What mechanisms can cause weight loss in hyperparathyroidism?

Mechanisms of Weight Loss in Hyperparathyroidism

Hyperparathyroidism can cause weight loss primarily through parathyroid hormone (PTH)-induced browning of white adipose tissue, which increases energy expenditure and leads to fat mass reduction. 1

Primary Mechanisms of Weight Loss in Hyperparathyroidism

• PTH and PTH-related protein (PTHrP) bind to the type 1 PTH receptor (PTH1R) in white adipose tissue, activating cyclic adenosine monophosphate (cAMP)-dependent protein kinase A, which stimulates thermogenic genes and causes adipose tissue browning 2
• This adipose tissue browning increases resting energy expenditure, leading to loss of muscle and fat mass, ultimately resulting in weight loss 2, 1
• Higher circulating PTH levels are associated with lower body weight independent of renal function, serum calcium, phosphorus, and albumin levels in primary hyperparathyroidism patients 1
• Patients with primary hyperparathyroidism exhibit both higher prevalence of detectable brown/beige adipose tissue and increased browning activities compared to control subjects 1

Secondary Mechanisms Contributing to Weight Loss

• In chronic kidney disease-related secondary hyperparathyroidism, elevated PTH contributes to increased energy expenditure through calcium-dependent and calcium-independent mechanisms 3
• PTH excess can result in protein-energy wasting, malnutrition, and cachexia, particularly in advanced cases 2
• Hyperparathyroidism is associated with myopathy and muscle weakness, which may contribute to weight loss through muscle mass reduction 2, 3
• Gastrointestinal symptoms like nausea, vomiting, and decreased appetite are common adverse effects in hyperparathyroidism that can contribute to reduced food intake and weight loss 4

Clinical Manifestations Related to Weight Loss

• In primary hyperparathyroidism, weight loss is often accompanied by other symptoms such as fatigue, weakness, and gastrointestinal disturbances 5
• Patients with parathyroid carcinoma (a rare cause of primary hyperparathyroidism) frequently experience anorexia (15%) and dehydration (15%), which can exacerbate weight loss 4
• Severe hypercalcemia (>14.0 mg/dL) can cause polyuria, polydipsia, nausea, vomiting, and abdominal pain, all of which may contribute to weight loss 6
• Patients with primary hyperparathyroidism should undergo regular monitoring of nutritional status during the course of the disease, with particular attention to changes in body weight 6

Pathophysiological Differences Between Types of Hyperparathyroidism

• In primary hyperparathyroidism, autonomous overproduction of PTH occurs from abnormal parathyroid tissue (usually adenoma), leading to hypercalcemia and its metabolic consequences 7, 8
• Secondary hyperparathyroidism, particularly in chronic kidney disease, involves phosphate retention leading to transient hyperphosphatemia, decreased ionized calcium, and compensatory PTH elevation 9
• Both primary and secondary hyperparathyroidism can lead to increased energy expenditure and weight loss through similar mechanisms, though the underlying causes differ 2, 3

Management Implications

• Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the definitive treatment for primary hyperparathyroidism and can reverse the metabolic effects causing weight loss 8, 5
• In secondary hyperparathyroidism due to chronic kidney disease, calcimimetic agents like cinacalcet can directly lower PTH levels by increasing the sensitivity of the calcium-sensing receptor 4
• Regular monitoring of nutritional status and body weight is recommended for all patients with hyperparathyroidism 6
• Treatment of hypercalcemia in hyperparathyroidism may include rehydration with IV crystalloid fluids, loop diuretics after correction of intravascular volume, and bisphosphonates 6