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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TL;DR: It is recommended that screening pituitary dysfunction for aSAH survivors with their aneurysms located in ICA or ACA is recommended, and it was not as high as that of previous European studies.
6 citations
TL;DR: In this article, a prospective, consecutive cohort of surgically managed (endoscopic transsphenoidal) pituitary adenoma (n = 304) were analyzed.
Abstract: Surgery for pituitary adenoma is indicated for relief of mass effect and control of endocrinopathy. Setting benchmarks for visual and hormonal outcomes is important for monitoring performance of surgical centres, while understanding the preoperative factors that predict endocrine cure and visual improvement facilitates tailored counselling for patients prior to surgery. A prospective, consecutive cohort of surgically managed (endoscopic transsphenoidal) pituitary adenoma (n = 304) were analysed. Preoperative and postoperative endocrine and visual field assessments were performed and compared to demographic, imaging and pathological data. Larger adenomas tended to have preoperative endocrine deficiency (p 2) or preoperative ophthalmoplegia. One-third of the cohort (102/304, 33.6%) had a preoperative field cut, most commonly an incomplete (51.0%) or complete (31.4%) bitemporal hemianopsia. Only two patients (2/304, 0.7%) had visual field worsening after surgery, while 71.6% (73/102) experienced partial or complete resolution of their field cut after surgery. Complete resolution of visual field defect was predicted by younger age and incomplete bitemporal hemianopsia. Surgery is a safe and effective therapy for pituitary adenomas. Nearly all patients experience improvement in visual fields, especially the young and those with incomplete bitemporal defects. Reoperative cases and those with cavernous sinus involvement (high Knosp grade/ophthalmoplegia) are less likely to have resolution of endocrinopathy. Visual worsening, new ophthalmoplegia or endocrinopathy were rare complications of surgery.
6 citations
TL;DR: By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement.
Abstract: Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective study. All patients underwent transsphenoidal surgery. Hypogonadism was defined as total serum testosterone levels of <2.4 ng/mL. The tumor volume was calculated based on the pre- and post-operative magnetic resonance images. We prescribed testosterone to patients with defined hypogonadism or clinical symptoms of hypogonadism. Hormone replacement for longer than 1 year was considered as long-term therapy. The need for long-term post-operative testosterone replacement was significantly associated with larger pre-operative tumor volume (p = 0.0067), and lower pre-operative testosterone level (p = 0.0101). There was no significant difference between the gross total tumor resection and subtotal resection groups (p = 0.1059). The pre-operative tumor volume and testosterone level impact post-operative hypogonadism. By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement.
6 citations
Dissertation•
07 Feb 2012
TL;DR: La disgenesia de tallo hipofisario es un hipopituitarismo congenito de grado variable asociado with alteraciones del desarrollo del area selar (adelgazamiento o la ausencia completa del tallo hipsario asociados o no con aplasia o hipoplasia of the hipofISis anterior y/o con neurohipofisis ectopica).
Abstract: Existen muy pocos datos cerca de la incidencia y prevalencia del hipopituitarismo en la poblacion general. En el ano 2001 se publico el primer estudio epidemiologico poblacional de hipopituitarismo de cualquier causa en pacientes adultos, siendo la prevalencia y la incidencia anual reportadas de 45,5 y 4,21 casos por cada cien mil habitantes. Los tumores hipofisarios y/o su tratamiento mediante cirugia y/o radioterapia hipofisaria, constituyen la causa mas frecuente de hipopituitarismo, representando hasta un 60% de los casos. La disgenesia de tallo hipofisario es un hipopituitarismo congenito de grado variable asociado con alteraciones del desarrollo del area selar (adelgazamiento o la ausencia completa del tallo hipofisario asociado o no con aplasia o hipoplasia de la hipofisis anterior y/o con neurohipofisis ectopica). Los primeros casos fueron descritos a partir de los anos 80 en pacientes con hipopituitarismo previamente considerado idiopatico con la generalizacion del uso de la resonancia magnetica en el diagnostico de la patologia hipotalamo hipofisaria. La prevalencia entre ninos con hipopituitarismo considerado idiopatico fue del 37-70%, mas alta en los casos de deficits hormonales multiples. Sin embargo, desconocemos su prevalencia e incidencia en la poblacion general y su frecuencia como causa de hipopituitarismo, ya que habitualmente no se ha considerado como causa especifica de hipopituitarismo.
