bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating LEAP-2 Levels in Adult Growth Hormone Deficiency and Their Relationship With IGF-1
Authors: Vergani Edoardo , Bruno Carmine , Gavotti Cesare , Capobianco Emmanuel , Currò Diego , Mancini Antonio
Published: May 2021

Liver enriched antimicrobial peptide-2 (LEAP-2) is an endogenous antagonist of ghrelin, which acts as an allosteric modulator of growth hormone secretagogue receptors. It is expressed predominantly in liver, followed by kidney, jejunum, duodenum and stomach. Its expression in conditions of metabolic impairment, obesity for instance, may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Weight gain and hyperglycaemia seem to be the main trigger factors for LEAP-2 production. Adult growth hormone deficiency (aGHD) is known as a pathological condition characterized by metabolic impairment (insulin resistance, weight gain, increased fat mass, decreased lean mass). To the best of our knowledge, no study in literature deals with the problem of circulating LEAP-2 levels in GHD. Therefore, the primary endpoint of this cross-sectional observational study was to evaluate circulating LEAP-2 levels in GHD in comparison to healthy controls whether the secondary endpoint was to evaluate any possible correlation with IGF-1 and metabolic parameters in such condition.

30 patients were included in the study. Group A included adult GHD: 15 patients, 7 females and 8 males, mean±standard error of the mean (SEM) age 54.6±3.51 years, BMI 29,95±1.63 kg/m2). The etiologies of GHD were empty sella (n=6), idiopathic (n=6), post-surgical hypopituitarism (n=2), pineal cyst (n=1). Group B was formed by controls: 15 patients, 11 females and 4 males, mean±SEM age 40.33±2.61 years, BMI 24.19±1.33 kg/m2. They were evaluated for: serum glucose and insulin, HOMA-index, QUICKI-index, Total/LDL/HDL cholesterol, triglycerides, IGF-1 and LEAP-2 (measured using Human LEAP-2 ELISA kit, Phoenix Pharmaceuticals Inc, according to manufacturer’s instructions).

Circulating LEAP-2 is significantly higher in GHD than in control group (26.98±3.12 vs 18.7±1.9 ng/ml, p=0.03). LEAP-2 levels in our cohort was not influenced by BMI, while a significant direct correlation between LEAP-2 and age was detected in aGHD group. A strong significative inverse correlation between LEAP-2 and IGF-1 was evidenced in aGHD (r2=0.5). Finally, in this group, LEAP-2 inversely correlates with total cholesterol (r2=0.45).

As expected circulating LEAP-2 levels, in a condition of metabolic impairment such as GHD, were higher than controls even if no correlation with BMI was evidenced in our cohort. The inverse correlation between LEAP-2 and IGF-1 in GHD patients may suggest a body adjustment in a worse clinical condition. LEAP-2 may act as a brake for ghrelin production, thus preventing further weight gain and fat mass increase, although losing its secretagogue effect.
Renal (Pro)renin Receptor Contributes to High Fat Diet-Induced Obesity
Authors: Culver Silas Allen , Siragy Helmy M
Published: May 2021

Recently we reported that (Pro)renin receptor (PRR) expression increases in the renal nephron during high fat diet intake. This study evaluated the role of renal PRR in the development of obesity. Eight-week old male mice with inducible nephron specific PRR knockout (KO) and wild type littermate (control) were fed either normal diet (ND, 12%kcal fat) or high fat diet (HFD, 45%kcal fat) for 6 months. KO Mice underwent induction of PRR KO with oral doxycycline 2mg/mL in 2% sucrose water for 12 days prior to starting diet. Compared to ND, HFD increased body weight by 40% (p<0.05) in control mice. In contrast, compared to control mice fed HFD, body weight of induced PRR KO on HFD was reduced by 56% (p<0.05). Total body fat increased by 179% (p<0.05) with HFD compared to ND control mice while it did not increase in PRR KO mice fed HFD. Twenty-four-hour caloric intake was not reduced in KO mice compared to controls while there were significant increases in nocturnal VO2 by 31% and respiratory exchange by 10% (p<0.05) in HFD PRR KO mice compared to HFD fed controls. Unexpectedly, urine glucose excretion significantly increased in PRR KO mice on both ND and HFD. Our results demonstrate that nephron specific PRR KO reduced diet induced obesity and adiposity, while increasing energy expenditure. Future investigations are warranted to elucidate the mechanisms by which renal PRR contributes to the development of obesity.
Polyciliation of GnRH Neurons in Vivo and in Vitro
Authors: Brewer Kathryn M , Bansal Ruchi , Engle Staci E , Antonellis Patrick J , Cummins Theodore R , Berbari Nicolas F
Published: May 2021

