Glucose-suppressed Growth Hormone Research Articles

Revisiting growth hormone nadir cut-offs for remission in patients with acromegaly.

Over the past decade, the growth hormone (GH) nadir cut-off during the oral glucose tolerance test for remission in patients with acromegaly was changed from 0.4 to 1.0 μg/L due to the limited use of ultrasensitive detection kits to measure GH levels. However, the optimal cut-off level for GH nadir remains unclear. This retrospective study aimed to investigate the association between different GH nadir cut-offs and prognosis in patients with acromegaly. A total of 285 patients with acromegaly with a glucose-suppressed GH nadir <1 μg/L at 3-6 months after trans-sphenoidal adenomectomy were divided into two groups according to the glucose-suppressed GH nadir levels at 3-6 months post-operatively (group A: <0.4 μg/L; group B: 0.4-1.0 μg/L). GH levels were measured using an ultrasensitive IRMA. The clinical, hormonal, metabolic, and neuroradiological data of the two groups were compared. Female sex, as well as confirmed macroadenomas, was significantly overrepresented in group B. The 5-year rate of patients who achieved nadir GH < 1.0 μg/L and age- and sex-matched normal IGF-1 was significantly higher in group A than that in group B. However, there was no significant difference between the two groups in metabolic parameters at 12 months post-operatively. Different GH nadir cut-offs were associated with different 5-year rates of patients who achieved nadir GH <1.0 μg/L and age- and sex-matched normal IGF-1, suggesting that a strict GH nadir threshold of 0.4 μg/L correlates better with remission.

Characteristics and treatment outcomes of micromegaly - acromegaly with apparently normal basal GH: A retrospective study and literature review.

Objective. Micromegaly describes a subgroup of patients with clinically evident acromegaly and elevated insulin-like growth factor I (IGF-I) with apparently normal basal growth hormone (bGH) and often a glucose-suppressed growth hormone (GH) of <1 ng/mL at diagnosis. It is controversial whether this condition is a distinct clinical entity or a classic acromegaly in early stages. The aim of the present article was to characterize the prevalence, clinical and biochemical characteristics, and therapeutic outcomes of micromegaly. Methods. A retrospective study of patients with an acromegaly followed ≥1 year at a tertiary center from 1995 to 2019. Patients without IGF-I or GH measurements at diagnosis were excluded. At diagnosis, bGH was considered normal if <2 ng/mL. Results. From 74 patients with acromegaly, 6 (8.1%) had normal bGH levels. There was no difference in the gender distribution, median diagnostic delay, and follow-up time between patients with normal bGH and elevated bGH. Patients with normal bGH were significantly older at time of the first acromegalic manifestation and diagnosis they had significantly lower nadir post-glucose GH and IGF-I levels, and tended to have a higher prevalence of obesity than patients with the elevated bGH. The frequency of acromegalic symptoms, signs, and other comorbidities than obesity was similar between groups. Five patients (83.3%) with normal bGH presented microadenomas. Post-operative remission and outcomes at last visit were comparable between patients with or without normal bGH. Conclusions. Normal bGH acromegaly is relatively uncommon in our patients. These patients showed differentiating characteristics from the classical acromegaly with elevated bGH. Further studies are needed to extend the knowledge about its clinical behavior, therapeutic outcomes, morbidity, and mortality.

Hypersomatotropism induced secondary polycythaemia leading to spontaneous pituitary apoplexy resulting in cure of acromegaly and remission of polycythaemia: ‘The virtuous circle’

A young man with subtle clinical features suggestive of hypersomatotropism presented with acute-onset severe headache. Relevant investigations confirmed polycythaemia and growth hormone (GH)-secreting pituitary macroadenoma with apoplexy. Secondary polycythaemia and...

Prevalence of colonic polyp and its predictors in patients with acromegaly.

