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THYROID FUNCTIONS AND
DISORDERS
By
Dr. Basil, B. C – MBBS (Nig),
Department of Chemical Pathology/Metabolic Medicine,
Benu...
OUTLINE:
• Introduction
• Anatomy
• Hormone synthesis/secretion
• Metabolism/Mechanism of action
• Functions and Control
•...
INTRODUCTION:
• The thyroid gland – largest single endocrine
gland in the body (15 – 20g)
• Produces the Thyroid hormones ...
ANATOMY
• Consist of 2 lobes and a central isthmus –
anterior to the trachea (shaped like a bow-tie)
• Posteriorly – parat...
HORMONE SYNTHESIS / SECRETION
• Thyroid hormone synthesis includes the
following steps:
– Iodide (I-
) trapping via Na-I-
...
HORMONE SYNTHESIS / SECRETION
• Steps contd:
– Combination of two DIT molecules to form T4 or
of MIT and DIT to form T3
– ...
HORMONE SYNTHESIS / SECRETION
HORMONE SYNTHESIS / SECRETION
• T4 & T3 Circulate predominantly (>99%) bound to
serum proteins
– Thyroxine binding globuli...
HORMONE SYNTHESIS / SECRETION
STRUCTURE OF THYROID HORMONES
METABOLISM
• 100nm of T4, 5nm each T3 and rT3 secreted daily
• T3 – active form; T4 – prehormone; rT3 –
metabolically inac...
MECHANISM OF ACTION
• T4 dissociates with its carrier protein and
diffuse though cellular membrane into the
cytosol where ...
MECHANISM OF ACTION
FUNCTIONS
• General metabolism:
– Increase the metabolic rate and oxygen consumption
of most of tissues of the body (excep...
FUNCTIONS
• Growth and Development:
– Essential for normal growth of soft tissue and
skeleton
– Required for production & ...
FUNCTIONS
• Cardiovascular:
– Increase number & affinity of beta-1, adrenergic
receptors in the heart, also increase its s...
FUNCTIONS
• Gastrointestinal:
– Increase secretion of digestive juices and motility
>> increase appetite and food intake
–...
FUNCTIONS
• Nervous System:
– Promotes growth and development of the brain
(fetal life & for the first few years)
– Essent...
FUNCTIONS
• Carbohydrate metabolism:
– Increases the rate of absorption of CHO from GIT,
thus blood glucose level increase...
FUNCTIONS
• Protein metabolism:
– Small doses of thyroid hormone increase the rate
of formation of proteins by the ribosom...
FUNCTIONS
• Lipid metabolism:
– All aspects of fat metabolism increased
– Thyroid hormone accelerates the oxidation of
fat...
CONTROL OF THYROID FUNCTION
CONTROL OF THYROID FUNCTION
CONTROL OF THYROID FUNCTION
• TRH >> (+)TSH >> (+)T4/T3 >> (-)TSH/TRH
• T4 released by the thyroid is mostly converted
to ...
CONTROL OF THYROID FUNCTION
• TSH/Thyrotropin – Primary Regulation
– Glycoprotein hormone
– Made up two units α and β (2 d...
CONTROL OF THYROID FUNCTION
• Actions of TSH:
– Increased proteolysis of the thyroglobulin (occurs
within minutes)
– Incre...
DISORDERS OF THYROID
• Hyper-functioning states
– Overt
– Subclinical
• Hypo-functioning states
– Overt
– Subclinical
• Ot...
HYPER-FUNCTIONING STATES:
• Definitions:
– Thyrotoxicosis: Hypermetabolic state produced
due an excess of thyroid hormones...
Causes:
• Primary hyperthyroidism:
– Graves’ disease (Diffuse toxic non-nodular goitre)
– Toxic multinodular goiter(Plumme...
Causes:
• Thyrotoxicosis without Hyperthyroidism:
– Subacute thyroiditis
– Silent thyroiditis
– Other causes of thyroid de...
Causes:
• Secondary hyperthyroidism:
– TSH-secreting pituitary adenoma
– Chorionic gonadotropin-secreting tumours e.g
Trop...
HYPER-FUNCTIONING STATES:
• Grave’s disease:
– accounts for more than 60% of all thyrotoxicosis
– diffuse glandular hyperp...
