Timing and protocol: retesting should be performed after growth hormone therapy has been discontinued for at least 1 month and when the patient has reached near-final height with a growth velocity of less than 2 cm per year and is pubertally mature.
Let's return to our conversation with Sam and his mother.
Mrs. Broeckert:
Do you think Sam will be ready to take responsibility for managing his medication?
Dr. Maniatis:
That’s something we'll assess together. Transition readiness is key. It includes helping Sam understand his condition, manage his medication, and feel confident talking to his providers. Based on our discussion, I know that he has been taking the shots himself with minimal assistance.
Mrs. Broeckert:
Right.
Dr. Maniatis:
We can use a few tools, like transition checklists, to guide this process and make sure he's supported emotionally and practically. We can also discuss potentially switching to a long-acting growth hormone at a different visit.
Sam:
Will I continue to see you?
Dr. Maniatis:
Well, we will test you here, and we'll guide you through every step. But once we confirm the path forward and if you need to continue with therapy, we'll coordinate with an adult endocrinologist to ensure a smooth handoff. Our nurse can provide you with a transition guide to help you understand the process, know what to expect, and consider important questions along the way.
Dr. Maniatis:
So as you saw above, transitioning care isn't just about switching providers—it's about empowering young adults like Sam to take ownership of their health. With the right tools, a supportive team, and a stepwise approach, we can ensure that this next chapter builds on the progress we've already made.
Most patients with idiopathic isolated childhood-onset growth hormone deficiency should undergo repeat growth hormone stimulation testing after reaching near-final height and discontinuing therapy for at least 1 month. Retesting is not necessary for those with 3 or more pituitary hormone deficiencies or confirmed genetic or permanent structural causes.
Clinicians should assess transition readiness by evaluating the patient's ability to manage their condition and communicate with providers. Tools such as checklists and educational handouts can help ensure a smooth and supported shift from pediatric to adult endocrine care.
Chapter 3
Dr. Maniatis:
Now let's go back to Mrs. Hosack and her son. In the first vignette you saw me counsel Mrs. Hosack about the diagnostic pathways. Matthew went on to fail 2 growth hormone stimulation tests and was started on daily growth hormone. He has been on daily injections for the past 3 years but now he's beginning to get fussy before his injections and has developed a phobia of injection time. Adherence is getting to be a challenge, and he and his mother are interested in switching to long-acting growth hormone. In today's visit, we'll be talking all about how to get him started on that switch and how to monitor from there on. So let's dive in.
Dr. Maniatis:
Hello, Mrs. Hosack, good to see you again. So what brings you in today?
Mrs. Hosack:
Hello, Dr. Maniatis. Matthew has been on daily growth hormone injections for some time now, and until recently, he was doing fine with it, but now it's becoming a struggle every single night. He gets anxious as soon as he sees the pen. He's calling it “injection time,” and it's like we're gearing up for battle. Last night, he cried and told me he didn't want to grow anymore if it means another shot.
Dr. Maniatis:
I'm really sorry to hear that. Injection fatigue can be tough, especially in kids who've been on long-term treatment. It's more common than people think, and you're not alone in this.
Mrs. Hosack:
I understand he needs this to grow and stay healthy—believe me, I do—but I can't keep forcing him like this. It's becoming traumatic for both of us. Is there anything else we can consider, maybe something that doesn't need to be given every single day?
Dr. Maniatis:
Yes, absolutely. It sounds like Matthew might be a good candidate for a long-acting growth hormone option. These formulations are designed to be given once weekly instead of daily, which can really ease the emotional burden and improve adherence. If he's otherwise doing well on therapy, this could be a very reasonable next step.
Mrs. Hosack:
Yes, that would be such a relief—for him and for us. I just want him to keep progressing without the fear and stress every day.
Dr. Maniatis:
Several long-acting growth hormone products are now approved globally, each using distinct mechanisms of action to extend half-life and alter pharmacokinetics.
Three are approved in the US. While all 3 agents are designed to reduce injection frequency and improve adherence, they differ significantly in structure, mechanism, and formulation.
Lonapegsomatropin uses transient PEGylation. It's a prodrug with a polyethylene glycol carrier, a linker, and somatropin. Once in the body, the linker dissociates, releasing unmodified somatropin.
Somapacitan uses a noncovalent albumin-binding strategy. The somatropin molecule has a single amino acid substitution with a hydrophilic spacer that then binds the serum albumin.
