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Fluorosis And THYROID

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Fluoride levels were found to be as high as 5 to 23 mg per liter, The permissible limit according to WHO is only 1.5 mg/L 7. Unfortunately, fluorosis has no cure. – PowerPoint PPT presentation

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Title: Fluorosis And THYROID


1
Fluorosis And THYROID
  • Dr.R.V.S.N.Sarma, M.D., M.Sc., (Canada)
  • Consultant Physician Chest Specialist
  • President - IMA Tiruvallur Branch
  • 5, Jayanagar, Tiruvallur - 602 001
  • 91 98940 60593, (04116) 260593

2
Objectives
  • To present a Snapshot view of the available
    evidence on the interaction of Fluorosis and
    Thyroid function
  • To sensitize the clinicians on the possible role
    of fluoride as a putative cause in hypothyroidism
    and to present some clinical guidelines
  • To request the elite group of researchers working
    on fluorosis to take up well designed studies
    to answer some of the puzzles of interaction of
    fluoride thyroid.

3
Resources Consulted
  • Second Look www.SLweb.org
  • NLM NCBI Pub Med searches
  • FAN Fluoride Action Network www.fan.org
  • ISFFR International Society for Fluorosis
    Research
  • FLUORIDE Official Journal of ISFFR
  • PFPC website on Thyroid
  • UNICEF publications
  • Endocrine Regulations China
  • Endemic medical problems of India a book

4
Cause Effect Relationship
  • Exposure to F must be for a prolonged period of
    time
  • The damage is proportional to the administered
    dose
  • Fluoride dose has to be of toxic level dose
    response
  • Anatomic functional changes of the thyroid take
    time.
  • Variable period of latency before changes
    manifest
  • An altered thyroid-hypophysial balance is the
    earliest
  • Later parenchymal hypertrophy of thyroid gland
    occurs
  • Leads to a hypofunction of the thyroid, and
  • Finally the strumiform degeneration of gland
    sets in

5
Thyroid Regulation
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
TSH -R
THYROID T4 and T3
PLASMA T4 to FT4
PLASMA T3 to FT3
TISSUES T4 to T3, rT3
6
Hormonogenesis
  • There are following 5 steps in the hormonogenesis
  • Trapping inorganic Iodine from dietary Iodides
  • Activation of Iodine to high valance I2
  • Incorporation of I2 into Tyrosine of Thyroid
    Globulin
  • Coupling of formed MIT and DIT to form T4 T3
  • Proteolysis of Thyroglobulin to release T4 T3

7
The Iodine Cycle
8
The Two Halogen Story
  • Fluorine and Iodine both belong to the Halogen
    group
  • Fluorine is more reactive than Chlorine gt Bromine
    gt Iodine
  • Both occur as soluble salts in water and are
    ingested
  • Fluorine is competitive to Iodine in chemical
    reactions
  • Iodine ?causes Goitre, Fluoride excess
    competitively inhibits I2 availability to thyroid
    and causes hypofunction
  • In our country both deficiency of I2 and excess
    of F2 are endemic (endemic goitre and endemic
    fluorosis).

9
T4 Catabolism
10
What happens in Fluorosis ?
Abnormal catabolism -Thyroxine FT4
T3 rT3 will be HIGH rT3 T3 ratio
will be HIGH Fluoride affects the
normal deiodination of T4
Normal catabolism -Thyroxine FT4
T3 rT3 will be LOW rT3 T3 ratio will
be LOW Normal deiodination of T4
11
Fluoride in Our Waters
  • Drinking water should not contain more than 1.5
    ppm of fluoride (WHO, 1994).
  • A much elevated concentration of fluoride,
    ranging from more than 1.5 ppm to 20 ppm in
    surface, subsurface and deep waters in nine
    states in India.
  • This is beyond the permissible limit

12
1. Himalayan Belt
  • 17 villages of endemic goitre in Himalayan belt
  • Water samples were analyzed for iodine content,
    fluoride level and hardness
  • Goitre prevalence v/s iodine content - P lt 0.01
  • Goitre prevalence v/s fluoride content - P lt 0.01
  • Goitre prevalence v/s hardness - P gt 0.06

