bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolactinoma in Two Brothers - Unidentified Genetic Cause Versus Co-Incidence?
Authors: Gundluru Rajani , Liu John Chen , Parimi Joseph Theressa Nehu , Naha Sowjanya , Gusov Timur , Syed Hasan 
Published: May 2021

Abstract
Background: Most prolactinomas occur sporadically. Familial prolactinomas are uncommon. Clinical Case(s): A 35 YO male with no significant past medical history presented to endocrine clinic with c/o fatigue, decreased libido, and erectile dysfunction. Labs showed low total testosterone of 177 ng/dl (normal range 250-1100 ng/dl), low free testosterone of 19.9 pg/ml (normal range 46-224), low LH 1.1 (normal range 1.5-9.3 mIU/ml) with elevated prolactin of 47 ng/ml (normal range 2-18). MRI pituitary showed a 4.2x4x6 mm pituitary microadenoma. Physical exam was unremarkable except for obese body habitus. No known family history of MEN syndromes or parathyroid /calcium disorders. Dopamine agonist therapy resulted in significant improvement in testosterone levels, fatigue, and libido. One year after patient’s diagnosis his 32 YO younger brother was evaluated for c/o fatigue, inability to lose weight, left breast enlargement, galactorrhea, and decreased libido. Work up showed markedly elevated prolactin levels of 2405 ng/ml (normal range 4-15), decreased total testosterone of 70 ng/dl (normal range 249-836), low free testosterone of 4.8 pg/ml (normal range 8.7 to 25.1), FSH &lt;0.1 mIU/ml (normal range 1.4-15.4), LH &lt; 0.1 mIU/ml (normal range 1.7-8.6). MRI Pituitary showed a 25x28x20 mm pituitary macroadenoma invading the right cavernous sinus, encasing the right internal carotid artery, and abutting the optic chiasma. Our patient had genetic testing done for sequencing and deletion/duplication analysis of MEN1 and AIP (Aryl hydrocarbon receptor interacting protein) genes—two well identified causes of familial pituitary adenomas—and tested negative for both. His brother was treated with dopamine agonists with marked improvement in Prolactin to undetectable levels within a few weeks. His energy levels, headaches, and sexual function improved and galactorrhea resolved. However, testosterone levels remained below normal range even after 11 months, despite normal prolactin levels. Discussion: Prolactinomas are the most common functional pituitary adenomas, majority of them sporadic. Familial pituitary adenomas in non-syndromic form are rare. Familial isolated pituitary adenoma (FIPA) and Multiple endocrine neoplasia type 1(MEN 1) are two main causes of familial pituitary adenomas. In FIPA, pituitary adenomas occur as a result of mutations or deletions in aryl hydrocarbon receptor interacting protein gene (AIP). Identifying these mutations is important as pituitary adenomas in FIPA tend to be more aggressive, present at a younger age and are resistant to treatment. Our patient tested negative for both MEN 1 and AIP gene mutations. Whether our patient has an unidentified genetic cause or whether it was a coincidence that two brothers have prolactinomas is unclear.
Pulmonary Embolism in Adipsic DI: Can Desmopressin Be a Contributing Factor?
