lengthy operation)

    Hypothesis:

• Exact Preoperative Localization by MIBI-SPECT
   helps identify easier and faster the Adenoma(s)

•   Intraoperative monitoring of PTH
     confirms the total excision of all abnormal tissue

       These may improve results and shorten the operation
2
 Protocol for Parathyroid Adenoma Localization
      with 99mTc-SESTAMIBI at UM/JMH


99mTc-SESTAMIBI     20 mCi IV
Planar and SPECT acquisition (Picker/Trionix)
immediately and at 2 hours post injection


Routine Reconstruction and Reprojection mode


Review of SPECT in the Reprojection mode
its 34 images and the rotating 3-D version
     Planar       99mTc-SESTAMIBI   Study

                 Reprojection mode = 34 images
30 min    2 hr


  SPECT
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
          PARATHYROID ADENOMA (Primary)
  RIGHT, LOWER POLE, WITHIN THE THYROID GLAND

                              MIBI Volume Images


Salivary glands       EARLY


Thyroid gland
Heart

                               ANT        R. LAT
Parathyroid adenoma
                       LATE



Strap Muscles


                                 ANT       R. LAT
                           PATHOLOGIC FOCI


•   PARATHYROID ADENOMAS/HYPERPLASIAS


•   THYROID TUMORS (BENIGN AND MALIGNANT)
    [99mTc04Na (123INa) may exclude functioning (benign) thyroid tumors but not
     carcinomas ]


•   MEDIASTINAL/NECK/CHEST TUMORS/LYMPH NODES
    [67Ga may exclude lymphomas, lung cancer]
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
         PARATHYROID ADENOMA (Primary)
 LEFT, LOWER, POSTERIOR, ADJACENT TO THE SPINE



  MIBI Planar Images               MIBI Volume (reprojection) Images
   Early             Late            Early




                                     Late



    Parathyroid adenoma
                                       Anterior   LAO      Left Lateral
But where exactly is it located?
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
        PARATHYROID ADENOMA (Primary)
LEFT, CAUDALLY AND IN THE SAME PLANE WITH THE
    THYROID (ECTOPIC IN THE THYMUS GLAND)

  MIBI Planar Images               MIBI Volume (reprojection) Images
      Early              Late      Early




                                   Late



    Parathyroid adenoma
But where exactly is it located?     Anterior    LAO      Left Lateral
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
            PARATHYROID ADENOMA (Primary)
         RIGHT, LOWER, INSIDE THE THE THYROID
          AND THYROID ADENOMA LEFT, UPPER


   MIBI Planar Images                 MIBI Volume (reprojection) Images
                                         ANT       LAO        L LAT




                                      EARLY

    EARLY             LATE
      Questionable Findings

   There is a lesion on the left

                                       LATE
There is also a lesion on the right
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
           PARATHYROID ADENOMA (Primary)
               FALSE NEGATIVE STUDY



MIBI Planar Images         MIBI Volume (reprojection) Images
   Early            Late
                             Early




           7/7

                             Late



           7 / 21
                              Right Lateral   RAO    Anterior
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
          TWO PARATHYROID ADENOMAS (Primary)
           RIGHT, UPPER AND LOWER, WITHIN THE THYROID


  MIBI Planar Images                   MIBI Volume (reprojection) Images




There is a lesion on the right upper

There is a lesion on the right lower

       There is a LN uptake
         MODE OF REPORTING

All abnormal foci in the neck and mediastinum
present early and active late are reported

Upper limit: thyroid cartilage (strap muscles?)
Lateral limit: 1cm lateral to thyroid margin
Inferior limit: myocardium

Foci are ordered by intensity of activity
and size of the abnormality
and are localized in relation to the thyroid

The surgeon reviews the study preoperatively
in consultation with the nuclear specialist
       A patient s/p renal transplant
is referred for Tc-Sestamibi (MIBI) study
        for parathyroid hyperplasia
       (hypercalcaemia / high PTH)
       PARATHYROID HYPERPLASIAS (Secondary)



MIBI Planar Images             MIBI Volume (reprojection) Images

     Early        Late              Early            Late




There are two lesions planar
                                     There are two lesions tomo
       Muscle uptake
SECONDARY HYPERPARATHYROIDISM
   All 4 parathyroid glands are hyperplastic
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
            PARATHYROID ADENOMA (Primary)
             ECTOPIC (MIDDLE MEDIASTINAL)

