Random Growth Hormone Research Articles

12533 A Rare Case of a Growth Hormone Releasing Hormone-Secreting Pulmonary Carcinoid Tumor: Clinical Presentation and Management

Abstract Disclosure: I. Yaseen: None. C. Woods: None. D.B. O'Shea: None. R.K. Crowley: None. D. O'Toole: None. H. Almeamar: None. We present a rare case of an ectopic Growth Hormone Releasing Hormone (GHRH)-secreting pulmonary neoplasm manifesting with acromegaly. A 62-year-old woman presented with Bell’s palsy. An incidental lung mass proved to be a 17.5cm carcinoid tumor, DOTATOC-avid, with bony and liver metastases, Ki67 1% on lung and bone biopsy. After pulmonary service referral to endocrinology, she was noted to have acromegalic features, the most troubling of which was macroglossia associated with mouth ulceration. IGF1 was 549ug/L (57-186), random growth hormone was 225. GHRH in serum was 1937ng/ml (reference < 60). MR Pituitary revealed hyperplasia.The multidisciplinary team discussion was that the lung lesion was unresectable, therefore she was commenced on somatuline autogel 120mg every 28 days and an opinion requested re suitability for Peptide Receptor Radionuclide Therapy. After 6 months of therapy IGF1 normalised to 90ug /L. GHRH reduced to 1056ng/L.Imaging at 8 months showed stability of lung primary and bone / liver metastases, with no benefit likely from PRRT at this time. This case highlights the importance of considering endocrine syndromes in the setting of a lung mass. The prevalence of acromegaly in Ireland is 69 per million people; this is the second Irish case known of GHRH-associated GH excess. Ectopic GH-secreting pulmonary tumors are a rare but important differential in patients presenting with acromegalic features. Complete surgical resection can be curative, underlining the significance of a multidisciplinary approach in management, encompassing endocrinology, thoracic surgery, and pathology. This case of successful medical management adds to the limited literature on such tumors and underscores the potential for non-pituitary neoplasms to cause systemic endocrinopathies. Presentation: 6/1/2024

Pseudoacromegaly-A challenging entity in the endocrine clinic: A systematic review.

Pseudoacromegaly 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. PubMed/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. Of 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. Pseudoacromegaly 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.

Consensus on criteria for acromegaly diagnosis and remission

PurposeThe 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy.MethodsFifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes.ResultsIn a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches.ConclusionConsensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.

