PDF herunterladen
Horm Metab Res 2022; 54(03): 153-161
DOI: 10.1055/a-1764-1260
Endocrine Care

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19

Mustafa Sait Gonen 
1   Division of Endocrinology and Metabolism, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Annamaria De Bellis 
2   Unit of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, Naples, Italy
,
Emre Durcan 
1   Division of Endocrinology and Metabolism, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Giuseppe Bellastella 
2   Unit of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, Naples, Italy
,
Paolo Cirillo
3   Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
,
Lorenzo Scappaticcio
3   Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
,
Miriam Longo
3   Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
,
Basak Ecem Bircan 
1   Division of Endocrinology and Metabolism, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Serdar Sahin 
1   Division of Endocrinology and Metabolism, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Cem Sulu 
1   Division of Endocrinology and Metabolism, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Hande Mefkure Ozkaya 
1   Division of Endocrinology and Metabolism, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Dildar Konukoglu 
4   Department of Medical Biochemistry, Istanbul University-Cerrahpasa, Istanbul, Turkey
,
Fatma Ferda Kartufan 
5   Department of Anaesthesiology and Reanimation, Yeditepe University, Istanbul, Turkey
,
Fahrettin Kelestimur 
6   Department of Endocrinology, Yeditepe University, Istanbul, Turkey
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Key words

COVID-19 - hypothalamic-pituitary axis - antihypothalamic antibodies - antipituitary antibodies - ACTH stimulation test - adrenal insufficiency


