Endocrine Microbiology module slide2024.ppt

About endocrine microbiology

1. 1
Endocrine Microbiology
•Endocrine Microbiology is the study of the role of microbial
interactions with mammalian hormones in conditions of disease.
Bacteria may infect the endocrine glands either by direct invasion or
local or hematogenous spread.
Mycoses may infiltrate endocrine organs and adversly affect their
function or produce metabolic complication such as hypopituitarism,
hypo/hyperthyroidism, pancreatitis, hypoadrenalism, hypogonadism,
hypercalcemia
Viral infections can induce several physiological changes in the
human endocrine system, resulting in cytokine mediated activation of
hypothalamo-pituitary-adrenal axis to increase cortisol production,
thus modulating the immune response.
•Pituitary infections are rare disorders that represent less than 1% of
all pituitary lesions and may be caused by bacterial, viral, fungal and
parasitic infections.

2. 2
•Infections may develop in a normal pituitary gland or in pre-
existing pituitary lesions and can occur by either
hematogenous spread or contiguous extension from adjacent
anatomical sites (meninges, sphenoid sinus, cavernous sinus
and skull).
•Also central nervous infections, paranasal sinusitis and
immunocompromised status due to:-
 diabetes mellitus
 Cushing’s syndrome
 tuberculosis
 organ transplantation
 HIV infection
 malignancy and
 chemotherapy
are risk factors for these conditions.

3. 3
Suppurative bacterial infections can involve the pituitary,
thyroid, adrenals, and gonads.
•In the majority of cases, specific risk factors predispose the
endocrine glands to such infections.
•This in turn may lead to temporary or permanent endocrine
dysfunction.
•This is particularly noted in cases of bacterial thyroiditis.
•Permanent endocrine dysfunction following bacterial
infections will warrant life-long hormone replacement
therapy

4. 4
Immunocompromised individuals are at greatest risk for either
primary adrenal infection or disseminated microbial disease
involving the adrenal gland.
The adrenal gland can be infected by a myriad of pathogens
including fungi, viruses, parasites, and bacteria.
Infection can directly or indirectly cause tissue damage and
alteration in endocrine function.

5. 5
Direct damage occurs via microbial replication and local
production of toxic compounds, such as endotoxins.
Indirect damage results from alterations in the regulation of a
host’s immunologic and endocrine mediators in response to
damage by a microbe at a distant site.
Variations in pathogen tropism, adrenal anatomy, and host
immune integrity contribute to the progression of active disease
and discernable adrenal dysfunction.

6. 6
•Adrenal and gonadal dysfunction, osteoporosis with increased
fracture risk, dyslipidemia with increased cardiovascular risk, are
some of the endocrine disorders prevalent in HIV-infected
patients that may negatively influence quality of life, and
increase morbidity and mortality.
•ARTs have dramatically increased life expectancy in the HIV-
infected population, they are not devoid of adverse effects,
including endocrine dysfunction.

7. 7
•Physicians caring for HIV-infected patients should be
knowledgeable and exercise a high index of suspicion for the
diagnosis of endocrine abnormalities, and in particular be aware of
those that can be life threatening.
•Endocrine evaluation should follow the same strategies as in the
general population, including prevention, early detection, and
treatment.

8. 8
Common microorganisms affecting the Endocrine System
i. Bacteria
Infectious diseases can affect the endocrine system by several
mechanisms
Exposure to ACTH increased attachment of E. coli O157:H7 to gut
epithelia, though the underlying mechanism for this response is not
clear
•In other case the use of radiolabelled thyrotropin has showed the
presence of receptor for thyrotropin in Yersinia enterocolitica.
•The thyrotropin specificity of the Y.enterocolitica binding activity
was similar to that of the thyrotropin receptor in human thyroid tissue.

