Growth Hormone (GH) Agonists & Antagonists

Growth Hormone Agonists

Growth hormone (Somatropin)

Recombinant growth hormone (somatropin), is primarily used to treat growth hormone deficiencies, but is also used in HIV-related wasting, and short bowel syndrome, as well as to enhance growth in children with non-GH related short stature, and other conditions.
As mentioned, it both acts on growth hormone receptors on a variety of target organs and also increases IGF-1 production.

Mecasermin

The IGF-1 agonist mecasermin is used to treat patients with growth hormone resistance and direct IGF1-deficiencies.
This drug acts directly on the IGF-1 receptors to enhance growth and metabolic effects.

Side Effects

Blood Glucose

There are numerous potential side effects to these medications, first we address effects on blood glucose.
GH stimulates synthesization and production of IGF-1.
IGF-1 can produce hypoglycemia – it’s insulin-like, thus it can drive glucose into the cells. For this reason, patients are encouraged to eat a snack before taking Mecasermin.
GH, itself, also has direct, anti-insulin like effects that reduce glucose uptake and produce hyperglycemia.

Additional Side Effects

In children they include slipped capital femoral epiphysis, hyperglycemia (remember GH induces an increase in blood glucose), pseudotumor cerebri, and peripheral edema. The role of growth-hormone replacement therapy in the exacerbation of scoliosis is debated.
In adults, the most common side effects are peripheral edema, myalgia, and arthralgia (all due to water retention in the tissues), and insulin resistance.
In obese adults and children with Prader-Willi syndrome, we should pay attention for inducing airway obstruction or sleep apnea.

Growth Hormone Antagonists

For reference, occurs from GH excess post-puberty, after the long bone epiphyses close (it’s more common); whereas gigantism refers to GH excess pre-puberty, before the long bone epiphyses close (it’s less common).
Note that growth hormone excess is typically due to pituitary adenoma, which is most often treated via surgical removal: endoscopic transsphenoidal resection. GH antagonists are used in non-surgical cases or as adjuvant therapy.

Somatostatin analogs: octreotide, lanreotide

They mimic the hormone somatostatin (aka growth hormone-inhibiting hormone), which blocks the production of growth hormone.
In addition to treating acromegaly and gigantism, they are also used to treat a variety of other illnesses, including non-GH secreting tumors and bleeding esophageal varices, as well as obesity, cancer, and hyper-insulinemic hypoglycemia.

Side Effects

The somatostatin analogs can reduce the production of cholecystokinin (CCK), a small intestinal hormone that stimulates post-prandial (after a meal) gallbladder contraction. And, thus, they can induce biliary sludge and, ultimately, gallstone formation.
Note that the somatostatin analogs also lower other GI hormones such as glucagon, insulin, and gastrin and can cause nausea, vomiting, abdominal cramping, diarrhea and flatulence – as a consequence, indicate that they can produce B12 deficiency.
Somatostatin reduces thyrotropin stimulating hormone (TSH) and thus can cause hypothyroidism, manifesting with bradycardia and hair loss amongst other symptoms.

Pegvisomant

The growth hormone receptor antagonist Pegvisomant, blocks growth hormone receptors, and suppresses excess growth hormone activity.
Key side effects include injection site reactions and elevated liver enzymes (transaminitis).