         MIBI Planar          MIBI SPECT Volume(reprojection)

                                  ANT        LAO         L LAT
    EARLY            LATE




                                EARLY




Ectopic Parathyroid Adenoma

                                LATE
       Bone marrow
                                 Ectopic Parathyroid Adenoma
  How deep is it located?               Retrosternal
  Additional scintigraphic studies for more Precise Localization
                   and Tissue Characterization

To Better Localize Mediastinal Lesions:
a) Simultaneous Sestamibi, Skeletal and Blood Pool SPECT:
    30 mCi MDP the night before (Bone Scan)
    20 mCi SESTAMIBI
    5(8) mCi Human Serum Albumin
b) Sestamibi SPECT/CT


To Differentiate Lymphoma from PTH Adenoma
Sequential SESTAMIBI-GALLIUM SPECT
    (Gallium showed only lymphoma)
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
     PARATHYROID ADENOMA (Primary)
      ECTOPIC (LOWER MEDIASTINAL)

Tc-SESTAMIBI         Tc-SESTAMIBI + Tc-HSA(for Blood Pool)




Ectopic Adenoma   Ectopic Adenoma on the ascending aorta
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
            (hypercalcaemia / high PTH)
           PARATHYROID ADENOMA (Primary)
                     ECTOPIC


                        PLANAR MIBI
                    EARLY             LATE




To Better Localize Mediastinal Lesions:
a) Simultaneous: Sestamibi, Skeletal and Blood Pool SPECT:
b) Sestamibi SPECT/CT
    PARATHYROID ADENOMA (Primary)
          Ectopic (Mediastinal, middle)
            Under the Aortic Arch




Adenoma        Skeleton              Aortic Arch
A patient is referred for Tc-Sestamibi (MIBI) study
for parathyroid adenoma S/P Hemithyroidectomy
             (hypercalcemia / high PTH)
PARATHYROID ADENOMA (Primary) ECTOPIC



                      PLANAR MIBI
                  EARLY             LATE




    Early Study                            Late Study
PARATHYROID ADENOMA (Primary) ECTOPIC

              Early Study


               PLANAR MIBI
           EARLY             LATE




               Late Study
PARATHYROID ADENOMA (Primary)
     Ectopic (Mediastinal, middle)
       Under the Aortic Arch
A patient is referred for SPECT/CT
    Tc-Sestamibi (MIBI) study
     for parathyroid adenoma
   (hypercalcemia / high PTH)
PARATHYROID ADENOMA (Primary) ORTHOTOPIC




                Early Study
PARATHYROID ADENOMA (Primary) ORTHOTOPIC



                 PLANAR MIBI
             EARLY             LATE




                 Late Study
A patient is referred for Tc-Sestamibi (MIBI) study
              for parathyroid adenoma
             (hypercalcemia / high PTH)
               PARATHYROID ADENOMA (Primary)
                    In a patient with Lymphoma
                The use of Gallium for differentiation


    Tc-Pertechnetate




    Tc-SESTAMIBI




   ANT         LAO       L LAT
                                           Lymphomas

Lymphomas. Is there an adenoma?           The Adenoma
            PROTOCOL OF OPERATION

PERIPHERAL VENOUS BLOOD IS DRAWN/PREPARED
  (FOR BSL-PTH)

THE MOST INTENSE/LARGER FOCUS IS EXCISED
  (RESECTION-1)

PERIPHERAL VENOUS BLOOD IS DRAWN 5 min LATER
  (FOR PRS-PTH) (T1/2 of PTH in the blood is 2-3 min)

IF PRS-PTH <1/2 BSL-PTH, OPERATION COMPLETED

WHEN ADDITIONAL LESIONS EXIST PTH REMAINS HIGH
THE SURGEON EXCISE THE NEXT MOST INTENSE/LARGE
FOCUS AND PERIPHERAL VENOUS BLOOD IS DRAWN
FOR PRS-PTH REPEATEDLY,UNTIL PRS-PTH <1/2 BSL-PTH
 QUICK INTRAOPERATIVE PTH ASSAY(qPTH)