9. 9
•Thyrotropin binding sites have been shown to be recognized by
antibodies from humans with Graves’ disease
•Prior infection by Y. enterocolitica has been implicated in the
pathogenesis of Graves’ disease.
•The outer membrane porins Omp A,C and F have been identified
as the Y. enterocolitica targets recognized by Graves’ patient
antibodies
•Catecholamines at the levels infused down intravenous catheter
lines were found to massively increase staphylococcal biofilm
formation

10. 10
Clinically attainable levels of catecholamines also increased
P. aeruginosa biofilm formation on endotracheal tubing as
well as enabling the pathogen to resist antibiotic treatment
Bacteria can directly use catecholamines as a kind of
siderophore to steal transferrin and lactoferrin Fe which
enables up to 100,000-fold increases in bacterial cell
numbers in what normally should be highly bacteriostatic
host tissue fluids

11. 11
• Chlamydia trachomatis is an important sexually transmitted
pathogen, especially in young women
•Reported showed that treatment of C. trachomatis with physiological
levels of oestrogen increased infection of human endometrial cells,
and enhanced Chlamydia colonization of female mice
•C. trachomatis infection of female mice was also increased
following pre-treatment with progesterone.
(experiment outcome).

12. 12
•Catecholamines can even catalyze recovery of bacteria severely
damaged by antibiotic treatment
• And rapidly promote exchange of genetic material between
different bacterial species
•Dopamine, noradrenaline and adrenaline exposure can also
induce pathogenic bacteria to become even more virulent by
*inducing expression of genes in toxin release
*increasing biofilm formation and
*enhancing attachment to host epithelial tissues.

13. 13
•Increased cortisol secretion has been shown to shift the balance in
the Th1/Th2 cell ratio towards a Th2 response.
• This shift, along with age-related changes in
dehydroepiandrosterone (DHEA), is thought to enhance the
infectivity of M. tuberculosis (where a Th1 dominated response is
considered to be protective) and a cycle of positive immunological
alterations is induced to the benefit of the bacteria.

14. 14
• In addition to the up-regulation of the hypothalamic–
pituitary–adrenal (HPA)-axis to secondary infection,
endotoxin and exotoxins can induce both functional
and pathological changes to the adrenal gland.
•Mycobacterium tuberculosis 
remains the most common
agent involving the endocrine gland
•In developing countries, tuberculosis remains the most
common cause of primary adrenal insufficiency.
Tuberculosis can also affect pituitary, thyroid, and gonads

15. 15
Bacterial infections of pituitary
•Infections of the pituitary gland are rare but may cause
clinical problems because of the non-specific nature of the
presentation.
• Among the various infectious agents, bacterial infections
including Mycobacterial infections seem to be the most
common.
• The common bacterial infections of the pituitary gland
are described below.

16. Bacterial Agents Causing Infection of Pituitary-Hypothalamus
16
Bacterial class
Gram positive bacteria
Gram negative bacteria
Spirochaete
Mycobacterium
Organism
Staphylococcus aureus,
Streptococcus pneumoniae
E coli, Pseudomonas aeruginosa,
Neisseria meningitides
Treponema pallidum
Mycobacterium tuberculosis

17. 17
Pituitary Abscess
Epidemiology and risk factors
•Pituitary abscesses are a very rare clinical entity and account for
less than 1% of pituitary lesions .
•Risk factors include underlying pituitary diseases such as a
pituitary adenoma, Rathke’s cyst, craniopharyngioma,
lymphocytic hypophysitis, immunocompromised states, history
of surgical exploration in pituitary hypothalamic region, and
spread of local infection from meninges and paranasal sinuses .
•Rarely, abscess may develop in a normal pituitary gland

18. 18
Hypopituitarism Caused by Treponema Pallidum Infection
•Syphilis caused by
 
Treponema pallidum 
(a spirochete) may
involve the pituitary- hypothalamic region causing syphilitic
gumma with non-caseating granulomas.
• It is more common in patients with underlying HIV
infection.
•Diagnosis can be made by demonstration of the spirochete in
the samples of sellar tissues following trans-sphenoidal
surgery.

