Pituitary Lesions Research Articles

Missed pituitary microadenoma during endoscopic transsphenoidal surgery for short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing with symptom relief: illustrative case.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare headache disorder that has been associated with pituitary adenomas. Resection has been posited to be curative. A 60-year-old female presented with a 10-year history of SUNCT, which had been medically refractory. Sellar magnetic resonance imaging (MRI) showed a 2 × 2 mm nodule in the right anterolateral aspect of the pituitary. Endoscopic endonasal transsphenoidal resection of the pituitary microadenoma with neuronavigation was performed. The patient felt immediate relief from the headaches. Postoperative MRI showed persistence of the pituitary microadenoma and the resection tract to be inferomedial to the lesion. The right middle and partial superior turbinectomy site was close to the sphenopalatine foramen (SPF). The patient was discharged on postoperative day 1 and remained headache-free without any medications at the 4-month follow-up. Resection of pituitary lesions associated with SUNCT may not necessarily be the cause of SUNCT resolution. Manipulation of the middle and superior turbinate close to the SPF may lead to a pterygopalatine ganglion block. This may be the mechanism of cure for SUNCT in patients with related pituitary lesions who undergo endonasal resection.

Role of fT4 and TSH-index fluctuations as early diagnostic tools in milder forms of central hypothyroidism: data from 221 patients with pituitary lesions from a single tertiary center

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

Differential diagnosis of the progressing pituitary lesion in a pregnant woman

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

Abstract #1401801: A Late Diagnosis of Cushing's Disease

Cushing’s disease is a well-known entity that is frequently described in the literature; however, amongst all pituitary lesions, ACTH-secreting tumors are among the least prevalent and are frequently diagnosed later in the disease course when compared to other functional adenomas. Here we describe a case of Cushing’s disease in a patient who had gone without a diagnosis for many years despite her vast symptomatology. A 60-year-old woman presented for a transsphenoidal resection of a pituitary tumor. Endocrinology was consulted for post-operative monitoring. Initially thought to be the usual case of watching for diabetes insipidus and secondary adrenal insufficiency, this patient provided an extensive and unusual history. About 15 years prior, the patient abruptly began to gain weight notwithstanding a healthy diet and a busy lifestyle. After a year of dedicated lifestyle modifications failing to allow for weight loss, the patient underwent bariatric surgery alongside her sister (who had also gained a tremendous amount of weight attributed to overeating). The patient’s sister succeeded in losing a great deal of weight, however the patient plateaued after losing approximately 35 pounds. During the next few years, the patient started breaking bones, first her hip, then her sternum. Her inpatient medical team checked her ACTH, which was found to be 747 pg/mL (reference range 7.2-63.3 pg/mL). They then checked her AM cortisol, which was not surprisingly elevated to 56.5 mcg/dL (reference range 6.0-18.4 mcg/dL). The patient endorsed numerous symptoms of Cushing’s disease and was referred to an endocrinologist who ordered an MRI of her brain, revealing a macroadenoma. The patient underwent tumor resection and was able to lose over 100 pounds over the course of the next year. Over the following 10 years, the patient remained asymptomatic, until she suddenly, and familiarly, began to gain a copious amount of weight and again experienced fatigability, easy bruising, and hair growth. The patient knew to re-present to her endocrinologist, at which time both her ACTH and cortisol were both elevated (1082 pg/mL and 39.0 mcg/dL, respectively). An MRI of the brain performed at that time revealed recurrence of her pituitary tumor. The patient went for a second resection of her pituitary lesion, after which time our endocrinology team was consulted. Patient did require treatment for diabetes insipidus, secondary AI, and central hypothyroidism, however her symptoms of Cushing’s quickly resolved, and her AM cortisol two days post-operatively was found to be 0.7 mcg/dL, indicating a successful tumor removal. This particular case of Cushing’s disease recurrence highlights the importance of continued post-operative monitoring. Although frequent monitoring may not be indicated, and blood work and imaging may be spaced out, it may be good practice to watch these patients closely to prevent further disease sequalae. Furthermore, we are reminded that a secondary workup of obesity is of paramount importance, as this patient likely would not have required bariatric surgery has she been properly workup up for endocrinological causes of weight gain.

