morbidity of thyroid disorders with other diseases like diabetes, dyslipidemia,alzeihmers,obesity,auto immune diseases, cva

1. HYPOTHYROID &
COMORBID CONDITIONS

3. HYPOTHYROIDISM with
• DIABETES
• HYPERTENSION
• CAD
• DYSLIPIDEMIA
• OBESITY
• PSYCHIATRY
• ALZHEIMER
• CVA / HASHIMOTO’S
ENCEPHALOPATHY
• CLD
• CKD
• ELDERLY
• PRE OP

4. HYPOTHYROIDISM WITH
DIABETES

7. THYROID DISORDERS IN INDIA

9. Prevalence of Thyroid disorders in Eight urban cities of
India

10. Prevalence of Thyroid disorders in Eight urban cities of
India

12. RESULTS….
• Hypothyroidism is highly prevalent 11%
• The older population (>35 years) at higher risk of
hypothyroidism(13.11% vs. 7.53%).
• Women- 3 times more likely to be affected by hypothyroidism
than men (15.86% vs. 5.02%).
• Hypertension- 20.4%
• Diabetes- 16.2%
• TPO positive – 20%

13. • Inland cities had higher prevalence of hypothyroidism
(11.73%) compared to coastal cities (Chennai, Goa, Mumbai)
(9.45%). Kolkata recorded the highest prevalence of
hypothyroidism (21.67%).

14. THE THYROID-DIABETES
CONNECTION
THYROID
DIABETES

15. • Autoimmunity
• Genetic–Epigenetic interaction
• HLA-DR3 allele
• CTLA-4 carries a major genetic risk
• PTPN22, FOXP3

16. Indirect Links
• Thyroid Hormones and Appetite Regulation-
patients with TH resistance
• Thyroid Hormones and Energy Expenditure-
increased REE. UCP1 is a major regulator
• Central Interactions of Thyroid Hormones on Glucose
and Lipid Regulation

17. Diabetes anD thyroiD
MultifaceteD relationship

18. Some special situations
• Older sulphonylureas can inhibit the synthesis of thyroid
hormone (arbutamide, tolbutamide, methahexamide, and
possibly chlorpropamide)
• Metformin reduces TSH
• Pioglitazone increases orbitopathy(TAO)
• Increased Statin Induced myopathy
• Thyroid hormone analogues- for treating Obesity and Diabetes

20. Polyglandular Autoimmune Endocrinopathy

21. PGA Type 2

22. DIABETES PLUS THYROID DISORDERS: LONG-TERM
MORTALITY AND MORBIDITY

23. Morbidity Data
• Sub-clinical hypothyroidism and hyperthyroidism have both
been linked to increased cardiovascular risk
Endocr Rev 2008;29:76–131.
• Sub-clinical hypothyroidism was associated with a higher
frequency of nephropathy Diabet Med 2007;24:1336–44
• Subclinical hypothyroidism had a higher prevalence of
retinopathy Diabetes Care 2010;33:1018–20.

24. Mortality Data
• Subclinical hyperthyroidism yielded a significant 1.49-fold
increase in relative likelihood of death from all cause.
Eur J Endocrinol2008;159:329–41
• In sub-clinical hypothyroidism age <65yrs all-cause
mortality was significantly higher than in the euthyroid
population. J Clin Endocrinol Metab 2008;93: 2998–3007

25. Screening for Thyroid Dysfunction in Patients with DM
• Close monitoring of thyroid function particularly in patients
with T1DM
• Ty 2 DM- Annual/Bi-annual screening justified in higher risk
groups like patients over 50 or 55, particularly with
suggestive symptoms, raised antibody titres or
Dylipidaemia.

26. Diabetic practice guidelines for thyroid screening in
patients with diabetes

28. DM + AITD+ PREGNANCY
• A risky dual gestational endocrinopathy
• Higher rate of infertility, cesarean sections, preterm
deliveries, and hypertensive disorders of pregnancy
• Independent risk factor for Pre-ecclampsia and Ecclampsia

29. • Thyroid disease and type 1 but also type 2 diabetes mellitus
(DM) are strongly associated
• Thyrotoxic patients usually lose their glucose control
• Important clinical implications for insulin sensitivity and
treatment requirements.
• Increased CV risk with SCH
• Increased long-term morbidity and mortality
• Periodic screening as per recommendations

30. HYPOTHYROIDISM WITH
OBESITY

31. • TSH seems to be positively related to the degree of obesity.
• A positive correlation has been identified between serum
leptin and serum TSH levels in obese individuals, which could
reflect the positive association between TSH and BMI
reported in some individuals.
• Leptin, adjusted for BMI, was found to correlate with TSH,
which suggests that the increase in TSH and leptin levels in
severe obesity could result from the increased amount of fat.