SAT604 An Extensively Invasive Giant Prolactinoma Associated With CDH23 Mutation

Abstract Disclosure: B. Alghamdi: None. L.A. Alobaid: None. M. Alswailem: None. E.O. Othman: None. M. Dababo: None. O. Alsagheir: None. A.S. Alzahrani: None. Pituitary adenomas (PA), renamed recently pituitary neuroendocrine neoplasms, are common and prolactinomas are the most common subtype of these tumors. The vast majority of PA are sporadic but they can also be due to germline (∼ 5%), mosaic (<1%) or somatic mutations (∼40%). PA with germline mutations might be part of a syndrome such as MEN1 or apparently sporadic, either due to de novo mutations or because of low penetrance of the underlying gene (e.g. AIP). Among the several genes that have been identified, CDH23 was reported to be associated with familial PA in a single study that included 12 families with PA (33% of them had CDH23 variants) and 125 sporadic PA (15 (12%) of them harbored CDH23 variants) compared to only 0.8% of 260 healthy controls. In this report, we describe a middle-aged woman who was incidentally found to have a huge macroprolactinoma with extensive invasion. Genetic testing revealed a novel germline CDH23 variant. Case report: A 53-year-old woman who with hypertension, diabetes and chronic renal insufficiency diagnosed 4 years before. She accidentally fell down on the back of her head. A CT and subsequent MRI scans of the head showed a huge mass extensively involving the Sella, suprasellar space, the cavernous sinuses and middle fossae. This mass extends inferiorly to the sphenoid and parasellar sinuses, nasopharynx, and appears at the nostrils. The patient reported chronic headaches, snoring and congested nose, and worsening hearing and vision over the last 4 years. She denied history of galactorrhea and her periods ceased 8 years before. She never got married and has no children. Her family history is negative for any pituitary or other tumors. The mass was initially thought to be a nasopharyngeal cancer. However, a bedside biopsy from the protruding mass in the right nostril revealed a pituitary tissue strongly positive for prolactin and weakly positive for growth hormone (GH). An undiluted serum prolactin level was 47 ug/l (3.4-24). After several dilutions for the hook effect, the level was 578,000 ug/l (3.4-24). IGF-1 253 ng/ml (93-245), random GH 4.7 ng/ml, TSH 1.9 mU/l (0.4-4.2), FT4 11.4 pmol/l (12-22), AM cortisol 235 nmol/l (159-620), ACTH 27.6 (5-60). Whole exome sequencing followed by Sanger sequencing revealed a novel variant in CDH23 (c.2621C>A, p.Ala874Asp). Several in silico analyses suggest that this variant is pathogenic and it is assigned variant of unknown significance (VUS) according to American College of Medical Genetics (ACMG) classification. It is not reported in EXAC and 1000G databases. All other known PA-associated genes and cancer-associated genes revealed no pathogenic variants. Conclusion: We report a massive prolactinoma, likely due to a novel CDH23 variant. This is the second report on the likely pathogenic role of this gene in PA. In the case reported here, it is associated with a huge and highly invasive pituitary macroadenoma. Presentation: Saturday, June 17, 2023

Predictors of Remission of Acromegaly following Surgical Treatment in Growth Hormone-Secreting Pituitary Adenoma.

Background and Objective Surgery is the treatment of choice for growth hormone (GH)-secreting pituitary adenoma. The remission of random GH depends on various factors. We aimed to evaluate the predictors related to remission of random GH following surgical treatment. Methods We collected the data retrospectively from the chart review from a single unit of neurosurgery. The diagnostic criteria for remission were a random GH < 1 ng/mL or nadir GH < 0.4 ng/mL after an oral glucose tolerance test. Results Data from a total of 110 (females 62 [56.4%]) patients were available for follow-up and were analyzed. The mean age was 36.5 years (14-69 years). Vision impairments were seen in 39 (35.5%) patients. The mean duration of symptoms before surgery was 34 months. The mean volume of the tumor was 7.2 mL (0.44-109.8 mL). Knosp grade 3 and 4 tumors were seen in 41.5% of cases. The mean preoperative random GH level was 68.9 ng/mL. Transsphenoidal surgery was done in 107 (97.3%) cases. The gross total resection could be done in 36 (32.7%) cases. At 3 months, 25 (26%) patients had a biochemical remission. In univariable analysis, lower Knosp grade, preoperative GH level < 40 ng/mL, gross total resection, and male gender were associated with remission at 3 months. In regression analysis, preoperative GH and male gender were related to remission at 3 months. Conclusion The preoperative GH level < 40 ng/mL is associated with higher chances of remission after surgery for GH-secreting pituitary adenoma.

Intraoperative Prediction of Long-Term Remission in Acromegaly.

