Acromegaly Treatment

Treatment

Pharmacotherapy

Recommended for patients where surgery is not suitable or in patients with persistent disease after surgical resection of adenoma

Somatostatin Analogs (SSA) or Somatostatin Receptor Ligands (SRL)

First generation: Lanreotide, Octreotide; Second generation: Pasireotide
Analogs of naturally occurring somatostatin with similar pharmacological actions but with prolonged duration of action
Bind to somatostatin receptor subtypes 2 and 5 on growth hormone-secreting adenomas to suppress growth hormone secretion
First-generation SRLs are 1st-line pharmacotherapy agents
May be used after surgery has failed to achieve biochemical control
May provide full or partial disease control, in the time between administration of radiation therapy and the onset of maximum benefit attained from radiation therapy
Available in long-acting release (LAR) depot, short-acting SC, and oral preparations
Pasireotide LAR, may be used in patients with clinically relevant residual tumor not suitable for resection and inadequately controlled by first-generation SRL
May be combined with dopamine agonists to improve therapeutic efficacy
Somatostatin analogs are effective in normalizing growth hormone and insulin-like growth factor-1 levels
Advantages include rapid onset, continued efficacy, with proven safety record
Common side effects include cramping and abdominal bloating, with a reduction over the first few months of treatment
To properly assess adequacy of treatment and the need for dose titration, it is recommended to have patients remain on the same dose for 3 months (if tolerated by patient)

Dopamine Agonists

Eg Bromocriptine, Cabergoline, Quinagolide
May be considered particularly in patients with mild biochemical activity (eg modestly elevated serum insulin-like growth factor-1 in the absence or concomitant presence of somatostatin analogs therapy)
Bind to D2 dopamine receptors expressed on growth hormone-secreting adenoma and reduce growth hormone production
Advantages include their low cost and that they are the only orally administered medications available for acromegaly
May very occasionally be a first-line therapy post-surgery in selected patients (eg those with markedly elevated prolactin levels and/or modestly elevated growth hormone and insulin-like growth factor-1 levels)
- Cabergoline may be considered in patients with persistent disease after surgery or added to SRL if insulin-like growth factor-1 levels <2.5 times the upper limit of normal
An additive therapy to somatostatin analogs in patients partially responsive to a maximum somatostatin analogs dose
- With combination therapy, approximately 50% of such patients may achieve control of insulin-like growth factor-1 and growth hormone levels
Bromocriptine was shown to provide benefit in a minority of patients with acromegaly in earlier studies but Cabergoline, a more selective dopamine-2 receptor agonist, may be effective in a larger percentage of patients
Repeated prolactin, growth hormone and insulin-like growth factor-1 levels should be determined 4-6 weeks after each dosage change of dopamine agonist
Potential side effects include gastrointestinal upset, orthostatic hypotension, headache and nasal congestion

Growth Hormone Receptor Antagonist (GHRA)

Pegvisomant

A GHRA that competes with endogenous growth hormone for its receptor and prevents functional dimerization and signal transduction by the growth hormone receptor
Indicated in patients with persistently elevated insulin-like growth factor-1 levels despite maximal therapy with other treatment modalities
- Effective in normalizing insulin-like growth factor-1 levels in >90% of patients, including those who are partially or completely resistant to other medical therapies
Often used as medical therapy in patients with inadequate response to or partial tolerability to somatostatin analogs
Potential side effects include flu-like illness, allergic reactions and elevated liver enzymes
- Serial liver function test monitoring is recommended: Monthly for the 1st 6 months; quarterly for the next 6 months; then biannually
- Patients with elevated baseline liver function tests require more frequent monitoring
Serum growth hormone levels are not specific and should not be monitored in patients receiving Pegvisomant
- Endogenous growth hormone levels increase with Pegvisomant administration and Pegvisomant may be cross-measured in growth hormone assays

Combination Therapy

In patients with partial or inadequate response to somatostatin analogs therapy, Cabergoline may be useful for further lowering of insulin-like growth factor-1 or growth hormone levels
In patients with a partial response to somatostatin analogs therapy, addition of daily, weekly or twice weekly Pegvisomant may be beneficial

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