THYROTOXICOSIS AND GRAVES

DISEASE (PART 1)
BY NAWA .M.S.
OUTLINE
• THYROID GLAND PHYSIOLOGY
• THYROTOXICOSIS
• GRAVES DISEASE
• CLINICAL FEATURES OF THYROTOXICOSIS AND GRAVES
DISEASE
• INVESTIGATIONS
THYROID GLAND PHYSIOLOGY
• Function: responsible for production of thyroid hormones and calcitonin

• THYROID HORMONE SYNTHESIS AND SECRETION

REGULATION OF THYROID HORMONES
HYPOTHALAMUS: releases thyrotropin releasing hormone(TRH) and goes to
the anterior pituitary gland.

ANTERIOR PITUITARY GLAND: TRH binds to its receptors of the thyrotropes

and stimulates the synthesis and release of thyroid stimulating hormone(TSH) via
increase of calcium and activation of protein kinase C.

THYROID GLAND: TSH binds to its receptors and stimulates thyroid(T3 and T4)
hormone synthesis via increased cyclic AMP and activation of protein kinase A.

NOTE: WHEN THE LEVELS OF THYROID HORMONES(T3 AND T4)

INCREASES, A NEGATIVE FEEDBACK RESPONSE IS SENT TO THE
HYPOTHALAMUS AND PITUITARY GLAND TO DECREASE THE LEVELS OF
TRH AND TSH.
EFFECTS OF THYROID HORMONES
• FACTORS THAT:
• Influence thyroid hormone increase
• Increasd TSH levels
• Elevated thyroid binding proteins(TBG)
• Autoantibodies(TSI,Anti-TPO,Anti-TG)
• Pregnancy
• Ioodine excess(Jod-bosedow phenomenon)
• Influence thyroid hormone decrease
• Decreased TSH levels
• Decreased iodine levels
• Iodine excess(wolff-chaikoff effect)
• Drugs(amiodarone)
• Decreased thyroid binding proteins
• Nephrotic syndrome
THYROTOXICOSIS
• TERMS:
• Thyrotoxicosis: state of thyroid hormone excess due to any
cause.
• Hyperthyroidism: increased thyroid gland function. One of the
causes of thyrotoxicosis.
• Primary hyperthyroidism: arises from an intrinsic thyroid
abnormality.
• Secondary hyperthyroidism: arises from outside the thyroid
gland.
• NOTE:hyperthyroidism and thyroitoxicosis are words used
interchangeably but are not the same meaning.
CAUSES OF THYROTOXICOSIS
GRAVES DISEASE
• Described by irish physician Dr Robert graves in 1935.
• Most common cause of thyrotxicosis(accounts 60-80% ofb
thyrotoxicosis)
• Common in females, with F:M ratio of 10:1
• rarely begins before adolescence but occurs between 20 and 50
years of age; also occurs in the elderly.
ETIOPATHOGENESIS
• Combination of genetic factors and environmental factors
• 1.) GENETIC FACTORS:
• Polymorphisms in HLA-DR3, CTLA 4, PTPN22, TSH-R gene,FCRL3, and CD226.
• Concordance rate in monozygotic twins is 20-30% compared to that of dizygotic twins
which is <5%.
• 2.) ENVIRONMENTAL FACTORS;
• Pregnancy
• Highly active antiretroviral therapy(HAART)- graves during the immune reconstitution
phase.
• Drugs- lithium, alemtuzumab therapy, iodine, amiodarone
• Infectious disease- yersinia histolytica and other gram negatives containing TSH
binding sites.
• Stress
• Smoking- major risk factor for graves opthalmopathy.
• 3.) ROLE OF AUTOANTIBODIES AND CYTOKINES
CLINICAL FEATURES OF THYROTOXICOSIS AND GRAVES DISEASE
SIGNS SPECIFIC TO GRAVES DISEASE
SOCRING SYSTEM TO EVALUATE OPTHALMOPATHY
• NOTE: In the elderly, features of thyrotoxicosis, may be subtle or
masked and patients may present mainly with fatigue and weight
loss, this condition is known as apathetic thyrotoxicosis.
IODINE 123 NUCLEAR
SCINTIGRAPHY
 REFERENCES
• DAVIDSONS PRINCIPLES AND PRACTICE OF INTERNAL
MEDICINE(24TH EDITION) BY IAN D, PENMAN, E’TAL..
• HARRISONS PRINCIPLES OF INTERNAL MEDICINE(20TH
EDITION) DR FAUCI, E’TAL..
• KUAMAR AND CLARK’S CLINICAL MEDICINE(10TH EDITION)
BY PROFESSOR DANE PARVEEN J KUMAR, E’TAL.
• BOARD BASICS: AN ENHANCEMENT TO MKSAP 19
• THYROID-PATHOLOGIES-INTRODUCTION-BENIGN-
DISEASE-AND-CARCINOMA-THYROID BY DR. B. SELVARAJ
• NEXT SLIDE(PART 02):NEONATAL GRAVES
DISEASE, MANAGEMENT OF THYROTOXICOSIS AND
GRAVES.
• THANK YOU..