A 48-year-old man presents to the endocrinology clinic with progressive changes in his facial appearance over the past 8 years. His wife notes that his face has become "coarser" and his jaw has protruded significantly. On examination, the feature marked **B** in the diagram is evident, along with dental malocclusion and increased spacing between his teeth. Serum IGF-1 is markedly elevated, and an oral glucose tolerance test shows failure of growth hormone to suppress below 1 ng/mL. MRI sella reveals a 2.5 cm pituitary adenoma with suprasellar extension. Which of the following best explains the pathophysiology of the clinical finding marked **B**?

Explanation

## Why option 1 is correct Prognathism (mandibular protrusion) in acromegaly results from chronic excess growth hormone stimulation of cartilage and bone growth in the mandible. Unlike gigantism (which occurs in childhood before epiphyseal plate closure and causes linear skeletal overgrowth), acromegaly develops in adults after plate closure, leading to acral and facial skeletal changes including mandibular enlargement, dental malocclusion, and increased interdental spacing. This is a hallmark feature of acromegaly and directly reflects the pathophysiology of GH excess in the post-epiphyseal closure period (Harrison 21e Ch 380; Williams Textbook of Endocrinology 14e). ## Why each distractor is wrong - **Option 2**: While prolactin co-secretion occurs in ~40% of GH-secreting adenomas (mammosomatotroph cells), prolactin does not directly stimulate mandibular bone growth. Prolactin's effects are primarily on breast tissue and reproductive function, not skeletal remodeling. - **Option 3**: IGF-1 is elevated in acromegaly, not deficient. IGF-1 is the mediator of many GH effects on bone and cartilage growth. Deficiency of IGF-1 would cause growth restriction, not mandibular protrusion. - **Option 4**: TSH-secreting pituitary adenomas are extremely rare and cause thyroid hormone excess, not acromegaly. Thyroid hormone affects bone turnover but does not cause the characteristic acral and facial changes of acromegaly. **High-Yield:** Prognathism with dental malocclusion and increased interdental spacing is a pathognomonic feature of acromegaly caused by chronic GH excess acting on mandibular cartilage and bone after epiphyseal plate closure; compare old photographs to detect the insidious onset. [cite: Harrison 21e Ch 380; Williams Textbook of Endocrinology 14e]