HYPER-FUNCTIONING STATES:
• Multi-nodular goiter:
– multiple nodules, maybe polyclonal or monoclonal in
origin
– usually d...
Biochemical findings:
• In primary hyperthyroidism – T4 and T3 are elevated,
while TSH is suppressed to undetectable
conce...
HYPOFUNCTIONING STATES
• Primary Hypothyroidism:
– Autoimmune hypothyroidism: Hashimoto’s
thyroiditis, atrophic thyroiditi...
Causes:
• Transient Hypothyroidism:
– Silent thyroiditis
– Subacute thyroiditis
– Withdrawal of thyroxine treatment in ind...
Causes:
• Secondary hypothyroidsm:
– Hypopituitarism: tumours, pituitary surgery or
irradiation,
– Infiltrative disorders,...
HYPOFUNCTIONING STATES
• Iodine deficiency:
– Commonest cause of worldwide
– Responsible for endemic goiter and cretinism ...
HYPOFUNCTIONING STATES
• Congenital hypothyroidism
– thyroid agenesis
– inborn errors of thyroid hormone synthesis
– TSH-R...
HYPOFUNCTIONING STATE
• Peripheral Resistance to Thyroid Hormones:
– The most common cause of the syndrome are
mutations o...
HYPOFUNCTIONING STATES
• Myxedema is a severe form of hypothyroidism in
which there is accumulation of mucopolysacchrides
...
Biochemical Findings:
• Primary hypothyroidism:
– Low T4 and T3 lead to pituitary hypersecretion
evidenced by elevated ser...
Biochemical Findings:
• Secondary hypothyroidism:
– Serum concentration of thyroid hormone is low,
but TSH is either low o...
OTHER DISORDERS
• Non-Thyroidal Illnesses/Sick Euthyroid Syndrome
– Any acute or chronic severe illness causing
abnormalit...
OTHER DISORDERS
• Biochemical Findings in Non-Thyroidal Illness/
Euthyrois sick syndrome:
– Low serum T3 level
– High seru...
OTHER DISORDERS
Thyroid Malignancies – 4 types:
• Papillary carcinoma (PC):
– Well differentiated, very good prognosis; 90...
OTHER DISORDERS
Thyroid Neoplasia:
•Solitary Thyroid Nodules:
– As many as 50% of these are benign
– Occasionally, thyroid...
OTHER DISORDERS
• Biochemical findings in Euthyroid Hyper-
thyroxinaemia:
– Serum total T4 level is high
– Serum T3, TSH a...
BIOCHEMICAL SCREENING AND
EVALUATION OF THYROID DISEASE
• NEONATAL SCREENING:
• When to screen:
– Normal hospital delivery...
BIOCHEMICAL SCREENING
Type of Screening:
•Primary TSH + Backup T4
– May miss:
• TBG deficiency
• Hypothalamic-pituitary Hy...
BIOCHEMICAL SCREENING
EVALUATION OF THYROID DISEASE
• EVALUATION OF THYROID DISEASE:
• TSH:
– The most useful test for assessing thyroid functio...
EVALUATION OF THYROID DISEASE
  Low free T4 Normal free T4 High free t4
Low 
TSH
Secondary
hypothyroidism
Severe NTI
Subcl...
EVALUATION OF THYROID DISEASE
• Thyroglobulin:
– Ideal tumor marker for thyroid cancer patients and its
detection is a pro...
EVALUATION OF THYROID DISEASE
• Thyroid Autoimmunity:
– In autoimmune thyroid disease, antibodies are
directed at thyroid ...
EVALUATION OF THYROID DISEASE
• Thyroid Autoimmunity – contd
– Both stimulating and blocking antibody assays will
be posit...
EVALUATION OF THYROID DISEASE
• Urinary Iodine measurements
– Iodine essential for normal thyroid gland function
– Iodine ...
EVALUATION OF THYROID DISEASE
• OTHER TOOLS:
– Nuclear Medicine Evaluation – RAIU Assay
• High uptake – metabolically acti...
TREATMENT OF THYROIDAL DISEASES
HYPERTHYROIDISM:
•Use of beta-blockers for symptomatic relief:
– To be commenced after ora...
TREATMENT OF THYROIDAL DISEASES
• Use of radioactive iodine-131 (131 I) therapy:
– 5-7 mCi single dose 131l therapy; 1/3 w...
