A 47-year-old man presents with a 6-year history of progressive coarsening of facial features, increasing ring and shoe sizes, and a doughy handshake. Examination reveals the structure marked **A** — broad, fleshy hands with soft tissue thickening, sausage-shaped digits, deep palmar furrows, and prominent enlarged knuckles. His wife reports he has developed loud snoring with witnessed apneic episodes (AHI 38). Biochemistry shows random GH 28 ng/mL with paradoxical rise to 32 ng/mL after oral glucose tolerance test, and IGF-1 880 ng/mL. MRI shows a 1.8 cm pituitary macroadenoma with suprasellar extension. Which of the following best explains the characteristic appearance of the structure marked **A** in this patient?

Question

Accepted Answer

B. Soft tissue hypertrophy and acral bone enlargement driven by sustained elevation of insulin-like growth factor-1 (IGF-1) secreted in response to excessive growth hormone from the pituitary adenoma. ## Why option 1 is right

The spade-shaped hands marked **A** with soft tissue thickening, sausage-shaped digits, and prominent knuckles are the pathognomonic acral manifestation of acromegaly. This appearance results from sustained elevation of insulin-like growth factor-1 (IGF-1), which drives soft tissue hypertrophy and acral bone enlargement (metacarpals, phalanges, and carpal bones). IGF-1 is the primary mediator of growth hormone's anabolic effects and integrates 24-hour GH secretion, making it the most reliable single screening test. The Katznelson guideline emphasizes that IGF-1 elevation (880 ng/mL in this case, markedly elevated for age) is the biochemical hallmark and directly causes the characteristic "doughy" handshake and broad fleshy appearance of the hands. The failure of GH to suppress below 1 ng/mL after glucose load (paradoxical rise to 32 ng/mL) confirms the diagnosis and explains the persistent IGF-1-mediated tissue growth.

## Why each distractor is wrong

- **Option 2**: Myxedematous changes and lipid deposition are features of hypothyroidism, not acromegaly. This patient's thyroid function is normal. Hypothyroidism causes puffiness and weight gain, not the characteristic acral bone enlargement and sausage-shaped digits seen here.
- **Option 3**: Hypercortisolism causes proximal muscle weakness, central obesity, and skin atrophy with striae — not acral soft tissue hypertrophy or bone enlargement. This patient's cortisol is normal; the macroadenoma is GH-secreting, not ACTH-secreting.
- **Option 4**: Thyroid hormone and catecholamine elevation cause tremor, tachycardia, and weight loss, not the progressive soft tissue thickening and acral bone growth characteristic of acromegaly. The pathophysiology is entirely different from IGF-1-driven hypertrophy.

**High-Yield:** Spade-shaped hands in acromegaly = IGF-1–driven soft tissue hypertrophy + acral bone enlargement; IGF-1 is the most reliable single screening test and integrates 24-hour GH secretion.

[cite:Katznelson L et al. Acromegaly: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2014;99(11):3933-3951.]

Answer

A. Subcutaneous lipid deposition and myxedematous changes secondary to hypothyroidism and impaired growth hormone-binding protein synthesis

Answer

C. Vascular proliferation and fibrosis of dermal and subcutaneous layers due to prolonged elevation of thyroid hormone and catecholamine sensitivity

Answer

D. Inflammatory infiltration of subcutaneous tissues and periosteal reaction caused by chronic hypercortisolism from adrenal hyperplasia

Explanation

Why option 1 is right

Why each distractor is wrong

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