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Expert Conversations: Treatment of Growth Hormone Deficiency

01/19/2022

 

In this podcast, authors Julie Silverstein, MD, and Alexandra Martirossian, MD, discuss the treatment of growth hormone deficiency and how to dose. This is part 3 of their podcast series on their recent Consultant review article, "Diagnosis and Management of Growth Hormone Deficiency in Adults."

Additional Resources:

Julie M. Silverstein, MD, is an associate professor of medicine and neurological surgery and medical director of the Pituitary Center at Washington University in St. Louis.

Alexandra Martirossian, MD, is a second-year fellow in the Endocrinology Department at Washington University in St. Louis.

 

TRANSCRIPTION:

Amanda Balbi: Hello, everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360. 

In part 3 of our podcast on the article, “Diagnosis and Management of Growth Hormone Deficiency in Adults,” I speak with the authors about the treatment of GHD and how to dose.

Dr Julie Silverstein is an associate professor of medicine and neurological surgery and medical director of the Pituitary Center at Washington University in St. Louis. Dr Alexandra Martirossian is a second-year fellow in the Endocrinology Department at Washington University in St. Louis.

Let’s listen in as they answer my questions.

As you mentioned before, the gold standard treatment of adult-onset GHD is growth hormone replacement therapy. Can you tell us a little bit more about the treatment and its benefits?

Julie Silverstein: Absolutely. But before talking about the benefits, I just wanted to review some of the signs and symptoms of growth hormone deficiency. As we mentioned, they’re nonspecific, but there are studies that show decreased quality of life in terms of having more depressed mood, anxiety. There are changes that have been demonstrated in body composition, like increased total body fat and a decrease in lean mass. GHD has been shown to be associated with decreased bone density and increased fracture risk. 

There are also studies that show decreased exercise capacity, increased atherogenesis, decreased insulin sensitivity. In terms of the benefits of treatment with growth hormone, a lot of the data is mixed with some studies showing benefit and some showing not. Most of the data that we have that supports the benefits of growth hormone replacement come from retrospective and open-label observational studies. So, it's important to keep in mind that we don't have any really robust perspective clinical trials, where you gave some patients growth hormone and some of the patients placebo to definitely compare, to determine if there's benefit. 

But there are studies that show growth hormone replacement does ameliorate central obesity. It increases the amount of lean body mass and bone mass. It has been shown to be associated with improvements in bone mineral density and decreased risk of fracture.

There are also studies that show that there's beneficial effects on cholesterol, such as on LDL, and that it lowers diastolic blood pressure, but we don't really have evidence that that is associated with really measurable changes in cardiovascular function.

The other thing that has been shown in several of these studies is improvement in quality of life when questionnaires are given and measuring parameters such as memory and concentration, fatigue, self-confidence, those kinds of things, there are benefits there.

The other thing that has come up is there is data to suggest that patients with hypopituitarism have increased morbidity and mortality. And some studies have debated whether or not that could be due to growth hormone deficiency, but there really is no conclusive data to say that treatment will reduce that mortality or morbidity.

Amanda Balbi: So, what treatments are currently available other than the hormone replacement therapy, and are there new treatments in the pipeline?

Julie Silverstein: The only treatment available for growth hormone deficiency is treatment with growth hormone right now. Up until recently, the only agent we've had is somatropin, which is a daily injection recombinant human growth hormone. It's a subcutaneous under the skin injection. There are multiple agents that are being investigated.

There is a long-acting, once a week agent that has been approved for treatment in adults, but it's not commercially available. Other things that are in the pipeline, so there are agents that are being developed that would be given biweekly and even monthly.

There are multiple brands of somatropin that there's really no difference in terms of efficacy or side effects. The differences have to do with delivery methods, whether it's a prefilled pen or you have to draw it up from a syringe; those kinds of things.

Amanda Balbi: And dosing is influenced by age, sex, comorbidities, and concomitant medications. Can you give us an example of how you would determine a dose for a new patient?

Julie Silverstein: So, the dosing of growth hormone depends on multiple factors, starting with age. But what I recommend is looking at the guideline. So, in 2019 the AACE/ACE published guidelines for management of growth hormone deficiency. As patients get older, you want to start with a lower dose, and that's because older individuals are more likely to experience side effects.

The typical dose in adults is 0.1 to 0.4 mg/d. So, unlike in children, we don't dose based on weight. If you have a patient who's younger than 30 years, generally start with 0.4 or 0.5 mg/d. If somebody is 30 to 62 years of age, the starting dose should be more 0.2 to 0.3, and if someone's over 60 years, you want to start even lower—0.1 to 0.2 mg/d.

In terms of differences in comorbidities, the biggest difference there would be if you have a patient…There can be a transit increase in glucose levels. In patients who have type 2 diabetes or are obese, it's recommended to start at lower doses of 0.1 to 0.2 mg/d.

One of the main things, in addition, that you have to be aware of when you're prescribing growth hormone is that women who take oral estrogen will need higher doses of growth hormone. That's because oral estrogen, which undergoes first pass metabolism in the liver, suppresses or decreases hepatic production of IGF-1. So, if you have a woman on oral estrogen, they will need higher doses. And then on the flip side, it would be important to realize that if you take that woman off the oral estrogen and, say, start transdermal estrogen, the dose will probably need to be decreased.

The other thing that's important is to make sure that other hormones are sufficiently replaced before you start treatment with growth hormones, such as make sure they're on adequate doses of thyroid hormone and adequate doses of glucocorticoid replacement if they have adrenal insufficiency, because growth hormone can change the metabolism of those medications.

Amanda Balbi: Thank you again so much for answering my questions.

Julie Silverstein: Thank you.

Alexandra Martirossian: Yeah, thank you for having us.