Long-term follow-up of five untreated acromegalic patients

1984 ◽  
Vol 106 (4) ◽  
pp. 437-442 ◽  
Author(s):  
J.W. R. Nortier ◽  
R.J. M. Croughs ◽  
J. H. H. Thijssen ◽  
F. Schwarz
Keyword(s):  
Tolerance Test ◽  
Clinical Activity ◽  
Oral Glucose ◽  
List Type ◽  
Treatment Protocols ◽  
Gh Secretion ◽  
Spontaneous Course ◽  
Long Term Follow Up ◽  
Plasma Gh

Abstract. The present study describes the clinical, biochemical and radiological follow-up of 5 patients with acromegaly, selected from a group of 53 patients, who did not receive treatment during a follow-up period of 5–16 years. The characteristics of these patients included: 1) older age (4 cases), 2) a long history of mild symptoms and signs (4 cases), 3) absence of diabetes mellitus (5 cases), 4) relatively low plasma GH levels (3 cases). The following observations were made during follow-up: clinical activity remained constant in 3 patients and lessonned in 2 patients, the lateral fossa area as calculated from a plain lateral X-ray of the skull remained constant and plasma GH levels measured during an oral glucose tolerance test remained constant in 3 cases, decreased substantially in one case and reached low levels in another case. In this last patient a reproducible increase of plasma GH was found after oral administration of a single dose of 2.5 mg bromocriptine, suggesting complete normality of GH secretion. It is concluded that acromegaly not necessarily progresses in all patients. The results re-emphasize the importance of taking the spontaneous course of pituitary adenomas into account when assessing the effect of various treatment protocols.

Seven cases with Williams-Beuren syndrome: endocrine evaluation and long-term follow-up

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Ayla Güven
Keyword(s):  
Glucose Tolerance ◽  
Tolerance Test ◽  
Hormone Deficiency ◽  
Overt Hypothyroidism ◽  
Oral Glucose ◽  
Long Term Follow Up ◽  
Male Patients ◽  
The Mean

AbstractBackground:Endocrine evaluation and long-term follow-up of seven (six male) patients with Williams-Beuren syndrome (WBS) are given.Method:Data were obtained from patients’ medical records. All patients underwent hormonal analyses and four of them underwent oral glucose tolerance test (OGTT).Results:They all had mild hypercalcemia. Three of them had overt hypothyroidism while subclinical hypothyroidism was detected in three patients. Four patients had thyroid hypoplasia and one had thyroid agenesis. Growth hormone deficiency (GHD) was determined in one patient. Impaired glucose tolerance (IGT) was found in three adolescents. All adolescents had early-onset puberty. The follow-up duration was 5.7±2.1 years. The mean growth velocity (GV) was 12.9±7.2 cm and 7.6±2 cm at the end of the first and second years of therapy, respectively. All patients had neurodevelopment retardation and were continuing to special education.Conclusions:Thyroid hypoplasia is common and agenesis can be seen in patients with WBS; therefore, thyroid hormones should be measured in the newborn period and annually. GHD should be kept in mind in patients with decreased GV. IGT might be detected in patients with WBS even in adolescence.

scholarly journals Long-Term Follow-Up Results of Postoperative Radiotherapy in 36 Patients with Acromegaly

2000 ◽  
Vol 85 (7) ◽  
pp. 2476-2482 ◽  
Author(s):  
Nienke R. Biermasz ◽  
Hans van Dulken ◽  
Ferdinand Roelfsema
Keyword(s):  
Serum Insulin ◽  
Effective Intervention ◽  
Clinical Activity ◽  
Oral Glucose ◽  
Pituitary Hormone ◽  
Age Related ◽  
Igf I ◽  
Long Term Follow Up

