Current Status of Surgery For
Primary and Secondary
Hyperparathyroidism
Surgery Grand Rounds
20 Aug., 2014
W. G. Schenk III
Disclosures
HYPERPARATHYROIDISM
Basic Physiology, Anatomy, Embryology
Primary Hyperpara
Clinical Presentations
Evolution of surgical approach and pre-op imaging
Secondary Hyperpara
Clinical Presentation
Indications for Surgical Rx
Surgical Options
PTH CALCIUM
PTH and CALCIUM HOMEOSTASIS
+
-
PTH
c-PTHn-PTH
Renal c-AMP
Bone Osteoclast
GI Absorption
GI, Renal : 1,25 D
CALCIUM
Ca++
(Albumin)Calcitonin
(?) +
_
PTH and CALCIUM HOMEOSTASIS
Vit D3 Phos
HYPERPARATHYROIDISM
Appropriate Hypersecretion in
Secondary Hyperparathyroidism
Inappropriate excess secretion of
Parathyroid Hormone
in Primary Hyperparathyroidism
HYPERPARATHYROIDISM
SURGICAL APPROACES
Embryology
3rd Branchial Pouch: Thymus and
Lower PTH’s
4th Branchial Pouch: Upper PTH’s
Ectopic (5%) and supranumerary (15%)
Primary
Secondary
Tertiary
FHH Syndrome
Malignancy
PTH Ca++ PO4 U. Ca++ Cl / PO4 Ca x PO4
> 33
DIAGNOSIS OF HYPERPARATHYROIDISM
Differential Diagnosis of Hypercalcemia
Primary Hyperparathyroidism
Malignancy
Bone Metastases
Paraneoplastic
Medication
Lithium, Vit. A,D, Thiazides
Granulomatous Disease
Excess intake,Dehydration, Immobilization Familial Hypocalciuric Hypercalcemia (FHH)
Symptoms of Primary Hyperparathyroidism
Constitutional
Fatigue, Wt loss, Anorexia
GI
Peptic Ulcer Disease
Nausea, Vomiting
Musculoskeletal
Bone and joint pain
Muscle weakness
Neurologic
Headache, memory loss
Neurosis, Psychosis
Cardiovascular
Hypertension
Nephrologic
Stones, Renal impairment
Dermatologic
Pruritis, brittle nails
Symptoms of Primary Hyperparathyroidism
“ASYMPTOMATIC”
Some symptoms can usually be elicited by careful questioning.
Rationale for surgical Rx in asyptomatic patient.
PRIMARY HYPERPARATHYROIDISM
Family History
MEN I (Wermer’s Syndrome)
Pituitary, Panc Islet Cell
MEN II (Sipple’s Syndrome)
MCT, Pheo
(MEN IIb)
FHH (Familial Hypocalciuric Hypercalcemia)
PRIMARY HYPERPARATHYROIDISM
Physical Exam
General : BP, Neuro, Cardiac, Operative risk
Neck Exam: Thyroid abnormality
adenopathy, palpable mass
Vocal cord function, neck mobility
Occult Malignancy (Breast, Prostate)
LABORATORY EVAL IN PRIMARY HYPER-PTH
Calcium Determination(s)
Cl, Po4, Alb, Tot Protein, BUN, Creat., Alk Phos.
