Hyperparathyroidsim
Hyperparathyroidism refers to excess secretion of parathyroid hormone.
Primary Hyperparathyroidism
Primary hyperparathyroidism is caused by the excess secretion of parathyroid hormone (PTH), resulting in hypercalcemia. 85% of cases are due to a parathyroid adenoma.
It peaks at 70+ years of age and is more common in women.
- Causes
- Solitary adenoma (85%)
- Hyperplasia of all glands (10%)
- Multiple adenoma (4%)
- Carcinoma (1%)
- Inherited disorders responsible for hyperparathyroidism
- Multiple endocrine neoplasia (MEN)
- Hyperparathyroidism jaw tumor syndrome
- Familial isolated primary hyperparathyroidism
- Risk factors
- Female sex
- Advanced age
- Family history – increased risk of multi-gland disease
- Pathophysiology
- Autonomous secretion of PTH → hypercalcaemia
- Signs and symptoms
- Often asymptomatic
- Signs and symptoms of hypercalcaemia
- Hypertension
- Polyuria
- Dehydration
- Paraesthesia
- Muscle cramps
- Weight loss
- Night sweats
- Differentials
- Familial hypocalciuric hypercalcaemia
- Malignancy-associated hypercalcaemia
- Secondary hyperparathyroidism
- Investigations
- Serum calcium and phosphate
- Hypercalcaemia
- Hypophosphataemia (unless in renal failure)
- Parathyroid hormone (PTH) to differentiate primary hyperparathyroidism and familial hypocalciuric hypercalcaemia
- Elevated or inappropriately normal
- Renal function tests to exclude secondary or tertiary hyperparathyroidism
- 25-hydroxyvitamin D Level to exclude secondary hyperparathyroidism
- Sestamibi scan (Technetium-99m) to localize an adenoma
- Ultrasound of the neck
- 4D CT-scan to identify ectopic or supernumerary parathyroid glands
- Genetic testing to identify inherited disorders such as MEN1, MEN2A, and hyperparathyroid jaw tumor syndrome (HPT-JT)
- Radiographs
- Osteitis fibrosa cystica due to severe resorption – subperiosteal erosions, cysts, or brown tumours of phalanges
- Acro-osteolysis
- Pepper-pot skull
- DEXA scan for osteopaenia and osteoporosis
- Serum calcium and phosphate
- Treatment
- Increased fluid intake to prevent calcium stones
- Avoid thiazide diuretics, high dietary calcium, and vitamin D
- Parathyroidectomy has a high cure rate (98%)
- Calcitonin – reduced calcium concentration by inhibiting bone and kidney resorption of calcium
- Cinacalcet – a calcimimetic that increases the sensitivity of the parathyroid cells to calcium, thereby reducing PTH secretion without affecting bone density or urinary calcium concentrations
- Desunomab – impairs calcium resorption
- Bisphosphonates
- Indications for parathyroidectomy
- High serum or urinary calcium
- Bone disease
- Osteoporosis
- Renal calculi
- Reduced renal function
- ≤ 50 years old
- Complications of untreated hypercalcaemia
- Osteoporosis and fragility fractures
- Kidney stones and kidney injury
- Hypertension and heart disease
- Peptic ulcer disease
- Pancreatitis
- Gall stones
- Complications of parathyroidectomy
- General surgical complications
- Recurrent or superior laryngeal nerve damage
- Transient hypocalcaemia
- Symptomatic hypocalcaemia (hungry bone syndrome)
- Recurrence (8% over 10 years)
Secondary Hyperparathyroidism
Secondary hyperparathyroidism is due to hypocalcemia, most commonly caused by chronic kidney disease, vitamin D deficiency, or impaired calcium absorption.
- Causes
- Reduced vitamin D intake
- Chronic kidney disease
- Pathophysiology
- Hypocalcaemia → increased secretion of PTH
- Treatment
- Correct underlying hypocalcaemia or vitamin D deficiency
- Phosphate binders
- Cinacalcet if PTH ≥ 85 pmol/L
- Renal transplant
- Parathyroidectomy – debulking surgery – if it is refractory to medical treatment
Tertiary Hyperparathyroidism
Tertiary hyperparathyroidism occurs following long-standing secondary hyperparathyroidism. Chronic stimulation of the parathyroid glands causes them to autonomously secrete PTH.
- Cause
- Long-standing secondary hyperparathyroidism in renal failure
- Pathophysiology
- Chronic hypocalcaemia → chronic stimulation of parathyroid glands → hyperplasia of parathyroid glands → autonomous secretion of PTH
- Renal transplant → hypercalcaemia due to normal renal function
- Treatment
- Parathyroidectomy with reimplantation of a small portion of the gland
Malignant Hyperparathyroidism
Malignant hyperparathyroidism is caused by the production of parathyroid-related protein (PTHrP) by squamous cell lung cancer, breast cancer, and renal carcinoma. PTHrP mimics PTH, resulting in hypercalcaemia.