IDENTITAS

Nama : Prof.Dr.dr.Banundari Rachmawati SpPK(K)

Tempat tanggal lahir. : Pemalang, 6 Juni 1960
Alamat : Puri Ayodya D6, Ngesrep Timur VI Semarang CURICULUM
Jabatan akademik : Guru Besar VITAE
PENDIDIKAN
Dokter Fakultas Kedokteran UNDIP Lulus tahun 1987
Spesialis Patologi Klinik (Sp 1) FK UNDIP Lulus tahun 1997
Sp2 (Konsultan) metabolism endokrinologi UNAIR/ Kolegium Lulus tahun 2007
Program Doktor Ilmu kedokteran dan Kesehatan Pasca Sarjana UNDIP Lulus tahun 2012
Short course: An International Training & Support program for the Control of Iodine Deficiency Disorders. CDC ATLANTA Mei-Sept 1991
The epidemiology in Action the School of Public Health, Emory University / CDC Atlanta April-Mei 1991
1
RIWAYAT PEKERJAAN
Staf pengajar S1, PPDSPK, PPDSIPD, PPDSGK, Sp2PK, PDIKK (S3) FK Undip 1987- sekarang
SPS2 PPDS I Patologi Klinik 1997-2005 Sekretaris Bagian PK FK UNDIP 2005-2008
Ketua
5 PPDS I Patologi Klinik FK UNDIP 2014-2018

Direktur
6 Unit Transfusi Darah PMI Provinsi Jawa Tengah 2003-2017
Ketua
7 Komisi Etik Penelitian Kedokteran(KEPK) FK UNDIP 2019- sekarang

Anggota
8 Dewan profesor Undip 2019 - sekarang
ORGANISASI
IDI , sejak 1987 PHTDI, sejak 1997 PEROSI: sejak 2021
PP PDSPatKLIn , 2000- 2003 PERKENI cabang Semarang, sejak 2001
PP PDSPatKLIn 2004-2007 PC PDSPatKLIn Cabang Semarang, 2004-2007
Ketua PDSPatKLIn Cab Semarang 2013-2016, 2016-2019 Anggota Kolegium PPDS Patologi Klinik 2016-2019, 2019-sekarang
ENDOCRINOLOGY UPDATE ON LABORATORY MEDICINE
COVID-19 PERSPECTIVE

BANUNDARI RACHMAWATI
FAKULTAS KEDOKTERAN UNDIP / RSUP DR KARIADI
 OUTLINE
• INTRODUCTION

• THE ENDOCRINE SYSTEM AS A TARGET OF BETA CORONAVIRUSRES

• POSSIBLE EFFECTS OF SARS-COV-2 ON THE ENDOCRINE SYSTEM

• PANCREAS

• THYROID

• PARATHYROID

• REPRODUCTIVE TRACT

• PANCREAS
• ADRENAL

• VITAMIN D
• CONCLUSIONS
INTRODUCTION
angka
 Viral entry and cellular pathogenesis.

Somasundaram NP et al. Journal of the Endocrine Society, Volume 4, Issue 8, August 2020, bvaa082, 
https://doi.org/10.1210/jendso/bvaa082. Published: 02 July 2020 . TMPRSS2, transmembrane serine protease2
THE ENDOCRINE SYSTEM
AS A TARGET OF BETA
CORONA VIRUSES
THE ENDOCRINE SYSTEM AS A TARGET OF BETA CORONAVIRUSRES
(eg SARS-CoV)
Different endocrine glands/organs that can be affected by COVID- 19
COVID-19 AND THE ENDOCRINE SYSTEM
POSSIBLE EFFECTS OF
SARS-COV-2 ON THE
ENDOCRINE SYSTEM
 Functional
Hypopituarism

Adrenal Insuficiency Subacute Thyroiditis Type 1 Diabetes Dysglicaemia

 POSSIBLE EFFECTS OF SARS-COV-2 ON THE ENDOCRINE SYSTEM
Effect on Management Issues
Pathology Possible Mechanism Clinical Features
Hormonal Axis and Solutions
Pituitary
Central hypocortisolism Hypophysitis resulting from Impaired ACTH/cortisol Postviral syndromes Cosyntropin/ACTH?Synacthen test 
and hypothyroidism  infiltration by virus [41]  production  [41]  TSH and free T4 
Hypothalamic involvement [41]  Low thyroid hormones If deficient, hormone replacement in
Destruction of ACE2 in sometimes with low TSH  physiological doses [41] 
hypothalamus [43, 44] 
Molecular mimicry of SARS-CoV-
1 to ACTH and subsequent host
defense mechanisms [46] 

