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

?