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Related Subjects: |PTH Physiology |Calcium Physiology |Magnesium Physiology |Calcitonin |Hypocalcaemia |Hypercalcaemia |Hypomagnesaemia |Hypermagnesaemia |Primary Hyperparathyroidism |Familial hypocalciuric hypercalcaemia (FHH) |Sarcoidosis

Watch for hypocalcaemia after surgery to ensure that it returns to normal and does not drop too low.

About

• An albumin adjusted serum calcium of over 2.6 mmol/L (UK).
• A common cause of mild asymptomatic hypercalcaemia
• 10% are seen as part of Autosomal dominant MEN I and II.
• Females > Males. Seen in 1 in 300

Physiology

• Most people have four parathyroid glands
• Located posteriorly to the thyroid
• Secretes PTH, a polypeptide, in response to low calcium levels
• PTH facilitates the synthesis of active vitamin D
• PTH regulates calcium and phosphate
• PTH binds to cell receptors coupled to G proteins
• CAMP is the secondary messenger

Aetiology of Primary hyperparathyroidism

• Single Adenoma (85%)
• Multiple adenomas (may be seen in MEN1)
• Diffuse Hyperplasia of all glands
• Parathyroid Carcinoma (<1%)

Clinical effects mainly of chronic hypercalcaemia

• Patients may be asymptomatic for years
• Bone pain, weakness and osteoporosis and fractures
• Renal stones, polyuria, renal tubular acidosis, nephrogenic diabetes insipidus
• Moans - psychiatric disease, depression. mood changes
• Abdominal - constipation, pancreatitis, peptic ulcer disease
• Rheumatic - gout, pseudogout
• Cardiac - hypertension and arrhythmias

Differential

• Malignant hypercalcaemia - measure PTHrp assay: Urinary calcium high/normal, exclude myeloma
• Familial hypocalciuric hypercalcaemia: there may be high calcium and elevated PTH (low urinary calcium) Autosomal dominant: Urinary calcium low
• Lithium or thiazide use: can result in elevated calcium and PTH. Stop the drugs and reassess

Investigations

• U&E: Raised Urea and Creatinine and calcium with dehydration
• Normal/Low phosphate (in 30%)
• Raised or normal Alkaline phosphatase with increased bone turnover
• Inappropriately raised PTH levels ( PTH should be undetectable with raised calcium)
• X-rays may show osteitis fibrosa cystica with bone resorption in fingers with subperiosteal erosions, cysts, or brown tumour of phalanges ± acro-osteolysis
• Urine calcium: increased in 30% of patients.
• DexaScan - shows reduced bone density and osteopenia
• USS of the neck to locate adenoma
• Sestamibi scintigraphy with CT techniques to localise adenoma
• Venous sampling of the veins from the parathyroid may be required in some difficult cases but this is uncommon

Management

• ABC, Rehydration and then later IV Bisphosphonates. Stop thiazide diuretics. Avoid Vitamin D or Vitamin A.
• Surgery: Parathyroidectomy is the treatment of choice. It is safe and has good outcomes and can be done under local anaesthesia. It can lead to an increase in bone mineral density over a year and this continues for up to 10 years. Surgery is recommended for symptomatic patients and for those who have skeletal and renal complications. Surgery enables removal of usually the adenoma and if hyperplasia then 3 and a half glands. May need post-op Calcium/Vitamin D
• In older patients a more conservative policy may be appropriate if hypercalcaemia and complications can be controlled medically.
• Indications for routine referral to endocrinology
  • Less than 70 years old and Calcium >2.79 mmol/l and eGFR 30-44 (CKD 3b)
  • Symptomatic (including renal stones), History of osteoporosis or fracture
  • If referral indicated. Check urinary calcium excretion index.
  • If referral not indicated the patient can be managed in primary care. Repeat calcium in 3 months. If calcium stable, then monitor annually. Every 2-3 years consider DEXA scan. If referral criteria met at later review refer to endocrinology
• Patients who decline surgery or not fit for
  • Keep a close eye on serum calcium, creatinine, and PTH annually. Monitor bone mineral density every 1-2 years.
  • Encourage ambulation and hydration. Keep calcium intake to less than 1000 mg/day. Avoid thiazide diuretics. Avoid Vitamin D or Vitamin A.
  • Bisphosphonates may be used but effects not sustained
  • Cinacalcet can help to reduce calcium and parathyroid hormone levels and increase the phosphate level
• Indications for Surgery: three and a half of the glands are removed
  • Serum Ca > 0.25 mmol/L above upper limit of normal
  • 24 hr urinary calcium excretion > 10 mmol (400mg)
  • Creatinine clearance < 30% or more
  • Bone mineral density T score < -2.5
  • Age younger than 50
  • Patient request, unlikely follow up
• Complications of Parathyroidectomy
  • Hypocalcaemia: post-surgical. Often seen but short term. Bones are 'hungry' for calcium and phosphate can be rapidly removed from your blood and deposited in your bones. Low calcium level because your remaining normal parathyroid glands aren't working properly yet - they are underactive (hypoparathyroidism).
  • Low blood calcium level goes back up to normal when your remaining normal parathyroid glands become sensitive again and can control your blood calcium level. However, sometimes hypoparathyroidism can persist and some people need long-term medication treatment with calcium and vitamin D supplements.
  • Recurrent laryngeal nerve can sometimes occur during the operation. This can cause a cough and a hoarse voice.
  • Bleeding. This can sometimes occur after surgery. Rarely, the blood can collect in your neck and put pressure on your airway, causing breathing difficulties. This needs quick treatment to remove the blood clot.
  • Infection. After any type of surgery, this is a possible complication. Persisting hyperparathyroidism. Occasionally, surgery is unsuccessful and hyperparathyroidism is not adequately treated.

References

• Pathophysiology of Primary Hyperparathyroidism
• Calcium Regulation