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Primary
Hyperparathyroidism
Presenter :Dr Junaid Ahmad Sofi ,Surgical Resident –II year
Moderator :Prof (Dr) Aijaz Ahmad Malik
Saturday
May’ 28
DEPARTMENT OF GENERAL & MINIMAL INVASIVE SURGERY , SKIMS, Srinagar , J&K
Parathyroids
Anatomy / Embryology and Physiology
 Four parathyroid glands –3 x 3 x 3 mm 30 – 50 mg
 Flat, ovoid and light beige and only slightly darker or
brown compared to adjacent fat.
 Variability in no (2-6). & position.
 2 Superiors are behind recurrent laryngeal nerve.
develop from 4th pharyngeal pouch hence called as
parathyroid IV
 MC location glands is within a distance of 1 cm from a point
centered where the inferior thyroid artery and RLN cross. The
upper parathyroidglands usually are superior to this junction
and dorsal (posterior)to the nerve, whereas the lower glands
are located inferior to thejunction and ventral (anterior) to the
recurrent nerve.
 Position of superior parathyroid glands is more
consistent, with 80% of these glands being found near
the posterior aspect of the upper and middle thyroid
lobes, at the level of the cricoid cartilage. Approximately
1% of normal upper glands may be found in the
paraesophageal or retroesophagealspace
POSSIBLE LOCATIONS FOR SUPERIOR THYROID GLANDS
• 2 inferior glands-variable in position,
develop from endoderm of 3rd pharyngeal
pouch hence called as parathyroid III,
usually in front of the recurrent laryngeal
nerve, lower part.
• Variations are common in inferior
parathyroids. It can be located in
thyrothymic ligament, superior pole of
thyroid,tracheooesophageal groove, behind
oesophagus, carotid sheath. Approximately
15% of inferior glands are found in the
thymus.
• Inferior thyroid artery – main blood supply
• 4th – 5th weeks of fetal life – pharyngeal
pouches developed
• 4th pouch + lateral thyroid anlage =
superior gland
• 3rd pouch + thymus = inferior gland
POSSIBLE LOCATIONS FOR INFERIOR THYROID GLANDS
 If one inferior gland is located find other on the opposite side at the same level
 This is not true for superior glands
 RLN crossing Simon’s triangle formed by trachea, ITA and common carotid artery
The superior parathyroid gland lies deep (dorsal) and the inferior parathyroid superficial
(ventral) to a coronal plane along course of RLN
Actions of parathormone hormone:
Increase serum calcium level by: Decrease serum phosphate level by:
Ca re-absorption from renal tubules.
Ca absorption from the GIT.
Bone resorption
Increase serum excretion of phosphate.
• Half life of PTH is 4 minutes.
Histologically
• chief cells and oxyphil cells
• arranged in trabeculae, within a stroma composed primarily of adipose cells.
• third group of cells- water-clear cells, also are derived from chief cells, are present in small
numbers, and are rich in glycogen.
• Although most oxyphil and water-clear cells retain the ability to secrete PTH, their functional
significance is not known.
Hyperparathyroidism
 Hyperparathyroidism 3rd most common endocrine disease
after diabetes and thyroid disease.
 excessive secretion of Parathyroid hormone (PTH) extensively above the
normal level (12-70 pg/mL) ,
 HPT can be characterized into primary, secondary, and tertiary forms
Hyperparathyroidism
Primary
Parathyroid
adenoma
Parathyroid
hyperplasia
Parathyroid
carcinoma
Secondary
Parathyroid
hyperplasia
Tertiary
Autonomous
nodule on
top of
hyperplasia
 Single adenoma
80% of cases
A rim of normal parathyroid tissue around the adenoma distinguishes
adenoma from hyperplasia
 Hyperplasia
15-20% of cases.
No rim of normal parathyroid tissue and lack of stromal fats
All 4 glands are involved.
The hyperparathyroidism of MEN syndromes is due to hyperplasia.
 Parathyroid carcinoma - <1% of cases.
Exceptionally high calcium or palpable neck mass should raise
suspicion.
Excision with thyroid lobectomy is indicated.
Radical neck dissection for recurrent disease. Recur locally 30%;
distant metastasis to lung liver and bone in 30%.
Difficult to distinguish adenoma from hyperplasia histologically
Primary Hyperparathyroidism
MEN type I (MEN 1 gene) MEN type II
•Parathyroid adenoma,
•(earliest & m.c manifestation is PHPT &
develops in 80-100% by 40 yrs )
•Pituitary adenoma
•Pancreatic islet cell tumor
•Parathyroid adenoma,
•Thyroid medullary carcinoma &
•Pheochromocytoma
Secondary hyperparthyroidism
 Hyperplasia of the parathyroid in response to decreased serum calcium level.
 Renal osteodystrophy/CRF
Tertiary hyperparathyroidism
 Autonomous parathyroid fuction on top of parathyroid hyperplasia even after renal
transplant
• PHPT occurs in 0.1% to 0.3% of the general population
• More common in women (1:500) than in men (1:2000).
• increased PTH production leads to hypercalcemia via :
• increased GI absorption of calcium
• increased production of vitamin D3,
• reduced renal calcium clearance.
• PHPT is characterized by increased PTH secretion that is independent of calcium levels.
 Classical Pentad : (Kidney Stones, Painful Bones, Abdominal groans,
Psychic moans & fatigue overtones)
 Most common clinical presentation of primary hyperparathyroidism ? ~
80 %
 Minimally symptomatic / asymptomatic hypercalcemia detected by
routine biochemical screening.B
 Biochemical screening tests that include measurements of serum calcium currently account for
the identification of at least 80 % of patients with primary hyperparathyroidism (PHPT) in
western countries .
 Minimal symptoms including : weakness, fatigue, polydipsia, polyuria, nocturia, bone and joint
pain, constipation, decreased appetite, nausea, heartburn, pruritus, depression, and memory loss
 Truly asymptomatic <5%
< Trabecular bone resorption
SALT PEPPER APPEARANCE
< Subperiosteal bone resorption
Phalangeal tufts.
Brown tumor
(osteitis fibrosa cystica)
 Replacement of bone by vascularized fibrous tissue
secondary to PTH stimulated osteoclastic activity
 Expansile lytic lesion with well defined non sclerotic
margin.
 Location: They are usually eccentric
Hyper parathyroidism
Skeletal
Osseous
Bone resorption
Diffuse
osteoporosis
Regional
osteosclerosis
Bone softening
Periostitis
Brown tumor
Articular
Erosive arthritis
Chondrocalcinosis
Soft tissue
Visceral
calcification
Soft tissue
calcification
Vascular
calcification
CLINICAL MANIFESTATIONS
 Renal
Polyuria ,Polydipsia ,Nephrolithiasis , Nephrocalcinosis ,Distal renal tubular acidosis , Nephrogenic
diabetes insipidus ,Acute and chronic renal insufficiency
 Gastrointestinal
Anorexia, nausea, vomiting Bowel hypomotility and constipation Pancreatitis Peptic ulcer disease
 Musculoskeletal
Muscle weakness ,Bone pain ,Osteopenia/osteoporosis
 Neurologic
Decreased concentration ,Confusion , Fatigue ,Stupor, coma
 Cardiovascular
Shortening of the QT interval, Bradycardia ,Hypertension (unknown )
Diagnosis
 elevated serum Ca2+ and intact PTH or two-site PTH
levels, without hypocalciuria, establishes the diagnosis
of PHPT with virtual certainty.
