Presentation is loading. Please wait.

Presentation is loading. Please wait.

Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders Anantha Harijith, MD Assistant Professor of Pediatrics University of Illinois, Chicago.

Similar presentations


Presentation on theme: "Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders Anantha Harijith, MD Assistant Professor of Pediatrics University of Illinois, Chicago."— Presentation transcript:

1 Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders Anantha Harijith, MD Assistant Professor of Pediatrics University of Illinois, Chicago

2 Case report Two month old male infant - recently migrated from Kabul. Parents worked as interpreters in the US embassy. Two month old male infant - recently migrated from Kabul. Parents worked as interpreters in the US embassy. Birth weight 3.1kg, Current weight 5.1kg-growing well Birth weight 3.1kg, Current weight 5.1kg-growing well Parents –happy, only complaint-baby passing stools once in 5-7days Parents –happy, only complaint-baby passing stools once in 5-7days no newborn screen report no newborn screen report

3 Case report Persistent jaundice, puffy coarse facies, large tongue, large anterior and posterior fontanelle, floppy, umbilical hernia, short arms, large pudgy hands Persistent jaundice, puffy coarse facies, large tongue, large anterior and posterior fontanelle, floppy, umbilical hernia, short arms, large pudgy hands Parents are extremely happy with the baby and want you to prescribe prune juice for constipation. They are confident that investigations are unnecessary. What will you do? Parents are extremely happy with the baby and want you to prescribe prune juice for constipation. They are confident that investigations are unnecessary. What will you do? Will you -Reassure the parents and see the patient again in two months OR will you investigate? Will you -Reassure the parents and see the patient again in two months OR will you investigate?

4 Knee & Skull XR- Knee & Skull XR- Our patient They agree for X rays but no blood tests What will you tell them? 1. X rays are normal and no further investigation needed now 2. Immediate blood tests are needed Another 2 month old healthy infant

5 Blood tests done! CBC Hematocrit 40%, WBC 9.8k, Platelet 202k CBC Hematocrit 40%, WBC 9.8k, Platelet 202k Serum Na141, K 4.6, Cl 105, HCO3- 25, Ca 9.8mg/dl Serum Na141, K 4.6, Cl 105, HCO3- 25, Ca 9.8mg/dl TSH-76 µIU/mL(Normal µIU/mL) TSH-76 µIU/mL(Normal µIU/mL) T4 and T3 – not detected T4 and T3 – not detected What is the diagnosis? What is the diagnosis?

6 Parathyroid glands

7

8 Thyroxine (T4, tetraiodothyronine) Liothyronine (T3, triiodothyronine) Iodinated diphenyl ether structure Built and stored on thyroglobulin >99% protein bound in plasma Only free form has physiologic effects T3 more potent; T4 longer lasting – Peripheral deiodination

9

10

11

12

13 HypothyroidEuthyroidHyperthyroid

14 Increases transcription (nuclear) Increases mitochondrial metabolism Net effects are target dependent – Oxygen consumption – Heat production – Metabolism, growth, differentiation – Promotes effects of hormones Steroids, catecholamines Physiological Effects

15 Congenital Hypothyroidism 1 in 4000 newborns 1 in 4000 newborns 90% Thyroid agenesis 90% Thyroid agenesis maternal T4 crosses the placenta, entering fetal blood well before the fetal thyroid is secreting its own T4 maternal T4 crosses the placenta, entering fetal blood well before the fetal thyroid is secreting its own T4 So early protection but in second trimester high demand for T4 not met by transfer- so signs of hypothyroidism sets in So early protection but in second trimester high demand for T4 not met by transfer- so signs of hypothyroidism sets in Treatment- T4 ie Thyroxine supplementation Treatment- T4 ie Thyroxine supplementation

16 Other causes -Primary -Primary Idiopathic Idiopathic Autoimmune Autoimmune Traumatic Traumatic Iatrogenic Iatrogenic-Secondary Pituitary dysfunction Pituitary dysfunction Increased protein binding Increased protein binding estrogen; HIV; liver dysfunction; heroinestrogen; HIV; liver dysfunction; heroin

17 Case Report 38 y/o computer professional lady reports over phone seeking an immediate appointment palpitations, tremulousness for 6 months palpitations, tremulousness for 6 months weight loss, heat intolerance of 12 weeks duration weight loss, heat intolerance of 12 weeks duration Menstrual periods have been scanty for 6months Menstrual periods have been scanty for 6months She used to be a regular in Chicago marathon until last year and wants to be tested for uterine problems because of lack of periods She used to be a regular in Chicago marathon until last year and wants to be tested for uterine problems because of lack of periods She is now walking into your office She is now walking into your office

18 PE reveals HR = 120 bpm HR = 120 bpm BP = 170/90 BP = 170/90 fine tremor of outstretched hands and fine tremor of outstretched hands and ….. …..