TREATMENT OF THYROIDAL DISEASES
• In thyroid crisis, treatment has to be aggressive:
– Propranolol 1-2 mg slowly IV or 40-...
TREATMENT OF THYROIDAL DISEASES
HYPOTHYROIDISM:
•Use of Levothyroxine (LT4) for Thyroid hormone
replacement – treatment of...
TREATMENT OF THYROIDAL DISEASES
• In pregnant women with hypothyroidism, the LT4 dose
should be adjusted so as to keep the...
TREATMENT OF THYROIDAL DISEASES
• In patients with myxedema coma:
– Give 4 µg of LT4 per kilogram of lean body weight
(app...
REFERENCES
• Teitz Textbook of Clinical Chemistry and Molecular
Diagnostics; 5th ed., by Burtis et al
• Clinical Chemistry...
Thyroid functions and disorders presentation
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Thyroid functions and disorders presentation

summary of thyroid hormone synthesis, secretion, metabolism, regulation, disorders, biochemical screening/evaluation and treatment.

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Thyroid functions and disorders presentation

  1. 1. THYROID FUNCTIONS AND DISORDERS By Dr. Basil, B. C – MBBS (Nig), Department of Chemical Pathology/Metabolic Medicine, Benue State University Teaching Hospital, Makurdi. February 2016.
  2. 2. OUTLINE: • Introduction • Anatomy • Hormone synthesis/secretion • Metabolism/Mechanism of action • Functions and Control • Disorders and Biochemical findings • Biochemical Screening and Evaluation of thyroid disease • Treatment of Thyroidal Diseases • Reference.
  3. 3. INTRODUCTION: • The thyroid gland – largest single endocrine gland in the body (15 – 20g) • Produces the Thyroid hormones and Calcitonin • Thyroid hormones are critical in regulating body metabolism, neurologic, developmental and other body functions • Calcitonin involved in calcium homeostasis – see calcium and phosphate disorders.
  4. 4. ANATOMY • Consist of 2 lobes and a central isthmus – anterior to the trachea (shaped like a bow-tie) • Posteriorly – parathyroid glands • Originate from Ratke’s pouch at the base of the tongue at 4-8wks IUL, and secretes hormones by 11wk – critical to neurologic development • Consist of many small spherical follicles (functional unit) surrounded by basement membrane, containing colloid and interspersed by para-follicular C cells
  5. 5. HORMONE SYNTHESIS / SECRETION • Thyroid hormone synthesis includes the following steps: – Iodide (I- ) trapping via Na-I- symporter (active transport) by follicular cells (Rate limiting step) – Diffusion of iodide to the apex of the cell and transport into the colloid – Oxidation of inorganic iodide to iodine (by thyroperoxidase) and incorporation of iodine into tyrosine residues within the thyroglobulin molecule in the colloid
  6. 6. HORMONE SYNTHESIS / SECRETION • Steps contd: – Combination of two DIT molecules to form T4 or of MIT and DIT to form T3 – Uptake of thyroglobulin from the colloid into the follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4 and T3 – Release of T4 and T3 into the circulation – MIT and DIT are split into iodine and tyrosine, and recycled
  7. 7. HORMONE SYNTHESIS / SECRETION
  8. 8. HORMONE SYNTHESIS / SECRETION • T4 & T3 Circulate predominantly (>99%) bound to serum proteins – Thyroxine binding globulin (TBG) – 75% – Thyroxine binding prealbumin (TBPA) – 15% – Albumin – 10% • The bound hormone is not biologically active • Only 0.04% of T4 and 0.4% of T3 - free • Changes in the concentration of serum binding proteins alter the total, but not the free hormone levels
  9. 9. HORMONE SYNTHESIS / SECRETION
  10. 10. STRUCTURE OF THYROID HORMONES
  11. 11. METABOLISM • 100nm of T4, 5nm each T3 and rT3 secreted daily • T3 – active form; T4 – prehormone; rT3 – metabolically inactive; Thyroglobulin – prohormone. • T4 >> T3: outer ring 5’monodeiodination (80% of T3) by iodothyronine deiodinase (3 types) – inhibited by Propylthiourasil etc • Inner ring deiodination >> rT3 (3,3’,5’ triiodothyronine) • 10% T4 cleared: 80% deiodinated, 20% glucuronidation in liver and sulfation in liver and kidneys • Half-life: T4= 7days, T3=1 day