Abstract #1412022: A Rare Case of Multiple Endocrine Neoplasia Type 1 (MEN1) Presenting with Recurrent Abdominal Pain

MEN1 is a rare genetic disorder characterized by combined occurrence of two or more tumors involving parathyroid, anterior pituitary and the neuroendocrine tissue of gastro-entero-pancreatic organ system. We present a case of a young male with recurrent abdominal pain who was later diagnosed with MEN1 syndrome. 27-year-old male with past medical history of chronic abdominal pain presented for an episode of acute upper abdominal pain which was constant and worsened with any movement or palpation. His family history was significant for father having parathyroid disorder and skin lesions. On examination, he was ill appearing with tachycardia, multiple skin lesions and tenderness in upper abdomen. Labs were significant for leukocytosis and hypercalcemia (corrected level 10.5 mg/dl). Rest of the electrolytes, kidney function, liver enzymes and lipase were normal. Computed tomography (CT) abdomen showed inflammatory changes and thickening along the distal stomach/proximal duodenum with scattered free air, concerning for a perforated ulcer. Indeterminate bilateral adrenal nodules were also noted. Patient underwent emergent exploratory laparotomy and was noted to have small perforation in the anterior proximal portion of the duodenum which was repaired. Post-operatively, work up for persistent hypercalcemia revealed parathyroid hormone levels of 152 pg/ml and 25-hydroxy vitamin D of 13.7 ng/ml. He was diagnosed with primary hyperparathyroidism and upon stabilization, discharged with plan for outpatient follow-up. After few months, he had another admission due to worsening epigastric pain. Repeat CT abdomen showed multiple pancreatic lesions involving head, tail and uncinate process and stable adrenal nodules. Presence of pancreatic lesions, gastric ulcers, hyperparathyroidism, adrenal nodules, and multiple skin lesions raised concern of MEN1. Further evaluation showed elevated gastrin level (633 pg/ml), chromogranin level (2464 ng/mL) and mildly elevated prolactin. Rest of pituitary and adrenal axis hormone levels were normal. MEN1 gene testing was positive. No pituitary lesion was identified on magnetic resonance imaging brain. He underwent subtotal parathyroidectomy and cervical thymectomy. He was continued on twice daily pantoprazole and was discharged home in stable condition. MEN1 tumor types and age of tumor onset can differ significantly, and tumors become evident either by hormonal overproduction or by tumor growth. There are no genotype phenotype correlations, even within the same family. Pharmacological therapies to suppress hypersecretion are often first line and can be successful in up to 50% patients. Surgery is an option for patients with hypersecretion unresponsive to medical therapy, compression of the optic nerves and/or chiasma endangering vision or when there is uncertainty of diagnosis requiring biopsy. MEN1 is linked with higher mortality. Approximately 70% of the MEN1 deaths are due to thymic neuroendocrine tumors (NETs) and duodenopancreatic-NETs. Early diagnosis of tumors with appropriate interventions can significantly improve patient survival.

Abstract #1393024: A Rare Case of ACTH-Producing Pituitary Carcinoma in Nelson’s Syndrome

A 55-year-old male with Nelson's Syndrome was originally diagnosed with Cushing’s disease 5 years prior after the identification of a 15 x 13 mm pituitary adenoma and ACTH 174 pg/mL. He had typical symptoms including proximal weakness, easy bruising, abdominal striae, weight gain, and atraumatic vertebral fractures. Pathology following TSRPT at that time showed an ACTH-producing tumor with MIB1 index 20%. He had initial improvement of his Cushing's stigmata but one year later developed proximal muscle weakness, hypokalemia requiring replacement, worsening diabetes, and weight gain. Repeat MRI was negative for new/recurring lesion. One and a half years after initial TSRPT, he started on ketoconazole 400 mg three times daily and cabergoline 1 mg TID as a repeat MRI showed a recurring pituitary lesion measuring 13 x 14 x 9 mm with corresponding ACTH level 159 pg/mL. He underwent radiotherapy with 20 Gy in one fraction and two months later underwent bilateral adrenalectomy with cessation of ketoconazole and cabergoline. Two years later, his ACTH level increased to 1,342 pg/mL and he underwent another fraction of radiotherapy of 20 Gy. A repeat MRI showed a decrease in the size of pituitary lesion. However, eight months later, his ACTH levels peaked at 45,510 pg/mL and he underwent a second TSRPT and a stereotactic radiosurgery series of 54 Gy in 30 fractions over three months. Surgical pathology showed a low-grade neuroendocrine neoplasm without any mitotic figures and an MIB-1 index 15% Two months following the SRS series, his ACTH levels peaked at 188,567 pg/mL. He presented to the ED for abdominal pain and CT Abdomen showed possible metastatic lesions in the liver, one of which was subsequently biopsied and positive for pituitary carcinoma. He is currently undergoing capecitabine chemotherapy and an SRS series to the liver with plans to add temozolomide upon completion of the SRS. A key learning point is to suspect metastatic disease with drastic ACTH increases. PET scan imaging is recommended in a patient with rapid or significant increase in ACTH level with or without progression of a lesion centrally. Additionally, although the original histology did not show carcinoma, the elevated MIB-1 index should raise the suspicion for malignant possibility and therefore, increased surveillance. Functional pituitary carcinoma has the twofold task of treating the excess hormone production and controlling the spread of metastatic disease. Given the rarity of this type of cancer, a multi-disciplinary approach best serves the patient including endocrinology, oncology, (neurological) surgery, and radiation oncology. More data and studies are needed to definitively assess efficacy of chemotherapeutics including capecitabine and temozolomide for these types of tumors.