Puberty and reproduction are initiated and controlled through the hypothalamic-pituitary-gonadal (HPG) axis. A critical surge of luteinizing hormone (LH) and follicle stimulating hormone (FSH) are released from the anterior pituitary upon release of gonadotrophins from gonadotrophin releasing hormone (GnRH) neurons. Thus, GnRH neurons are key regulators of the HPG axis. GnRH neurons become active when kisspeptin (Kiss1) neuropeptides are released from neurons in the arcuate nucleus. Kiss1 binds to the Kiss1 receptor (Kiss1R), a G-protein coupled receptor (GPCR) which localizes to the primary cilia of GnRH neurons. Loss-of-function mutations of Kiss1R cause hypogonadism in mouse and human models while gain-of-function mutations are associated with precocious puberty. Interestingly, the subset of GnRH neurons that express Kiss1R are observed to be polyciliated, possessing more than one primary cilia, an uncommon property as most neurons only possess a single, primary cilium. The mechanism and conditions leading to GnRH neuron polyciliation are unknown. It is also unclear if multiple cilia impact Kiss1R or other GPCR signaling in these neurons. Here, we utilize cultured mouse primary hypothalamic neurons to begin addressing some of these questions. We have confirmed with qPCR that the ligands GnRH and Kiss1, as well as Kiss1R, are all expressed in these cultures. Surprisingly, when treated with Kiss1 and GnRH ligands we observed a small subset of polyciliated neurons compared to vehicle treated neurons. These observations mirror what is seen during sexual maturation in vivo and suggest that our model system may help elucidate fundamental questions about how ciliary localization of Kiss1r and other GPCRs participate in initiation of puberty and regulation of reproduction. Future studies will focus on the mechanisms of polyciliation and the conditions needed to induce the formation of new cilia in GnRH neurons. Investigating neuronal polyciliation could provide insights into new signaling paradigm in hypogonadism and HPG signaling.
Sex and Genotype Dependent Effects of a Restricted Access Diet in Ghrelin-Deficient Mice
Authors: Prins Karina , Delhanty Patric J , Huisman Martin , Mies Rosinda , McLuskey Anke , Visser Jenny A
Published: May 2021

Ghrelin, a peptide hormone secreted by the stomach, stimulates both appetite and reward signalling. Its deletion in mice results in poor recovery from metabolic challenges, like starvation, but does not affect food intake or body weight. While sex differences in appetite and feeding behavior have been reported, little is known about the role of ghrelin herein. To investigate this, we used a metabolic cage system to continuously monitor responses of ghrelin-deficient (GKO) and wildtype (WT) mice to three different diets. Male and female mice (5 weeks old) were housed individually in a Promethion system (Sable Systems, USA) and provided one of three diets for 9 weeks: RA, continuous chow with restricted access to a Western-style diet (WD; 2h access, 3d/week) in the light phase; CA, continuous access to both diets; CC, continuous chow. Glucose tolerance was assessed at week 7 by IPGTT; food intake (kcal/g bodyweight), energy expenditure and locomotor activity at week 8; body weight and body composition (EchoMRI, USA) at week 9. On access days, RA mice ate up to 60% of their 24h intake during the WD access period. Following WD access GKO RA mice ate less chow than WT RA mice. Intriguingly, this compensatory reduction in food intake by GKO mice occurred at different times for males and females. GKO RA males ate 45% less chow in the dark phase immediately after WD access (p < 0.001). In contrast, this reduction in food intake (30% less) did not occur until the following, non-access, day in GKO RA females (genotype-sex: p < 0.05). Depending on diet, GKO mice showed differential regulation of energy expenditure in the light phase. Energy expenditure was 6–17% higher in GKO than WT mice in the RA group on access days and in the CA group. On non-access days, however, GKO mice in the RA group expended 13% less energy than WT RA mice (p < 0.005). Regardless of diet, locomotor activity in females was greater than in males (p < 0.001). However, GKO females in the RA and CC groups showed a marked 30% reduction in locomotor activity compared to WTs (genotype-sex: p < 0.05). After nine weeks, neither sex nor genotype effects were seen in body weight gain and composition of RA animals. CA females gained 17% more body weight and had a 6.1% higher fat percentage than CA males (both p < 0.001). In the CC group body weight gain did not differ, but GKO females had 3.1% more fat than WT females (genotype-sex: p < 0.01). Glucose tolerance (AUC) was similar in all groups. In conclusion, we demonstrated that ghrelin deficiency changes the response to the three diets in a sex-dependent manner. Especially, restricted access to WD differentially affected food intake timing and locomotor activity of male and female GKO mice. These results add to the growing body of evidence that ghrelin signalling is sexually dimorphic.
The Effect of the Synergy Between Opiates and Prolactin on the Growth of Chickens
Authors: Abdulateef Salwan M , Al-Hamdani Adel , Al-Ani Mohammed , Mosa Baraa
Published: May 2021

It is generally admitted that opioids can stimulate the release of both prolactin (PRL), the opiates induced hyperprolactinemia via dopamine receptor blockade. Prolactin hormone (PRL) plays an important role in conjunction with some hormones such as GH, PTH, ACTH, and T4 to stimulating body growth. The prolactin hormone has an important role in feeding behavior, as its role is evidenced by its effect on metabolism. In migratory birds, fat is stored in its body before migration, and the hormone prolactin activates the process of building and storing fats lipogenesis and Deposition of Fats. The hypothesis of this study is to investigate the role of natural stimuli such as sound in stimulating peptide hormones in the body and thus weight gain in chickens. 100 birds of 1 day old were used it was divided into two treatments, each treatment with 5 replications. The chicks heard different sounds and it was as follows: the first the control without sound CS, the second hen sound (mother sound) HS. The sound was heard from the one old day to 14 days, at a rate of 3 times a day, in the morning, in the afternoon and at night, for an hour each time. Chicks were raising to 42 day. The hormone was estimated in three stages, before exposure to sound 30 minutes during exposure directly after exposure for 30 minutes, and the prolactin hormone concentration was calculated each time, the results show: Significant increase (P<0.05) in live body weight cumulative, weight gain cumulative, relative growth rate cumulative, and total feed conversion ratio to HS compared with CS. Significant improvement (P<0.05) in the concentration of the hormone prolactin of HS in the period after exposure to sound 30 minutes during exposure directly after exposure for 30 minutes at the age of 14 days (the end of the exposure to the sound of the period). As mentioned above, the opioids stimulate prolactin, but the question here who is responsible for stimulating the opioids? Opioids secretion is linked to the body’s sense of well-being and well-being, as it is secreted naturally to aid in rest and relaxation, and this is often noticed on the organism when it feels safe and comfortable. Chicks, when it hearing her mother’s sound, gives it a powerful stimulus, and they become more active and more and less fearful and amazement. This will release the opioid, which in turn stimulates prolactin. PRL and GH are secreted from the anterior pituitary gland and affect a wide variety of physiological functions in birds. Similarly, a relationship between plasma GH concentration and body growth is well documented. There is a chemical similarity between prolactin hormone and growth hormone, so there is a similarity in biological functions, as prolactin stimulates physical growth and weight gain in birds, reptiles and mammals due to its similarity with growth hormone as the injection of prolactin causes a significant increase in body weight.
The Role of Microglia in the Polycystic Ovary Syndrome (PCOS)-Like Brain
Authors: Sati Aisha , Prescott Melanie , Jasoni Christine Louise , Desroziers Elodie , Campbell Rebecca Elaine
Published: May 2021

