Growth Hormone Deficiency & Excess for the ABIM

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Growth Hormone Deficiency & Excess for the American Board of Internal Medicine Exam

Growth Hormone Deficiency (GHD)

Congenital: Genetic mutations (e.g., GH1 gene mutations) or developmental abnormalities in the hypothalamus or pituitary gland.
Acquired:
Pituitary Tumors: Compression or destruction of somatotroph cells can lead to decreased GH production.
Trauma or Surgery: Injury to the hypothalamic-pituitary axis.
Radiation Therapy: Especially for head or neck cancers, can damage the pituitary gland.
Inflammatory and Infiltrative Diseases: Sarcoidosis, tuberculosis, and Langerhans cell histiocytosis can affect GH production.
Idiopathic: No identifiable cause in some patients.

Decreased Muscle Mass and Strength: Lack of GH leads to reduced protein synthesis, contributing to muscle wasting.
Increased Fat Mass: GH deficiency promotes fat deposition, especially visceral fat, leading to central obesity.
Impaired Cardiovascular Health: Increased risk of atherosclerosis, dyslipidemia, and decreased cardiac output.
Reduced Bone Density: GH deficiency can result in osteoporosis, increasing the risk of fractures.
Impaired Quality of Life: Symptoms include fatigue, depression, social isolation, and decreased physical performance.

Growth Failure: Slowed growth velocity, delayed skeletal maturation, and short stature.
Delayed Puberty: GH deficiency can delay the onset of puberty and sexual maturation.
Infantile Facial Features: Children may have a higher-pitched voice and a rounded face.

Insulin Tolerance Test (ITT): A gold standard test that assesses GH response to hypoglycemia. GH levels should rise in response to insulin-induced hypoglycemia.
Arginine Stimulation Test: Measures GH response after administering arginine.
IGF-1 Levels: Low IGF-1 levels, a marker of GH activity, support the diagnosis of GHD.
MRI of the Pituitary Gland: Imaging to evaluate structural abnormalities, such as tumors or congenital defects.

GH Replacement Therapy: Recombinant human growth hormone (rhGH) is used for both children and adults.
In Children: Helps normalize growth velocity and reach target height.
In Adults: Improves body composition, bone density, and quality of life.
Monitoring: Regular follow-up is required to adjust dosing and monitor for side effects (e.g., joint pain, insulin resistance).

Growth Hormone Excess (Acromegaly and Gigantism)

Pituitary Adenoma: A somatotroph adenoma is the most common cause of growth hormone (GH) excess. It leads to autonomous GH secretion, causing elevated levels of insulin-like growth factor-1 (IGF-1).
Ectopic GHRH Production: In rare cases, GH excess can occur due to ectopic GHRH secretion from tumors such as carcinoid or small-cell lung carcinoma.

GH stimulates the liver to produce IGF-1, which mediates many of the systemic effects of GH excess.
Chronic GH and IGF-1 elevation lead to excessive growth of bones and soft tissues, cardiovascular complications, and metabolic disturbances.

Skeletal Overgrowth: Enlarged hands and feet, jaw (mandibular prognathism), and frontal bossing (prominent forehead). Coarse facial features are common.
Arthropathy: Joint pain and arthritis due to bone overgrowth.
Cardiovascular Disease: Hypertension, left ventricular hypertrophy, and heart failure are common.
Metabolic Effects: Insulin resistance and hyperglycemia; some patients develop diabetes mellitus.
Skin Changes: Thickened skin, hyperhidrosis (excessive sweating), and acanthosis nigricans.
Sleep Apnea: Due to enlarged soft tissues of the airway.
Organomegaly: Enlargement of the liver, spleen, and kidneys.

Excessive Linear Growth: Before epiphyseal (growth plate) closure, children with GH excess experience rapid height increase.
Delayed Puberty: Puberty may be delayed or incomplete due to excess GH effects.

IGF-1 Levels: Elevated IGF-1 levels are a hallmark of GH excess and reflect chronic GH activity.
Oral Glucose Tolerance Test (OGTT): Normally, GH levels suppress after a glucose load, but in acromegaly, GH remains elevated.
MRI of the Pituitary Gland: Used to visualize pituitary adenomas or other structural abnormalities.
Additional Tests: In cases of ectopic GHRH production, chest or abdominal imaging may be needed to locate the source of the ectopic hormone.

Surgical Resection: Transsphenoidal surgery is the first-line treatment for pituitary adenomas. It can effectively reduce tumor size and GH levels.
Medications:
Somatostatin Analogs: Octreotide and lanreotide inhibit GH release and reduce IGF-1 levels.
GH Receptor Antagonists: Pegvisomant blocks GH receptors, reducing IGF-1 levels.
Dopamine Agonists: Cabergoline and bromocriptine can suppress GH secretion in some patients.
Radiation Therapy: Used as adjuvant therapy when surgery and medications fail to control GH levels.
Monitoring: Regular follow-up to monitor IGF-1 levels, MRI to check for tumor recurrence, and assessments for cardiovascular and metabolic complications.

Cardiovascular: Hypertension, heart failure, and increased risk of cardiovascular mortality.
Respiratory: Obstructive sleep apnea due to enlarged soft tissues of the upper airway.
Metabolic: Diabetes mellitus due to insulin resistance.
Neoplasms: Increased risk of colonic polyps and colorectal cancer.

Key Points

Congenital or acquired causes, with pituitary tumors being the most common.
Adults present with muscle wasting, central obesity, and cardiovascular risk; children present with growth failure.
Diagnosis includes low IGF-1 and stimulation tests (ITT, arginine).
GH replacement improves outcomes in both children and adults.

Pituitary adenoma is the primary cause, leading to acromegaly in adults and gigantism in children.
Clinical features include skeletal overgrowth, cardiovascular disease, and metabolic disturbances.
Diagnosis includes elevated IGF-1 and failed suppression of GH in an OGTT.
Treatment includes surgical resection, medications (somatostatin analogs, GH receptor antagonists), and radiation.