Unmasking the Diagnosis of Acromegaly

The diagnosis of acromegaly is still a difficult task, as the disease has a slow onset and progression, and some of its symptoms may resemble those of other common conditions. Delays in diagnosis are common. Moreover, due to the continuous requirement for mask-wearing in many healthcare settings to prevent the spread of COVID-19, it is crucial to conduct a comprehensive examination of each patient without a face mask.Copyright © The Author(s). 2022.

Pathogenetic therapy of COVID-19: focus on glucocorticoids

The problem of preventing excessive production of pro-inflammatory cytokines in the case of COVID-19 remains unre-solved. The use of steroids in the treatment of coronavirus pneumonia remains controversial. To date, there is insufficient literature data for the routine use of steroids in COVID-19 intensive care programs, and this issue remains the subject of continuous research and endless debate. The review of the scientific literature focuses on one of the areas of pathogenetic therapy for COVID-19 — the pre- vention and elimination of hyperproduction of pro-inflammatory cytokines using glucocorticoid drugs. The review presents modern international recommendations on the use of glucocorticoid drugs in severe COVID-19, examines the pathogenetic mechanisms of their action and side effects. © 2022. The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, CC BY, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.

Italian Association of Clinical Endocrinologists (AME) 20th National Congress

The proceedings contain 9 papers. The topics discussed include: dulaglutide and NAFLD risk reduction;correlation between plasmatic long pentraxin PTX3 and nodular thyroid disease: a preliminary report;the fructose-bisphosphate aldolase a act as autoantigen in primary autoimmune hypophysitis;cortisol deficiency in Lenvatinib treatment;side effects of mitotane treatment: a retrospective study in 35 patients with adrenocortical carcinoma in adjuvant therapy;non-functioning pituitary adenoma: do predictor factors exist?;incidence and features of adrenal crisis in a series of 133 patients with Addison's disease;serological evidence and self-reported outcomes in patients with adrenal insufficiency during the first waves of COVID-19 in the North-East Italy;and persistent effects of spironolactone after its withdrawal in patients with hyperandrogenic skin disorders.

SARS-CoV-2 Infection, A Risk Factor for Pituitary Apoplexy? A Case Series and Literature Review.

Introduction: Pituitary apoplexy (PA) is a rare phenomenon, characterized by a hemorrhagic or ischemic event of the pituitary gland, most often in association with a pituitary lesion. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the strain of virus responsible for the internationally recognized global pandemic COVID-19. Multiple clinical manifestations associated with this virus have been described, ranging from asymptomatic, mild flu symptoms to acute respiratory distress syndrome, end-organ failure leading to death. Cases of patients with concomitant COVID-19 infections and PA are being further recognized in the literature, but the causal association between the 2 entities remains speculative. Objectives: The objectives of this case series are 3-fold: to describe additional cases of patients with concomitant COVID-19 infection and PA (1), to review the current evidence regarding this potential complication associated with a COVID-19 infection (2), and to discuss physiopathological hypotheses, treatments, and prognoses of this newly recognized association (3). Method: We conducted an electronic chart review of patients treated for PA with concomitant COVID-19 infection from March 2020 to December 2021. A literature review was performed using MEDLINE, Web of Science, and Embase databases to identify other cases of COVID-19-associated PA. Results: From March 2020 to December 2021, 3 patients presented to our center with PA following a symptomatic COVID-19 infection. Two of these patients developed PA symptoms days following the viral infection, whereas the third patient developed PA after a 2-month period. The 2 first patients were managed surgically because of persistent visual symptoms. Results from our literature review yielded 12 other cases of COVID-19-associated PAs. Conclusions: The association between COVID-19 infection and PA has been increasingly reported in the literature. With the addition of the 3 cases described in our article, a total of 15 cases have been published. Many contributing mechanisms may lead to PA following COVID-19 infection. Coagulopathy is probable major contributing cause responsible for hemorrhage or infarction of the pituitary gland. Our case series provides further arguments that PA may be a direct manifestation of a COVID-19 infection.

Approach to the Patient With Pituitary Adenoma Using Telemedicine: Knowledge Gaps and Recommendations

Telemedicine (TM) can be defined as the practice of medicine using technology such as video teleconferencing, telephone calls, or emails in order to provide health care from a distance. The emergence of the coronavirus disease 2019 (COVID-19) pandemic and its potential complications have created an urgent need for the transformation of physical visits into virtual encounters. Pituitary adenomas are one of the common endocrine tumors and can manifest with hormonal or mass effects. COVID-19 impacted the common pathway of diagnosis and treatment of these masses. TM utilization for pituitary adenomas has not been addressed thoroughly in the literature despite how common they are. In this review article, we discuss and implement what has been written in the literature about TM for pituitary adenoma alongside our suggested protocol.