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, affecting roughly 1 in 8 women of reproductive age. Accumulating evidence from animal models suggests that the brain plays a key role in the development and maintenance of PCOS. In a well-characterised prenatally androgenised (PNA) mouse model of PCOS, aberrant neuronal wiring associated with PCOS deficits in adulthood are detected as early as postnatal day (P) 25, prior to disease onset. However, the mechanisms by which prenatal androgen exposure alters brain wiring remains unknown. Microglia, the immune cells of the brain, are active sculptors of neuronal wiring across development, mediating both the formation and removal of neuronal inputs. Therefore, microglia may play an important role in driving the abnormal neuronal wiring that leads to PCOS-like features in the PNA brain. Here, to assess whether microglia are altered in the brain of PNA mice, microglia number and morphology-associated activation states were quantified in two hypothalamic regions implicated in fertility regulation. Microglia were identified by immunolabelling for the microglia-specific marker, Iba-1, across developmental timepoints, including embryonic day 17.5, P0, P25, P40 and P60 (n = 7–14/group). At P0, PNA mice had significantly fewer “activated” amoeboid microglia compared to controls (P < 0.05). Later in development at P25, PNA mice exhibited significantly fewer “sculpting” microglia (P < 0.001), whereas at P60, PNA mice possessed a greater number of “activated” amoeboid microglia relative to controls (P < 0.01). This study demonstrates time-specific changes in the number and morphology of microglia in a mouse model of PCOS and suggests a role for microglia in driving the brain wiring abnormalities associated with PCOS. These findings support the need for future functional experiments to determine the relative importance of microglia function in shaping the PCOS-like brain and associated reproductive dysfunction.
Transcriptome of Distinct LH and FSH Cells Reveals Different Regulation Unique to Each Cell Type
Authors: Hollander-Cohen Lian , Golan Matan , Levavi-Sivan Berta
Published: May 2021

From mammals to fish, gametogenesis and sexual maturation are driven by LH and FSH, the two gonadotropic hormones temporally secreted from the pituitary. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin hormone since, unlike mammals; they synthesize and secrete LH and FSH from distinct cells. By performing cell specific transcriptome analysis of double-labelled transgenic Nile tilapia (Oreochromis niloticus) expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type. Though GnRH is considered the main neuropeptide regulating LH and FSH, we found that each LH and FSH cell express unique GPCR signature that reveals the direct regulation of additional metabolic and homeostatic hormones (like cholecystokinin, somatostatin and glutamate). Moreover, some of those GPCRs were conserved also in gonadotrophs of mammals (like PACAP receptor, Adropin receptor and GABBA receptor). Next, we had exploited the unique behavior of Nile tilapia where a behavioral hierarchy is created between males, to compare the gene expression in the pituitary and brain of dominant (reproducing) males to a subordinate (non-reproducing) males. By combining the two transcriptome sets we had identified novel players in the hypothalamic regulation of the HPG axis, and revealed how brain aromatase (cyp19a1b), that is enriched specifically in LH cells, is the key factor in regulating the activity of LH and FSH cells in dominant reproducing fish. Thereby, unraveling novel mechanisms in the differential regulation of LH and FSH. The research was funded by the Israel Science Foundation (ISF) no. 1540/17.
A Case of Acute Psychosis as Manifestation of Ectopic ACTH Producing Pancreatic Neuroendocrine Tumor
Authors: Motazedi Banafsheh , Cowen Laura E , Jonklaas Jacqueline
Published: May 2021

Introduction: Ectopic adrenocorticotrophic hormone (ACTH) producing Pancreatic Neuroendocrine Tumor (p-NET) are extremely rare with incidence of 1.2% and confer a poor prognosis (5-year survival <20%).

