Hyperparathyroidism

Hyperparathyroidism is a common cause of hypercalcaemia, especially in the outpatient setting. Primary Hyperparathyroidism (PHPT) is usually caused by a solitary parathyroid adenoma (80%), followed by four-gland hyperplasia (15%) and rarely carcinoma. It is most common in post-menopausal women. Secondary Hyperparathyroidism is a compensatory rise in PTH in response to low serum calcium, most commonly due to Chronic Kidney Disease (CKD) or Vitamin D deficiency. Tertiary Hyperparathyroidism occurs when the parathyroid glands become autonomous after a long period of secondary hyperparathyroidism (usually in end-stage renal failure). The biochemical hallmark of PHPT is 'high calcium, low phosphate, and high/inappropriate PTH'. Many patients are now diagnosed incidentally through routine blood tests. Management ranges from observation ('watch and wait') to surgical parathyroidectomy, which is the only definitive cure for PHPT.

PTH is secreted by the chief cells of the four parathyroid glands. Its primary role is to maintain serum calcium. PTH acts on: 1. Bone: Stimulates osteoclast activity (via RANK-L) to release calcium and phosphate. 2. Kidney: Increases calcium reabsorption in the distal tubule and increases phosphate excretion in the proximal tubule. 3. Kidney (Vitamin D): Stimulates 1-alpha-hydroxylase to convert 25-hydroxy vitamin D to its active form (1,25-dihydroxy vitamin D), which increases intestinal calcium absorption. In PHPT, the 'set-point' of the calcium-sensing receptor (CaSR) is shifted, leading to PTH secretion despite high calcium. In CKD, the inability to excrete phosphate and the failure to activate Vitamin D lead to hypocalcaemia, which chronically stimulates the parathyroid glands.

The mnemoninc 'Stones, Bones, Abdominal Groans, and Psychic Moans' summarizes the features: Stones: Nephrolithiasis (calcium oxalate/phosphate stones) and nephrocalcinosis. Bones: Bone pain and osteoporosis (pathological fractures). Chronic severe PHPT causes 'osteitis fibrosa cystica'. Abdominal Groans: Constipation, nausea, and notably peptic ulcer disease (calcium stimulates gastrin) and pancreatitis. Psychic Moans: Depression, fatigue, and confusion. Clinical signs: Hypertension and shortened QT interval on ECG. Many are asymptomatic ('moans' only).

Bloods: Corrected Calcium (raised), PTH (raised or inappropriately 'normal'), Phosphate (low), Urea & Electrolytes (check renal function). Urine: 24-hour urinary calcium (helps distinguish PHPT from Familial Hypocalciuric Hypercalcaemia/FHH, where urine calcium is very low). Imaging for localisation (pre-op): Sestamibi scan and Ultrasound of the neck. Bone density: DEXA scan to assess for osteoporosis.

Primary: 1. Observation: If asymptomatic, Ca2+ < 2.85 mmol/L, no renal/bone disease. 2. Surgical: Parathyroidectomy is recommended if symptomatic, age < 50, or significant hypercalcaemia. 3. Medical: Bisphosphonates (for bone protection) or Cinacalcet (increases sensitivity of CaSR, lowering PTH). Secondary: Treat underlying cause (e.g., Vitamin D replacement, phosphate binders in CKD). Tertiary: Often requires Cinacalcet or total parathyroidectomy.