  12. 12. MECHANISM OF ACTION • T4 dissociates with its carrier protein and diffuse though cellular membrane into the cytosol where it is converted to T3 by deiodinase enzyme • T3 binds with Nuclear receptor protein >> Hormone-Receptor protein complex >> binds to the hormone receptor element (or Thyroid Response Element) on the DNA >> initiation of transcription and protein synthesis
  13. 13. MECHANISM OF ACTION
  14. 14. FUNCTIONS • General metabolism: – Increase the metabolic rate and oxygen consumption of most of tissues of the body (exceptions include testes, uterus, lymph nodes, anterior pituitary) – Increase synthesis and activity of many intracellular enzymes e.g. Na+ -K+ ATPase utilizes energy, increase heat production – Increase the size, number & activity of mitochondria >> increase the rate of formation of ATP to energise cellular function
  15. 15. FUNCTIONS • Growth and Development: – Essential for normal growth of soft tissue and skeleton – Required for production & action of growth hormones and IGF • Respiration: – Increased respiration due to increased rate – Dissociation of oxygen from hemoglobin by increasing the amount of 2,3 DPG in RBC
  16. 16. FUNCTIONS • Cardiovascular: – Increase number & affinity of beta-1, adrenergic receptors in the heart, also increase its sensitivity to catecholamine – Increases rate of blood flow in the skin for heat elimination – Increased cardiac output >> ↑systolic BP, but ↓ diastolic blood pressure thus >> ↑ pulse pressure
  17. 17. FUNCTIONS • Gastrointestinal: – Increase secretion of digestive juices and motility >> increase appetite and food intake – Necessary for the hepatic conversion of carotene to Vit.A, so if thyroid hormones are decreased, carotenaemia result • Reproduction: – Essential for normal menstrual cycles and fertility – Increase milk secretion in lactating women
  18. 18. FUNCTIONS • Nervous System: – Promotes growth and development of the brain (fetal life & for the first few years) – Essential for normal myelination & development of the nervous system in infant – Increased response of the brain to catecholamines & increases activation of RAS
  19. 19. FUNCTIONS • Carbohydrate metabolism: – Increases the rate of absorption of CHO from GIT, thus blood glucose level increases after meal but fall again as rate of glucose utilization is also increased – Enhance gluconeogenesis & glycolysis – Increases cell metabolic enzymes acting on CHO
  20. 20. FUNCTIONS • Protein metabolism: – Small doses of thyroid hormone increase the rate of formation of proteins by the ribosomes – It increase RNA synthesis by the genes – Large doses of thyroid hormone lead to excess catabolism of muscle protein
  21. 21. FUNCTIONS • Lipid metabolism: – All aspects of fat metabolism increased – Thyroid hormone accelerates the oxidation of fatty acids by the cells – Lowers level of cholesterol, phospholipid & tryglycerides in the blood – Stimulate formation of LDL receptors
  22. 22. CONTROL OF THYROID FUNCTION
  23. 23. CONTROL OF THYROID FUNCTION
  24. 24. CONTROL OF THYROID FUNCTION • TRH >> (+)TSH >> (+)T4/T3 >> (-)TSH/TRH • T4 released by the thyroid is mostly converted to T3 by the liver and kidney by type 1 iodothyronine 5’-deiodinase • Type 2 iodothyronine 5’-deiodinase found in the brain and pituitary maintain constant levels of T3 in the CNS
  25. 25. CONTROL OF THYROID FUNCTION • TSH/Thyrotropin – Primary Regulation – Glycoprotein hormone – Made up two units α and β (2 different chromosomes) – α subunit is identical to that of LH, FSH, hCG – β subunit confers specificity – t½ is 60 minutes – Acts via the TSH receptor – G protein coupled (7 transmembrane domain)
  26. 26. CONTROL OF THYROID FUNCTION • Actions of TSH: – Increased proteolysis of the thyroglobulin (occurs within minutes) – Increased activity of the iodide pump – Increased iodination of tyrosine – Increased size and increased secretory activity of the thyroid cells – Increased number of thyroid cells
  27. 27. DISORDERS OF THYROID • Hyper-functioning states – Overt – Subclinical • Hypo-functioning states – Overt – Subclinical • Others – Inflammatory – Neoplastic disease – Non-thyroidal illnesses (Euthyroid Sick Syndrome) – Euthyroid hyperthyroxinaemia
