Pathophysiology and Causes
The etiology of gigantism may include infectious processes in the pituitary region or a pituitary adenoma with hyperplasia of eosinophilic cells.
The mechanism of development is associated with an excess of growth hormone (GH), which is an anabolic hormone. It stimulates the growth of all tissues by increasing the cellular uptake of amino acids and enhancing protein synthesis.
- Insulin-like growth factor I (IGF-I, somatomedin) — produced in the liver under the influence of GH. The combination of GH and IGF-I stimulates bone tissue growth during adolescence.
Gigantism is also a feature of Beckwith–Wiedemann syndrome, which is characterized by macroglossia, gigantism, microcephaly, and visceromegaly, involving chromosomal region 11p15.
Effects of Growth Hormone on Metabolism
The effect of GH on carbohydrate and lipid metabolism is biphasic:
- Initial phase — insulin-like effect. The hormone increases glucose uptake by muscle and adipose tissue and inhibits lipolysis.
- Second phase — anti-insulin effects. GH inhibits glucose uptake and utilization, enhances lipolysis, increases glucagon production, and activates hepatic insulinase. Ultimately, GH exerts a hyperglycemic effect.
Clinical Presentation and Complications
Accelerated growth persists for several years. Over time, patients develop acromegaloid coarsening of facial features. In addition to tall stature, systemic complications develop:
- Hypogonadism — underdevelopment of internal and external genitalia due to decreased gonadotropic function of the pituitary gland. Primary amenorrhea or early cessation of menstruation is noted from the onset of the disease.
- Carbohydrate metabolism disorders — hyperglycemia, which frequently leads to diabetes mellitus.
- Psychiatric disorders — emotional instability, irritability, sleep disturbances, asthenia, and reduced cognitive performance. This is associated with impaired neuronal function in the cortex and subcortical centers, stress responses to the illness, or concomitant hyperthyroidism.
- Somatic manifestations — muscle weakness, hypotonia, and muscle wasting.
Diagnosis and Management
Diagnosis involves measuring height and comparing it to standard growth curves. The median ("0" line) reflects the standard average height for a specific age and sex. A value above +2 and +3 standard deviations indicates tall stature or gigantism and serves as an indication for a comprehensive workup.
Conservative treatment involves synthetic analogs of hypothalamic hormones. The key pharmacological agent is octreotide (a somatostatin analog), which suppresses growth hormone secretion.
Distinction: Organ Gigantism
In clinical terminology, the root mega- or megalo- is used to denote the excessive enlargement of individual organs. For example, megacolon (megacolon) refers to gigantism of the large intestine, and megaduodenum refers to enlargement of the duodenum.