Recurrent Acromegaly Research Articles

Recurrent acromegaly: a systematic review on therapeutic approaches

Background and objectiveManagement of recurrent acromegaly is challenging for both neurosurgeons and endocrinologists. Several treatment options including repeat surgery, medical therapy, and radiation are offered for such patients. The efficacy of these modalities for the treatment of recurrence has not been studied previously in the literature. In this study, we aim to systematically review the existing cases of recurrence and come to a conclusion regarding the appropriate treatment in such cases.MethodA systematic review was performed through PubMed, Scopus, Web of Science, and Cochrane database to identify studies reporting the treatment outcome of recurrent acromegaly patients. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for primary and secondary treatment, complications, and outcomes of the secondary treatment.ResultsThe systematic review retrieved 23 records with 95 cases of recurrent acromegaly. The mean time of recurrence was 4.16 years after the initial treatment. The most common primary treatment was surgery followed by radiotherapy. The remission rate was significantly higher in medical and radiotherapy compared to surgical treatment.ConclusionIn cases of recurrent acromegaly, the patient may benefit more from radiotherapy and medical therapy compared to surgery. As the quality of evidence is low on this matter feature studies specifically designed for recurrent patients are needed.

Continuity of care in acromegaly: Detecting and managing recurrence after surgical intervention

Acromegaly is a rare disease being followed up by primary care team. It is usually caused by pituitary adenoma and the treatment would be resection of the tumour. But is surgical intervention the end of treatment for acromegalic patient? This case highlighted the continuity of care in a 65-year old gentleman who had been diagnosed acromegaly since the age of 31. He had undergone a transseptal transsphenoidal resection of his pituitary adenoma when he was 45-year-old. Postoperatively, there were still residual growth hormone (GH) and insulin like growth factor (IGF-1) secretions. However, during 20 years follow up after operation, despite the increasing level of GH and IGF-1, the management of acromegaly were neglected as the focus of treatment were shifted towards his other medical problem, which is diabetes and atrial fibrillation. During his latest follow up, his complaint of unspecified headache and expressed his worry regarding the recurrence of his condition. Repeated GH level showed an increase in its level and postulated the possibility of recurrent acromegaly. This case emphasizes the important of recognizing the level of GH and IGF-1 after surgical intervention in order to detect recurrence acromegaly by primary care and early referral to endocrine team.

Management of patients with persistent and recurrent acromegaly

Acromegaly is a multisystem chronic disease characterized by hypersecretion of growth hormone. Effective treatment of acromegaly is extremely necessary, as this pathology is often associated with comorbid conditions (diabetes mellitus, arterial hypertension, sleep apnea syndrome, cardiac hypertrophy) and rare complete clinical and laboratory remission. This article describes treatment options for persistent and recurrent acromegaly that include surgery, pharmacological therapy and radiation therapy.

MON-459 ONO-5788, a Novel Oral Small Molecule Somatostatin Receptor Type-2 (SST2) Agonist, Attenuates GH Hypersecretion in Human GH-Secreting, Pituitary Adenoma-Derived Cells

