ResearchPad - neuroendocrinology-and-pituitary https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-289 Pituitary Metastasis: A Systematic Review]]> https://www.researchpad.co/article/elastic_article_9550 Metastatic lesions to the pituitary are uncommon as well as concerning as they do not always have a characteristic radiographic appearance and can be easily missed. We conducted a systematic review of all the published cases and case series of pituitary metastasis to further understand the unique characteristics of these lesions. Using Pubmed and Embase as the primary search engines, we reviewed all cases published from January 1980 to July 2019. A total of 175 unique cases were included in the study. Over 400 cases were collected amongst which a total of 278 cases were included in the study. As part of a challenge with any retrospective study some data points were missing from cases reviewed. Only English language publications were included in the study. The study revealed a predominance of females with 121 cases. Median age was noted to be 61 years. Only 40 patients had previously known metastatic disease. 70 patients were noted have primary cancer arising in the breast which was noted to be the most common primary cancer followed by 64 cases of primary cancer arising from the lungs. Majority of the patients (162 cases) had pituitary hypofunction with deficiency of one or more pituitary hormones. 97 cases were reported to have diabetes insipidus on presentation. Only 40 patients had no visual field deficits whereas 77 patients were reported to have abnormal eye movements. Displacement of the gland superiorly towards optic chiasm was the most common radiographic features in 137 reported cases. Although not commonly reported in most of the published literature, 45 cases were noted to have bony erosion due to expansion of the gland. Only 5 cases were reported to have no contrast enhancement, although many case reports did not specify contrast enhancement of the pituitary. 22 cases were noted to have an aggressive or rapid growth pattern of the pituitary. 13 cases were noted to have edema around the optic chiasm. The pituitary should not be overlooked as a site of metastasis. Many cases can present asymptomatically without biochemical or radiographic characteristics of metastatic lesion. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Unique radiographic characteristics should alert the clinicians to consider this possibility. Our study revealed many unique characteristics of metastatic lesions of the pituitary. This should allow clinicians to become aware of the more common findings in these patients allowing prompt diagnosis.

]]>
<![CDATA[SAT-286 TSH Synthesis and Secretion Are Unperturbed in Male IRS4 Knockout Mice]]> https://www.researchpad.co/article/elastic_article_8806 It was recently reported that mutations in the insulin receptor substrate 4 (IRS4) gene cause a novel form of X-linked congenital central hypothyroidism (OMIM 300904). To date, four different mutations, three frameshift and one nonsense, have been reported, with two affected male patients showing decreased basal, pulsatile, and total thyroid-stimulation hormone (TSH) secretion (PMID 30061370).

Members of the IRS family canonically act as scaffold proteins between tyrosine kinase receptors and their downstream effectors. IRS4/Irs4 expression is enriched in the pituitary; however, its role in the hypothalamic-pituitary-thyroid (HPT) axis has not been studied in detail.

We generated novel whole-body Irs4-knockout mouse lines using CRISPR-Cas9. A specific guide RNA was used to target the Cas9 enzyme to the 5’ end of the single exon Irs4 gene. A two-nucleotide deletion was introduced into Irs4, resulting in a frameshift and premature stop codon. We hypothesized that like IRS4 deficient patients, these mice would exhibit central hypothyroidism. Given that Irs4 is X-linked, we focused our initial characterization on males.

Under normal laboratory conditions, Irs4 knockout mice do not exhibit differences in pituitary expression of Tshb, which encodes one of the subunits of the TSH heterodimer. Expression of the gene encoding the thyrotropin-releasing hormone (TRH) receptor, Trhr1, is also unperturbed in these knockout mice. Additionally, there are no differences in their serum thyroid hormones, T3 (triiodothyronine) and T4 (thyroxine). When Irs4 knockout males were placed on a low-iodine diet supplemented with propylthiouracil (PTU) for 3 weeks and rendered hypothyroid, their serum TSH increased similarly to wild-type males. Overall, Irs4 knockout males do not exhibit central hypothyroidism or phenocopy IRS4 deficient patients. Compensation by another IRS protein may explain euthyroidism in these mice.

]]>
<![CDATA[SAT-278 Vaginal Cabergoline: A Simple Solution to a Challenging Problem]]> https://www.researchpad.co/article/elastic_article_8802 Introduction: Prolactinomas is a common endocrine disorder that can be associated with significant morbidity. Generally, prolactinomas are more responsive to pharmacologic treatment than any other types of pituitary adenoma. Dopamine agonists (DA), including cabergoline and bromocriptine, are the first line of treatment in all sizes of prolactinomas and they decrease both the secretion and size of these adenomas. However, treatment remains challenging for patients who are intolerance to those medications. Case: We report a 32-year-old Hispanic woman who presented with secondary amenorrhea, she was found to have hyperprolactinemia of 1496 mcg/L. MRI of the brain showed a pituitary adenoma measuring 2.7 cm with sella turcica invasion and mass effect on the optic chiasma. She failed the lowest doses of oral cabergoline and bromocriptine and underwent TSS and gamma knife radiosurgery. Given her persistent symptoms (marked depression, insomnia, fatigue, short-term memory loss, and lack of concentration along with constipation) and elevation of prolactin, she was started on low dose vaginal cabergoline leading to a marked improvement of her symptoms and a steady decrease in serum prolactin. Discussion: Despite the availability of DA as a first-line treatment of Prolactinoma, treatment remains challenging, given the commonly reported side effects for all DA. Cabergoline is oftentimes the treatment of choice due to efficacy and favorable side-effect profile. However, intolerance to those medications can lead to discontinuation of therapy and increase morbidity. Other strategies, including transsphenoidal surgery (TSS) or radiation therapy, have been considered for the minority of patients whose adenomas are resistant to DA or who cannot tolerate these drugs. Interestingly, tolerance to DA can be improved by administering the drug intravaginally, which can have similar efficacy to the oral route and a more favorable side-effect profile. However, only a few studies assessed the effectiveness and tolerance of vaginal DAs in hyperprolactinemic patients intolerant to oral medications, little evidence supports the use of intravaginal DA to improve drug tolerance, and further studies are necessary to determine the safety and efficacy of vaginal cabergoline.