Somatrogon is a fusion protein. The somatropin molecule has 3 carboxy terminal peptides from human chorionic gonadotropin, or hCG, attached to it.
When initiating long-acting growth hormone, we start with weight-based dosing. This is consistent with how we approach daily growth hormone but with a few important nuances.
Now a key caveat here—consider a lower initial dose in certain populations. Specifically, this applies to children with obesity or those at increased risk of hyperglycemia, intracranial hypertension, severe growth hormone deficiency, or those with known genetic or chromosomal abnormalities. These individuals may have heightened sensitivity or altered pharmacodynamics, and starting conservatively can help minimize adverse events.
Just like with daily growth hormone, dose titration for long-acting growth hormone is ultimately at the provider's discretion. We base adjustments on a range of clinical indicators, including IGF-1 levels—if these rise above the target range, that's our first signal to reassess the dose; annualized height velocity—are we seeing the expected growth; pubertal staging—as the child progresses through puberty, growth velocity changes; bone age, which gives us a sense of maturation versus chronologic age; and estrogen supplementation in girls, which can impact growth and growth hormone responsiveness. If you're seeing elevated IGF-1 levels, the general recommendation is to reduce the dose by about 15% to 20%.
This brings us to an important pharmacologic principle. Because each long-acting growth hormone molecule has its own unique pharmacokinetic and pharmacodynamic profile and its own molecular weight, the per-milligram dosing calculations are not interchangeable. That means you can't compare milligram doses between different long-acting growth hormone formulations or between long-acting growth hormone and daily growth hormone on a 1:1 basis. Direct milligram-to-milligram comparisons are simply not appropriate.
It's important to understand the pharmacokinetics and pharmacodynamics of long-acting growth hormone therapies when monitoring IGF-1 levels. IGF-1 levels fluctuate over the dosing interval and the timing of lab sampling is critical for accurate interpretation.
For daily growth hormone, IGF-1 levels remain relatively stable across the week with minor day-to-day fluctuations. For long-acting growth hormone, IGF-1 rises to a peak 2 days after the injection then gradually declines to a trough before the next dose. Point B represents the average IGF-1 level, which is the target for long-term monitoring. The consensus recommendations suggest drawing blood near the average IGF-1 timepoint: lonapegsomatropin, day 4.5; somapacitan, day 4; somatrogon, day 4.
Let's return to our appointment with Matthew's mother.
Dr. Maniatis:
Let's walk through what that transition might look like. You would have to give it every week. The great thing about it is that, since it is weekly, you won't have to worry about giving him shots every day.
Mrs. Hosack:
Is it as good as the daily injections?
Dr. Maniatis:
Yes. Studies have shown that long-acting growth hormone works just as well as daily growth hormone. The main difference is how it moves through your system. With daily growth hormone, your IGF-1 levels stay pretty steady. With long-acting, the levels rise after the shot, peak a couple days in, then drop before your next dose. That's totally expected. It's how the medication is designed.
As far as safety is concerned, to date, the safety profile of long-acting growth hormone is comparable to that of the daily growth hormones.
Dr. Maniatis:
In early clinical experience with long-acting growth hormone, it has been observed that patients already accustomed to traditional daily growth hormone therapy may exhibit greater hesitation to transition to long-acting growth hormone compared to treatment-naïve individuals who may be more open to newer therapeutic options. This reluctance often stems from familiarity with daily growth hormone regimens and uncertainty around the pharmacokinetics, dosing adjustments, and monitoring protocols associated with long-acting growth hormone.
Across all pivotal phase 3 trials, the 3 currently approved long-acting growth hormone therapies—lonapegsomatropin, somapacitan, and somatrogon—have demonstrated noninferiority to daily growth hormone in promoting annualized height velocity over a 52-week period. This evolving landscape underscores the importance of patient education and shared decision-making when introducing long-acting growth hormone as a therapeutic alternative.
When initiating a new long-acting growth hormone, the key principle is to avoid overlapping dosing. For patients switching from daily growth hormone, the previous dose should be discontinued the night before, ensuring at least 8 hours between the last daily injection and the first long-acting growth hormone dose. For those transitioning from another long-acting growth hormone formulation, it's important to discontinue the prior long-acting growth hormone at least 7 days in advance to prevent cumulative exposure.
When selecting a long-acting growth hormone, it's important to consider device features and dosing format. Regardless of which long-acting growth hormone is used, more than one injection may be needed regularly based on weight threshold.