Background:There are conflicting data regarding the prevalence of colorectal polyp in patients with acromegaly.Subjects and Methods:Consecutive forty-seven acromegalic patients (21 men, 26 women), with a mean age of (40 ± 12 years) attending endocrinology outpatient department underwent full colonoscopy. All the patients underwent clinical and biochemical evaluation (glucose suppressed growth hormone (GH), Insulin-like growth factor-1 [IGF-1], fasting insulin, and glucose). The control group (n = 120) for colonoscopy was adult subjects undergoing evaluation for symptoms of irritable bowel syndrome. Clinical and biochemical parameters in acromegalic patients with colonic polyp were compared to those without a polyp.Results:Patients with acromegaly had significantly higher prevalence of colonic polyp as compared to control subjects (10.6% vs. 0.8%). None of the patients with polyp had skin tags. There was no significant difference between subjects with and without colonic polyp in duration of illness, basal, and glucose-suppressed GH and most recent IGF-1. Fasting blood sugar was significantly higher (P < 0.05) in adenoma group after adjusting for age, body mass index (BMI), and insulin levels. Patients in adenoma group showed a trend toward male gender and younger age as compared to those without adenoma.Conclusions:Subjects with acromegaly as compared to control have a higher prevalence of colonic polyps. There was no association of polyps seen with age, BMI, skin tags, homeostasis model assessment of insulin resistance index, duration of disease, and basal and glucose-suppressed GH and IGF-1 levels. There were no specific predictive factors detected. Screening full colonoscopy is recommended in all cases with acromegaly.

The role of primary pharmacological therapy in acromegaly

Background and objectivesPrimary pharmacological therapy may be the only viable treatment option for many patients with acromegaly, especially those presenting with advanced disease with large inoperable tumors. Long-acting somatostatin analogs are currently the first-line treatment of choice in this setting, where they provide biochemical control and reduce tumor size in a significant proportion of patients. We herein present a brief overview of the role of primary pharmacological therapy in the treatment of acromegaly within the context of Latin America and support this with a representative case study.Case descriptionA 20 year old male presented with clinical and biochemical evidence of acromegaly. The glucose-suppressed growth hormone (GH) was 5.3 μg/L, his insulin-like growth factor-1(IGF-1) was 3.5 times the ULN and serum prolactin greater than 4,000 μg/L. Pituitary MRI revealed a large and invasive mass, extending superiorly into the optic chiasm and laterally into the left cavernous sinus. He was treated with a combination of octreotide and cabergoline with remarkable clinical improvement, normalization of GH and IGF-1 values and striking shrinkage of the adenoma.ConclusionThis case illustrates how effective the pharmacological therapy of acromegaly can be and yet at the same time, raises several important issues such as the need for life-long treatment with costly medications such as the somatostatin analogs. Access to these agents may be limited in regions where resources are restricted and clinicians face challenges in order to make the most efficient use of available options.

Serum IGF-1 In the Diagnosis of Acromegaly and the Profile of Patients with Elevated IGF-1 but Normal Glucose-Suppressed Growth Hormone

To report the utility of insulin-like growth factor-1 (IGF-1) as a single biomarker for establishing the diagnosis of acromegaly and to examine the clinical and biochemical profile of patients with an elevated IGF-1 in whom a diagnosis of acromegaly could not be confirmed by means of the oral glucose tolerance test (OGTT). Between the years 1999 and 2010, we identified 101 patients who underwent pituitary surgery and had histologically proven somatotroph adenomas (Group 1, Gr 1). We selected 149 patients with non-growth hormone (GH) secreting pituitary macroadenomas (Gr 2, n = 97) and microadenomas (Gr 3, n = 52) to serve as control subjects. In addition, we identified 34 patients with elevated IGF-1values in whom acromegaly could not subsequently be proven by the OGTT (Gr 4). IGF-1 was elevated in all patients with acromegaly prior to therapy with a median (range) standard deviation score (SDS) of +9.52 (+2.34 to +9.2), compared to SDS -1.46 (-2.91 to +2.17) and -1.22 (-2.8 to +1.58) in Gr 2 and 3, respectively (P<0.001). IGF-1 SDS values were +3.28 (+2.05 to +6.1), and IGF-1 was less than twice the upper limit of normal in all patients in Gr 4. OGTT was performed in 51 of the 101 acromegalic patients. The nadir GH in these patients was 4.01 (0.2 to 46.7) in comparison with 0.2 (<0.05 to 0.6) in Gr 4 (P<0.001). Elevated IGF-1 levels, alone, are sufficient to establish a diagnosis of acromegaly in the majority of clinically suspected cases. The OGTT may be useful to obtain corroborative evidence when there is modest elevation of IGF-1 with absent or equivocal clinical features.