]]>
<![CDATA[SAT-281 Chronic, Excess Growth Hormone Action Alters the Development and Aging of the Microbial Community in the Mouse Gut]]> https://www.researchpad.co/article/elastic_article_8781 Emerging evidence proposes that the gut microbiome has an vital role in host growth, metabolism and endocrinology. That is, gut microbes impact growth by potentially altering the growth hormone (GH)/insulin-like growth factor-1 axis. Our previous research has also shown that GH - in states of absence and excess - is associated with altered gut microbial composition, maturity and predictive metabolic function in mice. Moreover, both GH and the gut microbiome are implicated in development and aging. Yet, it is unknown how GH impacts the longitudinal microbiome. This study thus aimed to characterize the longitudinal changes in the gut microbial profile of bovine GH transgenic mice (a model of chronic, excess GH action and accelerated aging). Microbial composition was quantified from fecal pellets of the same bGH and control mice at 3, 6 and 12 months of age through 16S rRNA gene sequencing and QIIME 2. Additional bioinformatic analyses assessed the unique signature and predictive metabolic function of the microbiome. The bGH mice had a distinct microbial profile compared to controls longitudinally. At 3 months, bGH mice had increased Firmicutes and Actinobacteria, decreased Bacteroidetes, Proteobacteria and Campylobacterota, and a significant reduction in microbial richness and evenness. By 6 months, all of the aforesaid phyla were increased with the exception of Firmicutes. By 12 months, bGH mice exhibited dysbiosis with increased Firmicutes and Proteobacteria and reduced Bacteroidetes, microbial richness and evenness. Moreover, abundance in Firmicutes, Bacteroidetes and Campylobacterota were significantly explained by the combined effect of genotype and age (p = 0.006, 0.005 and 0.02, respectively). Across all timepoints, bGH mice had a significantly different microbiome compared to controls (p = 0.002), and the development of microbial richness and evenness were also significantly different in bGH mice (p = 0.034 and 0.023). Bacterial genera Lactobacillus, Ruminococcaceae and Lachnospiraceae were identified as a unique candidates in bGH mice across all timepoints. Likewise, metabolic pathways involved in biosynthesis of heme b, menaquinol, acetate and butyrate differentiated the longitudinal bGH microbiome. Collectively, these results show that chronic, excess GH impacts the development and aging of the gut microbiome. Notably, several of the stated bacterial genera and metabolic pathways were associated with GH in our previous study, suggesting that GH may influence the longitudinal presence of certain gut microbes and metabolic functions. Additional studies will be performed to further explore the GH-associated gut microbiome and its impact on host health. Research was partially funded by the John J. Kopchick MCB/TBS Fellowship, a fellowship from the Osteopathic Heritage Foundation and the MMPC at UC, Davis (NIH grant U240DK092993).

]]>
<![CDATA[MON-256 A Late-Onset Case of Sheehan’s Syndrome Presenting as Life Threatening Adrenal Insufficiency]]> https://www.researchpad.co/article/elastic_article_8773 OBJECTIVE

Sheehan’s syndrome or postpartum pituitary necrosis, is an important but rare cause of hypopituitarism, caused due to severe postpartum hemorrhage. Seen more commonly in the developing world, it is less common in developed countries due to advanced obstetric practices. It can present acutely but more frequently has an insidious course (onset 10-20 years later) with variable hormonal deficiencies. Here, we report a late-onset case of Sheehan’s syndrome, 24 years after the incident event, presenting as life threatening adrenal failure.

CASE PRESENTATION

A 48-year-old female with no significant past medical history was admitted to the hospital after being found unresponsive at home. She had not seen a physician for many years. She complained of weakness and lethargy for a week and recently established care with a primary care physician. The patient was severely hypotensive in the emergency department and had an elevated temperature of 101°F. Physical examination showed no significant abnormalities. CBC and metabolic panel were not significantly altered. CSF analysis and CSF/blood cultures were negative for any infection. TSH was 4.29 mIU/mL (0.27-4.20) but the total and free T4 (fT4) were severely low at 1.1 mcg/mL (4.6-12) and 0.24 ng/dL (0.93-1.70) respectively. On further questioning, patient reported severe postpartum hemorrhage 24 years ago, needing multiple units of blood transfusion. This was followed by inability to lactate and menstruate but was never worked up as she had not seen any physician all these years. Pituitary hormonal panel was obtained, demonstrating multiple hormonal deficiencies with fT4 severely low at 0.24 ng/dL, ACTH of 2.6 pg/mL (7.2-63.3), prolactin (PRL) 1 ng/mL (4.8-23.3) and insulin like growth factor-1 (IGF-1) low at 10 ng/mL (56-194). Cortisol level was elevated in the hospital due to administration of high dose IV steroids but a morning cortisol level obtained 1 week prior by her primary was 1.5 mcg/dL (10-20). Estradiol levels were low with FSH and LH levels inappropriately normal. MRI of the pituitary was obtained which showed an empty sella turcica. Patient was diagnosed as late-onset Sheehan’s syndrome. She was started on hormone replacement with hydrocortisone followed by levothyroxine and had marked improvement in her symptoms. She continues to do well.

CONCLUSION

Our patient presented late due to lack of medical care and awareness. A great number of patients with Sheehan’s diseasae go undiagnosed due to subtle clinical presentations, thus delaying treatment. It is imperative to diagnose this condition timely with appropriate obstetric/gynecological history and clinical suspicion to avoid late manifestations of the disease, especially adrenal crisis. Patients at risk need long term follow-up. Early treatment is necessary to improve quality of life and reduce morbidity and mortality associated with this condition.