 PTH assays use immunoradiometric or
immunochemiluminescent techniques and can reliably
distinguish PHPT from other causes of hypercalcemia.
Furthermore, they do not crossreact with PTHrP
 Urinary calcium levels need not be
measured routinely, except in patients who have not
had previously documented normocalcemia or have a
family history of hypercalcemia to rule out FHH. In
FHH, 24-hoururinary calcium excretion is
characteristically low (<100 mg/d).
& serum calcium-to-creatinine clearance ratio usually is
<0.01 in patients with FHH, whereas it is typically>0.02
in patients with PHPT.
Hypercalcemic Crisis.
Patients with PHPT may occasionally present acutely with nausea,
vomiting, fatigue, muscle weakness, confusion, and a decreased level of
consciousness—a complex referred to as hypercalcemic crisis
• symptoms result from severe hypercalcemia from uncontrolled PTH secretion,
worsened by polyuria, dehydration, and reduced kidney function
• Treatment consists of therapies to lower serum calcium levels followed by surgery
to correct HPT.
• rehydration with a 0.9% saline solution to keep urine output >100 cc/h.
• Once urine output is established, diuresis with furosemide
• Occasionally, in life-threatening cases/ CRF -> hemodialysis
PHPT TREATMENT :
Medical options
 antiresorptive treatments such as
 bisphosphonates
 hormone replacement therapy (HRT),( other side effects )
 selective estrogen receptor
 Bisphosphonates and HRT are reasonable options in patients for whom skeletal
protection is needed.
 More recently, calcimimetics (CINACALCET) (modifiers of the sensitivity of the
CASR) have been used in randomized, multicenter controlledtrials and have been shown
to decrease both serum calcium and PTH levels in both symptomatic and asymptomatic
PHPT patients. Unfortunately, bone density failed to improve in medically treated
patients
Indications for Parathyroidectomy and Role of Medical
Management.
 patients who have developed complications and have “classic” symptoms of PHPT
should undergo parathyroidectomy
 asymptomatic PHPT has been the subject of controversy
Indications for parathyroidectomy in patients with asymptomatic primary
HPT (2009 NIH consensus conference guidelines)
 Serum calcium >1 mg/dL above the upper limits of normal
 GFR <60 mL/min
 Substantially decreased bone mineral density at the lumbar spine, hip, or distal radius (>2.5 SD
below peak bone mass, T score <−2.5
 Age <50 y
 Long-term medical surveillance not desired or possible
The significant changes from the previous guidelines pertain to the fact that
 (a) hypercalciuria (>400 mg/24 h), in the absence of nephrolithiasis, is no longer considered an
indication for parathyroidectomy;
 (b) an absolute glomerular filtration rate <60 mL/min, rather than a reduction of creatinine
clearance by 30%, is used as a thresholdfor recommending surgery
The Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism
reviewed evidence that has become available since the last Workshop in 2008.
2013GUIDELINES
(VFA vertebral fracture assessment) and trabecular bone score (TBS) by DXA
Surgical Management
 Successful parathyroidectomy results in resolution of osteitis fibrosa cystica
and decreased formation of renal stones in symptomatic (classic) patients.
 Improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years)
and fracture risk (by 50% at hip and upper arm and30% overall) after
adjustment for age, sex, and previous fractures over a 20-year observation
period.
 improves a number of the nonspecific manifestations of PHPT such as fatigue,
polydipsia, polyuria and nocturia, bone and joint pain, constipation, nausea,
and depression in many patients.
 Hence , it is recommended that parathyroidectomy should be offered
to virtually all patients except those in whom the operative risks are
prohibitive. This is also acknowledged by the panel of the latest
workshop, which stated that “even though patients may not meet the
guidelines for surgical intervention, it is always a reasonable option in
those who do not have medical contraindications.”
Surgical options – Primary Hyperparathyroidism
 With single adenoma, resection of the gland is
curative.
 For hyperplasia,
 3 ½ gland resection
 4-gland resection with ½ gland reimplanted in
the forearm or sternocleidomastoid muscle is
indicated.
 For parathyroid carcinoma
 Neck exploration with en bloc excision of the
tumor and the ipsilateral thyroid lobe, in
addition to the removal of contiguous lymph
nodes (tracheoesophageal, paratracheal, and
upper mediastinal).
 The recurrent nerve is not sacrificed unless it is
directly involved with tumor.
 Adherent soft tissue structures (strapmuscles or
other soft tissues) should also be resected.
 Modified radical neck dissection is recommended
in the presence of lateral lymph node metastases.
 suspected preoperatively by the presence of
severe symptoms,
 serum calcium levels>14 mg/dL,
 significantly elevated PTH levels (five times
normal),
 a palpable parathyroid gland.
 Initial exploration is successful in 90-95% of cases
without pre-op localization studies.
 Ectopic locations: Thymic – substernal – 20%;
Posterior neck – 5-10%; Intrathyroid – 5%; Carotid
sheath – 1%; Anterior mediastinum – 1-2%.
 If initial exploration fails – localization studies are
indicated.
Approaches for parathroidectomy :
 Standard Bilateral exploration-Conventional approach
 If parathyroid localization studies or IOPTH arent avaialable
 If localization studies fail to identify any abnormal glands
 If localization studies identify multiple abnormal glands
 If concomitant thyroid disorder requires B/L exploration
 Targeted/Focussed Approach
 Minimally invasive parathyroidectomy
 Radio Guided parathyroidectomy using hand held gamma probe
 Endoscopic approaches (especially for ectopic parathyroids in mediastinum)
 Robotic gasless , transaxillary techniques
Preoperative Localization
 imaging is not a diagnostic approach, and the decision for exploration should be made before any
imaging is performed
 Localization studies have permitted surgeons to perform more limited operations including
unilateral and focused neck exploration, radio-guided parathyroidectomy, and several endoscopic or
video-assisted approaches.
Benefits of Preoperative Localization:
 decreased operative times
 reduced duration of hospital stay
 Smaller Incision , improved cosmetic outcomes
 Success rates similar to those obtained with traditional bilateral neck explorations
 Different Anesthesia Options
 Ambulatory vs. Overnight
 Decrease Rate of Missed or Multiple Adenomas
PREOP NON INVASIVE LOCALIZATION
 Sestamibi or MIBI scintigraphy (methoxyisobutylisonitrile )
 taken up by the mitochondria in thyroid and parathyroid tissue.
 DISADVANTAGES :
- unrevealing in parathyroid hyperplasia, multiple parathyroid adenomas, and in
those with coexisting thyroid disease.
-falsely negative scans can also be caused by calcium channel blockers that interfere
with the take up of the isotope by parathyroid cells .
-Other gland characteristics that can increase the likelihood of a negative scan
include small size, superior position, and a paucity of oxyphil cells.
