Management of NFAs: medical treatment

Introduction

Non-functioning pituitary adenomas (NFPAs) are in general large tumors that present with symptoms secondary to local pressure on adjacent structures. Transsphenoidal surgery is the first line of treatment but residual tumor mass is often detected post-operatively. Medical therapy, in any stage of tumor management, is not well established.

Methods

A literature search was performed to review the available data on medical treatment of NFPAs.

Results

Medications investigated for the treatment of NFPAs include dopamine receptor agonists (DA) and somatostatin receptor ligands. Randomized controlled trials are lacking, but available data suggest that DA have a positive effect on tumor remnant stabilization after surgery and could be considered in this setting. Temozolomide is reserved for aggressive tumors, although future studies are required.

Conclusions

NFPA are often not amenable to complete surgical resection. Conservative follow-up after surgery is associated with a high prevalence of tumor remnant progression. DA therapy may prevent residual tumor enlargement in over 85% of these patients, with a substantial consequent reduction in the need for repeat surgery or radiation therapy. It is our view that DA treatment should be routinely considered for the management of NFPA patients with incompletely resected tumors.

     

Silent corticotroph adenomas

Purpose

Silent corticotroph adenomas (SCAs) present clinically as non-functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic hormone (ACTH) without biochemical and clinical manifestation of hypercortisolism. Pathologic examination of resected NFAs that demonstrate positive ACTH and/or TPIT expression confirms its corticotroph lineage. SCAs comprise up to 20% of NFAs and exhibit a higher rate of recurrence. Studies of molecular mechanisms have generated multiple hypotheses on SCA tumorigenesis, pathophysiology, and growth that as yet remain to be proven. An improved understanding of their pathologic and clinical characteristics is needed.

Methods

A literature review was performed using PubMed to identify research reports and clinical case series on SCAs.

Results

Up to date findings regarding epidemiology, mechanisms of pathogenesis, differentiation, progression, and growth, as well as clinical presentation, postoperative course, and treatment options for patients with SCAs are presented. Pooled results demonstrate that 25–40% of cases show cavernous sinus invasion, preoperative hypopituitarism, new-onset hypopituitarism, and recurrence.

Conclusion

This article reviews the incidence, molecular pathology, and clinical behavior of these unique non-functioning pituitary corticotroph adenomas, and highlights the need for rigorous monitoring for recurrences and hypopituitarism in patients with SCAs.

     

IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction

Purpose

To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology.

Methods

We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990–2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies.

Results

IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas.

Conclusions

IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

     

Sphenoid sinus microbiota in pituitary apoplexy: a preliminary study

Purpose

There is a high incidence of abnormal sphenoid sinus changes in patients with pituitary apoplexy (PA). Their pathophysiology is currently unexplored and may reflect an inflammatory or infective process. In this preliminary study, we characterised the microbiota of sphenoid sinus mucosa in patients with PA and compared findings to a control group of surgically treated non-functioning pituitary adenomas (NFPAs).

Methods

In this prospective observational study of patients undergoing trans-sphenoidal surgery for PA or NFPA, sphenoid sinus mucosal specimens were microbiologically profiled through PCR-cloning of the 16S rRNA gene.

Results

Ten patients (five with PA and five with NFPAs) with a mean age of 51 years (range 23–71) were included. Differences in the sphenoid sinus microbiota of the PA and NFPA groups were observed. Four PA patients harboured Enterobacteriaceae (Enterobacter spp., N = 3; Escherichia coli, N = 1). In contrast, patients with NFPAs had a sinus microbiota more representative of health, including Staphylococcus epidermidis (N = 2) or Corynebacterium spp. (N = 2).

Conclusions

PA may be associated with an abnormal sphenoid sinus microbiota that is similar to that seen in patients with sphenoid sinusitis.

     

Pituitary tumour apoplexy within prolactinomas in children: a more aggressive condition?

Objectives

To evaluate clinical presentations, diagnosis and management of paediatric patients presenting with pituitary apoplexy.

Methods

A retrospective case series describing a cohort of paediatric patients presenting with this condition from 2010–2016 to a tertiary referral children’s hospital in the United Kingdom.

Results

Pituitary apoplexy is a rare condition that seems to have a higher relative incidence in children than adults. Our series suggests that pituitary apoplexy in paediatric patients with adenomas appears more common than previously described. All our patients required surgery, either as an acute or delayed procedure, for visual compromise. Two patients had commenced growth hormone (GH) for GH deficiency two weeks prior to the onset of pituitary apoplexy.

Conclusions

With only a limited number of published case reports surrounding this topic our case series contributes to help further understand and manage this condition.