Case Report: 31-year old female with diabetes mellitus type 2 (DM-2) and hypertension (HTN) was found to be severely hypokalemic on routine labs and was sent to the Emergency Department for potassium replacement. Vitals; BP:139/87 mmHg, HR:108 bpm, RR:18, T:37°C and saturating 98% on ambient air. Examination revealed cushingoid features; hyperpigmented face, bilateral upper extremity pigmented papules, proximal muscle weakness, acanthosis nigricans, violaceous abdominal striae, truncal obesity, ecchymoses, bilateral lower extremity edema, memory impairment and anxiety. Initial labs; BG: 289 mg/dL, HbA1c: 9.5%, K: 2 mmol/L (N 3.5-5.2), WBC: 12.5 k/μL (N 4-10.8), Cortisol >150 mcg/dL (N 5-23), TSH: 0.325 μIU/mL (N 0.45-4.5), and FT4: 0.69 ng/dL (N 0.82-1.77). Diagnosis of Cushing’s syndrome was made based on elevated cortisol level and confirmed with elevated 24-hour urinary free cortisol: 13,294 μg (N<45), midnight salivary cortisol >15 ug/dL (N 0.09-1.5) and 1 mg dexamethasone suppression test (Cortisol >150 mcg/dL, ACTH: 621 pg/ml). Additional labs showed Chromogranin A: 717 ng/mL (N 0-160). She was started on prophylactic Enoxaparin & Trimethoprim/Sulfamethoxazole and treated with Spironolactone, Basal/Bolus insulin, and Ketoconazole for hypercortisolemia. Pituitary MRI was negative for pituitary adenoma. Abdominal/Pelvic CT scan demonstrated a solid 5 cm pancreatic head mass with innumerable haptic metastases consistent with metastatic p-NET which was confirmed on PET-CT Ga68 Dotatate scan. Liver biopsy was positive for a well differentiated p-NET with ki-67 <5% and negative ACTH staining. Hospital course was complicated by fluctuating cortisol levels with intermittent psychotic manifestations despite up-titration of Ketoconazole, addition of Octreotide as well as anti-psychotics. She later developed transaminitis on maximum dose of Ketoconazole and thus underwent laparoscopic total adrenalectomy for treatment of her hypercortisolemia. Post-operatively, she was started on Hydrocortisone & Fludrocortisone and Spironolactone was discontinued. She was transitioned to monthly Lanreotide and treated with Capecitabine and Temozolomide with adequate therapeutic response and subsequent down trending of her Chromogranin A: 188 ng/mL and ACTH: 228 pg/ml levels. Currently, she is doing well with significant improvement of her DM-2, HTN, psychiatric symptoms and overall clinical status.

Conclusions: Symptoms of ectopic Cushing’s syndrome may be delayed, however given the rare and aggressive nature of ACTH producing p-NET, timely diagnosis, prophylaxis and individualized treatment approach is crucial in achieving favorable prognosis.
A Case of Ectopic Cushing’s Syndrome From a Large Cell Neuroendocrine Lung Tumor With Small Cell Component/Features
Authors: Sallar Anthony Selase , Childress Richard Dale
Published: May 2021

Background: Endogenous Cushing’s syndrome is uncommon in clinical practice. Survival of patients with new onset ectopic Cushing’s syndrome at relapse of small cell lung cancer has been found to be poor, with death occurring within an average of 27.3 days.

Case Report: A 61-year-old African American male was seen by endocrinology service for inpatient evaluation of refractory hypokalemia of three months duration requiring recurrent potassium replacement with oral and intravenous therapy. He was inpatient for depressive symptoms and suicidal ideation. His admission lab showed hypokalemia of 2.7 mmol/L associated with elevated serum ACTH and serum cortisol. Past medical history is significant for unresectable large cell neuroendocrine neoplasm of the lung with small cell components/features diagnosed two years prior during lung cancer screening. He received chemotherapy with cisplatin/etoposide at diagnosis. He however had recurrence one year later with distant metastases. He was re-treated with cisplatin/etoposide in addition to palliative radiation therapy to painful bone met in his right hand. Three months prior to admission, imaging showed progression of the cancer with presence of new lesions in the liver for which he received one cycle of Nivolumab monotherapy. Social history was significant for 30-pack year smoking history. Physical exam findings were significant for: elevated blood pressure 167/96 mmHg, tachycardia of 107 bpm, oxygen saturation of 95% on 3-liters of intranasal oxygen, cachexia, absent buffalo hump, absent striae and decreased power in both lower limbs. Lab on supplementation showed serum potassium of 3.6, Serum magnesium of 2.0 and creatinine clearance greater than 60 Serum cortisol was 116.1 (5-25) mcg/dl and ACTH was 268.0 (9-52) pg/ml. An MRI by the referring team did not show a pituitary lesion. Patient was diagnosed with Cushing’s syndrome due to ectopic ACTH-production from a large cell neuroendocrine lung tumor with small cell component/features. Chart review showed his onset of hypokalemia occurred at the same time that imaging showed progression of the tumor three months prior. He was started on Ketoconazole and his cortisol level reduced to 14.0 within forty-eight hours with associated correction and stabilization of hypokalemia. The plan was to “block and replace” cortisol so that oncology could re-start chemotherapy. However, the patient developed acute respiratory decompensation requiring continuous BiPAP. Chest imaging showed progression of lung lesions with post obstructive pneumonia. The patient’s family opted for comfort measures and he was transferred to hospice care where he passed on ten days later.

Conclusion: In the setting of lung cancer, new onset paraneoplastic Cushing’s syndrome may have prognostic implications. Clinicians should be aware of this, provide treatment for hypercortisolism and refer early to palliative care.
A Rare Case of Metastatic Transformation to Pituitary Carcinoma
Authors: Woznick Walter K , Engel Ashley , Maas Diana
Published: May 2021

