This document discusses the diagnosis and management of parathyroid disease. It begins by reviewing calcium homeostasis and the role of parathyroid hormone. It then covers parathyroid anatomy, histopathology, and embryology. The clinical features, diagnosis, and surgical or medical management of hyperparathyroidism are examined. Localization studies and the molecular basis of these studies are also reviewed. Surgical techniques including minimally invasive parathyroidectomy are discussed. The document concludes by emphasizing the importance of surgical anatomy and embryology for properly diagnosing and treating parathyroid disorders.

1. Diagnosis and
Management of
Parathyroid Disease
BY
PROF/ GOUDA ELLABBAN
FOM/SCU
ellabbang@yahoo.com

2. Objectives
 Review calcium homeostasis
 Understand parathyroid anatomy and
histopathology
 Review embryo-anatomic relationships in
the central neck
 Recognize the clinical features, diagnosis
and surgical/medical management of
hyperparathyroidism
 Understand the molecular basis of
localization studies

3. CALCIUM HOMEOSTASIS AND
PARATHYROID HORMONE
SECRETION AND REGULATION
 Parathyroid hormone (PTH) contains
84 amino acids
 Degradation into amino(N) and
carboxyl(C)-terminal fragments.
 The N-terminal fragment biologically
active and rapidly cleared
 C-terminal fragment is biologically
inert and cleared by the kidney

4. Continued….
 PTH release governed by serum ionized
calcium levels.
 PTH secreted in response to decrease in
serum-ionized calcium and inhibited by an
increase serum-ionized calcium.
 Target end organs: kidneys, skeletal system,
and intestine.
 PTH binding to receptor sites results in
cAMP 2nd messenger system activation.
 Half-life PTH few minutes.

5. Continued….

6. Etiology and Pathogenesis
of Hyperparathyroidism
 Parathyroid adenomas (PA) considered
monoclonal or oligoclonal neoplasms.
 Propagation through clonal expansion of
cells with altered sensitivity to calcium.
 PRAD1 implicated in only some PA.
 Another mechanism involves alternation in
tumor suppressor gene expression.

7. Continued….

8. Continued….

9. Parathyroid Anatomy and
Histopathology: The Normal
Parathyroid Gland
 Supernumerary fifth parathyroid found
between 0.7%-5.8% patients
 5th glands found in the mediastinum
(thymus or related to the aortic arch),
thyrothymic tract

10. Parathyroid Gland
Location
 80% of superior parathyroid glands found at
the cricothyroid junction ~1 cm cranial to
juxtaposition of RLN & ITA.
 Inferior parathyroid glands (IPG) variable in
location.
 61% of (IPG) near the lower pole of the
thyroid gland and 26% in thyrothymic
ligament.
 Incidence of intrathyroidal parathyroid
glands ~0.5% to 3%.

11. Embryology

12. Morphologic Characteristics
of Parathyroid Glands
 Shape-oval, bean, or teardrop
appearance or flat shape when
juxtaposed to thyroid gland.
 Color-yellowish brown to reddish
brown in normal parathyroid glands
and lighter gray tone in pathological
states.

13. Vascular Anatomy of the
Parathyroid Glands
 Normal parathyroid glands most commonly
are supplied by a single dominant artery
(80%).
 The length of the dominant artery supplying
glands vary from 1 to 40 mm.
 ITA is dominant blood supply to both
superior & inferior parathyroid glands most
of the time.

14. Histopathology of the
Parathyroid Glands
 Parathyroid gland composed of chief cells,
oxyphilic cells and intermediate cells
 Solitary parathyroid adenoma ~80%-85% of
patients with primary hyperparathyroidism
 Variations in parathyroid adenoma includes
other subtypes (oncocytic adenoma,
lipoadenoma, large clear cell adenoma,
water-clear cell adenoma, and atypical
adenoma).

15. Continued….
 Primary parathyroid hyperplasia-proliferation
of parenchymal cells with increase in weight
in multiple glands with absence of stimulus
for parathyroid hormone secretion.
 Two types of parathyroid hyperplasia are
seen: the common chief cell hyperplasia and
the rare water cell or clear cell hyperplasia.

