A 38-year-old man from Delhi presents with recurrent nephrolithiasis (third episode in 2 years) and persistent hypercalcaemia (serum calcium 11.2 mg/dL). Imaging shows a 1.2 cm lesion in the right parathyroid gland on ultrasound. His father died of a pancreatic neuroendocrine tumour at age 52. What is the most appropriate next step in management?

## Clinical Context This patient presents with primary hyperparathyroidism (elevated calcium, parathyroid adenoma on imaging) and a significant family history of pancreatic neuroendocrine tumour — a classic presentation suggestive of **MEN1 syndrome**. ## Why Genetic Testing is the Next Step **Key Point:** MEN1 is an autosomal dominant syndrome caused by mutations in the *MENIN* gene (chromosome 11q13). The diagnosis is clinical, but genetic confirmation is essential for: - Confirming the diagnosis in the proband - Enabling cascade screening of family members - Guiding surveillance protocols (more frequent imaging, biochemical monitoring) - Informing surgical strategy (bilateral parathyroid exploration vs. unilateral adenomectomy) **High-Yield:** MEN1 diagnostic criteria include two of three features: (1) parathyroid tumour, (2) pancreatic neuroendocrine tumour (gastrinoma, insulinoma), (3) anterior pituitary adenoma. This patient meets criteria with hyperparathyroidism + family history of pancreatic NET. ## Rationale for Correct Answer Genetic testing should precede surgery because: 1. **Bilateral disease risk**: ~20% of MEN1 patients have bilateral parathyroid hyperplasia; unilateral adenomectomy alone has high recurrence. Genetic confirmation guides extent of surgery. 2. **Syndromic surveillance**: If MEN1 is confirmed, the patient requires lifelong screening for gastrinomas (fasting gastrin, secretin stimulation test), insulinomas (72-hour fast), and pituitary adenomas (prolactin, IGF-1). 3. **Family cascade screening**: Genetic confirmation allows testing of relatives (father's siblings, siblings of the proband). **Clinical Pearl:** In MEN1, parathyroid disease is the most common manifestation (~95% by age 50), but pancreatic NETs are the leading cause of death; early detection via genetic confirmation enables aggressive surveillance. ## Management Algorithm ```mermaid flowchart TD A[Hyperparathyroidism + Family Hx of Pancreatic NET]:::outcome --> B{Suspect MEN1?}:::decision B -->|Yes| C[Genetic testing for MEN1]:::action C --> D{Mutation confirmed?}:::decision D -->|Yes| E[Bilateral parathyroid exploration]:::action D -->|No| F[Unilateral adenomectomy]:::action E --> G[Lifelong surveillance: gastrin, insulin, prolactin]:::action F --> H[Standard follow-up]:::action ```