HYPOTHYROID

1. HYPOTHYROIDISM
PRESENTATION BY:ABHINAV KUMAR
MODERATOR:DR.MOHD.ASLAM

2. INTRODUCTION
• First endocrine disorder treated by replacement with the
deficient hormone
• Development of purified thyroid hormone preparationsmimic
the function of the normal thyroid gland with thyroid hormone
replacement therapy.
• Safe and well tolerated by most patients
• Thyroid glandthyroxine (T4) and triiodothyronine (T3).
• Autoimmune disorders of the thyroid glandglandular
destruction and hormone deficiency
(hypothyroidism)/thyrotoxicosis

3. ANATOMY
• two lobes connected by an isthmus.
• Location:Anterior to the trachea between the cricoid cartilage and the
suprasternal notch.
• 20 g in size, highly vascular, and soft in consistency.
• Four parathyroid glandsparathyroid hormone are located posterior
to each pole of the thyroid.

4. PATHOPHYSIOLOGY

6. REGULATION OF THE THYROID
AXIS

7. • Thyroid releases 100-125 nmol of T4 daily
• only small amounts of T3.
• Half-life of T4--7-10 days
• Compensatory mechanisms maintain T3 levels.

8. Thyroid Hormone Transport
• Bound to plasma proteins: TBG, TTR, Albumin
• 99.98% of T4 and 99.7% of T3 are protein-bound.

9. Causes of Hypothyroidism

10. Epidemiology
• The National Health and Nutrition Examination Survey
(NHANES 1999-2002) of 4392 individuals3.7%
hypothyroid. (defined as TSH levels exceeding 4.5
mIU/L)[22]
• World Health Organization (WHO) data from 130
countries taken from January 1994 through December
2006 found inadequate iodine nutrition in 30.6% of the
population.
• WHOurinary iodine concentrations100 to 199 μg/L
in the general population.
• 150-249 μg/L in pregnant women.

11. • Age-related demographics:The frequency increases with
age.
• Most prevalent in elderly populations-The Framingham
study found hypothyroidism (TSH > 10 mIU/L) in 5.9% of
women and 2.4% of men older than 60 years.[24]
• Sex-related demographics:2 to 8 times higher in females.
• Race-related demographics:NHANES 1999-2002 whites
(5.1%) and Mexican Americans than in African Americans
(1.7%).

12. • Iodine deficiencymore common in less-developed
countries.
• Out of an estimated world population of 5.8 billion in
different regions, 3.8% are estimated to be suffering
from iodine deficiency in some form, though only 12% is
affected by goitre.
• Areas of adequate iodine intake-Autoimmune thyroid
disease (Hashimoto disease).
• Prevalence of antibodies is higher in women and
increases with age.

14. Primary hypothyroidism
Types of primary hypothyroidism include the following:
• Chronic lymphocytic (autoimmune) thyroiditis
• Postpartum thyroiditis
• Subacute (granulomatous) thyroiditis
• Drug-induced hypothyroidism
• Iatrogenic hypothyroidism

15. Chronic lymphocytic (autoimmune)
thyroiditis
• Most frequent cause of acquired hypothyroidism
• Thyroid antigens as foreign  chronic immune reaction
ensues resulting in lymphocytic infiltration of the gland 
progressive destruction of functional thyroid tissue.
• Anti–thyroid peroxidase (anti-TPO) antibodies are the hallmark
of this disease.
• Antibody levels can vary over time.
• Absence of antibodies does not exclude the diagnosis

16. Postpartum thyroiditis
• Up to 10% of postpartum  develop lymphocytic thyroiditis in the
2-12 months after delivery.
• Transient (2-4 months).
• Increased risk of permanent hypothyroidism or recurrence of
postpartum thyroiditis with future pregnancies.
• In a 12-year longitudinal study, Stuckey et al found that
hypothyroidism developed in 27 of 71 women (38%) who had a past
history of postpartum thyroid dysfunction (PPTD). In comparison,
only 14 of 338 women (4%) who had not had PPTD developed
hypothyroidism.[5]

17. Subacute granulomatous thyroiditis
• Also known as de Quervain disease,
• Relatively uncommon disease
• Most frequently  middle-aged women.
• Low grade fever, thyroid pain, dysphagia, and elevated erythrocyte
sedimentation rate (ESR).
• Self-limited
• inflammatory conditions or viral syndromes may be associated with
transient hyperthyroidism  transient hypothyroidism.