Sestamibi scanning for parathyroid tissue can be
enhanced by combination with three-dimensional
imaging (SPECT) & Subtraction thyroid scan ie
Sestamibi -Technitium-99m subtraction scintigraphy
Technetium-sestamibi scans 15 minutes and 3 hours after
injection showing retention of isotope in a left inferior parathyroid
Sestamibi -Technitium-99m subtraction scintigraphy.
 most widely used and accurate modality with a sensitivity >80% for detection of parathyroid adenomas.
 useful for parathyroid localization due to the delayed washout of the radionuclide from hypercellular
parathyroid tissue compared to thyroid tissue.
Sestamibi Technitium-99m subtraction
scintigraphy.
• SPECT — Sestamibi-single photon emission computed tomography
(SPECT or MIBI-SPECT).
three-dimensional sestamibi scan that provides higher resolution imaging and
improves the performance of sestamibi scanning.
ADVANTAGE :
SPECT imaging substantially reduces the likelihood of missing multiglandular
disease compared to planar imaging
(MIBI SCAN)( Sestamibi scintigraphy) combined with sestamibi single photon
emission computed tomography (SPECT) has the highest positive predictive value
of the available imaging techniques and some prefer this as the localizing
procedure of choice for initial surgery
MIBI scan with single photon emission computed
tomography showing hot spot in anterior mediastinum
(arrow)
Neck ultrasonography (high Frequency USG)
 highly sensitive in experienced hands inexpensive, noninvasive, and reproducible
in the operating room.
 helpful for the characterization and evaluation of any thyroid pathology,
facilitating operative planning. This is a common problem, since concurrent
thyroid pathology is present in up to 30 percent of patients with primary
hyperparathyroidism.
 Operator dependent
 Sensitivity is reduced in patient With thyroid nodule
 Sonographic characteristics of parathyroid adenomas include homogeneous
hypoechogenicity and an extrathyroidal feeding vessel with peripheral vascularity
seen on color Doppler imaging .
 False-negatives result from substernal ,ectopic, and undescended tumors
Ultrasound views of parathyroid adenomas.
(A) Sagittal image of the upper pole of the right lobe of the thyroid gland,
demonstrating a hypoechoic parathyroid adenoma posterior to the thyroid
parenchyma.
(B) Sagittal image of the lower pole of the lower pole of the left lobe of the
thyroid gland with an adjacent hypoechoic parathyroid adenoma measuring 9
mm in greatest dimension
Magnetic resonance imaging
 Localization of ectopic tumors
 No radiation exposure
 Expensive
 False positive results from thyroid nodules & lymph nodes
Parathyroid adenoma characteristics on magnetic resonance imaging (MRI)
include intermediate to low signal intensity on T1 imaging and high intensity
on T2 imaging.
CT & 4D CT scan
 CT are less sensitive than sestamibi scans,but are helpful in localizing large paraesophageal and mediastinal glands.
 4 D C T Incorporates the perfusion of contrast in hyperfunctioning parathyroid tissue over time, thus providing
functional information in addition to the anatomic information provided by conventional three-dimensional CT
imaging.
 In one study 4D-CT showed improved sensitivity of 88% compared to that of sestamibi (65%) and ultrasound
(57%) for lateralization of the enlarged gland and also showed superiority when localization to the correct
quadrant was examined.
 A combination of 4D-CT and ultrasound has been reported to have a positive predictive value of 92% for single-
gland disease and 75% for multiple-gland disease.
 Non-localizing imaging studies should not preclude initial surgery
for patients with biochemically confirmed primary
hyperparathyroidism who meet operative criteria. In such
patients, a single adenoma is still the most likely intraoperative
finding (62 to 77 percent)
PREOPERATIVE , INVASIVE LOCALISATION
 prior neck surgery
 whom noninvasive testing has been unrevealing.
Selective venous sampling : A 1.5 to 2-fold increase in parathyroid hormone levels obtained from representative cervical
vein drainage locations (inferior, middle, superior thyroid, thymic, and/or vertebral veins
Selective arteriography positive localization is considered an increase in the parathyroid hormone level to 1.4 times the
baseline or a blush seen on arteriography
A baseline PTH value is obtained at the start of the procedure, PTH levels are then measured at following removal of the
suspected adenoma . A reduction of >=50 percent from the baseline following excision of the hyperfunctioning gland after
10 mins is an accepted standard for intraoperative confirmation of success.
INTAOPERATIVE LOCALISATION USING GAMMA PROBE
 1 to 2 mCi of the isotope is injected before surgery, and a hand-held gamma probe is used to guide the identification of
the enlarged gland
INTAOPERATIVE , INVASIVE LOCALISATION
Use of gamma probe intra op
Comprehensive Parathyroidectomy
Systematic Examination of all Parathyroid Glands in their Usual Anatomic Location and Appropriate
Resection of Diseased Parathyroids
 For patients with negative (non-localizing) preoperative imaging studies or when bilateral foci are
detected.
 Most forms of hereditary hyperparathyroidism are an indication for bilateral parathyroid
exploration due to the predictable involvement of multiple glands.
 Concomitant thyroid disease requiring surgical resection, such as biopsy proven papillary thyroid
cancer, necessitates bilateral exploration.
 pregnant patients due to the radiation required for some localization studies. However, if ultrasound
expertise is available and the results show an apparent single adenoma, a focused approach can be
planned.
 lithium associated hyperparathyroidism has a higher incidence of being associated with multiple
gland involvement and may require bilateral exploration.
■ Focused parathyroid exploration
When combined with use of intraoperative PTH monitoring, minimally invasive
parathyroidectomy techniques result in excellent outcomes that are comparable to a traditional
bilateral cervical exploration.
Advantages :
The smaller incisions and less extensive dissection lead to reduced postoperative pain and a
lower incidence of hypocalcemia from ischemia of other glands.
Indications:
-No discordance between sistamibi & USG
-imaging suggesting unilateral pathology.
-no suggestion of concomitant, thyroid disease requiring surgical intervention.
-no family history of multiple endocrine neoplasia.
How do we do it
1 . Consent for Possibilities of:
 persistent hyperparathyroidism (5 per cent);
 recurrent laryngeal nerve injury (1 per cent);
 postoperative haemorrhage (1 per cent);
 permanent hypoparathyroidism;
 recurrent hyperparathyroidism
 initially after first surgery HPT is corrected but recurs 12 months after surgery) is due
parathyromatosis, development of new adenoma, and hyperplasia of transplanted
parathyroid. Parathyromatosis is due to rupture and spillage of parathyroid tissue in
neck, mediastinum forming functioning nodules
Operative strategy and technique of parathyroidectomy
Conventional approach
 Helpful to mark incision site when patient is awake
 positioned in supine, neck extended with the head supported in a padded ring.
 A transverse collar incision is made, the subplatysmal plane developed superiorly till thyroid cartilage and
inferiorly till supra sternal notch and the avascular midline raphe is incised in the midline between the strap
muscles
 sternothyroid is are separated from Sternohyoid & loose areolar tissue between sternothyroid & thyroid is
taken down at the lateral edge of sternothyroid to prevent lateral displacement of parathyroid
 Thyroid lobes are mobilised with division of the middle thyroid vein when present. It is not normally necessary
to divide the superior thyroid vessels unless the exploration proves difficult
 Medial rotation of the thyroid lobe exposes the inferior thyroid artery and recurrent laryngeal nerve
 Inferior glands are identified first as superior glands require more medial rotation of thyroid
 Bloodless field is maintained , as blood staining makes parathyroids less noticable
The glands are identified in a systematic manner commencing with the common sites and
working sequentially through to the rare locations.