  28. 28. HYPER-FUNCTIONING STATES: • Definitions: – Thyrotoxicosis: Hypermetabolic state produced due an excess of thyroid hormones – Hyperthyroidism: Hypermetabolic state due to an excessive activity of the thyroid gland – Hyperthyroidism is a cause of thyrotoxicosis but Thyrotoxicosis is not always as a result of hyperthyroidism • Women are more prone to develop hyper- thyroidism than men
  29. 29. Causes: • Primary hyperthyroidism: – Graves’ disease (Diffuse toxic non-nodular goitre) – Toxic multinodular goiter(Plummer disease) – Toxic adenoma – Functioning thyroid carcinoma metastases – Activating mutation of the TSH receptor – Activating mutation of G (McCune-Albright syndrome) – Struma ovarii – Drugs: iodine excess (Jod-Basedow phenomenon)
  30. 30. Causes: • Thyrotoxicosis without Hyperthyroidism: – Subacute thyroiditis – Silent thyroiditis – Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma – Ingestion of excess thyroid hormone (thyrotoxicosis factitia)
  31. 31. Causes: • Secondary hyperthyroidism: – TSH-secreting pituitary adenoma – Chorionic gonadotropin-secreting tumours e.g Trophoblastic tumor (Hydatidform mole) – Gestational thyrotoxicosis
  32. 32. HYPER-FUNCTIONING STATES: • Grave’s disease: – accounts for more than 60% of all thyrotoxicosis – diffuse glandular hyperplasia – 10 times more common in women – Autoimmune basis: thyroid stimulating immunoglobulins (TSI) that bind to the TSH-Receptor • Toxic Adenoma: – solitary hyper-functioning nodules – acquired somatic activating mutations in the TSH-R. which induce constitutive receptor coupling to Gs – clinical features are milder than above
  33. 33. HYPER-FUNCTIONING STATES: • Multi-nodular goiter: – multiple nodules, maybe polyclonal or monoclonal in origin – usually do not have TSH-R mutations – may present with subclinical or mild thyrotoxicosis • Subacute Thyroiditis (De Quervain’s, Bacterial, Granulomatous, or Viral thyroiditis): – follicular destruction releases thyroid hormones – later phase may be hypothyroid, with depletion of thyroid hormones
  34. 34. Biochemical findings: • In primary hyperthyroidism – T4 and T3 are elevated, while TSH is suppressed to undetectable concentrations • Secondary hyperthyroidism is characterized by elevated levels of TSH, free T4 and/or free T3 levels. • T3 concentration is often elevated to a greater degree than is T4 in the early stages of Graves’ disease and in patients with T3 thyrotoxicosis (solitary or multinodular toxic goiters) • In subclinical hyperthyroidism, there is normal concentration of serum T3 and FT4 and persistently suppressed serum TSH
  35. 35. HYPOFUNCTIONING STATES • Primary Hypothyroidism: – Autoimmune hypothyroidism: Hashimoto’s thyroiditis, atrophic thyroiditis – Iatrogenic: 131 I treatment, subtotal or total thyroidectomy, – External irradiation of neck for lymphoma or cancer – Drugs: antithyroid drugs, amiodarone, lithium – Congenital hypothyroidism – Iodine deficiency – Infiltrative disorders
  36. 36. Causes: • Transient Hypothyroidism: – Silent thyroiditis – Subacute thyroiditis – Withdrawal of thyroxine treatment in individual with an intact thyroid – After 131 I treatment or subtotal thyroidectomy for Graves’ disease
  37. 37. Causes: • Secondary hypothyroidsm: – Hypopituitarism: tumours, pituitary surgery or irradiation, – Infiltrative disorders, Sheehan’s syndrome, trauma – Isolated TSH deficiency or inactivity – Hypothalamic disease: tumours, trauma, infiltrative disorders, – Idiopathic – Drugs: Dopamine, Corticosteroids – Congenital TRH deficiency (rare)
  38. 38. HYPOFUNCTIONING STATES • Iodine deficiency: – Commonest cause of worldwide – Responsible for endemic goiter and cretinism (mental and growth retardation in children) – Incidence also impacted by thiocynates in cassava and selenium deficiency • Hashimoto’s thyroiditis: – Autoimmune based disease – Destruction of thyroid cell by CD8+ cytotoxic T cells – Antibody markers include Anti TPO, TG and TSH-R blocking Ab – Clinical course: subclinical (or mild) to clinical (or overt)