]]>
<![CDATA[MON-287 Expression of Programmed Death-Ligand 1 (PD-L1) in Human Pituitary Neuroendocrine Tumor]]> https://www.researchpad.co/article/elastic_article_8770 Introduction

Some Pituitary NeuroEndocrine Tumors (PitNET) present an aggressive evolution and are resistant to standard management. Immunotherapy have shown durable efficacy in a variety of malignancies. The aim of this study was to explore the programmed death-ligand 1 (PD-L1) expression in varied subtypes of pituitary adenomas with assessment of their clinical behavior at diagnosis and follow-up.

Methods

We conducted a retrospective monocentric study, including all patients operated a PitNET between 2012 and 2018. PDL-1 immunostaining were performed using an European Conformity-In-Vitro-Diagnostic labeled anti-PDL1 antibody (Clone 22C3). PD-L1 immunostaining was evaluated as the percentage of tumor cell showing positive membrane staining, into four grades: grade 0 = <1%, grade 1 = 1 to 5%, grade 2 = 6 to 49% and grade 3 = ≥ 50%. PD-L1 expression was compared with tumor features (secretion, proliferation, invasion) and outcome.

Results

The study included one hundred and thirty-nine PitNET, including 84 (60%) nonfunctioning adenomas. Twenty-five PitNET were PD-L1 positive (18%), including 3 grade 3, 8 grade 2 and 14 grade 1. PD-L1 expression was not different between functioning and non-functioning adenomas (p=0.26). Among sixteen tumors with proliferative markers (Ki-67 ≥ 3% and p53 positive), only one was PD-L1 positive.

Conclusion

In our series, pituitary tumors rarely exhibit PD-L1 expression and this immune marker did not seem to be associated with any biological characteristic or behavior of the pituitary tumors. Thus, PD-L1 staining is necessary before considering PD-L1 blockage in PitNET, in case of therapeutic impasse.

]]>
<![CDATA[SAT-313 Synaptojanin 2 Binding Protein Is Required for Efficient Somatostatin Receptor 2A Phosphorylation by G Protein Coupled Receptor Kinases and Signaling to the ERK/MAPK Pathway]]> https://www.researchpad.co/article/elastic_article_8768 Somatostatin receptor 2A (Sst2A) agonists are the primary pharmacological treatment for growth hormone (GH) secreting pituitary tumors to inhibit GH secretion and limit the destructive effects of these tumors. Sst2A agonists are also widely used as imaging agents for neuroendocrine tumors, and are under investigation for treatment of these cancers. However, despite the clinical importance of Sst2A agonists, regulatory mechanisms controlling Sst2A internalization and signaling are not fully understood. Sst2A contains a C-terminal PDZ binding site that serves as a docking platform for PDZ domain containing proteins. In an unbiased screen for PDZ domain proteins that can interact with Sst2A, we identified Synaptojanin 2 binding protein (SYNJ2BP) / Outer mitochondrial protein 25 (OMP25). SYNJ2BP is an outer mitochondrial protein that has been shown previously to promote the internalization of the Activin Type II receptor. We find that SYNJ2BP interacts with Sst2A in a ligand-dependent manner. Importantly, we show that SYNJ2BP promotes interaction of Sst2A with the G protein couple receptor kinase 2 (GRK2), and that siRNA-mediated knockdown of SYNJ2BP dramatically inhibits Sst2A phosphorylation by endogenous GRKs. Moreover, overexpression of SYNJ2BP strongly potentiates Sst2A phosphorylation on the GRK phosphorylation sites. Modulation of SYNJ2BP expression also regulates somatostatin-stimulated β-arrestin recruitment to the plasma membrane. Interestingly, in contrast to the large effects on Sst2A phosphorylation and β-arrestin recruitment, modulation of SYNJ2BP expression only caused a small change in ligand-stimulated receptor internalization. When we assessed downstream signaling, we found that SYNJ2BP overexpression potently stimulated receptor-dependent activation of ERK1/2, but had little effect on the ability of Sst2A to repress forskolin-stimulated cAMP production. Taken together, these data demonstrate for the first time that interaction of Sst2A with a PDZ domain protein affects receptor regulation and signaling. Because multiple PDZ domain containing proteins have been shown to interact with Sst2A, these data also suggest that interaction of Sst2A with this class of proteins may be an important regulatory mechanism to bias its function within the cell.

]]>
<![CDATA[SAT-265 An Asynchronous Double Growth Hormone Secreting Pituitary Adenoma as a Cause of Rapid Tumor Regrowth After Initially Successful Surgery]]> https://www.researchpad.co/article/elastic_article_8762 Background. Double pituitary adenomas are a rare entity, which requires clinical attention and a careful follow-up. Case report. A 37-year-old man presented with left-sided painful gynecomastia. He denied typical symptoms of excessive growth hormone (GH) secretion and did not show any acromegalic features. Due to low testosterone and LH levels with mild hyperprolactinaemia, the patient was referred to pituitary MR, which revealed an 11x13 mm right-sided sellar tumor. An increased IGF-1 was noted subsequently (1482 ng/mL; N 109-284 ng/mL), together with the lack of GH suppression in OGTT. Transphenoidal resection of pituitary tumor performed in 2012 led to biochemical (IGF-1 260 ng/mL, GH 0.08 ng/mL) and radiological remission of the disease. A histopathology report revealed a densely granulated somatotropic pituitary adenoma with mild nuclear atypia, expressing somatostatin receptors [sstr2A (+), sstr5 (+/-)]. Due to gradually increasing IGF-1 levels (with low, although rising, GH values ranging from 0.07 to 0.92 ng/mL) in subsequent years, OGTT was repeated in 2015, showing appropriate GH suppression. In 2016, however, acromegaly recurrence was confirmed both biochemically (increasingly high IGF-1 - 664 ng/mL - and unsuppressed post-OGTT growth hormone) and in MR imaging. The patient was reoperated in June 2017. The second histopathology reported an oncocytic somatotropic acidophil stem cell pituitary adenoma with Ki-67 >3% and mitotic figures. Subsequent anterior pituitary lobe insufficiency (adrenal, thyroid and gonadal axis) was found and adequately treated. Complete tumor removal was confirmed by MR performed three months after repeated surgery, as well as a low GH level (0.97 ng/mL), although accompanied by borderline IGF-1 values (277 ng/mL). Eighteen months after surgery, the recurrence of acromegaly was again confirmed, with adenoma regrowth and increased GH (2.31 ng/mL) and IGF-1 (474 ng/mL) levels. Octreotide LAR was started (despite retina wrinkling which was observed when lanreotide was administered before the first surgery), which led to a normalization of GH (0.96 ng/mL) and IGF-1 levels (152 ng/mL), as well as partial pituitary tumor regression after six months therapy. Conclusion. In a case of GH-secreting pituitary adenoma recurrence after apparent successful surgery, a double pituitary tumor with more aggressive histology should be considered.