In acromegaly, pituitary irradiation is a slow, but effective, intervention in decreasing GH concentration. Few studies addressing the outcome of radiotherapy have used the currently accepted strict criteria for remission in the analysis of data. These studies report a low percentage of remission after radiotherapy. Doubt has especially been raised as to whether radiotherapy is effective in normalizing serum insulin-like growth factor (IGF)-I concentration. We analyzed the long-term follow-up data of postoperatively administered radiotherapy in 36 patients with postoperative persistent acromegaly, using both the normalization of GH suppression during oral glucose loading (GTT) and the normalization of IGF-I concentration as criteria for remission. Before radiotherapy, mean suppressed GH was 9.8 ± 1.9 mU/L (n = 31), and mean IGF-I concentration was 44.3 ± 3.9 nmol/L, equivalent to + 4.76 ± 0.78 age-related IGF-I sd score (n = 13). The median radiation dose was 40 Gray (range, 25–50 Gray). At 5, 10, and 15 yr follow-up, 18 out of 30 patients (60%), 23 out of 31 patients (74%), and 16 out of 19 patients (84%), respectively, achieved normal serum IGF-I concentration. At the last assessment of all patients, after a mean follow-up period of 139 ± 12 months, 27 out of 36 (75%) patients had a normal IGF-I concentration without additional medication, whereas 5 patients still required treatment with octreotide. Remission, as judged by normalization of GH suppression during GTT, was documented in 65% of patients from 2–5 yr after radiotherapy (n = 34); in 69% of patients, up to 10 yr after radiotherapy (n = 29); and in 71% of patients, up to 15 yr post irradiation (n = 17). At the latest assessment, a mean of 125± 11 months after radiotherapy, 71% of patients (n = 35) were in remission, as defined by normal suppression of serum GH during GTT. Remission, as judged by normalization of both GTT and IGF-I, was found in 40% of patients 3–5 yr after radiotherapy (n = 30); in 61% of patients, 6–10 yr after radiotherapy (n = 28); in 65%, after 11–15 yr after radiotherapy (n = 17); and in 63% of patients, at the end of the follow-up period (n = 35). Substitution of one or more pituitary hormone deficiencies was required in 11% of patients postoperatively; in 29%, 5 yr after radiotherapy; in 54%, 10 yr after radiotherapy; and in 58%, more than 15 yr after radiotherapy. Our findings support the use of radiotherapy as an effective intervention in the treatment of residual clinical activity of disease after surgery for acromegaly.

Gestational diabetes mellitus: are mothers being followed-up? A retrospective study

2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X697469
Author(s):  
Rebecca Ward ◽  
Fahmy W Hanna ◽  
Ann Shelley-Hitchen ◽  
Ellen Hodgson ◽  
Adrian Heald ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Median Time ◽  
Post Partum ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Tertiary Referral Centre ◽  
Alternative Approach ◽  
Nice Guidance ◽  
History Of

BackgroundWomen with gestational diabetes (GDM) have an elevated risk of developing type 2 diabetes (T2DM). NICE Guidance recommends women who develop GDM are screened 6 weeks post-partum and annually thereafter.AimTo evaluate conformity to guidance of screening in women with GDM by 6-week post-partum fasting plasma glucose (FPG) and annual FPG and determine time between delivery and development of T2DM.MethodRecords at a tertiary referral centre were used to identify women (n = 54) diagnosed with GDM by antenatal oral glucose tolerance test between July 1999 and January 2007. Data from laboratory records were used to collect investigations of glycaemic status during the follow-up period (median follow-up 12.4 years, range 9.5–17.1 years).ResultsOf 252 women, 102 (40.2%) did not have a FPG at 6 weeks (+/−2 weeks). Of these, median time to first test was 1.2 years (range 0.04–10.8 years), with only 43.1% followed-up within 1 year. In those who had a 6-week FPG, 17 (11.3%) women had no further tests. A total of 84 (33% of those with gestational diabetes in the index pregnancy) women were diagnosed with T2DM; median time from delivery to diagnosis was 5.2 years (range 0.35–15.95). We found the only significant factor for a follow-up test at 1-year post-partum was the use of insulin.ConclusionOur data suggest an alternative approach is needed for monitoring women with a history of GDM. This needs to be appropriate for a generally healthy group in which traditional screening mechanisms may not be adequate or sufficient.

scholarly journals Years of potential life lost in pre-diabetes and diabetes mellitus: data from a 40-year follow-up of the Israel study on Glucose intolerance, Obesity and Hypertension

2021 ◽  
Vol 9 (1) ◽  
pp. e001981
Author(s):  
Micha Rapoport ◽  
Angela Chetrit ◽  
Dror Cantrell ◽  
Ilya Novikov ◽  
Jesse Roth ◽  
...  
Keyword(s):  
Glucose Intolerance ◽  
Lifestyle Modification ◽  
Smoking Status ◽  
Age Groups ◽  
Tolerance Test ◽  
High Risk Group ◽  
Oral Glucose ◽  
Average Difference ◽  
Using Data

IntroductionWe examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up.Research design and methodsMen and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976–1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied.ResultsAt baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m2, at baseline. Adjusting for age, sex, country of origin, smoking status, BMI, and blood pressure, the average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 2.0 years (95% CI 1.2 to 2.8; p<0.001). Significant reductions of 5.9 years (95% CI 4.8 to 7.0) on average were observed for diabetes as compared with pre-diabetes and 7.9 years (95% CI 6.7 to 9.1) as compared with individuals with normoglycemia.ConclusionsThis study reveals that life expectancy of middle-aged individuals with pre-diabetes is shorter than of normoglycemic ones. These findings are especially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.

