bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyrotropin-Producing Pituitary Adenomas
Authors: Arguello Mingxue , Levy Shiri 
Published: May 2021

Abstract
Thyrotropin-producing pituitary adenomas are rare cause of hyperthyroidism and it compose about 0.5-3% of all functioning pituitary tumors. Diagnosis of thyrotropin-producing pituitary adenomas can be challenging because TSH concentrations can be normal with only elevated T4. As a result, patient would be simply treated as primary hyperthyroidism. The latency between onset of hyperthyroidism and diagnosis of pituitary adenoma was reported to be 4-6 years. Many patients had radioactive iodine treatment or thyroidectomy treatment for primary hyperthyroidism at the time of diagnosis.
A 35-year-old male with history of intermittent FT4 elevation for the past 3 years presented at endocrine clinic for evaluation. Patient also had recent headache and dizziness. TSH was only marginally elevated once in the past 3 years. Alpha-subunit was found to be 2.6 ng/mL with negative heterophile antibody. MRI showed a 13.7 mm x 20.4mm x16.1mm sellar and suprasellar mass without cavernous sinus invasion but with chiasmal compression. Other pituitary hormone co-secretion was not found in this patient. Patient was treated with octreotide 20mg monthly for 3 month with normalization of T4 and size of the tumor also decreased on the medication. Patients was prepared for transsphenoidal surgery.
Treatment for thyrotropin-producing pituitary adenomas is mainly surgery. However, medical therapy with somatostatin analogs does play an important part in terms of inducing euthyroid prior to surgery. There are also articles describing shrinkage of the tumor prior to surgery while on somatostatin analogs. There were also rare case reports of thyroid storm from thyrotropin-producing pituitary adenomas when patients were not treated with somatostatin analogs prior to surgery. The surgical outcome was determined by the size of the tumor. Transient hypothyroidism or hypopituitarism can happen after the surgery. However, it is more common in external beam radiotherapy or radiosurgery treatment. For thyrotropin-producing pituitary microadenomas, transsphenoidal surgery is the treatment of choice with high remission rate. In some difficult cases where octreotide was not controlling the hyperthyroidism, methimazole use in combination with octreotide after surgery was also documented in the literature. The idea of using somatostatin analogs as primary treatment of thyrotropin-producing pituitary adenomas due to the risk of hypopituitarism with transsphenoidal surgery was explored in some literature. But, no strong evidence of better outcome with medication treatment alone was found.
Unmasking of Neurosarcoidosis
Authors: Venugopal Sharini , Neupane Binita , Nepal Mahesh , Chavez Luis F 
Published: May 2021

Abstract
Introduction: Central diabetes insipidus is a rare complication of neurosarcoidosis. In patients with concomitant adrenal insufficiency (AI), the symptoms of Diabetes Insipidus (DI) can be masked. Case: A 55-year-old female with past medical history of sarcoidosis presented to the hospital with hematemesis, nausea and dizziness. She has a past medical history of cardiac sarcoidosis that was revealed on a PET scan done before 10 years for which she was being treated with methotrexate and prednisone. She was off prednisone for a year prior to hospitalization. She underwent an upper endoscopy that showed diffusely erythematous gastric mucosa in the antrum. She was also hypotensive on admission, and she received packed red blood transfusions after which her sodium increased from 145mmol/L to 165mmol/L (Normal: 135-145mmol/L) in 48 hours. Further workup revealed persistent hypernatremia and urine osmolality was 75mOsm/kg H2O. (Normal: 50-1200mOsm/kg H2O). She was also hypoglycemic and hypotensive requiring multiple fluid boluses throughout her hospitalization. This prompted us to perform a random cortisol that came back at 2.1ug/dl (Normal: 3-23ug/dl) and 1.8ug/dl on two occasions. Cortisol Stimulation test was subsequently ordered, but was done only at 30 minutes, and Cortisol increased from 1.8ug/dl to 6.3ug/dl. Free thyroxine was 0.5 ng/dl (Normal: 0.9-1.8 ng/dl) and her TSH was 7.58uIU/ml (Normal: 0.55-4.78uIU/ml). MRI of the brain revealed extensive areas of extra-axial supra-sellar/infundibular nodular homogeneous intense enhancement that is most consistent with neuro-sarcoid. She was started on prednisone 40 mg daily, Desmopressin 0.05 mg twice daily, and levothyroxine as well. Her sodium level normalized and was 137mmol/L at discharge. She followed up later with outpatient Endocrinology and reported around 90lbs weight gain and no more episodes of nausea or vomiting or epistaxis or lightheadedness. Conclusion: The involvement of the hypothalamic-pituitary axis in sarcoidosis is extremely rare and attributes to &lt; 1% of patients with a sellar mass. Small case series have shown that hypogonadism is the most common endocrine abnormality followed by DI. Our patient had a long-standing history of sarcoidosis with her pituitary dysfunction unmasked only on admission for other causes. She did not manifest any symptoms of DI or AI. There have been case reports where the symptoms of DI are masked due to underlying glucocorticoid deficiency. There have been theories that glucocorticoid deficiency impairs renal water excretion by both ADH (Anti-diuretic hormone) dependent and ADH independent pathways. Another notable feature in our case is that our patient presented with primary hypothyroidism. In fact, sarcoidosis has been commonly implicated in auto-immune polyglandular syndromes type 3, which can present with auto-immune thyroiditis more so in females.
Weiss-Kruszka Syndrome With Unreported Manifestations; Empty Sella Syndrome Associated With Growth Hormone Deficiency
Authors: Park Jisun , Kim Su Jin , Seo GoHun , Lee Ji-Eun 
Published: May 2021

