Nonfunctioning Pituitary Macroadenoma Research Articles

Moyamoya Disease with Non-Functional Pituitary Macroadenoma: A Case Report of a Rare Presentation

Moyamoya Disease with Non-Functional Pituitary Macroadenoma: A Case Report of a Rare Presentation

Coexisting Non-functioning Pituitary Macroadenoma and Sellar-Suprasellar Lipoma: A Case Report and Literature Review

Coexisting Non-functioning Pituitary Macroadenoma and Sellar-Suprasellar Lipoma: A Case Report and Literature Review

Severe Headache and Fever Associated with a Non-functioning Pituitary Macroadenoma: a Case Report

Severe Headache and Fever Associated with a Non-functioning Pituitary Macroadenoma: a Case Report

The Natural History of Clinically Non-functioning Pituitary Macroadenomas (NFPAs) managed conservatively

The Natural History of Clinically Non-functioning Pituitary Macroadenomas (NFPAs) managed conservatively

Long-term outcomes of non-operated non-functioning pituitary macroadenomas - results from the UK NFPA consortium

Long-term outcomes of non-operated non-functioning pituitary macroadenomas - results from the UK NFPA consortium

Natural history and surgical outcome of incidentally discovered clinically nonfunctioning pituitary macroadenomas.

The incidental diagnosis of nonfunctioning pituitary macroadenomas (NFPMAs) is becoming more prevalent with the spread of modern brain imaging techniques. We sought to uncover new data about their natural history and surgical outcome. This is a retrospective single-center observational study. Among 210 patients seen for a NFPMA between 2010 and 2019, 70 (33%) were discovered incidentally (i-NFPMA). We analyzed outcomes in a total of 65 patients with available follow-up data. Mean age at diagnosis (± s.d.) was 60 ± 14 years and mean maximal diameter was 20.0 ± 7.3 mm. At diagnosis, 29 patients (45%) had pituitary hormone deficits (LH/FSH 41%, TSH 29%, ACTH 15%) and 12% had visual field deficits. 26 patients underwent initial surgery, while 12 had delayed surgery after initial surveillance. In the surveillance group, the risk of tumor growth was estimated at 10%/year. Patients with hormonal deficits at diagnosis experienced earlier growth at 24 months (P < 0.02). Overall, surgical resection of the i-NFPMA led to stable or improved endocrine function in 91% of patients, with only 6% postoperative permanent diabetes insipidus. Moreover, surgery was more effective in preserving intact endocrine function (10/12) than restoring altered endocrine function to normal (6/22, P = 0.03). About one-third of NFPMAs are now discovered incidentally and a significant subset may be responsible for unrecognized endocrine and visual deficits. Under surveillance the risk of further tumor growth is significant (10%/year) and seems to occur faster in patients already harboring an endocrine deficit. Early surgical removal before onset of endocrine deficits appears to lead to better endocrine outcome.

FRI474 Panhypopituitarism And Central Hypothyroidism Presenting As Myoclonus And Hyperreflexia, An Unusual Presentation Likely Related To Thyrotropin-releasing Hormone

Abstract Disclosure: I. Nadeem: None. W.J. Khan: None. S. Thapa: None. Introduction: Panhypopituitarism may present with symptoms of predominantly one or more hormonal deficiencies. The thyrotropin-releasing hormone has been described as causing neuromuscular hyperexcitability via its modifying role in synaptic functions in addition to its effect on the pituitary. We present a panhypopituitarism due to macroadenoma presenting with weakness, tongue fasciculation, hyperreflexia, and myoclonic jerks. Case Presentation: A 78-year-old woman with a medical history of essential hypertension came to ER with generalized weakness, twitching of her tongue, and involuntary jerking movements of her lower limbs for the past month. On admission, vital signs were normal. Neurological examination revealed tongue fasciculation and bilateral lower extremity myoclonus. Her visual field testing was normal. CT scan of the head showed an apparent seller mass but ruled out any acute pathology. Further neurologic, infectious, and rheumatologic work-up revealed negative results. In addition, an MRI of the cervical, thoracic, and lumbar spine was negative for any mass effect. The pituitary showed a 2.0 x 1.5 x 2.3 cm sellar mass, deforming the optic chiasm and deviating the infundibular stalk to the right side. Laboratory work-up revealed secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, and hyperprolactinemia. The patient was diagnosed with non-functioning pituitary macro adenoma. Myoclonus significantly improved after initiating the hormone replacement with levothyroxine and a stress hydrocortisone dose, gradually tapered to a physiological dose, and cabergoline. Repeat MRI after three months showed a stable 1.5 x 2.0 x 2.3 cm sellar mass. Surgery was not recommended due to no visual compromise. Instead, she will be followed in the clinic with a 6-month head imaging and hormone testing. Discussion: Usual clinical manifestations of hypothyroidism are the same regardless of etiology. However, there may be additional findings related to hypothalamic or pituitary dysfunction in the case of secondary or tertiary hypothyroidism due to non-thyroidal illness. Muscle fasciculations are common with hypothyroidism. But myoclonus and hyperreflexia are the findings in hyperthyroidism except for one hypothyroid state, i.e., Hashimoto encephalopathy (HE). TRH plays an important role in the pathophysiology of myoclonus and hyperreflexia in patients with HE and without HE. Our patient had tertiary hypothyroidism with likely elevated TRH in the presence of low FT4 and TSH. Therefore, we propose a high level of TRH in central hypothyroidism as the reason for her hyperreflexia and myoclonus. Presentation: Friday, June 16, 2023