Background: Pituitary carcinomas are rare and comprise less than 0.5% of pituitary tumors and frequently arise from previously resected and/or radiated infiltrating adenomas.1 Radiation therapy is used to prevent regrowth but does not have significant data supporting improved prognosis.2 True pituitary carcinomas requires the presence of craniospinal and/or systemic metastases. Here, we present a case of benign pituitary adenoma that had progressed to a metastatic tumor and responded to radiation therapy. Clinical Case: Our patient was first diagnosed in 1982 with a pituitary mass after undergoing an MRI due to right eye blindness. He ultimately had a transcranial resection of the tumor and post-operative external radiation to residual tumor. Final pathology was consistent with a nonsecretory tumor. Additionally, he was diagnosed with panhypopituitarism and he was treated accordingly. Due to barriers of patient adherence, only one post-operative MRI was obtained, and he was lost to endocrine follow up. In 2007, he was again referred to endocrinology for new vision loss in the left eye. An MRI revealed a 3.0 x 3.8 x 4.4 cm tumor that compressed the optic chiasm. Additionally, multiple lesions were seen within the dural and leptomeningeal extra-axial areas including the largest left frontal lesion of 2.4 cm and a 1.7 cm lesion posterior to the cord within the foramen magnum. The patient underwent endonasal transsphenoidal resection of the sellar mass and biopsy of the frontal lesion in October 2007. Pathology showed pituitary adenocarcinoma in both the sellar and frontal lesions and immunoperoxidase staining was negative for all hormones. He completed salvage radiation to the sellar and craniospinal lesions in December 2007. MRI scans completed 7 months later showed stable residual pituitary and metastatic lesions. The patient received 6-month MRI screening exams for the first 2 years and then annually thereafter, as well as PET scanning, without significant progression or new metastatic lesions. Conclusion: We present a case of benign pituitary adenoma which transformed following resection to a malignant tumor with metastatic lesions in the brain and spinal cord that was treated with radiation with relative success. Despite the often-aggressive nature of these metastatic tumors, the patient has experienced a successful treatment course with minimal side effects and without progression 13 years after initial treatment of the metastatic pituitary carcinoma.
Acute Transient Central Diabetes Insipidus: A Rare Case of DI Secondary to Vasopressin Withdrawal
Authors: Cobb Crystal , Osakwe Ibitoro Nnenna
Published: May 2021

Introduction: Transient Central Diabetes Insipidus (tCDI) induced by vasopressin withdrawal is a rare condition which is possibly under recognized. It occurs in very sick, often critically ill patients and usually complicates an already complex clinical picture, so early recognition and treatment are critical to reduce morbidity.

Case Description: A 47-y/o male with a PMH of Coffin Lowry syndrome, atrial fibrillation, and GERD presented with abdominal pain and flu like symptoms. His home medications were metoprolol, loratadine and colestipol. Work up revealed bowel perforation for which he was taken to the OR for repair. Intraoperatively he developed septic shock requiring pressor support with norepinephrine and vasopressin. He was weaned off norepinephrine on post-op day (POD)1, and vasopressin on POD 2. Approximately three hours after withdrawal of vasopressin support his urine output increased dramatically up to a peak of 350 cc/hour with a recorded 24hr urine volume of >5L. Concurrently, his serum sodium was found to have increased from 147 mmol/L to 173 mmol/L (n 135-145) over the course of 13 hours. Clinically, he became increasingly lethargic with abnormal eye movements. His sodium did not improve with fluid management with D5W. His other laboratory values included a urine osmolality of 141 mOsm/kg, urine sodium of 60 mmol/L and a peak serum sodium of 177mmol/L. He was administered 1mcg desmopressin and his D5W rate was increased. His urine output dropped gradually to ~150cc/hr, his serum sodium level started to trend down to 168 mmol/L and his urine osmolality increased to 439 mOsm/kg five hours after desmopressin administration, with improvement in mental status. The patient received a total of two doses of desmopressin and continued support with IV fluids. His sodium eventually normalized, and his polyuria did not return.

Discussion: This patient’s clinical picture is consistent with tCDI secondary to discontinuation of vasopressin. Transient Central diabetes insipidus due to vasopressin withdrawal is a phenomenon that is not well understood, but there is a strong male preponderance, and it tends to occur more commonly in patients with underlying neurological conditions, as did our patient. Current proposed mechanisms include decreased production and release of exogenous ADH due to negative feedback, down regulation of the V2 receptors, and hypoperfusion to the posterior pituitary. This condition deserves more investigation to better understand the incidence, risk factors and pathophysiological mechanisms.
An Atypical Case of TSH-Secreting Pituitary Adenoma in a Patient Presenting With Low Libido and Insomnia
Authors: Popli Rakesh , Endo Mayumi
Published: May 2021

Background: TSH-secreting pituitary adenoma is an incredibly rare cause of hyperthyroidism. Most patients with TSHomas present with clinical hyperthyroidism, but some patients may have atypical signs. Here we present the case of a patient who had been suffering from low libido and insomnia who was found to have secondary hyperthyroidism from a TSH-secreting pituitary adenoma.

Clinical Case: A 47-year-old man presented with complaints of progressive headache, fatigue, depression, insomnia, low libido and erectile dysfunction. After questioning, he noted the presence of intentional tremor for more than 5 years. He denied anxiety, palpitations, heat intolerance, hyper defecation, proximal muscle weakness, local compressive symptoms of the neck and ocular symptoms. Physical exam was notable for fine tremor and mild thyromegaly, but otherwise patient had no evidence of anxiety, exophthalmos, hyperreflexia or diaphoresis. The patient was found to have a normal free testosterone (46 pg/mL, n 30-140 pg/mL) but had an elevated TSH (6.302 IU/mL, n 0.4-5 IU/mL), elevated Free T4 (3.6 ng/dL, n 0.6-1.2 ng/dL) and an elevated T3 (422 ng/dL, n 73-178 ng/dL). Further lab work revealed elevated alpha-subunit (4.4 ng/mL, n <0.5 ng/mL) suggestive of TSH-secreting pituitary adenoma. Prolactin and IGF-1 levels were normal. Patient had an MRI pituitary which showed a 2.3 cm sellar mass abutting the optic chiasm without involvement of the cavernous sinus. Patient proceeded to trans-sphenoidal resection. Post-operatively, TSH had dropped from 6.534 to 0.002 IU/mL (n 0.4-5 IU/mL) and Free T4 had dropped from 3.1 to 0.5 ng/dL (n 0.6-1.2 ng/dL). Interestingly, immunohistochemical staining was negative for TSH but the specimen did show histologic features characteristic of TSH-producing adenoma including extensive stromal fibrosis and nuclear pleomorphism. Patient was seen in clinic post-operatively where he noted a dramatic improvement in his headache and insomnia. He did show signs of hypothyroidism including constipation and weight gain. Patient was started on levothyroxine 75 mcg PO daily.

