thyroid gland disorders

1. Thyroid Gland
Hyperthyroidism
Deependra Shrestha

2. Clinical Scenario
• A 39-year-old female presents to the clinic for a routine health maintenance
exam.
• She reports that she is feeling nervous and anxious all the time with frequent
palpitations.
• On further questioning she reports having diarrhea and has been losing weight.
• She has also noticed a change in hair and fingernail growth and frequently feels
warm while others are cold or comfortable.
• She denies any history of depression or anxiety disorder and is not taking any
medications.
• On examination, her heart rate is 110 beats per minute. She has a slight tremor
and has increased reflexes in all extremities.
• A nontender thyroid enlargement is appreciated in the thyroid region.
• Presence of Exophthalmos

3. Laboratory studies
• Hematology:
• Hb: 13.9 mg/dl
• TC: 6300 (60%N,35%L,05%E) / mm3
• Platelets: 1,80,000 / mm3
• Biochemistry:
• RBS: 110 mg/dl
• Serum Urea : 4.6 mmol/L
• Serum Creatinine: 61 μmol/L
• Na+ / K+ : 144 / 5.1 mmol/L
• SGPT / SGOT : 23 / 20 U/L
• Alk Phosphatase: 40 IU/L
• Serum Calcium: 2.2 mmol/L

4. Special Tests:
• Iron: 70 μgm / L
• TIBC: 200 μgm / L
• Ferritin: 20 ng/ml
• Free T3 : 4.8 nmol / L ( Range: 1.8 – 2.9 nmol/L)
• Free T4 : 48.0 pmol / L (Range: 10 – 25 pmol/L)
• TSH : 0.1 mU/L (Range 0.5 – 5.0 mu/L)

5. Any other investigation??
• Anti TPO antibodiy
• RAIU
• TSIs

6. Diagnosis ??????

7. On further investigation..
• Thyroid Stimulating Immunoglobulins (TSIs) test is positive
• TPO antibodies are negative

8. Discussion:
• The patients has symptoms of nervousness, weight loss,
gastrointestinal and skin alterations, heart palpitations, heat
intolerance, and physical signs of hyperreflexia and a goiter.
• Likely diagnosis:
• Hyperthyroidism, likely Graves disease.
• Supporting points from biochemistry
• T3- High
• T4- High
• TSH – Low
• TSIs- Positive

9. • Biochemical mechanism:
• The most frequent cause of hyperthyroidism, Graves disease, is an
autoimmune process in which thyroid hypersecretion is caused by
circulating immunoglobulins that bind to the TSH receptor on the
thyroid follicular cells and stimulate thyroid hormone production.
• The diagnosis is confirmed by increased thyroid stimulating IgG
antibodies and is frequently seen in other family members.
• Hyperthyroidism, thyroid excess causes a tachycardia, tremor,
nervousness, thin skin, weight loss through the hypermetabolic state,
and hyperreflexia.
• If unchecked, the high levels of thyroid hormone can sometimes even
cause adrenergic crisis (so called thyroid storm), which has a high
rate of mortality.

10. • Normally, the thyroid hormone (thyroxine) is under tight control. The
pituitary release of thyroid stimulating hormone is stimulated by
insufficient thyroxine, and suppressed by excess thyroxine.
• In Graves disease, the most common cause of hyperthyroidism, an
autoimmune immunoglobulin is produced that stimulates the TSH
receptor of the thyroid gland.
• This is confirmed by either assaying for the Thyroid Stimulating
Immunoglobulin, or a radionuclide scan revealing diffuse increased
uptake throughout the thyroid gland.
• Treatment acutely includes β-adrenergic antagonists and agents that
inhibit the catabolism of thyroid hormone such as propylthiouracil
(PTU).

11. Clinical Conditions:
•Abnormal thyroid function
•Hypothyroidism
•Hyperthyroidism

12. Basic evaluation of thyroid disease

13. laboratory evaluation of thyroid function.

