3rd April 2024

Hyperparathyroidism

This occurs when there is excessive PTH secretion from the parathyroid glands. The aetiology can be primary, secondary or tertiary. Most patients with primary hyperparathyroidism are asymptomatic and the condition is detected on routine laboratory screening. Other patients may present with clinical and biochemical abnormalities related to hypercalcaemia, such as renal stones and pancreatitis.  

Clinical manifestations are non-specific with fatigue, myalgia, anxiety, and poor sleep the most common. Gastrointestinal symptoms such as constipation and nausea occur less frequently. The classical triad in MCQs is a patient with polyuria, polydipsia, and bony pain. A consequence of extremely high levels of PTH is abnormal bone turnover and/or mineralisation, which increases the risk of developing fragility fractures. 

Aetiology

Primary hyperparathyroidism occurs when there is autonomous overproduction of PTH. It is a common condition, predominantly affecting older and post-menopausal women. Most cases (80%) are caused by a single parathyroid adenoma, with multiple gland hyperplasia responsible for the remaining 10-20%. Parathyroid carcinoma occurs in around 1% of cases. Inherited conditions such as multiple endocrine neoplasia (MEN) 1 and 2 can predispose to gland hyper-productivity, with hyperparathyroidism the presenting feature of 90% of patients with MEN1. 

Secondary hyperparathyroidism is the result of increased PTH production in response to hypocalcaemia. Commonly due to chronic kidney disease (eGFR ≤ 45 ml/min/1.73m2) or vitamin D deficiency, hypocalcaemia, combined with calcitriol deficiency and phosphate retention, leads to a compensatory rise in parathyroid hormone to maintain homeostasis. In patients with end-stage renal failure (ESRF), hypocalcaemia commonly occurs due to 1a-hydroxylase deficiency, a renal enzyme responsible for the conversion of 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D (calcitriol). 

Tertiary hyperparathyroidism occurs when there is parathyroid gland hyperplasia due to chronic hypocalcaemia.

Untreated chronic hypocalcaemia in patients with advanced or dialysis-dependent kidney failure can lead to autonomous PTH secretion, irrespective of calcium concentrations, caused by gland hyperplasia.

Diagnostics

Diagnosis is by blood sampling looking at calcium, phosphate, parathyroid hormone, alkaline phosphatase and vitamin D levels. Other causes of hypercalcaemia, such as familial hypocalciuric hypercalcaemia, should be excluded. Table 1 shows the typical biochemical findings in primary, secondary and tertiary hyperparathyroidism. Whilst imaging is not necessary for diagnosis, CT neck or cervical ultrasonography may be useful for planning surgery and identifying concomitant thyroid disease. 

Table 1: Typical biochemistry in primary, secondary and tertiary hyperparathyroidism

Management

Curative treatment centres around elective parathyroidectomy, with pre-operative vitamin D repletion advised if deficient. Successful kidney transplantation removes the driving force for tertiary hyperparathyroidism and leads to spontaneous resolution in around 60% of patients after 2 years.

In patients with resistant hypercalcaemia, second line treatments such as intravenous bisphosphonates may be given, with an onset of action in 2-4 days; or denosumab, calcitonin or calcimimetics such as cinacalcet. Cinacalcet increases the sensitivity of calcium receptors on the parathyroid gland to serum calcium and thus reduces PTH secretion, with particular use in secondary hyperparathyroidism.

Emergency treatment centres around symptomatic management of hypercalcaemia and treatment of the underlying cause. Restoration of circulating volume via aggressive rehydration, occasionally requiring up to 10 litres of fluid in the first 24 hours, is key to emergency management. Patients with hypercalcaemia-induced renal failure may require dialysis.