Somatostatin receptor ligands (SRL) and GHR antagonists are used for persistent or recurrent acromegaly following noncurative surgery and as primary therapy for patients unsuitable for surgery. We tested in vitro action of a novel oral SRL compound ONO-5788 and its active metabolite (ONO-ST1-641) which signals via SST2. With IRB approval and informed consent, 12 human somatotroph adenomas, obtained at transsphenoidal resection were cultured. In the 1st cohort, 8 somatotroph adenomas were treated with ONO-ST1-641 (0, 100, 1000 nM) and octreotide (OCT, 100 nM) for 24 h, and media collected at 2, 6, and 24 h respectively to assess GH and PRL concentrations by ELISA. Cells harvested at 24 h were used to measure mRNA levels of SST2 and SST5, hormone genes and cell cycle genes CDKN1A, CDKN1B by qPCR. Three of 8 tumors (38%) responded to ONO-ST1-641 and OCT as early as 2 and 6 h. GH was significantly reduced by OCT (18% to 58% reduction, P<0.05) and similarly attenuated by ONO-ST1-641 (28 to 59% reduction, P<0.05). GH secretion in 6 of 8 tumors (75%) was decreased at 24 h, showing reduction by OCT and ONO-ST1-641 by up to 48% (P<0.01) and 50% (P<0.01), respectively. PRL levels were undetectable, very low or unchanged by treatments. Related compound ONO-5788 showed similar responses. SST2 and SST5 expression was unchanged during treatments in the 6/8 responders as assessed by TaqMan qPCR using HPRT1 and GAPDH as controls. Neither was GH, PRL, CGA, CDKN1A and CDKN1B mRNA expression altered by ONO-ST1-641 or OCT for 24 h, as assessed by SYBR qPCR using RPL13A, GAPDH and 18S as controls, suggesting that ONO-ST1-641 did not affect these hormone genes and cell cycle regulator mRNA levels. In the 2nd cohort, pretreatment baseline SST2 and SST5 expression were assessed in 4 cultured tumors treated with ONO-ST1-641 (0, 100, 1000 nM) or OCT (100 nM) for 6 h. Untreated tumor cell mRNA was extracted at baseline to assess SST2 and SST5 expression and GH and PRL measured at 6 h. Two of 4 tumors were unresponsive to both ONO-ST1-641 and OCT, 1 showed mild GH reduction by ONO-ST1-641 (15%) but not by OCT. Notably, 1 specimen expressing highly abundant baseline SST2 exhibited marked GH suppression by ONO-ST1-641 and OCT at 6 h (63 and 62%, respectively, P<0.01). High baseline SST2 expression further validated by Western blot and confocal immunofluorescence, imply that SST receptor expression associates with ONO-ST1-641 responsiveness. Available SRLs and GHR antagonists are parenteral, requiring lifelong injection, with variable and suboptimal efficacy, necessitating development of novel oral small molecule drugs for acromegaly. Our study provides preclinical evidence that ONO-5788 and its active metabolite attenuate GH hypersecretion in primary somatotroph adenoma cells cultures, suggesting the potential application of ONO-5788 for acromegaly patients.

Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study.

Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined. To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors. We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo. The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%. SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission.

Reoperation for growth hormone-secreting pituitary adenomas: report on an endonasal endoscopic series with a systematic review and meta-analysis of the literature.