18. Drug-induced& iatrogenichypothyroidism
• The following medications reportedly have the potential to cause
hypothyroidism:
• Iodine excess (including iodine-containing contrast media and
amiodarone),
• lithium,
• antithyroid drugs,
• p-aminosalicylic acid,
• interferon-
• tyrosine kinase inhibitors – Sunitinib, imatinib[6]
• Bexarotene[7]

19. • Radioactive iodine (I-131) for treatment of Graves disease  results
in permanent hypothyroidism within 3-6 months after therapy.
• External neck irradiation (for head and neck neoplasms, breast
cancer, or Hodgkin disease)
• Thyroidectomy-approximately 15-30%

20. Genetics
• Genome-wide association studies FOXE1 gene  hypothyroidism.
• 10% of patients with congenital hypothyroidism have an error in
thyroid hormone synthesis.[9]
• Mutations in the TPO gene appear to be the most common error of
hormone synthesis, causing failure to produce adequate amounts of
TPO.[10]
• Mutations in the TSHR and PAX8 genes  congenital hypothyroidism
without goiter.[11, 12]

21. • Pendred syndrome  mutation in the SLC26A4 gene defect in
the organification of iodine
congenital sensorineural hearing loss,
enlarged thyroid gland.
autosomal recessive manner.[13]
• Autoimmune polyendocrinopathy
typeIAIRE genecharacterized by the presence of Addison
disease, hypoparathyroidism, and mucocutaneous candidiasis.
• Autoimmune polyendocrinopathy type 2 (Schmidt syndrome) is
associated with adrenal insufficiency and hypothyroidism

22. Iodine deficiency or excess
• Most common cause of hypothyroidism. Excess iodine can transiently
inhibit iodide organification and thyroid hormone synthesis (the
Wolff-Chiakoff effect).
• Healthy individualsphysiologic escape from this effect. In patients
with iodine overloadsodium-iodide symporter shuts downallows
intracellular iodine levels to drop and hormone secretion to resume.
• The Wolff-Chiakoff effect is short-livedsodium-iodide symporter is
capable of rapidly downregulation.
• exposure to excess iodineprofound and sustained hypothyroidism
in individuals with abnormal thyroid glands.[15]

23. Goitre can be classified as
per WHO classification
• Grade 0 – no goitre presence is found (the
thyroid impalpable and invisible)
• Grade 1 – neck thickening is present in result of
enlarged thyroid, palpable,not visible in normal
position of the neck.
• Grade 2 – neck swelling, visible when the neck is
in normal position, corresponding to enlarged
thyroid – found in palpation.

24. Central hypothyroidism[16, 17]
• Central hypothyroidismhypothalamic-pituitary axis is
damaged. The following potential causes should be
considered :
Pituitary adenoma-exerting pressure on normal
pituitary cells
Tumors impinging on hypothalamus
Lymphocytic hypophysitis- cause death of cells.
Sheehan syndrome
History of brain or pituitary irradiation

25. • Drugs (eg, dopamine, prednisone, or opioids)-decreased TSH
secretion.
• Congenital non goiterous hypothyroidism type 4Mutation in
theTSHB geneautosomal recessive pattern
• TRH resistanceTRHR geneautosomal recessive manner.
hypothyroidism and, unsurprisingly, have insensitivity to
thyrotropin secretion.[19]
• TRH deficiencymutation in the TRH geneautosomal recessive
manner.[20]