Conclusion: This demonstrates the case of a patient with a TSH-secreting pituitary adenoma who presented with minimal thyrotoxic symptoms despite elevated thyroid hormones. Patients with this condition may present with atypical symptoms, thus requiring clinicians to have a high index of suspicion for this rare tumor.

References: (1) Beck-Peccoz, P., Lania, A., Beckers, A. et al. 2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J 2013; 2:76. (2) Cossu, G., Daniel, R.T., Pierzchala, K. et al. Thyrotropin-secreting pituitary adenomas: a systematic review and meta-analysis of postoperative outcomes and management. Pituitary 2019; 22:79.
An Unusual Case of Hypopituitarism in a 68 Year Old Man With a Normal Appearing Pituitary Gland and a Remote History of Severe Headache Attributed to Possible Apoplexy
Authors: Reddy Sai Rohit , Reddy Sravani Konatham , Mirza Lubna
Published: May 2021

A 66-year-old previously healthy man was admitted to the hospital with severe hypotension and gastroenteritis symptoms, which were attributed to food poisoning. No one else who ate with him got sick. Random morning cortisol was found to be 0.6, which was followed by the Cortrosyn stimulation test. Baseline cortisol was 0.9, which went up to 2.0 mcg/dL in 30 minutes after Cortrosyn stimulation and 2.9 mcg per dl after an hour. He was treated with high dose steroids during his inpatient stay and sent home on physiologic steroid doses. He followed up in the Endocrinology clinic after hospital discharge. A review of old records showed he was prescribed testosterone about ten years prior for symptoms of hypogonadism, but he never took it. Detailed workup revealed hypopituitarism. Serum prolactin, growth hormone, IGF-1, LH, FSH, Testosterone, TSH, and free T4 were all decreased. Brain/pituitary MRI, however, showed no pituitary abnormalities. All pituitary hormones were checked multiple times and were found to be consistently low. He was given hormone replacement therapy with levothyroxine and testosterone in addition to continuing steroids resulting in marked improvement. He gave a remote history of the worst headache of his life about twenty years ago. He stayed awake all night but never went to the hospital for an evaluation. A possible pituitary apoplexy several years ago was suspected in this case. We have not found any such case in the medical literature with hypopituitarism with a completely normal-appearing pituitary gland. This case illustrates the importance of detailed history, physical examination, hormonal testing, and appropriate hormone replacement in patients where an obvious acute cause may not be ascertained.
Co Existence of a Corticotroph Adenoma and a Multifunctional Pituitary Cyst
Authors: McDonnell David John , Kennedy Carmel , Qaoud Yazan , Heverin Karen , Smith Diarmuid , Javadpour Mohsen , Agha Amar
Published: May 2021

The co-existence of a corticotroph adenoma and a pituitary cyst is very unusual. We present the case of a 50-year-old female who presented with a Cushingoid phenotype, severe hypokalaemia, hyperglycaemia and hypertension. Urinary free cortisol was markedly elevated at 50 fold. ACTH levels were elevated at 121.4 pg/ml. She failed both the low and high dose dexamethasone suppression tests. The CRF test did not show a satisfactory rise in ACTH levels but the Inferior petrosal sinus sampling revealed a central to peripheral ACTH gradient highly suggestive of Pituitary dependant Cushing’s. MRI pituitary revealed a large cystic lesion with a small solid component. Computed Tomography (CT) of thorax abdomen and pelvis was normal. A trans-sphenoidal hypophysectomy was performed, during which a fine needle aspiration of the intra-cystic fluid was obtained. This showed markedly elevated pituitary hormone levels of ACTH (1399pg/ml), prolactin (353,084mIU/L), TSH (217IU/L) FSH (205mIU/ml) and GH (519 ng/ml) consistent with a multifunctional pituitary cyst. Neuropathology of the solid component confirmed a corticotroph adenoma. Post-operative am cortisol levels were persistently suppressed to less than 50 nmol/l with marked improvement in clinical features. This case highlights the challenges in the work up of Cushing’s syndrome and the limitations of diagnostic tests. The coexistence of a corticotroph adenoma and a multifunctional pituitary cyst is very unusual and to our knowledge has not been reported before.
Neurosarcoidosis and the Pituitary
Authors: Afreen Samina , Mittal Ashima , Hasan Farhad
Published: May 2021

Background: Sarcoidosis involves the nervous system in 3-10% of cases. Neurosarcoidosis (NS) can mimic other diseases, leading to delay in diagnosis and management. We present 2 cases of hypothalmo-pituitary (HP) NS with widely differing initial presentations.

