Endocrine Disorders

Expert Conversations: A Review of Human Growth Hormone Deficiency and Its Management



In this podcast, authors Julie Silverstein, MD, and Alexandra Martirossian, MD, discuss their recent Consultant review article, "Diagnosis and Management of Growth Hormone Deficiency in Adults." This is part 1 of a 3-part series. Listen to the next parts below.

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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.



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. Today I’m speaking with the authors of an article titled, “Diagnosis and Management of Growth Hormone Deficiency in Adults,” which was published on Consultant360 recently and will appear in the June issue of Consultant. 

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.

Adult-onset growth hormone deficiency (GHD) is a clinical syndrome caused by decreased production of or decrease tissue responsiveness to growth hormone that isn’t diagnosed until adulthood. What should primary care providers know about GHD?

Alexandra Martirossian: Sure, so growth hormone is one of several hormones that are secreted by the pituitary gland, anterior pituitary. And the anterior pituitary is a little gland in our brains, a few inches behind the eyes, and it regulates other hormones that are involved, including the thyroid, cortisol production, estrogen production in women, testosterone production in men, and, of course, growth hormone. 

In children, growth hormone is primarily responsible for growth in height, bone elongation, and muscle production. In adults, it's more anabolic effects, so maintaining muscle mass and bone density.

Growth hormone deficiency is very insidious in presentation, because in children, for example, if they have a growth hormone deficiency, they just don't get tall. That's usually a pretty obvious observation. But in adults, findings are usually more subtle. It could be things like fatigue, weight gain, decrease quality of life, increase in fat mass, decrease in muscle mass. and there's just a lot of clinical things out there that can present in a similar way.

And so, it's something that takes a higher index of suspicion to diagnose.

Julie Silverstein: The one thing I'll just add is that, generally, you probably don't want to just start testing people for growth hormone deficiency, just because of the nonspecific nature and how rare it is. The type of patient you want to be thinking about is someone who has pituitary disease, like a pituitary tumor, or they've had surgery or radiation, or they've had some kind of other trauma to the pituitary gland.

Amanda Balbi: Diagnosis of GHD is confirmed by laboratory testing, as you alluded to, in the setting of multiple pituitary hormone deficiencies and organic pituitary disease. What is the role of the primary care provider in that diagnosis process, and at what point should a primary care provider refer patients to an endocrinologist?

Alexandra Martirossian: The role of the primary provider is to know when to suspect it. So, kind of like what Dr Silverstein mentioned earlier; The clinical history is so important to diagnosis. If they've had some kind of pituitary tumor that was treated with surgery or radiation, or they have had any traumatic brain injury, then that puts them at risk of other hormone deficiencies and not just for growth hormone. 

It's important for primary care providers to start your normal evaluation, so they can check other things like thyroid and cortisol production, and testosterone or estrogen levels in suspected patients. Because that can be very helpful, even just getting the hormonal workup started or if there's any imaging of the brain that needs to be done.

If workup is abnormal, then it'd be good time to refer to an endocrinologist. A lot of it depends on the comfort level of the primary care provider. If they have a strong enough suspicion for a disorder in the pituitary hormone or growth hormone, then it would also be reasonable to refer to endocrinology early on.

Amanda Balbi: Okay, so then treatment for GHD might be lifelong. What is the gold standard of treatment for adult-onset GHD, and can primary care providers manage these patients long term?

Alexandra Martirossian: Sure, so the gold standard of treatment for growth hormone deficiency is just growth hormone replacement, or recombinant growth hormone. For years it's always just been a daily injection under the skin, but now there are newer drugs in development for once-weekly growth hormone injections. 

As far as management, if a primary care provider feels comfortable prescribing and they know what to look for as far as the diagnostic criteria and the complications you need to be aware of with treatment, then that's fine. But from a more practical standpoint, a lot of times insurance companies want to see that it's being prescribed by an endocrinologist. So, sometimes that ultimately makes the final decision.

But I’d say, at least in current practice, the majority of growth hormone prescriptions are coming from endocrinologists.

Julie Silverstein: And I would just add that I think this would be something that would be started by an endocrinologist, but depending on access to care for the patient, it may be that it would be more convenient for the patient if the primary care doctor took over management of it, possibly while maintaining communication with an endocrinologist.