26. • Sign or symptom Affected patients(%)
• Weakness 99
Skin changes (dry or coarse skin) Lethargy 97
Slow speech 91
Eyelid edema 91
Cold sensation 90
Decreased sweating 89
Cold skin 89
Thick tongue 83
Facial edema 82
Coarse hair 79
Skin pallor 76
Forgetfulness 67
Constipation 66

27. • Menstrual disturbances,infertility
• Paresthesias, nerve entrapment syndromes
• Blurred vision
• Decreased hearing
• Fullness in the throat, hoarseness
Hashimoto thyroiditis is difficult to distinguish clinically, but the
following symptoms are more specific to this condition:
• Feeling of fullness in the throat
• Painless thyroid enlargement
• Exhaustion
• Transient neck pain, sore throat, or both

28. LABORATORY ASSESSMENT

29. LABORATORY ASSESSMENT
1.Tests of the Hypothalamic-Pituitary-Thyroid Axis
• TSH secretion: precise and specific indicator of the thyroid
status
• Normal range of the serum TSH:0.5 to 4.7 mU/L
• Diurnal variation of TSH secretion with peak values in the early
evening

30. TSH as a screening test
:misleading
INCREASED TSH
• TSH-secreting pituitary tumor
• Thyroid hormone resistance
• Assay artifact
DECREASED TSH
• 1ST trimester of pregnancy (due to hCG secretion),
• After treatment of hyperthyroidism
• Response to high doses of glucocorticoids or dopamine
Secondary hypothyroidism:
• Low to high-normal TSH level, inappropriate for the low T4 level.

32. APPROACH TO PATIENT

33. Sick Euthyroid Syndrome
• Acute, severe illness causes abnormalities of TSH or
thyroid hormone levels in the absence of underlying
thyroid disease
• Major cause cytokines such as IL-6.
• M/C hormone patterndecrease in total and unbound
T3 levels (low T3 syndrome) with normal levels of T4 and
TSH.
• Magnitude of the fall in T3 correlates with the severity of
the illness.
• T4 conversion to T3 via peripheral deiodination is
impaired, leading to increased reverse T3 (rT3).

34. • Very sick patients :fall in total T4 and T3 levels (low T4
syndrome)
• TSH levels may range from <0.1 to >20 mIU/L
Diagnosis of SES
• Previous history of thyroid disease and TFT
• Evaluation of the patient's acute illness
• Measurements of Rt3 with unbound thyroid hormones
and TSH.
• Diagnosis of SES is presumptive
• Resolution of the test results with clinical recovery can
clearly establish this disorder.

35. BIOCHEMICAL MARKERS OF
THYROID STATUS

37. CLINICAL IMPROVEMENT
• Wt loss of 2 to 4 kg
• Pulse rate increase
• Appetite improves, Constipation disappears
• Psychomotor activity increases
• Hoarseness ,changes in skin and hair improve last

38. Special Treatment
Considerations
PREGNANCY:Increase in serum TBG
• The mean increment in dose is 50μg/dayapparent
by the end of the first trimester, though may be
delayed to as late as the 6th month of gestation in
some women.
• A similar up-titration of thyroxine dose may be
required in women who are on estrogen preparations
including the oral contraceptive pill.

39. • TOC : Synthetic levothyroxine
• Most patients with postpartum thyroiditis
require treatment during the hypothyroid phase
• Long-term follow-up of patientsrisk of
permanent hypothyroidism
• Subclinical hypothyroidism in pregnancy requires
replacement treatment

40. Hypocortisolemia:
• Co-existence of thyroid hormone deficiency and
glucocorticoid deficiency
• Important to replace glucocorticoid before starting
thyroxine.
• Thyroxine therapy may lead to an increased
metabolism,increased demand of cortisol increasing
the likelihood of precipitating an adrenal crisis.

41. Central hypothyroidism:
• Important to replace glucocorticoid before starting
thyroxine.
• Monitoring of therapyserum T4 levels instead of
serum TSH levelssample should be collected prior to
ingesting the morning dose of thyroxine.

