Questions & Answers

June 27, 2022


A 41-year-old woman presents with acromegaly. She previously underwent transsphenoidal surgery for a macroadenoma, and she has residual disease in the left cavernous sinus. Her postoperative IGF-1 concentration was 932 ng/mL (98-261 ng/mL) (SI: 122.1 nmol/L [12.8-34.2 nmol/L]). Octreotide long-acting release, 20 mg monthly, was initiated, which lowered her IGF-1 concentration to 850 ng/mL (111.4 nmol/L). The octreotide dosage was increased to 30 mg monthly, but her IGF-1 concentration remains unchanged and the tumor is slightly larger on MRI. 

Which of the following interventions would best reduce this patient’s tumor size and IGF-1 levels in the next 6 months?

A. Add cabergoline 
B. Add pegvisomant
C. Perform stereotactic radiotherapy
D. Switch to pasireotide
E. Switch to the oral octreotide capsule

Answer: D) Switch to pasireotide

This patient has a growing tumor and persistently elevated IGF-1 levels despite octreotide long-acting release at the highest dosage approved by the US FDA. The option with the most rapid response regarding tumor shrinkage and biochemical control is pasireotide (Answer D), the somatostatin receptor ligand. Pasireotide effectively normalizes IGF-1 in approximately 40% to 45% of patients and may result in tumor shrinkage. A common adverse event is hyperglycemia, which affects up to two-thirds of patients. 

The oral octreotide capsule (Answer E) is indicated in patients with acromegaly who previously responded to and tolerated treatment with octreotide or lanreotide. However, this patient is not responding well to parenteral octreotide, so the oral octreotide capsule is not indicated, as it will not likely be effective. 

Adding cabergoline (Answer A) is unlikely to improve biochemical control in a patient with significant biochemical activity and tumor growth. 

Adding pegvisomant (Answer B) may result in biochemical control, but given that it is a GH receptor antagonist, it is unlikely to further control tumor growth.

Stereotactic radiotherapy (Answer C) may control both tumor growth and GH hypersecretion, but it could take years to be effective and is unlikely to be effective within the next 6 months.  

Educational Objective

Recommend the best management of persistent acromegaly.


  • Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021;24(1):1-13. PMID: 33079318
  • Coopmans EC, van Meyel SWF, van der Lely AJ, Neggers SJCMM. The position of combined medical treatment in acromegaly. Arch Endocrinol Metab. 2019;63(6):646-652. PMID: 31939490 
  • Coopmans EC, Muhammad A, van der Lely AJ, Janssen JAMJL, Neggers SJCMM. How to position pasireotide LAR treatment in acromegaly. J Clin Endocrinol Metab. 2019;104(6):1978-1988. PMID: 30608534 

Male Reproduction

A 73-year-old man wishes to discuss treatment options for newly diagnosed hypogonadism. He is not keen on the idea of having to apply a testosterone gel or patch daily and expresses a preference for injections. He has a history of depression and hypertension, which are both well-controlled on citalopram and lisinopril. He has no history of cardiovascular disease. He has read about the long-acting depot formulation of testosterone undecanoate. He likes the fact that the injection must only be administered every 10 weeks and asks for additional information about its safety profile. 

Which of the following is a potential adverse effect that this patient might experience as a result of this regimen?

A. Cough and shortness of breath following the injection 
B. Flu-like illness 
C. Jaundice
D. Significant fluctuations in energy levels and mood
E. Significant increase in blood pressure

Answer: A) Cough and shortness of breath following the injection

A long-acting intramuscular formulation comprising testosterone undecanoate was approved for the treatment of male hypogonadism in the United States in 2014. This preparation has the advantage of having a superior pharmacokinetic profile compared with other injectable formulations such as enanthate and cypionate, and it has the ability to maintain testosterone levels more consistently in the normal range over a 10-week period. The absence of marked swings in serum testosterone levels means that fluctuations in mood and energy (Answer D) are not typical adverse effects.

The US FDA has stipulated that all injections of testosterone undecanoate must be administered in an office or hospital setting by a trained health care provider and that the patient be monitored for adverse effects for 30 minutes after the injection. The restrictions associated with use of this drug result from reported cases of pulmonary oil microembolism (1.5 cases/10,000 injections) and anaphylaxis (0.4 cases/10,000 injections). Symptoms of pulmonary oil microembolism include the urge to cough, dyspnea (Answer A), throat tightening, chest pain, dizziness, and syncope. These symptoms have been reported with all testosterone injections but are more common with testosterone undecanoate because of the larger injection volume (3 mL compared with 1 mL or less for the shorter-acting formulations). 

Flu-like symptoms (Answer B) have not been reported with testosterone undecanoate injections.

Increased blood pressure (Answer E) has been observed with a newly approved daily oral form of testosterone undecanoate but is not reported with long-acting intramuscular formulation.

When ingested orally, methyltestosterone (an older formulation of oral testosterone) is broken down by the liver and has the potential to cause liver damage, including cholestatic jaundice, peliosis hepatis, and hepatomas. However, testosterone formulations administered intramuscularly are not hepatotoxic, so jaundice (Answer C) is incorrect.

Educational Objective

Counsel patients about potential adverse effects of the long-acting intramuscular formulation of testosterone undecanoate.


  • Wang C, Harnett M, Dobs AS, Swerdloff RS. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial. J Androl. 2010;31(5):457-465. PMID: 20133964
  • Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. PMID: 29562364
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