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# 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.

Updated Nov 12, 2026

## Key points

- GH excess before epiphyseal closure = gigantism; after closure = acromegaly.
- GNAS activating mutation keeps Gs-alpha bound to GTP: constant cAMP and cell proliferation.
- Densely granulated tumours are eosinophilic and behave better; sparsely granulated ones are chromophobic, show keratin fibrous bodies and are more aggressive.
- Mammosomatotroph tumours make both GH and prolactin.
- Diagnosis: high IGF-1 and GH not suppressed by an oral glucose load.
- Main causes of death: cardiovascular (cardiomyopathy, hypertension) and diabetes; colon polyps and cancer risk rise.

## 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.

## Memory aid

GNAS jams the growth accelerator: the pedal is stuck, the engine (cAMP) keeps racing and the body keeps building.

## 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.

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## Elsewhere in DurgiPedia

- [The hypothalamic–pituitary system: overview](https://durgical.com/en/physiology/the-hypothalamic-pituitary-system-overview/)
- [IP₃, DAG and calcium pathway](https://durgical.com/en/biochemistry/topics/ip-dag-and-calcium-pathway/)

## Connections

## Related 4

- [Pituitary neuroendocrine tumours (PitNETs): overview](https://durgical.com/en/general-pathology/pituitary-neuroendocrine-tumours-overview/)
- [Lactotroph PitNET (prolactinoma)](https://durgical.com/en/general-pathology/lactotroph-pitnet/)
- [Hypertrophic cardiomyopathy](https://durgical.com/en/general-pathology/hypertrophic-cardiomyopathy/)
- [Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know](https://durgical.com/en/general-pathology/oncogenes-ras-myc-her2-bcr-abl-and-the-table-to-know/)

## Related conditions 5

- [Acromegaly and gigantism](https://durgical.com/en/conditions/acromegaly-and-gigantism/)
- [Pituitary adenoma](https://durgical.com/en/conditions/pituitary-adenoma/)
- [Fibrous dysplasia of bone and McCune–Albright syndrome](https://durgical.com/en/conditions/fibrous-dysplasia-of-bone-and-mccune-albright-syndrome/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Multiple endocrine neoplasia (MEN 1, 2A, 2B)](https://durgical.com/en/conditions/multiple-endocrine-neoplasia/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.ncbi.nlm.nih.gov/books/NBK554451/) (StatPearls (NCBI Bookshelf), 2025); [McCune-Albright syndrome](https://medlineplus.gov/genetics/condition/mccune-albright-syndrome/) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/somatotroph-pitnet-gigantism-and-acromegaly/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/somatotroph-pitnet-gigantism-and-acromegaly/