  39. 39. HYPOFUNCTIONING STATES • Congenital hypothyroidism – thyroid agenesis – inborn errors of thyroid hormone synthesis – TSH-R mediated • Iatrogenic – Radio iodine therapy – Subtotal/total thyroidectomy • Pituitary disease (Secondary hypothyroidism)
  40. 40. HYPOFUNCTIONING STATE • Peripheral Resistance to Thyroid Hormones: – The most common cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor – Mutations in MCT8 and SECISBP2 have also been associated with this condition – Also referred to as impaired sensitivity to thyroid hormone
  41. 41. HYPOFUNCTIONING STATES • Myxedema is a severe form of hypothyroidism in which there is accumulation of mucopolysacchrides in the skin and other tissues, leading to thickening of facial features and a doughy induration of the skin • Cretinism is the term used to describe severe hypothyroidism that develops in the newborn period • Congenital hypothyroidism: may be as a result of a complete absence of thyroid gland (athyreosis) or defects in thyroid hormone synthesis, which can lead to irreversible neurological damage without early treatment
  42. 42. Biochemical Findings: • Primary hypothyroidism: – Low T4 and T3 lead to pituitary hypersecretion evidenced by elevated serum TSH concentration an important finding particularly in early detection of thyroid failure – In mild or subclinical cases, thyroid hormone concentrations remain within the reference range but TSH is elevated. – Presence of a circulating autoantibodies especially TPOAb in serum
  43. 43. Biochemical Findings: • Secondary hypothyroidism: – Serum concentration of thyroid hormone is low, but TSH is either low or within the healthy reference interval • Peripheral resistance to thyroid hormones: – T4 and T3 are elevated but TSH is not suppressed (or not as suppressed as expected)
  44. 44. OTHER DISORDERS • Non-Thyroidal Illnesses/Sick Euthyroid Syndrome – Any acute or chronic severe illness causing abnormalities in circulating TSH or thyroid hormone levels in the absence of underlying thyroid disease. – Reduced T4 ->T3 conversion but normal/increased rT3 – Importance is because of misleading information from thyroid testing during periods of acute illness. – Unless a thyroid disorder is strongly suspected, routine testing of thyroid function should be avoided in acutely ill patients
  45. 45. OTHER DISORDERS • Biochemical Findings in Non-Thyroidal Illness/ Euthyrois sick syndrome: – Low serum T3 level – High serum rT3 level – Normal or Low serum T4 levels – If serum TBG levels are low, serum T4 would be low – Serum TSH levels are usually normal, but may show mild depression during acute phase and mild elevation during recovery phase
  46. 46. OTHER DISORDERS Thyroid Malignancies – 4 types: • Papillary carcinoma (PC): – Well differentiated, very good prognosis; 90% 20 year survival post treatment. •Follicular carcinoma (FC): – Well differentiated, very good prognosis; 90% 20 year survival post treatment. •Medullary carcinoma of thyroid (MCT): – Poorly differntiated. 50% 10 year survival – High calcitonin is a marker •Anaplastic carcinoma: – Poorly differentiated. Mortality approaches 100%
  47. 47. OTHER DISORDERS Thyroid Neoplasia: •Solitary Thyroid Nodules: – As many as 50% of these are benign – Occasionally, thyroid nodules can take on characteristics of malignancy and require either a needle biopsy or surgical excision
  48. 48. OTHER DISORDERS • Biochemical findings in Euthyroid Hyper- thyroxinaemia: – Serum total T4 level is high – Serum T3, TSH and TRH response are normal • FT4 level compares well with the functional condition of the thyroid than Total T4 • Causes: Bisalbuninaemia, increase oestrogen, pregnancy, liver disease, acutely hospitalized psychiatric pxt, familial dysalbuminaemia
  49. 49. BIOCHEMICAL SCREENING AND EVALUATION OF THYROID DISEASE • NEONATAL SCREENING: • When to screen: – Normal hospital delivery at term – (filter-paper collection ideally at 2 – 4days of age or at the time of discharge) – NICU/Preterm home birth – (within 7days of birth) – Maternal history of Thyroid medication/family history of Congenital hypothyroidism – (cord blood for screening)