19. 19
•Immunological diagnosis can be made by measuring
titers of anti-Treponemal antibody in the serum.
•Treatment consists of intravenous followed by oral
antibiotics.
• Penicillin is the drug of choice for syphilis.
•In patients who are allergic to penicillin, doxycycline is
a good alternative.

20. 20
Bacterial infections of the thyroid
•It is rare for bacteria to invade the normal thyroid
gland because of the rich vascular supply, good
lymphatic drainage, separation of thyroid gland from
other structures by fascial planes, high iodine content,
and production of hydrogen peroxide inside the
gland .
• Both iodine and hydrogen peroxide have bactericidal
properties.

21. 21
Acute Suppurative Thyroiditis
•Acute suppurative thyroiditis is rare and is usually due to bacterial
infection of the thyroid gland.
•In severe cases, it can lead to abscess formation and spread to
surrounding structures leading to acute obstruction of the
respiratory tract.
• The incidence of acute suppurative thyroiditis lies between 0.1%
and 0.7% of all thyroidal illnesses.
• In children acute suppurative thyroiditis is usually due to
persistent pyriform sinus.

22. 22
Risk Factors for Acute Suppurative Thyroiditis
•Pyriform sinus fistula – more common in children and young
adults and associated with recurrent disease
•Immunocompromised status
•Systemic autoimmune disorders
•Anterior esophageal perforation
•Underlying thyroid disorders like chronic autoimmune
thyroiditis, goiter, and thyroid malignancy
•Fine need aspirations/biopsy of thyroid

23. 23
Although bacterial agents account for the majority of cases, acute
suppurative thyroiditis can also be caused by fungal
(immunosuppressive status), parasitic, and tubercular etiology.
Common bacterial organisms include
 
Staphylococcus
aureus,
 Streptococcus pyogenes, Staphylococcus
epidermidis, 
and 
Streptococcus pneumoniae. 
•Rarely other causative bacteria include
 
Klebsiella 
species, 
Hemophilus
influenzae,
 Streptococcus viridans, Arcanobacterium
haemolyticum,
 Eikenella corrodens
,
 
Salmonella 
species,
and
 
Enterobacteriaceae.
•In the context of immunosuppressed states like HIV-AIDS, acute
suppurative thyroiditis can be caused by
 
Mycobacterium
tuberculosis, 
atypical mycobacteria
,
 Salmonella
 
species
,
Nocardia 
species and 
Treponema pallidum 

24. 24
Subacute Thyroiditis
Subacute thyroiditis (also termed as granulomatous, giant cell, or
deQuervain’s thyroiditis), is usually due to a viral illness
following respiratory illness.
Rarely, bacterial infections like
 
Mycobacterium tuberculosis,
Treponema pallidum, 
or 
Yersinia enterocolitica 
may cause
subacute thyroiditis

25. 25
Bacterial infections of adrenals
Tuberculosis of Adrenals
•Tuberculosis of the adrenal glands is the most common cause of
primary adrenal insufficiency in developing countries.
•Tuberculous infection of the adrenal gland occurs from
hematogenous spread from pulmonary or genitourinary sites.
• Adrenals are the most common endocrine gland involved in
tuberculosis
•Apart from
 
Mycobacterium tuberculosis, 
in the context of
immunocompromised states,
 
M. avium intracellular 
and 
M.
chelonae 
may also cause primary adrenal insufficiency.

26. 26
Adrenal Abscess
•An adrenal abscess is a rare clinical condition with very few
cases reported in the literature.
•Organisms that are implicated are
 
Mycobacterium,
anaerobes,
 
Salmonella, Nocardia, 
and 
E coli.
• In culture negative cases, broad spectrum antibiotics with
coverage for gram positive, gram negative, and anaerobic
organisms should be considered.