Neuroendocrine Disruptions Following Head Injury.

PURPOSE OF REVIEW: This article reviews hypopituitarism after TBI, the importance of pituitary hormones, and related controversies, concluding with a suggested patient approach. RECENT FINDINGS: While earlier studies focused on increased pituitary deficiencies after moderate-severe TBI, recent studies have focused on deficiencies after mild TBI. There has been increasing focus on the role of growth hormone after injury; growth hormone is the most frequent reported deficiency at 1 year post-TBI, and an area with unresolved questions. While more research is needed to quantify the risk of deficiencies in special populations, and establish the natural history, increasing data indicate an increase in hypopituitarism after other acquired brain injuries; the potential role of pituitary hormone deficiencies after stroke and after COVID-19 infection is an area of active inquiry. Given the negative health effects of untreated hypopituitarism and the opportunity to intervene via hormone replacement, it is important to recognize the role of pituitary hormone deficiencies after TBI.

AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report.

Introduction: The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion: Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.

Apropos of menstrual changes and abnormal uterine bleeding after COVID-19 vaccination.

It is news of 28 October 2022 that the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency has recommended to add heavy menstrual bleeding among the side effects of unknown frequency inside the package insert of nucleoside-modified messenger ribonucleic acid vaccines to prevent coronavirus disease 2019 (COVID-19). The decision has been made in the light of the numerous reports of unexpected menstrual changes or abnormal uterine bleeding following COVID-19 vaccination. Here we advance a possible involvement of the particular adenohypophyseal microcirculation in these strange and still unexplained events.

Imaging Features of COVID-19-Associated Acute Invasive Fungal Rhinosinusitis

Background Acute invasive fungal rhinosinusitis (AIFR) is a rare, rapidly progressive, and life-threatening infection involving the nasal cavity and paranasal sinuses. Purpose of this study is to describe imaging features of coronavirus disease-2019 (COVID-19)-associated AIFR.Methods This was a retrospective observational study. Inclusion criteria: (1) post-COVID-19 patients with fungal rhinosinusitis detected on potassium hydroxide smear or histopathology;(2) onset of symptoms (facial pain, dental pain, facial swelling or discoloration, nasal bleed, periorbital swelling, ptosis, redness of eyes, vision loss) less than 4 weeks;and (3) magnetic resonance imaging/computed tomography (MRI/CT) done within 5 days before surgery. Exclusion criteria: (1) cases of sinusitis without a history of previous COVID-19 infection;and (2) cases in whom fungal hyphae were not demonstrated on pathological examination. Noncontrast CT and dedicated MRI sequences were done initially. Site of involvement, unilateral/bilateral involvement, pattern of mucosal thickening, enhancement pattern, periantral invasion, orbital invasion, intracranial involvement, perineural spread, vascular involvement, and bony involvement were recorded. CT and MRI imaging features were compared.Results Analysis of 90 studies (CT and MRI) in 60 patients was done. Most common site of involvement was ethmoid followed by maxillary sinus. Bilateral disease was more common. Mucosal thickening with T2 hypointense septations was seen in 88.4% MRI studies. Periantral and orbital involvement was seen, respectively, in 84.6% and 55.7% cases of MRI. Intracranial involvement was noted in form of meningitis, cerebritis, abscess, infarct, hemorrhage, cavernous sinus, or perineural invasion. Vascular involvement was noted in form of vascular occlusion ( n = 3), vascular narrowing ( n = 3), and pseudoaneurysm ( n = 2). MRI was more sensitive in detecting periantral invasion, deep infratemporal fossa, cavernous sinus involvement, perineural invasion, optic nerve involvement, and vascular occlusion and narrowing, while CT was superior in identification of bony erosions.Conclusion Early recognition of AIFR in post-COVID-19 patients is important to prevent disease-related morbidity/mortality. Several rarely described findings are noted in our series of AIFR, like optic nerve involvement, pituitary fungal abscess, perineural spread, fungal aneurysms, and arteritis-related posterior circulation infarcts. MRI is superior for early detection of disease and in estimation of extent of disease, compared with CT. Imaging can help in early detection of AIFR, which has a significant impact on patient outcome.