Superior gland:
 1 in fat pad on surface of thyroid lobe above the inferior thyroid artery at level of
cricothyroid articulation then
 2 inferiorly behind the inferior thyroid artery and oesophagus then
 3 divide superior thyroid vessels and rotate upper pole anteriorly.
Inferior gland:
 1 along the thyrothymic axis then
 2 on or under the capsule of the lower pole of the thyroid then
 3 incise the fascia of the upper horn of thymus then
 4 extend this down into the accessible mediastinal thymus then
 5 within the carotid sheath (usually suggested by a tongue of ectopic thymus) then
 6 transcervical thymectomy achieved by gentle upper retraction on the thymic lobe then
 7 within the thyroid lobe which may require thyroid lobectomy.
 All abnormal glands are excised
 In sporadic four-gland disease, subtotal parathyroidectomy is carried out, preserving
approximately 50 mg of one gland marked with a non-absorbable suture to facilitate any
possible future re-exploration.
 In patients with four-gland disease, transcervical thymectomy is recommended to
reduce the risk of persistent or recurrent hyperparathyroidism.
 In patients with MEN-1, total parathyroidectomy reduces the risk of recurrence.
 The thin fascia overlying a “suspicious” fat lobule should be incised using a sharp
curved hemostat and scalpel.This maneuver often causes the parathyroid gland to “pop”
out. Alternatively, gentle, blunt peanut sponge dissection between the carotid sheath and
the thyroid gland often reveals a “float”sign, suggesting the site of the abnormal
parathyroid gland.
 Intra Op adenoma:
 Brown with gritty sensation on incising
 Sinks in water
Operative strategy and technique of parathyroidectomy
Focussed / Targeted approach
 General or local anaesthesia
 Confident preoperative localisation permits a 2–3 cm incision located over the
site of the adenoma
 Subplatysmal plane is incised and either a midline or lateral approach to the
strap muscles permits development of the plane between the thyroid capsule
and carotid artery and jugular veins
 Adenoma is mobilised staying close to but avoiding rupture of the capsule.
Identification of the recurrent laryngeal nerve is not routine and only bipolar
diathermy should be used.
Targeted parathyroid surgery; a 2-cm incision over left
inferior parathyroid adenoma.
Median Sternotomy (3%) Extension
 Median sternotomy is often needed when parathyroid is in anterior
mediastinum along with thymus. Often parathyroid may be 5, 6 in numbers
instead of four
Complication of parathyroidectomy ? :
 Hematoma
 Wound infection
 Postoperative hypocalcemia ( transient / hungry bone syndrome )
 Permanent hypoparathyroidism
 Recurrent laryngeal nerve injury(1%)
 Persistent hyperparathyroidism—5% (PTH never touches baseline -6 mo)
 Recurrent hyperparathyroidism—initially PTH decreases but
hypercalcaemia recurs 6 months after first parathyroid surgery
The hypocalcemia is generally transient , Transient hypoparathyroidism
may be due to manipulation of the blood supply to or removal of one
or more parathyroid glands during surgery .
In some cases, however, the postoperative hypocalcemia is severe and
prolonged despite normal or even elevated levels of parathyroid
hormone (PTH). This phenomenon, called the hungry bone syndrome.
most often occurs in patients who have developed bone disease
preoperatively due to a chronic increase in bone resorption induced by
high levels of PTH (osteitis fibrosa).
Hypocalcemia after parathyroidectomy
Time course of development of hypocalcemia in 25 patients
following parathyroidectomy for primary
hyperparathyroidism. Most of the fall in the plasma calcium
concentration occurred in the first 24 hours after surgery.
D/D for the patient with hypocalcemia ?
-Hungrey bone syndrome (PTH level normal ).
-Vitamine D deficiency.
-Both.
-Malabsorption.
-Permanent hypoparathyroidism (injuried glands )( low PTH ).
Criteria for diagnosis of hungrey bone syndrome ?
 serum calcium concentration below 8.5 mg/dL (2.13 mmol/L) and the
serum phosphate postoperative conentration below 3.0 mg/dL (0.96
mmol/L) on the third day post op.
Patients at risk ?
1-Volume of the resected adenoma.
2-Preoperative blood urea nitrogen concentration.
3-Preoperative alkaline phosphatase concentration.
4-Older age.
Preoperative serum calcium and PTH levels did not provide
additional predictive information.
Some studies do point towards pre-op calcium has a indicator for the same
Presentation of hungry bone syndrome :
-Hypocalcemia .
-Hypophosphatemia :
The decrease in bone resorption and increase in bone formation that
occurs after parathyroidectomy can also lead to hypophosphatemia.
-Hypomagnesemia : refractory hypocalcemia.
-Hyperkalemia (80 percent) ( unknown ).
How it can be prevented ?
Preoperative preparation
-starting oral calcium 2 to 3 grams per day two days prior to surgery, even in
patients who are hypercalcemic.
-intravenous calcitriol : in Vit D deficiency , CRF
(vitamin D2) (1000 IU per day or more depending on level) in vit D def pts ,
(2 mcg at the end of each hemodialysis treatment) in HD pts , begun three
to five days prior to surgery and continued postoperatively may be helpful
in preventing marked hypocalcemia.
How it can be treated ?
 Treatment is aimed at each of the abnormalities that can occur:
hypocalcemia, hypomagnesemia, hypophosphatemia, and hyperkalemia.
 the serum calcium concentration should be measured two to four times
per day for the first few postoperative day .
 Oral calcium supplementation (2 to 4 g of elemental calcium [50 to 100
mmol] per day) should be started as soon as the patient is able to swallow.
 If the serum phosphorus is normal or low, calcium should be administered
between meals to maximize intestinal absorption and minimize phosphate
binding.
Intravenous calcium is indicated if the patient develops a rapid and progressive
reduction in serum calcium or symptoms related to hypocalcemia, including
frank tetany, latent tetany (Chvostek's or Trousseau's sign), or a plasma
calcium concentration below 7.5 mg/dL (1.9 mmol/L).
the administration of phosphate to reverse hypophosphatemia is generally
avoided in patients with hungry bone syndrome, since phosphate can
combine with calcium and further reduce the plasma calcium
concentration. An exception to this general rule is the presence of severe
hypophosphatemia, in which the plasma phosphate concentration is below 1
mg/dL.
 TREATMENT OF CONCOMITANT VITAMIN D DEFICIENCY ?
the Third International Workshop on Asymptomatic Primary
Hyperparathyroidism recommends measuring 25OHD in all patients with
PHPT and repleting those with low levels (defined as ≤20 ng/mL [50
nmol/L]) prior to making any management decisions .
 Cautiously repleting vitamin D in patients with underlying
hyperparathyroidism since worsening hypercalcemia and hypercalciuria
have been reported in this setting .
