Parathyroid

Anatomy
- Normal: tan-red brown; reticulo-vascular pattern; ovoid
  - 40mg, 4x6mm, ectopic 15-20% time
- Blood supplied from inferior thyroid artery (arcade from lower to upper cephalad direction)
- Inf parathyroid
  - within 1cm of where the RLN crosses inferior thyroid artery
  - Assoc with thymus (styloid to aortic arch)
  - 3^rd pharyngeal pouch
- Sup gland
  - post surface of thyroid at upper and middle third of the gland: morgagni’s tubercle, insertion of sup laryngeal nerve: within 1 cm
  - 4^th pharyngeal pouch
- Physiology: Calcium and phosphate regulation
- PTH
  - Synthesis begins in the endoplasmic reticulum of chief cell
  - PreproPTH to ProPTH to 1-84 PTH: H3N and COO terminals
  - Excreted by kidneys: implications for accurate measurement of pth
  - Half-life= 3.5 min
Normal parathyroid gland turns bad by
- RB(p53) turns into Monoclonal carcinoma
- Men1 (MEN1 mutated in 20% of cases) /PRAD1 turns into Monoclonal adenoma (benign hyperactive)
- low ca, low vitd, high po4, vdr alleles genetics, reduced expression of casr, vdr turns into Polyclonal hyperplasia, monoclonal or oligoclonal hyperplasia, monoclonal adenoma
Hypercalcemia
- In gen population is mc d/t hyperparathyroid
- In hospitalized is mc d/t malignancy
- Alternative causes: lithium tx, thiazide diuretics, sarcoidosis, pagets, milk alkali, MEN1, MEN2a
- Hypercalcemia Ddx
  - Cancer
  - Hyperparathyroidism
  - Immobility
  - Paget’s disease
  - Endocrine: thyrotoxicosis, hypoadrenalism, acromegaly, pheochromocytoma
  - Pharm: thiazide diuretics, lithium, tamoxifen
  - Granulomatous disease: sarcoid, tb, histoplasmosis
  - Millk Alkali, Vit D and A excess
  - Benign familial hypocalcuric hyper calcemia
    - Low grade hypercalcemia, eval with 24 hour urine calcium
- Diagnosis
  - Hypercalcemia and inappropriately high intact PTH (1-84)
  - If low pth consider PTHrp
- Other useful data
  - Elevated or normal 24 hour urine Ca
  - Low serum po4
  - Increase in serum cl- (cl-::Po4 >33)
  - Increased serum alk phos
  - Bone densitometry
- Hypercalcemic crisis
  - Ca >13.5 mg/dl (parathyroid carcinoma)
  - Sx: mental confusion, dehydration, abd pain, vomiting, arrhythmia
  - Tx principles: resuscitate and re-expand vasc space, lower blood calcium level, rarely urgent parathyroidectomy (if hypercalcemia is PTH driven)
    - Hours: normal saline, loop diuretics
    - 1-2 Days: Bisphosphonates, etidronate (first generation) Pamidronate (second generation), Calcitonin
- Calciphylaxis: ischemia 2’ to calcium deposition in the end arterioles
  - Fatal if on trunk
  - 2’ and 3’ hyperpth
  - dx with punch bx shows onion skinning
  - tx/tx parathyroid and skin graft
Hyperparathyroidism
- Primary: disease due to one or more hyper functioning parathyroid glands
  - 80% adenoma 15 % hyperplasia:
    - adenoma is neoplasm
      - 88% d/t single adenoma (size determines): double adenoma 10%
    - hyperplasia: all parathyroid cells abnormal
  - Elevated PTH and calcium levels
  - Incidence .25-1/1000: F(mc post menopausal)>M
    - 2.3% in women 55-75yrs: 1/3 normocalcemic
    - 0.8% in men 55-75yrs
  - RF: radiation therapy, thyroid CA, breast ca 15x higher risk of hyperpth
    - Mutated PRAD protooncogene
  - Sx: stones, groans, abdominal moans, psychic overtones; fatigue, exhaustion, musc weakness, fatigue constipation, weakness, polydipsia, polyuria, nocturia, bone pain, constipation, depression, memory loss, joint pain, loss of appetite, nausea, heartburn, pruritus
  - Assoc Conditions: nephrolithiasis, nephrocalcinosis, hematuria, bone fracture, gout, pseudogout, joint swelling, osteopenia, osteitis fibrosis cystica, weight loss, duodenal ulcer, gastric ulcer, pancreatitis, htn
