Pharmacotherapeutic approach to Thyroid
and Parathyroid Disorders
Anantha Harijith, MD
Assistant Professor of Pediatrics
University of Illinois, Chicago
Case report
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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
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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
They agree for X rays but no blood tests
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Knee & Skull XR-
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
Blood tests done!
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CBC Hematocrit 40%, WBC 9.8k,
Platelet 202k
Serum Na141, K 4.6, Cl 105, HCO325, 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)
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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
Physiological Effects
• Increases transcription (nuclear)
• Increases mitochondrial metabolism
• Net effects are target dependent
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Oxygen consumption
Heat production
Metabolism, growth, differentiation
Promotes effects of hormones
• Steroids, catecholamines
Congenital Hypothyroidism
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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 transferso signs of hypothyroidism sets in
Treatment- T4 ie Thyroxine
supplementation
Other causes
-Primary
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Idiopathic
Autoimmune
Traumatic
Iatrogenic
-Secondary
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Pituitary dysfunction
Increased protein binding
• estrogen; HIV; liver dysfunction; heroin
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
PE reveals
 HR = 120 bpm
 BP = 170/90
 fine tremor of
outstretched hands
and
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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
Hyperthyroidism
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Pharmacologic Treatments
• Thionamides (thiourelynes)
• Methimazole (Tapazole)
– Typical dose 15 – 30 mg QD
– Rapidly absorbed (Cmax < 2 hours)
– Half-life 13 – 18 hours
• Propylthiouracil (PTU)
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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
Thionamide Side Effects
• Rash/itch
• Fever
• Rarely:
– Liver dysfunction
– Leucocytopenia
Cooper DS. N Engl J Med
005;352:905-917.
Other Antithyroid Options
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Iodide loading
• High doses can inhibit iodide formation
• Effect transient
• May be useful prior to RAI or surgery
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Debulk and devascularize gland
• Side effects
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Rash, hypersalivation, oral ulcers
CI in pregnancy (may cause fetal goiter)
Other Antithyroid Options
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Beta Blockers
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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
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Potentially life threatening
Combined treatment strategy
• High dose PTU
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Give 1st; iodide will reduce drug uptake in gland
• Iodide loading (IV Lugol’s solution)
• Beta blockers
• Corticosteriods
Parathyroid Basics
Chief cells
-Small dark numerous
-produce Parathyroid hormone (PTH)
Oxyphil cells
-No known physiological function
-May produce PTH related protein
Parathyroid Basics
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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 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.
Labs: hypocalcaemia,
Eyes-hyperphosphataemia
Posterior subcapsular cataract
CT Brain- basal ganglial calcification
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Dx: ?
Hypoparathyroidism
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Causes
• Surgical (most common)
• Idiopathic
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Genetic familial forms
Circulating receptor antibodies
• Functional
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Due to hypomagnesemia
• Mg2+ necessary for PTH release
Hypoparathyroidism
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Decreased bone resorption & osteocytic activity
Hypocalcemia
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Increased neuromuscular excitability
Tetanic muscle contractions/spasms
Seizure
Prolonged QT interval
Cataract
Trousseau Sign
Chvostek Sign
Low or absent iPTH
Psuedohypoparathyroidism
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Target organs resistant to PTH
• Congential defect of PTHR1
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Plasma Ca2+ low
Plasma phosphate high
Renal phosphatase activity high
Hypoparathyroidism
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Maintenance Treatment
• Combined oral calcium + Vitamin D
• Phosphate restriction may be used
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Acute Treatment
• Tetany or Hungry Bone Syndrome
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Parenteral calcium followed by vitamin D
supp + oral calcium
Hyperparathyroidism
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Primary
•Excess PTH
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high calcium, low phosphate
Tumor, adenoma, hyperplasia
•More common in women
•Marrow fibrosis
•Osteitis fibrosa cystica
•Metabolic acidosis
•Increased Alk Phos
•Kidney stones
Hyperparathyroidism
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Primary – Diagnosis
• Multiple elevated Ca2+ serum tests
• Elevated iPTH
• Alk Phos typically low
• Corticosteroid suppression test
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Prednisolone reduces serum Ca2+
• Indicates non-parathyroid origin
 Sarcoid, vitamin D intoxication, etc.
Hyperparathyroidism
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Treatment
• Acute Severe forms
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Adequate hydration, forced diuresis
• Other Agents
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Corticosteroids – Blood malignancies
Mythramycin
• Toxic antibiotic used to inhibit bone resorption –
hematologic and solid neoplasms
Hyperparathyroidism
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Treatment
• Other Agents
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Calcitonin
• Inhibits osteoclast activity and bone resorption
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Biphosphonates
• Given IV or orally to reduce bone resorption
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Estrogen
• Can be given to postmenopausal women with 1°
hyperparathyroidism as medical therapy
Hyperparathyroidism
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Treatment
• Surgery
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Definitive treatment
2° Hyperparathyroidism
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Adaptive & unrelated to intrinsic
disease of glands
Due to chronic stimulation of glands
by low serum Ca2+ levels
2° Hyperparathyroidism
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Causes
• Dietary deficiency of vitamin D or Ca2+
• Decreased intestinal absorption of vitamin D
or Ca2+
• Drugs such as phenytoin, phenobarbital
• Renal Failure
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Decreased activation of vitamin D3
• Hypomagnesemia