Abstract
Objective: Weiss-Kruszka syndrome (WSKA; MIM#618,619) is a rare, autosomal dominant disorder associated with zinc finger protein 462 (ZNF462) gene variation or deletion of 9q31.2 involving ZNF462 and various congenital anomalies. Its specific clinical findings are abnormal facial shape, prominent forehead, high arched eyebrow, ptosis, delayed development of motor and language and mild global developmental delay. The prevalence of WSKA is only 25 individuals from literatures. Brain lesions related to WSKA are known as ventriculomegaly and middle line brain abnormalities like corpus callosum hypoplasia in about 25 percent of the patients. However, there have not been reported a patient who has structural malformation of pituitary gland with endocrine dysfunction. Here, we present a Korean boy molecularly confirmed as WSKA, having newly clinical manifestation of primary empty sella syndrome(ESS) associated with growth hormone deficiency(GHD).
Case Presentation: A 16-year-old boy visited to our hospital presented with severe short stature and delayed puberty. He also complained mild hypotonia, congenital both ptosis, mild intellectual disability. In the anterior pituitary combined test, GHD was diagnosed. In the brain magnetic resonance image, ESS was showed. With starting and continuing recombinant human growth hormone replacement therapy, to identify the underlying genetic cause, chromosomal microarray analysis and whole exome sequencing test were conducted. Finally, a heterozygous novel frameshift variant, c.4185del(p.Met1396Ter) in ZNF462 confirmed by Sanger sequencing, which had not been reported was identified
Conclusions: This is the first case of WSKA of an Asian with novel pathogenic variant of ZNF462 and new clinical features including primary ESS associated with GHD. This case could contribute to diagnosis of this syndrome, identify clinical features and provided novel insight into studies for the role of ZNF462 gene.
When One Autoimmune Condition Predisposes You to Another!
Authors: Panday Deepika , Jyothinagaram Sathya G , Guo Rong Rong , Correa Ricardo Rafael , Vinales Karyne Lima 
Published: May 2021

Abstract
Introduction: Lymphocytic hypophysitis (LYH) is an autoimmune condition in which pituitary gland is infiltrated by lymphocytes, plasma cells and macrophages. It is more common in pregnant and postpartum women, presenting with headache, visual field changes and one or more pituitary hormone impairment.
Case Presentation: 32year-old female recently diagnosed with RA complicated by uveitis, presented to our facility with headache, shortness of breath, blurred vision and dysphagia. MRI head revealed a 1.9cm sellar mass with suprasellar extension displacing the optic chiasm. There was clear thickening of the pituitary stalk which raised suspicion for autoimmune hypophysitis. Exam in the ED revealed an anxious female wit hypertension, tachycardia and BMI 30. The rest of the physical exam was unremarkable. Her pituitary gonadal axis workup revealed panhypopituitarism with TSH 0.01uIU/ml, FSH &lt;0.3Miu/ml, LH &lt;0.3mIU/ml, ACTH &lt;5pg/ml, IGF-1 31ng/ml and prolactin 14.4ng/ml. She was started on prednisone 50mg daily and on levothyroxine 150mcg daily. On day 2, she developed polyuria and the work up revealed a serum sodium of 146 meq/L, serum osmolality 315mOsm/kg, urine osmolality 281mOsm/kg and urine output 5.6L in 24hrs. The diagnosis of DI was made and she was started on desmopressin. On day 7, the serum sodium normalized and she did not require any other dose of desmopressin. On the day of discharge, a repeat MRI head was done which showed reduced enhancement of the pituitary which was reassuring.
Discussion: LYH is a neuroendocrine disorder characterized by autoimmune inflammation of the pituitary gland with various degrees of pituitary dysfunction. Associated autoimmune diseases are seen in 18%– 50% of cases of AH. The most commonly-associated disease is autoimmune thyroid disease (15%–25%), while concurrent autoimmune conditions including RA are reported as well. Homogenous symmetrical enlargement of the pituitary gland, a thickened non deviated stalk, and a prompt, intense and homogenous enhancement of the mass after gadolinium contrast are the characteristic findings on MRI. Spontaneous resolution is the usual course and surgery is indicated only when the symptoms of sellar compression are serious and progressive.
Conclusion: LYH is predominantly a disease of young females. We present this case in order to create awareness about the co-existence of LH with other autoimmune conditions and its usual course of regression with steroids.
Abnormal Sodium is a Predictor for Respiratory Failure and Mortality in Hospitalized Patients With COVID-19
Authors: Tzoulis Ploutarchos , Waung Julian , Bagkeris Emmanouil , Hussein Ziad , Biddanda Aiyappa , Cousins John , Dewsnip Alice , Falayi Kanoyin , McCaughran P W , Mullins Chloe , Naeem Ammara , Nwokolo Munachiso , Quah Helen , Bitat Syed Rabha , Deyab Eithar , Ponnampalam Swarupini , Bouloux Pierre-Marc Gilles , Montgomery Hugh , Baldeweg Stephanie 
Published: May 2021