14. Hyperthyroidism:
• Increase in activities of thyroid hormones.
• Decrease in TSH due to feedback mechanism.
• Causes:
• Graves’ disease
• Toxic adenoma/hot nodule
• Multinodular goiter
• Thyroiditis(Hasitoxicosis)
• Exogenous iodine ingestion
• Excessive T3 and T4 ingestion.
• Ectopic thyroid tissue
• HCG dependent
• TSH dependent: Pituitary tumor.

15. Clinical Features:
• Cardiovascular:
• High thyroid hormones have a direct stimulatory effect on cardiac
muscle.
• Increase heart rate and stroke volume even at rest.
• Peripheral vascular resistance is reduced.
• Increase in cardiac output.
• Arrhythmias.
• Gastrointestinal:
• Weight loss
• Increase bowel movement.
• Liver unction can be markedly deranged, with hypoalbuminaemia and
elevation of plasma aminotransferase and alkaline phosphatase
activities.

16. • Nervous system:
• Generalized hyperkinesia
• Fine tremor of outstretch finger
• Loss of sleep
• Musculoskeletal:
• Weakness particularly proximal muscles.
• Due to impaired phosphorylation of creatine.
• Periodic paralysis, associated with hypokalaemia during attacks of
weakness

17. • Respiratory:
• Due to generalized myopathy, respiratory muscle function may be
impaired and pulmonary compliance may also be reduced.
• Dyspnoea
• Breathlessness
• Skin and hair:
• Hair loss
• Brittle nails
• Warm and moist skin.

18. • Skeleton
• Significant loss of mineral from the skeleton, which results from increased
bone turnover
• Hypercalciuria and hyperphosphaturia are found
• urinary hydroxyproline excretion is increased, reflecting the increase in
collagen turnover.
• Kidney:
• Increase magnesium excretion
• Increase thirst and mild polyuria even in the absence of hypercalcemia of
hyperglycemia.
• Endocrine:
• Menstrual irregularity
• Reduced fertility.
• Decrease sex steroid due to decrease binding protein.
• Gynaecomastia.

19. Graves’ Disease:
• Basedow-Graves disease
• Most common cause of Hyperthyroidism.
• An autoimmune disease.
• Female/Male: 6:1
• Peak onset 3rd-4th decade, but can occur at any age
• It most commonly affects the thyroid, frequently causing it to enlarge to twice its
size or more (goitre)
• It can also affect the eyes, causing bulging eyes (exophthalmos).
• It affects other systems of the body, including the skin.

20. Mechanism:
• Thyroid Stimulating Immunoglobulins (TSIs) bind to the TSH receptor
and mimic the action of TSH.
• Activates adenylate cyclase and the formation of cAMP.
• Genetic factor: MHC class II antigen HLA-DR3 increases risk by 3 fold

21. Signs and Symptoms:
• Nervousness
• Diaphoresis
• Heat intolerance
• Palpitations; tachycardia
• Insomnia
• Weight loss
• Hyper defecation
• Angina
• Atrial fibrillation
• Weakness
• Cachexia
• Graves’ opthalmopathy
• Graves’ dermopathy (pretibial
myxedema)
• Thyroid thrills or bruits

22. • Thyroid involvement
• Moderate enlargement of thyroid gland
• Gland is diffuse and soft in consistency
• Graves’ Opthalmopathy:
• Clinically evident in <50% of patients
• Exophthalmos
• Periorbital edema
• Extraocular muscle weakness
• Corneal ulceration
• Optic nerve damage (compression)

24. Graves’ Opthalmopathy:
Symptoms
• Gritty, dry eyes
• Periorbital puffiness
• Diplopia
• Decreased vision

25. Graves’ Ophthalmopathy:
• Pathogenesis
• Presumed autoimmune, likely due to shared antigens on thyroid and
retroorbital tissue (possibly the TSH receptor).
• Extraocular muscles enlarge with edema, glycosaminoglycan
deposition, mononuclear cell infiltrate, and fibrosis.