OBJECTIVE Surgery is generally the first-line therapy for acromegaly. For patients with residual or recurrent tumors, several treatment options exist, including repeat surgery, medical therapy, and radiation. Reoperation for recurrent acromegaly has been associated with poor results, with hormonal control usually achieved in fewer than 50% of cases. Extended endonasal endoscopic approaches (EEAs) may potentially improve the results of reoperation for acromegaly by providing increased visibility and maneuverability in parasellar areas. METHODS A database of all patients treated in the authors' center between July 2004 and February 2016 was reviewed. Cases involving patients with acromegaly secondary to growth hormone (GH)-secreting adenomas who underwent EEA were selected for chart review and divided into 2 groups: first-time surgery and reoperation. Disease control was defined by 2010 guidelines. Clinical and radiological characteristics and outcome data were extracted. A systematic review was done through a MEDLINE database search (2000-2016) to identify studies on the surgical treatment of acromegaly. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for surgical approach, tumor size, cavernous sinus invasion, disease control, and complications. Cases were divided into reoperation or first-time surgery for comparative analysis. RESULTS A total of 44 patients from the authors' institution were included in this study. Of these patients, 2 underwent both first-time surgery and reoperation during the study period and were therefore included in both groups. Thus data from 46 surgical cases were analyzed (35 first-time operations and 11 reoperations). The mean length of follow-up was 70 months (range 6-150 months). The mean size of the reoperated tumors was 14.8 ± 10.0 mm (5 micro- and 6 macroadenomas). The patients' mean age at the time of surgery was younger in the reoperation group than in the first-time surgery group (34.3 ± 12.8 years vs 49.1 ± 15.7 years, p = 0.007) and the mean preoperative GH level was also lower (7.7 ± 13.1 μg/L vs 25.6 ± 36.8 μg/L, p = 0.04). There was no statistically significant difference in disease control rates between the reoperation (7 [63.6%] of 11) and first-time surgery (25 [71.4%] of 33) groups (p = 0.71). Univariate analysis showed that older age, smaller tumor size, lower preoperative GH level, lower preoperative IGF-I level, and absence of cavernous sinus invasion were associated with higher chances of disease control in the first-time surgery group, whereas only absence of cavernous sinus invasion was associated with disease control in the reoperation group (p = 0.01). There was 1 case (9%) of transient diabetes insipidus and hypogonadism and 1 (9%) postoperative nasal infection after reoperation. The systematic review retrieved 29 papers with 161 reoperation and 2189 first-time surgery cases. Overall disease control for reoperation was 46.8% (95% CI 20%-74%) versus 56.4% (95% CI 49%-63%) for first-time operation. Reoperation and first-time surgery had similar control rates for microadenomas (73.6% [95% CI 32%-98%] vs 77.6% [95% CI 68%-85%]); however, reoperation was associated with substantially lower control rates for macroadenomas (27.5% [95% CI 5%-57%] vs 54.3% [95% CI 45%-62%]) and tumors invading the cavernous sinus (14.7% [95% CI 4%-29%] vs 38.5% [95% CI 27%-50%]). CONCLUSIONS Reoperative EEA for acromegaly had results similar to those for first-time surgery and rates of control for macroadenomas that were better than historical rates. Cavernous sinus invasion continues to be a negative prognostic indicator for disease control; however, results with EEA show improvement compared with results reported in the prior literature.

Abstract #826: Outcomes After Radiation Treatment for Patients with Persistent or Recurrent Acromegaly After Surgery

Abstract #826: Outcomes After Radiation Treatment for Patients with Persistent or Recurrent Acromegaly After Surgery

A Case of Recurrent Acromegaly: Medical Management of the Disease

Introduction: Acromegaly is a rare, chronic, insidious disease characterized by overproduction of growth hormone (GH) and its tissue mediator insulin-like growth factor 1 (IGF-1) typically from a pituitary adenoma. Recurrent acromegaly is established by GH hypersecretion after initial biochemical cure, and is even rarer than the disease itself, reported in only 2 to 3% of the cases. Case Report: We present a case of a 44 year-old Hispanic male with a past medical history of acromegaly diagnosed 20 years ago initially treated with transsphenoidal microsurgery and open brain surgery two years after the first procedure. He was lost to follow up and presented to our outpatient clinic 18 years later complaining of frequent headaches with nose and hands enlargement. Physical examination revealed an overweight male patient with a height of 75 inches, enlarged nose, lips, splayed teeth, coarse facial features, macroglossia, and enlargement of both hands with hyperhidrosis of his palms. Laboratory work up confirmed the diagnosis of recurrent acromegaly with elevated fasting IGF-1 level. MRI of the brain showed a 4.3 x 3.8cm pituitary macroadenoma with extensive suprasellar extension and optic chiasm compression. Medical treatment with Octreotide Long-Acting Release (LAR) was started immediately and subsequent repeat IGF-1 levels have shown progressive improvement. Discussion: This patient’s case of recurrent acromegaly shows the importance of follow up after any surgical or medical intervention in acromegaly patients. Recurrence, though infrequent, is possible and these patients have been identified as a subset of patients that can be difficult to manage. Therefore close monitoring with IGF-1 and GH levels is crucial to diagnose and treat recurrence of the disease and its comorbidities. Our goal was to achieve a biochemical cure, however given the fact that the patient refused any surgical intervention, makes the case even harder to manage. Somatostatin analogues have proven to be effective in cases like ours, yet its efficacy varies among studies.

