Presentation on theme: "Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders"— Presentation transcript:
1 Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders Anantha Harijith, MDAssistant Professor of PediatricsUniversity of Illinois, Chicago
2 Case reportTwo 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 wellParents –happy, only complaint-baby passing stools once in 5-7daysno newborn screen report
3 Case reportPersistent jaundice, puffy coarse facies, large tongue, large anterior and posterior fontanelle, floppy, umbilical hernia, short arms, large pudgy handsParents 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?
4 Knee & Skull XR- They agree for X rays but no blood tests Another 2 month oldhealthy infantOur patientWhat will you tell them?1. X rays are normal and no further investigation needed now2. Immediate blood tests are needed
5 Blood tests done! CBC Hematocrit 40%, WBC 9.8k, Platelet 202k Serum Na141, K 4.6, Cl 105, HCO3- 25, Ca 9.8mg/dlTSH-76 µIU/mL(Normal µIU/mL)T4 and T3 – not detectedWhat is the diagnosis?
8 Thyroxine (T4, tetraiodothyronine) Liothyronine (T3, triiodothyronine) Iodinated diphenyl ether structureBuilt and stored on thyroglobulin>99% protein bound in plasmaOnly free form has physiologic effectsT3 more potent; T4 longer lastingPeripheral deiodination
14 Physiological Effects Increases transcription (nuclear)Increases mitochondrial metabolismNet effects are target dependentOxygen consumptionHeat productionMetabolism, growth, differentiationPromotes effects of hormonesSteroids, catecholamines
15 Congenital Hypothyroidism 1 in 4000 newborns90% Thyroid agenesismaternal T4 crosses the placenta, entering fetal blood well before the fetal thyroid is secreting its own T4So early protection but in second trimester high demand for T4 not met by transfer- so signs of hypothyroidism sets inTreatment- T4 ie Thyroxine supplementation
16 Other causes -Primary -Secondary Idiopathic Autoimmune Traumatic Iatrogenic-SecondaryPituitary dysfunctionIncreased protein bindingestrogen; HIV; liver dysfunction; heroin
17 Case Report38 y/o computer professional lady reports over phone seeking an immediate appointmentpalpitations, tremulousness for 6 monthsweight loss, heat intolerance of 12 weeks durationMenstrual periods have been scanty for 6monthsShe used to be a regular in Chicago marathon until last year and wants to be tested for uterine problems because of lack of periodsShe is now walking into your office
18 PE revealsHR = 120 bpmBP = 170/90fine tremor of outstretched hands and...…..
19 Lab reports free T4 = 40 pmol/L, free T3 = 10.6 pmol/L TSH – undetectableelevated thyroid-stimulating globulins confirming a Dx of ?
20 Hyperthyroidism Causes Non-pharmacologic treatments Grave’s disease (TSHR autoantibodies)0.1% to 1% prevalence, higher in womenThyroiditisToxic adenomaNon-pharmacologic treatmentsSubtotal thyroidectomyRadioiodineArterial embolization (2005)
27 Other Antithyroid Options Iodide loadingHigh doses can inhibit iodide formationEffect transientMay be useful prior to RAI or surgeryDebulk and devascularize glandSide effectsRash, hypersalivation, oral ulcersCI in pregnancy (may cause fetal goiter)
28 Other Antithyroid Options Beta BlockersAdjunctive treatmentMay reduce T4 -> T3 conversionControl HR and palpitations, sweatsRapid actionCorticosteriodsReduce T4 -> T3 conversionMay reduce TSHR antibody effect in Grave’sContraindicated in asthma or reactive airways disease.28
30 Algorithm for the Use of Antithyroid Drugs among Patients with Graves' Disease. Figure 4. Algorithm for the Use of Antithyroid Drugs among Patients with Graves' Disease. Antithyroid drugs are an option for initial therapy in adults with mild-to-moderate hyperthyroidism or active ophthalmopathy and are the therapy of choice for children, adolescents, and pregnant or lactating women. Radioiodine may be preferable as initial therapy for adults in the United States1 but not for those in the rest of the world. 2 Subtotal or near-total thyroidectomy is also an option for some patients after treatment with antithyroid drugs. In adults who have a relapse, definitive radioiodine therapy is the preferred strategy. Some patients prefer a second course of antithyroid-drug therapy, and this strategy is preferable for children and adolescents. CBC denotes complete blood count.
31 Thyroid Storm Potentially life threatening Combined treatment strategy High dose PTUGive 1st; iodide will reduce drug uptake in glandIodide loading (IV Lugol’s solution)Beta blockersCorticosteriods
32 Parathyroid Basics Chief cells -Small dark numerous -produce Parathyroid hormone (PTH)Oxyphil cells-No known physiological function-May produce PTH related protein
33 Parathyroid Basics Parathyroid Hormone Small molecule (34 amino acids) Activity based on amino terminalNo disulfide linkagesEncoded on chromosome 11Half-life only 2 – 4 minutesSecreted 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 monthsshort 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.
36 Hypoparathyroidism Causes Surgical (most common) Idiopathic Functional Genetic familial formsCirculating receptor antibodiesFunctionalDue to hypomagnesemiaMg2+ necessary for PTH release
37 Hypoparathyroidism Decreased bone resorption & osteocytic activity HypocalcemiaIncreased neuromuscular excitabilityTetanic muscle contractions/spasmsSeizureProlonged QT intervalCataractTrousseau SignChvostek SignLow or absent iPTH
38 Psuedohypoparathyroidism Target organs resistant to PTHCongential defect of PTHR1Plasma Ca2+ lowPlasma phosphate highRenal phosphatase activity high
39 Hypoparathyroidism Maintenance Treatment Acute Treatment Combined oral calcium + Vitamin DPhosphate restriction may be usedAcute TreatmentTetany or Hungry Bone SyndromeParenteral calcium followed by vitamin D supp + oral calcium
40 Hyperparathyroidism Primary Excess PTH high calcium, low phosphate Tumor, adenoma, hyperplasiaMore common in womenMarrow fibrosisOsteitis fibrosa cysticaMetabolic acidosisIncreased Alk PhosKidney stones
41 Hyperparathyroidism Primary – Diagnosis Multiple elevated Ca2+ serum testsElevated iPTHAlk Phos typically lowCorticosteroid suppression testPrednisolone reduces serum Ca2+Indicates non-parathyroid originSarcoid, vitamin D intoxication, etc.
42 Hyperparathyroidism Treatment Acute Severe forms Other Agents Adequate hydration, forced diuresisOther AgentsCorticosteroids – Blood malignanciesMythramycinToxic antibiotic used to inhibit bone resorption – hematologic and solid neoplasms
43 Hyperparathyroidism Treatment Other Agents Calcitonin Biphosphonates Inhibits osteoclast activity and bone resorptionBiphosphonatesGiven IV or orally to reduce bone resorptionEstrogenCan be given to postmenopausal women with 1° hyperparathyroidism as medical therapy
45 2° Hyperparathyroidism Adaptive & unrelated to intrinsic disease of glandsDue to chronic stimulation of glands by low serum Ca2+ levels
46 2° Hyperparathyroidism CausesDietary deficiency of vitamin D or Ca2+Decreased intestinal absorption of vitamin D or Ca2+Drugs such as phenytoin, phenobarbitalRenal FailureDecreased activation of vitamin D3Hypomagnesemia