Hyperprolactinemia  Dopaminergic stress response Transient Asymptomatic  Prolactin levels may be high during
[48]  hyperprolactinemia  acute illness. 
Caution on interactions of DRA with
CYP450 inducing antivirals and
amine based pressors/inotropes
Somasundaram NP et al. Journal of the Endocrine Society, Volume 4, Issue 8, August 2020, bvaa082, 
[55, 56] 
https://doi.org/10.1210/jendso/bvaa082. Published: 02 July 2020
 POSSIBLE EFFECTS OF SARS-COV-2 ON THE ENDOCRINE SYSTEM

Effect on Hormonal Management Issues

Pathology Possible Mechanism Clinical Features
Axis and Solutions
Adrenal
Hypoadrenalism  Adrenal necrosis and vasculitis from Hypocortisolism  Postural hypotension  Serum 9 am cortisol 
direct cytopathic effect or inflammatory Persistently low blood Cosyntropin test 
response [29, 59]  pressure  Hydrocortisone therapy 
Hyperkalemia and
hyponatremia 
Thyroid
Hypothyroidism  Destruction of follicular and Primary Hypothyroid features   High TSH and low free T4 
parafollicular cells of thyroid [83]  hypothyroidism  Thyroxine replacement  
  Decreased activity of type 1 deiodinase Sick euthyroidism  Clinically not significant  Difficulty in differentiating
activity, increased activity of type 3 during acute illness, test
deiodinase activity, and down-regulation TSH and free T4 following
of hypothalamic pituitary axis [82]  recovery 
  Hypophysitis/ hypothalamic involvement Central Hypothyroid features  Low TSH and free T4 
[41]  hypothyroidism  Thyroxine replacement 

Somasundaram NP et al. Journal of the Endocrine Society, Volume 4, Issue 8, August 2020, bvaa082, 
https://doi.org/10.1210/jendso/bvaa082. Published: 02 July 2020
 POSSIBLE EFFECTS OF SARS-COV-2 ON THE ENDOCRINE SYSTEM

Effect on Clinical Management Issues

Pathology Possible Mechanism
Hormonal Axis Features and Solutions
Pancreas
Hypo-/hyperglycemi Direct viral injury on ACE2 expressing islet cells Possible hypoinsulinemia  Hyperglycemia  Hyperglycemia predicts poor
a  [89]  Stress response up- Mild pancreatitis: prognosis 
Hyperglycemia glycosylates ACE2 and viral S regulates cortisol, growth minimal or no Requires frequent monitoring
protein, facilitating viral entry [92]  hormone, and adrenergic symptoms  and titration of treatment 
Pancreatitis [90]: direct viral injury, response to activity with Potential anti-COVID therapies
systemic inflammation, immune-mediated injury hyperglycemic effects  may cause hypo- and
  hyperglycemia [100] 
Parathyroid
  No direct effect   Not identified  Not identified  None 
Gonads
Hypogonadism  Entry of virus into spermatogonia and somatic
cells using ACE2 receptors [123, 124] 
Destruction of seminiferous tubules and reduced
s

Somasundaram NP et al. Journal of the Endocrine Society, Volume 4, Issue 8, August 2020, bvaa082, https://
doi.org/10.1210/jendso/bvaa082. Published: 02 July 2020
PANCREAS
 Many studies report an atypical case of acute pancreatitis in a patient with SARSCoV2
infection. CT scan abdomen: suggestive of acute interstitial edematous pancreatitis.
 HRCT chest : multifocal ground glass opacities in both lungs, nasal swab : COVID RT-
PCR positive.
 COVID-19 pathogenesis is believed to be mediated by the ACE-2 receptor over the cell
surface for viral entry into host cells and are highly expressed in pancreatic cells.
 All the reported cases of COVID-19 pancreatitis so far are known cases of COVID 19
pneumonia, developed acute pancreatitis or pancreatic injury in due course or during
recovery of the illness.
 Further studies are needed to establish the real prevalence and clinical significance of
pancreatic injury in COVID-19 patients. (Ann Hepatobiliary Pancreat Surg 2020;24:539-541)
CLINICAL COMPLICATIONS OF COVID-19

Mild pancreatitis
Posible viral infection
Hypoxia
Pancreatitis could facilitate ARDS
 TRANSMISSION OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS
COV-2) TO THE PANCREAS AND MECHANISM OF THE VIRUS ENTRY.

