Addison's Disease: Diagnosis and Management Strategies.

We aim to overview Addison's disease (AD) with regard to current diagnosis and management. This is a narrative review of full-length articles published in English between January 2022 and December 2022 (including online ahead of print versions) in PubMed-indexed journals. We included original studies in living humans regardless of the level of statistical significance starting from the key search terms "Addison's disease" or "primary adrenal insufficiency" in title or abstract. We excluded articles with secondary adrenal insufficiency. Briefly, 199 and 355 papers, respectively were identified; we manually checked each of them, excluded the duplicates, and then selected 129 based on their clinical relevance in order to address our 1-year analysis. We organized the data in different subsections covering all published aspects on the subject of AD. To our knowledge, this is the largest AD retrospective from 2022 on published data. A massive role of genetic diagnosis especially in pediatric cases is highlighted; the importance of both pediatric and adult awareness remains since unusual presentations continue to be described. COVID-19 infection is a strong player amid this third year of pandemic although we still not do have large cohorts in this particular matter as seen, for instance, in thyroid anomalies. In our opinion, the most important topic for research is immune checkpoint inhibitors, which cause a large panel of endocrine side effects, AD being one of them.

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.

From New Endocrine Entities Requiring New Approaches to New Approaches Leading to New Endocrine Entities.

The dynamics pace of modern society is reflected by the medical community, the public health concerns, the quality of life, as well as the specific spectrum of various disorders [...].

COVID-19 infection: from stress-related cortisol levels to adrenal glands infarction.

Cortisol is a key element in acute stress including a severe infection. However, in coronavirus-associated disease, 20% of subjects experience hypocortisolemia due to direct or immune damage of pituitary and adrenal glands. One extreme form of adrenal insufficiency is found in 2∕3 of cases with viral and post-viral adrenal infarction (AI) (with∕without adrenal hemorrhage) that is mostly associated with a severe coronavirus disease 2019 (COVID-19) infection; it requires prompt glucocorticoid intervention. Some reports are incidental findings at computed tomography (CT)∕magnetic resonance imaging (MRI) scans for non-adrenal complications like pulmonary spreading and others are seen on post-mortem analysis. This is a review of PubMed-accessible, English papers focusing on AI in addition to the infection, between March 1, 2020 and November 1, 2021. Exclusion criteria were acute adrenal insufficiency without the histopathological (HP) and∕or imaging report of adrenal enlargement, necrosis, etc., respective adrenal failure due to pituitary causes, or non-COVID-19-related adrenal events. We identified a total of 84 patients (different levels of statistical evidence), as follows: a retrospective study on 51 individuals, two post-mortem studies comprising nine, respectively 12 patients, a case series of five subjects, seven single-case reports. HP aspects include necrosis associated with ischemia, cortical lipid degeneration (+/- focal adrenalitis), and infarcts at the level of adrenal cortex, blood clot into vessels, acute fibrinoid necrosis in arterioles and capsules, as well as subendothelial vacuolization. Collateral potential contributors to adrenal damage are thrombotic events, coagulation anomalies, antiphospholipid syndrome, endothelial dysfunction, severe COVID-19 infection with multiorgan failure, etc. Clinical picture is variable from acute primary adrenal insufficiency to asymptomatic or mild evolution, even a retrospective diagnostic; it may be a part of long COVID-19 syndrome; glucocorticoid therapy for non-adrenal considerations might mask cortisol deficient status due to AI∕hemorrhage. Despite its rarity, the COVID-19-associated AI/hemorrhage represents a challenging new chapter, a condition that is essential to be recognized due to its gravity since prompt intervention with glucocorticoid replacement is lifesaving.

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency.

We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3ßHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients' age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also-mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing' syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison's disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem-mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as "novel pathogenic mutation" (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3ßHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

The New Entity of Subacute Thyroiditis amid the COVID-19 Pandemic: From Infection to Vaccine.

