Pseudoacromegaly: A Differential Diagnostic Problem for Acromegaly With a Genetic Solution

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Acromegaly, caused by excess growth hormone (GH), presents with characteristic physical changes.
• Pseudoacromegaly describes conditions mimicking acromegaly without GH excess, posing diagnostic challenges.

Observation:

• A female patient exhibited tall stature and acromegalic features from infancy, with normal GH levels and pituitary imaging.
• Despite initial treatment to halt growth, progressive coarsening of features and enlargement of extremities led to repeated suspicion of acromegaly.
• At age 49, she presented with symptoms including weight gain, sweating, sleep apnea, headaches, and joint pain, with persistently normal GH axis function.

Findings:

• Genetic testing revealed a de novo mutation in the NSD1 gene (c.6605G>C; p.Cys2202Ser).
• This specific mutation is associated with Sotos syndrome, an overgrowth disorder.
• The patient's clinical presentation was consistent with Sotos syndrome, not acromegaly.

Implications:

• Sotos syndrome and other overgrowth syndromes can present with clinical features overlapping those of acromegaly or gigantism.
• Genetic assessment is crucial for accurate diagnosis in cases with suspected acromegaly but normal GH levels.
• Distinguishing between these conditions is vital for appropriate patient management and treatment.