A 48-year-old man presents to the endocrinology clinic with progressive facial changes over the past 8 years. On examination, he has frontal bossing, enlarged nose and lips, and the feature marked **C** in the diagram (mandibular prognathism) with malocclusion and dental spacing. His serum IGF-1 is markedly elevated at 680 ng/mL (normal: 90–235 ng/mL for his age). An oral glucose tolerance test shows GH remains at 2.8 ng/mL after 2 hours of 75 g glucose load. Pituitary MRI reveals a 1.8 cm sellar mass with suprasellar extension. Which of the following best explains the pathophysiology underlying the mandibular changes marked **C**?
A. Cortisol deficiency from ACTH suppression results in loss of bone density and mandibular resorption
B. Excess growth hormone stimulates hepatic IGF-1 production, which mediates bone and soft tissue overgrowth of the mandible
C. Thyroid hormone excess from TSH-secreting adenoma drives accelerated bone remodeling
D. Chronic elevation of prolactin from the pituitary adenoma causes direct stimulation of osteoblasts
Explanation
Why option 1 is right
Mandibular prognathism (marked C) in acromegaly results directly from excess GH secretion, which stimulates hepatic IGF-1 production. IGF-1 is the primary mediator of GH's systemic effects, including progressive bone and soft tissue overgrowth of the mandible, leading to the characteristic prognathism, malocclusion, and dental spacing seen in this patient. This is the hallmark pathophysiologic mechanism described in Harrison's 21e Ch 380 and the Endocrine Society Acromegaly Guidelines 2014.
Why each distractor is wrong
Option 2: While prolactin may be co-secreted in some GH-secreting adenomas, prolactin itself does not cause mandibular prognathism. Prolactin excess causes hypogonadism and galactorrhea, not skeletal overgrowth. The mandibular changes are driven by GH and IGF-1, not prolactin.
Option 3: TSH-secreting adenomas are extremely rare and would cause hyperthyroidism, not acromegaly. Thyroid hormone excess accelerates metabolism but does not produce the characteristic mandibular prognathism of acromegaly. The clinical and biochemical picture (elevated IGF-1, failure of GH suppression on OGTT) is diagnostic of GH excess, not thyroid disease.
Option 4: Cortisol deficiency would result in bone loss and osteoporosis, potentially causing mandibular resorption or recession—the opposite of the progressive mandibular overgrowth and prognathism seen here. Acromegaly typically causes osteoarthritis and soft tissue overgrowth, not bone loss.
High-YieldNEET PG
Mandibular prognathism in acromegaly is mediated by IGF-1, not GH directly—IGF-1 is the systemic effector of GH's skeletal and soft tissue effects.
Harrison's 21e Ch 380; Endocrine Society Acromegaly Guidelines 2014
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