  - Dx: hypercalcemia (>10.3) with inappropriately high serum pth levels in the setting of normal renal function: not necessarily out of nml range
    - Check: Ca, pth, 24 hr urine excretion (familial hypocalcuric hypercalcemia)
    - Cr clearance
    - Alk phos: bone derived, mildly elevated
    - PO4: depressed
    - Hypochloremic metabolic acidosis: Cl > Po4 = 33:1
- Secondary: factors other than primary parathyroid disease cause overproduction of pth (renal failure): pth works so hard to keep calcium up because of renal failure
  - Chronic renal failure
  - Vit d deficiency
  - Elevated PTH levels, low or normal calcium
  - Slight advantage to total with autotransplant preferably to upper extremity
- Tertiary: autonomous
  - Arises from longstanding secondary HPT leading to autonomous hypersecretion of PTH
  - Elevated pth and calcium
- Localizing Tests
  - Diagnose first: biochemical: high Ca, high/normal PTH
    - Dx is an indication for surgery: benefit from intervention
    - No need for further localization in 2’ or 3’ or familial
  - Ultrasound
    - Quick, convenient, relatively inexpensive, permits FNA of concomitant thyroid pathology, accuracy 60-80% (highly operator dependent). Anatomic information (parathyroid location/thyroid disease)
  - Sestamibi with SPECT
    - (originally used for muga scan-cadiolight, held by mitochondria)
    - 88%sn; Accuracy 60-80%: less accurate (0-38%) for multigland disease
    - Permits assessment of ectopic/mediastinal glands
    - Time-consuming
    - Expensive
    - Wide range of quality
    - Allows unilateral exploration
  - CT: 50-60% sensitive
  - Other localizing studies: Typically reserved for re-operative cases:
    - Mri
    - Venous Sampling
    - Arteriography
    - Four gland exploration 96% sensitive
- Surgical Indications in asymptomatic patients
  - Age <50
  - Serum Ca >1mg/dL above normal or 11.2 mg/dl
  - Creatinine clearance decreased by 30% now <60ml/min
  - Bone density: t-score >2.5sd: now and/or previous fragility fracture
  - Hypercalcuria >400mg
  - Mayo: asymptomatic hyperpth: 142pt with mild elevated Ca no overt renal/bone disease
    - ¼ of these pt had parathyroidectomy ultimately
    - 1/3 lost to follow up
    - 10% renal fxn decreased
Parathyroidectomy-terms
- Parathyroidectomy : Four gland b/l exploration
  - 4 big, 3.5 gland resection with autotransplantation
    - unilat 96% effective (4% double): would still do b/l
  - Focused v b/l exploration: Why focused parathyroidectomy
    - Doesn’t disturb normally functioning parathyroid glands
    - Decreased early hypocalcemia
    - Facilitates use of local anesthesia
    - Smaller incisions
    - Shorter operating times
    - Long term cure rate 97%
- Minimally invasive parathyroid (MIP) or Minimally invasive radioguided parathyroidectomy (MIRP)
  - Prelocalization: sestimebe
    - Alike sln: utilize gamma probe
    - Ex vivo: >20% of background
      - ex/ 40 count on background of 200
  - Monitored anesthesia care of awake patient
  - Surgeon-administered cervical block
  - Open 2.5-3.5cm incision or 1cm incision over hot gland
  - Intraop intact pth measurement
    - To confirm that all hypersecreting parathyroid tissue has been excised
    - To prevent overlooking multiglandular disease
    - By providing point of care information postoperative eucalcemia can be reliably predicted during surgery
    - Draw from IJ through neck
    - must drop by 50% in 10min; if still out of normal range must explore other side.