     

Pathology of GH-producing pituitary adenomas and GH cell hyperplasia of the pituitary

Introduction

Histologic, immunohistochemical and electron microscopic studies have provided conclusive evidence that a marked diversity exists between tumors which secrete growth hormone (GH) in excess. GH cell hyperplasia can also be associated with acromegaly in patients with extrapituitary GH—releasing hormone secreting tumors or in familial pituitary tumor syndromes.

Materials and methods

A literature search was performed for information regarding pathology, GH-producing tumors and acromegaly.

Results

This review summarizes the current knowledge on the morphology of GH-producing and silent GH adenomas, as well as GH hyperplasia of the pituitary.

Conclusion

The importance of morphologic classification and identification of different subgroups of patients with GH-producing adenomas and their impact on clinical management is discussed.

     

Double pituitary adenomas are most commonly associated with GH- and ACTH-secreting tumors: systematic review of the literature

Introduction

Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined.

Methods

Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: “double pituitary adenomas”, “multiple pituitary adenomas” and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included.

Results

We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting.

Conclusion

Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing’s Disease.

     

Effects of somatostatin and its analogues on progenitor mesenchymal cells isolated from human pituitary adenomas

Purpose

Progenitor mesenchymal cells (PMCs) have been found also in epithelial tumors and may derive from cancer stem cells (CSCs) by EMT mechanism. In this scenario, the effects of traditionally drugs on PMCs become of primary concern for therapeutic approaches. Previously, we isolated PMCs from acromegalic (GHomas) and not-functioning pituitary adenomas (NFPAs). Here we evaluate: (1) the role of EMT on their origin; (2) the presence of the somatostatin receptors (SSTR1–5); (3) the effects of somatostatin (SST) and its analogues (SSAs) on PMCs proliferation, apoptosis and SSTR1–5 expression.

Methods

PMCs were isolated from GHomas and NFPAs; the expression of E-CADHERIN and TGFβRII (referred to EMT), the expression of the SSTR1–5 as well as the proliferation and apoptosis were tested before and after drugs administration.

Results

Results show a decrease of E-CADHERIN and an increase of TGFβRII, confirming an EMT involvement; SSTR1–5 are more expressed by PMCs from GHomas than from NFPAs. SST and SSAs administration does not affect cell proliferation and SSTR1–5 expression on PMCs from NFPAs while in PMCs from GHomas, cell proliferation showed a marked decrease and a corresponding increase in the expression of SSTR1–2. Apoptosis rate and EMT were not affected by drugs administration.

Conclusions

Results indicate as EMT may be related to the presence of PMCs on pituitary tumors; SSAs, currently used in the management of human GHomas, exert anti-proliferative effect also in PMCs that, because of their derivation from CSCs, may be a new meaningful target for drugs treatment.

     

Ovarian hyperstimulation syndrome due to follicle-stimulating hormone-secreting pituitary adenomas

Purpose

Gonadotroph adenomas are pituitary adenomas with inefficient and variable secretory characteristics, that is why they are usually considered as a subgroup of nonfunctioning pituitary adenomas (NFPA) and are recognized only at immunohistochemistry. When gonadotroph adenomas secrete active hormones, they may cause spontaneous ovarian hyperstimulation syndrome (OHSS) in premenopausal women. Aim of our study is to describe three women with OHSS diagnosed before the removal of the adenoma and to calculate the prevalence of OHSS in premenopausal women with a clinical diagnosis of NFPA.

Methods

We reviewed clinical records of premenopausal women that underwent neurosurgery for NFPA at our centre between 1993 and 2014. OHSS was diagnosed in patients with high levels of FSH, suppressed LH, hyperestrogenism, abdominal symptoms, polymenorrhea, enlarged ovaries with cysts or previous surgery for ovarian cysts.

Results

171 women were included into the study; 62 (36.6%) had a gonadotroph adenoma diagnosed at immunohistochemistry. Two patients were retrospectively diagnosed as having OHSS due to gonadotroph adenoma and three had OHSS diagnosed before neurosurgery. The prevalence of OHSS was 2.9% in the overall group of patients with NFPA and 8.1% among patients with a gonadotroph adenoma detected at immunohistochemistry.

Conclusions

Frequency of OHSS due to a gonadotroph adenoma is not negligible. Increased awareness of the characteristic clinical and hormonal picture should permit an early detection of this condition in premenopausal women with a pituitary adenoma.

     

MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas

Purpose

Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas.

Methods

The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission.

Results

Low-to-moderate MGMT immunoexpression (<50%) was significantly more frequent in the group with persistent/recurrent disease than in cases of endocrine remission (66 vs. 21%, p?<?0.001). Furthermore, adenomas with low-to-moderate MGMT immunoexpression were significantly more often recurrent (76 vs. 30%, p?<?0.001) and invasive (64 vs. 28%, p?=?0.002).