27. Graves’ Dermopathy(Pretibial Myxedema)
• Patients with graves disease may develop indurated purple skin.
• It is due to glycosaminoglycan deposition
• Rare, generally accompanied by eye disease
• Usually asymptomatic
• Therapy typically topical glucocorticoids

28. Investigations:
• TFT
• USG neck.
• Radioiodine uptake.
• Thyroid stimulating antibodies
• Anti thyroid (anti-TPO and Tg) antibodies

29. Findings:
• TSH low (always measure this)
• Free T4, free T3 elevated (measure one or both if TSH is low)
• Radioiodine uptake increased (excludes subacute thyroiditis and
allows Rx with radioiodine)
• Thyroid stimulating antibodies present (could measure instead of
RAIU)
• Antithyroid (anti-TPO and Tg) antibodies often present (generally
don’t measure)

31. Other biochemical changes:
• High calcium level:
• Increase bone turnover.
• Low magnesium level:
• Increase excretion.
• Low LDL cholesterol:
• Increase lipolysis.
• High liver enzymes:
• Increase plasma transaminase, alkaline phosphatase

32. Treatment:
• Medical Therapy:
• Antithyroid drugs
• Methimazole, Propylthiouracil.
• Beta adrenergic blockers
• Iodide
• Radioiodine (I-131):
• Advantages: safe, outpatient, painless
• Disadvantages: slow, hypothyroidism, radiation

33. • Surgery:
• Subtotal thyroidectomy is highly effective.
• Advantages:
• Rapid (but must pre-treat with antithyroid drugs or β-blockers), may
not cause hypothyroidism
• Disadvantages:
• Inpatient surgery, general anesthesia, complications
(hypoparathyroidism, recurrent laryngeal nerve palsy)

34. Toxic multinodular goitre:
• Thyroid has multiple nodules, some of which may be too small to
palpate.
• Some of the nodules function autonomously.
• “Toxic” multinodular goiter signifies that the level of autonomous
function is sufficient to cause hyperthyroidism

35. • Shows all features of hyperthyroidism as mention earlier
• Generally the cause is not known, although some nodules have
activating mutations of the TSH receptor.
• Treat with radioiodine or surgery, as spontaneous remissions do not
occur.

37. Toxic adenoma:
• Less common cause of hyperthyroidism than Graves’ disease
• In most patients, the nodule produces too little thyroid hormone to
cause hyperthyroidism
• Generally must be >2.5 cm to cause clinical hyperthyroidism (“toxic
adenoma”)
• Constitutively activating mutations of the TSH receptor are causative
in many cases

38. • Lab findings are similar to Graves’ disease except TSI and anti-thyroid
Abs are negative.
• Spontaneous remissions are very rare.
• Thionamides will lower T4 and T3, but will not lead to cure.
• Therefore, preferred therapy is surgery or radioiodine.

40. Exogeneous Iodine ingestion
• Jod-Basedow Effect:
• Opposite of the Wolff-Chaikoff effect
• Excessive iodine loads induce hyperthyroidism
• Observed in hyperthyroid disease processes
Graves’ disease
Toxic multinodular goiter
Toxic adenoma
• This effect may lead to symptomatic thyrotoxicosis in patients who
receive large iodine doses from
Dietary changes
Contrast administration
Iodine containing medication ( Amiodarone )

41. Iodine containing medication ( Amiodarone )
• Amiodarone has a structure similar to that of thyroid hormones and inhibits
the peripheral conversion of T 4 to T 3 catalyzed by iodothyronine
deiodinase D1.
• Resulting concentrations of T4 may be high and T 3 low, with an increase in
rT 3.
• Thyroid stimulating hormone may rise transiently during the first few weeks
of treatment, but by four months, most patients who are euthyroid will have
normal or sometimes suppressed concentrations of TSH.
• The drug inhibits both iodine uptake by the thyroid and entry of T4 into cells
and can also cause both iodine-induced hypothyroidism and
hyperthyroidism.