Authors: Campos-Lopes Sara , Monteiro Ana Margarida , Marques Olinda 
Published: May 2021

Abstract
Background: Adipsic DI (ADI) is a rare disease associated with various morbidities. One of them is venous thromboembolism (VTE). In literature there are less than 10 reported cases and scarce management orientations. Classically, in ADI, VTE risk is due to dehydration and acute hypernatremia. Desmopressin should also be considered as it has a known role in blood coagulation such as increasing platelet cohesion and promoting von Willebrand factor release. Clinical Case: A 51-year woman with past medical history of obesity class 3 and a craniopharyngioma surgically intervened 8 months before, underwent a second craniotomy due to recurrent lesion. Postoperatively the patient developed an ADI, hypopituitarism and impairement of higher brain functions namely short-term memory and sleep-wake cycles impairment. She was discharged on desmopressin 0.35mg/day, levetiracetam 1500mg/day, hidrocortisone 15mg/day, levothyroxine 75mcg/day and quetiapine 25mg/day. Two weeks after discharge, the patient was admitted to the emergency room with anorexia and malaise. Tests were consistent with PE: elevated D-dimmer levels and CT angiography revealing bilateral PE. Treatment with enoxaparin was initiated. There was no hemoconcentration or polycythemia; kidney and liver function were normal, and sodium of 148 mEq/L (135-145 mEq/L). Three days before she had normal sodium levels. Respiratory insufficiency, deep vein thrombosis and infection were excluded. The patient did not present signs of dehydration. Brain CT did not show acute alterations. There was no personal history of smoking or family history of thrombosis and the patient was not on bed rest in the previous couple of weeks. During hospital stay abdominal and pelvic CT did not reveal malignancies. The patient was discharged on enoxaparin and posteriorly underwent a mammogram and colonoscopy; both exams without relevant alterations. At the last follow-up visit, she remained hypocoagulated and with desmopressin, with no further episodes of thrombosis. Conclusion: We report for the first time a case of PE in an obese patient with ADI treated with desmopressin and without overt hypernatremia or dehydration. All previously published cases of VTE in ADI have occurred in patients presenting with moderate to severe hypernatremia (sodium 157-181 mEq/L) and some degree of dehydration at the time of the event. Obesity and a recent hospitalization may have contributed to the development of VTE but desmopressin should also be taken into consideration due to its known effects on coagulation. Thromboprophylactic treatment after pituitary surgery and during acute episodes of hypernatremia and dehydration is already warranted in ADI but we additionally suggest considering at least short-term thromboprophylaxis in obese patients with recent ADI diagnosis treated with desmopressin as they might have this additional increased thrombotic risk.
Rathke’s Cyst and Adrenal Insufficiency: A Rare Case of Hyponatremia
Authors: Sen Ranjoy , Geerthan Kalaichelvi , Kapoor Ashutosh 
Published: May 2021

Abstract
Background: Hyponatremia is the most common electrolyte abnormality encountered in clinical practice, the diagnosis of which can be challenging. A holistic approach with appropriate investigations is imperative to its diagnosis and management. We report this peculiar case of a patient with hypopituitarism secondary to Rathke’s cyst resulting in secondary Adrenal Insufficiency, thus causing Hyponatremia.
Case Details: A 32 year male was admitted to hospital with an intractable headache and deterioration in his general wellbeing. His admission parameters revealed a GCS of 15 with normal observations. He had no evidence of meningism and examination of all other systems was unremarkable. He was not on any regular medications and there was no history of trauma. Bloods revealed a Sodium of 122mmol/l, the rest being normal. Investigations including a CT brain, CXR, paired serum & urine osmolality, urinary sodium, Thyroid functions and a 9am cortisol were conducted. Radiological imaging was unremarkable. Subsequently, he was fluid restricted due to a euvolemic fluid status.
Serum osmolality was 246 mmol/kg (275-295 mmol/kg), Urine osmolality 847 mmol/kg, urine sodium 85 mmol/l and a 9 am serum cortisol of 29 nmol/L, in keeping with Adrenal Insufficiency.
A further decline in his Sodium to 116 mmol/L resulted in Hyponatremic Encephalopathy. In view of impending Adrenal crisis, IV hydrocortisone was commenced in conjunction with hypertonic Saline. This was followed by strict monitoring with cautious correction. An anterior Pituitary profile, serum testosterone and Prolactin were requested.
Serum Testosterone levels were 0.4nmol/L (10.0-36nmol/L), FSH- 2.5 IU/L (1.0-11.0 IU/L) and LH- 1.9 IU/L (1.5-9.3 IU/L). Serum prolactin was 85mU/L (45-375 mU/L), TSH- 0.59 mU/L (0.30-6.00 mU/L), Free T4- 13.0 pmol/L (10.4-24.5 pmol/L), IGF1-135 ug/L (60-197 ug/L).
This was suggestive of partial hypopituitarism. An MRI Pituitary revealed appearances in keeping with a Rathke’s cyst occupying the pituitary fossa without compromise of the Optic Chiasma.
Once stable, he was safely discharged with follow-up appointments planned with the Endocrine and Neurosurgical teams.
Discussion: Rathke cleft cysts are non-neoplastic cysts arising from the embryological remnants of Rathke’s pouch in the pituitary gland. Hormonal and visual manifestations can occur if these cysts enlarge and interfere with the Pituitary production and optic chiasma. A proposed mechanism causing Hyponatremia in the context of Cortisol deficiency is increased hypothalamic secretion of Corticotropin releasing hormone (CRH), a Vasopressin secretagogue. Cortisol feeds back negatively on CRH, which is removed with adrenal insufficiency. Hyponatremia is thus often seen in patients with adrenal insufficiency, caused by an inappropriate increase in vasopressin due to cortisol deficiency and inability to excrete free water.
