Parathyroid Disease

Calcium Regulation

• 99% of body calcium in skeleton

• Miscible Pool: 40% bound to protein, 13% complexed w/ anions, 47% free ionized

• PTH: Increased Ca, Decreased PO4, Increased Vitamin D

• Vitamin D: Increased Ca, Increased PO4, Decreased PTH (slow)

• Kidney, Bones, GI Tract

Hyperparathyroidism

• Usually asymptomatic

• Fatigue and weakness – up to ½ resolve

• Bone and joint pain, stones and hematuria (Reflect decreased bone density & nephrolithiasis)

• Osteitis Fibrosa Cystica (Brown tumor) and Nephrocalcinosis rare

• Calciphylaxis

Hyperparathyroidism: Signs & Symptoms

• Ca=12 mg/dL-14 mg/dL

• Constitutional: fatigue, wt loss, anorexia

• Musculoskeletal: pain, weakness

• Renal: colic, hematuria

• GI: Pancreatitis, constipation, PUD, nausea

• Neuro: H/A, memory loss, psychosis, insomnia

• Skin: pruritus, brittle nails

lab

• Elevated serum Ca X 3

• Elevated PTH

• Other:

– Albumin

– Alkaline Phosphatase

– Phosphorous

– BUN/Cr

– 24-hour urine Ca

– Bone Mineral Density

Localization

• Location of Ectopic glands:

• Paraesophageal (28%)

• Mediastinum (26%)

• Intrathymic (24%)

• Intrathyroidal (11%)

• Carotid sheath (9%)

• High cervical (2%)

• Ultrasound

• CT

• FNA

• MRI

• Angiography w/ or w/o selective venous sampling (Angioablation)

Localization: Sestamibi

• 1989: Cardiac imaging, Technetium derivative

• SPECT imaging

• False Positives: Thyroid nodules

• False Negatives: Small adenomas, hyperplasia

• Cheap

Medical Management

• Q6months

– Ca

– Cr

– U/A

– PTH

• Severe Hypercalcemia:

– Saline-furosemide diuresis

– Bisphosphonates (onset of action 24-48h)

– Calcitonin (immediate onset)

– Hemodialysis

• Estrogen in post-menopausal women

• Chronic Renal Failure (Hypo-Vitamin D, Hyperphosphatemia, HyperPTH)

– Calcium salts

– Vitamin D or analogs

Surgical Management

• 95% Success Rate

• 50-85% in renal failure

• 1% morbidity

• Benign clinical course of hyperparathyroidism

• NIH Guidelines (1990)

– Symptomatic HyperPTH

– Serum Ca 1-1.6 mg/dL above normal

– H/o life-threatening hypercalcemic event

– ClCr <70% of expected – Kidney stones on radiograph – Elevated urine Ca (>400 mg/dL)

– Z-score>2

– Patient requests surgery

– Consistent followup unlikely

– Complicating comorbid condition

– Age<50 yo

• Renal failure (Unresponsive to medical tx)

– Renal osteodystrophy/pathologic fractures

– Intractable bone pain/pruritus

– Calciphylaxis

• New Tools of the Trade: Minimally Invasive Surgery

– Pre-operative Sestamibi

– Intraoperative rapid PTH (50%, 80%)

– Hand-held gamma probe

– Methylene blue

• Adenoma

– Unilateral vs. Bilateral Exploration

– rPTH vs. Frozen Section

• Hyperplasia/Multiple adenomata

– Subtotal – less hypocalcemia

– Subtotal w/ autotransplantation – MEN, Renal Failure

– Total w/ Cryopreservation – up to 1 year

Autotransplantation

• Iced saline bath

• 20-30 mg; 10-20 1-2 mm slices

• SCM vs. Brachioradialis

• Pockets marked with clips

• Up to 50% failure rate

Surgical Complications

• Failure: missed ectopic adenoma, incomplete resection in multi-gland dz.

• Hypocalcemia (20-30%)

– Wait for appearance of symptoms

• TVC paralysis (<1%)

• Hematoma

Multiple Endocrine Neoplasia

• MEN I

– Moderate-severe hyperPTH in 85%

– Zollinger-Ellison, prolactinomas

– Auto Dominant, MEN1(tumor suppressor), Chromosome 11

• MEN IIa

– Mild hyperPTH in 70%

– Medullary Carcinoma 100%

– Pheochromocytoma

– Auto Dominant, RET proto-oncogene

Hyperparathyroidism: Miscellany

• Parathyroid carcinoma

– Hi PTH, palpable neck mass, Hi Ca post-op

– Regional/distant mets in 25-30%, Local recurrence 30%

– Surgery: Ipsilateral thyroid lobe, skeletonization of RLN, paratracheal nodes

• Hyperparathyroidism-Jaw Tumor Syndrome

– Severe hypercalcemia in teenager

– Multiple parathyroid adenomas; 10% parathyroid carcinoma

Hypocalcemia/Hypoparathyroidism

• Neuro: Paresthesias, fasciculations, muscle spasm, tetany, irritability, movement disorder, SEIZURE, psychosis

• Visual: Cataracts, optic neuritis, papilledema

• Pulmonary: Bronchospasm

• CV: Prolonged QT, CHF, Hypotension

• GI: Dysphagia, abdominal pain, biliary colic

• GU: Preterm labor

• Acute Hypocalcemia: Parathyroidectomy

– PTH undetectable at 8 hours

– Normalizes by 30 hours

– Calcium nadir at 20 hours, normal Day 2-3

– Hungry bone syndrome – Old, Labs

• Medications: I-131, Cimetidine, ETOH, Cisplatin, Digoxin, Ampho-B

– Hypomagnesemia

Hereditary Hypoparathyroidism

• DiGeorge’s syndrome and velocardiofacial syndrome – agenesis

• Pseudohypoparathyroidism – peripheral resistance to PTH

– Short stature, round facies, obesity, mild MR, dental abscesses, short digits, thickened calvaria, ectopic calcification

• Acute severe hypocalcemia

– Check ionized Ca

– 100-300 mg (10-30 ml) 10% Ca-gluconate in 150 cc D5W over 10 minutes

– Continuous infusion at 0.5 mg/kg/hr

– EKG monitoring

– Check Magnesium

– Check Phosphorous

Frederick S. Rosen, MD

Anna M. Pou, MD