32. • Interestingly, a moderate increase in total T3 or free T3 (FT3)
levels has been reported in obese subjects.
• Progressive fat accumulation was associated with a parallel
increase in TSH and FT3 levels irrespective of insulin
sensitivity and metabolic parameters, and a positive
association has been reported between the FT3 to FT4 ratio
and both waist circumference and BMI in obese patients.
• This finding suggests a high conversion of T4 to T3 in patients
with central fat obesity due to increased deiodinase activity
as a compensatory mechanism for fat accumulation to
improve energy expenditure.

33. ROLE OF LEPTIN
• TSH levels are at the upper limit of the normal range or
slightly increased in obese children, adolescents, and adults
and are positively correlated with BMI.

34. AUTO IMMUNITY AND OBESITY
• There is some debate about the link between obesity and the
risk of autoimmune thyroid dysfunction (AITD), which is the
main cause of hypothyroidism in adults.
• The prevalence of AITD in obesity has been reported to be
12.4% in children and between 10 and 60% in adults.
• This discrepancy may be due to such factors as sex, age,
menopausal status, smoking habit, environmental factors,
iodine intake, and degree of obesity.

35. HYPOTHYROIDISM WITH
HYPERTENSION

36. • In a meta-analysis (A) of all cross-sectional studies to
investigate an association between SH and blood pressure
alterations, there was significant difference in both systolic
blood pressure and diastolic blood pressure in SH compared
to control groups, with a weighted mean difference of 1.89
mmHg and 0.75 mmHg for systolic and diastolic blood
pressure, respectively.
• However, there is no randomized controlled trial investigating
whether the treatment could modify blood pressure.

37. HYPOTHYROIDISM WITH
CAD

38. • The association of SH and heart failure has been
demonstrated in elderly patients, but no study has yet
assessed this association in younger age groups (A).
• In the Health, Aging, and Body Composition Study (A) SH was
related to a higher rate of incident and recurrent congestive
cardiac failure with TSH levels of 7.0 mU/L or greater,
compared with euthyroid participants, even after adjustment
for cardiovascular risk factors.

39. • Similarly, in the Cardiovascular Health Study (A), subjects
with TSH level ≥ 10 mU/L had a moderately elevated risk of
heart failure over a mean 12 year follow-up compared to
euthyroid subjects. In this study, the risk of congestive heart
failure was not increased among older adults with TSH < 10
mU/L.
• More recently, in The Prospective Study of Pravastatin in the
Elderly at Risk (PROSPER), SH was significantly associated with
a higher rate of heart failure (age- and sex- adjusted) at TSH
threshold > 10 mU/L (A) in elderly with known high
cardiovascular risk.

40. • Data concerning the effects of subclinical hypothyroidism on
the cardiac function and structure are conflicting.
• There are consistent evidence regarding the association of
subclinical hypothyroidism with congestive heart failure in
elderly patients, particularly for TSH level > 10 mU/L Grade A,
but not for younger patients.

41. HYPOTHYROIDISM WITH
HEART FAILURE

42. HEART FAILURE
• Heart failure Hypothyroidism has detrimental effects on the
cardiovascular system (D). Therefore, in patients with heart
failure, it is important to detect it and eventually treat it.
• With regards to SH, it has also been recognized as an important
risk factor for HF in older adults.
• A meta-analysis of six prospective cohort studies for a total of
2,068 patients with SH, specifically with TSH > 10 mU/l, showed
a higher risk of heart failure (A).
• Therefore, heart failure patients would also be good candidates
for whom hypothyroidism must be ruled out (D).

43. HYPOTHYROIDISM WITH
DEPRESSION

44. • Although it has been related to hypothyroidism, several studies have
failed to find a consistent relationship between these two entities.
• On the other hand, in positive TPOAb subjects, depression was found
to be more frequent.
• Prevalence of a lifetime of depression was higher in subjects with
positive TPOAb (24.2%) in comparison to those without TPOAb
(16.7%), with a relative risk of 1.4 (95% CI 1.0-2.1; p = 0.04 after
adjustment for confounders) .
• Therefore the need to rule out hypothyroidism in a depressive patient
is still an unresolved matter.