Hyponatremia in Empty Sella Syndrome: Is it a Covid Sequelae?

The symptoms associated with empty sella syndrome (ESS) include headache, giddiness, vomiting, visual field deficits, and endocrine problems, as well as the radiological appearance of an enlarged sella turcica. This case report highlights a 45-year-old female who had a COVID-19 infection 2 months back and presented with chronic headache, giddiness, and lethargy having persistent hyponatremia later diagnosed as empty sella syndrome on brain magnetic resonance imaging. In this case, we tried to correlate all of these clinical and radiological features as COVID-19 sequelae due to post-Covid hypothalamic-pituitary axis dysfunction.Copyright © 2023 Authors. All rights reserved.

Characterising approaches to steroid therapy in paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2.

AIM: We describe approaches to steroid therapy use in paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and examine the association between steroid therapy and key clinical markers of severity. METHODS: We conducted a retrospective review of children (<18 years) admitted to a tertiary paediatric hospital in the UK with PIMS-TS. We collected data on if and why steroid therapy was used; the duration, type and dosing of steroids prescribed; and approaches to hypothalamo-pituitary-adrenal (HPA) axis monitoring, if performed. We examined associations between steroid exposure/total steroid dose (mg/m2 /day) and paediatric intensive care unit admission, mechanical ventilation and inotropic support. RESULTS: Steroid therapy was commenced in most children (84.9%, n = 104) with a median total daily steroid dose (hydrocortisone equivalent) of 271.0 mg/m2 /day (interquartile range 232.5-355.5) and treatment length of 26.0 days (interquartile range 19.0-32.0). Dosing regimens predominantly involved a short course of high-dose methylprednisolone followed by tapering oral prednisolone. Basal and/or dynamic testing of the HPA axis was conducted in a minority (11.8%, n = 15) and was normal. Duration of steroid therapy correlated positively with durations of paediatric intensive care unit admission (r = 0.407, P < 0.001) and mechanical ventilation (r = 0.797, P < 0.001). A greater proportion of children receiving steroid therapy also received inotropic support compared to those that did not receive steroid therapy (71.4% vs. 45.5%, P = 0.025). CONCLUSION: Prolonged, high-dose steroid therapy is often used in the management of severe PIMS-TS with the potential for HPA axis suppression and should be withdrawn carefully.

Bridging the Gap between Ophthalmology and Emergency Medicine in Community-Based Emergency Departments (EDs): A Neuro-Ophthalmology Guide for ED Practitioners.

Coordination of care for patients with neuro-ophthalmic disorders can be very challenging in the community emergency department (ED) setting. Unlike university- or tertiary hospital-based EDs, the general ophthalmologist is often not as familiar with neuro-ophthalmology and the examination of neuro-ophthalmology patients in the acute ED setting. Embracing image capturing of the fundus, using a non-mydriatic camera, may be a game-changer for communication between ED physicians, ophthalmologists, and tele-neurologists. Patient care decisions can now be made with photographic documentation that is then conveyed through HIPAA-compliant messaging with accurate and useful information with both ease and convenience. Likewise, external photos of the anterior segment and motility are also helpful. Finally, establishing clinical and imaging guidelines for common neuro-ophthalmic disorders can help facilitate complete and appropriate evaluation and treatment.

Surgical approach to the treatment of pituicytoma. Report of five cases and a literature review.

Background: Pituicytoma (PTs) is a rare tumor of the sella and suprasellar region, derived from the pituicytes of the neurohypophysis, having distinct histological characteristics of glial neoplasms. We reported, the clinical data, neuroimaging studies, surgical approaches and pathology in five patients with PTs and also, we reviewed the literature. Methods: Retrospective chart from five consecutive patients with PTs treated at one University Hospital from 2016 to 2021 were reviewed. In addition, we conducted a search in PubMed/Medline databases using the term "Pituicytoma". Data regarding age, gender, pathological findings, and treatment modality applied were extracted. Results: All patients were female, aged 29-63, complaining of headaches, visual loss and field defects, dizziness and normal or abnormal levels of circulating pituitary hormones. Magnetic Resonance Imaging (MRI) showed in all patients a sellar and suprasellar mass, which was removed through an endoscopic transsphenoidal approach. Our third patient had a subtotal resection followed by close observation. Histopathology showed a glial non-infiltrative tumors with spindle cells, and a final diagnosis of pituicytoma was made. After surgery, visual field defects in all patients were normalized, and in two patients normal levels of plasma hormones were restored. After a mean of three years follow-up, the patients were managed post-operatively through close clinical observation and serial MRI. None of the patients had recurrence of the disease. Conclusion: PTs is a rare glial tumor of the sellar and suprasellar region that arises from neurohypophyseal pituicytes. Disease control may be achieved by total excision.