But as Dr Martirossian has mentioned, prescribing growth hormone often comes along with a lot of paperwork to get approval, and often there's questions about who's prescribing it, so that may be a barrier, as she mentioned.

Amanda Balbi: So, after therapy is initiated, patients should follow-up in 1- to 2-month intervals at first, which can later be spaced out to 6- to 12-month intervals once a stable dose has been reached. What is the role of the primary care provider in the long-term management of patients with adult-onset GHD?

Julie Silverstein: I think this can be a difficult thing to monitor in terms of figuring out if someone's getting benefit from it. Certainly, we monitor IGF-1 levels, at first, every 1 to 2 months as you're increasing the dose. And really what you're trying to do is you want to avoid side effects and, of course, you want to avoid underdosing and symptoms of growth hormone deficiency. So, you're aiming for an IGF-1 level within the normal range. Data does not support keeping people at a higher level.

The other thing you want to assess include clinical improvement in terms of symptoms. The objective measures of that could be using quality of life questionnaires every 6 months to a year. Other things that should be assessed are fasting glucose because, as I said, growth hormone replacement can translate and induce glucose.

There are tools to measure waist circumference and waist-to-hip ratio to see objective evidence of benefit, as well as you should measure things like the fasting lipid profile. So, I think that's where the primary care doctor could have a role—in some of the routine testing that you would do anyway for these patients, such as the fasting glucose and the A1c. 

So again, I think that could be something done in coordination with an endocrinologist. I think a lot of primary care doctors and even endocrinologists don't have the tools to measure lean waist-to-hip ratio, waist circumference readily available necessarily in their clinic.

And the other thing I would say is that I think it's important to reassess periodically whether or not the patient is having benefit from the growth hormone replacement. Again, this could be done with primary care and endocrinology.

So, again, looking at those parameters that I discussed but also trying to assess if a patient is having symptomatic improvement, because if there’s really no symptomatic improvement or no other objective signs of improvement after 1 to 2 years, it's reasonable to stop giving the growth hormone. But that should be a joint discussion with the patient.

Amanda Balbi: Recombinant human growth hormone has a high financial cost and the possibility of adverse effects. What are your tips for health care providers managing these patients long-term who may not be adherent to the medication?

Julie Silverstein: First, to address the side effects. Again, I think it's important to understand that the side effects are dose-dependent. So, if someone develops side effects and you decrease the dose or you stop growth hormone, those should go away.

But the things that we need to look out for are joint and muscle pain, soft tissue swelling, paresthesias, carpal tunnel syndrome, development of sleep apnea, potentially making blood pressure worse, insomnia, and, as I mentioned, hyperglycemia.

I mean if you give someone too much growth hormone, you could have features of acromegaly, but that's pretty rare. So, it's important I think to assess those things as you're treating patients.

In terms of adherence, I think that's really more of an issue in the pediatric population, because the patients need the growth hormone to grow as they should. In adults, and even in pediatrics sometimes, it’s not always dosed every single day of the week. And kids are sometimes given breaks.

In adults, it's reasonable to skip a day here and there if patients are having side effects or if it's just too hard to get fitted into the busy schedule. This is really where the once-a-week formulations, which I do think will be coming out and will be available, are going to be helpful, even potentially a once-a-month formulation.

The other thing I would say for following these patients and something for the primary care doctor is, there's a debate about whether or not growth hormone replacement increases malignancy risk. Because its growth hormone, it stimulates growth of cells, but we have data in patients with hypopituitarism where there's no increased risk of cancer or mortality in those patients.

But the growth hormone replacement is contraindicated in someone with an active malignancy. So, that's somewhere where the primary care doctor would have to be aware of that.

Alexandra Martirossian: And I think I have one more thing I would add, too, is that there's a potential for abuse in society, because I think some people may view it in sports for athletic performance enhancement, or maybe some people might view it as a way to prevent the aging process. Really, growth hormone should never be prescribed for either of those things. It should really only be prescribed for documented growth hormone deficiency, or it's also been approved for lipodystrophy.

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

Julie Silverstein: Thank you.

Alexandra Martirossian: Yeah, thank you for having us.