Central adrenal insufficiency: who, when, and how? From the evidence to the controversies – an exploratory review

Bitencourt, Mariana Rechia; Batista, Rafael Loch; Biscotto, Isabela Peixoto; Carvalho, Luciani R.

doi:10.20945/2359-3997000000493

Cited by 5 publications

(6 citation statements)

References 78 publications

(151 reference statements)

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“…These corticosteroids may have inadvertently induced temporary remission of hypophysitis [ 41 ]. Since the treatment of autoimmune hypophysitis can last for several weeks, this prescription may have suppressed the inflammatory processes temporarily without curing them, allowing for the persistence of postinfectious symptoms [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Corticotropic deficiency typically presents with nonspecific symptoms, including profound fatigue, hypoglycemia, hypotension, and gastrointestinal disturbances. Another lesser-known aspect of corticotropic deficiency is its involvement in the pathogenesis of cognitive impairment, particularly concentration difficulties [ 41 , 42 ]. These symptoms strongly resemble those described in long COVID syndrome [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

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Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis

Ach,

Ben Haj Slama,

Gorchane

et al. 2024

Journal of the Endocrine Society

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Background In some patients, symptoms may persist after COVID-19, defined as Long COVID. Its pathogenesis is still debated and many hypotheses have raised. Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing Post COVID-19 syndrome to detect any deficiencies that may explain Long COVID. Design A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a post-infection period of 3 months or less to 15 months, divided into two groups. The first group (G1) comprised of fully recovered patients, while the second group (G2) included patients experiencing Long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions. Results 64 patients were divided into two groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1(p = 0.045). For the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (p = 0.045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (p = 0.01). For the somatotroph axis, the IGF-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (p = 0.369). The peak GH level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (p = 0.041). Conclusions The results showed that Long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain the Long COVID.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis

Ach,

Ben Haj Slama,

Gorchane

et al. 2024

Journal of the Endocrine Society

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“…The diagnosis of adrenocorticotropic hormone (ACTH) deficiency was based on an extremely low basal cortisol at 8:00 a.m. below 3 µg/dL (83 nmol/L) concomitant with low normal or low ACTH level (<8.3 pg/mL, 1.83 pmol/L) ( 7 ). In the case of suspicion of central adrenal insufficiency, low-dose (1 µg) synacthen test was performed for diagnosis, and ACTH stimulation was based on a peak serum cortisol <18 µg/dL (496 nmol/L) ( 8 ). TSH deficiency was diagnosed based on a low serum-free T4 with inappropriately low serum TSH levels (<10 mIU).…”

Section: Methodsmentioning

confidence: 99%

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes

Kırkgöz,

Gürsoy,

Acar

et al. 2023

Archives of Endocrinology and Metabolism

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Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1 , GLI2, PROP-1 , POU1F1 , and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR , two in POU1F1 , one in GLI2 , and one in LHX4 . In all patients, these variants were most frequently found in GLI2 , followed by PROP-1 and GHRHR . Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

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“…However, the presenting symptoms of OIAI tend to be vague and diffuse and might be readily attributed to the underlying condition rather than the opioid therapy [20]. Secondary adrenal insufficiency in general is challenging to diagnose [21,22]. Diagnostic delays are common, with an estimated six-month lag time between the onset of symptoms and clinical diagnosis [23].…”

Section: Diagnosismentioning

confidence: 99%

A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review

Coluzzi

LeQuang

Sciacchitano

et al. 2023

IJMS

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Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy.

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Central adrenal insufficiency: who, when, and how? From the evidence to the controversies – an exploratory review

Cited by 5 publications

References 78 publications

Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis

Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes

A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review

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