The Lancet, May 27, 1972 - T. K. DAY P. R.
POWELL-JACKSON,
Fluoride, Water hardness and Endemic goitre
13
2. Dental Fluorosis and Goitre
  • 22,276 individuals were examined in Gujarat
  • Presence of goitre and dental fluorosis
  • Fluoride and iodine content of the water tested
  • Goitre prevalence 14.1, Fluorosis 12.2
  • Only 0.3 were Goitre of Grade II or more
  • All cases of goitre were euthyroid
  • Only anatomical but no functional effect

Desai VK, et al. (1993). Epidemiological study of
goitre in
endemic fluorosis district of
Gujarat. Fluoride. 26187-90.
14
3. Fluoride in Hyperthyroidism
  • NaF 5 mg t.i.d was given to 19 pt of hyperthyroid
  • Thyroidal, blood and urinary radio-iodine studies
  • Fluoride inhibits thyroid iodide concen.
    mechanism
  • In abundance of Iodine this does not occur
  • If total Iodine pool is low It imposes a
    serious limitation on hormone synthesis
  • 5 to 10mg of fluoride daily for long periods
    reduced hyperthyroidism in animal experiments

Journal of Clinical Endocrinology 1978
181102-1110. Effect of fluorine on thyroid
metabolism in hyperthyroidism - PIERRE-M.
GALLETTI, M.D., PH.D AND GUSTAVE JOYET, D.Sc.
15
4. Punjab endemic areas
  • In the neighborhood of Hundewali, Aravalli rocks
    emerge through the alluvium.
  • Samples of these rocks were found to have
    fluorine content, varying from 30 to 3200 parts
    per million.
  • These extend between the Chenab and Ravi rivers,
  • The distribution of Endemic Goitre correlated
    with high fluoride content of water and also
    dental fluorosis the milder form of Fluorosis

The Lancet, February 15, 1981 Fluorine in the
etiology of endemic goitre by DAGMAR
CURJEL WILSON, M.D. WOMEN'S MEDICAL SERVICE,
INDIA (RETD.)
16
5. The Assam Story
  1. It is colourless, odourless water that is
    wreaking havoc on hundreds of thousands of people
    in many families in Assam.
  2. Around 2,00,000 people are in the grip of
    hydro-fluorosis.
  3. In Karbi Anglong, Naogaon and Kamrup districts,
    hundreds of villages are endemic due to excess
    fluoride.
  4. More than six million children suffer from
    fluorosis. Of these, at least 25,000 are in
    Assam.
  5. In Karbi Anglong, one-seventh of its 7,00,000
    people suffer from either dental or skeletal
    fluorosis. Many have thyroid hypofunction

Health News, India Fluoride in water takes its
toll in Assam
A SPECIAL FEATURE ARTICLE ON
23-June-2004
17
5. The Assam Story contd..
  • 6. Fluoride levels were found to be as high as 5
    to 23 mg per liter, The permissible limit
    according to WHO is only 1.5 mg/L
  • 7. Unfortunately, fluorosis has no cure. The
    only way out is prevention at an early stage.
  • 8. Initial symptoms are sporadic pain and
    stiffness of joints, going into chronic joint
    pain, arthritis and calcification of ligaments.
    Symptoms of hypothyroidism develop slowly
  • 9. Fluoride can enter the human body through
    food, toothpaste, mouth rinses and, of course,
    more swiftly through drinking water.

Health News, India Fluoride in water takes its
toll in Assam
A SPECIAL FEATURE ARTICLE ON
23-June-2004
18
6. Sialic Acid - Fluorosis
  • Effect of fluoride in 36 villages of Mehsana
    district, North Gujarat  was studied
  • Concentration of Sialic acid was significantly
    decreased (P lt 0.01) in the fluorotic population
    as compared to control population
  • Sialic acid concentration is now a marker for the
    diagnosis of fluorosis.
  • Thyroid hormones regulate prostatic glycoprotein
    metabolism and Sialic acid levels