Case Presentations: Case 1: A 58 year old African American (AA) male presented with decreased libido and hot flashes of 8-10 months duration. He also reported headaches, pain in the face and behind the eyes and dyspnea on exertion. On evaluation, he had central hypogonadism. MRI brain showed thickening and enhancement of pituitary infundibulum (PI). CT chest showed lung lesions and bilateral hilar adenopathies. EBUS with biopsies of lung and hilar lymph node showed non caseating granulomas (NCG). He was started on Prednisone and testosterone leading to symptomatic relief. However, he stopped prednisone after 3 months due to weight gain. He was then started on azathioprine. 9 months later, he presented with recurrence of neurologic symptoms and weight loss of 30 lbs. Labs showed new findings of low prolactin, low IGF-1, central hypothyroidism and central adrenal insufficiency (AI). MRI pituitary showed diffuse thickening of 3rd and 5th cranial nerves and of PI. He was re-started on Prednisone and levothyroxine (LT4) was started with improvement of symptoms. Plan was to start him on Infliximab instead of Azathioprine. Case 2: A 26 year old AA female presented with near syncope and visual impairment in the left eye that started a few weeks prior. Testing showed superior visual field loss and evidence of optic neuropathy, disc edema with mild dyschromatopsia in the left eye. She had had polyuria and polydipsia for the preceding 2-3 months and amenorrhea for 2 years. Lab testing revealed hyperprolactinemia and central DI, hypothyroidism, AI and hypogonadism. Pituitary MRI revealed a suprasellar mass measuring 20 x 19 x 11 mm, displacing the optic chiasm. CT scan showed bilateral hilar lymphadenopathy and lesions in liver and spleen. EBUS and biopsy of mediastinal lymph nodes showed NCG. Patient was treated with IV steroids leading to improved vision. She was started on DDAVP and LT4 and initiated on methotrexate and prednisone on discharge.

Discussion: Pituitary hormone abnormalities due to HP NS include anterior hypopituitarism, hyperprolactinemia and DI. The most common (MC) presentation is of DI. Among anterior pituitary hormone deficits, central hypogonadism is the MC. Systemic high dose glucocorticoids (GC) are the mainstay of initial treatment. Optic atrophy is the MC neuro-ophthalmologic manifestation of NS. Only 10 - 20 % of patients have been found to have biochemical improvement of HP axis in response to high-dose GC treatment. Since pituitary involvement commonly leads to permanent endocrine deficits, it is essential to recognize it early and to treat it aggressively to prevent further permanent hormonal and neurologic deficits.
New Treatment Options for Pituitary Granulomatosis With Polyangiitis
Authors: Boharoon Hessa , AlAmeri Majid , Alnuaimi Abdulla Mohamed , Mendoza Nigel , McAdoo Stephen , Tomlinson James , Levy Jeremy , Wernig Florian
Published: May 2021

Background: Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland and has been reported in 1% of all cases of GPA. Most frequently, it presents with pituitary mass effect and diabetes insipidus (DI). To date, there are no treatment guidelines for this rare condition. Case Presentation: Case 1: A 55 year old female with a history of ANCA-positive pulmonary GPA, previously treated with glucocorticoids and immunosuppressants, presented two years later with cranial DI and bitemporal hemianopia. MRI showed a large sellar mass with suprasellar extension. High dose glucocorticoids resulted in good clinical and radiological response. Further treatment consisted in a combination of Cyclophosphamide and Rituximab (RTX). Further doses of RTX are planned aiming for a period of B-cell depletion. Case 2: A 38 year old female, presented with polyuria, recurrent nosebleeds, headaches and a left visual field defect. Pituitary profile revealed ACTH deficiency and MRI showed a heterogenous cystic lesion with peripheral enhancement and stalk thickening. Steroid replacement led to immediate improvement in her symptoms. Cranial DI was confirmed and raised Proteinase 3 (PR3) antibody suggested GPA. A combination of prednisolone and Methotrexate led to significant improvement of MRI appearances and declining PR3 antibody levels. For remission maintenance, two cycles of RTX were given with further radiological and biochemical improvement, and, following dynamic assessment of her HPA axis, she could be fully weaned off steroids. Case 3 is a 47 year old female with a history of childhood asthma. She was found to have cavitating lung lesions. ANCA positivity confirmed GPA and she was commenced on high-dose steroids. During follow-up, she developed headache, polyuria and polydipsia. MRI pituitary showed a suprasellar lesion and pituitary biopsy revealed inflammatory hypophysitis. Cranial DI was confirmed by water deprivation testing. Previous allergic reactions to both RTX and Ofatumumab precluded anti-CD40 monoclonal antibodies and she was commenced on Azathioprine. A further recurrence of pituitary GPA necessitated escalation of the steroid dose and switch of azathioprine to mycophenolate mofetil. She remains in remission and her steroids reduced to a maintenance dose. Conclusion: GPA pituitary has been observed to occur at variable time after diagnosis often in the absence of any other systemic features. A combination of glucocorticoids and RTX has been approved for severe relapsing pulmonary GPA, however, limited data is available for pituitary GPA. In this case series, the response to high dose steroids and RTX for remission maintenance has been encouraging. Experience with ‘conventional’ immunosuppresants remains limited and therapeutic responses remain variable. Further clinical studies are required to establish effective treatment for pituitary GPA.
Antiandrogens Target TMPRSS2 and Reduce SARS-CoV-2 Virus Entry in Lung Cells
Authors: Leach Damien A , Andrea Mohr , Zwacka Ralf , Giottis Stathis , Yates Laura , Lloyd Clare , Brooke Greg N , Bevan Charlotte Lynne
Published: May 2021

The SARS-CoV-2 coronavirus is the cause of the COVID-19 pandemic. Entry of the virus into host cells, most destructively lung cells, requires two host cell surface proteins, ACE2 and TMPRSS2, downregulation of which is thus a potential therapeutic approach for COVID-19. Both of these cell surface proteins are steroid regulated: TMPRSS2 is a well-characterised androgen-regulated target in prostate cancer. Analysis of sequencing data shows co-expression of the androgen receptor (AR) and TMPRSS2 in key human lung cell types that are targeted by SARS- CoV-2. We show that treatment with antiandrogens such as enzalutamide (a well-tolerated drug widely used in advanced prostate cancer) significantly reduces TMPRSS2 levels in human lung cells and in vivo in mouse lung. We demonstrate that AR binding in the region of the TMPRSS2 gene differs between lung and prostate, identifying distinct regulatory regions. Together, the data and evidence presented supports clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.
Sellar Plasmacytoma: An Unusual Presentation of Anaplastic Multiple Myeloma
Authors: Motlaghzadeh Yasaman , Sellmeyer Deborah
Published: May 2021

