Special Surgery 4. Surgery of the Parathyroid Gland

I. Parathyroid Anatomy and Physiology

Anatomy

• Usually 4 parathyroid glands
• Located on posterior surface of thyroid gland
• Superior glands: usually more constant position near posterior upper/middle thyroid
• Inferior glands: more variable position because of embryologic descent with thymus
• Ectopic locations:

• Thymus / thyrothymic ligament
• Intrathyroidal
• Carotid sheath
• Retresophageal / paraesophageal
• Mediastinum

• Blood supply usually from inferior thyroid artery
• Close surgical relation to recurrent laryngeal nerve

Physiology

• Parathyroid glands secrete parathyroid hormone (PTH)
• PTH regulates calcium and phosphate balance
• Low serum Ca2+ → calcium-sensing receptor activation decreases → increased PTH secretion
• PTH effects:

• Bone: increased osteoclast-mediated bone resorption indirectly → increased Ca2+ release
• Kidney: increased Ca2+ reabsorption
• Kidney: decreased phosphate reabsorption → phosphaturia
• Kidney: increased vitamin D activation → increased intestinal Ca2+ absorption

• Excess PTH → hypercalcemia + bone loss
• PTH deficiency → hypocalcemia

II. Hyperparathyroidism: Types, Symptoms and Diagnosis

Definition

• Hyperparathyroidism = excessive PTH effect
• PTH excess → increased bone resorption + renal calcium retention + vitamin D activation → hypercalcemia in primary/tertiary disease
• Most common in 6th decade
• More common in women
• Children/young patients → consider hereditary syndromes, especially MEN1/MEN2

Etiologic Classification

1. Primary Hyperparathyroidism

• Autonomous hyperfunction of one or more parathyroid glands
• Most common cause of hypercalcemia in outpatients
• Laboratory pattern: high PTH, high Ca2+, low phosphate
• Causes:

• Single parathyroid adenoma: about 80-85%
• Double adenoma
• Multiglandular hyperplasia
• Parathyroid carcinoma: rare, under 1%
• MEN1/MEN2A-associated disease: usually multiglandular

2. Secondary Hyperparathyroidism

• Physiological compensatory PTH secretion due to chronic hypocalcemic stimulus
• Typical causes:

• Chronic kidney disease
• Vitamin D deficiency
• Malabsorption

• CKD pattern: high PTH, low/normal Ca2+, high phosphate
• Vitamin D deficiency pattern: high PTH, low/normal Ca2+, low/normal phosphate

3. Tertiary Hyperparathyroidism

• Long-standing secondary hyperparathyroidism → parathyroid hyperplasia → autonomous PTH secretion
• Glands no longer respond normally to serum Ca2+ feedback
• Often seen in chronic renal failure or after renal transplantation
• Laboratory pattern: high PTH, high Ca2+, often high phosphate if renal failure persists

Clinical Features

• Classical mnemonic: bones, stones, groans and psychic overtones

• Bones: bone pain, osteopenia/osteoporosis, fragility fracture, osteitis fibrosa cystica
• Stones: nephrolithiasis, nephrocalcinosis, recurrent urinary tract symptoms
• Groans: constipation, nausea, abdominal pain, peptic ulcer, pancreatitis
• Psychic overtones: fatigue, depression, confusion, mental changes

• Other hypercalcemia signs: muscle weakness, polyuria, polydipsia, dehydration
• Secondary hyperparathyroidism in CKD:

• Renal osteodystrophy
• Bone pain/fractures
• Pruritus
• Vascular/soft tissue calcification
• Calciphylaxis in severe cases

Diagnosis

1. Biochemical Diagnosis

• Diagnosis is biochemical first; imaging is not used to prove the disease
• Serum total calcium corrected for albumin or ionized calcium
• Serum intact PTH
• Serum phosphate
• Creatinine/eGFR
• 25-OH vitamin D
• Alkaline phosphatase if bone turnover suspected
• 24-hour urinary calcium:

• High/normal urine calcium supports primary hyperparathyroidism
• Low urine calcium suggests familial hypocalciuric hypercalcemia (FHH)
• Important before unnecessary surgery

2. Assessment of Complications

• Bone mineral density (BMD / DXA): lumbar spine, hip, distal radius
• Vertebral imaging if fracture suspected
• Renal imaging: ultrasound/CT/X-ray for nephrolithiasis or nephrocalcinosis
• Urine stone-risk profile if recurrent stones/hypercalciuria

3. Localization Imaging Before Surgery

• Used only after biochemical diagnosis and decision for surgery
• Goal: localize adenoma and plan focused operation
• Modalities:

• High-resolution neck ultrasound
• Tc-99m sestamibi scintigraphy / SPECT-CT
• 4D-CT if ultrasound/sestamibi negative or discordant
• MRI or PET in selected difficult/reoperative cases

• Negative imaging does not exclude primary hyperparathyroidism

III. Indications and Types of Parathyroid Surgery

Indications for Surgery

1. Primary Hyperparathyroidism

• Parathyroidectomy is definitive treatment
• Indicated in all symptomatic patients if medically fit
• Indications in asymptomatic primary hyperparathyroidism: any one is enough

• Serum Ca2+ > 1.0 mg/dL = 0.25 mmol/L above upper normal limit
• Age < 50 years
• Osteoporosis: T-score <= -2.5 at lumbar spine, hip or distal radius
• Fragility fracture or vertebral fracture
• Renal involvement: nephrolithiasis, nephrocalcinosis or eGFR/creatinine clearance < 60 mL/min
• Hypercalciuria: >250 mg/day in women or >300 mg/day in men
• Parathyroid carcinoma suspected
• Patient preference if no contraindication
• Inability/unwillingness to comply with observation