16. Continued….
 Parathyroid carcinoma (PC) ~0.1% to 5.0% cases
of primary hyperparathyroidism.
 PC tend to be large tumors, (30% to 50% palpable
presentation).
 May measure up to 6 cm in diameter, mean ~3 cm.
 Lesion adheres to surrounding tissues including soft
tissues of the neck (thyroid gland, strap muscles,
trachea & recurrent laryngeal nerve).
 Regional metastasis rare.
 Pulmonary metastasis most common distant
metastasis site.

17. Continued….
 PC tends to be an indolent tumor.
 Multiple recurrences after resection
common and may occur over a 15- to
20-year period.
 Death results from from effects of
excessive PTH secretion and
uncontrolled hypercalcemia rather
than growth of the tumor mass.

18. Clinical features Primary
Hyperparathyroidism (PH)
 Incidence 27 cases annually per
100,000
 Prevalence PH general population
0.1%-0.3%
 Prevalence women >60 years more
than 1%

19. CALCIUM HOMEOSTASIS AND
PARATHYROID HORMONE
SECRETION AND REGULATION

20. Continued….
 Osteitis fibrosis cystica
 Nephrolithiasis
 Hypercalcemic crisis
 Osteitis fibrosis occurs ~1% of patients
 Renal stones ~10%-20% of patients have renal
stones.
 Nonspecific symptoms: malaise, fatigue,
depression, sleep disturbance, weight loss,
abdominal pains, constipation, vague
musculoskeletal pains in the extremities, and
muscular weakness

21. Continued….
 Kidney/Urinary Tract: 4% with nephrolithiasis
and nephrocalcinosis (stone composition, calcium
oxylate or calcium phosphate). Sx of urolithiasis:
renal colic, hematuria, pyuria.
 Skeletal System:
1. Osteitis fibrosis cystica (rare)
2. Subperiosteal erosion of the distal phalanges
3. Bone wasting and softening
4. Chondrocalcinosis as a result of bone demineralization
5. Bone pain
6. Pathologic fracture
7. Cystic bone changes
8. Bone loss: cortical bone sites sparing trabecular bone

22. Continued….
 Neuromuscular:
1. Muscle weakness, (proximal extremity muscle groups
with fatigue and malaise)
2. Neuromuscular syndrome improves in 80%-90% of
patients.
 Neurologic:
1. Depression, nervousness, and cognitive dysfunction
2. Deafness, dysphagia, and dysosmia
3. Many psychiatric symptoms improve after
parathyroidectomy. Fifty percent of patients with
depression or anxiety, or both will improve after surgery.

23. Continued….
 Cardiovascular
1. Hypertension (50% of patients)
2. Parathyroidectomy results in a reduction in BP in
minority of patients.
 Hypercalcemic syndrome
1. polydipsia and polyuria, anorexia, vomiting,
constipation, muscle weakness and fatigue, mental
status changes.
2. Metastatic calcifications at the corneal/scleral junction,
so-called band keratopathy
3. Shortened Q-T interval on electrocardiogram, ectopic
calcium deposits, and pruritus.

24. Continued….
 Band Keratopathy

25. Continued….
 Diagnosis:
1. Elevated serum Ca
2. Elevated PTH (suppressed in PTH-rp induced
hypercalcemia)
3. Other:
 Albumin
 Phosphorous
 BUN/Cr
 24-hour urine Ca (r/o FHH)
 Bone Mineral Density

26. Localization Studies
 Noninvasive preoperative methods
1. Ultrasonography
2. Radioiodine or technetium thyroid scan
3. Thallium-technetium scintigraphy
4. Technetium-99m sestamibi scintigraphy
5. Computed tomography scan
6. Magnetic resonance imaging
 Invasive preoperative methods
1. Fine-needle aspiration
2. Selective arteriography or digital subtraction angiography
3. Selective venous sampling for parathyroid hormone assay
4. Arterial injection of selenium-ethionine
 Intraoperative Methods
1. Intraoperative ultrasonography
2. Toluidine blue or methylene blue
3. Urinary adenosine monophosphate
4. Quick parathyroid hormone intraoperative

27. Sestamibi-Technetium 99m
Scintography
 Sestamibi taken up mitochondria of parathyroid cells greater
than surrounding parenchyma.
 Inject 20 to 25 millicuries of technetium-99m sestamibi.
Images obtained at 10-15 minutes then 2-3 hours after the
injection.
 Late phase preferable for detecting parathyroid adenomas, as
thyroid nodules clear uptake faster than do parathyroid
neoplasms.
 Sensitivity (solitary adenoma) ~100%, Specificity ~90%.
 False-positive:
1. Solid thyroid nodules (adenomas)
2. Hurthle cell carcinoma
3. Malignant thyroid lymph node metastases
4. No false-positive with cystic lesions of the thyroid gland