Background: Anaplastic multiple myeloma (AMM) is an extremely rare morphological subtype of multiple myeloma that has been reported only sporadically. Furthermore, pituitary involvement by multiple myeloma is rare and can be misdiagnosed as a nonfunctioning pituitary adenoma, due to its radiological and clinical similarities. Clinical Case: A 46-year-old man with no past medical history presented with a 3-month history of left shoulder pain. Initial physical exam revealed a large left neck mass, which prompted a left shoulder x-ray remarkable for left supraclavicular mass. Chest CT scan showed a bony mass (7 x 4 x 4 cm) in the left anterior second rib with extra osseous soft tissue involvement. CT also noted left supraclavicular/infraclavicular and left axillary adenopathy. Patient also reported lightheadedness and double vision for a few months and found to have diplopia with upward gaze on exam. Brain MRI revealed uniformly enhancing mass in right sphenoid sinus involving the sella measuring 2.3x2.6x3.2cm. With exception of low Hemoglobin (10.5, 13.5 - 17.7 g/dL) and mildly elevated prolactin (29.9, 2.0 - 20.0 ng/mL), laboratory testing was within normal limits including complete blood count, metabolic panel and pituitary hormone levels. Patient underwent fine needle aspiration of the supraclavicular node, which showed anaplastic plasma cell neoplasm. Further work up noted elevated M-spike, Kappa light chain 92.7 (0.3-2.0 mg/dl), kappa/lamda ratio 23 (0.3-1.6) and beta-2 microglobulin 4324 (600-2,200 ng/mL). Bone marrow biopsy confirmed 70% myeloma involvement with kappa monotypic plasma cell population expressing CD20, CD138, CD38, and CD117. Patient underwent endoscopic endonasal trans-sphenoidal biopsy of the mass. Frozen section pathology revealed a plasma cell neoplasm, and a subtotal resection was performed. Final surgical pathology confirmed anaplastic plasma cell neoplasm. He was started on systemic chemotherapy and external beam radiation. Conclusion: Sellar involvement by myeloma is very rare with less than 50 cases reported in the literature. While rare, these tumors should be considered in the differential diagnosis for lesions involving the sella as the therapeutic approach is different from other sellar masses. While the radiographic appearance can be similar, pituitary plasmacytomas typically present with headache and neurological signs such as cranial nerve palsies and visual changes, with preserved pituitary function. Close attention to physical exam and lab parameters can provide clues to this rare diagnosis.
She Has a Big and Weak Heart
Authors: Vallepu Shirisha R , Bantu Sravani , Gunda Mouna , Tadisina Shourya , Thudi Vaishali
Published: May 2021

Background: Acromegaly is a rare clinical syndrome caused by excessive production of growth hormone. The incidence rate is 3 to 4 cases per million people per year. It is a sporadic disease seen in middle-aged adults. Anterior pituitary adenoma secreting the growth hormone (GH) is the most common etiology. Other rare causes include hypothalamic and neuroendocrine tumors. Treatment modalities include surgical, radiotherapeutic and pharmacological with a goal to reduce or remove the tumor, prevent recurrences, and improve comorbidities. The persistent hypersecretion of GH and insulin-like growth factor-1 (IGF-1) leads to an overgrowth in many tissues, including connective tissue, cartilage, bone, skin, and visceral organs. Cardiovascular disease is one of the critical systemic complications resulting in about 60% of the deaths. The cardiovascular manifestations include hypertension, cardiomyopathy (CMP), congestive heart failure, and arrhythmias. Our patient presented with congestive heart failure and dilated CMP in the setting of undiagnosed Acromegaly. Clinical Case: 45 -year old Caucasian lady presented with complaints of worsening shortness of breath, chest tightness, and palpitations for one month. Past medical history includes hypertension, type 2 diabetes mellitus, obesity, and hyperlipidemia. She was diagnosed with dilated CMP in her early 30s, AICD placement seven years ago and normal cardiac catheterization three years ago. On physical exam, she was found to have an enlarged nose and bibasilar crackles. Vitals were stable and proBNP: 4,699 (1-150 pg/ml). ECHO revealed EF of 30-35%, severely dilated left ventricle. Cardiac catheterization showed severely decreased left ventricular systolic dysfunction and elevated LVEDP. Further workup - GH: 16 (<10 ng/ml) and IGF-1: 637 (62 - 205 ng/ml), A1C 13.2%. Pituitary MRI showed a 1.6 cm macroadenoma, extending to the right cavernous sinus border with a deviation of the pituitary stalk to the left. On neurosurgical evaluation, she was considered to be a poor surgical candidate due to her underlying CMP. Currently, she is in the process of getting started on oral octreotide treatment. Conclusion: Cardiovascular disease is the most captious complication and a leading cause of mortality in Acromegaly patients. The subtle clinical presentation results in a diagnostic delay for 5-10 years. A careful review of history and physical examination is vital to identify acromegalic features in non-ischemic DCM. Early diagnosis with prompt treatment has shown improvement in cardiac function and reduced mortality. This case underscores the importance of considering Acromegaly as one of the differentials in patients with dilated cardiomyopathy.