  - Can allow same day discharge
    - If pth falls local and day op is fine, if not, to sleep and explore
  - Conversion to general anesthesia occasionally needed
- Endoscopic parathyroidectomy
- Subtotal parathyroidectomy (2/4, 3/4, 3.5/4)
Surgery: B/l neck exploration: Systematic search for all parathyroid tissue
- Superior Parathyroid glands:
  - Dorsal on thyroid
  - Posterolateral to RLN; above intersection of inf thyroid artery and nerve 80%
    - 12% more cranial, assoc with fat, rarely intrathyroidal
  - If missing superior gland: mc in tracheoesophageal groove of posterior superior mediastinum
    - Re-explore the retro-esophageal space as far down into the mediastinum as possible
    - Explore the superior thyroid pedicle
    - Explore carotid sheath
    - Ligate/mobilize the superior pole of thyroid lobe
    - Palpate thyroid lobe: consider thyroid lobectomy
    - Consider sup thymecotmy
    - Don’t do sternotomy first go round: close and eval in the am: possibly infarcted
- Inferior Parathyroid:
  - Anteromed to rln
  - If missing inferior parathyroid gland: more variable; key is thymus; cranial horn of the thyrothymic ligament best place to look 44%, 26% within thymic tissue, intra thyroidal 17%
    - 1^st Mobilize thymus, pull up into neck, check esophageal tracheal grove, posterotracheal, explore superior mediastinum
    - Can explore carotid sheath to angel of mandible: almost never lateral to carotid sheath
    - Palpate thyroid lobe, carefully inspect thyroid capsule- consider thyroid lobectomy (reasonable), can check intraop u/s
  - If not able to locate missing gland: CLOSE (do everything you can in the neck)
    - Do not perform median sternotomy
    - Confirm diagnosis: repeat labs
    - Repeat localizing studies
    - Role of cross-sectional imagine (4dct) and selective venous sampling
    - Don’t remove normal glands
- NIM: nerve monitoring
  - Overall risk: 15% neuropraxia, 9% permanent after re-op
  - Helpful in redo
  - 1^st time no survival benefit
- Intraop PTH: no benefit 1^st time surgery: success <50% of highest value or within normal range
  - Miami protocol: 4 blood draws: pre incision, pre excision, 5min after excision and 10 min after excision
- Redo: 85-90% “ectopic” within normal locations
  - If not within first 2 weeks, then wait 6-8 wks
  - Can approach lateral from sternohyoid dissection
  - Always start with neck reexploration
  - MC true ectopic: ant sup mediastinum: lower gland in the thymus.
Familial Hyperparathyroidism
- r/o pheo in men2
  - genetic testing widely available
- obtain longest duration of eucalcemia
- minimize risk of surgically-induced hypoparathyroidism
- facilitate future surgery for recurrent disease
- Surgical options
  - Total parathyroidectomy with autotransplantation
    - In arm: if recurrent can re explore under local and can cuff test the efficacy
  - Subtotal parathyroidectomy
    - Use of intraoperative pth (more stringent criteria >80% drop)
    - Cryopreservation remainder
Multiglandular disease tx
- Subtotal parathyroidectomy
- Total parathyroidectomy with autotransplant
Parathyroid carcinoma
- Grey white/translucent and don’t shell out
- p/w high high ca level (15), palpable mass in neck
- Dx clinical or local invasion
- Tx/ hemi thyroidectomy, or en bloc soft tissue resection and lymphadenectomy with ipsilateral thyroidectomy
  - Postop rad dec local recurrence, no chemo

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