28. Continued….
 False-negatives
1.Smaller parathyroid adenoma size.
2.Suboptimal dosing of technetium-99m
sestamibi.

29. Continued….
 Four gland hyperplasia

30. Continued….
 Double adenoma

31. Medical Management
 Intravascular volume expansion + loop
diuretics (avoid thiazide diuretics)
 Bisphosphonates
 Calcitonin
 Plicamycin
 Estrogens therapy
 Oral phosphate salts
 Calcimimetic agents (investigational drug R-
568)

32. Case 1
 65 y.o. male with history of a left
thyroid mass underwent, FNA atypical
follicular lesion. Patient underwent L.
thyroid lobectomy with final diagnosis
of follicular adenoma. Patient had
been noted in past to have
asymptomatic hypercalcemia. PTH
126, 24-hour urine calcium 380mg,
Ionized Ca 1.4

33. Continued….
 Tc-99m
Sestamibi
suggested
parathyroid
adenoma in R
inferior pole of
thyroid gland.

34. Continued….
 Patient taken to OR for MIRP using a
Neoprobe.

35. Continued….
 664 mg right superior parathyroid
gland identified
 PTH decreased from 126 to 15

36. Surgical Management
 Clinical indicators for surgery*
1. Serum calcium is >1.0 mg/dL above the upper
limit of normal.
2. Creatinine clearance is reduced >30% for age in
the absence of another cause.
3. Twenty-four hour urinary calcium is >400 mg/dL.
4. Patients are younger than 50 years of age.
5. Bone mineral density measurement at the lumbar
spine, hip, or distal radius is reduced >2.5
standard deviations (by T score).
6. Patients request surgery, or patients are unsuitable
for long-term surveillance.
*Consensus conference held by the National Institutes of Health in 2002

37. Continued….
 Adenoma
1. Directed unilateral cervical
exploration.
2. Curative in >95% of patients
3. Preoperative localization with
technetium-99m sestamibi + IOPTH

38. Continued….
 MEN 1
1. Subtotal vs. total with autotransplantation.
 Men 2a-
1. 100% cure rate with no recurrences
whether total parathyroidectomy,
subtotal parathyroidectomy, or excision
of enlarged glands performed.
2. R/O pheochromocytoma prior to OR trip
(hypertensive crisis).

39. Continued….
 Non-MEN familial
hyperparathyroidism (NMFH).
1. Subtotal or total (autotransplant) with
bilateral cervical thymectomy.
 Familial neonatal
hyperparathyroidism.
1. Total (autotransplant) + bilateral
transcervical thymectomy

40. Continued….
 Renal failure-induced hyperparathyroidism.
1. Subtotal vs. total parathyroidectomy (autotransplant)
with or without cryopreservation.
 Parathyroid Carcinoma
1. en bloc resection of the tumor and areas of potential
local invasion and/or regional metastasis (ipsilateral
central neck contents including the thyroid lobe and
tracheoesophageal soft tissues, lymphatics, and
resection of soft tissues within the superior anterior
mediastinum)
2. RLN, esophageal wall, or strap muscles may require
sacrifice if the tumor adheres to them.
3. Not enough data to recommend for or against
chemotherapy or RT.

41. Continued….
 MIRP
1. Preoperative administration of technetium 99m sestamibi
before operation + intraoperative hand-held gamma probe.
2. Advantages:
1. Improved patient comfort postoperatively.
2. Performance of ambulatory procedures.
3. Reduced cost.
4. Avoidance of general anesthetic.
3. Disadvantages:
1. Potential for conversion to bilateral dissection in event of failed
exploration.
2. Patient anxiety when conversion needed (general anesthesia).

42. Conclusion
 No substitute for strong foundation
surgical embryology, anatomy, and
technique for approaching parathyroid
disease.

43. Bibliography
 Cummings Otolaryngology Head and
Neck Surgery. 2005.
 Rosen F., Pou A., Parathyroid
Disease. March 2002. UTMB site
 http://www.mrcophth.com/corneacom
moncases/bk.html (Image-Band
Keratopathy)