TMPRSS2, transmembrane serine protease2; ACE2, angiotensin receptor 2.

J. Samanta, R. Gupta, M.P. Singh et al., Coronavirus disease 2019 and the pancreas, Pancreatology, https://doi.org/ 10.1016/j.pan.2020.10.035
PROPOSED FUNCTIONS OF PANCEATIC β-CELL MOLECULES FOR
INTERACTION WITH SEVERE ARDS SARS-CoV-2
 The ACE2 receptor is widely expressed within the epithelial
cells of the respiratory tract, tubular epithelial cells, mucosal
cells of the GI tract, vascular endothelial cells, cardiac
myocytes and the pancreatic b-cells
 SARS-CoV-2 enters the host cell utilising the envelope spike
glycoprotein on its surface to bind the ACE2 enzyme,
modulates the enzyme’s activity, potentiating cell damage and
respiratory failure. Hypokalaemia: a feature of people who are
critically ill from COVID-19 as a result of renal potassium
wasting from excess aldosterone secretion.
 Hyperglycaemia induces the glycosylation of the ACE2
receptor, promoting cellular linkage to the SARS-CoV-2 virus
and infection of the host cell and causing a higher disease
severity
ACE2: angiotensin-converting enzyme 2;
TMPRRS2: transmembrane protease serine 2;
 INCIDENCE OF PANCREATIC INJURY IN COVID-19 PATIENTS.

Pancreatic injury:
8.3-17.3%
Raised amylase:8.5-
13.5% (3 studies)
Raised lipase: 8.5-
16.8%

J. Samanta, R. Gupta, M.P. Singh et al., Coronavirus disease 2019 and the pancreas, Pancreatology, https://doi.org/ 10.1016/j.pan.2020.10.035
CASE REPORTS/SERIES OF ACUTE PANCREATITIS WITH COVID-19 INFECTION.

21 cases
* CT Imaging:19
Only 3 : normal
*Raised Amylase : 18

J. Samanta, R. Gupta, M.P. Singh et al., Coronavirus disease 2019 and the pancreas, Pancreatology, https://doi.org/ 10.1016/j.pan.2020.10.035
DIABETES and THE COVID-19 PANDEMIC
COVID-19 and diabetes: In need of answers – type of diabetes?
Mechanisms? Metabolic interventions? - Endo-ERN!

SARS-CoV-2 + COVID-19 Glucose Diabetes

dysregulation mellitus

Treatment
Higher age,
obesity,
hypertension,
coagulopathy,
dyslipidemia,
Insulin Insulin effect CVD
secretion in target Treatment
organs

COVID-19 outcome (severity

Glucose dysregulation pneumonia, complications,
mortality)
 Re as o ns fo r g luc o s e fluc tuatio n in patie nts with diabe te s and COVID-19

Th e re m a y b e in t e rru p t io n o r n o n -
2 s t a n d a rd t re a t m e n t w it h OAD in
is o la t io n w a rd s , re s u lt in g in
I rre g u la r d ie t , re d u c e d g lu c o s e flu c t u a t io n
1 e x e rc is e , g a s t ro in t e s t in a l
s y m p t o m s , e t c . , a ffe c t d ie t ,
re s u lt in g in g lu c o s e
flu c t u a t io n

Fe a r, a n x ie t y a n d t e n s io n
m a y in c re a s e g lu c o s e le v e l 3
a n d in d u c e g lu c o s e
S t re s s c o n d it io n s lik e flu c t u a t io n
4 in fe c t io n in c re a s e
g lu c o c o rt ic o id s s e c re t io n

COVI D - 1 9 c a n c a u s e h u m a n b o d y
t o p ro d u c e a la rg e n u m b e r o f
Th e u s e o f g lu c o c o rt ic o id s
in fla m m a t o ry c y t o k in e s a n d le a d 6
in t re a t m e n t c a n le a d t o a
5 t o e x t re m e s t re s s in s o m e s e v e re
s h a rp ris e in g lu c o s e
a n d c rit ic a l p a t ie n t s

Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219
 OPEN RESEARCH QUESTIONS

 Is CovID-19 a new aetiology for acute pancreatitis?

