Biochemical discrepancies in the evaluation of the somatotroph axis: Elevated GH or IGF-1 levels do not always diagnose acromegaly

Peixe, Carolina; Sánchez-García, Miriam; Grossman, Ashley; Korbonits, Márta; Marques, Pedro

doi:10.1016/j.ghir.2022.101467

Cited by 11 publications

(8 citation statements)

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“…Pseudoacromegaly cases referred to endocrinologists had more often measured IGF‐1 and OGTT‐GH, and a higher rate of combined biochemical tests. These findings support the relevance of endocrine specialists in the management of pseudoacromegaly patients, where adequate assessment of GH/IGF‐1 axis is crucial to conclusively rule out (or diagnose) acromegaly 53–55 . Endocrinologists must ensure that every pseudoacromegaly case have a normal GH/IGF‐1 axis before assuming a certain condition as the cause of acromegaloid features, 56,57 as acromegaly may coexist with other pseudoacromegaly disorders, as reported in Seip‐Berardinelli syndrome, 58 Tatton‐Brown‐Rahman syndrome, 59 pachydermoperiostosis, 60 and Klinefelter syndrome, 61 or in families with both GH‐related pituitary and non‐pituitary gigantism 62 .…”

Section: Discussionsupporting

confidence: 63%

“…However, by including only pseudoacromegaly patients who presented with a strong suspicion for acromegaly and where the pseudoacromegaly diagnosis was established, we identified and characterized the pseudoacromegaly conditions more likely to be referred to the endocrine clinic, while at the same time, we prevented the risk of including pseudoacromegaly conditions with a low likelihood to masquerade as acromegaly, 1,2 less likely to be referred to endocrinologists, as well as patients with acromegaly with apparently normal GH secretion, inappropriate/ discrepant assessment of the somatotroph axis, or with "burnt out" acromegaly. 54,[76][77][78] In summary, pseudoacromegaly is a challenging entity with pachydermoperiostosis and insulin-mediated pseudoacromegaly being the most often conditions mimicking acromegaly that may be encountered by adult and paediatric endocrinologists. Adequate assessment of the GH/IGF-1 axis by an endocrinologist is crucial to exclude acromegaly, and further work-up should be undertaken to diagnose the underlying pseudoacromegaly condition.…”

Section: Discussionmentioning

confidence: 99%

“…Also, it is worth noting that we included only pseudoacromegaly cases where an underlying disease has been elucidated, which may lead to an overrepresentation of rare causes of pseudoacromegaly, while other etiologies of pseudoacromegaly, including individuals with pseudoacromegaly of no clear cause, or even normal subjects with physical acromegalic traits, are not represented. However, by including only pseudoacromegaly patients who presented with a strong suspicion for acromegaly and where the pseudoacromegaly diagnosis was established, we identified and characterized the pseudoacromegaly conditions more likely to be referred to the endocrine clinic, while at the same time, we prevented the risk of including pseudoacromegaly conditions with a low likelihood to masquerade as acromegaly, 1,2 less likely to be referred to endocrinologists, as well as patients with acromegaly with apparently normal GH secretion, inappropriate/discrepant assessment of the somatotroph axis, or with “burnt out” acromegaly 54,76–78 …”

Section: Discussionmentioning

confidence: 99%

“…These findings support the relevance of endocrine specialists in the management of pseudoacromegaly patients, where adequate assessment of GH/IGF-1 axis is crucial to conclusively rule out (or diagnose) acromegaly. [53][54][55] Endocrinologists must ensure that T A B L E 3 Demographic, clinical, biochemical and imaging features of the pseudoacromegaly cases referred directly to endocrinologists or paediatric endocrinologists versus cases presenting to non-endocrine departments.…”

Section: Discussionmentioning

confidence: 99%

“…The chronological amplitude of the case reports should be also taken into account, as we included few cases from the decades 80 and 90, where the diagnostic work-up for acromegaly is different from recent cases, as a result of the evolution of laboratorial tests and advancement of the scientific knowledge. These aspects, together with the intrinsic limitations associated with GH and IGF-1 immunoassays, including issues on the lack of standardization between different laboratories, technical differences between manufacturers or antibodies used in the different assays, difficulties in establishing the normal reference intervals of GH and IGF-1 assays,54,63 impose some caution in the interpretation of the biochemicalrelated findings regarding the somatotroph axis in our cohort of pseudoacromegaly cases.…”