Abstract #1401381: Rare Case of Asymptomatic Multiple Sclerosis Lesions in Hyperprolactinemia

Hyperprolactinemia is associated with established multiple sclerosis (MS) and MS progression/relapse. An association between hyperprolactinemia and asymptomatic MS lesions, also known as radiologically isolated syndrome (RIS), has not been reported. A 29-year-old African American man presented with gynecomastia during a primary care visit. Medical history included prediabetes, hypertension, and obesity. He denied galactorrhea, decrease in libido, blurred vision, fatigue, enlarged hands/feet, hyperpigmentation, depression, easy bruising, skin changes, polyuria, and any neurological symptoms. His physical exam was unremarkable except for bilateral gynecomastia and obesity. Laboratory results revealed elevated prolactin 30.6 ng/mL. Thyroid function test was normal. Magnetic resonance imaging (MRI) brain showed normal pituitary gland size with a 0.3-cm rounded hypo-enhancing region, enhancement of the left optic nerve, and areas of abnormal T2/FLAIR lesion involving the juxtacortical and subcortical white matter in the left temporal region. Enhancements in the right occipitotemporal region and a small juxtacortical lesion in the medial inferior left frontoparietal region were also observed. The patient was referred to endocrinology. His only complaint was fatigue, and physical exam was unremarkable. Repeat prolactin was higher than before at 78 ng/mL. TSH was elevated at 6.44 mIU/mL with a free T4 of 1.03 ng/dL. Labs including ANA, AQP 4, Lyme, HIV, JC virus, and syphilis panel were negative. He was started on cabergoline 0.5 mg twice weekly for treatment of hyperprolactinemia. He was also started on levothyroxine for fatigue, which was attributed to subclinical hypothyroidism. Neurology initiated treatment for MS with diroximel fumarate. Follow-up in 2 months showed a prolactin level of 1 ng/mL and a normal TSH and free T4. The patient will be followed with MRI pituitary surveillance at 1 year and 5 years. This is a very rare case of hyperprolactinemia associated with RIS. The decision to treat the patient for MS was made to prevent or delay potential clinical symptoms or progression to overt disease. One study has noted a 34% risk of conversion of RIS lesions to the first clinical event of MS in 5 years, especially with risk factors like young age and male gender. However, it is still debatable whether RIS lesions progress and should be treated, given that medications used to treat MS are associated with possible side effects including allergic reaction. Follow-up will focus on presence of new neurological symptoms concerning for MS and change in the size of the pituitary lesion.

