UCI Otolaryngology Head and Neck Surgery

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UCI Otolaryngology Head and Neck Surgery

• Thursday Morning Conference
• March 29, 2007
• Paul K. Holden, MD

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Case Presentation

• 47 yo female referred to you for the following
  laboratory value
• Ca 11.9

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HPI / PMH

• Otherwise Healthy
• Hi Ca found on routine annual screening
• Repeat tests confirm similar result
• No h/o renal calculi, bone pain, other pain
• Admits to some vague symptoms of fatigue and low
  energy
• Takes hormone replacement and calcium
  supplements, otherwise no meds
• Wants to know if it is serious

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Question 1

• Name the FOUR main organs that regulate blood Ca
  levels.

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Question 2

• Upon which main organ(s) does PTH directly act to
  regulate blood Ca levels?
• Kidney
• Bone (osteoclasts)
• Bonus How do the kidneys act on the gut?

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• V
• I
• T
• A
• M
• I
• N
• D

1, 25-dihyroxyvitamin D3
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• C
• H
• I
• M
• P
• A
• N
• Z
• E
• E
• S

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• Calcium - exogenous
• Hyperparathyroidism
• Immobility
• Metastasis to bone
• Pagets disease of bone
• Addisons disease
• Neoplasm (prostate, lung, colon, breast, HNC)
• Zollinger Ellison Syndrome
• Excess of Vit A or D, thiazide, lithium, estrogen
• Endocrine disorder (other) thyroid, pheo, FHH
• Sarcoid (granulomatous diseases)

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Question 3

• What is the most common presentation for a
  patient with hyperparathyroidism?
• Asymptomatic
• Some will give vague symptoms of fatigue or limb
  discomfort after being prompted.
• Severe cases can present with bones, stones,
  groans, psychic overtones

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Question 4

• Which of the following is most likely primary
  hyperparathyroidism?
• ?Ca ?PTH ?Phos
• ?Ca ?PTH ?Phos
• ?Ca ?PTH ?Phos
• High or normal PTH in the face of high serum
  calcium and low phos is usually primary HPT.

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Primary Hyperparathyroidism

• 85 caused by single adenoma
• Hyperplasia (8-10)
• Double adenoma (3-5)
• Parathyroid Carcinoma (1)
• Tx is usually surgical.

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Secondary Hyperparathyroidism

• Most common cause is Renal insufficiency causes
  increased Phosphate, poor retention of Ca, poor
  conversion of 25 Vit D3 to 1,25 D3
• Other diseases affecting bone OI, Pagets,
  myeloma, bone mets, Addisons
• Tx is control cause, usually medical mgmt,
  phosphate binders, vit D, calcimimetics

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Tertiary Hyperparathyroidism

• Development of uncontrollably high PTH levels due
  to long-term secondary hyperparathyroidism,
  calcium levels can also be high.
• Tx is usually surgical.

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Pseudo Hyperparathyroidism

• Autosomal Dominant disease characterized by low
  calcium, high phosphate and insensitivity to PTH.
• Short stature, round face, shortened bones of
  hands and feet, dental hypoplasia, soft tissue
  calcifications
• Also called Albright Hereditary Osteodystrophy
  (AHO)

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Back to Our Patient

• What additional studies will help with the
  diagnosis/management of this patients disease?
• 24hr Urine Calcium is 550mg
• Intact PTH level is mildly elevated
• DEXA Shows T-Scores -2.0 in spine, hip, distal
  radius.

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Is she a surgical candidate?

• NIH Position Statement (Updated 2002)
• Surgery indicated if one of the following is
  true
• Ca gt 1mg/dL over ULN (repeated)
• 24hr Urine Ca gt 400mg
• CrCl decreased by 30 from normal
• T-score gt2.5 of spine, hip or distal radius (any
  one site)
• Age lt 50 yrs
• Pt request or surveillance will be difficult or
  impossible

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Preoperative Imaging

• Which of the following has approximately 90
  sensitivity in detecting a single cervical
  adenoma?
• MRI with contrast
• CT with contrast, fine cuts
• High resolution ultrasound
• Tc99 Sestamibi Scan

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Preoperative Imaging

• Tc99 has a 91 sensitivity and 97 positive
  predictive value helps localization, reduces
  morbidity, also good (less sensitive) for double
  adenoma.
• Tc99-SPECT incorporates 3-D positional
  information, no evidence it changes diagnostic
  sensitivity.
• Hi Res Ultrasound 90 sensitivity, esp helpful
  with negative/marginal Tc99 scan, helps
  localization and volume approximation, less
  sensitive with multinodular goiter.