19 Lab reports free T4 = 40 pmol/L, free T3 = 10.6 pmol/L Lab reports free T4 = 40 pmol/L, free T3 = 10.6 pmol/L TSH – undetectable TSH – undetectable elevated thyroid-stimulating globulins confirming a Dx of ? elevated thyroid-stimulating globulins confirming a Dx of ?

20 Hyperthyroidism Causes – Grave’s disease (TSHR autoantibodies) 0.1% to 1% prevalence, higher in women – Thyroiditis – Toxic adenoma Non-pharmacologic treatments – Subtotal thyroidectomy – Radioiodine – Arterial embolization (2005)

21 Grave’s Disease

22 Pharmacologic Treatments Pharmacologic Treatments Thionamides (thiourelynes)Thionamides (thiourelynes) Hyperthyroidism Methimazole (Tapazole) – Typical dose 15 – 30 mg QD – Rapidly absorbed (Cmax < 2 hours) – Half-life 13 – 18 hours Propylthiouracil (PTU) – Typical dose 50– 600 mg BID – Good bioavailability – Half-life 2 – 4 hours – Blocks peripheral T4 -> T3 conversion

23 Thionamide MOA Coupling is also highly sensitive to drug

24

25 Rash/itch Fever Rarely: – Liver dysfunction – Leucocytopenia Thionamide Side Effects

26 Cooper DS. N Engl J Med 005;352:

27 Other Antithyroid Options Iodide loading Iodide loading High doses can inhibit iodide formationHigh doses can inhibit iodide formation Effect transientEffect transient May be useful prior to RAI or surgeryMay be useful prior to RAI or surgery Debulk and devascularize gland Debulk and devascularize gland Side effectsSide effects Rash, hypersalivation, oral ulcers Rash, hypersalivation, oral ulcers CI in pregnancy (may cause fetal goiter) CI in pregnancy (may cause fetal goiter)

28 Other Antithyroid Options Beta Blockers Beta Blockers Adjunctive treatmentAdjunctive treatment May reduce T4 -> T3 conversionMay reduce T4 -> T3 conversion Control HR and palpitations, sweatsControl HR and palpitations, sweats Rapid actionRapid action Corticosteriods Corticosteriods Reduce T4 -> T3 conversionReduce T4 -> T3 conversion May reduce TSHR antibody effect in Grave’sMay reduce TSHR antibody effect in Grave’s

29

30 Algorithm for the Use of Antithyroid Drugs among Patients with Graves' Disease.

31 Thyroid Storm Potentially life threatening Potentially life threatening Combined treatment strategy Combined treatment strategy High dose PTUHigh dose PTU Give 1 st ; iodide will reduce drug uptake in gland Give 1 st ; iodide will reduce drug uptake in gland Iodide loading (IV Lugol’s solution)Iodide loading (IV Lugol’s solution) Beta blockersBeta blockers CorticosteriodsCorticosteriods

32 Chief cells -Small dark numerous -produce Parathyroid hormone (PTH) Oxyphil cells -No known physiological function -May produce PTH related protein Parathyroid Basics

33 Parathyroid Hormone Parathyroid Hormone Small molecule (34 amino acids)Small molecule (34 amino acids) Activity based on amino terminalActivity based on amino terminal No disulfide linkagesNo disulfide linkages Encoded on chromosome 11Encoded on chromosome 11 Half-life only 2 – 4 minutesHalf-life only 2 – 4 minutes Secreted by chief cellsSecreted by chief cells

34 Case report A 17 year old male was admitted with history of generalized seizures for 8 years & involuntary movements for 2 months history of generalized seizures for 8 years & involuntary movements for 2 months short statured (138 cm),had hypoplastic dentition, thick dystrophic nails. short statured (138 cm),had hypoplastic dentition, thick dystrophic nails. The patient demonstrated tetany, a positive Chvostek's sign and generalized hyper-reflexia. Systemic examination was normal. The patient demonstrated tetany, a positive Chvostek's sign and generalized hyper-reflexia. Systemic examination was normal.

35 Labs: hypocalcaemia, hyperphosphataemia Labs: hypocalcaemia, hyperphosphataemia Eyes- Posterior subcapsular cataractCT Brain- basal ganglial calcification Dx: ?