Lonapegsomatropin uses an autoinjector with fixed weight-based cartridges. It has a 60.5-kg threshold for requiring 2 injections and the full dose is delivered per cartridge. Somapacitan and somatrogon are pen based. Their thresholds for 2 injections are 50 kg and 45 kg, respectively. They offer more flexible dose graduations but will more frequently require 2 injections based on partial remaining dosage in the pen to avoid waste.
Regardless of product, it is important to rotate sites to avoid lipoatrophy and always document day and time of the dosing.
When it comes to missed doses of long-acting growth hormone, each product has a specific makeup window. For lonapegsomatropin, the missed dose should be given within 2 days of the scheduled shot. For somapacitan and somatrogon, you have a 3-day window. If the dose is missed outside of that window, skip it and resume dosing on the next scheduled day. Most importantly, emphasize to patients and caregivers that consistent dosing is critical. Missing doses can reduce efficacy and pose potential safety risk, such as hypoglycemia.
As far as safety is concerned, to date, the safety profile of the long-acting growth hormone formulations is comparable to that of daily growth hormone. These formulations have several potential advantages over daily growth hormone, including the potential for improved adherence, reduced treatment burden, and positive impact on quality of life.
Now let's see if Matthew's mother has any more questions.
Mrs. Hosack:
Is the dose the same as what Matthew takes now?
Dr. Maniatis:
Not quite. The milligram dosing is different because it is a different molecule designed for once-weekly use. But don't let the higher number throw you off. We'll calculate a starting dose based on Matthew's current weight and adjust it based on his labs and how he responds.
Mrs. Hosack:
Okay, so will the monitoring be the same?
Dr. Maniatis:
We’ll still check his IGF-1 levels, but we'll time the blood draw differently. Depending on the medication, we might ask you to come in on day 4 or 4.5 after the injection. That's when we get the most accurate reading. We'll use that to fine-tune the dose if needed.
Mrs. Hosack:
What about side effects? Do you think he'll have any side effects? We've been really lucky. He's done great on daily injections, but now that he's developing a fear of injections, I have to chase him down every night. I'm tired of all the crying, and it's painful to watch him go through this every day.
Dr. Maniatis:
So far, it's been very well tolerated. Nothing new or unexpected has shown up compared to daily growth hormone. The side effects profile of the long-acting growth hormone products is the same as that of daily growth hormone.
Mrs. Hosack:
Do a lot of people switch?
Dr. Maniatis:
Many do, especially parents whose children are taking multiple medications or those who are expressing difficulty with daily growth hormone adherence and are looking for something less burdensome. It's not for everyone, but it can be a good fit if you're consistent with follow-up.
Dr. Maniatis:
When considering long-acting growth hormone therapy, think about children who may struggle with daily injections. These include teenagers and others with a history of poor adherence; children on multiple medications; or those with neurodiverse conditions, like autism or ADHD, who may find injections especially distressing; children or caregivers with injection-related fear or anxiety, where treatment could impact the parent-child dynamic; children with more than 1 home where coordinating treatment across locations can be challenging; those with busy schedules like travel for sports, music, or frequent sleepovers, where daily dosing becomes a burden; and families facing socioeconomic challenges for whom growth hormone therapy adds stress.
It's important to note that long-acting growth hormone is approved for pediatric growth hormone deficiency from as early as 1 to 3 years of age, depending on the country and product.
Currently, 3 globally approved long-acting growth hormone formulations—lonapegsomatropin, somapacitan, and somatrogon—have shown noninferiority to daily growth hormone in efficacy with comparable safety profiles.
While long-acting growth hormone holds promise beyond growth hormone deficiency, more data are needed. Until then, our best outcomes will continue to come from early intervention, thoughtful transitions, and collaborative informed choices with our patients and their families.
As we reflect on the cases we've discussed today, several themes come into focus. First, the importance of early diagnosis in growth hormone deficiency—timely recognition sets the foundation for better long-term outcomes.
Second, the need for structured, individualized transitions to adult care, especially as patients complete growth and move into new therapeutic goals focused on metabolic health and quality of life.
We've also seen how shared decision-making plays a central role, whether it's preparing a teenager to manage their care independently or supporting a family exploring alternatives to daily injections. For some, this includes transitioning to long-acting growth hormone therapy, which offers the potential for improved adherence, decreased treatment burden, and positive impact on quality of life.
Thank you for joining me for our Patient-Clinician Connection vignettes on growth hormone deficiency. I hope this program will be helpful for your practice.
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