Pharmacotherapeutic approach to Thyroid and Parathyroid Disorders
Anantha Harijith, MDAssistant Professor of Pediatrics
University of Illinois, Chicago
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
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?
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 now2. Immediate blood tests are needed
Another 2 month old healthy infant
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(Normal0.5 - 4.70 µIU/mL)
T4 and T3 – not detected What is the diagnosis?
Parathyroid glands
• 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
Hypothyroid Euthyroid Hyperthyroid
• 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
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
Other causes
-Primary Idiopathic Autoimmune Traumatic Iatrogenic
-Secondary Pituitary dysfunction Increased protein binding
• estrogen; HIV; liver dysfunction; heroin
Case Report38 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
PE reveals HR = 120 bpm BP = 170/90 fine tremor of
outstretched hands and
... …..
Lab reports free T4 = 40 pmol/L, free T3 = 10.6 pmol/L
TSH – undetectable elevated thyroid-stimulating
globulins confirming a Dx of ?
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)
Grave’s Disease
Pharmacologic Treatments• 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
Thionamide MOA
Coupling is also highly sensitive to drug
• Rash/itch• Fever• Rarely:
– Liver dysfunction– Leucocytopenia
Thionamide Side Effects
Cooper DS. N Engl J Med 005;352:905-917.
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)
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
Algorithm for the Use of Antithyroid Drugs among Patients with Graves' Disease.
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
Chief cells-Small dark numerous -produce Parathyroid hormone (PTH)
Oxyphil cells -No known physiological function-May produce PTH related protein
Parathyroid Basics
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
Case reportA 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.
Labs: hypocalcaemia, hyperphosphataemiaEyes- Posterior subcapsular cataract CT Brain- basal ganglial calcification
Dx: ?
Hypoparathyroidism
Causes• Surgical (most common)• Idiopathic
Genetic familial forms Circulating receptor antibodies
• Functional Due to hypomagnesemia
• Mg2+ necessary for PTH release
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
Psuedohypoparathyroidism
Target organs resistant to PTH• Congential defect of PTHR1
Plasma Ca2+ low Plasma phosphate high Renal phosphatase activity high
Hypoparathyroidism
Maintenance 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
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
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.
Hyperparathyroidism
Treatment• Acute Severe forms
Adequate hydration, forced diuresis• Other Agents
Corticosteroids – Blood malignancies Mythramycin
• Toxic antibiotic used to inhibit bone resorption – hematologic and solid neoplasms
Hyperparathyroidism
Treatment• Other Agents
Calcitonin• 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
Hyperparathyroidism
Treatment• Surgery
Definitive treatment
2° Hyperparathyroidism
Adaptive & unrelated to intrinsic disease of glands
Due to chronic stimulation of glands by low serum Ca2+ levels
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