42. Ischemic heart disease:
• Thyroxine therapyimproves myocardial
function reduces peripheral vascular resistance
• Increases the myocardial oxygen demand
angina in 2% patients.
• Patients with pre-existing angina should ideally
undergo a cardiac evaluation prior to initiating
thyroxine therapy.
• Therapystarted at 25μg/day or even less and
increased no faster than at 4 weekly intervals.

43. Patients unable to take oral
thyroxine:
• Intravenous thyroxine can be given in a dose
approximately 70% of the oral dose, which
reflects the fractional absorption of the oral
dose.

44. Persistently elevated TSH
despite thyroid hormone
replacement
• poor compliance- try ‘catch up’ when a physician
visit approachesfree T4 NORMAL,TSH
ELEVATED
• Tissue-level unresponsiveness to thyroid
hormoneRARE
• Only 300 families have been identified with this
genetic mutation.

45. Myxedema Coma
• Myxedema coma is a severe life threatening situation
• Most commonly occurs in individuals with undiagnosed
or untreated hypothyroidism who are subjected to an
external stress, such as low temperature, infection,
myocardial infarction, stroke.
• Respiratory depression,Bradycardia, Hypotension,
decreased intestinal motility, Hyponatremia, Altered
sensorium, Infections and Hypothermia.
• Most patients need ventilatoryat least 24-48
hoursmeasurement of arterial blood gases is
mandatory.

46. TREATMENT
• Management includes maintaining of vital parameters
• Administration400 to 500 mcg of L-thyroxine through
nasogastric tube initially and subsequently 100 mcg/day.
• route is suboptimalconcerns of erratic
absorption(gastric atony)
• Corticosteroids may be given along with assisted
ventilation and O2 administration.
• Hypothermiainsulating blankets.

47. Subclinical Hypothyroidism
• Persistently elevated TSH levels and free
thyroxine (T4) levels are not below normal
• May resolve on its own or remain unchanged.
• Rest of the patients proceed to develop overt
hypothyroidism (low free T4 and raised TSH
levels) within a few years.
• Patients with raised TSH elevations and
detectable anti-thyroid antibody
levelsincreased risk of developing overt
disease.

48. • mild hypothyroid symptoms
• subtle serum lipoprotein
• cardiac function abnormalities
• Progression to overt hypothyroidism5 to 20%
per year in patients with both mildly elevated
TSH levels and antithyroid antibodies.

50. Important clinical pointers when
monitoring thyroid replacement
therapy
• Serial TSH measurements in patients with an intact
hypothalamic-pituitary axis.
• Important to keep in mind that changes in TSH levels lag
behind changes in thyroid hormone levels.
• Subsequent to adjustment of levothyroxine dosage, TSH
levels should be assessed only at least after four weeks.
• Changes in TSH levelsafter eight weeks of therapy with
thyroid hormone replacement.

51. • Adequacy of treatment in patients with pituitary
insufficiency measurements of free T4 and T3
levels.
• Increasing age is associated with declining
thyroid binding and serum albumin levels,dosage
requirementreduced by up to 20%.
• Elderly patientsannual monitoring for thyroid
function in order to avoid over replacement.

52. • Most hypothyroid patientstested annually for
TSH or free T4 levelsno data exists to support
this practice.
• Stable maintenance dosage of levothyroxine is
achieved, it is adequate to maintain a euthyroid
state until the patient becomes 6o to 70 years
old.

53. Potential adverse effects of
treatment
• Regular monitoring of serum TSH levelsmid-
normal serum TSH values ensuresis safe and
free from adverse events.
• In the event that thyroxinesuppressive
dosesafter carcinoma thyroid
surgerypotential adverse effectsskeletal and
cardiovascular system.
• A TSH value of <0.1mU/lrisk factor for
atrial fibrillation,
left ventricular hypertrophy and
enhanced risk for ischemic heart disease.