Pioglitazone in acromegaly – an open‐label, prospective study

Preclinical studies demonstrate that thiazolidinediones (TZDs) decrease growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, suggesting that they might be effective treatments for acromegaly. This study investigated the effect of pioglitazone on biochemical indices of disease activity in acromegaly. This was a 4-month open-label prospective study in 16 patients with active acromegaly who were attending public hospital endocrinology clinics. The intervention was pioglitazone 45 mg/day. The primary outcome was change in serum IGF-1; the secondary outcome was change in area under the curve of glucose-suppressed GH. Serum IGF-1 did not change during treatment with pioglitazone (P = 0·95). After 4 months, the mean (95% CI) change from baseline was -1 μg/l (-51, 49). GH levels following oral glucose loading were unchanged during pioglitazone therapy. After 4 months, the mean (95% CI) change from baseline in area under curve for glucose-suppressed GH was 31 μg/l (-75, 138, P = 0·54). Short-term treatment with conventional doses of pioglitazone did not improve biochemical measures of disease activity in acromegaly.

Pituitary Gigantism: A Case Report

Objective:To present a rare case of gigantism.Case Report:A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

Efficacy and Safety of Radiotherapy in Acromegaly

Transsphenoidal surgery remains the treatment of choice in acromegaly, yet 40-50% of patients require secondary forms of therapy such as radiation therapy (RT) and somatostatin analogues (SA). We undertook this study to evaluate the efficacy and safety of RT in acromegaly. Forty patients with acromegaly treated with RT (mean dose, 52 Gy) after failed pituitary surgery between 1993 and 2007 were analyzed; all were clinically and biochemically active. Patients were evaluated with yearly hormonal measurements [basal and glucose-suppressed growth hormone (GH), IGF-1, thyroid-stimulating hormone (TSH), free T4, cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone or estradiol and prolactin (PRL)] and with magnetic resonance imaging every 2 years. Mean age of patients was 52.9 ± 12.1 years and 85% were female. All subjects had been followed for 1 year, 75% for 3 years, 70% for 5 years and 35% for 10 years. The median basal GH level fell from a baseline of 8.8 ng/mL to 2.27 ng/mL at 5 years (p = 0.001) and to 1.88 ng/mL at 10 years (p = 0.001). A GH <1 ng/mL was achieved by 46% and 57% of the patients at 5 and 10 years of follow-up, respectively. The proportion of patients achieving a normal IGF-1 was 36% at 5 years and 43% at 10 years. Before RT, hypothyroidism, hypocortisolism and hypogonadism were present in 44%, 26% and 74% of patients, respectively. After 5 years of follow-up (n = 28), these figures increased to 51%, 41% and 79% and over a third of the group had panhypopituitarism. One patient developed optic neuritis and another patient was diagnosed with a meningioma 10 years after RT. No cerebrovascular events or deaths occurred. RT is an effective, low-cost and reasonably safe means of controlling acromegalic activity, particularly useful in parts of the world where SA are not readily available.

Should We Still Use Glucose-Suppressed Growth Hormone Levels for the Evaluation of Acromegaly?