Conclusion

In our series, low-to-moderate MGMT immunoexpression was the only marker that significantly correlated with surgical invasiveness and recurrence in functioning pituitary macroadenomas. Therefore, in the future, MGMT status may be considered an additional marker for understanding the biological behavior of pituitary adenomas.

     

Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy

Purpose

In pituitary apoplexy (PA), there are preliminary reports on the appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of this study was to evaluate the incidence and clinical significance of SSMT in patients with PA and a control group of surgically treated non-functioning pituitary adenomas (NFPAs).

Methods

Retrospective review of clinical and imaging variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic regression was used to identify factors associated with SSMT.

Results

There were 50 NFPA and 47 PA patients. PA patients were managed conservatively (N?=?11) or surgically (N?=?36). The median sphenoid sinus mucosal thickness was greater in the PA than NFPA groups (2.0 vs. 0.5 mm; p?<?0.001). In multivariate analysis of both the PA and NFPA groups, the presence of PA was the only factor associated with SSMT (OR 0.043, 95% CI 0.012–0.16; p?<?0.001). In multivariate analysis of the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR 0.12, 95% CI 0.026–0.54; p?=?0.006) and a more severe grade of apoplexy (OR 7.29, 95% CI 1.10–48.40; p?=?0.04), were associated with SSMT.

Conclusion

The incidence of SSMT is higher in patients with PA, especially during the acute phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory and/or infective changes.

     

Pituitary tumors in MEN1: do not be misled by borderline elevated prolactin levels

Purpose

The objective of this case report is to demonstrate that the simple expedient of measuring periodic prolactin levels in patients with MEN1 who have modest hyperprolactinemia and normal pituitary MRI scans is insufficient to monitor for the development of pituitary adenomas.

Methods

Review of relevant literature and chart review.

Results

A 25 year old man with known MEN1 manifested by hyperparathyroidism and a gastrin-producing neuroendocrine tumor was found to have a prolactin [PRL] level of 20.0 ng/mL [1.6–16 ng/mL] but a normal pituitary MRI scan. The impression then was that he had prolactinoma too small to be visualized on the MRI. Over the next 3.5 years his PRL levels remained in this mildly elevated range but he then presented with severe headaches and visual field defects. An MRI showed a 3.1 × 1.7 × 1.9 cm pituitary adenoma with compression of the optic chiasm and invasion of the left cavernous sinus. Surgery revealed a gonadotroph adenoma and he subsequently required gamma knife radiotherapy for residual tumor. Postoperative PRL levels were normal.

Conclusions

Small, intrasellar microadenomas may be associated with elevated PRL levels due to possible direct hormone production [prolactinoma] or possibly to interference with portal vessel blood flow. In monitoring hyperprolactinemic MEN1 patients for the development of pituitary adenomas, measurement of PRL levels is insufficient and periodic MRI scans are necessary at a more frequent interval than every 3–5 years. This may also pertain to patients with “idiopathic” hyperprolactinemia.

     

Pituitary abscess: clinical manifestations,diagnosis and treatment of 66 cases from a large pituitary center over 23 years

Purpose

Pituitary abscess (PA) is rare and commonly described in case reports or small case series. This study aimed to better determine salient clinical manifestations related to the diagnosis and appropriate treatment of PA using by far the largest case series of this disease.

Methods

A total of 6361 consecutive patients underwent surgery for pituitary diseases in Peking Union Medical College Hospital between January 1991 and December 2013. Among this cohort, sixty-six patients were diagnosed with PA based on both intraoperative findings and postoperative histopathological evidence.

Results

The most common clinical presentation was anterior pituitary hypofunction (81.8 %), followed by common headache (69.7 %), diabetes insipidus (DI; 47.9 %), visual disturbances (45.5 %) and symptoms related to infection (43.9 %). Forty patients (66.7 %) showed typical rim enhancement after gadolinium injection on magnetic resonance imaging (MRI). Most patients (63 of 66, 95.5 %) underwent transsphenoidal surgery (TSS), and the remaining 3 patients (4.5 %) were treated with transcranial surgery (TC). After follow-up for 7.2 ± 4.9 years, PA was diminished in most patients (81.8 %), as demonstrated by post-operative MRI, and eight patients underwent at least one additional operation due to recurrence.

Conclusions

For patients with hypopituitarism and DI with rim enhancement on MRI, we should consider the possible diagnosis of PA. Proper use of antibiotics, complete drainage via surgery and hormone replacement for hypopituitarism are the key treatments for PA.

     

Aggressive tumors and difficult choices in acromegaly

Purpose

The current article looks at some of the factors associated with pituitary adenomas displaying unusually aggressive biological and clinical behaviour in patients with acromegaly.