This is a review of full-length articles strictly concerning subacute thyroiditis (SAT) in relation to the SARS-CoV-2 virus infection (SVI) and COVID-19 vaccine (COV) that were published between the 1st of March 2020 and the 21st of March 2022 in PubMed-indexed journals. A total of 161 cases were reported as follows: 81 cases of SAT-SVI (2 retrospective studies, 5 case series, and 29 case reports), 80 respective cases of SAT-COV (1 longitudinal study, 14 case series, 17 case reports; also, 1 prospective study included 12 patients, with 6 patients in each category). To our knowledge, this represents the largest cohort of reported cases until the present time. SAT-SVI was detected in adults aged between 18 and 85 years, mostly in middle-aged females. SAT-COVID-19 timing classifies SAT as viral (synchronous with infection, which is an original feature of SATs that usually follow a viral infection) and post-viral (during the recovery period or after infection, usually within 6 to 8 weeks, up to a maximum 24 weeks). The clinical spectrum has two patterns: either that accompanying a severe COVID-19 infection with multi-organ spreading (most frequent with lung involvement) or as an asymptomatic infection, with SAT being the single manifestation or the first presentation. Either way, SAT may remain unrecognized. Some data suggest that more intense neck pain, more frequent fever, and more frequent hypothyroidism at 3 months are identified when compared with non-SAT-SVI, but other authors have identified similar presentations and outcomes. Post-COVID-19 fatigue may be due to residual post-SAT hypothyroidism. The practical importance of SAT-SVI derives from the fact that thyroid hormone anomalies aggravate the general status of severe infections (particular concerns being tachycardia/arrhythmias, cardiac insufficiency, and ischemic events). If misdiagnosed, SAT results in unnecessary treatment with anti-thyroid drugs or even antibiotics for fever of unknown cause. Once recognized, SAT does not seem to require a particular approach when compared with non-COVID-19 cases, including the need for glucocorticoid therapy and the rate of permanent hypothyroidism. A complete resolution of thyroid hormone anomalies and inflammation is expected, except for cases with persistent hypothyroidism. SAT-COV follows within a few hours to a few weeks, with an average of 2 weeks (no particular pattern is related to the first or second vaccine dose). Pathogenesis includes molecular mimicry and immunoinflammatory anomalies, and some have suggested that this is part of ASIA syndrome (autoimmune/inflammatory syndrome induced by adjuvants). An alternative hypothesis to vaccine-related increased autoimmunity is vaccine-induced hyperviscosity; however, this is supported by incomplete evidence. From what we know so far concerning the risk factors, a prior episode of non-SVI-SAT is not associated with a higher risk of SAT-COV, nor is a previous history of coronavirus infection by itself. Post-vaccine SAT usually has a less severe presentation and a good outcome. Generally, the female sex is prone to developing any type of SAT. HLA susceptibility is probably related to both new types of SATs. The current low level of statistical evidence is expected to change in the future. Practitioners should be aware of SAT-COV, which does not restrict immunization protocols in any case.

Anorexia nervosa: COVID-19 pandemic period (Review).

Anorexia nervosa is an eating disorder characterized by restrictive eating and an intense fear of gaining weight. It is a disease with an increasing incidence during the last few decades, and represents a complex psychiatric condition which includes secondary amenorrhea, nutritional and metabolic damage, and impaired endocrine panel up to bone loss as well as cardiac, gastrointestinal and hematological complications. This is a narrative review which includes an update on this eating disorder from the perspective of an endocrine panel of anomalies, especially of the skeleton, considering the pressure of the recent global COVID-19 pandemic changes. Practically affecting every organ, anorexia nervosa needs to be taken into consideration during the pandemic period because of the higher risk of relapse due to new living conditions, social distancing, self-isolation, changes in food access, more intense use of social media platforms, disruption of daily habits, and more difficult access to healthcare practitioners. The lack of physical activity in addition to vitamin D deficiency related to low sun exposure or to the use of facial masks may also be connected to further bone damage related to this disease.

COVID-19-related thyroid conditions (Review).

In patients who were not previously diagnosed with any thyroid conditions, the scenario of COVID-19-related anomalies of the hypothalamus-pituitary-thyroid axes may include either: A process of central thyroid stimulating hormone (TSH) disturbances via virus-related hypophysitis; an atypical type of subacute thyroiditis which is connected to the virus spread or to excessive cytokine production including a destructive process with irreversible damage of the gland or low T3 (triiodothyronine) syndrome (so called non-thyroid illness syndrome) which is not specifically related to the COVID-19 infection, but which is associated with a very severe illness status. Our objective here was to briefly review thyroid changes due to the COVID-19 infection. Ongoing assessment of the effects of the COVID-19 pandemic will reveal more information on coronavirus-induced thyroid conditions. Routine thyroid assays performed in patients with severe infection/at acute phase of COVID-19 are encouraged in order to detect thyrotoxicosis. After recovery, thyroid function should be assessed to identify potential hypothyroidism. There remain unanswered questions related to the prognostic value of interleukin-6 in infected patients, especially in cases with cytokine storm, and the necessity of thyroid hormone replacement in subjects with hypophysitis-related central hypothyroidism.