  50. 50. BIOCHEMICAL SCREENING Type of Screening: •Primary TSH + Backup T4 – May miss: • TBG deficiency • Hypothalamic-pituitary Hypothyroidism • Hypothyroxinemia with delayed TSH elevation – For better sensitivity – use sensitive TSH assay and age adjusted TSH cutoff (20 – 25mU/L at 24hr of age) •Primary T4 + Backup TSH: – Will miss delayed TSH elevation with initial normal T4 •Primary T4 and TSH: – Ideal screening approach
  51. 51. BIOCHEMICAL SCREENING
  52. 52. EVALUATION OF THYROID DISEASE • EVALUATION OF THYROID DISEASE: • TSH: – The most useful test for assessing thyroid function – Used to monitor and adjust thyroid hormone replacement therapy as well as screen for both hyperthyroidism and hypothyroidism – Have been deployed in the management of subclinical thyroid disease – For pregnant women with previously diagnosed hypothyroidism, serum TSH levels should be measured every 3-4 weeks during the first half of pregnancy and every 6-10 weeks thereafter
  53. 53. EVALUATION OF THYROID DISEASE   Low free T4 Normal free T4 High free t4 Low  TSH Secondary hypothyroidism Severe NTI Subclinical hyperthyroidism NTI Hyperthyroidism Normal  TSH Secondary hypothyroidism Severe NTI Normal Artifact Pituitary hyperthyroidism Lab draw within 6hrs of thyroxine dose High  TSH Primary hypothyroidism Subclinical Hypothyroidism Test artifact Pituitary hyperthyroidism Thyroid hormone resistance
  54. 54. EVALUATION OF THYROID DISEASE • Thyroglobulin: – Ideal tumor marker for thyroid cancer patients and its detection is a proof of thyroid tissue either benign or malignant – The accuracy of the assay is primarily dependent on the specificity of the antibody used and the absence of antithyroglobulin autoantibodies which interfere with measurements – Its prevalence is noted to be 3% of the general population, 12 – 30% of patients with Graves’ disease, and 35 – 60% with Autoimmune hypothyroidism
  55. 55. EVALUATION OF THYROID DISEASE • Thyroid Autoimmunity: – In autoimmune thyroid disease, antibodies are directed at thyroid tissue with variable responses – In Graves’ disease (the most common cause of hyperthyroidism), the antibody is directed to the TSH receptor, stimulating it and leading to growth of the thyroid gland and production of an excess amount of thyroid hormone – Tests for TSH receptor antibodies detect any antibody (stimulating or blocking) against TSH receptor
  56. 56. EVALUATION OF THYROID DISEASE • Thyroid Autoimmunity – contd – Both stimulating and blocking antibody assays will be positive in most patient with Graves’ disease – In Hashimoto’s thyroiditis, Thyroid peroxidase antibody mediate decreased thyroid hormone production
  57. 57. EVALUATION OF THYROID DISEASE • Urinary Iodine measurements – Iodine essential for normal thyroid gland function – Iodine deficiency responsible for endemic goitre and cretinism – Majority of ingested iodine is excreted in the urine – Only reflects recent dietary pattern – Major use is for epidemiologic purposes – Use 24 hour urine sample
  58. 58. EVALUATION OF THYROID DISEASE • OTHER TOOLS: – Nuclear Medicine Evaluation – RAIU Assay • High uptake – metabolically active gland • Concurrent TSH assay done • Low uptake - – Thyroid Ultrasound – detects very small nodules – Fine-Needle Aspiration Biopsy – first step and most accurate tool in the evaluation of thyroid nodules
  59. 59. TREATMENT OF THYROIDAL DISEASES HYPERTHYROIDISM: •Use of beta-blockers for symptomatic relief: – To be commenced after oral rehydration if necessary, and avoided in known asthmatics – If beta-blockers are contraindicated or poorly tolerated, calcium channel blockers (verapramil or diltiazem) can be administered •Use of anti-thyroid drugs(e.g Carbimazole, Methimazole, Propylthiouracil): – Carbimazole, initial dose 30-40mg/day; maintainance 15-20 mg/day – Preferred in younger age group, especially children – More useful in Small diffuse gland and mild disease and in cases of expected remission, especially immunological background – Therapy needs to be continued up to 12 months. Remission rate is 40-50%