45. • There are controversial results in the published literature
regarding the effects of SH on symptoms, quality of life,
cognition and depression, but the panel concludes that there
are hardly any symptoms or global neuropsychological
dysfunction associated with SH (D).

46. HYPOTHYROIDISM WITH
ALZHEIMER’S

48. HYPOTHYROIDISM WITH
ENCEPHALOPATHY

50. HYPOTHYROIDISM WITH
DYSLIPIDEMIA

51. DYSLIPIDEMIA
• Hypothyroidism is a recognized cause of secondary dyslipidemia
and in any person who presents with elevated LDL cholesterol (>
160 mg/dL), it has been recommended to test for hypothyroidism
(D).
• A recent prospective study in Japan reported that the prevalence of
hypothyroidism was 4.3% in patients with hypercholesterolemia
(1.4% with primary overt hypothyroidism, 2.3% with subclinical
hypothyroidism, and 0.4% with central hypothyroidism) (B).
• These values are relatively similar to those of the general
population, nevertheless, the early detection of hypothyroidism
and its treatment with levothyroxine would avoid unnecessary life-
long use of antilipemic agents in these patients.

52. • Thyroid hormone has multiple effects on the lipid synthesis
and metabolism, and overt hypothyroidism is consistently
associated to lipid abnormalities which are reversible with
levothyroxine therapy but this relationship is controversial in
patients with SH(D).
• Data emerging from the NHANES III study showed no lipids
abnormalities when adjusted for confounding variables (B)
and similar results were obtained from the Japanese-Brazilian
Thyroid Study in Latin America (A).

53. • Multiple interventional studies have evaluated the effects of
levothyroxine on lipid profiles in patients with SH, with mixed results.
• A meta-analysis of 13 studies found a significant decrease of serum
total cholesterol levels following levothyroxine therapy, mainly in
patients with elevated cholesterol values, but most of the selected
studies had a non-randomized design.
• In contrast, a recent Cochrane systematic review of 12 randomized
controlled trials comparing levothyroxine therapy with placebo or no
treatment in adults with SH found only marginal evidence indicating
that levothyroxine replacement improved total cholesterol levels, but
no favorable effects were found on the other parameters of the lipid
profile, such as HDL-C, LDL-C, triglycerides, ApoA, ApoB, or Lp(a).
• Most recently, several small randomized controlled trials found
favorable effects of levothyroxine replacement therapy on the lipid
profile .

54. HYPOTHYROIDISM WITH
RENAL INSULT

58. HYPOTHYROIDISM WITH
LIVER INSULT

59. • Liver diseases are also frequently associated with thyroid test
abnormalities or dysfunctions, particularly elevation of
thyroxine-binding globulin and thyroxine.
• Hepatitis C virus infection has been connected with thyroid
abnormalities.
• In addition, antithyroid drug therapy may result in hepatitis,
cholestasis or transient subclinical hepatotoxicity, whereas
interferon (IFN) therapy in liver diseases may also induce
thyroid dysfunctions.
• These thyroid-liver associations may cause diagnostic
confusions.

60. • In patients with chronic hepatitis associated with primary
biliary cirrhosis (PBC) or chronic autoimmune hepatitis, there
is an increased prevalence of autoimmune thyroid disease.
• Thus abnormalities may arise from thyroid gland dysfunction
or as a consequence of the liver disease.
• Autoimmune hypothyroidism is a prominent feature in PBC,
occurring in 10–25% of patients.
• There is often an increase in total T4 in PBC, due to an
increase in thyroid-binding globulin levels, and this may mask
hypothyroidism, emphasizing the need to perform a free
T4 and TSH assay.