The features of long-term remission in acromegaly adenomectomy are incompletely understood. An intraoperative predictor for long-term outcome would be valuable for assessing resection of growth hormone (GH)-secreting tumors in real-time. To evaluate whether intraoperative GH measurement could predict long-term outcomes for acromegaly. In 47 patients, peripheral blood GH levels were measured thrice intraoperatively: once before tumor dissection, once during tumor dissection, and once after tumor dissection. Long-term remission was defined by age-appropriate, normalized insulin-like growth factor-1 at most recent follow-up and a random GH less than 1.0 ng/mL. Patients were only considered to be in long-term remission without the use of postoperative medical therapy for acromegaly or radiation therapy. The median length of follow-up was 4.51 (range: 0.78-9.80) years. Long-term remission was achieved in 61.7% (29/47) of operations. Like previous studies, cavernous sinus invasion (odds ratio [OR]: 0.060; 95% CI: 0.014-0.260; P value < .01), suprasellar extension (OR: 0.191; 95% CI: 0.053-0.681; P value<.01), and tumor size greater than 1 cm (OR: 0.177; 95% CI: 0.003-0.917; P value = .03) were associated with not being in long-term remission. The minimum GH measured intraoperatively predicted long-term outcome (area under the curve: 0.7107; 95% CI: 0.537-0.884; P value < .01). The odds ratio of remission in patients with the lowest quartile minimum intraoperative GH compared with patients with the highest quartile minimum intraoperative GH was 27.0 (95% CI: 2.343-311.171; P value < .01). Minimum intraoperative GH may predict long-term outcome for acromegaly, which in principle could provide the pituitary neurosurgeon with real-time feedback and inform intraoperative decision making.

PMON49 Checkpoint Inhibitor Induced Hypophysitis with Growth Hormone Deficiency and Implications for the Treatment of ACTH Deficiency

Abstract Background/Purpose Hypophysitis is a known complication of immune checkpoint inhibitor (ICI) therapies used in the treatment of malignant cancers. In general, central adrenal insufficiency (AI) and hypothyroidism are the most recognized deficiencies following a diagnosis of ICI induced hypophysitis. As a result, other hypothalamic-pituitary axes (HPAs) are either incompletely evaluated or are disregarded from a therapeutic standpoint. Of particular importance is the growth hormone axis which is well established to affect tissue level metabolism of cortisol and cortisone through its effect on 11 beta hydroxysteroid dehydrogenase in target tissues. Our hypothesis is that growth hormone deficiency is also present in ICI induced hypophysitis. Methods We queried current and legacy electronic medical records of patients who received ICI for clinical notes mentioning adrenal insufficiency and concern for hypophysitis using the EMERSE tool. Patients with ICI exposure were included if they had 2 of the following 3 criteria; new onset central AI as defined by a low ACTH and cortisol, pituitary imaging suggestive of hypophysitis, or clinical presentation concerning hypophysitis. Patients were excludedfrom the analysis if there was a history of brain irradiation or in whom the diagnosis was not clear due to high dose steroid exposure prior to biochemical evaluation. Results Twenty-nine patients met inclusion criteria. Out of 29 patients, 16 underwent testing of the growth hormone axis with IGF-1 (11) and/or random growth hormone level (5). Seventeen patients (59%) had biochemical evidence of deficiency of 3 or more HPAs. Twenty-six patients (90%) had biochemical evidence of 2 or more PHAs. Two patients only underwent evaluation of 2 pituitary axes so it is unknown if they indeed suffered from panhypopituitarism. Most patients (28/29) were prescribed hydrocortisone for AI with an average dose of 20 mg per day. Conclusions Our findings are suggestive that growth hormone deficiency may be present in ICI induced hypophysitis. This finding holds implications for cortisol replacement therapy for coexisting AI. When one considers the average adrenal cortisol production is 5.7–7.4 mg/m2/day or 9.5–9.9 mg/day, 20 mg of daily cortisol replacementmay be too high in the face of concomitant growth hormone deficiency. Practice changes may include lower doses ofhydrocortisone replacement or adjustment to cortisone acetate which has been shown to have more favorable effectson tissue level metabolic effects. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Determinants of immediate and long-term remission after initial transsphenoidal surgery for acromegaly and outcome patterns during follow-up: a longitudinal study on 659 patients.

Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features. This prospective, single-center, longitudinal cohort study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors' institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission. A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524-5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522-6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006-1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224-3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified. Cavernous sinus invasion, age at diagnosis, and sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity.

High Prevalence of Vertebral Fractures Associated With Preoperative GH Levels in Patients With Recent Diagnosis of Acromegaly.

Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease. We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly. We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data. We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL. For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly.

Correlation Between Clinical and Biochemical Markers in Patients With Acromegaly on Different Modalities of Treatment.