36 Hypoparathyroidism Causes Causes Surgical (most common)Surgical (most common) IdiopathicIdiopathic Genetic familial forms Genetic familial forms Circulating receptor antibodies Circulating receptor antibodies FunctionalFunctional Due to hypomagnesemia Due to hypomagnesemia Mg2+ necessary for PTH releaseMg2+ necessary for PTH release

37 Hypoparathyroidism Decreased bone resorption & osteocytic activity Decreased bone resorption & osteocytic activity Hypocalcemia Hypocalcemia Increased neuromuscular excitabilityIncreased neuromuscular excitability Tetanic muscle contractions/spasmsTetanic muscle contractions/spasms SeizureSeizure Prolonged QT intervalProlonged QT interval CataractCataract Trousseau SignTrousseau Sign Chvostek SignChvostek Sign Low or absent iPTH Low or absent iPTH

38 Psuedohypoparathyroidism Target organs resistant to PTH Target organs resistant to PTH Congential defect of PTHR1Congential defect of PTHR1 Plasma Ca2+ low Plasma Ca2+ low Plasma phosphate high Plasma phosphate high Renal phosphatase activity high Renal phosphatase activity high

39 Hypoparathyroidism Maintenance Treatment Maintenance Treatment Combined oral calcium + Vitamin DCombined oral calcium + Vitamin D Phosphate restriction may be usedPhosphate restriction may be used Acute Treatment Acute Treatment Tetany or Hungry Bone SyndromeTetany or Hungry Bone Syndrome Parenteral calcium followed by vitamin D supp + oral calcium Parenteral calcium followed by vitamin D supp + oral calcium

40 Hyperparathyroidism Primary Primary Excess PTH high calcium, low phosphateExcess PTH high calcium, low phosphate Tumor, adenoma, hyperplasia Tumor, adenoma, hyperplasia More common in womenMore common in women Marrow fibrosisMarrow fibrosis Osteitis fibrosa cysticaOsteitis fibrosa cystica Metabolic acidosisMetabolic acidosis Increased Alk PhosIncreased Alk Phos Kidney stonesKidney stones

41 Hyperparathyroidism Primary – Diagnosis Primary – Diagnosis Multiple elevated Ca2+ serum testsMultiple elevated Ca2+ serum tests Elevated iPTHElevated iPTH Alk Phos typically lowAlk Phos typically low Corticosteroid suppression testCorticosteroid suppression test Prednisolone reduces serum Ca2+ Prednisolone reduces serum Ca2+ Indicates non-parathyroid originIndicates non-parathyroid origin Sarcoid, vitamin D intoxication, etc. Sarcoid, vitamin D intoxication, etc.

42 Hyperparathyroidism Treatment Treatment Acute Severe formsAcute Severe forms Adequate hydration, forced diuresis Adequate hydration, forced diuresis Other AgentsOther Agents Corticosteroids – Blood malignancies Corticosteroids – Blood malignancies Mythramycin Mythramycin Toxic antibiotic used to inhibit bone resorption – hematologic and solid neoplasmsToxic antibiotic used to inhibit bone resorption – hematologic and solid neoplasms

43 Hyperparathyroidism Treatment Treatment Other AgentsOther Agents Calcitonin Calcitonin Inhibits osteoclast activity and bone resorptionInhibits osteoclast activity and bone resorption Biphosphonates Biphosphonates Given IV or orally to reduce bone resorptionGiven IV or orally to reduce bone resorption Estrogen Estrogen Can be given to postmenopausal women with 1° hyperparathyroidism as medical therapyCan be given to postmenopausal women with 1° hyperparathyroidism as medical therapy

44 Hyperparathyroidism Treatment Treatment SurgerySurgery Definitive treatment Definitive treatment

45 2° Hyperparathyroidism Adaptive & unrelated to intrinsic disease of glands Adaptive & unrelated to intrinsic disease of glands Due to chronic stimulation of glands by low serum Ca2+ levels Due to chronic stimulation of glands by low serum Ca2+ levels

46 2° Hyperparathyroidism Causes Causes Dietary deficiency of vitamin D or Ca 2 +Dietary deficiency of vitamin D or Ca 2 + Decreased intestinal absorption of vitamin D or Ca 2 +Decreased intestinal absorption of vitamin D or Ca 2 + Drugs such as phenytoin, phenobarbitalDrugs such as phenytoin, phenobarbital Renal FailureRenal Failure Decreased activation of vitamin D3 Decreased activation of vitamin D3 HypomagnesemiaHypomagnesemia


Download ppt "Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders Anantha Harijith, MD Assistant Professor of Pediatrics University of Illinois, Chicago."

Similar presentations


Ads by Google