Chinoy et al. Thyroid,Flurosis and prostatic
monosaccharides"
Int J Androl
23(3)156-62 (2000
19
7. Tribal Areas of Vizag -AP
  • Upon invitation by the ITDA of Andhra Pradesh
  • We have lead an ICMR team of doctors to study
    Goitre in Paderu taluk of Vizag district in A.P.
    in the year 1983
  • Myself, 2 Asst. professors from Medicine and PSM
    - AMC
  • The tribals of Paderu, Munchenput, Seethampet
    have high prevalence(26) of endemic goitre of
    iodine deficiency
  • Dental fluorosis was seen prevalent in children
    6
  • No skeletal fluorosis was detected in this study
  • This study did not include blood tests for
    thyroid function

Dr.Sarma RVSN et al ICMR special report to ITDA
AP 1983
20
8. Fluorosis in Tamilnadu
  • Drinking water samples from 255 villages in the
    Krishnagiri block of Dharmapuri district of
    Tamilnadu were analyzed
  • Fluoride endemic areas of the region were
    identified
  • The prevalence of dental fluorosis is found the
    high and low
  • The relationship of fluoride on drinking water
    was assessed by simple and multiple correlation
    analysis.
  • Clinical survey for Dental, Skeletal thyroid
    effects was done
  • Dental Fluorosis, Skeletal Fluorosis, Thyroid
    hypofunction

Fluoride Vol. 33 No. 3 121-127 2000, Report 121
Mapping and fluoride dependence on water quality
in Krishnagiri, Tamilnadu G Karthikeyan, A
Shunmugasundarraj.
21
9. The Somerset Study
  • In Somerset, England, in the rural district of
    Longport, in the rural areas of Charlton
    Mandeville and Long Sutton
  • 378 children in seven local schools were
    examined.
  • An adjoining village of Somerton, was the
    control, and all the 203 children in four schools
    were examined
  • High Incidence of dental fluorosis and Goitre
    were positively correlated Absence of dental
    fluorosis in the control area where endemic
    goitre was absent

The Lancet, February 15, 1981 Fluorine in the
etiology of endemic goitre by DAGMAR
CURJEL WILSON, M.D. WOMEN'S MEDICAL SERVICE,
INDIA (RETD.)
22
10. Sub-clinical Endemic Cretinism
  • Cretinism in iodine-deficiency areas is well
    known,
  • The milder form is called "semi-cretinism," or
    cretinoidism.
  • It was named as "sub-clinical endemic cretinism"
    in a symposium held in Xinzhou, China 1985. TSH
    ?, FT4 and FT3 Normal
  • Area A low Iodine, high fluoride rT3 58
    ng/dl, rT3/T3 was 7.91
  • Area B low Iodine, normal fluoride - rT3 32
    ng/dl, rT3/T3 was 5.80
  • Area C Iodine supl. normal fluoride - rT3 21
    ng/dl, rT3/T3 was 2.90
  • The excess fluoride ion affects normal
    deiodination.

Iodine Deficiency Disorder Newsletter 1991 August
Vol. 7 No. 3, The Relationship of a Low-Iodine
and High-Fluoride rT3, rT3/T3 ratio in Xinjiang
- Lin Fa-Fu, Aihaiti, Zhao Hong-Xin, Lin Jin,
Jiang Ji-Yong, Maimaiti, and Aiken.
23
11. Xingjian Experience
  • 769 school children 7 to 14 yrs. in three areas
    studied
  • 104 children with MR were detected in all.
  • Area A low Iodine, High fluoride 25 MR
  • Area B low Iodine, normal fluoride 16 MR
  • Area C Iodine supplemented and Normal fluoride
    8
  • A low iodine intake high fluoride intake ? the
    somatic and the CNS developmental disturbance of
    iodine deficiency