  60. 60. TREATMENT OF THYROIDAL DISEASES • Use of radioactive iodine-131 (131 I) therapy: – 5-7 mCi single dose 131l therapy; 1/3 will require a second dose – Recommended for more than 35 years of age and in cases of Severe thyrotoxicosis, Systemic illness that prevents other methods of treatment and Recurrence after antithyroid drugs, surgery or radioablation – There is minimal risk involved; symptoms abate in 3 weeks to 3 months • Surgical approach (thyroidectomy): – Subtotal thyroidectomy (leave 2-3 g of tissue; prepare suitably with antithyroid drugs) is preferred in cases where there is • Large size of gland • Multinodularity • Pressure symptoms • Retrosternal goiter
  61. 61. TREATMENT OF THYROIDAL DISEASES • In thyroid crisis, treatment has to be aggressive: – Propranolol 1-2 mg slowly IV or 40-80 mg orally is the first step. This can be repeated 6 hourly. – Appropriate sedation by phenobarbitone may relieve anxiety. Barbiturates retard the peripheral deiodination of the hormone – Thyroid hormone release can be inhibited by IV iodine in the form of sodium iodide 1 g IV in 24 hours or by oral Lugol’s iodine 5 drops every 6 hours. Drugs such as amiodarone can be used as well. – This is followed by thionamide or thiouracil administration in regular dosage. – Corticosteroids (especially dexamethasone) are indicated if there is slightest suspicion of limitation of the adrenocortical reserve – Fluid and electrolyte balance should be adequately corrected.
  62. 62. TREATMENT OF THYROIDAL DISEASES HYPOTHYROIDISM: •Use of Levothyroxine (LT4) for Thyroid hormone replacement – treatment of choice: – Started as full replacement in young individuals but in the elderly and those with IHD, treatment with quarter to half the required dose is initiated and raised gradually over 4-6wks – For mild to moderate conditions, starting dose is about 50-75µg/day – Clinical benefits begin btw 3-5days and level off after 4- 6wks but TSH take several months to get to target range due to delayed re-adaptation of the hypothalamic- pituitary axis – In central hypothyroidism, T4 levels are used to guide treatment instead of TSH levels
  63. 63. TREATMENT OF THYROIDAL DISEASES • In pregnant women with hypothyroidism, the LT4 dose should be adjusted so as to keep the serum TSH below 2.5 mIU/L. TSH and free T4 levels should be measured 3- 4 weeks after every dosage adjustment. • In subclinical hypothyroidism, guidelines from the American Association of Clinical Endocrinologists (AACE) recommend treatment in patients with TSH levels higher than 10 mIU/L and in patients with TSH levels of 5-10 mIU/L in conjunction with goiter or positive anti-TPO antibodies; – These patients have the highest rates of progression to overt hypothyroidism. – An initial LT4 dosage of 50-75 µg/day can be used, which can be titrated every 6-8 weeks to achieve a target TSH of between 0.3 and 3 mIU/L
  64. 64. TREATMENT OF THYROIDAL DISEASES • In patients with myxedema coma: – Give 4 µg of LT4 per kilogram of lean body weight (approximately 200-250 µg) as an IV bolus in a single or divided dose, depending on the patient’s risk of cardiac disease – 24 hours later, give 100 µg IV – Subsequently, give 50 µg/day IV, along with stress doses of IV glucocorticoid • Adjust the dosage on the basis of clinical and laboratory findings
  65. 65. REFERENCES • Teitz Textbook of Clinical Chemistry and Molecular Diagnostics; 5th ed., by Burtis et al • Clinical Chemistry – Principles, Techniques and Correlations, 7th ed., by Micheal L. Bishop et al. • Thyroid Function and Disorders; Abuja Revision Course, NPMCN, Feb 2016, by Christian Ogoegbunem Isichie. • Robbins and Cotran - Pathologic Basis of Disease 7th ed., by Kumar et al. • Bolarin’s Aids to Chemical Pathology, New ed., by Debayo M. Bolarin • Clinical Chemistry and Metabolic Medicine, 7th ed., by Martin Crook. • Clinical Chemistry in Diagnosis and Treatment, 6th ed., by Philip D. Mayne

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