54. References:
• WILLIAMS TEXT BOOK OF ENDOCRINOLGY
• HARRISONS 18TH EDITION
• Facts of Iodine Supplementation-RK Marwaha*, S Gopalakrishnan* -©
SUPPLEMENT TO JAPI • JANUARY 2011 • VOL. 59
• Update Article-Drugs and Thyroid Joe George*, Shashank R Joshi* ©
JAPI • VOL. 55 • MARCH 2007
• Hypothyroidism shashank r Joshi-MEDICINE UPDATE
• Management of Hypothyroidism in Adults-Nikhil Tandon-©
SUPPLEMENT TO JAPI • JANUARY 2011 • VOL. 59
• Thyroid Disorders in Pregnancy-Samar Banerjee-©SUPPLEMENT TO JAPI
• JANUARY 2011 • VOL. 59
• Think Thyroid-Siddharth N Shah*, Shashank R Joshi**-©SUPPLEMENT
TO JAPI • JANUARY 2011 • VOL. 59
• Clinical Approach to Thyroid Disease-RV Jayakumar*-©SUPPLEMENT TO
JAPI • JANUARY 2011 • VOL. 59
• Laboratory Evaluation of Thyroid Function-Shashank R Joshi-
©SUPPLEMENT TO JAPI • JANUARY 2011 • VOL. 59
• Thyroid Emergencies-Siddharth N Shah-©SUPPLEMENT TO JAPI •
JANUARY 2011 • VOL. 59

55. 5-Stuckey BG, Kent GN, Ward LC, Brown SJ, Walsh JP. Postpartum thyroid
dysfunction and the long-term risk of hypothyroidism: results from a 12-year
follow-up study of women with and without postpartum thyroid
dysfunction. Clin Endocrinol (Oxf). Sep 2010;73(3):389-95. [Medline].
6-Wolter P, Dumez H, Schöffski P. Sunitinib and hypothyroidism. N Engl J
Med. Apr 12 2007;356(15):1580; author reply 1580-1. [Medline].
Smit JW, Stokkel MP, Pereira AM, Romijn JA, Visser TJ. Bexarotene-induced
hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid
hormones. J Clin Endocrinol Metab. Jul 2007;92(7):2496-9. [Medline].
9-Vono-Toniolo J, Rivolta CM, Targovnik HM, Medeiros-Neto G, Kopp P.
Naturally occurring mutations in the thyroglobulin gene. Thyroid. Sep
2005;15(9):1021-33. [Medline].
10-Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med
Genet. May 2005;42(5):379-89.[Medline]. [Full Text].
11-Paschke R, Ludgate M. The thyrotropin receptor in thyroid diseases. N Engl J
Med. Dec 4 1997;337(23):1675-81. [Medline].

56. 12-Macchia PE, Lapi P, Krude H, Pirro MT, Missero C, Chiovato L, et al.
PAX8 mutations associated with congenital hypothyroidism caused by
thyroid dysgenesis. Nat Genet. May 1998;19(1):83-6. [Medline].
13-Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, et al.
Pendred syndrome is caused by mutations in a putative sulphate
transporter gene (PDS). Nat Genet. Dec 1997;17(4):411-22. [Medline].
15-Woeber KA. Iodine and thyroid disease. Med Clin North Am. Jan
1991;75(1):169-78. [Medline]
16-Yamada M, Mori M. Mechanisms related to the pathophysiology
and management of central hypothyroidism. Nat Clin Pract Endocrinol
Metab. Dec 2008;4(12):683-94. [Medline].
17-Nebesio TD, McKenna MP, Nabhan ZM, Eugster EA. Newborn
screening results in children with central hypothyroidism. J Pediatr. Jun
2010;156(6):990-3. [Medline].
19-Bonomi M, Busnelli M, Beck-Peccoz P, Costanzo D, Antonica F, Dolci
C, et al. A family with complete resistance to thyrotropin-releasing
hormone. N Engl J Med. Feb 12 2009;360(7):731-4. [Medline].
20-Katakami H, Kato Y, Inada M, Imura H. Hypothalamic
hypothyroidism due to isolated thyrotropin-releasing hormone (TRH)
deficiency. J Endocrinol Invest. Jun 1984;7(3):231-3. [Medline].