BackgroundAcromegaly is a disabling disease caused by growth hormone (GH) over-secretion, associated with increased morbidity and mortality through different metabolic and somatic consequences involving soft tissue, acral overgrowth, and skin thickening, which will lead to different clinical manifestations. The study aimed to assess the correlation between biochemical markers of acromegaly with different clinical findings and biochemical control with the clinical findings.MethodsA cross-sectional study was done on 56 patients with acromegaly attending a tertiary center for diabetes, endocrine, and metabolism in Southern Iraq Basrah. They were 32 (57.1%) males. Fatigue, headache, excessive sweating, joint pain, backache, soft tissue swelling, numbness, snoring, and visual problems were assessed on a four-point Likert scale. In addition, biochemical dynamic GH testing was done using a five-point random GH curve and/or standard GH suppression under the oral glucose tolerance test (OGTT).ResultsNo significant correlation was found between symptoms severity and five-point GH parameters in respect of mean, peak, and nadir. Only backache showed a significant correlation with GH under OGTT suppression parameters in respect to mean, peak, and nadir (P-values < 0.01, < 0.01, and < 0.01), respectively. No particular biochemical control cut-off value in the 9 am random GH, mean five-point GH curve, or nadir GH under OGTT was correlated with the degree of severity for any of the clinical symptoms, as there was no difference between the biochemically controlled and uncontrolled groups in respect to any of the clinical symptom’s severity scale.ConclusionOnly backache correlated with the biochemical tests of disease activity in the form of GH under OGTT. It appears in this study that the severity of the clinical symptoms does not correlate with biochemical control so that thorough evaluation and treatment of clinical complaints besides biochemical control is an essential part of the management plan in patients with acromegaly.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency

Background Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. Methods This is a retrospective chart review of all random GH levels obtained in neonates ≤28 days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. Results The study included 138 neonates with the mean age of 9.07 ± 6.6 days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73 ± 1.19 ng/ml) as compared to the ARF-GHD (9.4 ± 7.96 ng/ml, p = .002) and non-GHD groups (14.86 ± 14.42 ng/ml, p = .027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5 ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. Conclusion This study demonstrates that random GH levels obtained in the first 28 days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

Soluble Alpha Klotho in Acromegaly: Comparison With Traditional Markers of Disease Activity.

ContextSoluble alpha klotho (sαKL) has been linked to growth hormone (GH) action, but systematic evaluation and comparisons with traditional biomarkers in acromegaly are lacking.ObjectiveTo evaluate the potential of sαKL to aid classification of disease activity.MethodsThis retrospective study at 2 academic centers included acromegaly patients before surgery (A, n = 29); after surgery (controlled, discordant, or uncontrolled) without (B1, B2, B3, n = 28, 11, 8); or with somatostatin analogue treatment (C1, C2, C3, n = 17, 11, 5); nonfunctioning pituitary adenomas (n = 20); and healthy controls (n = 31). sαKL was measured by immunoassay and compared with traditional biomarkers (random and nadir GH, insulin-like growth factor I [IGF-I], IGF binding protein 3). Associations with disease activity were assessed.ResultssαKL was correlated to traditional biomarkers, particularly IGF-I (rs=0.80, P <0.0001). High concentrations before treatment (A, median, interquartile range: 4.04 × upper limit of normal [2.26-8.08]) dropped to normal after treatment in controlled and in most discordant patients. A cutoff of 1548 pg/mL for sαKL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4%-99.9%) sensitivity and 100% (77.1%-100%) specificity. sαKL was below the cutoff in 84% of the discordant subjects. In the remaining 16%, elevated sαKL and IGF-I persisted, despite normal random GH. Sex, age, body mass index, and markers of bone and calcium metabolism did not significantly affect sαKL concentrations.ConclusionOur data support sαKL as a biomarker to assess disease activity in acromegaly. sαKL exhibits close association with GH secretory status, large dynamic range, and robustness toward biological confounders. Its measurement could be helpful particularly when GH and IGF-I provide discrepant information.