The Utility of Metabolic Testing in the Diagnosis of Residual and Recurrent Acromegaly

The Utility of Metabolic Testing in the Diagnosis of Residual and Recurrent Acromegaly

Pregnancy Associated with Recurrent Acromegaly: A Case Report

Acromegaly is an uncommon endocrine disorder. Pregnancy is an unusual event in acromegalic females because fertility is often reduced. With the advent of advanced surgical and medical management, more acromegalic women will achieve pregnancy. Reports of pregnancy in acromegaly and recurrent acromegaly postpartum are rare. To present a rare occurrence of pregnancy in acromegaly after macroadenectomy and recurrent acromegaly postpartum. Clinical and biochemical evaluation of a 39-year-old female Nigerian with features of acromegaly before and after macroadenectomy and postpartum was done. Investigations carried out included oral glucose tolerance test with serial growth hormone assays and insulin-like growth factor 1 as well as computed tomography scan and magnetic resonance imaging of the pituitary. There was a history of menorrhagia, swelling of the feet and increasing coarsening of the facial appearance. She had biochemical evidence of acromegaly and subsequently had a transsphenoidal macroadenectomy. There was postoperative clinical and biochemical remission. Magnetic resonance imaging done six months postsurgery showed no evidence of tumour regrowth. Clinical and biochemical evidence of acromegaly recurred after pregnancy. Magnetic resonance imaging confirmed tumour regrowth. Pregnancy in treated acromegaly, though a rare occurrence, is achievable but is capable of provoking recurrence of acromegaly.

Medical therapy in acromegaly

Acromegaly is a rare disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. The disease is associated with increased morbidity and premature mortality, but these effects can be reduced if GH levels are decreased to <2.5 μg/l and IGF-1 levels are normalized. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant. Medical therapy is currently most widely used as secondary treatment for persistent or recurrent acromegaly following noncurative surgery, although it is increasingly used as primary therapy. This Review provides an overview of current and future pharmacological therapies for patients with acromegaly.

A new therapeutic era for pituitary tumors

The medical management of pituitary tumors is entering a new era. Novel compounds that directly target the pituitary tumor have shown promise in patients with treatment-refractory or recurrent Cushing disease and acromegaly. Furthermore, the alkylating agent temozolomide provides clinical benefit for patients with aggressive pituitary adenomas or carcinomas.

Repeat Transsphenoidal Surgery for the Treatment of Remaining or Recurring Pituitary Tumors in Acromegaly

Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone-secreting pituitary adenoma. To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.

The role of stereotactic radiosurgery in the multimodal management of growth hormone–secreting pituitary adenomas

Growth hormone (GH)-secreting pituitary adenomas represent a common source of GH excess in patients with acromegaly. Whereas surgical extirpation of the culprit lesion is considered first-line treatment, as many as 19% of patients develop recurrent symptoms due to regrowth of previously resected adenomatous tissue or to continued growth of the surgically inaccessible tumor. Although medical therapies that suppress GH production can be effective in the management of primary and recurrent acromegaly, these therapies are not curative, and lifelong treatment is required for hormonal control. Stereotactic radiosurgery has emerged as an effective adjunctive treatment modality, and is an appealing alternative to conventional fractionated radiation therapy. The authors reviewed the growing body of literature concerning the role of radiosurgical procedures in the treatment armamentarium of acromegaly, and identified more than 1350 patients across 45 case series. In this review, the authors report that radiosurgery offers true hormonal normalization in 17% to 82% of patients and tumor growth control in 37% to 100% of cases across all series, while minimizing adverse complications. As a result, stereotactic radiosurgery represents a safe and effective treatment option in the multimodal management of primary or recurrent acromegaly secondary to GH-secreting pituitary adenomas.