THU088 Perioperative Management Of Patients With Pituitary Tumors Undergoing Surgery: A Retrospective Review

Abstract Disclosure: J.T. Batch: None. H. Belal: None. G.Y. Gandhi: None. Background: Pituitary tumors account for 10% of brain neoplasms with transsphenoidal resection of these tumors responsible for 20% of all intracranial operations performed for primary brain tumors. Hypothesis: We suspected significant heterogeneity and lack of standardized protocols in the perioperative endocrine evaluation and management of patients undergoing resection of sellar masses. Methods: From June 2016 through November 2022, we identified 46 adult patients (23 females, mean age 52 years, age range 25 to 84 years) who underwent pituitary mass resection (44 transsphenoidal and two transcranial approaches) at our institution. We abstracted information about perioperative endocrine evaluation from their medical records. Results: The vast majority (32 patients) had nonfunctioning pituitary macroadenomas. Other indications for surgery included Cushing’s disease (3), prolactinomas (2), acromegaly (3), pituitary metastasis (1), gonadotroph adenomas (2), Rathke cleft cyst (2), and epidermoid cyst (1). Preoperative cortisol level was not measured in 8 patients. The decision to administer intraoperative corticosteroids was not consistently based on preoperative cortisol levels. 24 patients had cortisol levels &amp;lt;11 mcg/dL; 22 received intraoperative corticosteroids at anesthesia induction. 13 patients had cortisol levels ≥11 mcg/dL, and 11 received intraoperative steroids. Two patients had very large pituitary masses (over 4 cm), and one received intraoperative corticosteroids. Of the two patients with Cushing’s disease, one received intraoperative corticosteroids. Cortisol level was checked in 27 patients in the first four weeks after surgery; in the rest, it was measured between 2 months and three years after surgery. All five patients with confirmed adrenal insufficiency with cortisol levels &amp;lt;3 mcg/dL were treated with corticosteroids. 22 patients had cortisol levels in the equivocal zone (3 to 15 mcg/dL), and 16 were treated with corticosteroids. Nine patients ultimately did not have a follow-up in endocrinology. The long-term permanence of the diagnosis of diabetes insipidus could not be established due to a lack of uniform follow-up testing. Conclusions: Patients with pituitary gland tumors represent a heterogeneous yet commonly encountered neurosurgical population. Successful surgical management is critically dependent on the quality of perioperative care. Understanding preoperative evaluation, intraoperative management, potential complications, their management, and strategies for avoidance are fundamental to reduce morbidity and mortality. High-quality evidence guiding perioperative practices in this population is needed. We have used the information gathered in this study to create a multidisciplinary perioperative protocol with expertise from endocrinologists, neurosurgeons, neuro-ophthalmologists, and neuroradiologists. Presentation: Thursday, June 15, 2023

Health-Related Quality of Life Analysis in Patients with Non-Functioning Pituitary Macroadenomas Treated with Transsphenoidal Surgery with or without Radiation Therapy