Letter to the Editor Regarding “The Oculomotor Cistern and its Role in the Management of Pituitary Lesions: An Anatomical, Radiographic, and Clinical Scoping Review”

Our aim was to assess the 5-year h-index (h5)-index by nation. We aimed to assess the relationship between a nation’s h5-index and numbers of neurosurgeons, population, gross domestic product (GDP), and expenditure on both health and research.Using Web of Science we collected data on each nation’s h5-index and number of publications for the 5-year period 2016 to 2020. Neurosurgical data were collected from the global neurosurgical workforce map provided by the World Federation of Neurosurgical Societies. National economic data were collected from the World Bank Open Data provided. We analyzed how economic and neurosurgical factors correlated with h5-index and publication numbers.We report the top 28 countries ranked according to their h5-index. Regarding the h5-index the strongest positive relationship was found with GDP, proportion of GDP spent on health and total amount spent on health per capita. In regard to the total number of publications (2016 to 2020), the strongest positive relationship was found with GDP and total number of neurosurgeons.This is the first study to explore the h-index between nations on an international level. GDP and proportion of GDP spent on health expenditure are the strongest correlates of the h5-index. Although a higher number of neurosurgeons in a nation does result in more publications, this is not necessarily translated into higher quality research.

Abstract #1407012: ACTH Producing Pituitary Adenoma Found After Transsphenoidal Resection of Meningioma

ACTH-dependent Cushing's disease (CD) is a condition characterized by pituitary hypersecretion of ACTH, leading to adrenal cortisol upregulation. Hypercortisolism has long-term complications, notably metabolic syndrome, cardiovascular disease, and osteoporosis, to name a few. The incidence of CD is approximately 1-2 cases per million. ACTH can be secreted by pituitary macroadenomas and microadenomas, and in some cases, ectopic sources. This case report describes a case of ACTH-dependent CD caused by a pituitary microadenoma with a history of planum sphenoidal meningioma. 48-year-old female with a past medical history of planum sphenoidal meningioma s/p transsphenoidal partial resection, central hypothyroidism on levothyroxine, and hypogonadotropic hypogonadism presented with worsening truncal obesity and prediabetes. The physical exam was remarkable for obesity and hyperpigmentation of knuckles. Labs were significant for elevated AM cortisol at 27.2 mcg/dL with a significantly elevated ACTH level of 81.8 pg/L. Saliva cortisol at 11pm was also mildly elevated at 0.154 ug/dL. The cortisol level was not suppressed with the low-dose dexamethasone suppression test at 8.5 mcg/dL, while High-dose dexamethasone suppressed cortisol to 2.0 mcg/dL, indicating a possible pituitary source. Other biochemical tests such as Prolactin, TSH, and HGH levels were normal. MRI of the pituitary was performed to locate the potential source and was significant for hypo-enhancing lesions suspicious for bilateral synchronous pituitary microadenomas (9x5 mm right and 4x4 mm left). To confirm that there are no ectopic sources for the ACTH, a PET Dotatate scan was done and showed hypermetabolic meningioma corresponding to the findings of the pituitary MRI and confirmed no other abnormal focal radiotracer uptake. Non-functioning pituitary tumors are common, hence, to confirm the pituitary source of ACTH prior to surgery, she underwent inferior petrosal sinus sampling (IPSS). This revealed a significantly elevated ACTH secretion from the right microadenoma. Transsphenoidal resection of the pituitary tumor was performed. Post-procedure, AM cortisol levels were undetectable and ACTH level was low at 5.8 pg/mL. She was then started on hydrocortisone for presumed adrenal insufficiency post pituitary lesion resection. No signs of diabetes insipidus were shown after surgery—the patient will follow up with endocrinology for eventual weaning off hydrocortisone. Simultaneous occurrence of pituitary adenoma and meningioma without a history of radiotherapy is extremely rare, with only 49 cases described before 2019. Even more rare, is an ACTH secreting pituitary adenoma coexisting with a meningioma. IPSS procedure was performed after MRI in this case to get even more accurate localization of the source before surgical excision, as it is the best test to differentiate pituitary from ectopic ACTH-dependent Cushing’s. In approximately 1 out of 3 patients, remission is not achieved with surgical excision alone. For this reason, patients need post-operative monitoring and secondary medications to control their symptoms.

