Superior parathyroids – 4th pharyngeal pouch; associated with thyroid complex
• Found lateral to recurrent laryngeal nerves (RLNs), posterior surface of superior portion of gland, above inferior thyroid artery
Inferior parathyroids – 3rd pharyngeal pouch; associated with thymus
• Found medial to RLNs, more anterior, below inferior thyroid artery
• Inferior parathyroids have more variable location and are more likely to be ectopic
• Occasionally are found in the tail of the thymus (most common ectopic site) and can migrate to the anterior mediastinum
• Other ectopic sites – intra-thyroid, mediastinal, near tracheoesophageal groove
90% have all 4 glands
Inferior thyroid artery – blood supply to both superior and inferior parathyroid glands
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PTH – increases serum Ca
• ↑ kidney Ca reabsorption in the distal convoluted tubule, ↓ kidney PO4 absorption
• ↑ osteoclasts in bone to release Ca (and PO4−)
• ↑ vitamin D production in kidney (↑ 1-OH hydroxylation) → ↑ Ca-binding protein in intestine → ↑ intestinal Ca reabsorption
Vitamin D – ↑ intestinal Ca and PO4 absorption by increasing calcium-binding protein
Calcitonin – decreases serum Ca
• ↓ bone Ca resorption (osteoclast inhibition)
• ↑ urinary Ca and PO4 excretion
Normal Ca level: 8.5–10.5 (ionized 4.4–5.5)
Normal PTH level: 5–40 pg/mL
Normal PO4 level: 2.5–5.0
Normal Cl− level: 98–107
Most common cause of hypoparathyroidism is previous thyroid surgery
PRIMARY HYPERPARATHYROIDISM
Women, older age
Due to autonomously high PTH
Dx: ↑ Ca, ↓ PO4−; Cl− to PO4− ratio > 33; ↑ renal cAMP; HCO3− secreted in urine
Can get hyperchloremic metabolic acidosis
Osteitis fibrosa cystica (brown tumors) – bone lesions from Ca resorption; characteristic of hyperparathyroidism
Most patients have no symptoms – ↑ Ca found on routine lab work for some other problem or on checkup
Symptoms: muscle weakness, myalgia, nephrolithiasis, pancreatitis, PUD, depression, bone pain, pathologic fractures, mental status changes, constipation, anorexia
Hypertension can result from renal impairment
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Indications for surgery:
• Symptomatic disease
• Asymptomatic disease with Ca > 13, ↓ Cr clearance, kidney stones, substantially ↓ bone mass
Single adenoma – occurs in 80% of patients
Multiple adenomas – occur in 4% of patients
Diffuse hyperplasia – occurs in 15%; patients with MEN I or IIa have 4-gland hyperplasia
Parathyroid adenocarcinoma – very rare; can get very high Ca levels
Treatment
• Adenoma – resection; inspect other glands to rule out hyperplasia or multiple adenomas
• Parathyroid hyperplasia
• Do not biopsy all glands → risks hemorrhage and hypoparathyroidism
• Tx: resect 3½ glands or total parathyroidectomy and autoimplantation
• Parathyroid CA → need radical parathyroidectomy (need to take ipsilateral thyroid lobe)
• Pregnancy – surgery in 2nd trimester; ↑ risk of stillbirth if not resected
Intraop frozen section → can confirm that the tissue taken was indeed parathyroid
Intraop PTH levels → can help determine if the causative gland is removed (PTH should go to < ½ of the preop value in 10 minutes)
Missing gland – check inferiorly in thymus tissue (most common ectopic location, can remove tail of the thymus and see if PTH drops), near carotids, vertebral body, superior to pharynx, thyroid
Still cannot find gland – close and follow PTH; if PTH still ↑, get sestamibi scan to localize
At reoperation for a missing gland, the most common location for the gland is normal anatomic position
Hypocalcemia postop – from bone hunger or failure of parathyroid remnant/graft
• Bone hunger – normal PTH, decreased HCO3−
• Aparathyroidism – decreased PTH, normal HCO3−
Persistent hyperparathyroidism (1%) – most commonly due to missed adenoma remaining in the neck
Recurrent hyperparathyroidism – occurs after a period of hypocalcemia or normocalcemia
• Can be due to new adenoma formation
• Can be due to tumor implants at the original operation that have now grown
• Need to consider recurrent parathyroid CA
Reoperation associated with ↑ risk of RLN injury, permanent hypoparathyroidism
Sestamibi scan
• Will have preferential uptake by the overactive parathyroid gland
• Good for picking up adenomas but not 4-gland hyperplasia
• Best for trying to pick up ectopic glands
SECONDARY HYPERPARATHYROIDISM
Seen in patients with renal failure
↑ PTH in response to low Ca
Most do not need surgery (95%)
Ectopic calcification and osteoporosis can occur
Tx: Ca supplement, vitamin D, control diet PO4, PO4-binding gel, ↓ aluminum
• Surgery for bone pain (most common indication), fractures, or pruritus (80% get relief)
• Surgery involves total parathyroidectomy with autotransplantation or subtotal parathyroidectomy
TERTIARY HYPERPARATHYROIDISM
Renal disease now corrected with transplant but still overproduces PTH
Has similar lab values as primary hyperparathyroidism (hyperplasia)
Tx: subtotal (3½ glands) or total parathyroidectomy with autoimplantation
FAMILIAL HYPERCALCEMIC HYPOCALCIURIA
Patients have ↑ serum Ca and ↓ urine Ca (should be ↑ if hyperparathyroidism)
Caused by defect in PTH receptor in distal convoluted tubule of the kidney that causes ↑ resorption of Ca
Dx: Ca 9–11, have normal PTH (30–60), ↓ urine Ca
Tx: nothing (Ca generally not that high in these patients); no parathyroidectomy
PSEUDOHYPOPARATHYROIDISM
Because of defect in PTH receptor in the kidney, does not respond to PTH
PARATHYROID CANCER
Rare cause of hypercalcemia
↑ Ca, PTH, and alkaline phosphatase (can have extremely high Ca levels)
Lung most common location for metastases
Tx: wide en bloc excision (parathyroidectomy and ipsilateral thyroidectomy)
50% 5-year survival rate
Mortality is due to hypercalcemia
Recurrence in 50%
MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES
Derived from APUD cells
Neoplasms can develop synchronously or metachronously
Autosomal dominant, 100% penetrance
MEN I
• Parathyroid hyperplasia
• Usually the 1st part to become symptomatic; urinary symptoms
• Tx: 4-gland resection with autotransplantation
• Pancreatic islet cell tumors
• Gastrinoma #1 – 50% multiple, 50% malignant; major morbidity of syndrome
• Pituitary adenoma
• Prolactinoma #1
• Need to correct hyperparathyroidism 1st if simultaneous tumors
MEN IIa
• Parathyroid hyperplasia
• Medullary CA of thyroid
• Nearly all patients; diarrhea most common symptom; often bilateral
• #1 cause of death in these patients
• Usually 1st part to be symptomatic
• Pheochromocytoma
• Often bilateral, nearly always benign
• Need to correct pheochromocytoma 1st if simultaneous tumors
MEN IIb
• Medullary CA of thyroid
• Nearly all patients; diarrhea most common symptoms; often bilateral
• #1 cause of death in these patients
• Usually 1st part to be symptomatic
• Pheochromocytoma
• Often bilateral, nearly always benign
• Mucosal neuromas
• Marfan’s habitus, musculoskeletal abnormalities
• Need to correct pheochromocytoma 1st if simultaneous tumors
MEN I – MENIN gene
MEN IIa and IIb – RET proto-oncogene
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