Symptoms of Growth Hormone Tumors
Growth hormone-secreting tumors present with dramatically different symptoms depending on whether they occur before or after epiphyseal closure: children develop accelerated growth velocity and tall stature (gigantism), while adults develop acromegalic features with tissue overgrowth. 1
Primary Clinical Manifestations in Children and Adolescents
The most prominent clinical feature of GH excess in children before epiphyseal closure is increased growth velocity. 1 Serial height measurements and photographs are particularly useful for timing disease onset. 1
Growth-Related Symptoms
- Height >2 standard deviation scores (SDS) above age-adjusted and sex-adjusted normal values or 2 SDS above mid-parental target height 1
- Persistently elevated growth velocity (>2 SDS) 1
- Delayed bone age despite excessive height 1
- Pubertal delay or arrested puberty (due to gonadotrophin inhibition from prolactin co-secretion or mass effects) 1
Acromegalic Features in Children
- Acral enlargement (disproportionately enlarged hands and feet) 1
- Coarsened facial features 1
- Prognathism (jaw protrusion) 1
- Dental malocclusion and teeth separation 1
- Frontal bossing 1
Mass Effect Symptoms
- Headache 1
- Visual field defects (from optic chiasm compression) 1, 2
- Cranial nerve palsies, particularly oculomotor nerve dysfunction with large tumors 2
Metabolic and Systemic Symptoms
- Joint pain and arthritis 1, 3
- Excessive sweating (hyperhidrosis) 1, 4
- Insulin resistance and occasionally secondary diabetes mellitus 1
- Hypertension 1
- Sleep disturbance and sleep apnea 1
- Increased appetite and BMI (particularly in X-linked acrogigantism) 1
Adult Acromegalic Manifestations
Adults with GH-secreting tumors develop the classic features of acromegaly, as epiphyseal closure prevents further linear growth. 3
Characteristic Physical Changes
- Enlarged hands, feet, and facial features 3, 5
- Prognathism and dental malocclusion 3
- Coarsened facial features 3
- Soft tissue swelling 3
Common Systemic Symptoms
- Headaches 4, 5
- Arthralgias and joint pain 3, 5
- Fatigue 5
- Hyperhidrosis (excessive sweating) 4, 5
- Decreased libido (particularly with dual-staining tumors) 4
Associated Comorbidities
- Glucose intolerance and diabetes mellitus 1, 3, 5
- Hypertension 1, 3, 5
- Carpal tunnel syndrome 1
- Left ventricular hypertrophy and diastolic dysfunction 1
- Sleep apnea 1
- Kyphosis 1
Syndrome-Specific Presentations
X-Linked Acrogigantism
- Tall stature onset before age 5 years (usually before 2 years) in all patients 1
- Disproportionately enlarged hands, feet, and teeth separation 1
- Acanthosis nigricans 1
- Markedly increased BMI and appetite 1
McCune-Albright Syndrome
- Early-onset GH excess (from 3 years onwards) 1
- Café-au-lait pigmentation 1
- Fibrous dysplasia 1
- Precocious puberty or other hormone excess conditions 1
Carney Complex
Hormonal Co-Secretion Symptoms
Hyperprolactinemia occurs in 65% of pediatric acromegaly cases and 34-36% of gigantism cases, causing additional symptoms. 1
- Galactorrhea 1
- Amenorrhea in females 1
- Hypogonadism and loss of libido in males 1
- Further pubertal delay (exacerbating gigantism) 1
Rare Ectopic Presentations
When GH excess results from ectopic GHRH-secreting tumors (carcinoid, pancreatic neuroendocrine tumors), additional symptoms may include: 6
Critical Diagnostic Indicators
Testing for GH excess should be offered to children and young people with excess height (>2 SDS) or consistently elevated height velocity and acromegalic features, with or without delayed/arrested puberty or family history of pituitary adenoma. 1
The diagnosis is supported by elevated serum IGF-1 levels (age-adjusted, sex-adjusted, and Tanner stage-matched) and failure of GH suppression below 1 μg/L after oral glucose load. 1
Almost 50% of pediatric gigantism cases have an identifiable genetic basis, making genetic assessment particularly important. 1 Evaluation for syndromic causes (MEN1, Carney complex, McCune-Albright syndrome) should be performed in all children with GH excess. 1