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confidence: 99%

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Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

Marques,

Sapinho,

Korbonits

2024

Clinical Endocrinology

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ObjectivePseudoacromegaly encompasses conditions with features of acromegaly/gigantism, but no growth hormone (GH) or insulin‐like growth factor‐1 (IGF‐1) excess. We aimed to review published pseudoacromegaly cases evaluated due to clinical suspicion of acromegaly.Design/PatientsPubMed/Medline search was conducted to identify reported pseudoacromegaly cases, which were systematically reviewed to ensure they met eligibility criteria: (1) presentation suggestive of acromegaly; (2) acromegaly excluded based on normal GH, IGF‐1 and/or GH suppression on oral glucose tolerance test (OGTT‐GH); (3) diagnosis of the pseudoacromegaly condition was established. Data were retrieved from each case and analysed collectively.ResultsOf 76 cases, 47 were males, mean ages at presentation and at first acromegaloid symptoms were 28 ± 16 and 17 ± 10 years, respectively. Most common conditions were pachydermoperiostosis (47%) and insulin‐mediated pseudoacromegaly (IMP) (24%). Acromegaloid facies (75%) and acral enlargement (80%) were the most common features. Measurement of random GH was reported in 65%, IGF‐1 in 79%, OGTT‐GH in 51%. GH excess was more frequently excluded based on two tests (53%). Magnetic resonance imaging (MRI) was performed in 30 patients, with pituitary adenoma or hyperplasia being reported in eight and three patients, respectively. Investigations differed between cases managed by endocrine and non‐endocrine specialists, the former requesting more often IGF‐1, OGTT‐GH and pituitary MRI.ConclusionsPseudoacromegaly is a challenging entity that may be encountered by endocrinologists. Pachydermoperiostosis and IMP are the conditions most often mimicking acromegaly. Adequate assessment of GH/IGF‐1 is crucial to exclude acromegaly, which may be better performed by endocrinologists. Pituitary incidentalomas are common and require careful judgement to prevent unnecessary pituitary surgery.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

Marques,

Sapinho,

Korbonits

2024

Clinical Endocrinology

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Long-term control of acromegaly after pituitary surgery in South-Eastern Norway

Falch,

Dupont,

Olarescu

et al. 2023

Acta Neurochir

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Purpose Sustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors. Methods Patients operated for GH-secreting pituitary adenomas between 2005–2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control. Results A total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38–59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96–0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57–1.00), p = 0.053). Conclusion In unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

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Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience

et al. 2022

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Introduction Acromegaly is a chronic disease with systemic complications. Disease onset is insidious and consequently typically burdened by diagnostic delay. A longer diagnostic delay induces more frequently cardiovascular, respiratory, metabolic, neuropsychiatric and musculoskeletal comorbidities. No data are available on the effect of diagnostic delay on skeletal fragility. We aimed to evaluate the effect of diagnostic delay on the frequency of incident and prevalent of vertebral fractures (i-VFs and p-VFs) in a large cohort of acromegaly patients. Patients and methods A longitudinal, retrospective and multicenter study was conducted on 172 acromegaly patients. Results Median diagnostic delay and duration of follow-up were respectively 10 years (IQR: 6) and 10 years (IQR: 8). P-VFs were observed in 18.6% and i-VFs occurred in 34.3% of patients. The median estimated diagnostic delay was longer in patients with i-VFs (median: 11 years, IQR: 3), in comparison to those without i-VFs (median: 8 years, IQR: 7; p = 0.02). Age at acromegaly diagnosis and at last follow-up were higher in patients with i-VFs, with respect to those without i-VFs. The age at acromegaly diagnosis was positively associated with the diagnostic delay (p < 0.001, r = 0.216). A longer history of active acromegaly was associated with a high frequency of i-VFs (p = 0.03). The logistic regression confirmed that patients with a diagnostic delay > 10 years had 1.5-folds increased risk of developing i-VFs (OR: 1.5; 95%CI: 1.1–2; p = 0.017). Conclusion Our data showed that the diagnostic delay in acromegaly has a significant impact on VF risk, further supporting the clinical relevance of an early acromegaly diagnosis.

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Biochemical discrepancies in the evaluation of the somatotroph axis: Elevated GH or IGF-1 levels do not always diagnose acromegaly

Cited by 11 publications

References 118 publications

Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway

Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience

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