Acromegaly is associated with increased mortality if not adequately treated (1). Currently accepted biochemical criteria for cure of acromegaly include a mean 24-h GH level less than 2.5 g/liter (5 mU/liter) and/or a glucose-suppressed GH level of less than 1 g/liter (2 mU/liter) and a normal IGF-I (2). These criteria wereproposedbyBatesetal. (3)whoshowedthatpatientswithGH levels less than 2.5 g/liter did not show an increase in mortality. Since l993, this GH cutoff has been widely applied based on the relative paucity of data relating normal IGF-I levels to normal life expectancy. More recently, Holdaway et al. (4) demonstrated that IGF-I (expressed as an SD score) was significantly associated with mortality. Specifically, they showed that patients with last follow-up IGF-I of at least 2 SD had a mortality ratio 3.5 times higher than thosewithan SD score less thanzero (4).Theyalso showed that mortality was 1.6 times higher in patients with last follow-up GH levels less than 2 g/liter, whereas mortality was similar to the control population in patients with last follow-up GH levels less than 1 g/liter, suggesting that cure criteria should be modified, at least for levels of GH. No data are available concerning mortality and the GH nadir after glucose, yet it is included in almost all studies examining the efficacy of treatment in acromegaly. There are several areas of debate related to the value of the GH response to glucose. First, the additional diagnostic value over a fasting GH level is limited when the IGF-I level is elevated (5), and additionally, a similar diagnostic accuracy of a GH profile and nadir GH after glucose was demonstrated in a large series of patients (6). Second, the clinical implication of a single unsuppressed GH level in patients studied after surgery and showing normal serum IGF-I levels and GH levels below the threshold of cured patients is still a matter of discussion. In this setting, Freda et al. (7) showed that patients considered cured after surgery (normal IGF-I and postglucose GH nadir 0.14 g/liter) did not demonstrate recurrence of acromegaly in long-term follow-up. These data suggest a very relevant role for assessment of GH after glucose to detect patients with a likelihood for recurrence, which is clearly an important clinical outcome. The threshold GH nadir of no more than 0.14 g/liter is, however, well below that mentioned in the 2000 consensus criteria for cured acromegaly (2); the lower threshold was justified by using a highly sensitive GH assay able to detect levels as low as 0.05 g/liter. Lower nadir GH values of 0.25 and 0.26 g/liter after glucose, also using a highly sensitive GH assay, were reported by Costa et al. (8) and Gullu et al. (9), respectively. Thus, the question as to which GH cutoff value should be used for postglucose GH nadir immediately rises. The assay sensitivity is a crucial aspect of diagnostic accuracy of any biochemical test. It is now known that previously used polyclonal RIAs for GH were insufficiently sensitive to discriminate GH levels around 2 g/liter (5). Modern immunoradiometric assays for GH have a detection limit of 0.05 g/liter, so the ability to discriminate postglucose GH levels in patients with active acromegaly vs. healthy subjects is improved. In this issue of the Journal, Arafat et al. (10) have compared different assays to address further the issue of the appropriate GH nadir after glucose currently used in the treatment evaluation of acromegaly. They measured GH after 75 g glucose in 46 acromegaly patients, 18 with controlled disease and 28 with uncontrolled disease, and in 213 healthy subjects using three commercially available assays (Immulite, Nichols, and DSL) that were calibrated against therecentlyrecommendedGHstandards.Asexpected, their results showed that GH levels measured with all assays were stronglycorrelated(rvalues0.8–0.996)Importantly,however,GH levels assessed with the Immulite assay were, on average, 2.3-fold higher than thoseobtainedwith theNichols assayand6-foldhigher than those obtained with the DSL assay (10). Therefore, in centers where Immulite is thestandardmethod, the likelihoodthatapatient with normal IGF-I will have a discrepant unsuppressed GH after glucose is higher than in centers using other methods. To provide clinical advice, the authors propose that a cutoff GH level of 1 g/liter be used with the Immulite method and 0.5 g/liter with the Nichols method; this allowed the authors to identify 95% of patients with active disease and 78–80% of patients in remission.

Acromegaly Symptoms Without Pituitary Adenoma in an Adolescent

The diagnosis of acromegaly requires a glucose-suppressed growth hormone (GH) nadir greater than 1 microg/l associated with clinical symptoms and signs. Here, we present a patient who has acromegalic clinical findings associated with a nadir GH level < 1 microg/l during an oral glucose tolerance test.

Long-term treatment outcome in acromegaly.

A number of groups have developed guidelines to indicate whether an individual with acromegaly has been cured by treatment. However, studies to date do not provide a robust definition of biochemical remission of the disorder based on correlation with long-term outcome. Available data suggest that those with a random serum growth hormone (GH) level of <2.5 microg/l, or a glucose-suppressed GH level of <1 microg/l following treatment have mortality figures indistinguishable from the general population. However, the confidence limits for these mortality estimates are quite wide. It remains possible that growth hormone levels lower than 1 microg/l for random samples, or even lower when using ultrasensitive GH assays, may indicate superior outcome, but this remains to be confirmed. There are limited data relating serum insulin-like growth factor-I (IGF-I) levels to outcome, although normalisation of serum IGF-I clearly improves outcome compared with continued elevation of measurements after treatment. Current evidence suggests that a post-treatment random serum GH <2.5 microg/l and a normal serum IGF-I value defines biochemical cure. Available data suggest that achieving similar growth hormone levels after treatment also reduces the prevalence of chronic complications of the disorder, which is subsequently reflected in improved mortality.