IMMUNORADIOMETRIC (12 min)
IRMAIMMUNOCHEMILUMINESCENCE (5 min)


PTH HAS SHORT HALF LIFE (3-4 min)


DRAW BLOOD BEFORE AND 5 min AFTER EXICISION
SPIN/INCUBATE COUNT IN THE OPERATING ROOM
RESULTS AVAILABLE BEFORE PATHOLOGY REPORT
IF THERE IS A 50% DROP IN qPTH , AWAKE PATIENT
         THE ROLE OF PREOPERATIVE
SPECT 99mTc-SESTAMIBI TUMOR LOCALIZATION
 AND INTRAOPERATIVE PTH MONITORING IN
           PARATHYROIDECTOMY




    G. N. Sfakianakis, J. Foss, M. Georgiou, G.
   Irvin III S. Levis-Dusseau, S. Chandarlapaty

     University of Miami School of Medicine,
                    Miami, FL
MIBI-SPECT/RPJ IN
PARATHYROIDECTOMY
          THE UM EXPERIENCE
 Preoperative scintigraphy (MIBI-SPECT/RPJ)
 Intraoperative measurements of PTH (QPTH)

 Total patients studied:   75
 Patients operated:        58
 (10:52,20:4,MEN:2)

 SPECT: Sensitivity = 94%, Specificity = 92%
 SPECT+QPTH: 98% cure rate in 30%less time
           INITIAL RESULTS OF SCINTIGRAPHY


36 PATIENTS (36 STUDIES)
WITH PRIMARY HYPERPARATHYROIDISM

FINDINGS
                                   SPECT   PLANAR
POSITIVE                             32      26
CONFUSING/QUESTIONABLE                1       8
NEGATIVE                              3       6

THERE WERE 2 CASES WITH MEDIASTINAL TUMORS
                CORRELATION OF
            99mTc-SESTAMIBI IMAGING

            WITH OPERATIVE FINDINGS


OPERATED:    22 PATIENTS (JAN. 5, 1994)

RESULTS                             SPECT/R    PLANAR

ACCURATE LOCALIZATION                     21    16
CONFUSING IMAGE                            1     5
FALSE NEGATIVE                             -     1
               RESULTS (PRELIMINARY)



TOTAL PATIENTS : 49
FOCI IDENTIFIED:    ONE TWO    THREE   FOUR MEDIASTINAL
       PATIENTS :    35  5       6       3      4

OPERATED PATIENTS: 39
TUMORS EXCISED:   ONE    TWO   THREE    MEDIASTINAL
     PATIENTS :     24    3      1          1

TUMORS NOT FOUND: 1   (MEDIASTINAL,UNACCESSIBLE)
     RESULTS (PRELIMINARY) CON’T


TUMORS EXCISED BUT NO CURE: 3
 (SCAN IDENTIFIED ADDITIONAL TUMOR BUT
   ASSAY/INTERPRETATION ERROR)

LESIONS MIMICKING PARATHYROID ADENOMA: 3
  1. THYROID ADENOMA
  2. LYMPH NODES (NORMAL/LYMPHOMA)
      USEFULNESS OF SPECT SESTAMIBI
          FOR LOCALIZATION OF
         PARATHYROID ADENOMAS

IT IS MORE SENSITIVE THAN PLANAR IMAGING


IDENTIFIES EXACT LOCATION OF LESION (DEPTH)


AND RESULTS IN FASTER RECONGNITIION OF LESIONS
AND SHORTENING OF THE OPERATION TIME BY 50%


AN AVERAGE TIME OF SAME SURGEON 90--> 36 min
A MINIMUM OPERATIVE TIME (SKIN TO SKIN) 13 min
ENABLES OPERATION ON AN OUTPATIENT BASIS
               CONCLUSION



THE PREOPERATIVE LOCALIZATION OF PARATHYROID
ADENOMAS WITH SPECT 99mTc-SESTAMIBI


AND THE INTRAOPERATIVE QPTH MEASUREMENT


RESULTED IN BETTER PATIENT CARE


AND THEY WERE ALSO COST EFFECTIVE
REDUCING OPERATING TIME AND HOSPITALIZATION