Recent advances in the treatment of acromegaly

Description of recent outcomes and approaches to the treatment of patients with de-novo and recurrent acromegaly. Radiosurgery for acromegaly results in a higher likelihood of remission and an earlier time to remission than does conventional radiotherapy. Somatostatin analogs results in control of acromegaly and one half of patients. Combining treatment with pegvisomant and somatostatin analogs results in overall improved quality of life. Existing treatments offer patients and their treating physicians opportunities to restore life expectancy to normal and reverse many of the symptoms and signs of acromegaly.

Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria.

The results of transsphenoidal surgery as initial therapy for GH-secreting pituitary adenomas in 57 acromegalic patients were analyzed retrospectively. Patients with prior surgery or radiation therapy were excluded from the study. Three different criteria were used to define remission: glucose-suppressed (nadir) GH less than 1.0 microg/liter, a normal sex- and age-adjusted IGF-I level, and postoperative random GH levels of 2.5 microg/liter or less. Additionally, we analyzed the neuropathological data, including immunohistochemistry and ultrastructural categorization, and the surgical complications. The short-term remission rate (6-wk postoperative follow-up visit), as determined by a random GH measurement of 2.5 microg/liter or less, was 48.8%; the remission rate, as determined by nadir GH, was 51.4%. For 57 patients followed for 12 months or more after surgery (mean, 37.7 months), surgical remission was achieved in 70.2%, 66.7%, and 61.1%, respectively, for patients assessed by normal IGF-I, random GH, and nadir GH. One patient (1.1%) developed recurrence of active acromegaly 81 months after initially successful surgical therapy. Extrasellar growth of the tumor (P = 0.04) and dural invasion by the adenoma (P = 0.008) were significant univariate predictors of a poor outcome. Tumor size was significantly greater in patients with persistent or recurrent acromegaly (P = 0.02). Patients with tumors of the ultrastructural categories of mixed GH/PRL cell and mammosomatotroph adenomas had the lowest remission rates (50% and 42.9%, respectively). There were no perioperative deaths, and there was no serious morbidity. The permanent complication rate was 3.3% (1 permanent DI and 2 nasal septal perforations). Surgical management of acromegaly currently provides prompt, effective, and satisfactory initial treatment for the majority of patients. Using stringent criteria for remission, primary transsphenoidal surgery for GH-secreting pituitary adenomas is effective and often definitive therapy for acromegaly. These results provide a benchmark for the contemporary results of surgical management as assessed by modern outcome criteria.

Surgical outcome after repeated transsphenoidal surgery in acromegaly.

Transsphenoidal selective adenomectomy is the most efficient primary treatment for acromegaly. However, management of persistent or recurrent disease remains controversial. The objective of the present study was to evaluate the early and long-term efficacy and safety of a second transsphenoidal surgery performed in those cases. The results of a retrospective study of 16 patients undergoing reoperation by the senior author (J.H.) between 1970 and 1991 are reported. Reoperation was performed for persistent or progressive acromegaly in 11 patients, visual impairment in four, and disease recurrence in one. Normalization of growth hormone (GH) was defined as a basal GH level of less than 5 micrograms/L and suppression to less than 2 micrograms/L during the oral glucose tolerance test. Long-term follow-up data were available in 15 patients. The second transsphenoidal surgery induced a greater than 50% decrease of GH level in 11 patients. Three (19%) of 16 patients were cured according to the authors' criteria and remained so after 2, 7, and 20 years. Two more patients had a postoperative basal GH level of less than 5 micrograms/L but incomplete suppression during the oral glucose tolerance test. Thus, a total of five patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient who had no initial improvement after the second transphenoidal surgery had spontaneous normalization of his GH level after 13 years. The following complications of the second surgery occurred in three patients: one subarachnoid hemorrhage, two new visual field defects, one cranial nerve palsy, and one meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary hormone deficiencies. In conclusion, reoperation for persistent or recurrent acromegaly has low success and high complication rates. According to the authors' experience, this procedure should be reserved for patients unresponsive to other forms of therapy or with progressive visual impairment despite medical therapy.

Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness.

Epidermal growth factor (EGF) has been localized in several human neoplasms and has been shown to have a significant correlation to prognosis. We investigated the potential role of the EGF receptor (EGF-R) system in pituitary tumorigenesis by examining the expression of EGF and EGF-R in the different types of human pituitary adenomas. EGF was identified by immunohistochemistry in all cell types of the nontumorous adenohypophysis and in all types of morphologically characterized functional (n = 9) and nonfunctional (n = 17) adenomas. To confirm local EGF synthesis, ribonucleic acid (RNA) from human pituitary adenomas was reverse transcribed and PCR amplified. Transcript signals of the expected size were identified, with marked variation in 41 of 48 adenomas. To assess possible secretion in vitro, EGF was measured in pituitary tumor culture medium. No measurable quantities of EGF were present in conditioned culture medium from all 35 adenomas examined, consistent with the rapid uptake of EGF by unoccupied functional EGF-R sites. Using a specific monoclonal antibody that recognizes the extracellular ligand-binding domain of the human EGF-R, we found EGF-R in cells in the normal pituitary and in some functional and nonfunctional adenomas with extremely variable intensity. By RT-PCR, EGF-R messenger RNA (mRNA) expression was also identified, with marked variation in all 48 adenomas examined and in the nontumorous pituitary. The highest degrees of EGF-R mRNA expression were present in somatotroph adenomas and the aggressive silent subtype 3 adenomas. Tumors from patients with recurrent acromegaly demonstrated significantly higher levels of EGF-R mRNA than those from patients with nonrecurrent disease. In conclusion, EGF and EGF-R are expressed in a variable manner in all types of human pituitary adenomas. The overexpression of EGF-R in recurrent somatotroph adenomas and aggressive silent subtype 3 adenomas suggests a selective mechanism for the EGF/EGF-R family in the growth of aggressive pituitary tumors.

TRH/GnRH Test in Acromegaly

We investigated the rate of recurrence in acromegaly in 20 patients who were found to have a TRH and GnRH induced GH response postoperatively after primarily successful transsphenoidal selective adenomectomy in a retrospective study. All operations had been carried out by the same neurosurgeon (R.F.). Successful therapy was defined as basal GH-levels < or = 2 ng/ml and no evidence of residual tumour in the postoperative neuroradiological examination. The follow-up period ranged from 5 to 14 years (mean 7.7 years). At the last follow-up visit an OGTT was performed and SmC measured. In spite of the long-follow-up period we did not find patients with recurrent acromegaly in this investigation. We conclude that, in contrast to previous studies, a stimulation of GH in the TRH/GnRH test does not necessarily predict likely recurrence of acromegaly in patients with an adequate suppression of GH during an OGTT following operative microsurgical treatment.

Persistent or recurrent acromegaly. Long-term endocrinologic efficacy and neurologic safety of postsurgical radiation therapy

As in other clinics, pituitary surgery was definitive treatment in less than 50% of cases of acromegaly treated at one institution over several decades. From 1965 to 1989, 24 acromegalic patients who had noncurative pituitary surgery received radiation therapy at the National Institutes of Health, with a basal human growth hormone level of greater than 5 ng/ml as the criterion for active disease. Using megavoltage irradiation, more than 60% of these patients stabilized at a normal hormonal range, and the overwhelming majority had decreasing growth hormone levels with time. No major side effects of irradiation were encountered except panhypopituitarism of varying degrees. The authors evolved a policy of surgery as the first option, followed by irradiation for patients with postoperative growth hormone levels more than 5 ng/ml.