Progression of Acromegalic Arthropathy in Long-Term Controlled Acromegaly Patients

9 Years of Longitudinal Follow-Up

Iris C.M. Pelsma; Nienke R. Biermasz; Wouter R. van Furth; Alberto M. Pereira; Herman M. Kroon; Margreet Kloppenburg; Kim M.J.A. Claessen

Disclosures

J Clin Endocrinol Metab. 2021;106(1):188-200. 

In This Article

Abstract and Introduction

Abstract

Context: Joint complaints in patients with acromegaly are common, although the long-term disease course is largely unknown.

Objective: This study aims to evaluate the long-term course of acromegalic arthropathy.

Design and Setting: A prospective longitudinal cohort study was conducted in controlled acromegaly patients followed at a tertial referral center, with 3 study visits: at baseline and after a median of 2.6 and 9.1 years.

Patients: We included 31 patients with biochemically controlled acromegaly for 2 or more years (49% female; median age, 60 years) at baseline.

Main Outcome Measures: Radiographic arthropathy of the knee, hip, hand, and cervical and lumbar spine were evaluated using Kellgren and Lawrence (KL) scores, developed for assessment of primary osteoarthritis (OA). Radiographic progression was defined as a KL increase above the smallest detectable change. Joint symptoms were assessed using self-reported questionnaires. Progression was defined using existing clinically important cutoff values. Risk factors for progression were investigated using a multivariable model.

Results: All patients had definite radiographic OA at 1 or more joints at baseline. Radiographic progression was observed in 29%, 48%, 84%, and 94% of patients in the knees, hips, hands, and axial joints, respectively. Deterioration in hand-related pain and function was observed in 10 (32.3%) and 11 patients (35.5%), respectively. Solely baseline KL scores of the hip were associated with hip OA progression (OR 1.88; 95% CI, 1.09–3.16).

Conclusions: Acromegalic arthropathy showed significant radiographic progression over 9.1 years of follow-up in patients in remission, whereas clinical progression was observed less frequently. Future studies should focus on adequate prevention and treatment strategies of acromegalic arthropathy.

Introduction

Acromegaly is caused by a growth hormone (GH)-producing pituitary adenoma in most cases, resulting in pathologically high GH and insulin-like growth factor-1 (IGF-1) levels.[1] Despite the amelioration of clinical symptoms and life expectancy following the reversal of GH excess, several consequences of acromegaly persist despite achievement of biochemical control.[2] One of these long-term complications is acromegalic arthropathy, significantly impairing quality of life (QoL).[3–5]

The prevalence of arthropathy is increased in patients with acromegaly compared to the general population, despite biochemical disease control, and manifests with a symptomatic arthropathy in the majority of patients, and radiographic osteoarthritis-like deformities in nearly all patients.[5] Clinically, acromegalic arthropathy is thought to be a 2-phased process.[6,7] During the first, "reversible" phase, hypertrophy and increased laxity of the periarticular ligaments result in a limited range of motion.[6] Unfortunately, if the GH excess persists, the changes in joint structure become irreversible.[7] At this point, acromegalic arthropathy—at least partly—resembles primary osteoarthritis (OA), and therefore is regarded as a degenerative joint disorder.[8–11] Radiographically, acromegalic arthropathy is characterized by severe osteophytosis (OP or osteophytes, ie, bony enlargements at the joint margins) and widened joint spaces, indicating cartilage hypertrophy,[6,11] being largely irreversible following biochemical disease control.[7,12] In the minority of acromegaly patients, joint space narrowing (JSN) reflecting cartilage loss—more characteristic of primary OA—is also observed, which has previously been associated with higher cumulative GH exposure or delayed postoperative cure.[13]

Acromegalic arthropathy has been associated with known risk factors for primary OA, such as female sex, increased age, and increased body mass index (BMI), but also with acromegaly-specific risk factors, including uncontrolled disease duration and enhanced GH responsiveness due to the deleted exon 3 GH receptor polymorphism (d3-GHR). Studies on the relationship with pretreatment IGF-1 levels are, however, equivocal.[14–20]

In our previous short-term follow-up study among long-term controlled acromegaly patients, progressive radiographic OA was observed in more than 70% of patients after 2.6 years of persistent remission, of whom older patients and patients with higher GH/IGF-1 activity showed the highest radiographic progression rates.[21] Interestingly, most radiographic OA progression was reported in pharmacologically treated patients compared to surgically cured patients, probably caused by slightly persistent disease activity in the former group. Moreover, a considerable proportion of patients showed clinical progression over time, without any relationship between the clinical and radiographic course of arthropathy.[22] To date, prolonged follow-up of acromegalic arthropathy is scarce. The Leiden acromegaly cohort is a unique cohort with respect to long-term longitudinal data on arthropathy. In the present follow-up study, we evaluated the 9-year clinical and radiographic course of arthropathy and its risk factors in a cohort of long-term, well-controlled acromegaly patients.

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