Abstract
Background: Hypernatremia and hyponatremia (serum sodium &gt; 145 mmol/L and &lt; 135 mmol/L, respectively) are independent risk factors for excess mortality in patients with bacterial pneumonia. We sought, for the first time, an association of sodium [Na] abnormalities with mortality, need for advanced respiratory support and Acute Kidney Injury (AKI) in hospitalized patients with coronavirus disease 19 (COVID-19). Methods: This retrospective, longitudinal, cohort study included 488 adults, 277 males and 211 females, with a median age of 68 years, who were hospitalized with COVID-19 to two hospitals in London over an 8-week period (February to May 2020). Results: The in-hospital mortality rate was 31.1% with a medial length of stay of 8 days. High [Na] levels at any timepoint during hospital stay were associated with significantly increased mortality rate (56.6% vs 21.1% in patients who remained constantly normonatremic; odds ratio 3.05, 95% CI 1.69-5.49; p&lt;0.0001). On day 3 and on day 6, high [Na] values predicted mortality with an estimated odds ratio of 2.34 (95% CI 1.08 – 5.05, p=0.0014) and 2.40 (95% CI 1.18 - 4.85, p=0.001), respectively. Non-survivors had a significantly higher 5-day rise in serum [Na] when compared to survivors (3.60 mmol/L vs 1.14 mmol/L respectively, p&lt;0.05). Patients with low serum [Na] levels on admission had a 2.18-fold increase (95% CI 1.34-3.46, p=0.001) in the likelihood of needing advanced ventilatory support compared to those with normal [Na] (31.7% vs 17.5%, respectively). However, exposure to hyponatremia at any timepoint, including at presentation or on day 3 or day 5, was not associated with excess risk of
death. AKI affected 37.1% of patients (21.3%, 7.4% and 8.4% stages 1, 2 and 3 respectively) but was not related to serum sodium values. Conclusions: In hospitalized COVD-19 patients, hypernatremia at any timepoint was associated with excess mortality, suggesting that [Na] concentration may facilitate risk stratification. In addition, whilst our data cannot prove causality, these findings highlight the significance of judicious rehydration in such patients.
Acute and Chronic Posterior Pituitary Insufficiency Among Traumatic Brain Injury Patients at a Tertiary Care Center
Authors: Bhat Imtiyaz Ahmad , Bhat Moomin Hussain , Masoodi Shariq Rashid , Bhat Javid Ahmad , Shah Zafar A , Wani Arshad I , Sood Mona , Arif Sajad Hussain 
Published: May 2021

