Acromegaly and Gigantism

Classification of hyperpituitarism and pathogenesis mechanisms

Globally, hyperpituitarism is divided into partial and total. The total form is extremely rare, and its existence is questionable. Partial forms of hyperpituitarism encompass a spectrum of endocrine disorders:

1. Pituitary gigantism.
2. Acromegaly.
3. Hyperprolactinemia.
4. Hypermelanotropinemia.
5. Pituitary (true) precocious puberty syndrome.
6. Pituitary hyperthyroidism.
7. Pituitary hypercorticism (Cushing's disease).

The development of gigantism and acromegaly is associated with disturbances at various levels of regulation. Three key forms of pathogenesis (initial links) are distinguished:

• Centrogenic mechanism. Occurs as a result of damage to neurons in the cerebral cortex and/or hypothalamus. This leads to massive hyperproduction of growth hormone-releasing hormone (somatoliberin) and growth hormone (GH) itself. In some cases, the triggering factor is a decrease in the normal production of somatostatin, which normally inhibits GH secretion.
• Primary glandular (pituitary) mechanism. Is a direct consequence of increased GH synthesis directly by acidophilic cells of the adenohypophysis.
• Post-glandular (receptor) mechanism. In this case, hormone levels may not be critically high, but there is increased hyperaffinity (pathological affinity) of receptors in target tissues and organs for GH molecules.

Clinical manifestations of gigantism

Gigantism is characterized by large-scale systemic alterations affecting not only appearance but also internal systems.

Skeletal and organ changes The leading symptom is height growth exceeding the physiological norm (over 200 cm in young men and 190 cm in young women). The underlying mechanism is accelerated epiphyseal and periosteal growth of tubular bones. There is often a mismatch between internal organ sizes and body parameters. As a rule, splanchnomegaly (organ enlargement) develops, but in rare cases, internal organs may relatively lag in growth. In both scenarios, this leads to functional insufficiency of, for example, the heart or liver, as their capacities cannot keep pace with the increased load of a massive body.

Muscular and reproductive systems Muscle development is disproportionate. At the onset of the disease, muscle mass still corresponds to overall body dimensions. However, as it progresses, muscle growth critically lags behind. Degenerative changes begin in the myofibrils, and muscle tissue is replaced by connective tissue, which clinically manifests as hypotonia, hypotrophy, and marked muscle weakness. Concurrently, hypogenitalism (underdevelopment of internal and external genitalia) develops, driven by insufficient synthesis or effects of gonadotropins.

Metabolism and psyche Since GH is a potent counter-regulatory hormone, patients predictably experience impaired carbohydrate metabolism: hyperglycemia is recorded, and diabetes mellitus frequently manifests. The psychiatric status of patients is characterized by emotional instability, irritability, sleep disturbances, asthenia, and reduced mental performance. This is associated with impaired functions of cortical and subcortical neurons, a stress response to severe illness, and concomitant hyperthyroidism.

Specifics of the clinical picture of acromegaly

While gigantism occurs during active ontogenesis, acromegaly has its own characteristic course associated with the effects of excess GH on an already formed organism.

Musculoskeletal system and soft tissues Characterized by enlargement of the hands and feet due to somatotropin-stimulated periosteal bone growth. Soft tissues become denser, the skin thickens, and facial features become coarse. Macroglossia (enlarged tongue) and splanchnomegaly are observed. These changes are the result of excessive proliferation of connective tissue and parenchymal elements directly under the influence of GH.

Neurological and psychiatric symptoms Due to bone thickening and soft tissue hypertrophy, bone canals and depressions narrow. This leads to compression of passing nerve trunks. Clinically, this is expressed as paresthesias, especially acroparesthesias (marked discomfort, numbness, and tingling in the hands and feet). Various psychiatric disorders are also recorded.

Metabolism and reproductive function

• Carbohydrate metabolism: persistent hyperglycemia is noted (in more than 50% of patients), and every tenth patient develops full-blown diabetes mellitus.
• Lipid metabolism: blood concentrations of cholesterol, lecithin, free fatty acids (FFAs), ketone bodies (KBs), and lipoproteins (LPs) are elevated.
• Reproductive sphere: excessive GH effects provoke decreased libido, impotence, and in women—dysmenorrhea and galactorrhea.

Class and exam questions

What else to study on this topic

• Mechanisms of development of pituitary hypercorticism (Cushing's disease)
• Pathogenesis and clinical picture of pituitary hyperthyroidism
• Pituitary precocious puberty syndrome: differential diagnosis
• Detailed alterations in the lipid profile during hyperpituitarism
• Interaction of GH and gonadotropins in the development of hypogenitalism

Other topics in "Chapter 27. Typical Forms of Endocrine System Pathology"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.