Iodine Deficiency Disorder Newsletter 1991 August
Vol. 7 No. 3, The Relationship of a Low-Iodine
and High-Fluoride Environment to Sub-clinical
Cretinism in Xinjiang - Lin Fa-Fu, Aihaiti, Zhao
Hong-Xin, Lin Jin, Jiang Ji-Yong, Maimaiti, and
Aiken.
24
12. Endemic Cretinism
  • (a) average IQ 71, 77, 96
  • (b) average auditory threshold (in dB)24, 20,
    16
  • (c) bone age retardation () 28, 13, 4
  • (d) thyroid I131 uptake () 60, 50, 24 and
  • (e) serum TSH (mU/ml) 21, 11, 6.
  • All these differences are statistically
    significant
  • Total attack rate of sub-clinical endemic
    cretinism 9.
  • Sub-clinical endemic cretinism in children with
    mental retardation was 69,

Ma Xin-Yuan, et al . 1987 The study of sub
clinical endemic cretinism in Fujian province .
Proceedings of the 3rd National Conference on
Endemic Goitre and Endemic Cretinism. Chinese
Centre for Endemic Disease Control and Research,
pp 120-125.
25
13. Shandong Study
Parameter examined Low I, High F area Control area
Thyromegaly Adults 3.8 lt 1
Thyromegaly Children 29.8 lt 5
Dental fluorosis Adults 35.48 Absent
Dental fluorosis Child 72.9, Low
Average I.Q of pupil 76.67 /- 7.75 88.88 /- 6.2
Urinary Iodine Low 816.25 mcg/l
Urinary Fluorine 2.08 mg/l, Low
I 131 uptake 3 and 24 h 9.36 and 9.26 High
Serum TSH levels Higher Normal
Zhonghua Liu Xing Bing Xue Za Zhi. 1994
Oct15(5)296-8.
Effects of high iodine and
high fluorine, Yang Y, Wang X, Guo X.
26
14. Water Fluoride and Thyroid
Parameter examined Group A Group B Group C
Clinical Diagnosis Healthy Hyperthyroid Hypothyroid
Number of subjects 47 43 33
? fluorine content (122 /- 5 mµmol/l of water T3? TSH?, RAIU? Mild improvement Worsened
normal F of 52 /- 5 mµmol/l in water No change No change No change
Probl Endokrinol (Mosk). 1985 Nov-Dec31(6)25-9.
Body fluorine of healthy persons and
thyroidopathy patients Bachinskii PP, Gutsalenko
OA, Naryzhniuk ND, Sidora VD, Shliakhta .
27
15. Fluorosis - Immunity
  • In factory workers continuously exposed to
    fluorine
  • Thyroid and immune statuses were studied
  • The workers with euthyroid status
  • immune disorders with an allergic tendency
  • increase of B-lymphocytes, immunoglobulin A
  • Sub-clinical hypothyrodism cases
  • the immune alterations were more evident,
  • T-lymphocytes count?, but their functional
    activity declined, indicating impaired T helper
    function

Ter Arkh. 199567(1)41-2. The thyroid and immune
statuses of workers with long-term fluorine
exposure Balabolkin MI, Mikhailets ND,
Lobovskaia RN, Chernousova NV.
28
16. Industrial Fluorosis
  • In 165 workers of electrolysis shops of aluminum
    production
  • With expressed signs of chronic fluoride
    intoxication
  • Correlated with longer service and fluorosis
    progress
  • Toxic involvement of the liver in fluorosis
    patients,
  • Low T3 syndrome is observed more frequently (in
    75.6)
  • Liver abnormalities lead to ?in peripheral
    conversion of T4 to T3,
  • The detected thyroid abnormalities were
  • Moderate reduction of iodine-absorbing function
    of the thyroid,
  • Low T3 with normal T4 level, and an?in TSH.

Probl Endokrinol 1996 42 6-9. Thyroid function
during prolonged exposure to fluorides.
MIKHAILETS ND, BALABOLKIN MI, RAKITIN VA, DANILOV
IP.
29
17. Fluorosis- Calcitonin
  • Workers engaged in fluorine production were
    studied
  • RIA of thyrotropin and thyroid hormones in the
    blood
  • Moderate functional impairment of the
    hypophysis-thyroid gland system without overt
    hypo thyroidism
  • Elevation of calcitonin concentration indicated
    stimulation of thyroid glands parafollicular
    cells.