429 Long-term analysis of MASTERKEY-265 phase 1b trial of talimogene laherparepvec (T-VEC) plus pembrolizumab in patients with unresectable stage IIIB-IVM1c melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A454-A454
Author(s):  
Georgina Long ◽  
Reinhard Dummer ◽  
Douglas Johnson ◽  
Olivier Michielin ◽  
Salvador Martin-Algarra ◽  
...  
Keyword(s):  
Pigment Cell ◽  
Objective Response ◽  
Stage Iiib ◽  
List Type ◽  
Talimogene Laherparepvec ◽  
Unresectable Stage ◽  
Long Term Follow Up ◽  
Phase 1B

BackgroundPrevious findings from the MASTERKEY-265 phase 1b study showed that the combination of T-VEC and pembrolizumab was well tolerated and produced a high complete response (CR) rate of 43% in patients with advanced melanoma.1 The 3-year progression-free survival (PFS) and overall survival (OS) rates at that time were 53.6% and 71%, respectively. Here, we report the results of the long-term follow-up efficacy analyses.MethodsThe MASTERKEY-265 phase 1b trial (NCT02263508) was an open-label, single-arm study that enrolled patients who had unresectable, stage IIIB-IVM1c melanoma with injectable, measurable lesions and no prior systemic treatment. T-VEC was administered intralesionally at the approved dosing starting day 1 of week 1. Pembrolizumab (200 mg) was administered intravenously Q2W beginning on day 1 of week 6. The maximum treatment period was 2 years. The primary endpoint was dose-limiting toxicities; key secondary endpoints included objective response rate and PFS per modified irRC, OS, and safety.ResultsAs of the data cutoff (Mar 2, 2020), all 21 patients enrolled were off treatment; 6 died and 15 are in long-term follow-up. The median follow-up time was 58.6 months (range: 1.4–61.6). The CR rate remained 43% (9/21 patients). Twelve of the 13 responders (92.3%) are still in response, including all 9 patients with a CR. Median duration of response was not reached (range: 2.8+–54.3+ months). Median PFS and OS were not reached at the data cutoff. KM estimates of 4-year PFS and OS rates were 55.9% and 71.4%, respectively, which have held stable since the 3-year analysis. Patients who achieved a CR or partial response had better OS (p=0.0056) compared to those who did not respond. Median OS for non-responders was 24.4 months and was not reached for responders. No additional safety signals were detected.ConclusionsAt almost 5 years of follow-up, median PFS and OS were not reached for patients treated with the combination of T-VEC and pembrolizumab in this phase 1b study of unresectable metastatic melanoma. 92% of responders remained in response with improved OS observed in responders compared with non-responders. The corresponding randomized phase 3 trial has completed enrollment and is currently ongoing.Trial RegistrationNCT02263508Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.ReferenceLong G, Dummer R, Andtbacka R, et al. Follow-up analysis of MASTERKEY-265 Phase 1b (ph1b) trial of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). Pigment Cell Melanoma Res 2019;32:133–134.

Evaluation of selective transsphenoidal adenomectomy by endocrinological testing and somatomedin-C measurement in acromegaly

1989 ◽  
Vol 70 (4) ◽  
pp. 561-567 ◽  
Author(s):  
Marco Losa ◽  
Reinhard Oeckler ◽  
Jochen Schopohl ◽  
O. Albrecht Müller ◽  
Julia Alba-Lopez ◽  
...  
Keyword(s):  
Tolerance Test ◽  
Oral Glucose ◽  
Slow Increase ◽  
Insulin Hypoglycemia ◽  
Somatomedin C ◽  
Content Type ◽  
Gh Secretion ◽  
Effective Form ◽  
Transsphenoidal Adenomectomy ◽  
Favorable Prognostic Factor