Abstract
Background: Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Disorders of salt and water balance are the most commonly recognized medical complications in the immediate post-TBI period and contribute to early morbidity and mortality. Objective: We aimed to evaluate the prevalence of acute (during hospital stay) and chronic posterior pituitary dysfunction in patients of head injury admitted at our tertiary care hospital. Study Design: Prospective, Observational study. Participants: 136 patients, attending tertiary care in North India with TBI with radiological evidence of head injury. Methodology: The severity of brain injury was assessed by the Glasgow Coma Scale (GCS), and Modified Rankin Scale (MRS) score at the time of admission. Lab measurements, apart from routine CBC and biochemical tests, included tests of serum and urinary osmolality, serum sodium, cortisol, and thyroid function test during the hospital stay. All patients were monitored closely during the hospital stay. Surviving patients were evaluated at 3, 6, and 12 months of follow-up. Urinary output and water deprivation tests were done to determine chronic posterior pituitary dysfunction. The results were compared against normative data obtained from 25 matched, healthy controls. Serum & urinary osmolality was measure by the freezing point method. Diabetes insipidus (DI) and Syndrome of inappropriate ADH secretion (SIADH) were diagnosed according to standard criteria. Results: Of 136 patients admitted, 61 (44.85%) had a mild head injury (GCS, ≤8), 47 (35.55%) had a moderate injury (GCS, 9-12), and 27 (19.85%) had a severe injury (GCS, 13-15). DI occurred in 10 patients (7.4%), while SIADH was observed in 4 patients in the immediate TBI period. Risk factors for diabetes insipidus were GCS of ≤ 8 at admission, midline shift, and surgical intervention. DI was an independent risk factor for death. There was a negative correlation between the presence of DI and GCS score (r, -0.367). Most of the patients with DI (8 out of 10) died during the hospital stay. One patient persisted to have partial diabetes insipidus and another one SIADH at three months post-TBI; both patients had recovered at six months of follow-up. No new case of DI or SIADH occurred on the follow up to 12 months. Conclusion: The incidence of acute DI in severe head injury (GCS ≤ 8) could be an indicator of the severity of TBI, and associated with increased mortality as most of our patients died during the hospital stay.
Resolution of Abnormal Gonadotropin Secretion After Surgical Cure in Men With ACTH-Dependent Cushing Syndrome
Authors: Shekhar Skand , Tonelu Joselyne Tessa , Cutler Gordon B , Nieman Lynnette K , Hall Janet Elizabeth 
Published: May 2021

Abstract
Background: Hypothalamic-pituitary-gonadal (HPG) dysfunction is known to occur in male patients with Cushing Syndrome (CS) but the underlying mechanisms of HPG dysfunction remain unclear. We performed frequent blood sampling and GnRH stimulation tests to assess gonadotropin secretion in males before and after surgical cure of CS. Methods: We evaluated eight males age 32.5±12 years (mean ± SD) enrolled for surgical cure of ACTH-dependent CS at a tertiary care research center. Urinary free cortisol (UFC) was measured before and after surgery. Blood was sampled every 20 minutes for 24-hours with measurement of LH and FSH, before and 2 weeks to 160 weeks (median 80 weeks) after surgery. Patients received 100 μg of gonadotropin releasing hormone (GnRH) iv with measurement of LH and FSH at 0, 10 and 20 min before and 15, 30, 45, 60, 120 and 180 min after administration. Non-normative data was log-transformed before analysis using paired two-tail t-tests. A p-value of &lt;0.05 was considered significant. Gonadotropin values are expressed in U/L as equivalents of the 2nd International Preparation of human menopausal gonadotropins with normal adult male ranges of 6-26 and 5-25 IU/L for LH and FSH, respectively. Results: Mean UFC was elevated ~ 6 times above the upper normal limit before surgery and returned to the reference range after surgery. 24-hour LH rose from 7.82 ± 1.48 preoperatively to 13.07 ± 2.96 IU/L (mean ± sem) after surgery (p=0.026) while mean FSH was unchanged (8.48 ± 1.51 vs 6.92 ± 1.29, p=0.37). LH pulse frequency, a marker of pulsatile GnRH secretion, recovered from a subnormal value of 6.88 ± 0.55 pulses/24 hr before to 12.13 ± 0.72 pulses/24 hr after surgery (p&lt;0.0001) while LH pulse amplitude did not change (6.47 ± 1.21 vs 4.76 ± 0.88 IU/L, p=0.21). In response to GnRH there was a robust increase in LH that was not affected by curative surgery for CS (27.0 ± 7.2 vs 21.2 ± 7.6 IU/L; p=0.14) as was also the case for FSH (3.7 ± 1.2 vs 2.3 ± 0.5 IU/L; p=0.48), consistent with the absence of an effect of CS on gonadotroph responsiveness to LHRH. Conclusion: In men with Cushing Syndrome, hypogonadism is associated with inhibition of endogenous GnRH secretion but preservation of the pituitary response to GnRH. Hypothalamic suppression of the HPG axis is reversible after cure of CS.
The Effect of Hypothalamic Involvement and Growth Hormone Treatment on Cardiovascular Risk Factors in Patients With Childhood-Onset Craniopharyngioma
Authors: Park Sang Hee , Jung Hae Woon , Lee Yun Jeong , Cheon Jung-Eun , Lee Young Ah , Shin Choong Ho 
Published: May 2021