 If so, how frequently does it complicate the course of CovID-19?
 In case of an association, can SarS-Cov-2 infection cause acute pancreatitis without
causing typical CovID-19 disease with respiratory symptoms, hence patients could
present with an idiopathic acute pancreatitis and be recognized as SarS-Cov-2
positive only by a screening swab?
 as acute pancreatitis has been reported during the course of CovID-19, are there
other aetiologies — for example, drug-induced cases of acute pancreatitis in these
patients — or is it a result of the SarS-Cov-2 infection itself?
 Is the putative mechanism for the association between acute pancreatitis and CovID-
19 related to direct viral damage of pancreatic cells or to endothelial damage and/or
thrombosis and ischaemic pancreatitis?
 What is the effect of acute pancreatitis on the prognosis of CovID-19?
THYROID
POTENSIAL MECHANISMS FOR EFFECTS OF SARS-C0V-2 INFECTIONS
ON THYROID, HYPOTHALAMIC-PITUITARY-THYROID, NTIS, SAT

Viral Infection

Infection HT/Pituitary Activation of inflamatory

status injury Direct Infection Factors and cytokines

HPT axis Thyroid cell

NTIS Immune mediated
dysfunction dysfunction damage

Thyroid dysfunction SAT

NTIS: Nonthyroidal illness syndrome; SAT: Sub acute thyroiditis

Schematic representing potential mechanisms of Covid-19-related thyroid disorders emerged
hypothalamic–pituitary–thyroid (HPT) axis injury by from the analysis of the current literature
SARS-CoV- 2 infection

Scappaticcio L et al. Reviews in Endocrine and Metabolic Disorders . https://doi.org/10.1007/s11154-020-09615-z

ACE-2 RECEPTORS IN THYROID
FOLLICULAR CELLS AND SARS-
COV-2 ENTRY

Giovanella L et al .Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00419-y

 Thyroid
hormone Oxidative stress

Aging Multiple disorders

Immuno
Antioxidants
modulation

COVID-19
Comorbidity
EFFECT OF THYROID
HORMONES ON RENIN-
ANGIOTENSINOGEN tiroid
SYSTEM

Heliyon 6 (2020) e05712

SISTIMATIC REVIEW : Giovanella L et
al

7 studies
Abn TFT : 13.1-64%
Low TSH: 5,4-56%
N TSH: 44-93,7%
High TSH: 0-8%

7 studies :
Differences : TFT covid-19 vs control: 3
Correlation: TFT vs severity Cov : 4
Correll: Tyr disfunc vs Cov mortality : 2

Giovanella L et al .Clinical and Translational Imaging

https://doi.org/10.1007/s40336-021-00419-y
Scappaticcio L et al
Comparison of clinical features among COVID-19, non-COVID-19 pneumonia patients and healthy subjects.

Wang W
SUMMARY OF FINDINGS REGARDING THE RELATIONSHIP BETWEEN THYROID AND COVID-19
(Scappaticcio L et al. Reviews in Endocrine and Metabolic Disorders . https://doi.org/10.1007/s11154-020-09615-z )

• ACE2 and TMPRSS2 expression levels are high in thyroid and more than in lungs

• Abnormal immune responses and cytokine storm associated to COVID-19 may induce thyroid gland
inflammation
• Two mechanisms (i.e. indirect and direct) might account for the changes in the thyroid gland and HPT axis

• COVID-19-related thyroid disorders could include thyrotoxicosis, hypothyroidism, nonthyroidal

illness syndrome

• Thyrotoxicosis in absence of neck pain is frequent in patients hospitalized for COVID-19

• Low TSH and T3 and thyrotoxicosis appear to be predictors of poor outcome of patients hospitalized for COVID-19

• Further research is necessary to explore COVID-19

ACE2, Angiotensin-converting–enzyme 2; TMPRSS2, transmembrane protease serine 2; HPT, hypothalamic–pituitary–thyroid; SAT, subacute thyroiditis
PARATHYROID
 THE EFFECT OF COVID-19 ON PARATHYROID GLANDS

