Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas
01 Oct 1999-The Journal of Clinical Endocrinology and Metabolism (Endocrine Society)-Vol. 84, Iss: 10, pp 3696-3700
TL;DR: Patients with hypopituitarism after neurosurgery should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.
Abstract: Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypopituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.
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01 Apr 2011
TL;DR: In this article, early postoperatively, insufficient adrenal function was observed in 16 patients (18%), which was transient in eight and irreversible in eight other patients in the first year of postoperative follow-up.
Abstract: Results: Early postoperatively, insufficient adrenal function was observed in 16 patients (18%), which was transient in eight and irreversible in eight other patients in the first year of postoperative follow-up. Therefore, after the first year, the prevalence of adrenal insufficiency was 9%. Late, new-onset adrenal insufficiency developed in only three patients 13, 18, and 24 yr after surgery. The incidence rate of late adrenal insufficiency after successful surgery was 2/1000 person-years. After long-term follow-up, a median of 8.1 (1–31 yr), the prevalence of secondary adrenal insufficiency was 12% in patients in remission after surgery for acromegaly.
15 citations
TL;DR: Surgical goal is a poor predictor of actual tumor resection and a more aggressive surgical goal does not correlate with pituitary gland dysfunction, which should improve prognostication and preoperative counseling.
Abstract: BACKGROUND The influence of the surgeon's preoperative goal regarding the extent of tumor resection on patient outcomes has not been carefully studied among patients with nonfunctioning pituitary adenomas. OBJECTIVE To analyze the relationship between surgical tumor removal goal and patient outcomes in a prospective multicenter study. METHODS Centrally adjudicated extent of tumor resection (gross total resection [GTR] and subtotal resection [STR]) data were analyzed using standard univariate and multivariable analyses. RESULTS GTR was accomplished in 148 of 171 (86.5%) patients with planned GTR and 32 of 50 (64.0%) patients with planned STR (P = .001). Sensitivity, specificity, positive predictive value, and negative predictive value of GTR goal were 82.2, 43.9, 86.5, and 36.0%, respectively. Knosp grade 0-2, first surgery, and being an experienced surgeon were associated with surgeons choosing GTR as the goal (P < .01). There was no association between surgical goal and presence of pituitary deficiency at 6 mo (P = .31). Tumor Knosp grade (P = .004) and size (P = .001) were stronger predictors of GTR than was surgical goal (P = .014). The most common site of residual tumor was the cavernous sinus (29 of 41 patients; 70.1%). CONCLUSION This is the first pituitary surgery study to examine surgical goal regarding extent of tumor resection and associated patient outcomes. Surgical goal is a poor predictor of actual tumor resection. A more aggressive surgical goal does not correlate with pituitary gland dysfunction. A better understanding of the ability of surgeons to meet their expectations and of the factors associated with surgical result should improve prognostication and preoperative counseling.
15 citations
Seoul National University Hospital1, Yonsei University2, Kyung Hee University3, Catholic University of Korea4, Samsung Medical Center5, Hallym University6, Inha University7, University of Ulsan8, Chungnam National University9, Kosin University10, Ajou University11, Chonbuk National University12, Dongguk University13, Chung-Ang University14, Kangwon National University15, Korea University16, Kwandong University17, Hanyang University18, Gachon University19, New Generation University College20
TL;DR: The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency, based on a systematic review of evidence and expert opinions.
Abstract: Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency This position statement is based on a systematic review of evidence and expert opinions
13 citations
Cites background from "Recovery of hypopituitarism after n..."
...Hypopituitarism can also occur after the removal of pituitary tumors, but surgery can lead to a 50% recovery of tumor-induced hypopituitarism [5]....
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01 Mar 2014-Endocrinología y nutrición : órgano de la Sociedad Española de Endocrinología y Nutrición
TL;DR: O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors, and should therefore not be a determinant factor in selection of patients to be treated with TMZ.
Abstract: Non-functioning pituitary adenomas are the most common pituitary macroadenomas in adults, accounting for approximately 14%-28% of all clinically relevant pituitary tumors. They are a heterogeneous group of tumors that cause symptoms by compression and/or hormone deficiencies. The possibility of tumor growth is increased in macroadenomas and solid tumors as compared to microadenomas and cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance imaging), but there are studies reporting promising potential biomarkers. Transsphenoidal surgery remains the first therapeutic option for large tumors with compressive symptoms. There is no evidence that endoscopic procedures improve outcomes, but they decrease morbidity. There is no unanimity in finding prognostic predictors of recurrence. Radiosurgery achieves tumor control and, sometimes, adenoma size reduction. Its adverse effects increase with higher doses and tumor sizes>4cm(3). Drug treatment is of little value. In aggressive non-functioning tumors, temozolomide (TMZ) may be used with caution because no controlled studies are available. TMZ achieves tumor control in 38%-40% of aggressive non-functioning tumors. The optimal treatment regimen and duration have not been defined yet. Lack of response to TMZ after 3 cycles predicts for treatment resistance, but initial response does not ensure optimal mid or long-term results. O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors. It should therefore not be a determinant factor in selection of patients to be treated with TMZ.
13 citations
TL;DR: HPA axis recovery can occur as late as 9-12 months following TSA demonstrating the need for periodic reassessment of patients who initially 'fail' SST post-TSA.