✓ A series of 29 previously untreated patients with acromegaly underwent transsphenoidal adenomectomy. Pre- and postoperative evaluation consisted of measuring growth hormone (GH) secretory dynamics during an oral glucose tolerance test (OGTT), the insulin hypoglycemia test, and the thyrotropin- and gonadotropin-releasing hormone (TRH/GnRH) test, and by obtaining the basal somatomedin-C level. After surgery, clinical and biochemical amelioration was achieved in all but two patients. In the whole group, basal GH and somatomedin-C levels decreased from a mean (± standard error of the mean) of 52.3 ± 12.7 to 11.1 ± 6.3 ng/ml and from 7.6 ± 0.7 to 2.5 ± 0.5 U/ml, respectively. Application of different criteria of cure revealed that 19 patients (66%) had basal GH levels below 5 ng/ml, 17 patients (59%) had normal somatomedin-C values, 16 patients (55%) had complete GH suppression (< 1 ng/ml) during OGTT, and 13 patients (45%) met the above-mentioned criteria with disappearance of the paradoxical GH response to TRH/GnRH test. Evaluation of GH secretion by insulin hypoglycemia testing was useless in assessing the outcome after neurosurgery. When only patients with a normal somatomedin-C level and complete GH suppressibility during OGTT were considered “cured,” the main favorable prognostic factor was intrasellar tumor localization, since 15 (75%) of 20 patients were “cured,” as opposed to only one (11%) of nine with extrasellar extension of the adenoma. During the follow-up period, no tumor recurrence was detected in any of the “cured” patients. In these subjects somatomedin-C levels remained stable in all except two patients, who showed a slow increase within the normal range of somatomedin-C concentration. These data confirm that transsphenoidal surgery is the most effective form of treatment in previously untreated acromegalic patients and that normalization of somatomedin-C levels reflects normal GH secretion. Measurement of somatomedin-C could replace more extensive endocrinological testing during monitoring of treated acromegalic patients.

scholarly journals Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly

2006 ◽  
Vol 154 (5) ◽  
pp. 659-666 ◽  
Author(s):  
S Pekic ◽  
M Doknic ◽  
D Miljic ◽  
M Joksimovic ◽  
J Glodic ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Provocation Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Provocative Test ◽  
Gh Secretion ◽  
Control Subjects ◽  
Igf I ◽  
Secretory Capacity ◽  
Igfbp 3

Objective: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly. Design and methods: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test - oral glucose tolerance test (OGTT) and the GH provocation test - ghrelin test (1 μg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects. Results: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 μg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 μg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (±s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 ± 0.2 μg/l vs 20.1 ± 2.4 μg/l vs 31.1 ± 2.5 μg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different. Conclusions: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.

scholarly journals Basic lifestyle advice to individuals at high risk of type 2 diabetes: a 2-year population-based diabetes prevention study. The DE-PLAN intervention in the HUNT Study, Norway

2018 ◽  
Vol 6 (1) ◽  
pp. e000509 ◽  
Author(s):  
Anne Jølle ◽  
Bjørn Olav Åsvold ◽  
Jostein Holmen ◽  
Sven Magnus Carlsen ◽  
Jaakko Tuomilehto ◽  
...  
Keyword(s):  
High Risk ◽  
Sex Education ◽  
Tolerance Test ◽  
Population Based ◽  
Oral Glucose ◽  
Diabetes Incidence ◽  
Lifestyle Advice ◽  
Prevention Study ◽  
Family History Of Diabetes

ObjectiveAmong individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes.Research design and methodsAmong 50 806 participants in the HUNT3 Survey (2006–2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC ≥15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended. Among them, 2380 people without diabetes were included in the prevention study with repeated examinations and education sessions after 6, 12, and 24 months. We examined participation, diabetes incidence, glycemia, and adiposity during follow-up.ResultsOf 2380 participants, 1212 (50.9%) participated in ≥3 of the four examinations. Diabetes was detected in 3.5%, 3.1%, and 4.0% of individuals at the 6-month, 12-month, and 24-month examinations, respectively, indicating a 10.3% 2-year diabetes incidence. Mean (95% CI) increases from baseline to 2-year follow-up were 0.30 (0.29 to 0.32) percentage points (3.3 (3.2 to 3.5) mmol/mol) for Hemoglobin A1c, 0.13 (0.10 to 0.16) mmol/L for fasting serum-glucose, 0.46 (0.36 to 0.56) mmol/L for 2-hour OGTT s-glucose, 0.30 (0.19 to 0.40) kg/m2 forbody mass index (BMI) (all p<0.001) and −0.5 (-0.9 to −0.2) cm for waist circumference (p=0.004), with broadly similar estimates by baseline age, sex, education, depressive symptoms, BMI, physical activity, and family history of diabetes. Only 206 (8.7%) participants had evidence of >5% weight loss during follow-up; their fasting and 2-hour s-glucose did not increase, and HbA1c increased less than in other participants.ConclusionBasic lifestyle advice given to high-risk individuals during three group sessions with 6-month intervals was not effective in reducing 2-year diabetes risk.

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