Abobaker A, Alzwi A, The effect of COVID-19 on parathyroid glands, Journal of Infection and Public Health (2021), doi:
https://doi.org/10.1016/j.jiph.2021.04.002
 Several studies showed a key role of calcium in viral fusion for many enveloped viruses
such as SARS-CoV, MERS-CoV and Ebolavirus, Ca promoted their replication directly
interacting with fusion peptides of these viruses .
 Hypocalcemia had already shown to be common in patients with SARS (60% of patients
at hospital admission), although generally mild
 Very recently, found in a retrospective single Institution study ( 531 patients with COVID-
19) a high prevalence of hypocalcemia (in about 80% of cases) on initial hospital
evaluation, more frequently: elderly males with linear correlation between Ca levels and
LDH and PCR levels.
 In multivariate analyses, hypocalcemia was an independent risk factor associated with
hospitalization, where- as it predicted ICU admission and mortality only in univariate
analysis.
 Finally, since hypocalcemia may have negative impact on cardiac outcomes , Ca
evaluation, monitoring and adequate supplementation if needed in all hospitalized
patients with COVID-19 infection is recommended.
VITAMIN D
POSTULATED MECHANISMS OF VITAMIN D IN PREVENTION OF COVID-19 INFECTION

ACE1, angiotensin-converting enzyme 1; ACE2,

angiotensin-converting enzyme 2; AT1R, type 1
angiotensin 2 receptor; AT1-7, heptapeptide
angiotensin (1-7); DPP4/ CD26, dipeptidyl
peptidase 4/cluster of differentiation 26; Th1, T
Somasundaram et al .doi: 10.1210/jendso/bvaa082 | Journal of the Endocrine Society | 15 helper 1 cells; Th2, T helper 2 cells.
Vitamin D: increases the expression of anti- inflammatory cytokines while reducing
the expression of pro-inflammatory cytokines, which are all beneficial in COVID-19

a recent meta-analysis concludes that oral vitamin D3 supplementation reduced

the risk of acute respiratory tract infections (OR 0.88%).

In the current COVID-19 pandemic, there are some data suggesting that
European countries with lower mean vitamin D levels had higher rates of infection
and mortality related to COVID-19.

It would be prudent to ensure patients have sufficient levels of vitamin D and

initiate supplementation, especially in the elderly who have a higher risk of vitamin
D deficiency.

The Endocrine Society recommends supplementation with 1000 to 4000 IU/d of

vitamin D
REPRODUCTIVE
TRACT
 SCHEMATIC REPRESENTATION OF THE POTENTIAL LOCATION OF
THE ACE2 RECEPTOR AND SARS-COV-2 RNA IN THE HUMAN
REPRODUCTIVE TRACT OF MEN (A) AND NONPREGNANT WOMEN (B).

Fabr ıcioMorell
́ et al. Am. J. Trop. Med. Hyg., 104(3), 2021, pp. 814–825 doi:10.4269/ajtmh.20-1098
Copyright © 2021 by The American Society of Tropical Medicine and Hygiene
MALE REPRODUCTIVE
  On the left: localization of renin–
angiotensin system (RAS) components
in human male reproductive system
(1, prostate; 2, vas deferens; 3, epididymis; 4,
seminal plasma).

 On the right: RAS components at

the cellular level in spermatidis,
spermatocytes, Sertoli cells,
spermatogonia, basal lamina, Leydig
cell.
(ACE: angiotensin-converting enzyme; sACE:
somatic ACE; tACE: testicular ACE; TMPRRS2:
transmembrane protease serine 2; AT1R:
angiotensin II type 1 receptor; AT2R: angiotensin
II type 2 receptor; MAS: Mas receptor).

Pascolo L et al . Microorganisms 2020, 8, 1492 ; doi:10.3390/microorganisms . 8101492 www.mdpi.com/journal/microorganisms

RENIN–ANGIOTENSIN SYSTEM COMPONENT LOCALIZATION IN THE MALE REPRODUCTIVE SYSTEM.

Pascolo L et al. Microorganisms 2020, 8, 1492; doi:10.3390/microorganisms . 8101492 www.mdpi.com/journal/microorganisms

 SCHEMATIC REPRESENTATION OF THE REGULATION OF HPG AXIS IN
HEALTHY AND COVID-19 CONDITIONS.
a Represents the healthy human brain and
testes in association with the HPG axis.
b Represents a SARS-CoV-2 infected human brain and testes with
neuroinflammation and dysregulation of the HPG axis in association
with reduced steroidogenesis and spermatogenesis due to
testicular inflammation and oxidative stress.