** Cl/Po4 ratio > 33
24-hr Urine ** Ca > 100 mg / day
U-creat., Ca/Cr Clearance ratio, Cyclic AMP
Chest X-ray
Hand, Bone Xrays (optional)
PTH Radioimmunoassay
PTH Levels in Primary Hyperparathyroidism
INDICATIONS FOR SURGERY IN
PRIMARY HYPERPARATHYROIDISM
Diagnosis of
Hyperparathyroidism Questionable Secure
Symptomatic Asymptomatic Significant
Calcium 10.5 11.0
Surgical risk Prohibitive Low
(No prior neck surgery)
HYPERPARATHYROIDISM
SURGICAL APPROACES
ANATOMIC CORRELATION:
“Sporadic” Primary – single gland (95%)
Familial Primary
Secondary Multigland Hyperplasia
Tertiary
Sporadic Primary Hyperpara: Single Parathyroid Adenoma
Hypercellular Parathyroid
800 mg
Rationale for Pre-op
Imaging in Primary Hyper-PTH
Identify ectopic and supernumerary glands
Identify multiple adenomas
Provide pre-op anatomic confirmation of biochemical Dx
Reduce incidence of persistent/recurrent hyper-para
Permit “limited exploration”
Reduce complication risk
“The only pre-op localization necessary is to locate an experienced neck surgeon”
John DoppmanNIH Concensus Conference1980
Hyperparathyroidism
Evolution of Imaging Relevence
Improvement in imaging technology
Popularity of limited exploration
Development of rapid PTH Assay
Economic pressures
Jim Norman (based on the past 15,000 PTH operations):
Norman J, Lopez J, Politz D; Abandoning Unilateral Parathyroidectomy; JACS Mar 2012 ; 214(3) : 260-269
“Our patients get the exact same operation regardless of scan findings – we simply do not care if their scans are positive or negative”
Surgeon-Performed Ultrasound
for
Primary Hyperparathyroidism
Convenience, Efficiency
Schenk WG, Hanks JB, Smith PW
Surgical / Anatomic Correlation
Volume of positive studies
Additional relevant findings
Surgeon-Performed Ultrasound
for
Primary Hyperparathyroidism
Class 1: Hi Confidence
Classification of pre-op Neck Ultrasound
Class 2: “Possible”
Class 0: None seen
Primary Hyper PTH: Pre-Op Imaging
Results
Class 1: 111/200 (55%)
3 patients deferred surgery
107/108 Intra-op agreement
108/108 Cured
Results
Class 1: 111/200 (55%)
3 patients deferred surgery
107/108 Intra-op agreement
108/108 Cured
Class 0 : 4-D CT Scan
Class 2 : Surgery w or w/o imaging
Tc-99m sestamibi scan Coronal slice and 3D reconstruction from a 4DCT
CURRENT CONTROVERSIES:
“SPORADIC” PRIMARY HYPERPARA
“Limited Exploration” vs. Complete Exploration
Pre-op Imaging
Intra-op PTH Assay
Evolving Approaches:
Minimally invasive / Robotic
Regional Anesthesia
Ambulatory/Outpatient
SECONDARY HYPERPARATHYROIDISM
Appropriate PTH level (Nutritional or Renal).
Renal Failure:
Numerous influences on Ca homeostasis
High proportion of Dialysis pts have elevated PTH.
Less than ten percent should require surgical Rx.
Effects of Renal Failure on PTH Homeostasis
Diminished renal hydroxylation of D3
Decreased GI absorption of Calcium
Decreased suppression of PTH by D3
Decreased (total) serum Calcium
Decreased renal excretion of phosphorus
Direct effect of Hyperphosphatemia
Decreased ionized Calcium
Elevated “set point” of PTH responsiveness
Osteoblast resistance to PTH
Autonomous Hypersecretion from Hyperplasia
Primary
Secondary
Tertiary
FHH Syndrome
Malignancy
PTH Ca++ PO4 U. Ca++ Cl / PO4 Ca x PO4
+ >55
DIAGNOSIS OF HYPERPARATHYROIDISM
PTH Levels in Secondary Hyperparathyroidism
The majority of
dialysis patients have
some elevation in PTH.
A level in the 100- 300
pg/ml range is common.
Elevated level alone
is not an indication
for surgical Rx.
SECONDARY HYPERPARATHYROIDISM
Indications for Surgery
Failure of reliable maximal medical Rx.
Development of significant symptoms: Musculo-
skeletal, pruritis, calcinosis cutis, neuro-psych.
Calcium x Phosphorus product above 70.
Osteopenia, decreasing measured bone density,
bone biopsy.
Development of Tertiary Hyper-PTH
SECONDARY HYPERPARATHYROIDISM
PRE-OP EVALUATION
General condition - operative risk.
Virtually all are dialysis-dependant
Alk Phos
Ultrasound (optional); Sestamibi scan not helpful.
Neck Exploration
Identification of all Parathyroid Glands
SECONDARY HYPERPARATHYROIDISM
Surgical Options
Subtotal Parathyroidectomyor
Total Parathyroidectomy with PTH Autotransplant
Essential Components of Either Procedure:
• Complete Neck Exploration
• Identification of All PTH’s
• Ablation of Hyperplastic Glands
• Leave 40-70 mg Functioning PTH
• Consider temporary central line
SURGERY:
FAMILIAL PRIMARY (MEN)
SECONDARY AND TERTIARY
Subtotal (3 ½ gland) resection
Total Parathyroidectomy with Autotransplant.
Special Considerations
MEN I Syndrome
Calcinosis/Calciphylaxis
Tertiary after transplant
Subtotal PTH-x vs Total PTH-x with AutoTx
Complexity and Duration of Surgery
Long – term Recurrence of Secondary Hyper PTH
Ease / Cost of Post-op Care
Patient Compliance
Calcinosis – special situation
Any
Questions
?