Systemic amyloidosis may infiltrate the thyroid or other endocrine glands but rarely causes endocrine dysfunction. We describe a 45 years old female patient with diffusely enlarged goiter and hypopituitarism secondary to amyloid infiltration of the thyroid gland and possibly pituitary gland, respectively. She was on chronic haemodialysis for 3 years due to systemic amyloidosis. While she was being prepared for thyroidectomy, adrenal failure developed. Her anterior pituitary hormone levels were low and magnetic resonance imaging of the hypophysis showed low signal intensity in right part of the adenohypophysis. She improved with corticosteroid replacement therapy and underwent subtotal thyroidectomy without any complication. Histopathologically, amyloid deposition was demonstrated in the thyroid gland. To our knowledge, this is the first case with amyloid goiter and hypopituitarism secondary to systemic amyloidosis. Amyloid infiltration should be considered in a systemic amyloidosis patient presenting with rapidly enlarged thyroid gland and signs of hypopituitarism.