Pituitary Apoplexy in Patients with Pituitary Neuroendocrine Tumors (PitNET).

Various complications of pituitary neuroendocrine tumors (PitNET) are reported, and an intratumor hemorrhage or infarct underlying pituitary apoplexy (PA) represents an uncommon, yet potentially life-threatening, feature, and thus early recognition and prompt intervention are important. Our purpose is to overview PA from clinical presentation to management and outcome. This is a narrative review of the English-language, PubMed-based original articles from 2012 to 2022 concerning PA, with the exception of pregnancy- and COVID-19-associated PA, and non-spontaneous PA (prior specific therapy for PitNET). We identified 194 original papers including 1452 patients with PA (926 males, 525 females, and one transgender male; a male-to-female ratio of 1.76; mean age at PA diagnostic of 50.52 years, the youngest being 9, the oldest being 85). Clinical presentation included severe headache in the majority of cases (but some exceptions are registered, as well); neuro-ophthalmic panel with nausea and vomiting, meningism, and cerebral ischemia; respectively, decreased visual acuity to complete blindness in two cases; visual field defects: hemianopia, cranial nerve palsies manifesting as diplopia in the majority, followed by ptosis and ophthalmoplegia (most frequent cranial nerve affected was the oculomotor nerve, and, rarely, abducens and trochlear); proptosis (N = 2 cases). Risk factors are high blood pressure followed by diabetes mellitus as the main elements. Qualitative analysis also pointed out infections, trauma, hematologic conditions (thrombocytopenia, polycythemia), Takotsubo cardiomyopathy, and T3 thyrotoxicosis. Iatrogenic elements may be classified into three main categories: medication, diagnostic tests and techniques, and surgical procedures. The first group is dominated by anticoagulant and antiplatelet drugs; additionally, at a low level of statistical evidence, we mention androgen deprivation therapy for prostate cancer, chemotherapy, thyroxine therapy, oral contraceptives, and phosphodiesterase 5 inhibitors. The second category includes a dexamethasone suppression test, clomiphene use, combined endocrine stimulation tests, and a regadenoson myocardial perfusion scan. The third category involves major surgery, laparoscopic surgery, coronary artery bypass surgery, mitral valvuloplasty, endonasal surgery, and lumbar fusion surgery in a prone position. PA in PitNETs still represents a challenging condition requiring a multidisciplinary team from first presentation to short- and long-term management. Controversies involve the specific panel of risk factors and adequate protocols with concern to neurosurgical decisions and their timing versus conservative approach. The present decade-based analysis, to our knowledge the largest so far on published cases, confirms a lack of unanimous approach and criteria of intervention, a large panel of circumstantial events, and potential triggers with different levels of statistical significance, in addition to a heterogeneous clinical picture (if any, as seen in subacute PA) and a spectrum of evolution that varies from spontaneous remission and control of PitNET-associated hormonal excess to exitus. Awareness is mandatory. A total of 25 cohorts have been published so far with more than 10 PA cases/studies, whereas the largest cohorts enrolled around 100 patients. Further studies are necessary.

COVID-19 and Male Reproduction: A Thorny Problem.

With the global epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the increasing number of infections, little is known about how SARS-CoV-2 affects the male reproductive system during infection or after recovery. Based on the existing research data, we reviewed the effects of SARS-CoV-2 on the male reproductive system and discussed its possible mechanism of action. SARS-CoV-2 enters host cells through the angiotensin-converting enzyme 2 (ACE2)/transmembrane serine protease 2 (TMPRSS2) pathway, and males are more susceptible than females. After infection, immunopathological damage is noticed in the testicles, and the semen index is significantly reduced. Second, abnormalities of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were also observed, suggesting that there may be dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis. Even after recovery, the effect of SARS-CoV-2 on the male reproductive system can last for at least a period. There are still many unresolved questions about the effect of SARS-CoV-2 infection on the male reproductive tract. Other receptors involved during the invasion of human cells by SARS-CoV-2 remain to be identified. Will the mutation of SARS-CoV-2 increase the diversity of receptors? How does SARS-CoV-2 affect the HPG axis? The long-term effects of SARS-CoV-2 on the male reproductive system remain to be evaluated. SARS-CoV-2 infection can affect male reproductive function. Standard treatment strategies should be developed in time to protect the fertility of infected patients. For recovered patients with fertility requirements, fertility assessments should be performed and professional fertility guidance should be provided at the same time.

