Parathyroid

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  • 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)
      • 3rd 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
      • 4th 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%
        • 1st 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
      • 1st time no survival benefit
    • Intraop PTH: no benefit 1st 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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