Selvaraj K et al. Reproductive Sciences https://doi.org/10.1007/s43032-020-00441-x

SARS-COV-2 INFECTION MEDIATED OXIDATIVE STRESS AND INVOLVEMENTS OF
ENDOCRINE AXES IN THE REGULATION OF MALE REPRODUCTIVE HORMONES
POSSIBLE MECHANISMS OF SARS-COV-2 INFECTION INDUCED
IMPAIRMENT IN MALE REPRODUCTIVE FUNCTIONS

Dutta. S et al.
 ANGIOTENSIN-CONVERTING ENZYME 2 RECEPTOR AND SARS-COV-2
RNA DETECTION IN THE MALE REPRODUCTIVE TRACT

Morell F et al . Am. J. Trop. Med. Hyg., 104(3), 2021, pp. 814–825 doi:10.4269/ajtmh.20-1098. Copyright © 2021 by The
American Society of Tropical Medicine and Hygiene
 POSSIBLE EFFECTS OF SARS-COV-2
ON THE FUNCTION OF MAIN TYPES OF
TESTICULAR CELLS BY AN ALTERED
ACE-2 SIGNALLING PATHWAY.

ACE2: angiotensin-converting enzyme-2

ASA: anti-sperm antibody

Imbalance of RAAS System Breakdown of the blood-testis barrier Hormonal alteration

Increased inflamation Increase autoimmune responses Asa Potential hypogonadism
Disrupted spermatogenesis formation Disrupted steroidogenesis

Haghpanah A et al . Andrologia. 2020;00:e13883. wileyonlinelibrary.com/journal/and © 2020

Impaired gonadal function Wiley-VCH GmbH | 1 of 9 https://doi.org/10.1111/and.13883
MALE INFERTILITY
 Possible mechanisms of SARS-CoV-2
infection induced sperm DNA damage,
abnormal motility and male infertility
through disruption of ACE2/Ang (1–
7)/Mas/PI3K/AKT signalling axis and
systemic oxidative stress and
inflammation.

 ACE2, angiotensin- converting enzyme-2; Ang,

angiotensin; PI3K/AKT, phosphatidylinositol-3-kinase
and protein kinase B

Haghpanah A et al . Andrologia. 2020;00:e13883.

wileyonlinelibrary.com/journal/and © 2020 Wiley-VCH GmbH | 1 of 9
https://doi.org/10.1111/and.13883
FEMALE REPRODUCTIVE
 ANGIOTENSIN-CONVERTING ENZYME 2 RECEPTOR AND SARS-COV-2
RNA DETECTION IN THE NONPREGNANT FEMALE REPRODUCTIVE TRACT

Fabr ıcioMorell
́ et al . Am. J. Trop. Med. Hyg., 104(3), 2021, pp. 814–825 doi:10.4269/ajtmh.20-1098. Copyright © 2021 by The American
Society of Tropical Medicine and Hygiene
 MECHANISMS OF
Ovarian
IMMUNOPATHOLOGY IN OVARIAN
cancer
CANCER AND COVID19
 Both in ovarian cancer and COVID-19 activated
and/or infected macrophages induce an
inflammatory response with prolonged and
excessive production of proinflammatory
cytokines, Interferon, ROS, and procoagulant
factors that results in immunopathological
changes, thus leading to symptoms associated
with sickness behavior, including anorexia and
specific changes in energy metabolism.
 Abbreviations: IL, Interleukin; TNF, Tumor Necrosis Factor; CRH,
corticotrophin releasing hormone; GH, growth hormone; IGF, Insulin
growth factor

Macciò et al. Journal of Ovarian Research (2021) 14:28

ROLE OF IL-6 IN IMMUNOPATHOLOGY
ASSOCIATED TO OVARIAN CANCER AND
COVID-19

 IL-6 is one of the key cytokines driving the

immunopathology caused by prolonged a
specific inflammation. IL-6 induces the
transcription of several liver-specific genes in
acute inflammatory states, such as CRP,
thrombopoietin, and hepcidin thus contributing
to associated immunodepression, anemia and
thrombocytosis (with related hypercoagulability)
SYSTEMIC EFFECTS OF IL-6 IN
OVARIAN CANCER AND COVID-19

 Systemic effects of IL-6 in ovarian cancer and COVID-

19. IL-6 exerts systemic effects on energy metabolism,
including the induction of peripheral muscle insulin
resistance and the impairment of insulin signaling,
which are associated with increased amino acid
oxidation, negative energy balance, and muscle
proteolysis.
 Abbreviations: IL, Interleukin; LPL, lipoprotein-lipase
 OVERLAP BETWEEN COMMON FACTORS WHICH PROMOTE AN UNFAVORABLE
PCOS CARDIO-METABOLIC PROFILE IN WOMEN WITH PCOS AND FACTORS WHICH, BASED
ON THE EXISTING DATA, APPEAR TO INCREASE THE RISK FOR SEVERE COVID-19