Add on
 Intra op Parathyroid adenomas are brown with gritty feel
 Parathyroids sink in water ; fat doesnt
 ??Intraop indocyanin green(as for hepatic functions) assay for parathyroid
localisation..infra red light
 2 site pth assay
 Sandwich assays (two antibodies for C n N terminus of Intact PTH
 Two site sampling IJV & peripheral vein sampling
 Calcium replacement(1-1.5meq/kg/day replacement)
 Persistant hyperparathyroidism : elevated calcium & PTH within 6 months
of surgery
 Recurrent hyperparathyroidism :levated calcium & PTH that occurs more
than 6-12 months after surgery
 Implantation in forearm for easy reexplloration

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Primary Hyperparathyroidism: Causes, Symptoms, Diagnosis and Treatment

  • 1. Primary Hyperparathyroidism Presenter :Dr Junaid Ahmad Sofi ,Surgical Resident –II year Moderator :Prof (Dr) Aijaz Ahmad Malik Saturday May’ 28 DEPARTMENT OF GENERAL & MINIMAL INVASIVE SURGERY , SKIMS, Srinagar , J&K
  • 3. Anatomy / Embryology and Physiology  Four parathyroid glands –3 x 3 x 3 mm 30 – 50 mg  Flat, ovoid and light beige and only slightly darker or brown compared to adjacent fat.  Variability in no (2-6). & position.  2 Superiors are behind recurrent laryngeal nerve. develop from 4th pharyngeal pouch hence called as parathyroid IV  MC location glands is within a distance of 1 cm from a point centered where the inferior thyroid artery and RLN cross. The upper parathyroidglands usually are superior to this junction and dorsal (posterior)to the nerve, whereas the lower glands are located inferior to thejunction and ventral (anterior) to the recurrent nerve.  Position of superior parathyroid glands is more consistent, with 80% of these glands being found near the posterior aspect of the upper and middle thyroid lobes, at the level of the cricoid cartilage. Approximately 1% of normal upper glands may be found in the paraesophageal or retroesophagealspace POSSIBLE LOCATIONS FOR SUPERIOR THYROID GLANDS
  • 4. • 2 inferior glands-variable in position, develop from endoderm of 3rd pharyngeal pouch hence called as parathyroid III, usually in front of the recurrent laryngeal nerve, lower part. • Variations are common in inferior parathyroids. It can be located in thyrothymic ligament, superior pole of thyroid,tracheooesophageal groove, behind oesophagus, carotid sheath. Approximately 15% of inferior glands are found in the thymus. • Inferior thyroid artery – main blood supply • 4th – 5th weeks of fetal life – pharyngeal pouches developed • 4th pouch + lateral thyroid anlage = superior gland • 3rd pouch + thymus = inferior gland POSSIBLE LOCATIONS FOR INFERIOR THYROID GLANDS
  • 5.  If one inferior gland is located find other on the opposite side at the same level  This is not true for superior glands
  • 6.  RLN crossing Simon’s triangle formed by trachea, ITA and common carotid artery
  • 7. The superior parathyroid gland lies deep (dorsal) and the inferior parathyroid superficial (ventral) to a coronal plane along course of RLN
  • 8. Actions of parathormone hormone: Increase serum calcium level by: Decrease serum phosphate level by: Ca re-absorption from renal tubules. Ca absorption from the GIT. Bone resorption Increase serum excretion of phosphate. • Half life of PTH is 4 minutes. Histologically • chief cells and oxyphil cells • arranged in trabeculae, within a stroma composed primarily of adipose cells. • third group of cells- water-clear cells, also are derived from chief cells, are present in small numbers, and are rich in glycogen. • Although most oxyphil and water-clear cells retain the ability to secrete PTH, their functional significance is not known.
  • 9. Hyperparathyroidism  Hyperparathyroidism 3rd most common endocrine disease after diabetes and thyroid disease.  excessive secretion of Parathyroid hormone (PTH) extensively above the normal level (12-70 pg/mL) ,  HPT can be characterized into primary, secondary, and tertiary forms
  • 11.  Single adenoma 80% of cases A rim of normal parathyroid tissue around the adenoma distinguishes adenoma from hyperplasia  Hyperplasia 15-20% of cases. No rim of normal parathyroid tissue and lack of stromal fats All 4 glands are involved. The hyperparathyroidism of MEN syndromes is due to hyperplasia.  Parathyroid carcinoma - <1% of cases. Exceptionally high calcium or palpable neck mass should raise suspicion. Excision with thyroid lobectomy is indicated. Radical neck dissection for recurrent disease. Recur locally 30%; distant metastasis to lung liver and bone in 30%. Difficult to distinguish adenoma from hyperplasia histologically Primary Hyperparathyroidism
  • 12. MEN type I (MEN 1 gene) MEN type II •Parathyroid adenoma, •(earliest & m.c manifestation is PHPT & develops in 80-100% by 40 yrs ) •Pituitary adenoma •Pancreatic islet cell tumor •Parathyroid adenoma, •Thyroid medullary carcinoma & •Pheochromocytoma
  • 13. Secondary hyperparthyroidism  Hyperplasia of the parathyroid in response to decreased serum calcium level.  Renal osteodystrophy/CRF Tertiary hyperparathyroidism  Autonomous parathyroid fuction on top of parathyroid hyperplasia even after renal transplant
  • 14. • PHPT occurs in 0.1% to 0.3% of the general population • More common in women (1:500) than in men (1:2000). • increased PTH production leads to hypercalcemia via : • increased GI absorption of calcium • increased production of vitamin D3, • reduced renal calcium clearance. • PHPT is characterized by increased PTH secretion that is independent of calcium levels.
  • 15.  Classical Pentad : (Kidney Stones, Painful Bones, Abdominal groans, Psychic moans & fatigue overtones)  Most common clinical presentation of primary hyperparathyroidism ? ~ 80 %  Minimally symptomatic / asymptomatic hypercalcemia detected by routine biochemical screening.B  Biochemical screening tests that include measurements of serum calcium currently account for the identification of at least 80 % of patients with primary hyperparathyroidism (PHPT) in western countries .  Minimal symptoms including : weakness, fatigue, polydipsia, polyuria, nocturia, bone and joint pain, constipation, decreased appetite, nausea, heartburn, pruritus, depression, and memory loss  Truly asymptomatic <5%
  • 16.
  • 17. < Trabecular bone resorption SALT PEPPER APPEARANCE < Subperiosteal bone resorption Phalangeal tufts.
  • 18. Brown tumor (osteitis fibrosa cystica)  Replacement of bone by vascularized fibrous tissue secondary to PTH stimulated osteoclastic activity  Expansile lytic lesion with well defined non sclerotic margin.  Location: They are usually eccentric
  • 19.
  • 20. Hyper parathyroidism Skeletal Osseous Bone resorption Diffuse osteoporosis Regional osteosclerosis Bone softening Periostitis Brown tumor Articular Erosive arthritis Chondrocalcinosis Soft tissue Visceral calcification Soft tissue calcification Vascular calcification
  • 21. CLINICAL MANIFESTATIONS  Renal Polyuria ,Polydipsia ,Nephrolithiasis , Nephrocalcinosis ,Distal renal tubular acidosis , Nephrogenic diabetes insipidus ,Acute and chronic renal insufficiency  Gastrointestinal Anorexia, nausea, vomiting Bowel hypomotility and constipation Pancreatitis Peptic ulcer disease  Musculoskeletal Muscle weakness ,Bone pain ,Osteopenia/osteoporosis  Neurologic Decreased concentration ,Confusion , Fatigue ,Stupor, coma  Cardiovascular Shortening of the QT interval, Bradycardia ,Hypertension (unknown )
  • 22. Diagnosis  elevated serum Ca2+ and intact PTH or two-site PTH levels, without hypocalciuria, establishes the diagnosis of PHPT with virtual certainty.  PTH assays use immunoradiometric or immunochemiluminescent techniques and can reliably distinguish PHPT from other causes of hypercalcemia. Furthermore, they do not crossreact with PTHrP  Urinary calcium levels need not be measured routinely, except in patients who have not had previously documented normocalcemia or have a family history of hypercalcemia to rule out FHH. In FHH, 24-hoururinary calcium excretion is characteristically low (<100 mg/d). & serum calcium-to-creatinine clearance ratio usually is <0.01 in patients with FHH, whereas it is typically>0.02 in patients with PHPT.