Abstract #1413579: Rathke Cleft Cyst Unveiling Incidental Prolactin Producing Adenoma

Rathke cleft cysts (RCCs) are benign sellar and or/suprasellar lesions that arise from remnants of Rathke's pouch. Pituitary hormonal dysfunction associated with RCCs most often present as hormonal deficiencies due to compression. However pituitary hyper-secretion may coexist with RCC challenging diagnosis and management. A 37-year-old female presented with worsening headache, bilateral blurry vision and pressure-like eye pain for two weeks. She denied any galactorrhea or irregular periods. Her medications included as-needed butalbital-acetaminophen-caffeine and alprazolam. CT Head without IV contrast revealed a pituitary lesion measuring 1.9 cm extending near the inferior margin of the optic chiasm. Subsequent MRI Pituitary with and without IV contrast revealed an enhancing sellar/suprasellar solid lesion measuring 1.6 x 2.7 x 1.9 cm with small hypoenhancing components associated with expansion of the sella, rightward infundibulum deviation, mass effect on the optic chiasm and left cavernous sinus invasion. Pituitary secretion workup revealed an elevated serum prolactin level of 50.4 ng/mL (range 4.8 - 23.3 ng/mL). Repeat prolactin level was 75.7 mg/ml. Dilution studies 1:10 and 1:100 revealed prolactin levels of 78.3 ng/mL and 75.9 ng/mL respectively; absence of hook effect. Her elevated prolactin was attributed to stalk effect given the large size of her sellar mass and relatively minimally elevated prolactin level. Serum Alpha Subunit, ILGF-1, TSH, FT4, LF, FSH, AM cortisol and ACTH level were all normal. She underwent endoscopic transsphenoidal pituitary mass resection with pathology results revealing prolactin producing adenoma and RCC. Immunostains were strongly positive for chromogranin A and prolactin while negative for FSH, ACTH, TSH, beta hCG, GH. Prolactin levels 11 days post-resection remained elevated at 50.7 ng/mL. She continued to have regular periods without galactorrhea. Additionally, she expressed desire to attain pregnancy. This case illustrates the presence of a secreting pituitary prolactinoma in the setting of an RCC. Whether these two entities share a common pathophysiology or simply co-exist is unknown. In one study of 33 surgically treated RCC at presentation, 60% had gonadotroph deficiency, 36% had ACTH deficiency, 36% had TSH deficiency, 18% had ADH deficiency and 31% had hyperprolactinemia (1). It is possible that the majority of this patient 's sellar mass was comprised of RCC as a much higher prolactin level would have been expect for the size of her mass. Interesting, her sellar mass exhibited enhancement which is uncharacteristic for RCC, classical described as cystic lesions without calcification or enhancement. Given that her post-resection prolactin level remained elevated and she desires pregnancy, she may require dopamine agonist therapy.

Otolaryngology Considerations of Pituitary Surgery: What an Endocrinologist Should Know.

Endoscopic endonasal skull base surgery is the preferred surgical approach for the management of pituitary adenomas. Perioperative management of pituitary lesions requires multidisciplinary care and typically includes a dual surgeon team consisting of a neurosurgeon and an otolaryngologist. The involvement of the otolaryngologist allows for a safe surgical approach with excellent intraoperative visualization of the tumor to enable an effective resection of the tumor by the neurosurgeon. Detection and treatment of sinonasal pathology is essential prior to surgery. Patients may experience sinonasal complaints following endoscopic transsphenoidal surgery, although this is typically temporary. Sinonasal care in the postoperative period can expedite recovery to baseline. Here we discuss the perioperative factors of endoscopic pituitary surgery that endocrinologists should be aware of, ranging from preoperative patient selection and optimization to postoperative care, with a particular emphasis on anatomic and surgical factors.