 (*further research is required to clarify the potential

links between adverse COVID-19-related outcomes
and hyper-cytokinemia, hyperandrogenemia, and
vitamin D deficiency)

Kyrou et al. BMC Medicine (2020) 18:220

https://doi.org/10.1186/s12916-020-01697-5
PCOS may increase susceptibility to coronavirus disease 2019 via its associated comorbidities (non- alcoholic fatty
liver disease, metabolic syndrome, obesity, insulin resistance and alterations in the gut microbiome); the gut-lung axis
is apparently implicated.
SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; IL-22: Interleukin 22, IL-6: Interleukin 6; PCOS: Polycystic ovary syndrome;
NAFLD: Non-alcoholic fatty liver disease; COVID-19: Coronavirus disease 2019; MetSy: Metabolic syndrome.
Ioannis Ilias et al, World J Clin Cases 2021 April 26; 9(12): 2711-2720
 IMPACT OF COVID-19 ON FEMALE FERTILITY

 There are no comprehensive reviews to explore the association between COVID-19 and female
fertility comprehensively
 SARS-CoV-2 may invade target cells by binding to ACE2, thereby affecting female fertility. ACE2,
which is widely expressed in ovaries, uterus, vagina and placenta, regulates the levels of
angiotensin II (Ang II) and Ang-(1–7) to exert its physiological functions. ACE2, Ang II and Ang-
(1–7) could regulate follicular development and ovulation, regulate corpus luteum angiogenesis
and degeneration, and affect endometrial tissue growth. Ovarian reserve is a key determinant of
female fertility. Diminished ovarian reserve could affect fecundity by reducing egg quality. Besides,
ACE2 is highly expressed in the ovaries.
 The ovarian reserve function should be the primary observation indicator for the impact of COVID-
19 on female fertility. Routinely performed markers of the ovarian reserve include a basal FSH or
LH concentration, E2, AMH and assessment of AFC

Li F, et al. BMJ Open 2021;11:e045524. doi:10.1136/bmjopen-2020-045524

ADRENAL
 SARS (and COVID-19) might affect the
hypothalamic- pituitary-adrenal (HPA) axis as well.
 Biochemical evidence of HPA axis involvement in
SARS was first reported by Leow et al.
 Leow et al studied hypocortisolism in patients who
had recovered from SARS-CoV.. Three months
after recovery, nearly half of the patients had
hypocortisolism, majority had central
hypocortisolism as evident by low ACTH levels.
The majority of these patients had not received
any systemic steroids for SARS. Interestingly,
hypocortisolism was transient.
 Irrespective of serum cortisol levels,
glucocorticoids have been used in patients with
critical illnesses including SARS
Mao et al: Effect of SARS-CoV-2 on Adrenal Cortex
ADRENAL INSUFFICIENCY – RISK OF ADRENAL CRISIS
ADRENAL ISUFFICIENCY AND COVID-19
 LEARNING POINT

 COVID-19 can affect adrenal function and cause both primary and
secondary adrenal insuficiency.
 High index of suspicion should be there for adrenal insuficiency in
patients with COVID-19 with hyponatraemia and hypotension.
 Routine use of glucocorticoids in patients with COVID-19 is
controversial, but clinicians must consider relative cortisol deficiency in
these patients.
 Adrenal insuficiency in COVID-19 might be transient but follow-up is
warranted.
CONCLUSIONS
 CONCLUSIONS

Research on clinical The need for multifaceted

In the absence of literature relating to
effects and follow-up of research include collection of
the effects of SARS-CoV-2 on
recovered patients is a clinical data, histological and
endocrine organs, scientists have
priority, considering the autopsy studies, as well as basic
made speculations based on the
potential for multitude of science studies to understand
evidence from SARS-CoV-1 infection
effects on endocrine the effect of SARS-Cov-2 on the
during the years 2002 through 2003.
organs. endocrine system.

Studies on viral genomics to fill

Clinicians should be encouraged to report their
the gaps in the knowledge on
experience in managing patients with preexisting
effects of direct viral invasion and
endocrine diseases to improve current practices,
immune-mediated injury are
laboratories, which are mostly empirical.
needed.
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