The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to assess patient-reported QoL in our institutional experience using a cross-sectional survey. We identified 488 patients with NFPMA treated at our institution from 1980-2010 who underwent transsphenoidal surgery (TSS) with or without adjuvant salvage therapy with radiation therapy (RT) and/or surgery. The following validated patient-reported outcome measures were collected: the RAND Short Form-36 Health Survey (SF-36), the Multidimensional Fatigue Inventory (MFI-20), and the Cognitive Failures Questionnaire (CFQ). Clinical characteristics of patients who did and did not receive RT were compared using Wilcoxon rank-sum test or Fisher's exact test. We used multivariable linear regression and reported mean score differences between comparison groups. The response rate to survey invitation was 47% (229 patients). Median age at the time of initial TSS was 55 years (18-85 years). 35% of patients were female. 25% of participants received RT a median of 2.0 years (0.1-22.5) after initial TSS, and 15% of patients had >1 additional surgery after initial TSS. The patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28 mm v 22 mm, p < 0.0001) and were more likely to have visual symptoms (65% v 34%, p = 0.0002 and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients completed QoL questionnaires a median of 7.7 years (1.3-29.9) after initial TSS, at which point patients with hypopituitarism reported worse energy and fatigue (SF-36 Energy/Fatigue: -7.95, p = 0.026) and cognitive function (CFQ: 5.35, p = 0.026). Patients who received RT reported significantly worse general health (SF-36 General Health Perceptions subscale: -8.44, p = 0.032), physical health (SF-36 Physical Health Composite: -4.07, p = 0.042), physical fatigue (MFI-20 Physical Fatigue subscale: 11.68, p = 0.024) and cognitive functioning (CFQ: 6.64, p = 0.0298). The largest QoL differences were seen in patients who experienced a financial stressor after treatment, independent of treatment type. These patients reported significantly worse QoL for most outcomes, including emotional well-being, physical and mental health, social functioning, energy level, and motivation. RT was associated with self-reported unstable/insecure or very dire financial circumstances (28% v 7%, p < 0.0001). Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with decreased QoL in several domains, and these factors may identify patients who can benefit most from early multidisciplinary care, including financial counseling and additional psychosocial support.

Marginless 5-Fraction Robotic Radiosurgery for Unfavorable Nonfunctioning Pituitary Macroadenoma: 5-year Outcomes from a Single Institution Protocol

Nonfunctioning macroadenoma is a commonly diagnosed pituitary tumor. Resection is the favored treatment, with radiosurgery often utilized for residual or progressing disease. Long-term outcomes are established for single-session radiosurgery, but mature outcomes are lacking for multisession radiosurgery. We report our institution's 5-year efficacy and safety results for unfavorable nonfunctioning pituitary macroadenoma patients treated with marginless 5-fraction robotic radiosurgery. Between 2010-2020, patients who completed marginless 5-fraction radiosurgery for the treatment of unfavorable nonfunctioning pituitary macroadenomas were included. A tumor was considered unfavorable if the gross tumor volume (GTV) was larger than 5 cc or if it closely approached a critical structure (optic apparatus, brainstem or pituitary gland). Local control was calculated using the Kaplan-Meier Method. Twenty predominately female patients (60%), age from 21-77 (median: 53 years) were included in this study. All underwent primary resection. Indications for radiosurgery included unresectable recurrence (85%) and residual disease progression (70%). Median tumor volume was 3.4 cm3 (range: 0.3-20.8 cm3) and 40% of the tumors were suprasellar. A mean dose of 28.8 Gy (range: 25 Gy-30 Gy), was delivered to a median isodose line of 80% (range: 75%-89%). The median optic chiasm maximum point dose was 21.8 Gy (range: 12.0-25.9 Gy). Toxicity was minimal with 12 patients (40%) developing acute short-lived headaches and 1 patient (5%) developing a brief ipsilateral 6th nerve palsy. There was no radiation induced optic or pituitary dysfunction identified in this cohort. At a median follow up of 5 years local control was 95%. There was 1 in-field failure pathologically confirmed following surgery for pituitary tumor hemorrhage and 2 radiographically confirmed out-of-field failures in patients with large tumors (>20 cc). The treatment of unfavorable nonfunctioning pituitary macroadenoma with marginless 5-fraction robotic radiosurgery provides excellent local control to date, with minimal toxicity. However, tumors with GTV's greater than 20 cc may require conventionally fractionated treatment with a margin to optimize local control.

Health-related quality of life analyses in nonfunctioning pituitary macroadenoma patients identifies at-risk populations.