27. 27
Waterhouse-Friderichsen Syndrome
•Waterhouse-Friderichsen syndrome (WFS) or purpura fulminans
is an uncommon clinical entity associated with bilateral adrenal
hemorrhage in the setting of severe bacterial sepsis, which was
first reported by Rupert Waterhouse and Carl Friderichsen.
• The initial version of this syndrome was classically described
with
 
Neisseria meningitidis 
sepsis.
•But later it was found that a similar clinical picture was seen with
other bacterial infections such as
 
S. pneumoniae,
 H influenzae, E.
coli,
 S. aureus, Group A beta-
hemolytic
 Streptococcus, Enterobacter cloacae, Pasteurella
multocida, N. gonorrhoeae,
 Moraxella duplex, Rickettsia
rickettsia,
 B. anthracis, T. pallidum, and Legionella pneumophi
l
•These bacteria may invade the adrenals directly or may produce
endotoxins to cause adrenal necrosis and hemorrhage

28. 28
Bacterial infections of gonads
Bacterial Infections of Test
•Infection of the epididymis can occur in both children and adults.
• In severe cases, the inflammation can spread further into testis and
present as epididymo-orchitis.
•If the duration of illness is less than 6 weeks, it is termed as acute
epididymo-orchitis, whereas duration more than 6 weeks is termed
as chronic.
•In children, it usually occurs between two and thirteen years of
age, whereas in adults, it is common between twenty and thirty
years of age.

29. 29
•Causative organisms in younger males less than 35 years of age
are
 
Neisseria gonorrhoeae 
and 
Chlamydia trachomatis.
•In older men, causative organisms include
 
Escherichia coli, other
coliforms, and
 
Pseudomonas.
•Rare bacterial causesinclude
 
Ureaplasma 
species, 
Mycoplasma
genitalium,
 
Mycobacterium tuberculosis, and
 
Brucella 
species.
•Risk factors for epididymitis include urinary tract infections,
STD, bladder outlet obstruction, prostate enlargement, and
urinary tract surgeries or urogenital procedures.
• In homosexual men, an enteric bacterial etiology is common

30. 30
Bacterial Infections of Ovaries
•Isolated infection of ovaries is not common.
•It is usually part of pelvic inflammatory disease.
• In severe cases, it may present as tubo-ovarian abscess.
•Tubo-ovarian abscesses are often polymicrobial and typically
contain a predominance of anaerobic bacteria.
•Common organisms include
 
E. coli, Bacteroides fragilis,
other
 
Bacteroides 
spp, 
Pepto-streptococci,& anaerobic
streptococci .
•Diagnosis is based on history, physical examination, ultrasound
suggesting tubo -ovarian mass or abscess, and microbiological
diagnosis.
•Treatment consists of admission, intravenous antibiotic therapy,
and aspiration of abscess if needed.
•Patients who do not respond, will need surgical intervention.

31. 31
Other links between bacteria and endocrine disorders
•Yersinia enterocolitica 
has been implicated in the pathogenesis of
autoimmune thyroid disease.
• Immunoglobulins from patients with
 
Yersinia 
infection inhibit binding
of TSH to thyrocytes.
• This could be explained by structural similarity between
 
Yersinia 
outer
membrane proteins (YOP) and epitopes of the TSH receptor .
•Role of gut microbiome has recently implicated in the metabolic
syndrome, obesity, and diabetes.
•Many metabolites produced by gut microbes get absorbed into the
circulation.
•They may act on specific receptors to regulate metabolism.
•Also, some bacterial components can act as endocrine factors controlling
metabolism .

32. 32
•Additional organisms associated with disease in the setting of high
systemic cortisol levels include S. aureus, & fungi (H. capsulatum)
•Mycobacterial disease, such as M. tuberculosis or M. chelonae.
•Waterhouse—Friderichsen syndrome is a rapidly progressing entity in
which bacterial sepsis appears to induce bilateral adrenal hemorrhage.
•The most common etiological agent associated with the syndrome is
N.meningitidis
•However it can also occur during systemic disease due to group A
streptococcus, pneumococci, H. influenzae, K, oxytoca, and
Pasteurella multocida
• -/-