]]>
<![CDATA[MON-238 A Diagnostic “Headache” in a Pregnant Woman with Diabetes Insipidus: Blame the Placenta or the Pituitary?]]> https://www.researchpad.co/article/elastic_article_8754 Background

Diabetes insipidus (DI) occurs in 1/30,000 pregnancies and can be difficult to recognize due to normal peripartum physiology. The most common etiology is excess production of placental vasopressinase, which degrades maternal anti-diuretic hormone. Although rare, hypothalamic and pituitary disorders must also be considered in pregnant patients presenting with DI. We present the case of a pregnant woman presenting with diabetes insipidus and pituitary apoplexy.

Clinical case

We were called to see a 33 year old female with polyuria and polydipsia on post-partum day #2. She had presented to the ED at 29.4 weeks of her 5th pregnancy (G5P4) with an unrelenting headache, nausea, and vomiting for 12 hours. She was tachycardic, hypertensive, and had no focal neurologic deficits. Fetal evaluation was reassuring. Admission labs included serum sodium of 147 mEq/L (n 136-145), serum potassium 2.8 mEq/L (n 3.4-4.4), and urine specific gravity of 1.003 (n 1.005-1.030). Glycemic parameters, renal function, and hepatic function were normal. She remained tachycardic despite vigorous IV fluid administration. Overnight into hospital day #3 she began to have uterine contractions with fetal decelerations, and betamethasone was given. It was noted that she had produced 8L of urine over the preceding 24 hours. Serum sodium was 159 mEq/L with urine osmolality of 78 mOsmol/kg (n 300-900). A presumptive diagnosis of gestational DI was made and 2 mcg of subcutaneous DDAVP was given. Shortly thereafter she delivered a healthy infant. Maternal blood loss was minimal. Over the next 12 hours her urine became concentrated and her serum sodium decreased, but by the next morning she re-developed dilute polyuria.

At the time of our evaluation, her headache had resolved and she had no focal neurologic deficits. She had no apparent signs of glucocorticoid or thyroxine deficiency but had not begun to lactate. Biochemical evaluation included early morning cortisol of 4.6 ug/dL (n 3.5-18.3), TSH 0.46 uIU/mL (n 0.35-4.94), free T4 0.76 ng/dL (n 0.70-1.48), and prolactin 26.6 ng/mL (n 5.2-26.5). Pituitary MRI showed a mildly enlarged gland with central T1 hyperintensity, consistent with apoplexy. A regimen of hydrocortisone and DDAVP was initiated.

Conclusion

Pituitary apoplexy is uncommon during pregnancy but is potentially life-threatening for the mother and fetus if it goes unrecognized. The significant physiologic growth of the pituitary during pregnancy may increase the risk of apoplexy. A severe headache is the most common symptom and may be accompanied by signs of pituitary dysfunction. Although diabetes insipidus is more often caused by placental physiology, pituitary apoplexy must also be considered in a pregnant woman who has concurrent neurologic symptoms.

]]>
<![CDATA[SAT-251 New Diagnosis of Acromegaly with DKA as Initial Presentation]]> https://www.researchpad.co/article/elastic_article_8744 Background: While diabetes mellitus from growth hormone related insulin resistance is not uncommon in GH secreting tumors, initial presentation with diabetic ketoacidosis is rare.

Clinical Case: 31 YO male with no significant past medical history presented with c/o fatigue, 40 lb weight loss, polyuria, polydipsia. Clinical features of acromegaly with frontal bossing, protruding jaw, large hands and feet, thick spade like fingers, hammer toes, high arches and thickened fat pads on both feet were noted. Initial labs were consistent with DKA with anion of 31 mmol/L (0-20), blood glucose 241 mg/dl, bicarb 12 mmol/L (22-29), serum betahydroxy butyrate > 8 mmol/L (0-0.29), urine positive for glucose, ketones, protein. Patient was initially treated with IV insulin per DKA protocol, transitioned to subcutaneous insulin.

MRI brain showed 2.1x1.3x2.1 cm pituitary macro adenoma. Labs showed elevated IGF1 LC/MS, S 1094 ng/ml (54-310), IGFBP3 14 mcg/ml (3.5-7), Z score IGF MS Mayo > 3 (-2 to +2), normal FSH 7.1 m unit/ml (1.5-12.4), normal LH 3.4 m unit/ml (1.7-8.6), normal prolactin 6 ng/ml (4-15), normal ACTH 10 pg/ml, cortisol 13.4 mcg/dl, low total testosterone 48.2 ng/dl (193-836), normal free testosterone 7.92 ng/dl (4.85-19), normal TSH 1.55 mc unit/ml (0.27-4.2) and free T4 1.17 ng/dl (0.93-1.7). The patient was discharged home on 120+ units of total daily dose of insulin, after initial hospital admission.

He underwent trans sphenoidal resection of pituitary macro adenoma one month after his initial presentation. Surgical pathology confirmed growth hormone producing adenoma. He was successfully weaned off from insulin in one month following surgery.

Conclusion: DKA is an unusual initial presentation of growth hormone producing tumors. As more cases are being reported it is important to be vigilant to look for DKA presentation in these patients and adjust/wean patients insulin once the growth hormone producing tumor is treated either with surgery or medications.