The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to investigate associations between patient factors, clinical data, and patient-reported QoL in patients with NFPMA. Patients with treated NFPMA and > 1 year of follow up after transsphenoidal surgery (TSS) and with no evidence of progressive disease were evaluated utilizing the following patient-reported outcome measures: RAND-36-Item Health Survey, Multidimensional Fatigue Inventory, Cognitive Failures Questionnaire. 229 eligible patients completed QoL questionnaires a median of 7.7 years after initial transsphenoidal surgery (TSS). 25% of participants received radiation therapy (RT) a median of 2.0 years (0.1-22.5) after initial TSS. Patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28mm v 22mm, p < 0.0001), were more likely to have visual symptoms (65% v 34%, p = 0.0002), and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients with hypopituitarism reported worse energy and fatigue and cognitive function (p < 0.03). Patients who received RT reported significantly worse general health, physical health, physical fatigue and cognitive functioning (p < 0.05). The largest QoL differences were in patients who experienced a financial stressor, independent of treatment type. Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with more impaired QoL in patients with NFPMA. Awareness of these factors can better guide use and timing of radiation therapy in addition to identifying patients who can benefit from multidisciplinary surveillance.

Non-functioning pituitary macroadenoma following surgery: long-term outcomes and development of an optimal follow-up strategy.

Recurrence and regrowth of non-functioning pituitary macroadenomas (NFPMs) after surgery are common but remain unpredictable. Therefore, the optimal timing and frequency of follow-up imaging remain to be determined. We sought to determine the long-term surgical outcomes of NFPMs following surgery and develop an optimal follow-up strategy. Patients underwent surgery for NFPMs between 1987 and 2018, with a follow-up of 6 months or more, were identified. Demographics, presentation, management, histology, imaging, and surgical outcomes were retrospectively collected. In total, 383 patients were included; 256 were men (256/383; 67%) with median follow-up of 8 years. Following primary surgery, 229 patients (229/383; 60%) achieved complete resection. Of those, 28 (28/229; 11%) developed recurrence, including six needed secondary surgery (6/229; 3%). The rate of complete resection improved over time; in the last quartile of cases, 77 achieved complete resection (77/95; 81%). Reoperation-free survival at 5, 10 and 15 years was 99%, 94% and 94%, respectively. NFPMs were incompletely resected in 154 patients (154/383; 40%); of those, 106 (106/154; 69%) had regrowth, and 84 (84/154; 55%) required reoperation. Surgical reintervention-free survival at 5, 10 and 15 years was 74%,49% and 35%, respectively. Young age and cavernous sinus invasion were risk factors for undergoing reoperation (P < 0.001 and P < 0.0001, respectively) and radiotherapy (P = 0.003 and P < 0.001, respectively). Patients with residual tumour required reoperation earlier than those underwent complete resection (P = 0.02). Radiotherapy to control tumour regrowth was delivered to 65 patients (65/383; 17%) after median time of 1 year following surgery. Radiotherapy was administered more in patients with regrowth of residual disease (61/106; 58%) than those who had NFPMs recurrence (4/28; 14%) (P ≤ 0.001) Following postoperative radiotherapy, one patient (1/65; 2%) had evidence of regrowth, seven (7/65; 11%) had tumour regression on imaging, and no patients underwent further surgery. NFPMs recurrence and regrowth are common, particularly in patients with residual disease post-operatively. We propose a follow-up strategy based on stratifying patients as "low risk" if there is no residual tumour, with increasing scan intervals, or "high risk" if there is a residual tumour, with annual scans for at least five years and extended lifelong surveillance after that.

Pituitary function at presentation and following therapy in patients with non-functional pituitary macroadenomas: a single centre retrospective cohort study

