Gigantism

Gigantism, also referred to as giantism, is a rare condition characterised by excessive growth and height significantly above average. It results from the over-production of growth hormone (GH) during childhood, most commonly due to abnormal tumour growths on the pituitary gland. This condition should not be confused with acromegaly, which is the adult form of the disorder manifesting as somatic enlargement of the extremities and face.

Introduction

Gigantism is primarily caused by an excess of growth hormone (GH), typically due to pituitary adenomas on the anterior pituitary gland. These adenomas can also cause overproduction of GH's hypothalamic precursor, growth hormone-releasing hormone (GHRH). This hormonal imbalance leads to children achieving heights well above normal ranges, with symptoms often appearing around the age of 13.

Hormonal Mechanisms

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play significant roles in growth plate formation and bone growth. Their specific pathways remain partially understood, but both GH and IGF-I are involved in various stages of growth: embryonic, prenatal, and postnatal. GH acts as a precursor to IGF-I, with both hormones converging to influence growth.

Signs and Symptoms

The primary symptom of gigantism is abnormal growth in height or size. Additional symptoms include weakness, insomnia, excessive sweating, delayed puberty, severe or recurrent headaches, strokes, vomiting, high fevers, sleepiness, dry mouth, frequent diarrhoea, stomachaches, ear pains, memory loss, back pains, excessive muscle cramps, and chest pains.

Diagnosis

Evaluating GH hypersecretion involves more than a single GH level due to diurnal variation. However, a markedly elevated random blood GH level can confirm the diagnosis. A high-normal GH level that does not suppress with glucose administration is also indicative of GH hypersecretion. Insulin-like growth factor-1 (IGF-1) testing is particularly effective as it does not undergo diurnal variation and remains consistently elevated in cases of GH hypersecretion.

Genetics

Identifying a genetic cause for gigantism is challenging, though some common mutations have been linked to the condition. Duplications of genes on chromosome Xq26 are associated with early-onset gigantism symptoms. Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene, found in about 29% of gigantism patients, can lead to pituitary adenomas. Other genetic disorders influencing gigantism include multiple endocrine neoplasia types 1 and 4, McCune–Albright syndrome, Carney complex, familial isolated pituitary adenoma, and X-linked acrogigantism (X-LAG).

Treatment

Treatment options for gigantism include both surgical and pharmaceutical approaches, though they often receive criticism and are not universally accepted.

Pharmaceuticals

Pegvisomant, a pharmaceutical drug, has shown potential as a treatment for gigantism by reducing IGF-I levels, which in turn can decrease the high growth rates characteristic of the condition. This drug can serve as a powerful alternative to somatostatin analogues, commonly used for acromegaly, when paired with radiation therapy. Proper titration of pegvisomant is very important to ensure normal body growth is not adversely affected.

Surgical Treatment

Surgical removal of the enlarged pituitary gland is another treatment option for gigantism. This approach aims to directly address the source of excessive GH production.

In summary, gigantism is a complex condition with multiple treatment avenues. A thorough understanding of its hormonal and genetic underpinnings is essential for effective diagnosis and management.

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Self-assessment MCQs (single best answer)

What is the primary cause of gigantism?

What is the key difference between gigantism and acromegaly?

What diagnostic test is particularly effective for confirming GH hypersecretion?

Which gene mutation is found in approximately 29% of gigantism patients?

What is a common symptom of gigantism besides excessive growth in height?

Which treatment option for gigantism involves directly addressing the source of excessive GH production?

Which hormone acts as a precursor to insulin-like growth factor-I (IGF-I)?

Which genetic disorder is associated with gigantism?

What is the role of pegvisomant in the treatment of gigantism?

Which symptom is not commonly associated with gigantism?