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Preoperative Imaging

• MRI much less sensitive (appx 60) but can help
  with mediastinal localization, expensive, no
  radiation.
• CT essentially equivalent sensitivity to MRI,
  though less expensive, has radiation, also helps
  with mediastinal localization.

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Wheres the Adenoma??
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Wheres the Adenoma??
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Wheres the Adenoma??
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Wheres the Adenoma??
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Our Patients Results

• Pt has Tc99 Sestamibi scan showing left inferior
  adenoma. HR Ultrasound confirms a 1cm nodule in
  approximately the same location.

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What operation do you perform?

• A) Subtotal parathyroidectomy with reimplantation
• B) Bilateral exploration with selective gland
  removal, possible reimplantation
• C) Unilateral exploration of both glands, removal
  of adenoma
• D) Unilateral w/ possible bilateral exploration,
  intraopertive PTH monitoring

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Intraoperative PTH Monitoring

• PTH has short half life, allowing for
  confirmation of appropriate drop in levels by 50
  within 10 minutes.
• Can repeat at 20 mins if dropped but not quite
  enough.
• Most surgeons also prefer to see a drop into
  normal range.
• Limitation in patients with normal preop PTH
  levels.

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Medical Management

• 25 progression of disease in 10 yrs (more likely
  in pts lt 50yrs)
• Bisphosphonates studies show increased bone
  denisty
• Ca/Vit D help reduce bone loss
• Calcimimetics (Cincacalcet) currently in use
  for parathyroid ca and secondary HPT
• SERMs tamoxifen or raloxifene
• Monitor bone density every year and Ca level
  every 6 months

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Hereditary Hyperparathyroidism

• Familial Hypocalciuric Hypercalcemia Dx with 24
  hr Urine Ca lt 50mg/24 hrs
• MEN I and IIa
• Hyperparathyroidism Jaw Tumor Syndrome
• Fibro-osseous jaw tumors Renal cysts/tumors
• Familial Isolated Hyperparathyroidism Other
  family members with HPT and no other hereditary
  issues. Usually hyperplasia.

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FHH

• Autosomal Dominant
• Elevated Serum Calcium
• PTH low normal
• Low urinary excretion of Ca (lt50mg/24hr)
• Hypermagnesemia
• Surgery is NOT corrective
• Prognosis excellent w/ confirmation of FHx and
  hypocalciuria

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MEN I

• Hyperparathyroidism (95) Hyperplasia
• Gastrinoma (45) tumor of pancreas
• Pituitary Adenoma (25)
• Also have facial angiofibromas (85) and
  collagenomas (70)
• Subtotal parathyroidectomy high success rate, but
  50 recurrence at 10 yrs.
• Higher rate of postop hypocalcemia.

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MEN IIa

• Medullary Thyroid Ca (95)
• Pheochromacytoma (50)
• Hyperparathyroidism (20) usu adenoma
• RET mutation (98)
• Higher surgical cure rate than MEN I and far less
  likely recurrence rate.

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Final Quiz Questions

• 49 yo male with hyperparathyroidism and history
  of an ossifying fibroma of the mandible. Which
  of the following should you order
• MRI of the IACs pre/post Gad
• Renal U/S
• Spiral Chest CT
• Barium Swallow

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Final Quiz Questions

• Hyperparathyroidism plus the below findings, what
  is the disease?

MEN I
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Final Quiz Questions

• Identify any medications below that can cause
  hypercalcemia
• Lithium
• Prilosec
• Cinacalcet
• Hydrochlorothiazide
• Aleve

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Final Quiz Questions

• Recall the following numbers from the NIH
  guidelines
• Serum Ca gt ___ above ULN
• 24hr Urine Ca gt ____ mg
• CrCl reduced by ____ below normal
• DEXA T-score of ____ in spine, wrist, hip
• Age lt ____

1.0
400
30
2.5
50
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Final Quiz Questions

• You are in multidisciplinary clinic presenting a
  patient with hyperparathyroidism. You are asked
  What is the calcium-creatinine clearance ratio?
• You reply ask an endorinologist
• You ask the calcium creatinine what?
• You say Let me just answer this page, Ill be
  right back
• You ask can I phone a friend?

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The Trivia

• CA/CRT ratio (24 hr urine calciumXserum crt)/(24
  hr urine crtXserum calcium)
• Rarely used in cases of tertiary HPT to decide
  for surgery referral. In those cases, the ratio
  is gt70.

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Thank You!