]]>
<![CDATA[SUN-288 Atypical Teratoid Rhabdoid Tumor of the Sellar Region: An Unusual Cause of Hypopituitarism]]> https://www.researchpad.co/article/elastic_article_8736 Background: Atypical teratoid/rhabdoid (AT/RT) tumor of the sellar region is an extremely rare malignant tumor in adults. To date, there are no definitive guidelines for optimal treatment and the prognosis of this tumor is poor. The pituitary insufficiency was rarely mentioned in previous literature and might be overlooked.

Clinical case: A 43 years old female presented to our clinic with severe periorbital pain. The magnetic resonance imaging of the brain revealed a 1.5x1.5x 3 cm sellar mass which showed inhomogeneous enhancement after gadolinium administration. Hormonal work up showed 8AM cortisol of 1.86 mcg/dL, free T4 1.0 (0.8–1.8 ng/dL), TSH 0.05 (0.3 - 4.1 uIU/ml), FSH 6.0 (1.6–9.3 IU/L), LH 1.8 (2.4–9.3 IU/L), estradiol <18.35 (80–790 pmole/L), IGF-1 96.6 (50.6–263.7 ng/ml), prolactin 56.6 ng/ml.

She underwent transsphenoidal surgery with tumor removal. The pathological result showed a mixture of pleomorphic spindle cell, oval shape tumor and poorly differentiated cell. The tumor was negative for INI1 (SMARCB1) compatible with AT/RT WHO grade IV. She developed pan hypopituitarism after surgery. She received 6 courses of 5950 cGy/25 fractions cranial irradiation and 6 courses of ifosfamide, cisplatin and etoposide. She completed the treatment regimen without significant toxicity. She continued hormonal replacement for panhypopituitarism and is still being followed at our clinic for 4 years without tumor progression or other complications.

In previously reported cases, all of the sellar AT/RT were female with a median age of 45 years old (range 20–61). The clinical presentations are rapidly enlarged sellar mass with compressive symptoms to the adjacent structures. The radiological findings of sellar AT/RT are non-specific. The diagnosis is based on histopathological findings. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 help in establishing a diagnosis of AT/RT.

Currently, there are no definitive guidelines for optimal treatment. Multimodality treatment consisted of surgery, radiation and chemotherapy are the mainstays of treatment of the AT/RT. Of the 16 adults reported in the literature, 9 patients survived more than 12 months resulted in 47% of one-year survival rate. To our knowledge, this case is the sellar AT/RT with the longest survival to date.

Conclusion: AT/RT is one of the most aggressive tumors in the sellar area. Due to its aggressiveness, hypopituitarism is anticipated. Our patient had postoperative secondary adrenal insufficiency, secondary hypothyroid and hypogonadotropic hypogonadism. Apart from multimodality treatment required for tumor control, pituitary hormones should be evaluated preoperatively to prevent perioperative mortality and long-term improvement in the quality of life.

]]>
<![CDATA[OR23-03 Post-Operative Day One Morning Cortisol Value as a Biomarker to Predict the Recurrence of Cushing Disease]]> https://www.researchpad.co/article/elastic_article_8729 Tumor removal by transsphenoidal surgery (TSS) is the first line treatment for Cushing disease (CD). However, recurrence is relatively common. A one week post-operative (post-op) nadir cortisol has been used as a biomarker to predict recurrence1. We identified 299 CD patients from our longitudinal multidisciplinary clinic or our institutional RPDR search tool who met biochemical diagnostic criteria1 and had undergone TSS between May 2008 and May 2018, to evaluate post-op cortisol levels as biomarkers to predict long-term remission and to characterize clinical features of Cushing syndrome. Predictors of recurrence were identified with logistic regression, using recurrence as the dependent variable, and a Kaplan-Meier survival curve analysis was performed to compare long-term remission after TSS among the 202 patients who reached initial remission and had at least 1 year of follow-up. The post-op day 1 morning (AM) cortisol had significant association with CD recurrence (OR=1.025, 95%CI:1.002-1.048, p=0.032). The time to recurrence was significantly longer in patients with post-op day 1 AM cortisol <5 μg/dL. In contrast, one week post-op nadir cortisol (OR=1.081, 95%CI: 0.989-1.181, p=0.086), urinary free cortisol (OR=1.032,95%CI: 0.994-1.07, p=0.098), or late night salivary cortisol (OR=1.383, 95%CI:0.841-2.274, p=0.201) had no significant correlation with recurrence. There were no significant differences in time to recurrence for post-op day 2 AM cortisol <5 μg/dL. Among patients who developed post-op adrenal insufficiency, recurrence was significantly lower if glucocorticoid replacement continued for more than one year. In addition, tumor proliferative index (MIB-1) had a significant correlation with recurrence (OR=1.287, 95%CI:1.106-1.498, p=0.001). The most common symptoms and signs of initial presentation of CD were weight gain (91.6%), central obesity (79.6%), menstrual disorders (77.9%), round face (65.9%), hypertension (63.2%), mood disorders (60.2%), dorsocervical fat deposition (59.9%), supraclavicular fat deposition (59.9%), osteoporosis (58.9%), fatigue (58.2%), bruising (55.9%) and facial hirsutism (54.2%). Most of the best discriminating CD features did not have high sensitivity, such as purple striae (31.4%), facial plethora (33.4%) and proximal muscle weakness (30.8%). Our data show that post-op day one morning cortisol level above 5 μg/dL had significant association with recurrence. In contrast, the one week post-op nadir cortisol level had no significant value to predict recurrence. Our data also suggest that nonspecific symptoms and signs of CD are more common than stereotypical signs. Reference: Nieman LK, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:2807-2831

]]>
<![CDATA[SAT-267 Pregnancy in Acromegaly: Report of Five Cases]]> https://www.researchpad.co/article/elastic_article_8728 Introduction: In acromegaly, there are changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin, hormones very important in pregnancy as well. Despite novel treatments, pregnancy in acromegaly is uncommon, remaining a challenge for clinicians.

We report seven pregnancies in five women with acromegaly.