BackgroundNon-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.ObjectivesTo assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up.MethodsAll patients treated surgically with and without radiotherapy for NFPMs between 1987 and 2018 who had longer than six months follow-up were identified. Demographics, presentation, investigation, treatment, and outcomes were collected.ResultsIn total, 383 patients were identified. The median age was 57 years, with a median follow-up of 8 years. Preoperatively, 227 patients (227/375; 61%) had evidence of at least one pituitary deficiency. Anterior panhypopituitarism was more common in men (p = 0.001) and older patients (p = 0.005). Multiple hormone deficiencies were associated with large tumours (p = 0.03). Patients treated with surgery and radiotherapy had a higher incidence of all individual pituitary hormone deficiency, anterior panhypopituitarism, and significantly lower GH, ACTH, and TSH deficiencies free survival probability than those treated with surgery alone. Recovery of central hypogonadism, hypothyroidism, and anterior panhypopituitarism was also less likely to be reported in those treated with surgery and radiotherapy. Those with preoperative hypopituitarism had a higher risk of pituitary impairment at latest review than those presented with normal pituitary function (p = 0.001).ConclusionNFPMs are associated with a significant degree of hypopituitarism at time of diagnosis and post-therapy. The combination of surgery and radiotherapy is associated with a higher risk of pituitary dysfunction. Recovery of pituitary hormone deficit may occur after treatment. Patients should have regular ongoing endocrine evaluation post-treatment to assess changes in pituitary function and the need for long-term replacement therapy.

Is a 20% decrease in free T4 (fT4) levels a reliable marker of secondary hypothyroidism in patients with non-functioning pituitary macroadenoma (NFPA)?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1401779: Rare Case of Functional Gonadotroph Adenoma

Of all pituitary adenomas, approximately 25-35% are clinically nonfunctioning or "silent" and of those approximately 70-90% are gonadotropin adenomas making them the most common nonfunctional pituitary macroadenoma. However, it is important to know that gonadotropin adenomas can be functional and that gonadotropin excess can result in clinical symptoms and lab abnormalities. This case demonstrates an example of a functional gonadotropin pituitary adenoma overproducing FSH resulting in high-normal testosterone level in addition to compressive symptoms of the optic chiasm. 57-year-old African-American male with pre-diabetes mellitus and gout (only home meds are allopurinoL 300 MG once daily and indomethacin 50 MG three times daily) presented for evaluation of vision loss and large sellar mass on MRI. Vision loss first noted January 2022 along with occasional headaches for 3-4 months (no headaches prior). Patient eventually saw a neuro-ophthalmologist for visual field testing demonstrating left field deficits concerning for optic nerve compression. He then underwent orbital MRI which demonstrated a large sellar mass extending into bilateral cavernous sinus and effacing and displacing the optic chiasm. During visit, patient admitted to fatigue, constipation, polyuria, and nocturia. He denied‌ breast tenderness, nipple discharge, weight change, temp intolerance, skin/hair change, palpitations, tremors, increase hand/foot size, teeth spacing change, worse glycemic control, hypertension, joint pain, acne, hirsutism, striae, clotting disorders, fractures, decreased libido, or erectile dysfunction. He had no known allergies. Blood pressure109/83 | Pulse 101 | Ht 5' 10" (1.778 m) | Wt 88.2 kg (194 lb 7.1 oz) | SpO2 97% | BMI 27.90 kg/m2. Physical exam: Visual fields intact to confrontation but with some patchy deficits in the left eye only. No other notable findings. Subsequent labs demonstrated appropriate cortisol 11.8 ng/dL with normal ACTH of 17 pg/mL, normal IGF-1 of 95 ng/mL, normal TSH of 1.6 uIU/mL with normal free T4 of 0.8 ng/dL. However, prolactin was mildly elevated at 36.5 ng/mL (presumably from stalk effect given size of tumor) and FSH was impressively elevated at 70.3 mIU/mL with a normal LH of 6.5 mIU/mL and a high-normal total testosterone level of 890 ng/dL which was highly suggestive an FSH-producing functional gonadotropin adenoma. It is important to realize the efficacy of surgical resection of functional non-prolactinoma pituitary tumors, especially when the optic chiasm is involved. Patient underwent transsphenoidal resection of pituitary adenoma and indeed pathology revealed a gonadotroph adenoma with SF1 and alpha subunit. He reported slightly improved vision in left eye and had some residual occasional headaches. Awaiting post-operative labs but anticipate normalization of prolactin and FSH and a likely decrease in testosterone level. Awaiting post-operative visual field testing to demonstrate objective improvement. These should be available by the time of the conference.