Use of the oral glucose tolerance test to define remission in acromegaly

An oral glucose tolerance test (OGTT) was used to assess growth hormone (GH) secretion in patients with acromegaly prior to (n = 26) and after (n = 71) transsphenoidal adenomectomy as well as in 196 controls. In controls, suppressed concentrations of GH showed a negative relationship both with body mass index (BMI) and with age. Having calculated the reference intervals for suppressed GH concentrations to be expected for any given age and BMI, we compared these individually predicted ranges to GH concentrations actually observed in patients with acromegaly during OGTT. Preoperatively, concentrations exceeded the normal range in all patients. Postoperatively, glucose-suppressed concentrations of GH were less than 2.0 ng/mL in 56 (79%) patients and less than 1.0 ng/mL in 44 (62%). However, only 37 of 71 (52%) patients had glucose-suppressed GH concentrations within the calculated reference intervals (defined by the 95th percentile of normal). Comparing these data with the patient's concentrations of insulin-like growth factor-1 (IGF-1; normal range first established and corrected for age and sex in 494 healthy individuals), congruency of both parameters was found in 59 (77%) patients with an unexplained discrepancy between GH and IGF-1 in the remaining in 16 (23%) patients. Our results confirm that concentrations of IGF-1 must be corrected for sex and age, whereas glucose-suppressed concentrations of GH depend on age and BMI. “Across-the-board” cut-off-values are clearly inadequate and should not be used. Rather, serum GH measurements obtained during an OGTT must be interpreted individually by comparison to control values taking into account both age and BMI. Copyright 2003, Elsevier Science (USA). All rights reserved.

Changing patterns of insulin-like growth factor-I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly.

According to a recent consensus statement on the treatment of acromegaly, its biochemical cure is defined as the normalization of age- and sex-adjusted insulin-like growth factor (IGF)-I levels and the suppression of growth hormone (GH) by glucose to lower than 1 ng/ml. The present study was prompted by the clinical observation that many cases of acromegaly can be considered cured according to one criterion but not others at different moments in a patient's postoperative course. Fifty-three patients with acromegaly (30 women and 23 men) harboring nine microadenomas and 44 macroadenomas were evaluated after surgery by assessing age- and sex-adjusted IGF-I levels as well as glucose-suppressed GH levels. Fifty of these patients were studied more than once during follow up. Acromegaly was categorized as cured if the patient's IGF-I level was normal and their glucose-suppressed GH level was lower than 1 ng/ml; the disease was considered to be active if the patient's IGF-I level was high and the GH nadir was higher than 1 ng/ml following administration of glucose. Discordant categories of the disease were found in patients with high IGF-I levels and a GH nadir lower than 1 ng/ml after glucose administration and in those with normal IGF-I levels and a GH nadir higher than 1 ng/ml after glucose intake. At the first postoperative biochemical evaluation (1-3 months), 34% of patients harboring macroadenomas were classified as having been cured of acromegaly, 39% as having the active disease, and 27% as having the discordant form of the disease. When last evaluated (> or = 12 months postoperatively), the percentage of patients with the discordant form dropped to 14% and the proportion of cases cured and active was 44% and 41%, respectively. Of the nine patients with microadenomas, 44.4% were cured of acromegaly, 33.2% had the active disease, and 22% had the discordant variety on first evaluation. Twelve months or longer after transsphenoidal surgery, 55.5% of cases were cured, 11.1% were active, and 33% were discordant. In most cases, the discordant variety developed because of a persistently elevated level of IGF-I, followed by an incompletely suppressed GH level. Nineteen patients (38%) modified their biochemical category. In 15 of these patients this change in category was due to a change in IGF-I levels, becoming normal in 12 patients and rising to above normal range in three. A tumor remnant was demonstrated on magnetic resonance images in only four of these 19 patients. The authors conclude that the discordance rate between the biochemical markers that define cure in acromegaly is higher than previously reported, and the biochemical status assigned to a patient early in the postoperative course is very likely to change later, particularly when initially discordant.

Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients.