Clinical Cases: Five acromegalic patients (17 – 35 years-old) underwent seven pregnancies. All patients had macroadenoma: four were submitted to non-curative neurosurgery and two of them had gamma-knife radiosurgery. One patient had medical treatment prior to curative transsphenoidal surgery (TSS).

One patient being treated with estroprogestative for hypogonadism had a spontaneous pregnancy; three others had pregnancy just before biochemical diagnosis of acromegaly, one of them had also a spontaneous abortion and another successful pregnancy during treatment with somatostatin receptor ligand (SRL); the last patient become pregnant during treatment with SRL, prior to TSS.

Monitoring was made with IGF-1, GH (assay with no distinction of pituitary GH versus placental GH), prolactin (PRL) and visual field; pituitary imaging was performed after pregnancies in all.

All women conceived naturally, two being on treatment with SRL (discontinued after confirmation of pregnancy). No treatment for acromegaly was administered before delivery. All patients had physiologic pregnancies, delivered full-term healthy babies, no malformations or metabolic disruptions; one did not breast-feed; another one had a spontaneous abortion 2 days after confirmation of pregnancy.

No patient developed either hypertension, pre-eclampsia or gestational diabetes.

In three cases, the clinical suspicion of acromegaly had risen during pregnancy and the diagnosis was made 1 year after delivery. The one with three pregnancies had controlled secretion of GH on Lanreotide and GH and IGF-1 levels remained stable during pregnancy.

The woman with gonadotroph deficiency after TSS and GK and substitutive therapy had a decrease in IGF-1 during pregnancy (45 %), which after delivery returned pathologically to before pregnancy values; GH levels remained stable.

The last patient, who became pregnant with uncontrolled acromegaly on Pasireotide, had increased, but stable GH and IGF-1 (2 X upper limit of normal) before, during and after pregnancy. TSS performed 3 years after delivery cured the disease.

Conclusion: From our experience, patients with acromegaly may have normal babies, even in patients with uncontrolled hypersecretion and lack of medical treatment during pregnancy. The consensus is, however, that there is no indication to use medication to control GH hypersecretion or tumor size in acromegaly patients during pregnancy (1).

Reference: (1) Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy andacromegaly. Pituitary. 2017;20(1):179–184. doi:10.1007/s11102-016-0740-3

]]>
<![CDATA[OR23-01 Intrapatient ACTH Variability in Cushing’s Disease: Prognostic Significance]]> https://www.researchpad.co/article/elastic_article_8719 Introduction: In patients with Cushing’s Disease (CD), intrapatient variability of hormone measurements creates significant clinical challenges, therefore multiple measurements are recommended.1 Urinary and salivary cortisol variation has been well described. However, intrapatient variation of adrenocorticotropic hormone (ACTH) in CD remains unknown. In CD patients, ACTH levels are inherently elevated from baseline but the coefficient of diurnal variation is reduced.2Additionally, at each diurnal time point, these exists a significant variation around the mean for the ACTH levels. In this study, we first analyzed the intrapatient variablility of ACTH at each diurnal timepoint in patients with CD. CD is primarily a disorder of ACTH excess, and treatment directed at pituitary adenomas would presumably perturb ACTH levels prior to affecting serum or urine cortisol. We hypothesized that the coefficient of variation at each diurnal time-point can help predict remission from CD following surgery.

Methods: We conducted a retrospective review of patients (n = 645) who had histopathologically confirmed diagnosis of CD from 2005-2019 (NCT NCT00060541). We selected patients that had ≥ 3 plasma ACTH values over a 7 day span prior to surgical or medical intervention. We grouped the ACTH measurements into morning (AM) and midnight (PM) values to account for diurnal variation in ACTH secretion. We then analyzed post-operative hormone measurements performed every 6 hours prior to administration of replacement corticosteroids. Remission was assigned to patients with nadir serum cortisol level ≤5 mcg/dL within ten days post-operatively3,4.

Results: We found 54 patients with multiple PM (n = 27) and AM (n = 41) ACTH measurements within a 7 day span. We found that the median coefficient of variation (CV) of intra-patient variability was 19.7% (N=41) (95% CI:12.5-27.5) for the AM and was 24% (N=27) (95% CI: 9.6-31.8) for the PM. Age, the number of tests, or the length of test period were not correlated with CV or absolute levels of ACTH. The intraclass correlation coefficient (ICC) of the AM data set was 0.59 and the PM data set was 0.79 which demonstrates a good and excellent reliability respectively. We found that that, in general, 30-60% decrease from pre-operative ACTH levels predicted remission from CD. ACTH decrease >50% on POD2 and 3 had 100% specificity and sensitivity in predicting remission. The decrease in ACTH preceded cortisol nadir in 3/10 patients by 24 hours.

Conclusion: We found significant intra-patient variability in plasma levels of ACTH at individual diurnal timepoints in CD patients. We also found that the change in ACTH >50% on POD2 or 3 is an excellent predictor of remission from CD.

]]>
<![CDATA[MON-303 Giant Growth Hormone Secreting Pituitary Adenomas: A Single Institution Case Series]]> https://www.researchpad.co/article/elastic_article_8718 The prevalence of growth hormone (GH)-secreting pituitary adenoma is around 11-13% of all pituitary adenomas. Giant GH-secreting pituitary adenomas (≥ 4 cm) are rare tumors, and its prevalence of among acromegalic patients is <5%.

This is a retrospective cohort study including patients with giant GH-secreting pituitary adenomas. The study population consisted of 10 patients (5 M/5 F). The mean age at diagnosis was 33.0±12.9 yrs (11-55 yrs). The mean delay between first symptom onset and diagnosis was 2.9 years. The most frequent symptoms were acral enlargement and facial changes (80%), followed by headache (70%) and visual deterioration (50%). One patient had epilepsy. Amenorrhea was presented in three females but obvious galactorrhea in two. The mean adenoma diameter was 42.6±4.7 mm (40-51 mm) at diagnosis. The vast majority of adenomas presented suprasellar extension (100%) or cavernous sinus invasion (80%). Cystic adenomas accounted for 50%. At presentation, mean GH and IGF-1 levels were 40.0±21.4 ng/mL (14.8-51.0) and 2.62±1.09 x ULN (1.08-3.96), respectively. Six patients presented with PRL cosecretion. At diagnosis maximal tumor diameter was not correlated with GH or IGF-1 levels.