A comprehensive diagnostic approach in suspected neurosarcoidosis

Neurosarcoidosis presents a diagnostic challenge in clinical settings, as it has no pathognomonic symptoms or signs and a wide range of differential diagnoses. The aim of this report is to present the pathological features of our group of patients, obtained through a systematic diagnostic approach. This retrospective cohort study enrolled all adult patients primarily diagnosed with neurosarcoidosis at the neurology department of a tertiary center in Sweden over a period of 30 years, from 1990 to 2021. We identified 90 patients, 54 with possible neurosarcoidosis and 36 with probable neurosarcoidosis. CNS biopsy revealed an alternative diagnosis for 24 patients, who were then excluded. The collected data from medical records included demographic and clinical characteristics, systemic and/or neurological isolated involvement, various laboratory tests, including cerebrospinal fluid (CSF), serum analysis, imaging studies (MRI, FDG-PET/CT, and HRCT), nerve conduction studies, electromyography, and pathology reports of central nervous system (CNS), and extra-neural tissue biopsies. Sixty-six patients were included in our cohort. The median age at onset of symptoms was 49 years, with a similar sex distribution. Cranial neuropathies (38%), motor deficit (32%), headache (16%), and pituitary dysfunction (12%) were the most common presenting features. CSF studies were abnormal in 77% of the patients, who showed lymphocytosis (57%), elevated protein (44%), oligoclonal bands (40%), elevated ACE (28%), and raised T lymphocyte CD4+/CD8+ ratios (13%). Strikingly, MRI showed that 17% of the patients presented with isolated pituitary gland lesions. FDG-PET/CT was performed in 22 patients (33%) and confirmed systemic sarcoidosis in 11. Despite our extensive workup, the final classification for our patients only allowed for a definite diagnosis in 14 patients; the remainder were classified as probable (32) or possible (20) neurosarcoidosis. Since 2007, the employment of a structured laboratory and imaging approach and the increasing number of CNS biopsies have facilitated and improved the process of correct attribution in patients with presumptive neurosarcoidosis, especially in patients with isolated neurological lesions. We highlight a higher frequency of pituitary lesions due to neurosarcoidosis than has been classically described. A detailed laboratory diagnostic workup is included.

Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes

Pituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs. To document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy. Twenty-six client-owned dogs with acute onset of neurological dysfunction. Retrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports. Common presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1-weighted hypo- to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7-641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41-1719 days). Dogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome.

Reversibility in male idiopathic osteoporosis possible.

A 44-year-old athletic man presented in 2009 with severe low back pain. Dual-energy x-ray absorptiometry revealed severe osteoporosis; serum testosterone was 189 ng/dL while serum estradiol (E2) measured by liquid chromatography/mass spectrometry was 8 pg/mL. DNA was extracted and sequenced from a blood sample from the patient since his maternal first cousin also had low bone mass and both patients were screened for aromatase dysfunction by PCR analysis for the CYP19A1 gene, which encodes aromatase. No known pathologic mutations were observed in the coding exons, but novel single nucleotide polymorphisms were detected both in the proband and in his cousin. Treatment with topical testosterone started in August 2010. Over the next 8 years, testosterone dosage was varied and switched from topical gel to injections and maintained on depo-injections of testosterone at about 60 mg once per week. Re-examination in March 2012 included a brain MRI to exclude pituitary lesions; hyperparathyroidism was ruled out (normal serum parathyroid hormone, calcium, and calcium to phosphorous ratio) and celiac disease was excluded (negative transglutaminase antibodies). Follow-up in October 2018 showed improved bone mineral density of the lumbar spine by 29% and of the left femoral hip by 15% compared to baseline measurements. This reveals the importance of measuring serum E2 for making the correct diagnosis, as well as for monitoring a therapeutic effect. Herein, we propose treatment of male osteoporosis where serum E2 levels are below about 20 pg/mL with testosterone to reverse osteoporosis. Estrogen deficiency in the diagnosis of male idiopathic osteoporosis. Importance of serum estradiol in male osteoporosis. Role of polymorphisms in aromatase gene on bone health. Reversal of osteoporosis. Tailored testosterone treatment for bone health.

The Oculomotor Cistern and Its Role in the Management of Pituitary Lesions: An Anatomical, Radiographic, and Clinical Scoping Review.

The oculomotor cistern (OMC) is a cerebrospinal fluid space bound by meningeal layers that surrounds the oculomotor nerve as it crosses the oculomotor triangle to reach the lateral wall of the cavernous sinus at the level of the anterior clinoid process. Although several anatomical and radiological studies are available, its anatomy and relationship with pituitary adenomas (PAs) are still matter of discussion. The aim of the study is to provide an updated and focused overview of the OMC, highlighting the different perspectives and descriptions from anatomical, radiological, and clinical points of view. A scoping review was conducted up to 29th October 2022, according to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) criteria. PubMed, Web of Science, Scopus databases, and correlated citations were investigated. Of the 562 records identified, 22 were included in the present analysis. There were 13, 5, and 4 anatomo-surgical, radiological, and clinical studies, respectively. Though there is general consensus on its definition, data are variable on different features of OMC. Defects or absence of dural layers adjacent to the oculomotor nerve were described in only 4 papers. The transition from meningeal to neural layers is still unclear. PAs with OMC involvement are poorly studied and have unique clinical characteristics. To date, 21 patients have been described; the reported prevalence of OMC involvement by PAs ranges from 4.1% to 14.6%. Clarifying the OMC features with further systematic studies may not only broaden theoretical knowledge but also have implications on endoscopic transnasal pituitary surgery.