Reduced Visual Field Activity Due to Covid-19 in a Patient With a Pituitary Macroadenoma
Authors: Rosner Matthew Norman , Aridi Ribal Al 
Published: May 2021

Abstract
Background: Vision changes can be the presenting symptom of pituitary macroadenomas. The first-line therapy is transsphenoidal resection except for macroprolactinomas where medical therapy with dopamine agonist (DA) is the initial treatment of choice. Surgical resection is reserved if treatment with DA did not result in decreased serum prolactin (PRL), size of adenoma and/or alleviation of symptoms. With the Covid-19 pandemic, there have been a variety of symptoms reported including ophthalmic manifestations (1). We will present how an acute decrease in vision from Covid-19 nearly led to surgical intervention of macroprolactinoma.
Clinical Case: A 61-year-old woman presented to the emergency room (ER) with complaints of headache in 6/2020. MRI Brain showed a 4.0 x 4.0 x 4.5 cm pituitary macroadenoma with suprasellar extension and invasion of the cavernous sinuses. The mass engulfed the adjacent circle of Willis, the MCAs bilaterally, the PCAs and the superior aspect of the vertebrobasilar system. Initial PRL was 7441 ng/mL (5.2-26.25 ng/mL). She was discharged on Cabergoline 0.25 mg twice weekly. Visual field exam showed mild nonspecific field defects in the right eye and larger diffuse field defects in the left eye slightly more temporal. One month later, Cabergoline dose was increased to 0.5 mg twice weekly with PRL drop to 1161.7 ng/mL. In 8/2020, she started to complain of worsening vision. Ophthalmological exam showed worsening visual fields in both eyes and the optic discs showed temporal pallor. She was referred to ER where she tested positive for Covid-19 and was admitted. CT Head showed stable partially calcified enhancing sellar and suprasellar mass. Repeat PRL was 635.6 ng/mL. Despite reduction in PRL, transsphenoidal resection was considered but was deferred to 9/2020 due to Covid-19. Follow up appointment with Neuro-ophthalmology in 9/2020 prior to scheduled surgery, showed visual field improvement with just mild nonspecific defects and surgery was canceled. PRL in 10/2020 decreased to 239.1 ng/mL. Patient’s visual fields continued to improve after recovery from Covid-19 and with reduction in PRL. It was determined that the patient’s reduction in visual fields was due to Covid-19 and not her macroadenoma.
Conclusion: There have not been many reported cases of decreased visual fields due to Covid-19 (1). Proposed mechanisms include expression of ACE-2 receptors in the aqueous humor, which is the main receptor for Covid-19, and thromboembolic disease (1). More studies and data are needed to conclude the mechanism of decreased visual fields. This will avoid unnecessary surgical interventions for patients with macroprolactinomas.
References: 1. Ho, D., Low, R., Tong, L., et al. COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations. Ocul Immunol Inflamm. 2020 Jul 3;28(5):726-734.
Remitting Seronegative Symmetrical Synovitis With Subsequent IgA Hypergammaglobulinemia. A Case of Chronic Inflammation Causing Macroprolactinemia and a Misdiagnosis
Authors: Zarghamravanbakhsh Paria , Sanchez Jose Gonzalo 
Published: May 2021

Abstract
Prolactin is a pituitary hormone that functions in breast development and milk production in women and also plays an important role in immunoregulation and human immune responses, including autoimmune diseases. Macroprolactin, known as “big-big prolactin”, is due to the presence of marked hyperprolactinemia associated with evidence of prolactin-Ig (typically IgG4 or less frequently IgA) circulating complexes. We describes a case of 51 year-old female, with more than a 4 year history of reported hyperprolcatinemia who was treated with Cabergoline 0.5 mg weekly. Prior to treatment, she reported menses every 30-40 days, but denied galactorrhea or symptoms of sellar mass effect. Our patient had mildly elevated prolactin levels of 40-50 ng/dl. Her Thyroid function test were within normal limits. Patient had two pituitary MRIs in 2017 and 2019 which did not show sellar abnormalities. Prior to cabergolibe initiation, she was diagnosed with RS3PE syndrome (Remitting seronegative symmetrical synovitis with pitting edema) due to bilateral swelling in the dorsum of her hands. She was found to have hypergammaglobulinemia which was related to IgA elevation from chronic inflammation. Further investigation showed actual bio-active monomeric prolactin level was normal (4.8 ng/dl) and macroprolactin elevation from hypergammagolbulinemia. Before diagnosing her paraproteinemia and her macroprolactin predominance, she had received years of dopamine agonist therapy which was discontinued after diagnosis.