All patients underwent pituitary surgery as first-line treatment. Three cases were treated with an endoscopic approach and four cases with a microscopic approach. Transcranial approach was also employed in three cases. Postoperative mean GH and IGF-1 levels were 14.9±16.1 ng/mL (0.6-51.0) and 2.25.±0.82 x ULN (1.48-3.74), respectively. After first surgery, only one patient had more than 50% reduction in IGF-1 levels. Five patients (50%) underwent repeat surgery on two to three procedures because remission was not achieved. Postoperative somatostatin receptor ligands (SRLs) were used by all patients. Six patients were treated with dopamine agonist in combination with SRL. Six patients (60%) received postoperative radiotherapy.

The mean follow-up period was 12.6±5.3 yrs (4-21 yrs). The mean GH and IGF-1 levels were 1.47±1.54 ng/mL (0.08-5.25) and 0.73±0.44 x ULN (0.08-1.56), respectively at the last visit. Residual adenoma was present at the last MRI in eight patients (mean diameter 9.0±3.6 mm). Panhypopituitarism rose from 10% at baseline to 30% at the last visit. During follow-up, one patient diagnosed breast cancer, while another diagnosed thyroid papillary cancer.

Giant GH-secreting pituitary adenomas can have a clinically aggressive behavior with mass effect. Moreover, treatment in patients with giant GH-secreting pituitary adenoma is complex and multimodal therapy is necessary.

]]>
<![CDATA[SUN-312 Strikingly Low Prevalence of Pituitary Incidentalomas in Our Hospital]]> https://www.researchpad.co/article/elastic_article_8717 Introduction: Pituitary incidentalomas (PIs) have been reported in 10.6% of autopsies, 4-20% in computed tomography scans (CT) and 10-38% in magnetic resonance imaging (MRI), most of them microincidentalomas(<1cm). They may be have autonomous hormonal activity or impair normal gland function. The frequency of PIs in Uruguay is unknown. We aimed to investigate the prevalence of pituitary incidentalomas in our Hospital. Methods: We retrospectively identified all patients who underwent brain CT and MRI at our hospital over a 1-year period for disorders other than known or suspected pituitary disease. The period covered was from January 1 to December 31, 2017. We reviewed all scans; anamnesis and biochemical evaluation was performed on patients who presented PIs. Results: During this period 3894 patients underwent imaging studies. MRI was performed in 1146 patients, and CT in 2748 of them. Mean age was 53,1 ± 19 years, with similar gender distribution (50.6% women). Most imaging studies where ordered in the emergency department (43%), followed by the outpatient clinics (29%) and inpatient wards (28%). Most common reasons that led to request the image were trauma (20.4%), headaches (11.3%) and stroke (10.9%). We detected two PIs, which accounts for a prevalence of 5 cases per 10,000 individuals per year (0.05%). Both where detected by CT, with a MRI done later to further evaluate them. Final diagnosis was of a vascular aneurysm and a sellar meningioma. Work-up showed a secondary hypothyroidism in the patient with the sellar meningioma. No cases of pituitary adenomas were found. Discussion: We observed a strikingly lower prevalence of PIs than that reported in the literature. In addition, no PIs where found in MRI. Moreover, no pituitary adenoma was discovered. The reasons for these findings are unknown. In our study scans were not focused to the pituitary fossa so small lesions may have been missed. However, Esteves et al(1) reported a prevalence of PIs 5.8% in 1232 patients who had head MRI/CT, not pituitary MRI. In addition, the majority were pituitary adenomas, almost 40% of them microadenomas. Slices of 2-mm thickness were obtained in the scans, similar to imaging techniques used in other studies. Most reports have longer study duration (3-5 years).Our hospital is a teaching hospital where fellows evaluate scans initially, which are then reevaluated by neuroradiologists. This may account for the prevalence found, as sensitivity may be lower when professionals in training evaluate scans. In addition, frequency of pituitary hipointensity areas may decrease as the number of reviewers increase. Furthermore, this low prevalence could be related to difference in population characteristics.Conclusions: We found a very low prevalence of PIs in our hospital. More studies are warranted to further investigate frequency of PIs in our country. (1)Esteves et al. Pituitary. 2015;18(6):777-81.

]]>
<![CDATA[SUN-LB47 Extended Release Octreotide Pharmacokinetics in Healthy Subjects After Subcutaneous Injection of MTD201]]> https://www.researchpad.co/article/elastic_article_8706 An open-label, randomised, single-dose Phase I study in healthy subjects evaluated octreotide pharmacokinetics after deep-intramuscular (IM) or subcutaneous (SC) injection of MTD201 (30mg). All subjects received Sandostatin® (100μg immediate release; SIR) by deep SC injection 24h before MTD201. MTD201 is manufactured by Q-Sphera™ printing technology to minimize particle size variation and afford simpler reconstitution and less painful injection via a 21G needle. Plasma octreotide concentrations were measured over 63 days to ascertain the potential for a 6- to 8-week dosing interval. MTD201 is being developed as a next generation long-acting somatostatin analogue for maintenance management of acromegaly and neuroendocrine cancer patients. Methods: 28 healthy subjects were randomised to two groups. The reference product SIR (100μg) was injected SC, followed 24 hours later by MTD201 administered by either IM (n=14, 38mm 21G needle) or SC (n=14, 16mm 21G needle) injection. MTD201 was resuspended in WFI to give a final injection volume of 1.5mL. Plasma samples for determination of octreotide and serum samples for IGF-1 and GH levels were drawn pre-dose and over the 63-days post-dosing. Injection site reactions and AEs were recorded, scored and compared across groups. Results: MTD201 was very well tolerated by both groups with 3 mild TEAEs observed per group. Transient and mild injection site reactions were similar after all treatments. Upon MTD201 injection, a low initial burst of octreotide (<1ng/mL) was followed by a sustained period of release that extended beyond the final sampling point at Day 63. Cmax values of 5.42ng/mL (SC) and 3.68ng/mL (IM) were within the plasma exposure range reported for marketed octreotide products. Octreotide bioavailability was 47% (IM) and 62% (SC) relative to SIR. Sustained suppression of IGF-1 concentration was achieved throughout the study period to similar levels for both groups. Octreotide PK profiles and overall exposures were similar between groups, indicating that these routes may be interchangeable in clinical use.Conclusions: MTD201 (30mg) by either IM or SC injection produced continuous octreotide release over a period of at least 63 days at levels predicted to maintain efficacious plasma concentrations at steady state with a dosing interval of up to 8 weeks. Reduced plasma IGF-1 concentrations were maintained throughout the study period. Unlike marketed octreotide depot products, MTD201 can be simply and rapidly reconstituted in WFI to give a stable suspension injectable via 21G needle in a 1.5mL volume. MTD201 can be developed as an easy to inject SC or IM depot for acromegaly and NETs, with an expected dose interval of 8 weeks, and confirmed patient-centric advantages.