Publikationsverlauf

Eingereicht: 21. November 2021

Angenommen nach Revision: 27. Januar 2022

Artikel online veröffentlicht:
11. März 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Johns Hopkins University. “COVID-19 dashboard by the center for systems science and engineering (CSSE) at Johns Hopkins University (JHU).” Im Internet: https://gisanddata.maps.arcgis.com/apps/dashboards/bda7594740fd40299423467b48e9ecf6Stand: 11/09/2021
    PubMed
  • 2 Baj J, Karakuła-Juchnowicz H, Teresiński G. et al. COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge. J Clin Med 2020; 9: 1-22
    CrossrefPubMedGoogle Scholar
  • 3 Roberts CM, Levi M, McKee M. et al. COVID-19: a complex multisystem disorder. Br J Anaesth 2020; 125: 238-242
    CrossrefPubMedGoogle Scholar
  • 4 Wang W, Xu Y, Gao R. et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020; 323: 1843-1844
    PubMedGoogle Scholar
  • 5 Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020; 215: 108427
    CrossrefPubMedGoogle Scholar
  • 6 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506
    CrossrefPubMedGoogle Scholar
  • 7 Li B, Yang J, Zhao F. et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol 2020; 109: 531-538
    CrossrefPubMedGoogle Scholar
  • 8 Chang L, Yan Y, Wang L. Coronavirus disease 2019: coronaviruses and blood safety. Transfus Med Rev 2020; 34: 75-80
    CrossrefPubMedGoogle Scholar
  • 9 Liu F, Long X, Zhang B. et al. ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection. Clin Gastroenterol Hepatol 2020; 18: 2128-2130.e2
    CrossrefPubMedGoogle Scholar
  • 10 Marazuela M, Giustina A, Puig-Domingo M. Endocrine and metabolic aspects of the COVID-19 pandemic. Rev Endocr Metab Disord 2020; 21: 495-507
    CrossrefPubMedGoogle Scholar
  • 11 Lundholm MD, Poku C, Emanuele N. et al. SARS-CoV-2 (COVID-19) and the Endocrine System. J Endocr Soc 2020; 4: 1-13
    CrossrefPubMedGoogle Scholar
  • 12 Somasundaram NP, Ranathunga I, Ratnasamy V. et al. The impact of SARS-Cov-2 virus infection on the endocrine system. J Endocr Soc 2020; 4: bvaa082
    PubMedGoogle Scholar
  • 13 Mongioì LM, Barbagallo F, Condorelli RA. et al. Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model. Endocrine 2020; 68: 467-470
    CrossrefPubMedGoogle Scholar
  • 14 Pal R, Banerjee M. COVID-19 and the endocrine system: exploring the unexplored. J Endocrinol Invest 2020; 43: 1027-1031
    CrossrefPubMedGoogle Scholar
  • 15 Rhee E-J, Kim JH, Moon SJ. et al. Encountering COVID-19 as endocrinologists. Endocrinol Metab 2020; 35: 197-205
    CrossrefPubMedGoogle Scholar
  • 16 Puig-Domingo M, Marazuela M, Giustina A. COVID-19 and endocrine diseases. A statement from the European Society of Endocrinology. Endocrine 2020; 68: 2-5
    CrossrefPubMedGoogle Scholar
  • 17 Chiloiro S, Capoluongo ED, Tartaglione T. et al. The changing clinical spectrum of hypophysitis. Trends Endocrinol Metab 2019; 30: 590-602
    CrossrefPubMedGoogle Scholar
  • 18 Tanriverdi F, De Bellis A, Teksahin H. et al. Prospective investigation of pituitary functions in patients with acute infectious meningitis: Is acute meningitis induced pituitary dysfunction associated with autoimmunity?. Pituitary 2012; 15: 579-588
    CrossrefPubMedGoogle Scholar
  • 19 Alzahrani AS, Mukhtar N, Aljomaiah A. et al. The impact of COVID-19 viral infection on the hypothalamic-pituitary-adrenal axis. Endocr Pract 2021; 27: 83-89
    CrossrefPubMedGoogle Scholar
  • 20 Hashim M, Athar S, Gaba WH. New onset adrenal insufficiency in a patient with COVID-19. BMJ Case Rep 2021; 14: e237690
    CrossrefPubMedGoogle Scholar
  • 21 Heidarpour M, Vakhshoori M, Abbasi S. et al. Adrenal insufficiency in coronavirus disease 2019: a case report. J Med Case Rep 2020; 14: 134
    CrossrefPubMedGoogle Scholar
  • 22 Tan T, Khoo B, Mills EG. et al. Association between high serum total cortisol concentrations and mortality from COVID-19. Lancet Diabetes Endocrinol 2020; 8: 659-660
    CrossrefPubMedGoogle Scholar
  • 23 Mao Y, Xu B, Guan W. et al. The adrenal cortex, an underestimated site of SARS-CoV-2 infection. Front Endocrinol (Lausanne) 2021; 11: 593179
    PubMedGoogle Scholar
  • 24 National Health Commission of the People’s Republic of China. Full-text: diagnosis and treatment protocol for COVID-19 patients (Tentative 8th Edition). In Internet: http://regional.chinadaily.com.cn/pdf/DiagnosisandTreatmentProtocolforCOVID-19Patients(Tentative8thEdition).pdfStand: 01/17/2021
    PubMed
  • 25 Bidlingmaier M, Friedrich N, Emeny RT. et al. Reference intervals for insulin-like growth factor-1 (IGF-I) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab 2014; 99: 1712-1721
    CrossrefPubMedGoogle Scholar
  • 26 Fliers E, Bianco AC, Langouche L. et al. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol 2015; 3: 816-825
    CrossrefPubMedGoogle Scholar
  • 27 Dickstein G. Low dose ACTH test: a word of caution to the word of caution: when and how to use it. J Clin Endocrinol Metab 1997; 82: 322-322
    PubMedGoogle Scholar
  • 28 Patti G, Calandra E, De Bellis A. et al. Antibodies against hypothalamus and pituitary gland in childhood-onset brain tumors and pituitary dysfunction. Front Endocrinol (Lausanne) 2020; 11: 16