33. ii. Virus
Many viral infections impact different endocrine organs, either by
direct viral invasion or by systemic or local inflammation resulting
in transient or permanent endocrinopathies; both hyper and
hypofunction of endocrine organs may ensue.
Viruses can encode production of specific viral proteins that have
structural and functional homology to human hormones.
33

34. Since endocrine hormones have immunoregulatory functions,
endocrinopathies may alter the susceptibility of human body for
viral infections.
Viruses can transiently or permanently damage endocrine
organs by directly attacking endocrine cells or via indirect
mechanisms.
It activates the antiviral immune response in the host organism,
leading to local or systemic inflammation or organ-specific
autoimmunity resulting in certain endocrinopathies.
34

35. 35
Various viral infections can lead to endocrinopathies.
•HIV can affect the endocrine system at several levels.
•Endocrine abnormalities have been identified in patients with AIDS.
•Pathological and clinical studies demonstrate that the HIV can affect
adrenal, thyroid and gonadal function.
•Evidence suggests that infection with viruses may trigger an
autoimmune reaction to islet cells, causing insulin dependent
diabetes mellitus in susceptible persons
•The recent discovery of the infectious prions also points to the
involvement of endocrine organs in these diseases.

36. 36
•In addition, the effect of bacterial infections on the pathogenesis
of endocrinopathies has long been recognized.
•Adrenocortical abnormalities are probably the most common
endocrine dysfunction reported, occurring in 5-10% of all HIV-
positive patients .
•Gonadal dysfunction is frequently reported in male patients, with
hypogonadism occurring in 50% of AIDS patients.
•Thyroid gland disturbances, particularly subclinical
hypothyroidism, are also common.

37. 37
•Adrenal insufficiency has long been suspected in HIV-infected
patients based on the common clinical findings of weight loss,
diarrhea, fever, fatigue, hypotension and electrolyte disturbances
•The involvement of the adrenal gland in AIDS has been
confirmed by multiple autopsy findings.
•And also adrenocortical lesions on autopsy show infections with
cytomegalovirus, M.tuberculosis, Cryptococcus &
Toxoplasmosis.

38. 38
•The most common pathology, necrotizing adrenalitis due to CMV
infection, was identified in 51%.
•Multiple AIDS autopsy reports have identified the adrenal gland as
a common site of CMV infection.
•Adrenal function in AIDS appears to be heterogeneous and in most
autopsies less than 50% of the adrenal tissue is affected.
•Microscopic examination revealed the pathognomonic viral
inclusions in both the adrenal cortex and the medulla.

39. 39
•In glandular infection, variations of the particular tropism of the
implicated agent determine the differential rates of adrenal
involvement from organism to organism regardless of Host
immune integrity.
•Infection of the pancreas disturbs endocrine and exocrine
functions, leading to diabetic manifestations and increased serum
amylase levels.
•Mumps virus infection of the pancreas has been reported to be a
triggering mechanism for onset of juvenile insulin-dependent
diabetes mellitus (IDDM)
•However, a causal relationship has not been established

40. 40
Herpes simplex virus (HSV) similarly can cause damage to the
adrenals in fulminant disease in neonates.
Other less common hemorrhagic viruses also have a high potential
for catastrophic adrenal disease.
Lethal infections with filoviruses, such as Ebola virus, are
characterized by massive apoptotic lysis of cells in multiple organs
including liquefaction of the adrenals.
Although the Marburg viruses have a lower case fatality rate, they
can cause damage to the adrenal, particularly the cortical cells.
Similarly, Lassa virus, an arenavirus, has been shown to infect the
adrenals.