Prevalence and outcome of comorbidities associated with acromegaly.

Acromegaly is associated with various comorbidities, such as arterial hypertension (aHT), type 2 diabetes mellitus (DM2), obstructive sleep apnoea syndrome (OSAS), carpal tunnel syndrome (CTS) and polyposis coli. For therapeutic decisions, it is essential to know if, and to what extent, these associated morbidities are reversible or preventable. The aim of this study is to assess the prevalence and course of aHT, obesity, OSAS, CTS, DM2 and polyposis coli in acromegalic patients. The following criteria for inclusion in this database study were used: treatment for acromegaly at the authors' institutions; full endocrinological and radiological work- and follow-up; screening for aHT, DM2, CTS, OSAS, obesity and polyposis coli. All patients were followed-up for > 3months, and treatments were indicated with the intent of biochemical remission (normal IGF-1 and random growth hormone level). Sixty-three patients were included. Twelve (19%), 45 (71%) and 6 (10%) patients harboured micro-, macro- and giant adenomas, respectively. Nineteen tumours (30%) invaded the cavernous sinus. Mean tumour volume was 5.4 cm3. Mean follow-up time was 42months. Sixty-one (97%) patients had transsphenoidal surgery; two patients only had drug therapy. Surgery led to remission in 31 (51%) patients. Intracavernous growth and larger tumour volume were negative predictors for cure. Drug therapy lead to remission in 22 (73%) patients within a mean follow-up of 54months. The pretherapeutic prevalence of associated morbidities was as follows: aHT, 56%; DM2, 25%; OSAS, 29%; CTS, 29%; polyposis coli, 5%. There were neither age nor gender preferences for the respective prevalences. Surgery leads to remission of aHT and DM2 in 6% and 25%, respectively. Additional drug therapy resulted in remission of aHT, DM2 and CTS in 17%, 14% and 14%, respectively. Other associated morbidities persisted regardless of therapeutic efforts. Even if criteria for remission were not met, no new comorbidities of acromegaly developed during follow-up. Treating acromegaly may relieve threatening associated morbidities such as aHT and DM2; nevertheless, only few comorbidities are reversible, which highlights the importance of treating acromegaly as early as possible.

First but not second postoperative day growth hormone assessments as early predictive tests for long-term acromegaly persistence

PurposePostoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence.Materials and methodsForty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH.ResultsAfter a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility.ConclusionsD1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.

In patients with controlled acromegaly, indices of glucose homeostasis correlate with IGF-1 levels rather than with type of treatment.

Acromegaly is accompanied by abnormalities in glucose and lipid metabolism which improve upon treatment. Few studies have investigated whether these improvements differ between treatment modalities. This study aimed to compare glucose homeostasis, lipid profiles and postprandial gut hormone response in patients with controlled acromegaly according to actual treatment. Cross-sectional study at a tertiary care centre. Twenty-one patients with acromegaly under stable control (ie insulin growth factor 1 [IGF1] levels below sex- and age-specific thresholds and a random growth hormone level <1.0µg/L) after surgery (n=5), during treatment with long-acting somatostatin analogues (n=10) or long-acting somatostatin analogues+pegvisomant (n=6) were included. Glucose, insulin, total cholesterol and high-density lipoprotein-cholesterol were measured in fasting serum samples. Glucose, insulin, triglycerides, glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were measured during a mixed meal test. Insulin sensitivity was evaluated by a hyperinsulinaemic-euglycaemic clamp. There were no significant differences in glucose tolerance, insulin sensitivity or postprandial gut hormone responses between the three groups. Positive correlations between IGF1 levels and HbA1c, fasting glucose and insulin levels and postprandial area under the curve (AUC) of glucose and insulin and also an inverse association between IGF1 and glucose disposal rate were found in the whole cohort (all p<.05, lowest p=.001 for postprandial AUC glucose with rs =0.660). In this cross-sectional study in patients with controlled acromegaly, there were no differences in glucose homeostasis or postprandial substrate metabolism according to treatment modality. However, a lower IGF1 level seems associated with a better metabolic profile.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency.

Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. This is a retrospective chart review of all random GH levels obtained in neonates ≤28days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. The study included 138 neonates with the mean age of 9.07±6.6days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73±1.19ng/ml) as compared to the ARF-GHD (9.4±7.96ng/ml, p=.002) and non-GHD groups (14.86±14.42ng/ml, p=.027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. This study demonstrates that random GH levels obtained in the first 28days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

The impact of variations in laboratory measurements of IGF-1 and random growth hormone on the classification of acromegaly disease activity status: Lessons from the UK Acromegaly Register Reference Laboratory

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Long-term endocrinological outcomes of gamma knife radiosurgery in acromegaly patients

Gamma knife radiosurgery (GKS) is a treatment option for recurrent or persistent disease in patients with acromegaly. ObjectiveWe aimed to retrospectively evaluate acromegaly patients who had undergone GKS in terms of pituitary hormone status, efficacy of GKS, and prognostic factors. MethodOne-hundred and ten acromegaly patients who underwent GKS, and who were referred to our outpatient endocrinology clinic between 2007 and 2017, were included in the study. Anterior pituitary hormones and radiology imaging during follow-up were recorded. Remission for acromegaly was defined as a normal insulin-like growth factor 1 (IGF-1) level adjusted for age and gender, and a random growth hormone (GH) level < 1 ng/ml. Endocrine control was defined as normal GH and IGF-1 levels under medication. ResultsAfter a mean follow-up of 6.5 ± 4.7 years; remission, endocrine control, and uncontrolled status was observed in 16.4%, 60%, and 23.6% of patients; respectively. Adenoma volume was decreased after GKS (P < .0001). Remnant adenoma diameter was higher in the uncontrolled group compared to the remission and endocrine control group. The presence of tumor extension was associated with disease status (P = .03) and higher initial GH and IGF-1 levels. The mean time after GKS to remission was 26.5 months. Six (5.4%) patients had new-onset pituitary deficiency after GKS. In the multivariate analysis, pre-GKS IGF-1 levels and patient's age were associated with disease status. ConclusionGKS is an effective adjuvant treatment with minimal side effects to control GH and IGF-1 levels, increase remission rates, endocrine control, and reduce tumor diameter in persistent acromegaly patients after surgery.

Reappraisal of microscopic microsurgical transsphenoidal surgery for GH-secreting pituitary macroadenoma in patients with acromegaly: Historical data from Vietnam (2010–2013)

ObjectiveIn Vietnam, microscopic transsphenoidal surgery has been implemented to treat acromegaly patients since 2000. However, no specific outcome studies have been conducted. We assess outcomes of this technique and factors associated with remission. MethodsThis prospective observational study was conducted in 43 patients with acromegaly resulting from Growth Hormone (GH)-secreting pituitary macroadenoma. The primary outcome of interest was remission status, as defined by random GH levels below 2.5 ng/mL and Insulin-like Growth Factor-1 (IGF-1) within the normal range three months post-operation. ResultsThe proportion of patients with remission three months after surgery was 69.8% with a 95% confidence interval (CI) = 53.9–82.8%. The proportions of residual tumors three months after surgery in the remission and non-remission groups were 10.0% (3/27) and 23.1% (3/10), respectively, but there was no significant difference between these proportions (Fisher's exact test, p = 0.35). In a multivariate logistic regression analysis adjusted for sex and age, remission was associated with the absence of cavernous sinus invasion, with an odds ratio (OR) = 5.2 (95% CI = 1.1–26.5). In addition, remission was also associated with a post-operative GH level < 2.5 ng/mL (OR = 7.4, 95% CI = 1.1–48.0). ConclusionWe report that the proportion of patients with disease remission three months after surgery was high, indicating that microscopic transsphenoidal surgery was efficacious. More studies should be conducted to assess outcomes of various acromegaly treatment methods in the current context of Vietnam.