Rare case of double seronegative ocular myasthenia gravis and non-functional pituitary macroadenoma

Chronic autoimmune neuromuscular disorder known as Myasthenia Gravis (MG). The relationship of myasthenia gravis with pituitary adenomas is relatively uncommon, despite the fact that it is widely known that people with the condition have a higher prevalence of other autoimmune diseases. Here, we describe the case of a 45-year-old Indian man who had complained of severe cephalgia, associated with ocular pain, dizziness, diplopia, ptosis of the unilateral right eye. Although he has a history of severe headaches that started prior to 3 months, his complaints became more obvious at the end of the day. An MRI of the brain revealed an increased pituitary gland that measured 13.7 × 15.5 x 16. 9 mm. Furthermore, post admission histological examinations supported the diagnosis of a double seronegative ocular myasthenia gravis and non-functional pituitary macroadenoma. Following treatment, it was discovered that Pyridostigmin and Prednisolone considerably reduced his myasthenia symptoms. Finally, it should be noted that pituitary tumours are one potential underlying cause of headache in myasthenic patients.

Mental Health, Emotional Stability, and Green-PsychoChemistry through Quality of Life Increased After Treatment for Non-Functioning Pituitary Macroadenomas: - A Systematic Approach

Mental Health, Emotional Stability, and Green-PsychoChemistry through Quality of Life Increased After Treatment for Non-Functioning Pituitary Macroadenomas: - A Systematic Approach

Symptoms at presentation in conservatively managed patients with non-functioning pituitary adenomas

Hypopituitarism and tumor growth are rare in patients with non-functioning pituitary microadenomas (NFPmA). However, patients often present with non-specific symptoms. The aim of this brief report is to examine presenting symptomatologyin patients with NFPmA compared to patients with non-functioning pituitary macroadenomas (NFPMA). We performed a retrospective review of 400 patients (347 NFPmA and 53 NFPMA) who were conservatively managed; no patients had indications for urgent surgical intervention. Average tumor size was 4.5 ± 1.9 and 15.5 ± 5.5mm for NFPmA and NFPMA, respectively (p < 0.001). At least one pituitary deficiency was present in 7.5% of patients with NFPmA and 25% of patients with NFPMA. Patients with NFPmA were younger (41.6 ± 15.3 vs. 54.4 ± 22.3years, p < 0.001) and more commonly female (64.6 vs. 49.1%, p = 0.028). There was no significant difference reported for similarly high rates of fatigue (78.4% and 73.6%), headache (70% and 67.9%), and blurry vision (46.7% and 39.6%). There were no significant differences in comorbidities. Despite smaller size and lower rate of hypopituitarism, patients with NFPmA presented with a high prevalence of headache, fatigue, and visual symptoms. This was not significantly different from patients with NFPMA who were conservatively managed. We conclude that symptoms of NFPmA cannot fully be attributed to pituitary dysfunction or mass effect.

SDHx mutation and pituitary adenoma: can in vivo 1H-MR spectroscopy unravel the link?

Germline mutations in genes encoding succinate dehydrogenase (SDH) are frequently involved in pheochromocytoma/paraganglioma (PPGL) development and were implicated in patients with the '3PAs' syndrome (associating pituitary adenoma (PA) and PPGL) and with isolated PA. However, the causality link between SDHx mutation and PA remains difficult to establish and in vivo tools for detecting hallmarks of SDH deficiency are scarce. Proton magnetic resonance spectroscopy (1H-MRS) can detect succinate in vivo as a biomarker of SDHx mutations in PGL. The objective of this study was to demonstrate the causality link between PA and SDH-deficiency in vivo using 1H-MRS as a novel non-invasive tool for succinate detection in PA. Three SDHx-mutated patients suffering from a PPGL and a macroprolactinoma and one patient with an apparently sporadic non-functioning pituitary macroadenoma underwent MRI examination at 3 T. An optimized 1H-MRS semi-LASER sequence (TR = 2500 ms, TE = 144 ms) was employed for the detection of succinate in vivo. Succinate and choline containing compounds were identified in the MR spectra as single resonances at 2.44 and 3.2 ppm, respectively. Choline compounds were detected in all the tumors (3 PGL and 4 PAs), while a succinate peak was only observed in the 3 macroprolactinomas and the 3 PGL of SDHx-mutated patients, demonstrating SDH deficiency in these tumors. In conclusion, detection of succinate by 1H-MRS as a hallmark of SDH deficiency in vivo is feasible in PA, laying the groundwork for a better understanding of the biological link between SDHx mutations and the development of these tumors.

Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study.

The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow-up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment. Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up terminated if the patient underwent surgery, received cabergoline or was lost to follow-up. Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm. The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow-up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty-three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth. Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.