  • 23. Hypercalcemic Crisis. Patients with PHPT may occasionally present acutely with nausea, vomiting, fatigue, muscle weakness, confusion, and a decreased level of consciousness—a complex referred to as hypercalcemic crisis • symptoms result from severe hypercalcemia from uncontrolled PTH secretion, worsened by polyuria, dehydration, and reduced kidney function • Treatment consists of therapies to lower serum calcium levels followed by surgery to correct HPT. • rehydration with a 0.9% saline solution to keep urine output >100 cc/h. • Once urine output is established, diuresis with furosemide • Occasionally, in life-threatening cases/ CRF -> hemodialysis
  • 24.
  • 25. PHPT TREATMENT : Medical options  antiresorptive treatments such as  bisphosphonates  hormone replacement therapy (HRT),( other side effects )  selective estrogen receptor  Bisphosphonates and HRT are reasonable options in patients for whom skeletal protection is needed.  More recently, calcimimetics (CINACALCET) (modifiers of the sensitivity of the CASR) have been used in randomized, multicenter controlledtrials and have been shown to decrease both serum calcium and PTH levels in both symptomatic and asymptomatic PHPT patients. Unfortunately, bone density failed to improve in medically treated patients
  • 26. Indications for Parathyroidectomy and Role of Medical Management.  patients who have developed complications and have “classic” symptoms of PHPT should undergo parathyroidectomy  asymptomatic PHPT has been the subject of controversy
  • 27. Indications for parathyroidectomy in patients with asymptomatic primary HPT (2009 NIH consensus conference guidelines)  Serum calcium >1 mg/dL above the upper limits of normal  GFR <60 mL/min  Substantially decreased bone mineral density at the lumbar spine, hip, or distal radius (>2.5 SD below peak bone mass, T score <−2.5  Age <50 y  Long-term medical surveillance not desired or possible The significant changes from the previous guidelines pertain to the fact that  (a) hypercalciuria (>400 mg/24 h), in the absence of nephrolithiasis, is no longer considered an indication for parathyroidectomy;  (b) an absolute glomerular filtration rate <60 mL/min, rather than a reduction of creatinine clearance by 30%, is used as a thresholdfor recommending surgery
  • 28. The Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism reviewed evidence that has become available since the last Workshop in 2008. 2013GUIDELINES
  • 29. (VFA vertebral fracture assessment) and trabecular bone score (TBS) by DXA
  • 30. Surgical Management  Successful parathyroidectomy results in resolution of osteitis fibrosa cystica and decreased formation of renal stones in symptomatic (classic) patients.  Improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) and fracture risk (by 50% at hip and upper arm and30% overall) after adjustment for age, sex, and previous fractures over a 20-year observation period.  improves a number of the nonspecific manifestations of PHPT such as fatigue, polydipsia, polyuria and nocturia, bone and joint pain, constipation, nausea, and depression in many patients.
  • 31.  Hence , it is recommended that parathyroidectomy should be offered to virtually all patients except those in whom the operative risks are prohibitive. This is also acknowledged by the panel of the latest workshop, which stated that “even though patients may not meet the guidelines for surgical intervention, it is always a reasonable option in those who do not have medical contraindications.”
  • 32. Surgical options – Primary Hyperparathyroidism  With single adenoma, resection of the gland is curative.  For hyperplasia,  3 ½ gland resection  4-gland resection with ½ gland reimplanted in the forearm or sternocleidomastoid muscle is indicated.  For parathyroid carcinoma  Neck exploration with en bloc excision of the tumor and the ipsilateral thyroid lobe, in addition to the removal of contiguous lymph nodes (tracheoesophageal, paratracheal, and upper mediastinal).  The recurrent nerve is not sacrificed unless it is directly involved with tumor.  Adherent soft tissue structures (strapmuscles or other soft tissues) should also be resected.  Modified radical neck dissection is recommended in the presence of lateral lymph node metastases.  suspected preoperatively by the presence of severe symptoms,  serum calcium levels>14 mg/dL,  significantly elevated PTH levels (five times normal),  a palpable parathyroid gland.  Initial exploration is successful in 90-95% of cases without pre-op localization studies.  Ectopic locations: Thymic – substernal – 20%; Posterior neck – 5-10%; Intrathyroid – 5%; Carotid sheath – 1%; Anterior mediastinum – 1-2%.  If initial exploration fails – localization studies are indicated.
  • 33. Approaches for parathroidectomy :  Standard Bilateral exploration-Conventional approach  If parathyroid localization studies or IOPTH arent avaialable  If localization studies fail to identify any abnormal glands  If localization studies identify multiple abnormal glands  If concomitant thyroid disorder requires B/L exploration  Targeted/Focussed Approach  Minimally invasive parathyroidectomy  Radio Guided parathyroidectomy using hand held gamma probe  Endoscopic approaches (especially for ectopic parathyroids in mediastinum)  Robotic gasless , transaxillary techniques
  • 34.
  • 35. Preoperative Localization  imaging is not a diagnostic approach, and the decision for exploration should be made before any imaging is performed  Localization studies have permitted surgeons to perform more limited operations including unilateral and focused neck exploration, radio-guided parathyroidectomy, and several endoscopic or video-assisted approaches. Benefits of Preoperative Localization:  decreased operative times  reduced duration of hospital stay  Smaller Incision , improved cosmetic outcomes  Success rates similar to those obtained with traditional bilateral neck explorations  Different Anesthesia Options  Ambulatory vs. Overnight  Decrease Rate of Missed or Multiple Adenomas
  • 36. PREOP NON INVASIVE LOCALIZATION  Sestamibi or MIBI scintigraphy (methoxyisobutylisonitrile )  taken up by the mitochondria in thyroid and parathyroid tissue.  DISADVANTAGES : - unrevealing in parathyroid hyperplasia, multiple parathyroid adenomas, and in those with coexisting thyroid disease. -falsely negative scans can also be caused by calcium channel blockers that interfere with the take up of the isotope by parathyroid cells . -Other gland characteristics that can increase the likelihood of a negative scan include small size, superior position, and a paucity of oxyphil cells. Sestamibi scanning for parathyroid tissue can be enhanced by combination with three-dimensional imaging (SPECT) & Subtraction thyroid scan ie Sestamibi -Technitium-99m subtraction scintigraphy Technetium-sestamibi scans 15 minutes and 3 hours after injection showing retention of isotope in a left inferior parathyroid
  • 37. Sestamibi -Technitium-99m subtraction scintigraphy.  most widely used and accurate modality with a sensitivity >80% for detection of parathyroid adenomas.  useful for parathyroid localization due to the delayed washout of the radionuclide from hypercellular parathyroid tissue compared to thyroid tissue.