41. SARS-CoV and SARS-CoV-2 enter target cells through the
binding of the viral spike (S) protein to the cellular receptor
angiotensin-converting enzyme 2 (ACE2) and after S protein
priming by the host cell transmembrane serine protease 2
(TMPRSS2).
 In humans, ACE2 and TMPRSS2 mRNAs are expressed in
several endocrine tissues, including the hypothalamus; the
pituitary, thyroid, and adrenal glands; the ovaries; the testes; and
the pancreatic islets.
41

42. 42
Adrenal involvement can also occur during infection with the
relatively recently identified severe acute respiratory syndrome
associated coronavirus (SARS-CoV).
 However, the cellular abnormalities seen in the adrenal could
be due to direct cytopathic effects by the virus or due to
systemic inflammatory responses.
Interestingly, SARS-CoV deregulates the host’s corticosteroid
stress response by producing peptides that are molecular
mimics of ACTH.

43. 43
Antibodies to the viral peptides bind both viral protein and host
ACTH, which reduces the host’s ability to secrete corticosteroids,
resulting in a state of adrenal insufficiency.
It has been postulated that the administration of glucocorticoids in
SARS-CoV infection may abrogate or otherwise modify infection.
It is also noteworthy that influenza virus type A infection can
affect the production or release of ACTH.

44. Chronic HCV and HBV infections with endocrine disorders,
such as autoimmune thyroiditis, T2D, and erectile dysfunction
(ED).
Chronic HCV infection increases the likelihood of
hypothyroidism.
The HCV-induced inflammatory process may lead to the
destruction of thyroid follicular cells and the appearance of
autoimmune thyroiditis or thyroid cancer.
Chronic HBV infections trigger increased serum TSH levels
while lowering free triiodothyronine (FT3) and free thyroxine
(FT4) levels.
Patients with chronic HCV infection also have low serum levels
of total testosterone and aberrant sperm parameters, including
low sperm volume, count, and motility, suggesting the negative
influence of HCV on spermatogenesis.
44

45. Coxsackievirus B (CVB), an enterovirus (EV) species, is likely
involved in T1D pathogenesis.
CVB initiates autoimmunity against pancreatic β cells through
molecular mimicry, activation of pre-existing autoreactive
 
T cells,
and altering tolerance to β-cell antigens resulting from thymus
infection.
EV infection leads to thyroid diseases.
 Maternal EV infection has been linked to the development of
thyroiditis in neonates and hypothyroidism in 60% of children
with antibodies against EV were reported.
45

46. 46
iii. Fungi
•Fungal infections of the pituitary region are extremely rare and
usually occur in immunocompromised patients
 
•Candida albicans is a opportunistic fungal pathogen of
immunocompromised which has been shown to interact with several
human peptide hormones.
•Luteinizing hormone (LH) is required for ovulation and the
formation of a corpus luteum in the female menstrual cycle.
•C. albicans has been shown to bind human LH and chorionic
gonadotropin used (125I)-labeled LH and chorionic gonadotropin to
demonstrate the presence of specific binding sites for both hormones
in C. albicans, and C. tropicalis.

47. 47
•The binding activity was found to be highly specific and was not
surface associated instead being at greatest levels in microsomes
and cytoplasmic fractions.
•Also, of considerable relevance to C. albicans infectivity,
interaction with the LH was found to stimulate germination of
Candida spores and germ tube formation
•C. albicans is a major source of fungal infections in women of
reproductive age which has been shown to possess an oestrogen
binding protein of high affinity and specificity.

48. 48
Contact with oestrogen has been reported to increase C. albicans
growth as well as its infectivity, causing the yeast to shift into to a
more invasive hyphal morphology
Additional mycoses associated with adrenal failure include
coccidioidomycosis and candidiasis.
Like the other dimorphic fungi, Blastomyces dermatitidis has a
high affinity for the adrenal gland, however, it does not appear to
cause a similar rate of overt adrenal failure.

49. 49
•Administration of high dose corticosteroids, is associated with
a significant increased risk for infection with Nocardia
asteroides, Aspergillus spp, Cryptococcus neoformans, and
Pneumocystis (carinii) jirovecii.
•Autopsy studies have shown that adrenal involvement occurs
in 85—90% of infections due to Paracoccidioides brasiliensis,
a dimorphic fungus, regardless of host immune status

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