Methods

This was a retrospective, narrative review of previously published evidence chosen at the authors’ discretion and presented from the perspective of a Latin American case study.

Findings and Conclusions

Although most pituitary tumors in acromegalic patients are benign and non-aggressive many can behave more aggressively, compromising local surrounding structures. These lesions tend to respond poorly to somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a worse prognosis. Patients with more aggressive tumors constitute a particular challenge, as they often require several therapeutic approaches and may be difficult to manage, especially when options are restricted due to limited resources.

     

A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas

Purpose

Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1 and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas.

Methods

We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays containing specimens from the pituitary adenomas of different hormonal types from 246 patients. In positive samples, the status of the IDH1 gene was further examined by molecular genetic analyses.

Results

In all but one patient, there was no expression of mutated IDH1(R132H) protein in the tumor cells by immunohistochemistry. Only one patient with a recurring clinically non-functioning gonadotroph adenoma demonstrated IDH1(R132H)-immunostaining in both the primary tumor and the recurrence. However, no mutation in the IDH1 gene was detected using different molecular genetic analyses.

Conclusion

IDH1(R132H) mutation occurs only exceptionally in pituitary adenomas and does not play a role in their pathogenesis. Patients with pituitary adenomas do not seem to be candidates for treatment with the inhibitors of mutant IDH1.

     

The experience with transsphenoidal surgery and its importance to outcomes

Purpose

Surgical experience is considered paramount for excellent outcome of transsphenoidal surgery (TSS). However, objective data demonstrating the surgical success in relation to the experience of pituitary surgery units or individual experience of pituitary surgeons is sparse.

Methods

Based on literature data, we have investigated the influence of experience with TSS for pituitary adenomas on endocrinological remission rates and on operative complications. The surgical experience was assessed by calculating the number of transsphenoidal operations per year.

Results

For TSS of microprolactinomas, mean remission rates were 77% in centers with <?2 operations per year for microprolactinomas, 82% with 2–4 operations, 84% with 4–6 operations, and 91% with >?6 operations. A yearly experience with more than 10 initial operations for Cushing’s disease (CD) warrants a remission rate exceeding 70%. Remission rates in CD exceeding 86% have only been reported for single surgeon series. Extraordinarily high complication rates were found in some series with <?25 yearly total operations for pituitary adenomas. Major vascular complications were less than 2% and revision rates for rhinorrhea usually?<?2.5% in centers performing?>?25 transsphenoidal operations per year.

Conclusions

We conclude that a center with experience of >?25 transsphenoidal operations for pituitary adenomas per year provides a high likelihood of safe TSS. Surgery for CD requires a particularly high level of practice to guarantee excellent remission rates. The endocrinologist has the unique opportunity to audit the surgical success by hormone measurement and to refer patients to neurosurgeons with proven excellence.

     

Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis

Purpose

IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear.

Methods

In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence.

Results

APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases.

Conclusions

Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

     

Risk-adapted,long-term management in childhood-onset craniopharyngioma

Purpose

This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management.

Methods

Literature search on Pubmed for paper published after 1994.

Results

Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome.

Conclusions

It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients’ by experienced multidisciplinary teams in the context of multicenter trials.

     

Lymphocytic hypophysitis: modern day management with limited role for surgery

Purpose

We set out to describe the modern day management of Lymphocytic hypophysitis (LH) with respect to its diagnosis, treatment and long-term endocrine and visual outcomes. We deliberately included patients with a clinical diagnosis of LH and compared them with those with a histological diagnosis following surgery.

Methods

A multi-centre observational study was performed. Twenty-two patients were included and studied over a mean follow-up period of 8.6 years (range 4–26 years).

Results

Patients presented with headache (N = 15; 68 %), visual field disturbances (N = 7; 32 %) or a combination of these symptoms (N = 5; 23 %). The time lag between onset of symptoms and diagnosis was <1 month, 1–6 months or >6 months in approximately a third of the patients each, respectively. In two-thirds of the patients (N = 14) LH was diagnosed based on their clinical, biochemical and radiological findings. The surgical cohort (N = 8) was statistically more likely to have presented with larger lesions, with suprasellar extension and greater visual field defects. During follow-up there was improvement in headaches and visual symptoms, but the rate of hypopituitarism as reflected by the need for on-going pituitary hormone replacement persisted. At the 1, 5 and 10 year follow-up there was no significant difference between the medically and surgically managed cohorts in terms of ongoing symptomatology or need for pituitary hormone replacement.

Conclusions

In the modern era, most patients with LH are diagnosed by non-surgical means and managed medically. There remains a significant time lag between the onset of symptoms and the eventual diagnosis of LH. Despite the considerable morbidity attached to LH, overall prognosis is good.