{"id":21488,"date":"2026-07-08T19:50:11","date_gmt":"2026-07-08T15:50:11","guid":{"rendered":"https:\/\/medscriptum.org\/?p=21488"},"modified":"2026-07-08T19:50:31","modified_gmt":"2026-07-08T15:50:31","slug":"rethinking-the-diagnosis-and-management-of-acromegaly-interview-with-professor-aart-jan-aj-van-der-lely","status":"publish","type":"post","link":"https:\/\/medscriptum.org\/en\/rethinking-the-diagnosis-and-management-of-acromegaly-interview-with-professor-aart-jan-aj-van-der-lely\/","title":{"rendered":"Rethinking the Diagnosis and Management of Acromegaly – Interview with Professor Aart Jan (AJ) van der Lely"},"content":{"rendered":"

There are diseases that do not announce themselves – they accumulate. A change in ring size, a shift in facial features, a persistent headache dismissed for years before the diagnosis finally arrives. By the time acromegaly is identified, the body has often already carried its consequences for a decade. It is a condition that demands both clinical vigilance and sophisticated long-term management – ground that Professor Aart Jan (AJ) van der Lely, MD, PhD has navigated and helped define throughout his career. Former Head of Endocrinology at Erasmus University Medical Center in Rotterdam and past president of the European Society of Endocrinology, and the Pituitary Society, he brings to the subject a perspective shaped by decades at the field’s center.<\/span><\/p>\n

We had the opportunity to speak with Professor van der Lely at the 8th Annual International Congress of Clinical Endocrinology<\/a> in Tbilisi, where he presented on the diagnosis and management of acromegaly. The conversation that followed ranged from surgical strategy and pharmacological sequencing to the systemic burden of the disease and the emerging role of gut hormones in endocrine research.<\/span><\/p>\n

Acromegaly is associated with a prolonged diagnostic delay – patients have symptoms for years before anyone recognizes it. What factors contribute to this – gradual disease progression, nonspecific clinical features, or other causes?<\/i><\/b><\/p>\n

It depends somewhat on age. If a child – which is very rare – has a growth-hormone-secreting pituitary tumor, they become markedly large, and that is noticed immediately. If you are 12 or 14 and already 1.8 meters tall, someone will almost certainly see a doctor and the diagnosis will be made.<\/span><\/p>\n

At older ages, however, the changes are much more gradual. For someone aged 50 to 70, family members often assume the changes are just normal aging or that \u2018this is how Uncle Sam is.\u2019 Because the progression is slow, relatives may not recognize anything abnormal over the years. Occasionally a neighbor or a family member with medical knowledge will raise a concern, but that doesn\u2019t happen reliably.<\/span><\/p>\n

The second hurdle is primary care. General practitioners rarely expect to encounter acromegaly in their careers. In the Netherlands we tried a simple intervention: we sent a one-page leaflet to GPs showing a picture of a patient with acromegaly, provided a phone number, and asked them to measure IGF\u20111 if they saw a patient who looked like that. We repeated it four months later and hoped to see an increase in diagnoses. Nothing happened.<\/span><\/p>\n

From my experience, shortening the time between disease onset and diagnosis is very difficult. It\u2019s a nightmare. It shouldn\u2019t be, but this is the curse of rare diseases: even physicians do not believe they will ever see a patient with such a condition because it is so uncommon.<\/span><\/p>\n

The main test is IGF-1, but sometimes GH results are not straightforward. What role does GH testing play in the diagnostic process, and how do you confirm acromegaly in patients with less obvious or equivocal findings?<\/i><\/b><\/p>\n

In clear-cut cases I can usually tell clinically that a patient does not have acromegaly, even before any blood tests. If there is uncertainty, measure IGF\u20111. A normal IGF\u20111 essentially rules out the disease and no further testing is needed. An elevated IGF\u20111 establishes the diagnosis in most patients – the important exception being individuals who may be using exogenous growth hormone, such as some bodybuilders.<\/span><\/p>\n

If uncertainty persists, an oral glucose tolerance test (OGTT) with serial GH measurements remains the gold standard: failure of GH to suppress during a glucose load confirms the diagnosis. In practice, however, needing the OGTT is uncommon. It is safe to perform and can always be done when needed.<\/span><\/p>\n

One practical tip I give to clinicians who rarely see acromegaly: forget random GH measurements and rely on IGF\u20111 as the primary screening test.<\/span><\/p>\n

Treatment also has shifted dramatically. First-generation treatments achieved control in about 40% of patients, but newer drugs push that to 60-70%. What\u2019s the reason behind this? How do newer somatostatin analogs differ from earlier options?<\/i><\/b><\/p>\n