Severe Obesity Associated With Pituitary Corticotroph Hyperplasia and Neoplasia

ObjectiveTo investigate the incidence of corticotroph hyperplasia (CH) or lymphocyte infiltration in the pituitary of patients with obesity. MethodsThe pituitary and adrenal glands from 161 adult autopsies performed between 2010 and 2019 at our institution were reviewed. The clinical history, body mass index (BMI), and cause of death were recorded. Routine hematoxylin and eosin staining, reticulin staining, and immunohistochemical staining for adrenocorticotropic hormone, CD3, and CD20 were performed. The results were analyzed using the Fisher and chi-square statistics. Decedents were separated into 4 groups based on BMI (kg/m2): (1) lean (BMI, <25.0), (2) overweight (BMI, 25.0-29.9), (3) obesity class I (BMI, 30.0-34.9), and (4) obesity classes II to III (BMI, >34.9). ResultsCH/neoplasia was identified in 44 of 161 pituitary glands. Four (9.1%) of 53 lean patients had pituitary lesions, whereas 27.3% (12) of overweight, 22.7% (10) of obesity class I, and 40.9% (18) of obesity class II patients had hyperplasia (P < .0001). Small corticotroph tumors were identified in 15 patients; only 1 was a lean patient, and the tumor was associated with the Crooke hyaline change of nontumorous corticotrophs. The presence of CH and neoplasia was associated with adrenal cortical hyperplasia and lipid depletion. Microscopic foci of T and B lymphocytes were identified in the pituitaries of patients in each weight category; no independent association between BMI and lymphocyte inflammation was found. ConclusionOur data indicate an association between CH/neoplasia and obesity. It remains unclear whether obesity is the cause or effect of adrenocorticotropic hormone and cortisol excess.

Rhinologic outcome of endoscopic transnasal-transsphenoidal pituitary surgery: an institutional series, systematic review, and meta-analysis

PurposeWe aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery.MethodsRetrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed.ResultsThe institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher’s exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0–2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1–3.0), a postoperative synechiae rate of 7.5% (IQR 1.8–19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5–5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting.ConclusionEarly and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.

Primary pituitary lymphoma successfully treated with Bruton’s tyrosine kinase inhibitor monotherapy: case report

Introduction: Primary pituitary lymphoma (PPL) is a rare disease characterized by lymphoma confined to the sella or parasellar region without systemic involvement. The clinical symptoms of PPL may include headache, hypopituitarism, visual field disturbance and visual impairment. To date, there is no established standard treatment for this condition. Here, we present a case of successful treatment with a Bruton’s tyrosine kinase (BTK) inhibitor. Case report: A 78-years-old man with a history of severe left renal insufficiency caused by retroperitoneal fibrosis, and sequential right nephrostomy, underwent brain magnetic resonance imaging (MRI) due to the altered hormonal status. An enlarged pituitary stalk was noted and led to a diagnosis of lymphocytic hypopituitarism. Six months later, visual field disturbance and visual acuity deterioration developed, and an MRI revealed a neoplastic lesion and further enlargement of the stalk and the pituitary itself, with an obvious optic nerve compression. Expedited transsphenoidal partial resection was performed to relieve the compression. Pathohystology led to the diagnosis of the large B-cell lymphoma of the germinal center origin. Because of the patient’s poor renal function, high-dose methotrexate therapy was not an option; rather, the patient was treated with a BTK inhibitor - tirabrutinib. Symptoms improved within a week, and a follow-up MRI confirmed a marked reduction of the pituitary lesion. Conclusion: BTK inhibitors may be considered as a first-line treatment option for PPL, especially in patients with contraindications for other treatment protocols.

A complex case of metastatic pituitary lesions with unusual presentation

Metastases to the pituitary gland and hypothalamus commonly occur with breast cancer in women. It is unusual and rare if these metastases are discovered late (10 or more years of primary tumor diagnosis), follow an indolent course and have radiological features suggestive of the inflammatory process.

Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature

BackgroundResistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists.Case presentationA 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week.ConclusionsSurgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.