Gig Tr Prof Zabol. 1989(9)19-22. Chronic effects
of fluorides on the pituitary-thyroid system
in industrial workers, Tokar' VI, Voroshnin VV,
Sherbakov SV.
30
Pathology
  • Effect of sodium fluoride on the thyroid glands
  • Depletion of colloid from the follicles.
  • Shrinkage of follicles.
  • Disruption of follicular basement membrane
  • Edema and degeneration of the follicular
    epithelial cells.
  • Increased follicular vascularity.
  • Fatty degeneration in the inter-follicular
    connective tissue.
  • Vacuolations in the colloid

31
Fluoride may Affect
  1. Iodine pump, Peroxidase reactions
  2. Coupling reactions, Lysosomal hydrolysis
  3. Peripheral conversion of T4 to T3?, Reverse T3?
  4. Hypothalamic TRH causes TSH release from
    thyrotroph using DAG/IP3/Ca2 mechanism (Gq)
  5. TSH via cAMP (Gs/PKA) mechanism activates all
    aspects of follicular cell thyroid hormone
    synthesis, processing and release, as well as
    cell growth

32
Biochemical Basis
  1. TSH stimulation of thyroid Adenyl Cyclase (AC) is
    absolutely dependent on the regulatory
    nucleotides, the G proteins
  2. Sodium fluoride has dual actions on AC
  3. The AC activity increased as the concentration of
    NaF increased from 0.01 to 1 mM,
  4. PFDA alters biochemical processes at cellular
    level
  5. Fluoride stimulation of Adenyl Cyclase (AC)
    activity is two to three fold higher than that of
    TSH.

33
Fluorosis
  • Fluoride Toxicity
  • Nausea, vomiting, diarrhea, abdominal pain,
  • numbness/tingling in extremities
  • Fluorosis
  • Pitted enamel and discoloration of the teeth
  • Skeletal Fluorosis pain and stiffness of
    joints, going into chronic joint pain, arthritis
    and calcification of ligaments etc.

34
UNICEFs Clinical Test
  • Three simple clinical tests
  • Forward flexion of spine
  • Chin to Chest test
  • Hands on the occiput test
  • Normal person can do
  • Person with skeletal fluorosis can not.

Left figures Normal, Right Abnormal
35
For The Clinicians
  • Look for signs of Fluoride excess
  • May be clinically euthyroid
  • Hypothyroidism itself is a subtle disease
  • High index of suspicion is needed
  • Association with fluorosis must be thought
  • Especially if the pt is from fluorosis endemic
    region
  • Goitre, clinical and sub-clinical cretinism in
    children
  • A word of caution on use of NaF for otosclerosis

36
Diagnostic Tests
  • FT4, TSH to diagnose clinical sub-clinical hypo
    function
  • FT3 to identify low T3 syndrome, rT3 and T3/rT3
    ratio
  • Sialic Acid in plasma and urine, urinary fluoride
    excretion
  • Drinking water sample analysis for fluoride
    levels
  • Chronology of Thyroid Function Test abnormalities
  • 1. Normal FT4, FT3, ?TSH Sub clinical
    Hypofunction
  • 2. Normal FT4, FT3, ?TSH, ?rT3 Sub clinical
    Hypofunction
  • 3. Normal FT4, FT3, ?TSH, ?rT3 , ?rT3 /T3 ratio
    - Sub clinical
  • 4. Normal FT4, ?FT3, ?TSH, ?rT3 , ?rT3 /T3 ratio
    ?T3 syn
  • 5. FT4?,?FT3, ?TSH, ?rT3 , ?rT3 /T3 ratio
    Frank Hypo

37
Future Research Needs
  1. Methodologically rigorous studies on the cause
    effect relationship of Fluorosis and Thyroid
    function
  2. Multidisciplinary approach for such studies
  3. The exact mechanism of thyroid functional
    derangement needs to be elucidated
  4. Combined clinico-epidemiological studies on
    endemic fluorosis in areas of endemic goitre
  5. Study on drugs which can modify fluoride toxicity

38
Our Obeisance
Sukham Samagram Vijnane Vimale cha Pratishthitam
All happiness is rooted in the Good
Science - Charaka Samhita
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