Transsphenoidal surgery is the preferred treatment modality for growth hormone (GH)-secreting pituitary adenomas. In many series, the reported postoperative remission is based mainly on achievement of GH levels less than 2 ng/ml. Strict criteria for insulin-like growth factor I normalization and even lower GH levels (<1 ng/ml) are now suggested to define cure of acromegaly, but the evidence does not yet support such low GH levels in epidemiological follow-up. We analyzed our postoperative results in a large cohort of patients with acromegaly. Ninety-eight patients harboring GH-secreting adenomas (46 microadenomas and 52 macroadenomas) underwent transsphenoidal surgery between 1990 and 1999. Ninety-one patients were operated for the first time, and 12 patients underwent reoperations because of previous surgical failure (7 had undergone surgery elsewhere previously). Biochemical remission was defined as a repeated fasting or glucose-suppressed GH level of 2 ng/ml or less, and a normal insulin-like growth factor I level. Remission was achieved in 74% of all patients after one operation, including 84% of patients with microadenomas and 64% of patients with macroadenomas. Seventy-three percent of patients with macroadenomas 11 to 20 mm in size achieved remission, as compared with a 20% remission rate for patients with adenomas larger than 20 mm. Patients with preoperative random GH levels lower than 50 ng/ml had a better outcome (85% remission), whereas GH greater than 50 ng/ml was associated with remission in 30% of the patients. Only one of the patients (8%) with postoperative active disease who underwent a second operation achieved remission. Recurrence was rare (one patient), and all failed surgical attempts could be detected during the immediate postoperative evaluation. On the basis of strict postoperative GH and insulin-like growth factor I criteria to define remission, our series demonstrates the efficacy of transsphenoidal surgery for acromegalic patients with microadenomas and noninvasive macroadenomas. However, patients with large adenomas (>20 mm) and preoperative GH greater than 50 ng/ml have a poor prognosis and require adjunctive medical or radiation therapy to control GH hypersecretion.

Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly.

The results of surgical therapy for acromegaly were assessed using carefully conducted endocrinological testing in 115 patients who underwent transsphenoidal surgery from 1981 to 1995. Ninety-nine of the 115 patients could be contacted for follow-up review; in 57 of the patients an endocrinological assessment was performed by the authors. Biochemical cure was strictly defined as a normalization of the insulin-like growth factor(IGF)-I level (obtained in 100 patients) and/or a basal or glucose-suppressed growth hormone (GH) level of 2 ng/ml or less. The mean length of follow up from transsphenoidal surgery to laboratory testing was 5.4 years with a maximum of 15.7 years. After transsphenoidal surgery alone, 61% of the patients achieved a biochemical remission; the remission rate was 88% for patients with microadenomas and 53% for those with macroadenomas. Tumor size and preoperative GH level tended to correlate negatively with outcome of surgery. Early postoperative GH level tended to correlate with long-term outcome; in cases in which the early postoperative GH level was lower than 3 ng/ml, the chance of long-term remission was 89%. Thirty-two patients received postoperative radiotherapy: in 10 (31%) of these patients the disease is currently in remission after surgery and radiotherapy only and in three others the disease is in remission with the addition of medical therapy. The overall complication rate was 6.9% with no cerebrospinal fluid leaks, meningitis, permanent diabetes insipidus, or new hypopituitarism. The overall recurrence rate was low at 5.4%. This series shows, based on IFGF-I measurements and strict GH suppression criteria to define remission, that transsphenoidal surgery provides an excellent chance for long-term cure in patients with microadenomas. Surgery alone is successful in most patients with noninvasive macroadenomas; however, most patients with invasive macroadenomas will require adjunctive therapy. Recurrences are uncommon when biochemical remission is clearly documented postoperatively.

Results of surgical treatment for growth hormone-secreting pituitary adenomas

The results of surgical therapy for acromegaly were reviewed in a series of 175 patients treated between 1972 and 1983. Patients with prior surgery or radiation therapy were excluded from the study. Postoperative radiation therapy was given to 54 patients. The criterion of achieving a postoperative basal or glucose-suppressed growth hormone level of 2 ng/ml or less was used to indicate remission. Utilizing the most recently available growth hormone determinations, 90 (51.7%) of 174 patients were in remission. The actuarial probability of remission at 1 and 5 years after surgery was 48.8% and 62.7%, respectively. Tumor size and the preoperative basal growth hormone level were correlated with outcome. Surgical excision of a pituitary adenoma is the most effective therapy currently available for acromegaly.