We report a novel association of IgA predominant hypergammaglobulinemia from a chronic rheumatologic condition, leading to a misdiagnosed hyperprolcatinemia. Care should be taken to determine monomeric Prolactin levels prior to treatment, specially when symptoms are equivocal and/or imaging studies are negative.
Tolvaptan Use in SIAD (Syndrome of Inappropriate Antidiuresis)
Authors: Burri Sushma , Parthasarathy Sathish Babu 
Published: May 2021

Abstract
Background: SIAD (Syndrome of Inappropriate Antidiuresis) is the commonest cause of hyponatraemia in hospital inpatients. Hyponatraemia is associated with increased length of stay and worse primary clinical outcomes. Our study aimed to evaluate the effectiveness of Tolvaptan, a selective, non-peptide, Vasopressin receptor antagonist, treatment in hospitalised patients with SIAD. Method and Baseline Characteristics: A Retrospective analysis of 9 patients treated with Tolvaptan for a confirmed diagnosis of SIAD was carried out. Information was collected from the inpatient records and biochemical test results. Serum Sodium levels on admission ranged between 104- 124mmol/ L (Normal range 136 -145 mmol/L). Average inpatient days solely due to hyponatraemia was 24 days. The number of in-patient days on fluid restriction ranged from 8-22 days depending on timing of referral to endocrine department. Tolvaptan was only started at a stable serum sodium at 118 mmol/L or greater. Four patients also had a prior trial of demeclocycline. Tolvaptan was started at its smallest dose of 7.5mg OD under strict monitoring of serum sodium with locally agreed protocol. Aetiology of SIAD included lung malignancy, acute demyelinating polyneuropathy, listeria meningitis, autoimmune encephalitis, SSRI (Selective Serotonin Reuptake inhibitor) use, Aspergillosis and Idiopathic (n=3). Results: Serum sodium level improved to &gt;128 mmol/L in 2 days of starting Tolvaptan in all cases. After discharge, there was remote virtual clinic monitoring from the endocrinology team at 2 weeks, 4- 6 weeks and 3 months with a view to stop the medication. No adverse events were observed during use of Tolvaptan in the patient population. Tolvaptan 7.5mg OD was either stopped completely after 4-6 weeks or switched to 7.5mg alternate days depending on the clinical course of underlying pathology. Average duration of Tolvaptan treatment was 4.5 months excluding one patient with chronic lung pathology. 3 patients had further hospital admission on stopping Tolvaptan treatment and treatment with Tolvaptan had to be re-initiated. Conclusion: This study confirms the efficacy of Tolvaptan use in SIAD related hyponatremia. Tolvaptan serves as a cost effective treatment option for hospitalised patients who have either failed to respond to demeclocycline or fluid restriction. In our case cohorts, cost comparison of Low dose Tolvaptan with retrospective calculation of total inpatient days of fluid restriction and use of demeclocycline showed a better outcome and clinical effectiveness with low dose Tolvaptan. We recommend earlier use of Tolvaptan in SIAD under guidance from specialist team as a safe, cost effective and in some cases, as a hospital admission-avoidance strategy.
Underappreciation of the “Hook Effect” leading to Mismanagement of a Patient, a Tale of Preventable Disaster
Authors: Amini Mehdia , Kaur Harsimranjit , Kang Mandip , Naing Soe 
Published: May 2021

Abstract
Introduction: When evaluating pituitary adenomas, one needs to be cognizant of the “hook effect” - an assay artifact leading to under-reporting of extremely high prolactin levels. We report a case of a patient with a macroprolactinoma with an initial reported prolactin level of less than 1.0 ng/dl. Such an extreme case of the “hook effect” in a prolactinoma has not been reported yet.