Pituitary and SARS CoV-2: An unremitting conundrum.

There is increased interest related to the impact of coronavirus disease 19 (COVID-19) on the endocrine system and in particular on the pituitary gland. Over the course of the severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are both acute and delayed effects on the pituitary, related to infection and/or treatment. Hypopituitarism, pituitary apoplexy and hypophysitis have been all reported, as well as arginine vasopressin deficiency (diabetes insipidus) and syndrome of inappropriate antidiuretic hormone secretion. Furthermore, patients with acromegaly, Cushing's disease and hypopituitarism are theoretically at increased risk of complications with COVID-19 and require close monitoring. Evidence regarding pituitary dysfunction in patients with COVID-19 continues to be gathered, as the breadth and depth of knowledge also continues to rapidly evolve. This review summarizes data analysis to date on the possible effects of COVID-19 and COVID-19 vaccination on patients with normal pituitary function and patients with known pituitary pathology. Though clinical systems were significantly affected, it seems there is no overall loss of biochemical control in patients with certain pituitary pathologies.

[Pituitary apoplexy and SARS-CoV-2 (COVID-19) infection]

Coronavirus disease (SARS-CoV-2/COVID-19) is responsible for a wide variety of extrapulmonary manifestations, among which direct or indirect neurological compromise stands out. Pituitary apoplexy is a clinical and neurosurgical entity of variable severity, usually associated with a pituitary adenoma. Literature is scarce regarding the association between these diseases. This paper reports a case of pituitary apoplexy, manifested concomitantly to the diagnosis of COVID 19 in a patient with unknown pituitary macroadenoma, and its therapeutic management, reviewing the mechanisms potentially underlying the link between both entities.

Pituitary apoplexy following adenoviral vector-based COVID-19 vaccination

Pituitary apoplexy (PA) may complicate the course of coronavirus disease 2019 (COVID-19), posing a potential threat to life. Among vaccines designed to prevent COVID-19, there are those adenoviral vector-based, such as Vaxzevria® (formerly COVID-19 Vaccine AstraZeneca). The product insert states that it can cause very rare coagulation disorders, in particular thrombosis with thrombocytopenia syndrome in some cases accompanied by bleeding, cerebrovascular venous or sinus thrombosis, and thrombocytopenia, including immune thrombocytopenia, also associated with bleeding. Here, we report the onset of PA after Vaxzevria® in a 28-year-old healthy Caucasian female, who experienced long-lasting tension-type headache, hyperprolactinemia and menstrual changes, without thrombocytopenia or thrombosis.

The effect of COVID-19 process on patients with endocrinological disease in a pandemic hospital: What happened to the others?

Objective: To evaluate the effects of the pandemic process on those with an endocrinological disease that will require close follow-up from the last visit before the pandemic. Materials and Methods: Patients of 3,903 with thyroid, calcium-bone metabolism, adrenal gland, pituitary diseases, and neuroendocrine tumor (NET) were retrospectively scanned. The remaining 855 (656 females and 199 males) patients with active disease or who still needed multidisciplinary approaches were included. The number of patients who continued the disease-related medical procedures and could complete these procedures on time in the pandemic period was determined, and medical deprivation rate (MDR) was calculated. Results: The prepandemic period of our patients with thyroid disease (n = 594), calcium-bone metabolism disorder (n = 130), adrenal disease (n = 85), pituitary disease, and NET (n = 46) had MDRs of 85%, 56%, 81%, and 89%, respectively. For each subgroup of patients, the lowest MDR (67%) was in medullary thyroid carcinoma, the highest MDR (89%) was in differentiated thyroid carcinoma; the lowest MDR (6%) was in osteoporosis, the highest MDR (100%) was in the active Paget's disease; the lowest MDR (0%) was in primary adrenocortical insufficiency, the highest MDR (100%) was in hyperfunctional adrenal adenomas; the lowest MDR (81%) was in pituitary nonfunctional adenomas, and the highest MDR (100%) was in Cushing's disease, active prolactinoma, TSHoma, and NET, respectively. Conclusion: This study showed that not only those who had COVID-19 but also those who had medical deprivation due to their current endocrinological disease were not to be underestimated during the pandemic period.