]]>
<![CDATA[SUN-307 Partial Secondary Adrenal Insufficiency and Growth Hormone Deficiency in Fibromyalgia]]> https://www.researchpad.co/article/elastic_article_8704 Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement.

Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol < 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use.

Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology.

All patients achieved hypoglycemia <=40 mg/dL during the insulin tolerance test. Peak median cortisol level was 11 mcg/dL (range 5.4-17). Nineteen patients (86%) also had partial GH deficiency (defined as a peak GH < 4 ng/mL) with a median GH level of 0.36 ng/mL (range 0.03-3.83). Cosyntropin stimulation test was performed in 13 patients (59%) with a 1 mcg dose in 2 patients and 250 mcg dose in 11 patients. The peak cortisol was >=18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment.

Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency.

1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506.

2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.

]]>
<![CDATA[MON-318 Acute, Life-Threatening and Perioperative Complications in Cushing’s Syndrome: Predictors and Outcomes]]> https://www.researchpad.co/article/elastic_article_8700 Introduction

Cushing’s syndrome is associated with significant chronic and acute comorbidities including acute thromboembolic and cardiovascular events. To date, there are no data on the prevalence and predictors of acute and perioperative complications in patients with active Cushing’s syndrome.

Methods

In a single-center cohort analysis we evaluate predictors and outcomes of acute, life-threatening and perioperative complications in patients with active biochemically verified Cushing’s syndrome attending our endocrine department between 1978 and 2016. Any medical complications necessitating hospitalization, including admission to intensive care units (ICUs), from the time of appearance of first symptoms of hypercortisolism until one year after biochemical remission by surgery (or where surgical remission was not achieved, during continuing follow-up) were recorded and classified. Baseline factors related to and predicting acute complications were tested using uni- and multivariate analysis.

Results

The study included 242 patients (m/f n=54/188) with Cushing’s syndrome (pituitary n=99, adrenal n=116, ectopic n=27), 14.0% of which had malignant disease.

At least one acute complication was observed in 54.5% of patients; these included electrolyte disturbances (24.4%), infections (27.7%), thromboembolic events (14.9%), cardiac arrhythmias necessitating medical intervention (5.4%), hypertensive crises (8.7%), acute coronary events (3.3%) and cerebrovascular events (4.1%). At least one ICU admission (excluding post-surgical observance) was required in 13.2% of patients. The majority of complications occurred prior to surgery (60-90%); infections occurred pre- and postoperatively (51.7% vs 48.3%, respectively).

Patients with ectopic Cushing’s syndrome demonstrated a higher likelihood of infection (p<0.001), hypokalemia (p<0.001) and ICU stays (p=0.009) compared to patients with pituitary or adrenal Cushing’s syndrome. Patients with diabetes mellitus at diagnosis (n=81) had a significantly higher frequency of infection (p<0.001), hypokalemia (p<0.001), hypertensive crises (p=0.004), acute coronary events (p=0.029), arrhythmias (p=0.025) and a higher likelihood of an ICU stay (p<0.001).

The total number of acute complications and the number of days at ICU correlated positively with parameters of cortisol excess including urinary free cortisol and the time of hypercortisolism.

Conclusion

This cohort analysis identifies a significantly high prevalence of acute and perioperative complications in Cushing’s syndrome, with one in eight patients suffering a life-threatening situation necessitating ICU admission. These acute complications are positively predicted by the degree of hypercortisolism, emphasizing the necessity for acute interventions aiming to reduce cortisol excess even before definitive disease cure is achieved.

]]>
<![CDATA[MON-310 Factors Associated with Remission After Surgery for Acromegaly]]> https://www.researchpad.co/article/elastic_article_8699 Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas.

Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma.

Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test <0.4 ng/mL.

Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL (<2.5). Macroadenomas were more common than microadenomas (48 vs 12). The average maximum tumor diameter was 15.6 mm and 21 patients were graded as Knosp 3 or 4, which indicated cavernous sinus invasion. Patients were follow for 11.8 years. Overall, the remission rate was 50.0% after surgery. Mean age of patients in surgical remission (51.6 years) was higher than those patients not in remission (47.5 years) (p=0.439). Remission rates for microadenomas and macroadenomas were 75.0% and 44.9%, respectively (p=0.04). Patients who achieved remission had smaller tumors compared with those who failed to attain remission (mean diameter 11.6mm versus 17.8 mm). Using the Knosp classification system and preoperative magnetic resonance images to determine cavernous sinus invasion, Knosp grade 3 to 4 tumors were found in 5 patients in remission and in 16 patients with persistence of disease (p=0.003). Patients who achieved remission had a significantly lower preoperative IGF-1 level (650.5 ng/mL) compared with those who did not (1211.0 ng/mL) (p=0.04). Preoperative GH levels were lower for the patients who achieved remission (18.7 ng/mL) than for those who did not (32.5 ng/mL, p=0.006).

Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.

]]>