Case Presentation: A 53-year-old male with a medical history of type II DM initially presented in 2017 with blurred vision. Vital signs and labs, including pituitary hormone levels, were all within normal range. Prolactin level was reported as less than 1.0 ng/dl (normal 2-18 ng/dl). MRI brain showed a large pituitary mass and he was diagnosed with a non-secreting pituitary macroadenoma with mass effect. The patient subsequently underwent transsphenoidal resection of the pituitary adenoma. Prolactin level was noted to be elevated at 1608 ng/dl after the procedure. Unfortunately, the patient was lost to follow up. Two years later, the patient presented again with persistent headaches and worsening vision. MRI brain revealed a large suprasellar mass, measuring at 4.9 x 4 x 3 cm, with extension into the third ventricle and left cavernous sinus, indicating a recurrence of the pituitary adenoma. Prolactin levels measured were elevated 12,030 ng/dl. At this time, the patient was started on cabergoline with significant improvement in symptoms and reduction in prolactin levels to 1792 ng/dl within 4 weeks after initiation of therapy. He is currently still in remission with weekly cabergoline therapy. Conclusion: The most used prolactin assay typically reports the presence of detectable heterotrimeric immune complex formations made up of prolactin antigens sandwiched between ‘capture antibodies‘ at one end and ‘reported antibodies’ at the other end of the prolactin antigen. In prolactinomas, prolactin levels are usually present in relative excess to the two assay antibodies. This leads to the oversaturation of antibody sites with most of prolactin being complexed to only a single antibody instead of two antibodies, thus impairing adequate immune complex formation. Only a few remaining prolactin antigen are “sandwiched” to form the heterotrimeric complex and are therefore reported as “detectable.” As a result, true prolactin levels are substantially underreported, potentially leading to incorrect diagnosis, treatment delay, exposure to surgical risk and complications and increased economic burden to the patient and the healthcare system. The best method to avoid the “hook effect” and to correctly interpret prolactin values would be to obtain prolactin levels in appropriately diluted serum specimens (10-100-fold dilution of the sample). This will lead to appropriate immune complex formations and increase the sensitivity and specificity of the prolactin assay.
A Clinical Audit on Diagnosis and Management of Hypopituitarism in Scarborough General Hospital
Authors: Abraham Santhosh , Ssemmondo Emmanuel , Abobaker Anis , Humphriss David , Pawlak Tadeusz 
Published: May 2021

Abstract
Objectives: The main objective was to evaluate the use and compliance to the guidelines issued by the Endocrine Society in diagnosis and management of hypopituitarism and their impact on the clinical practice in Scarborough General Hospital (SGH). Design: A retrospective review of secondary data of patients with a diagnosis of hypopituitarism in SGH. Methodology: The data was collected from both patients’ case notes and electronic medical records. Data analysis was performed using Microsoft excel. Results: 18 patients with the diagnosis of Hypopituitarism were identified. 5 patients were females and 13 were males. 11 patients aged between 60-80 years, 4 patients were between 51-60 years and 3 patients were between 31-50 years. All the patients had low cortisol levels; however, cortisol was checked at 9AM in only 4 patients. All the patients had their thyroid stimulating hormone levels checked, which were low in all of them. Free T4 levels were normal in 2 patients, and low in 16 patients. 17 patients had low follicular stimulating hormone levels, whereas 15 had low luteinising hormone levels. Testosterone levels were checked in 9 male patients out of which 7 had low levels. Insulin-like growth factor-1(IGF1) was done in all patients and levels were low in 10 patients. All those with low IGF1 had glucagon stimulation test. Serum sodium levels were low in 3 patients and high in 5 patients. Plasma osmolality was only checked in 8 patients (was high in 5 patients). Urine osmolality was checked in 10 patients, and it was low in 5 patients. Brain MRI was performed in 16 patients, and 2 patients had brain CT. The most common cause of hypopituitarism was non-functioning pituitary adenoma (44.4%), and the least common causes were empty Sella syndrome (5.6%) and craniopharyngioma (5.6%). All patients received glucocorticoid replacement therapy, 17 received thyroid hormone replacement therapy, 8 received testosterone replacement therapy, 3 received desmopressin (DDAVP) treatment, and one patient received growth hormone replacement therapy. Conclusion: This Audit shows that our practice in diagnosis and management of hypopituitarism is mostly in line with the recommendation of the Endocrine Society. However, cortisol levels were not always measured at 9:00 am and we are not compliant with performing Growth Hormone stimulation test in every patient.