Abstract: CONTEXT Secondary adrenal insufficiency is a potential complication of transsphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis after TSA, but, to our knowledge, there are no data predicting likelihood of recovery or the frequency of later recovery of HPA function. OBJECTIVE To assess timing and predictors of HPA axis recovery after TSA. DESIGN Single-center, retrospective analysis of consecutive pituitary surgeries performed between February 2015 and September 2018. PATIENTS Patients (N = 109) with short Synacthen test (SST) data before and at sequential time points after TSA. MAIN OUTCOME MEASURES Recovery of HPA axis function at 6 weeks, and 3, 6, and 9 to12 months after TSA. RESULTS Preoperative SST indicated adrenal insufficiency in 21.1% Among these patients, 34.8% recovered by 6 weeks after TSA. Among the 65.2% (n = 15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months, respectively. Of the 29% of patients with adrenal insufficiency at the 6-week SST, 16%, 12%, and 6% subsequently recovered at 3, 6, and 9 to 12 months, respectively. Preoperative SST 30-minute cortisol, postoperative day 8 cortisol, and 6-week postoperative SST baseline cortisol levels above or below 430 nmol/L [15.5 μg/dL; AUC ROC, 0.86]; 160 nmol/L (5.8 μg/dL; AUC ROC, 0.75); and 180 nmol/L (6.5 μg/dL; AUC ROC, 0.88), were identified as cutoffs for predicting 6-week HPA recovery. No patients with all three cutoffs below the threshold recovered within 12 months after TSA, whereas 92% with all cutoffs above the threshold recovered HPA function within 6 weeks (OR, 12.200; 95% CI, 5.268 to 28.255). CONCLUSION HPA axis recovery can occur as late as 9 to 12 months after TSA, demonstrating the need for periodic reassessment of patients who initially have SST-determined adrenal insufficiency after TSA. Pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement.
13 citations
References
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TL;DR: Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery, although the number of tumors studied is small.
Abstract: The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.
433 citations
TL;DR: There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically forpituitary tumours and the incidence increases after external radiotherapy and endocrine testing is recommended on an annual basis.
Abstract: The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.
419 citations
TL;DR: It is suggested that compression of the portal circulation is a possible mechanism for hypopituitarism in this setting and significant improvement in pituitsary function may occur after surgical adenomectomy for nonsecreting pituitary tumors.
Abstract: Detailed pituitary function studies were conducted on 26 patients with large nonfunctioning pituitary adenomas before and 2-3 months after transsphenoidal adenomectomy. Basal serum PRL, GH, TSH, LH, FSH, and ACTH levels were measured, and dynamic studies of their secretion were made. Preoperatively, GH deficiency was found in all 26 patients (100%), hypogonadism in 25 patients (96%), hypothyroidism in 21 patients (81%), and adrenal insufficiency in 16 patients (62%). Serum PRL levels were low (1.5-4 ng/ml) in 5 patients, normal (5-20 ng/ml) in 9 patients, and mildly elevated (21-53 ng/ml) in the remaining 12 patients. After selective adenomectomy, variable improvement in pituitary function occurred in 17 patients, worsening in 1 patient, and persistence of hypopituitarism in 8 patients. After surgery, normal thyroid function was documented in 12 of the 21 patients (57%) who were hypothyroid preoperatively. Similarly, 6 of the 16 patients (38%) with adrenal insufficiency recovered normal adrenal function, and 8 of the 25 patients (32%) with hypogonadism recovered normal gonadal function. GH deficiency persisted in all but 4 patients (15%). Serum PRL levels decreased in all patients, and only 5 had midly elevated levels after surgery. The presence of a normal or mildly elevated serum PRL level before surgery in these patients was of value in predicting possible recovery of pituitary function after surgery; none of the 5 patients with low preoperative serum PRL levels had any improvement in pituitary function after surgery. A rise in serum TSH levels after TRH administration before surgery also was helpful in predicting possible recovery from hypopituitarism. Most patients who had a rise in serum TSH level in response to TRH stimulation preoperatively recovered some pituitary function after adenomectomy. In contrast, no improvement in pituitary function occurred in patients who had blunted responses to TRH preoperatively. Improvement in pituitary function occurred more often in patients with tumors measuring 25 mm or less than in those with larger tumors. In conclusion, significant improvement in pituitary function may occur after surgical adenomectomy for nonsecreting pituitary tumors. A rise in serum TSH levels in response to TRH stimulation preoperatively suggested the presence of viable pituitary tissue in these patients with hypopituitarism. The presence of a normal or mildly elevated serum PRL level before surgery also suggested the presence of functioning pituitary lactotrophs. These observations suggest that compression of the portal circulation is a possible mechanism for hypopituitarism in this setting.(ABSTRACT TRUNCATED AT 400 WORDS)
271 citations
TL;DR: Data indicate that trans‐sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.
Abstract: From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.
244 citations
TL;DR: The results of transsphenoidal pituitary surgery for acromegaly were analyzed to assess the longer‐term outcome for patients not offered further treatment when post‐operative levels of GH < 5 mU/l were achieved.
Abstract: OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved.
DESIGN We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew’s Hospital between 1985 and 1993.
PATIENTS One hundred consecutive patients (53 male, mean age 46 years, range 18–68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5–8 years) after operation.
MEASUREMENTS GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured.
RESULTS Post-operatively, 42% of patients achieved a mean GH level of 100 mU/l achieved post-operative GH values < 5mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission postoperatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5–8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted.
CONCLUSIONS The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.
199 citations