In the early 1980s, the first available pharmacological option was bromocriptine, followed later in the same decade by octreotide as a subcutaneous injection. Subsequently, long-acting release (LAR) preparations became available, as did lanreotide autogel. These two agents are broadly equivalent in efficacy, though it is worth noting that there are very few prospective studies that have assessed efficacy in an unbiased patient population. That figure stands at approximately 40-50%, meaning that roughly half of patients remain inadequately controlled and eligible for further treatment. However, this is not the case for tumor size control, where efficacy exceeds 80%.<\/span><\/p>\n

The availability of GH receptor antagonists since 2004 has made a substantial difference. In our experience, virtually all patients can achieve biochemical control with a GH receptor antagonist. The only currently available agent in this class is pegvisomant, though new compounds are in development. I have collaborated extensively with Pfizer to encourage physicians to prescribe adequate doses, because what we observe over a ten-year horizon is that approximately 70% of patients treated with pegvisomant – either as monotherapy or in combination with somatostatin analogs – achieve control. Yet the average dose being prescribed remains just over 20 mg per day, despite the label permitting up to 30 mg. It is still not well understood why physicians continue to treat at 20 mg in patients with persistently elevated IGF-1. There is clearly room to escalate. In selected, dedicated patients, we use it off-label at considerably higher doses.<\/span><\/p>\n

From a pharmacological standpoint, pegvisomant is a competitive GH receptor blocker. Consequently, basic pharmacology dictates that if administered in sufficient quantities, it can occupy all available receptors – and both in theory and in practice, it is possible to render even acromegaly patients functionally GH deficient. So if pegvisomant is available, it should be used at an appropriate dose.<\/span><\/p>\n

There is also a common misconception around its time course of action, which stems from clinicians being accustomed to the six-month wait typically required to assess the efficacy of somatostatin analogs. That paradigm does not apply to pegvisomant. Steady state is reached within six weeks, so if IGF-1 remains elevated at that point, the dose should be increased without delay. In terms of administration, while the label specifies daily injections, patients who respond well can be transitioned to weekly injections, which many find considerably more manageable.<\/span><\/p>\n

The question isn’t just ‘what works’ – it’s ‘what’s the right sequence?’ For a patient with a large tumor: do you start with surgery, then medication, or medication first to shrink before surgery?<\/i><\/b><\/p>\n

In a considerable number of cases, the tumor has extended beyond the sellar region, and parasellar invasion of the cavernous sinus in particular is a strong predictor of surgical outcome. In such situations, if somatostatin analogs are available, pre-surgical tumor reduction is a worthwhile strategy. The underlying rationale is straightforward: removing as much tumor as can be safely resected means that the remaining tissue produces less GH. With a lower GH burden to suppress, the probability that somatostatin analogs alone can achieve adequate biochemical control is meaningfully increased.<\/span><\/p>\n

On the other hand, in older patients presenting with a relatively smaller – though still macro – adenoma, we are increasingly inclined not to operate, as these individuals can often be well managed with somatostatin analogs, supplemented by pegvisomant where necessary. In this context, surgical debulking is not required to optimize the pharmacological response.<\/span><\/p>\n

The appropriate approach, therefore, is inherently patient-dependent. That said, it is worth emphasizing that contemporary endoscopic surgery has a considerable capacity for tumor removal – whether in a primary procedure or in the setting of a second intervention. However, when there is true invasion of the cavernous sinus – genuine invasion, not merely impression or displacement – the probability of surgical cure drops to below 10%. In these cases, it becomes essential for the clinician and patient to engage in a careful, shared discussion weighing the realistic likelihood of cure against the procedural risks and the available medical alternatives.<\/span><\/p>\n

Today you can hardly encounter patients with only single conditions. When you’re managing a patient with multiple comorbidities – heart disease, diabetes, maybe bone issues – how do you decide which risk to prioritize first? Is it the tumor itself, the metabolic risk, or the cardiovascular risk? (because we know some drugs normalize IGF-1 but don’t shrink the tumor, while others shrink the tumor but may worsen glucose control)<\/i><\/b><\/p>\n

This is where the choice of pharmacological agent becomes particularly consequential. First-generation somatostatin analogs – octreotide and lanreotide – have a variable effect on glycemic control; they may either improve it or worsen it depending on the individual patient. The second-generation analog, pasireotide, is a different matter entirely: it reliably deteriorates glycemic control and can even precipitate new-onset diabetes. Given that acromegaly patients already carry an elevated cardiovascular risk, I reserve pasireotide for highly selected cases where other options have been exhausted, precisely because alternative agents with a more favorable metabolic profile are available.<\/span><\/p>\n