    PubMedGoogle Scholar
  • 29 Bellastella G, Rotondi M, Pane E. et al. Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up. J Clin Endocrinol Metab 2010; 95: 3750-3757
    CrossrefPubMedGoogle Scholar
  • 30 Michalaki M. Dissociation of the early decline in serum T3 concentration and serum IL-6 rise and TNF in nonthyroidal illness syndrome induced by abdominal surgery. J Clin Endocrinol Metab 2001; 86: 4198-4205
    PubMedGoogle Scholar
  • 31 Croce L, Gangemi D, Ancona G. et al. The cytokine storm and thyroid hormone changes in COVID-19. J Endocrinol Invest 2021; 44: 891-904
    CrossrefPubMedGoogle Scholar
  • 32 Leow MK-S, Kwek DS-K, Ng AW-K. et al. Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). Clin Endocrinol (Oxf) 2005; 63: 197-202
    CrossrefPubMedGoogle Scholar
  • 33 Wang W, Ye Y, Yao H. Evaluation and observation of serum thyroid hormone and parathyroid hormone in patients with severe acute respiratory syndrome. J Chin Antituberculous Assoc 2003; 25: 232-234
    PubMedGoogle Scholar
  • 34 Chen M, Zhou W, Xu W. Thyroid function analysis in 50 patients with COVID-19: a retrospective study. Thyroid 2021; 31: 8-11
    CrossrefPubMedGoogle Scholar
  • 35 Chen T, Wu D, Chen H. et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020; m1091
    CrossrefPubMedGoogle Scholar
  • 36 Gao W, Guo W, Guo Y. et al. Thyroid hormone concentrations in severely or critically ill patients with COVID-19. J Endocrinol Invest 2021; 44: 1031-1040
    CrossrefPubMedGoogle Scholar
  • 37 Arnold J, Campbell IT, Samuels TA. et al. Increased whole body protein breakdown predominates over increased whole body protein synthesis in multiple organ failure. Clin Sci 1993; 84: 655-661
    CrossrefPubMedGoogle Scholar
  • 38 Baxter RC. Changes in the IGF–IGFBP axis in critical illness. Best Pract Res Clin Endocrinol Metab 2001; 15: 421-434
    CrossrefPubMedGoogle Scholar
  • 39 Langouche L, Van den Berghe G. Hypothalamic–pituitary hormones during critical illness. Handb Clin Neurol 2014; 124: 115-126
    CrossrefPubMedGoogle Scholar
  • 40 Lubrano C, Masi D, Risi R. et al. Is growth hormone insufficiency the missing link between obesity, male gender, age, and COVID-19 severity?. Obesity 2020; 28: 2038-2039
    CrossrefPubMedGoogle Scholar
  • 41 Gilliver SC. Sex steroids as inflammatory regulators. J Steroid Biochem Mol Biol 2010; 120: 105-115
    CrossrefPubMedGoogle Scholar
  • 42 Xu J, Qi L, Chi X. et al. Orchitis: A complication of severe acute respiratory syndrome (SARS)1. Biol Reprod 2006; 74: 410-416
    CrossrefPubMedGoogle Scholar
  • 43 Channappanavar R, Fett C, Mack M. et al. Sex-based differences in susceptibility to severe acute respiratory syndromecoronavirus infection. J Immunol 2017; 198: 4046-4053
    CrossrefPubMedGoogle Scholar
  • 44 Ma L, Xie W, Li D. et al. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J Med Virol 2021; 93: 456-462
    CrossrefPubMedGoogle Scholar
  • 45 Vilar L, Abucham J, Albuquerque JL. et al. Controversial issues in the management of hyperprolactinemia and prolactinomas – an overview by the neuroendocrinology department of the Brazilian society of endocrinology and metabolism. Arch Endocrinol Metab 2018; 62: 236-263
    CrossrefPubMedGoogle Scholar
  • 46 Gu WT, Zhou F, Xie WQ. et al. A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors. Endocrine 2021; 72: 340-348
    CrossrefPubMedGoogle Scholar
  • 47 Aygen B, Inan M, Doğanay M. et al. Adrenal functions in patients with sepsis. Exp Clin Endocrinol Diabetes 2009; 105: 182-186
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 48 Wheatland R. Molecular mimicry of ACTH in SARS – implications for corticosteroid treatment and prophylaxis. Med Hypotheses 2004; 63: 855-862
    CrossrefPubMedGoogle Scholar
  • 49 Pal R. COVID-19, hypothalamo-pituitary-adrenal axis and clinical implications. Endocrine 2020; 68: 251-252
    CrossrefPubMedGoogle Scholar
  • 50 Tanriverdi F, Karaca Z, Unluhizarci K. et al. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress 2007; 10: 13-25
    CrossrefPubMedGoogle Scholar
  • 51 Karaca Z, Lale A, Tanriverdi F. et al. The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary 2011; 14: 134-140
    CrossrefPubMedGoogle Scholar
  • 52 Simsek Y, Karaca Z, Tanriverdi F. et al. A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin Endocrinol (Oxf) 2015; 82: 45-52
    CrossrefPubMedGoogle Scholar
  • 53 Karaca Z, Grossman A, Kelestimur F. Investigation of the hypothalamo-pituitary-adrenal (HPA) axis: a contemporary synthesis. Rev Endocr Metab Disord 2021; 22: 179-204
    CrossrefPubMedGoogle Scholar
  • 54 Dökmetaş HS, Çolak R, Keleştimur F. et al. A comparison between the 1-mg adrenocorticotropin (ACTH) test, the short ACTH (250 μg) test, and the insulin tolerance test in the assessment of hypothalamo-pituitary-adrenal axis immediately after pituitary surgery. J Clin Endocrinol Metab 2000; 85: 3713-3719
    PubMedGoogle Scholar
  • 55 Clarke SA, Phylactou M, Patel B. et al. Normal adrenal and thyroid function in patients who survive COVID-19 infection. J Clin Endocrinol Metab 2021; 106: 2208-2220
    CrossrefPubMedGoogle Scholar