Primary Hyperparathyroidism: Misunderstood and Underdiagnosed

Introduction

Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by elevated or normal serum calcium levels in the presence of elevated or inappropriately normal parathyroid hormone (PTH) levels. The incidence varies from 0.4 to 82 cases per 100,000. Females account for about three-fourths of all cases but the incidence rates are similar in men and women less than 45 years of age.

What Causes Primary Hyperparathyroidism?

• Almost 90% of the patients are found to have sporadic, non-familial and non-syndromic disease.
• Sporadic PHPT is usually caused by a single gland adenoma (85% of patients), but may also be caused by hyperplasia of all four glands (10%), double adenomas (2–5%) or rarely, parathyroid carcinomas (<1%).
• 5–10% of patients may be associated with syndromic and hereditary disease:
• Multiple endocrine neoplasia type 1 (MEN1)
• Multiple endocrine neoplasia type 2A (MEN2A)
• Multiple endocrine neoplasia type 4 (MEN4)
• Hyperparathyroidism jaw-tumor syndrome (HPT-JS)
• Familial isolated primary hyperparathyroidism (FIHP)

Regulation of Calcium Homeostasis

Clinical Phenotypes of PHPT:

The clinical and biochemical profile of PHPT varies in different parts of the world.

1. Symptomatic PHPT – Associated with overt skeletal and renal complications. In India, > 90% of the patients present with symptomatic disease compared to the West, where asymptomatic disease has been the dominant clinical phenotype.It has a varied clinical presentation which includes:

• Generalised weakness
• Bone pain, fractures
• Renal stones
• Pancreatitis, gastritis
• Constipation
• Abdominal pain
• Hypertension
• Anxiety, depression
• Pathological fracture
• Palpable mass
• Hypercalcemic crisis

2. Asymptomatic PHPT – No overt symptoms or signs, typically discovered by biochemical screening. On evaluation, target organ involvement may or may not be present.

3. Normocalcemic PHPT – Precursor or subclinical form of classical PHPT.

PHPT – Indian Scenario

• Primary hyperparathyroidism (PHPT) in the Indian population has a wide spectrum of clinical presentations.
• Most common presentations include generalized weakness (80%), bone pain (35%) and renal stone disease (20%).
• Asymptomatic disease is seen in 15% of the patients.

Who’s Most at Risk?

• Age – Most common in people above 60 years, but it can also occur in young adults.
• Female gender; women are more often affected than men.
• Radiation to the head and neck.
• Inherited endocrine problems.
• Conditions that cause low levels of calcium or vitamin D in the body.

Diagnosing Primary Hyperparathyroidism

• Biochemical – Serum calcium, phosphorous, intact PTH, vitamin D, creatinine
• Skeletal – 3 site dual-energy x-ray absorptiometry (DEXA)
  High-resolution peripheral quantitative CT (HRpQCT)
• Renal – 24-hour urinary calcium, and creatinine clearance
• Genetic Evaluation – Patients < 30 years, those with multigland disease, those with a positive family history

Pre-Operative Localisation

• High-resolution neck ultrasound
• Technetium 99-M-sestamibi scintigraphy
• Four-dimensional computed tomography (4D-CT)

Treatment

• Most PHPT features are likely to improve with a surgical cure.
• Surgery is the only curative treatment, is cost-effective and is indicated for all symptomatic patients.
• Surgical options include:
  • Bilateral neck exploration + parathyroidectomy
  • Focused parathyroidectomy
  • Minimally invasive parathyroidectomy

Dr. Dhalapathy Sadacharan
Consultant Surgical Endocrinologist,
Kauvery Hospital, Chennai