61. NAFLD
• NAFLD was significantly linked to hypothyroidism (30.2% patients in
the case group vs 19.5% patients in the control group; p<0.001).
• Additionally, the prevalence of NAFLD and abnormal liver enzyme
levels (ALT, which is defined as greater than 33/25 IU/L)
progressively increased as the grade of hypothyroidism increased.
•
• For patients who had subclinical hypothyroidism, 29.9% of them
had NAFLD, and for patients who had overt hypothyroidism, 36.3%
of them had NAFLD (p<0.001).
• Journal of Hepatology, March 2012

62. HYPOTHYROIDISM WITH
ELDERLY

63. • There is good evidence suggesting that SH is not related to
symptoms or with disorders of cognition and mood in older
persons (A,B,B), and there is strong evidence (A,A) against
treating elderly patients with SH aiming to improve cognitive
function, quality of life and symptoms.
• SH has been consistently related to a higher risk of incident
and recurrent congestive heart failure in elderly subjects,
particularly at TSH level ≥ 10 mU/L (A).
• However, it has been proposed that moderately increased
serum TSH levels (4.5-10 mU/L) may represent a protective
factor against cardiovascular risk and be associated with
prolonged life span (A,A,B,B).

64. • The panel recommends against routine treatment for elderly
(> 65 yr) and very-elderly (> 80 yr) patients with subclinical
hypothyroidism at TSH levels < 10 mU/L. Grade A.
• The panel also recommends against treatment of SH if the
aim is to improve cognitive function in elderly people Grade
A.

65. HYPOTHYROIDISM IN
PRE-OP STATUS

67. • The half-lives of T4 and T3 are 7
and 1.5 days respectively.
• Thus, a patient who is taking T4
does not need to take it on the
day of surgery while the patient
who is taking T3 does;
• Radiograph the cervical region to
determine if goiter is going to
interfere with tracheal
intubation.
Arq Bras Cardiol 2007; 89(6) : e172-e209

68. Arq Bras Cardiol 2007; 89(6) : e172-e209

69. • Subclinical hypothyroidism — Based upon the studies in patients
undergoing coronary artery bypass graft (CABG) and percutaneous
transluminal coronary angioplasty (PTCA) , panel suggest not
postponing surgery in patients with subclinical hypothyroidism
(elevated serum TSH, normal free T4).
• Moderate (overt) hypothyroidism — Based upon the retrospective
studies cited above panel suggest that patients with moderate
overt hypothyroidism undergo urgent or emergent surgery without
delay, with the knowledge that minor perioperative complications
might develop.
• On the other hand, it is prudent to postpone surgery until the
euthyroid state is restored when hypothyroidism is discovered in a
patient being evaluated for elective surgery.

73. Interaction of Metformin and Thyroid Function
• Metformin activates Hepatic AMPK
• Transported via OCT1 & OCT2
• Metformin crosses BBB
• Metformin has the opposite effects on hypothalamic AMPK
• Counteracts T3 effects at the hypothalamic level
• Suppresses pituitary TSH secretion
• Shrinks nodule size- 30%, Metabolic Syndrome and Related Disorders,
9, 69–75.

74. • On the other hand, in an individual participant data analysis,
CHD outcomes in adults with SH did not differ significantly
across age groups, for the specific age.
• In group of 80 years or older, there was neither a significant
increased nor decreased risk of total mortality and CHD
endpoints (A).
• Physicians should acknowledge that TSH distribution curves
for thyroid disease-free subjects appear to shift progressively
to higher TSH concentrations with age, suggesting that the
increase in median TSH with age mainly reflects population
shifts in TSH distribution rather than a thyroid dysfunction
(B,D).

75. • Concerning the operative treatment of patients with
hypothyrosis, especially in nonthyroid and emergency
surgery, disorders of different organs and systems, associated
with hypothyrosis, should be considered.
• When it comes to surgical treatment of patients with
hypothyroidism as a co-morbidity, especially in emergency
surgery, one think should be kept in mind, that the
disturbances of various organs and organ systems, which are
associated with hypothyroidism.

76. • In terms of preoperative preparation, of particular importance are:
• • cardiovascular disorders (possible myocardial depression and
bradycardia)
• • respiratory system disorders (reduced spontaneous ventilation)
• • metabolic disorders and hydroelectrolyte and acidobase
disbalance (especially hyponatremia, and hypoglycemia)1
• Due to slow metabolism in patients with hypothyroidism, there is a
risk of an overdose of anesthetics and other medications that are
used in the surgical treatment.
• It is therefore necessary to carefully titrate doses, with the general
recommendation to reduce dose by 30%

77. • In patients with expressed hypothyrosis it is necessary to
introduce substitution therapy.
• The optimal preparation period before the surgery is 2-4
weeks.
• Patients older than 60 years of age, especially with coronary
disease or long term aggravated hypothyrosis, should not be
given full doses of substituents in the beginning.