2. Secondary Hyperparathyroidism

• First-line treatment is medical and treatment of underlying cause
• Surgery if severe disease is refractory to medical treatment
• Typical surgical indications:

• Persistent very high PTH despite phosphate binders, vitamin D analogues and calcimimetic therapy
• Severe renal osteodystrophy / bone pain / fractures
• Severe pruritus
• Calciphylaxis
• Progressive soft tissue or vascular calcification

3. Tertiary Hyperparathyroidism

• Surgery if autonomous PTH secretion causes persistent hypercalcemia
• Common after long-standing CKD or renal transplantation
• Indications: symptomatic hypercalcemia, renal/bone complications, graft dysfunction risk or failed medical therapy

Types of Parathyroid Surgery

1. Focused / Minimally Invasive Parathyroidectomy

• For localized single adenoma
• Small targeted incision
• Preoperative localization guides side and depth
• Often combined with intraoperative PTH monitoring
• Intraoperative PTH should fall appropriately after adenoma removal → suggests cure
• If PTH does not fall or multigland disease found → convert to bilateral neck exploration

2. Bilateral Neck Exploration

• Traditional standard operation
• Explore both sides and identify all 4 glands if possible
• Indications:

• Negative or discordant localization
• Suspected multiglandular disease
• Familial/MEN disease
• Reoperative or complex anatomy depending on case
• Surgeon preference/resources

3. Subtotal Parathyroidectomy

• Usually for parathyroid hyperplasia
• Remove 3.5 glands
• Leave small well-vascularized remnant in neck
• Used in secondary/tertiary HPT or hereditary multigland disease
• Balance: prevent recurrence but avoid permanent hypoparathyroidism

4. Total Parathyroidectomy with Autotransplantation

• Remove all identified parathyroid tissue
• Implant small pieces of parathyroid tissue into forearm muscle or sternocleidomastoid muscle
• Forearm implantation allows easier reoperation if graft becomes hyperfunctional
• Used in severe hyperplasia, renal hyperparathyroidism or recurrent disease

5. Parathyroid Carcinoma Operation

• Rare cause of primary hyperparathyroidism
• Suspicion:

• Very high Ca2+ and PTH
• Palpable hard neck mass
• Local invasion
• Recurrent laryngeal nerve palsy

• Treatment: en bloc resection of tumor with ipsilateral thyroid lobe and involved tissues if needed
• Avoid capsular rupture → reduces recurrence risk
• Simple shell-out excision is inadequate if carcinoma suspected

Surgical Access and Principles

• Incision: Kocher collar incision above suprasternal notch
• Identify and protect recurrent laryngeal nerve
• Preserve normal parathyroid glands and their blood supply if not diseased
• Check for ectopic glands if expected gland is missing
• Assess concomitant thyroid disease preoperatively; treat thyroid pathology during same operation if indicated

IV. Medical Treatment, Postoperative Care and Complications

Medical Treatment

1. Primary Hyperparathyroidism When Surgery Is Deferred/Contraindicated

• Hydration and avoidance of dehydration
• Avoid thiazide diuretics and lithium if possible
• Maintain vitamin D sufficiency
• Cinacalcet:

• Calcimimetic
• Increases calcium-sensing receptor sensitivity
• Decreases PTH secretion and lowers serum calcium

• Bisphosphonates or denosumab → improve bone mineral density by inhibiting bone resorption
• Monitoring if no operation: serum Ca2+, renal function, BMD, renal stones

2. Secondary Hyperparathyroidism

• Treat underlying cause
• Chronic kidney disease management:

• Dietary phosphate restriction
• Phosphate binders → decrease GI phosphate absorption
• Vitamin D analogues / calcitriol → suppress PTH secretion
• Calcimimetics such as cinacalcet → decrease PTH
• Dialysis adequacy and renal transplant evaluation if relevant

• Vitamin D deficiency → vitamin D replacement

Postoperative Monitoring

• Observe for neck hematoma and airway compromise
• Monitor serum calcium
• Monitor PTH if needed
• Check magnesium/phosphate in severe disease or hungry bone risk
• Assess voice postoperatively
• Long-term cure in primary HPT: normal calcium more than 6 months after surgery
• Long-term follow-up for recurrent or persistent hyperparathyroidism

Complications

1. Hypocalcemia

• Most important postoperative metabolic complication
• Mechanism: sudden fall in PTH after removal of hyperfunctioning tissue
• Symptoms:

• Perioral numbness
• Tingling in fingers
• Muscle cramps
• Chvostek sign, Trousseau sign
• Tetany, seizures, arrhythmia in severe cases

• Treatment: oral or IV calcium depending on severity + vitamin D/calcitriol

2. Hungry Bone Syndrome

• Severe/prolonged hypocalcemia after parathyroidectomy
• Mechanism: high bone turnover stops → calcium and phosphate rapidly enter bone
• Risk factors:

• Severe primary HPT
• Long-standing secondary/tertiary HPT
• High alkaline phosphatase
• Bone disease/osteitis fibrosa cystica

• Treatment: aggressive calcium + calcitriol + monitoring

3. Recurrent Laryngeal Nerve Injury

• Unilateral injury → hoarseness, weak voice, aspiration risk
• Bilateral injury → airway obstruction/stridor
• Risk higher in reoperative surgery and carcinoma invasion

4. Other Complications

• Neck hematoma → airway emergency
• Wound infection
• Persistent hyperparathyroidism → hypercalcemia within 6 months
• Recurrent hyperparathyroidism → hypercalcemia after more than 6 months of normocalcemia
• Permanent hypoparathyroidism if too much functioning tissue is removed/damaged