Somatotroph PitNET: gigantism and acromegaly
- Lesion
A tumour that makes too much growth hormone makes children grow very tall and makes adults' hands, feet and face slowly enlarge.
What it is
Somatotroph tumours secrete growth hormone, which drives the liver to make IGF-1. Before the growth plates close the result is gigantism; after closure, acromegaly, a slow overgrowth of bone, soft tissue and organs. About two in five tumours carry activating GNAS mutations that lock the stimulatory G protein on, the same mutation that, in mosaic form, causes McCune-Albright syndrome.
Structure
- Usually a macroadenoma at diagnosis because acromegaly develops slowly.
- Densely granulated: acidophilic cells, diffuse strong GH staining, low keratin.
- Sparsely granulated: chromophobic cells with juxtanuclear keratin aggregates (fibrous bodies) on CAM5.2 staining.
- Both express PIT1.
Step by step
- An activating GNAS mutation (or another driver) arises in a somatotroph.
- Gs-alpha stays active, cAMP stays high and the cell divides and secretes GH without GHRH.
- GH stimulates IGF-1 production in the liver and tissues.
- IGF-1 drives growth of bone, cartilage and soft tissue; GH itself opposes insulin.
- Result: tall stature in children, coarse features, organomegaly and glucose intolerance in adults.
Clinical notes
- Acromegaly: enlarged hands and feet (rings and shoes no longer fit), prognathism, frontal bossing, spaced teeth, thick skin, sweating.
- Systemic: arthropathy, carpal tunnel syndrome, sleep apnoea, hypertension, cardiomyopathy, diabetes.
- GH excess also appears in MEN1 and in McCune-Albright syndrome.
Test yourself
Think of the answer, then tap the question to see it.
Why does growth hormone excess cause gigantism in children but acromegaly in adults?
Before the epiphyseal plates fuse, long bones can lengthen; after fusion, GH and IGF-1 can only thicken bone and enlarge soft tissue.
What does an activating GNAS mutation do in a somatotroph?
It blocks GTP hydrolysis by Gs-alpha, so adenylyl cyclase and cAMP stay on, driving proliferation and GH release.
Which test confirms growth hormone excess?
A raised IGF-1 with failure of GH to suppress after an oral glucose load.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Pituitary Adenoma (StatPearls (NCBI Bookshelf), 2025); McCune-Albright syndrome (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.