Su etiopatogenia no esta clara. Se han descrito mutaciones en genes que codifican factores de transcripcion involucrados en el desarrollo hipofisario como son el Hesx1, Lhx4, Lhx3 y OTX2 y en menor medida T-Pit, PROP-1 y Pit-1, asociadas a los cambios anatomicos y/o funcionales que caracterizan a la disgenesia del tallo hipofisario.
El hipopituitarismo, independientemente de su causa, se asocia con un aumento en la morbilidad y mortalidad respecto a la registrada en poblacion sana de igual edad y sexo, siendo la tasa de mortalidad en pacientes con hipopituitarismo el doble que en la poblacion general. Un metanalisis y varios estudios, aunque no todos han demostrado que el aumento en la mortalidad en los pacientes con hipopituitarismo es debido fundamentalmente a enfermedad cardio y cerebrovascular. Sin embargo, los pacientes con hipopituitarismo por lo general son un grupo heterogeneo y existen multiples condiciones clinicas y comorbilidades que pueden influir en el pronostico de estos pacientes, cuyo peso en la tasa final de mortalidad no han sido evaluadas de manera especifica.
Ante los escasos datos con los que contamos respecto a la epidemiologia del hipopituitarismo en la poblacion y sobre la disgenesia de tallo hipofisario como causa de hipopituitarismo, y ante la ausencia de estudios recientes que evaluen el exceso de mortalidad y cuales son los factores que se asocian al pronostico de los pacientes nos propusimos la realizacion de la presente Tesis Doctoral con el objeto de profundizar en la epidemiologia, la morbi mortalidad y las causas que la determinan en los pacientes con hipopituitarismo del area sanitaria de Santiago de Compostela.
Las principales conclusiones de este estudio son: 1- En este estudio, la prevalencia y la incidencia anual de hipopituitarismo en la poblacion general adulta correspondiente al area de Santiago de Compostela fue de 37,5 casos y 2,07 casos respectivamente, por cada cien mil habitantes.
2- La disgenesia de tallo hipofisario represento el 10,5% de los casos de hipopituitarismo en esta muestra. Su prevalencia en la poblacion general fue de 3,95 casos por cada cien mil habitantes y su incidencia anual fue de 0,5 casos / millon de habitantes.
3- El 15,3% de los pacientes (46,9% mujeres) con hipopituitarismo fallecieron durante el periodo del estudio. La razon de mortalidad estandarizada por todas las causas fue de 8,05, mayor en los hombres y en los menores de 45 anos.
4- Los factores asociados a incremento de la mortalidad fueron el diagnostico de acromegalia, la radioterapia hipofisaria previa, un mayor IMC y circunferencia de la cintura, la diabetes con mal control metabolico (HbA1c superior al 7%) y el desarrollo de cancer.
5- El tiempo de supervivencia en los pacientes con hipopituitarismo disminuyo significativamente en relacion con la mayor edad al diagnostico, el antecedente de radioterapia hipofisaria convencional o mediante el uso de radiocirugia, el mal control de la diabetes (HbA1c superior a 7%) y el desarrollo de cancer (especialmente de colon y pulmon). Por el contrario, las causas tumorales de hipopituitarismo se asociaron con una supervivencia mayor.
6 citations
TL;DR: The Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) as discussed by the authors developed guidelines for nonfunctioning pituitary adenomas, low grade gliomas, vestibular schwannomas, and metastatic brain tumors.
Abstract: Evidence-based, clinical practice guidelines in the management of central nervous system tumors (CNS) continue to be developed and updated through the work of the Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS). The guidelines are created using the most current and clinically relevant evidence using systematic methodologies, which classify available data and provide recommendations for clinical practice. This update summarizes the Tumor Section Guidelines developed over the last five years for non-functioning pituitary adenomas, low grade gliomas, vestibular schwannomas, and metastatic brain tumors.
6 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