42. Ectopic thyroid tissue.
• Metastatic thyroid follicular carcinoma may rarely produce sufficient
thyroid hormone to result in hyperthyroidism.
• Other tumors, such as ovarian teratomas, may contain functional thyroid
tissue in sufficient quantity to produce symptoms and signs of
thyrotoxicosis (struma ovarii).
• Endogenous thyroid radioisotope uptake will be suppressed and
functioning tissue demonstrable in the tumor under these most
uncommon circumstances.

43. HCG dependent
• Human chorionic gonadotropin (hCG)–induced hyperthyroidism is observed in
gestational transient thyrotoxicosis.
• hCG possesses intrinsic human thyroid stimulating activity
• So causes hyperthyroidism
• Usually occurs during pregnancy.
• TSH receptor sensitivity to appropriate hCG concentrations during pregnancy,
and hCG-secreting tumors.
• Gestational transient thyrotoxicosis occurs in 2 to 3% of all pregnancies, and
results from activation of TSH receptors by hCG, which is greatly elevated
during pregnancy.
• Trophoblastic tumours such as choriocarcinoma, hydatidiform mole and
metastatic embryonal testicular carcinoma may secrete human chorionic
gonadotrophin (hCG).
• The degree of hyperthyroidism is typically mild, and treatment is not usually
required.

44. Hashitoxicosis
• During the clinical course of Hashimoto thyroiditis, if a period of
accelerated destruction of thyroid follicular cells occurs, subsequent
release of thyroid hormone can produce a transient interval of
hyperthyroidism, termed Hashitoxicosis.
• Hashitoxicosis should be differentiated from Graves’ disease because
the treatments for these two conditions are different.
• Hashitoxicosis is self-limited
• TSIs are usually positive in patients with Graves’ disease and negative
in Hashitoxicosis.
• In addition, the RAIU is elevated in Graves’ disease but is not elevated
in Hashitoxicosis.

45. Postpartum Thyroiditis
• Patients with postpartum thyroiditis can experience a period of
transient, usually self-limited, hyperthyroidism from accelerated
breakdown of thyroid tissue.
• Subacute or acute thyroiditis can produce a period of transient
hyperthyroidism.

46. Central hyperthyroidism
• It is caused by pituitary adenomas and is rare condition
• It secrete TSH hormone excessively which causes hyperthyroidism.
• This diagnosis is suggested by
• Clinical hyperthyroidism,
• Elevated FT4
• Normal to elevated TSH concentration,
• Evidence of a pituitary mass on computed tomography (CT) scan or magnetic
resonance imaging (MRI).
• Hyperthyroidism is also caused when there is pituitary resistance to
thyroid hormone in feedback mechanism

47. T3 Toxicosis
• T3 toxicosis is defined by the presence of clinical hyperthyroidism in a
patient with suppressed TSH, normal FT4, and elevated T3 (or FT3).
• When a very mild excess of thyroid hormone is causing increased
thyroidal and peripheral deiodination of T4 to T3.
• D1 conversion of T4 to T3 is enhanced in hyperthyroidism.
• Raise in T3 occurs in contrast to T4
• T3 toxicosis is also possible
• when hyperthyroidism occurs in the presence of mild iodine deficiency
• when iodine is sufficient to synthesize excessive amounts of T3 but not T4.
• TSHR enhances the production of T3 more than T4.

48. Thyroid Storm:
• Medical Emergency
• Occurs in ~ 1% of pregnant pts with hyperthyroidism
• Thyroid storm is a decompensated state of thyroid hormone–induced,
severe hypermetabolism involving multiple systems and is the most
extreme state of thyrotoxicosis.
• The clinical picture relates to severely exaggerated effects of THs due to
increased release (with or without increased synthesis) or increased
intake of TH.
• Thyroid storm, also referred to as thyrotoxic crisis, is an acute,

49. • Life-threatening, hypermetabolic state induced by excessive release
of thyroid hormones (THs) in individuals with thyrotoxicosis.
• The clinical presentation includes fever, tachycardia, hypertension,
and neurological and GI abnormalities.
• Hypertension may be followed by congestive heart failure that is
associated with hypotension and shock.

50. •Thank you