Abstract
Background: We evaluated cardiovascular risk factors at the time of growth hormone (GH) retesting after completion of linear growth in patients with childhood-onset craniopharyngioma (CP). We also investigated the effects of postoperative hypothalamic involvement (HI) and GH discontinuation during transition period on cardiovascular risk factors. Methods: Forty-two CP patients (24 males, mean age 17.7 years) who reached final adult height after GH therapy between 1995 and 2012 from a tertiary center were included. We measured anthropometric data and components of the metabolic syndrome at the time of GH retesting. The period of GH discontinuation was classified as &lt; 6 months vs. ≥ 6 months. The extent of HI was categorized into “no”, “mild”, and “extensive” HI according to Puget grading system. Results: The mean age of initial operation after CP diagnosis was 7.5 ± 3.6 years, and 23 (54.8%) patients showed extensive HI. All patients were treated with GH during childhood for median 5.8 years (range 2.4-8.2years). Duration of GH discontinuation was median 1.5 years (range 0.5-3.2 years), and 32 (76.2%) had GH discontinuation ≥ 6 months. At the time of GH retesting, 13 (31.0%) were obese, and the proportion of patients with impaired fasting glucose (≥ 100 mg/dL), high triglycerides (≥ 150 mg/dL), low high-density lipoprotein (HDL) cholesterol (male, &lt; 40 mg/dL; female, &lt; 50 mg/dL), and hypertension (systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85mmHg) was 5 (11.9%), 18 (42.9%), 24 (57.1%), and 5 (11.9%), respectively. When multivariate-adjusted models were constructed including age, sex, postoperative duration, extent of HI, duration of GH discontinuation, and family history of cardiovascular disease, the extent of HI was significantly predictive for increased body mass index z-score (β = 1.27, P = 0.017), fasting insulin levels (β = 7.1, P = 0.049), HOMA-IR (β = 1.61, P = 0.020), and decreased HDL cholesterol levels (β = -9.9, P = 0.012). GH discontinuation more than 6 months was significantly associated with decreased
HDL cholesterol levels (β = -10.23, P = 0.026). Conclusion: In this study, impaired fasting glucose or hypertension accounted for one-tenth, and dyslipidemia was detected in more than half of childhood-onset CP patients with GH deficiency at the time of GH retesting. The more extensive HI and the longer duration of GH discontinuation were associated with increased risk of metabolic disturbance during the transition period.
Clinical Outcomes in Patients With NFPAs Treated With Stereotactic Linear Accelerator Radiation Therapy
Authors: Ordaz-Candelario Karla Krystel , Godoy-Alonso Juan Pablo , Vázquez-Aguirre Marlon Vladimir , Gonzalez-De-la-Cruz German , Silva-Serrano Juanita , Gómez-Sámano Miguel Ángel , Gómez-Pérez Francisco Javier , Cuevas-Ramos Daniel 
Published: May 2021

Abstract
Background: Non-functioning pituitary adenoma (NFPAs) are benign tumors of the pituitary gland characterized by the absence of hormonal hypersecretion. Surgical treatment and fractionated stereotactic radiotherapy (FSRT) are necessary in majority of patients. NFPAs appear to cause higher mortality compared to the general population. Objective: To assess outcomes in patients with NFPAs treated with stereotactic linear accelerator radiation therapy. Material and Methods: Comparative, observational, longitudinal study, with prolective evaluation, from January 1987 to August 2019. Results: 264 patients (65.5% women and 34.5% men, mean age 43 ± 16 years) with a diagnosis of non-functional adenomas were evaluated. 30 patients received FSRT (14%), 93% were macroadenomas, and 80% of the cases were operated as a first line of treatment. The mean number of surgeries before radiotherapy was 1.2+-.847 (0-4). FSRT were used in 91.7% (n=21) because of post-surgical recurrence. Diabetes insipidus after surgery was transitory in 5.4%, and persistent in 4.0%. Hypopituitarism was identified in 59.4% before radiation (n=19), and in 13 patients (7.7%) after mean of 6.5+-5.5 years of FSRT. Dyslipidemia (62.0% vs. 45.9%), high blood pressure (16.5% vs. 23%), type 2 diabetes mellitus (10% vs. 77%) and heart failure (10% vs. 8.4%) were observed in the irradiated vs. non-irradiated groups, respectively (p&lt;0.05). Conclusions: FSRT is a useful and safe strategy as an adjuvant treatment in patients with NFPA.