Our current approach is to place virtually every patient on a combination of somatostatin analogs and low-dose pegvisomant, and there is a clear physiological rationale for this. Somatostatin analogs are effective at suppressing IGF-1 generation – normalizing it in approximately half of patients – but they are considerably less effective at reducing GH concentrations directly, which may remain elevated. Patients, of course, do not report their GH levels; they report their symptoms. They present with persistent headaches, fatigue, and arthralgias – manifestations of ongoing GH activity in peripheral tissues beyond the liver, even while IGF-1 appears controlled. This is an important point: relying solely on IGF-1 during somatostatin monotherapy risks overestimating treatment efficacy. A patient with a normal IGF-1 may still have residual, low-grade acromegaly activity in other tissues.<\/span><\/p>\n

By adding low-dose pegvisomant to block that residual GH effect, we observe meaningful improvements across multiple domains – quality of life, glycemic control, hypertension, and edema – in virtually all patients. For this reason, we strongly advocate for combination therapy from the outset, rather than a sequential strategy in which somatostatin analogs are trialed first and pegvisomant introduced only upon failure. In our view, the combination represents the most physiologically rational and clinically effective approach.<\/span><\/p>\n

More broadly, do you see acromegaly as a systemic disorder rather than only a pituitary tumor, especially given its metabolic and cardiovascular effects?<\/i><\/b><\/p>\n

To appreciate the systemic complexity of acromegaly, it is instructive to consider how GH and IGF-1 behave in other metabolic contexts. Take type 1 diabetes: even when managed with insulin – whether via subcutaneous pump or multiple daily injections – these patients exhibit GH levels in the acromegalic range, yet their IGF-1 remains low. Paradoxically, their risk of cardiovascular disease and cancer is lower than that seen in type 2 diabetes. In type 2 diabetes, the inverse pattern prevails: IGF-1 is relatively elevated while GH is markedly suppressed – often indistinguishable from GH deficiency – yet the risks of atherosclerotic cardiovascular disease and malignancy are substantially higher than in the general population. What this illustrates is that the pathological consequences are not attributable to any single hormone in isolation, but rather to the dynamic interplay between GH, IGF-1, and insulin.<\/span><\/p>\n

In acromegaly, both GH and IGF-1 are elevated, which might lead one to anticipate a markedly increased cancer burden. In practice, however, this does not appear to be the case. There may be a modest elevation in cancer risk, but it is considerably smaller than that observed in type 2 diabetes or obesity. The picture is, in short, highly complex – and any attempt to interpret it by focusing on a single hormonal axis in isolation will inevitably yield an incomplete and potentially misleading understanding.<\/span><\/p>\n

The cardiovascular risk profile in acromegaly is also distinct in character. Rather than being driven predominantly by atherosclerosis, the predominant mechanism is one of pathological organomegaly – the heart enlarges, becoming prone to arrhythmias and structural dysfunction. This risk is particularly pronounced in patients who received pituitary irradiation in the past, where the incidence of cerebrovascular accidents is elevated approximately fourfold. So it’s a very complicated picture.<\/span><\/p>\n

Your research on gastrointestinal hormones in health is as significant as your pituitary work. There is growing interest in whether gut hormones such as GLP-1 and gastrin may modulate GH secretion. Do you see a biologically meaningful pathway here, and could it carry any clinical relevance for future therapies?<\/i><\/b><\/p>\n

Gut hormone pathways are undoubtedly of considerable interest for future therapeutics across a broad range of conditions – though I am less convinced, at least at this stage, that acromegaly will be among them. I was recently in contact with the president of the Pituitary Patient Support Organization in the United States, and she mentioned that a notable number of acromegaly patients are currently using GLP-1 receptor agonists and reporting substantial symptomatic improvement. The mechanistic basis for this remains unclear to me. One possibility worth exploring is the presence of aberrant GLP-1 receptors on pituitary tumor tissue. There is already evidence that ectopic GIP receptors on somatotroph adenomas may contribute to abnormal glucose tolerance test responses, which suggests that incidental receptor expression on tumor tissue is not without precedent. These observations may yet yield important physiological insights. That said, I do not currently see a well-defined mechanistic link between gut hormones and the core pathophysiology of acromegaly.<\/span><\/p>\n



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There are diseases that do not announce themselves – they accumulate. A change in ring size, a shift in facial features, a persistent headache dismissed for years before the diagnosis finally arrives. By the time acromegaly is identified, the body has often already carried its consequences for a decade. It is a condition that demands […]<\/p>\n","protected":false},"author":5,"featured_media":21489,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1653],"tags":[6165,6166,6157,1738],"class_list":["post-21488","post","type-post","status-publish","format-standard","has-post-thumbnail","category-interview","tag-aart-jan-aj-van-der-lely","tag-acromegaly","tag-gaem","tag-interview"],"acf":[],"_links":{"self":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/21488","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/comments?post=21488"}],"version-history":[{"count":2,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/21488\/revisions"}],"predecessor-version":[{"id":21722,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/21488\/revisions\/21722"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/media\/21489"}],"wp:attachment":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/media?parent=21488"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/categories?post=21488"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/tags?post=21488"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}