  • 39. • SPECT — Sestamibi-single photon emission computed tomography (SPECT or MIBI-SPECT). three-dimensional sestamibi scan that provides higher resolution imaging and improves the performance of sestamibi scanning. ADVANTAGE : SPECT imaging substantially reduces the likelihood of missing multiglandular disease compared to planar imaging (MIBI SCAN)( Sestamibi scintigraphy) combined with sestamibi single photon emission computed tomography (SPECT) has the highest positive predictive value of the available imaging techniques and some prefer this as the localizing procedure of choice for initial surgery
  • 40. MIBI scan with single photon emission computed tomography showing hot spot in anterior mediastinum (arrow)
  • 41. Neck ultrasonography (high Frequency USG)  highly sensitive in experienced hands inexpensive, noninvasive, and reproducible in the operating room.  helpful for the characterization and evaluation of any thyroid pathology, facilitating operative planning. This is a common problem, since concurrent thyroid pathology is present in up to 30 percent of patients with primary hyperparathyroidism.  Operator dependent  Sensitivity is reduced in patient With thyroid nodule  Sonographic characteristics of parathyroid adenomas include homogeneous hypoechogenicity and an extrathyroidal feeding vessel with peripheral vascularity seen on color Doppler imaging .  False-negatives result from substernal ,ectopic, and undescended tumors
  • 42. Ultrasound views of parathyroid adenomas. (A) Sagittal image of the upper pole of the right lobe of the thyroid gland, demonstrating a hypoechoic parathyroid adenoma posterior to the thyroid parenchyma. (B) Sagittal image of the lower pole of the lower pole of the left lobe of the thyroid gland with an adjacent hypoechoic parathyroid adenoma measuring 9 mm in greatest dimension
  • 43. Magnetic resonance imaging  Localization of ectopic tumors  No radiation exposure  Expensive  False positive results from thyroid nodules & lymph nodes Parathyroid adenoma characteristics on magnetic resonance imaging (MRI) include intermediate to low signal intensity on T1 imaging and high intensity on T2 imaging.
  • 44. CT & 4D CT scan  CT are less sensitive than sestamibi scans,but are helpful in localizing large paraesophageal and mediastinal glands.  4 D C T Incorporates the perfusion of contrast in hyperfunctioning parathyroid tissue over time, thus providing functional information in addition to the anatomic information provided by conventional three-dimensional CT imaging.  In one study 4D-CT showed improved sensitivity of 88% compared to that of sestamibi (65%) and ultrasound (57%) for lateralization of the enlarged gland and also showed superiority when localization to the correct quadrant was examined.  A combination of 4D-CT and ultrasound has been reported to have a positive predictive value of 92% for single- gland disease and 75% for multiple-gland disease.
  • 45.  Non-localizing imaging studies should not preclude initial surgery for patients with biochemically confirmed primary hyperparathyroidism who meet operative criteria. In such patients, a single adenoma is still the most likely intraoperative finding (62 to 77 percent)
  • 46. PREOPERATIVE , INVASIVE LOCALISATION  prior neck surgery  whom noninvasive testing has been unrevealing. Selective venous sampling : A 1.5 to 2-fold increase in parathyroid hormone levels obtained from representative cervical vein drainage locations (inferior, middle, superior thyroid, thymic, and/or vertebral veins Selective arteriography positive localization is considered an increase in the parathyroid hormone level to 1.4 times the baseline or a blush seen on arteriography
  • 47. A baseline PTH value is obtained at the start of the procedure, PTH levels are then measured at following removal of the suspected adenoma . A reduction of >=50 percent from the baseline following excision of the hyperfunctioning gland after 10 mins is an accepted standard for intraoperative confirmation of success. INTAOPERATIVE LOCALISATION USING GAMMA PROBE  1 to 2 mCi of the isotope is injected before surgery, and a hand-held gamma probe is used to guide the identification of the enlarged gland INTAOPERATIVE , INVASIVE LOCALISATION
  • 48. Use of gamma probe intra op
  • 49. Comprehensive Parathyroidectomy Systematic Examination of all Parathyroid Glands in their Usual Anatomic Location and Appropriate Resection of Diseased Parathyroids  For patients with negative (non-localizing) preoperative imaging studies or when bilateral foci are detected.  Most forms of hereditary hyperparathyroidism are an indication for bilateral parathyroid exploration due to the predictable involvement of multiple glands.  Concomitant thyroid disease requiring surgical resection, such as biopsy proven papillary thyroid cancer, necessitates bilateral exploration.  pregnant patients due to the radiation required for some localization studies. However, if ultrasound expertise is available and the results show an apparent single adenoma, a focused approach can be planned.  lithium associated hyperparathyroidism has a higher incidence of being associated with multiple gland involvement and may require bilateral exploration.
  • 50. ■ Focused parathyroid exploration When combined with use of intraoperative PTH monitoring, minimally invasive parathyroidectomy techniques result in excellent outcomes that are comparable to a traditional bilateral cervical exploration. Advantages : The smaller incisions and less extensive dissection lead to reduced postoperative pain and a lower incidence of hypocalcemia from ischemia of other glands. Indications: -No discordance between sistamibi & USG -imaging suggesting unilateral pathology. -no suggestion of concomitant, thyroid disease requiring surgical intervention. -no family history of multiple endocrine neoplasia.
  • 51. How do we do it 1 . Consent for Possibilities of:  persistent hyperparathyroidism (5 per cent);  recurrent laryngeal nerve injury (1 per cent);  postoperative haemorrhage (1 per cent);  permanent hypoparathyroidism;  recurrent hyperparathyroidism  initially after first surgery HPT is corrected but recurs 12 months after surgery) is due parathyromatosis, development of new adenoma, and hyperplasia of transplanted parathyroid. Parathyromatosis is due to rupture and spillage of parathyroid tissue in neck, mediastinum forming functioning nodules
  • 52. Operative strategy and technique of parathyroidectomy Conventional approach  Helpful to mark incision site when patient is awake  positioned in supine, neck extended with the head supported in a padded ring.  A transverse collar incision is made, the subplatysmal plane developed superiorly till thyroid cartilage and inferiorly till supra sternal notch and the avascular midline raphe is incised in the midline between the strap muscles  sternothyroid is are separated from Sternohyoid & loose areolar tissue between sternothyroid & thyroid is taken down at the lateral edge of sternothyroid to prevent lateral displacement of parathyroid  Thyroid lobes are mobilised with division of the middle thyroid vein when present. It is not normally necessary to divide the superior thyroid vessels unless the exploration proves difficult  Medial rotation of the thyroid lobe exposes the inferior thyroid artery and recurrent laryngeal nerve  Inferior glands are identified first as superior glands require more medial rotation of thyroid  Bloodless field is maintained , as blood staining makes parathyroids less noticable
  • 53. The glands are identified in a systematic manner commencing with the common sites and working sequentially through to the rare locations. Superior gland:  1 in fat pad on surface of thyroid lobe above the inferior thyroid artery at level of cricothyroid articulation then  2 inferiorly behind the inferior thyroid artery and oesophagus then  3 divide superior thyroid vessels and rotate upper pole anteriorly. Inferior gland:  1 along the thyrothymic axis then  2 on or under the capsule of the lower pole of the thyroid then  3 incise the fascia of the upper horn of thymus then  4 extend this down into the accessible mediastinal thymus then  5 within the carotid sheath (usually suggested by a tongue of ectopic thymus) then  6 transcervical thymectomy achieved by gentle upper retraction on the thymic lobe then  7 within the thyroid lobe which may require thyroid lobectomy.
