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Questions and Answers on GHD
Questions and Answers From the ENDO 2023 Symposium: Addressing Treatment Challenges in Growth Hormone Deficiency With Novel Long-Acting Therapies

Released: July 11, 2023

Expiration: July 11, 2024

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Key Takeaways
  • In adults, duration of GH replacement therapy depends on the goal of treatment; evidence of clinical benefit or improvement in quality of life should determine whether treatment is continued.
  • Patients receiving GH replacement therapy should be monitored for adrenal insufficiency and hypothyroidism, which can be done by counseling and patient reporting of signs and symptoms. 
  • Contraindications to GH replacement therapy include active or recent malignancy other than nonmelanoma skin cancer, history of childhood cancer, and uncontrolled diabetes mellitus and hypertension.  

In this commentary, Laurence Katznelson, MD, answers questions about growth hormone (GH) replacement therapy for patients with GH deficiency (GHD) based on the program, “Addressing Treatment Challenges in Growth Hormone Deficiency With Novel Long-Acting Therapies” presented at ENDO 2023.

How can insulin-like growth factor 1 (IGF-1) level be used in the diagnosis of GHD? 
Because GH is secreted in a pulsatile fashion, such that the GH level in healthy individuals during the day is low to undetectable at its interpulse trough, random assessment of GH levels is not useful for accurately determining GH reserve. Assessing an IGF-1 level is more useful as this is an integrated marker of GH. Although IGF-1 levels are usually low in adult patients with GHD, this level may be normal in up to 20% of cases. Thus, a normal IGF-1 level does not rule out the presence of GHD, and a low IGF-1 value is not sufficient for a diagnosis of GHD. In patients with possible GHD, GH stimulation testing is necessary to confirm the diagnosis. However, in a patient with hypopituitarism, the more endocrine axes that are deficient, the higher the chance of the patient having prevalent GHD. If a patient has at least 3 deficient axes, then further GH stimulation is not necessary.  

In which patients should testing for GHD be avoided?
GHD is the most common pituitary axis deficiency in patients with pituitary disorders, in those who experience a brain injury, or in those who have received radiation therapy to the base of the skull. In adults, GH therapy may be considered in any patient with GHD, barring any clear contraindications including the presence of active or recent malignancy other than nonmelanoma skin cancer. In such patients, testing for GHD is unnecessary as GH therapy would not be provided. In adults with a history of childhood cancer, there may be risk of secondary cancers, particularly if the patient received radiation therapy for central nervous system malignancies. In these patients, the decision to test for GHD and initiate GH therapy should be made on a case-by-case basis, depending on the severity of the potential GHD signs and symptoms. Another potential contraindication to GH therapy is the presence of either diabetes mellitus or hypertension, as both may be exaggerated by treatment, and these comorbidities should be controlled before considering GH therapy.

In a patient receiving GH replacement therapy, how are glucocorticoids dosed and thyroid hormone replacement typically managed? 
GH therapy may result in catabolism of both cortisol and thyroxine (T4). Therefore, patients receiving GH therapy may require an increase in the glucocorticoid dose and T4 replacement. All patients starting GH therapy should be counseled on the signs and symptoms of adrenal insufficiency and hypothyroidism so they can self-monitor for these conditions. Healthcare professionals can also screen for such conditions during follow-up appointments. Free thyroxine (FT4) should be measured at follow-up visits, and if there is a decline in FT4 level, initiation of levothyroxine or an increase in levothyroxine dose should be considered. Similarly, in patients with hypopituitarism receiving glucocorticoid therapy, the glucocorticoid dose does not need to be automatically increased at initiation of GH therapy unless there is concern for adrenal insufficiency. Patients who stop GH therapy should have their glucocorticoid dose reduced and FT4 level monitored and T4 replacement dose reduced if this level rises.

What is the typical duration of GH replacement therapy?
In children, GH therapy is usually continued until their predicted/peak height is achieved, usually in the later teens, at which time GH dosing is usually stopped. If patients are at continued risk for GHD into adulthood, such as those with pituitary disorders, then either continuation of GH therapy or repeat testing for GHD should be considered. In adults, there is no end date for GH therapy. However, there are different practice approaches to determine response to GH therapy in adults. If the clinical endpoint is well-being, then patients often describe beneficial effects of therapy within 6 months. In my practice, if the endpoint is well-being, I ask patients if they have experienced an improvement in their quality of life at 6 months and continue the GH therapy if they report an improvement. In addition, the use of GHD-specific questionnaires, such as the Assessment of Growth Hormone Deficiency in Adults questionnaire, can be useful to assess patient-reported improvement. If the goal of GH replacement is to improve bone mineral density, then repeat bone density testing should be performed at 18 months and further GH dosing considered if therapy demonstrates beneficial effects on bone density. Although some healthcare professionals may suggest continuing GH therapy in all adults for presumed cardiovascular risk benefit, this point is still debated. Of course, as with any therapeutic intervention, incident adverse effects may also limit use of GH therapy.

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