Presentation is loading. Please wait.

Presentation is loading. Please wait.

Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders

Similar presentations


Presentation on theme: "Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders"— 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. Birth weight 3.1kg, Current weight 5.1kg-growing well Parents –happy, only complaint-baby passing stools once in 5-7days 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 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?

4 Knee & Skull XR- They agree for X rays but no blood tests
Another 2 month old healthy infant Our patient What will you tell them? 1. X rays are normal and no further investigation needed now 2. 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/dl TSH-76 µIU/mL(Normal µIU/mL) T4 and T3 – not detected 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 Hypothyroid Euthyroid Hyperthyroid

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

15 Congenital Hypothyroidism
1 in 4000 newborns 90% Thyroid agenesis 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 Treatment- T4 ie Thyroxine supplementation

16 Other causes -Primary -Secondary Idiopathic Autoimmune Traumatic
Iatrogenic -Secondary Pituitary dysfunction Increased protein binding estrogen; 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 weight loss, heat intolerance of 12 weeks duration 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 is now walking into your office

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

19 Lab reports free T4 = 40 pmol/L, free T3 = 10.6 pmol/L
TSH – undetectable elevated 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 women Thyroiditis Toxic adenoma Non-pharmacologic treatments Subtotal thyroidectomy Radioiodine Arterial embolization (2005)

21 Grave’s Disease

22 Hyperthyroidism Pharmacologic Treatments Thionamides (thiourelynes)
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 Thionamide Side Effects
Rash/itch Fever Rarely: Liver dysfunction Leucocytopenia

26 Cooper DS. N Engl J Med 005;352:905-917.

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

28 Other Antithyroid Options
Beta Blockers Adjunctive treatment May reduce T4 -> T3 conversion Control HR and palpitations, sweats Rapid action Corticosteriods Reduce T4 -> T3 conversion May reduce TSHR antibody effect in Grave’s Contraindicated in asthma or reactive airways disease. 28

29

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 PTU Give 1st; iodide will reduce drug uptake in gland Iodide loading (IV Lugol’s solution) Beta blockers Corticosteriods

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 terminal No disulfide linkages Encoded on chromosome 11 Half-life only 2 – 4 minutes Secreted 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 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.

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

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

37 Hypoparathyroidism Decreased bone resorption & osteocytic activity
Hypocalcemia Increased neuromuscular excitability Tetanic muscle contractions/spasms Seizure Prolonged QT interval Cataract Trousseau Sign Chvostek Sign Low or absent iPTH

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

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

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

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

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

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

44 Hyperparathyroidism Treatment Surgery Definitive treatment

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

46 2° Hyperparathyroidism
Causes Dietary deficiency of vitamin D or Ca2+ Decreased intestinal absorption of vitamin D or Ca2+ Drugs such as phenytoin, phenobarbital Renal Failure Decreased activation of vitamin D3 Hypomagnesemia


Download ppt "Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders"

Similar presentations


Ads by Google