  • 54.  All abnormal glands are excised  In sporadic four-gland disease, subtotal parathyroidectomy is carried out, preserving approximately 50 mg of one gland marked with a non-absorbable suture to facilitate any possible future re-exploration.  In patients with four-gland disease, transcervical thymectomy is recommended to reduce the risk of persistent or recurrent hyperparathyroidism.  In patients with MEN-1, total parathyroidectomy reduces the risk of recurrence.  The thin fascia overlying a “suspicious” fat lobule should be incised using a sharp curved hemostat and scalpel.This maneuver often causes the parathyroid gland to “pop” out. Alternatively, gentle, blunt peanut sponge dissection between the carotid sheath and the thyroid gland often reveals a “float”sign, suggesting the site of the abnormal parathyroid gland.  Intra Op adenoma:  Brown with gritty sensation on incising  Sinks in water
  • 55. Operative strategy and technique of parathyroidectomy Focussed / Targeted approach  General or local anaesthesia  Confident preoperative localisation permits a 2–3 cm incision located over the site of the adenoma  Subplatysmal plane is incised and either a midline or lateral approach to the strap muscles permits development of the plane between the thyroid capsule and carotid artery and jugular veins  Adenoma is mobilised staying close to but avoiding rupture of the capsule. Identification of the recurrent laryngeal nerve is not routine and only bipolar diathermy should be used.
  • 56. Targeted parathyroid surgery; a 2-cm incision over left inferior parathyroid adenoma.
  • 57. Median Sternotomy (3%) Extension  Median sternotomy is often needed when parathyroid is in anterior mediastinum along with thymus. Often parathyroid may be 5, 6 in numbers instead of four
  • 58. Complication of parathyroidectomy ? :  Hematoma  Wound infection  Postoperative hypocalcemia ( transient / hungry bone syndrome )  Permanent hypoparathyroidism  Recurrent laryngeal nerve injury(1%)  Persistent hyperparathyroidism—5% (PTH never touches baseline -6 mo)  Recurrent hyperparathyroidism—initially PTH decreases but hypercalcaemia recurs 6 months after first parathyroid surgery
  • 59. The hypocalcemia is generally transient , Transient hypoparathyroidism may be due to manipulation of the blood supply to or removal of one or more parathyroid glands during surgery . In some cases, however, the postoperative hypocalcemia is severe and prolonged despite normal or even elevated levels of parathyroid hormone (PTH). This phenomenon, called the hungry bone syndrome. most often occurs in patients who have developed bone disease preoperatively due to a chronic increase in bone resorption induced by high levels of PTH (osteitis fibrosa).
  • 60. Hypocalcemia after parathyroidectomy Time course of development of hypocalcemia in 25 patients following parathyroidectomy for primary hyperparathyroidism. Most of the fall in the plasma calcium concentration occurred in the first 24 hours after surgery.
  • 61. D/D for the patient with hypocalcemia ? -Hungrey bone syndrome (PTH level normal ). -Vitamine D deficiency. -Both. -Malabsorption. -Permanent hypoparathyroidism (injuried glands )( low PTH ).
  • 62. Criteria for diagnosis of hungrey bone syndrome ?  serum calcium concentration below 8.5 mg/dL (2.13 mmol/L) and the serum phosphate postoperative conentration below 3.0 mg/dL (0.96 mmol/L) on the third day post op.
  • 63. Patients at risk ? 1-Volume of the resected adenoma. 2-Preoperative blood urea nitrogen concentration. 3-Preoperative alkaline phosphatase concentration. 4-Older age. Preoperative serum calcium and PTH levels did not provide additional predictive information. Some studies do point towards pre-op calcium has a indicator for the same
  • 64. Presentation of hungry bone syndrome : -Hypocalcemia . -Hypophosphatemia : The decrease in bone resorption and increase in bone formation that occurs after parathyroidectomy can also lead to hypophosphatemia. -Hypomagnesemia : refractory hypocalcemia. -Hyperkalemia (80 percent) ( unknown ).
  • 65. How it can be prevented ? Preoperative preparation -starting oral calcium 2 to 3 grams per day two days prior to surgery, even in patients who are hypercalcemic. -intravenous calcitriol : in Vit D deficiency , CRF (vitamin D2) (1000 IU per day or more depending on level) in vit D def pts , (2 mcg at the end of each hemodialysis treatment) in HD pts , begun three to five days prior to surgery and continued postoperatively may be helpful in preventing marked hypocalcemia.
  • 66. How it can be treated ?  Treatment is aimed at each of the abnormalities that can occur: hypocalcemia, hypomagnesemia, hypophosphatemia, and hyperkalemia.  the serum calcium concentration should be measured two to four times per day for the first few postoperative day .  Oral calcium supplementation (2 to 4 g of elemental calcium [50 to 100 mmol] per day) should be started as soon as the patient is able to swallow.  If the serum phosphorus is normal or low, calcium should be administered between meals to maximize intestinal absorption and minimize phosphate binding.
  • 67. Intravenous calcium is indicated if the patient develops a rapid and progressive reduction in serum calcium or symptoms related to hypocalcemia, including frank tetany, latent tetany (Chvostek's or Trousseau's sign), or a plasma calcium concentration below 7.5 mg/dL (1.9 mmol/L). the administration of phosphate to reverse hypophosphatemia is generally avoided in patients with hungry bone syndrome, since phosphate can combine with calcium and further reduce the plasma calcium concentration. An exception to this general rule is the presence of severe hypophosphatemia, in which the plasma phosphate concentration is below 1 mg/dL.
  • 68.  TREATMENT OF CONCOMITANT VITAMIN D DEFICIENCY ? the Third International Workshop on Asymptomatic Primary Hyperparathyroidism recommends measuring 25OHD in all patients with PHPT and repleting those with low levels (defined as ≤20 ng/mL [50 nmol/L]) prior to making any management decisions .  Cautiously repleting vitamin D in patients with underlying hyperparathyroidism since worsening hypercalcemia and hypercalciuria have been reported in this setting .
  • 69.
  • 70. Add on  Intra op Parathyroid adenomas are brown with gritty feel  Parathyroids sink in water ; fat doesnt  ??Intraop indocyanin green(as for hepatic functions) assay for parathyroid localisation..infra red light  2 site pth assay  Sandwich assays (two antibodies for C n N terminus of Intact PTH  Two site sampling IJV & peripheral vein sampling  Calcium replacement(1-1.5meq/kg/day replacement)  Persistant hyperparathyroidism : elevated calcium & PTH within 6 months of surgery  Recurrent hyperparathyroidism :levated calcium & PTH that occurs more than 6-12 months after surgery  Implantation in forearm for easy reexplloration