Course:PHAR501/Thyroid Therapeutics

Thyroid Therapeutics
PHAR 501
Section:
Instructor:	Dr. Peter Loewen
Email:	peter.loewen@ubc.ca
Office:	PHRM 6624
Office Hours:
Class Schedule:
Classroom:
Important Course Pages
	Syllabus
	Lecture Notes
	Assignments
	Course Discussion

Pre-session Objectives

1. Be able to describe the physiology of thyroid function.
2. Be able to explain the biochemical parameters used to evaluate thyroid function.
3. Be able to describe the pathophysiology of the most common causes of hyper- and hypothyroidism.
4. Be able to name the signs and symptoms of hyper- and hypothyroidism.

Session Objectives

By the end of the the session and upon further study and reflection, students should be able to

1. identify and manage drug related-causes of hyper- and hypothyroidism.
2. rationalize a diagnosis of thyroid dysfunction on the basis of biochemical tests combined with signs and symptoms.
3. design, implement and monitor (for efficacy & toxicity) an effective pharmacotherapeutic plan for managing Graves’ disease, primary hypothyroidism, and drug-induced hypothyroidism.
4. explain to a patient the therapeutic implications of subclinical hyper- and hypothyroidism.

Prereadings

1. PL's Thyroid Physiology, Pharmacology, & Pharmacotherapy PLOP.
2. ASCE / ATA Clinical Practice Guidelines for Hypothyroidism in Adults Endocrine Practice 2012;18(6):989-1027.
3. Bahn RS, Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the ATA and AACE. Endocrine Practice. 2011;17:456–520.
4. Review the cases below

Preparatory self-assessment questions

1. The predominant hormone secreted by the thyroid gland is

a. Triiodothyronine

b. Tetraiodothyronine

c. Liothyronine

d. Parathyroid hormone

2. The metabolically active thyroid hormone, (________), is produced mainly (_________)

a. T3, in peripheral tissues

b. T4, in peripheral tissues

c. T3, in the thyroid

d. T4, in the thyroid

3. The most common cause of hypothyroidism in North America is

a. Iodine deficiency

b. Graves’ disease

c. Amiodarone

d. Autoimmune thyroiditis

4. The most common cause of hyperthyroidism in North America is

a. Iodine excess

b. Graves’ disease

c. Autoimmune thyroiditis

d. Toxic multinodular goitre

5. Which constellation of symptoms is most consistent with hyperthyroidism

a. Depression, constipation, ascites, bradycardia

b. Normocytic anemia, pleural effusion, menorrhagia, myalgia

c. Bradyphasia, eczema, proptosis, paresthesia

d. Thinning of hair, amenorrhea, osteoporosis, muscle weakness

Resources

• Levy M. How to interpret thyroid function tests. Clin Med 2013;13:282–6.

Hypothyroidism

• Nygaard B. Hypothyroidism (Primary). ClinicalEvidence 2010;01:605.
• Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med. 2010 Dec 13;170(22):1996-2003.
• McDermott MT. Hypothyroidism. Ann Intern Med. 2009; ITC6 (1DEC09)

Hyperthyroidism

• Bruere H, Fauchier L, Bernard Brunet A, et al. History of Thyroid Disorders in Relation to Clinical Outcomes in Atrial Fibrillation. Am J Med. 2015;128(1):30-37.
• Nygaard B. Hyperthyroidism (Primary). ClinicalEvidence 2010;07:611.
• Chiha M, Samarasinghe S, Kabaker AS. Thyroid Storm: An Updated Review. J Intensive Care Med 2013;
• Brent GA. Graves’ Disease. N Engl J Med 2008;358:2594-605.

Subclinical Thyroid Disorders

• Chaker L, van den Berg ME, Niemeijer MN, et al. Thyroid Function and Sudden Cardiac Death Circulation. 2016;134(10):713-722
• Hennessey, J. V., & Espaillat, R. Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature. Journal of the American Geriatrics Society, 2015:63(8), 1663–1673.
• Garg A, Vanderpump MPJ. Subclinical thyroid disease. British Medical Bulletin 2013;107:101–16.
• Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012;172(10):799-809
• Pham & Shaugnessy. Should we treat subclinical hypothyroidism? BMJ 2008;337:a834 doi:10.1136/bmj.a834

Hypothyroidism & Pregnancy

• Jouyandeh, Z., Hasani-Ranjbar, S., Qorbani, M., & Larijani, B. (2014). Universal screening versus selective case-based screening for thyroid disorders in pregnancy. Endocrine, 1–8.
• Maraka, S., O’Keeffe, D. T., & Montori, V. M. (2015). Subclinical Hypothyroidism During Pregnancy—Should You Expect This When You Are Expecting?: A Teachable Moment. JAMA Internal Medicine, 175(7), 1088.
• Nathan N, Sullivan SD. Thyroid disorders during pregnancy. Endocrinology and Metabolism Clinics of North America. 2014 Jun;43(2):573–97.
• Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014 Jun;3(2):76–94.
• Casey B, de Veciana M. Thyroid screening in pregnancy debate. Am J Obstet Gynecol. 2014 Aug 17.

Case 1

ID/CC: 74-year-old F was brought to the emergency room after being discovered unconscious by her daughter. Shortly after arrival, she had a generalized tonic clonic seizure.

HPI: The daughter reported that her mother had become senile during the past year, appearing to be withdrawn and uninterested in her surroundings. In recent weeks, she had experienced severe constipation and abdominal bloating and had become very unsteady on her feet.

PMH: Unremarkable.

MPTA: None.

O/E: In the emergency room, the patient could be aroused but was incoherent and disoriented. BP 170/110 mm Hg, pulse 50 bpm and regular, and rectal temperature 35°C. The skin was yellowish, dry, and coarse. The precordial pulse was not palpable; Rub apparent on heart auscultation. Shifting dullness on abdominal exam and pitting edema of the legs.

LABS/DIAGNOSTICS: Na 133 mmol/L, SCr 203 mcmol/L. CSF normal. CT Head normal. CXR: bilateral pleural effusions, increased cardiothoracic ratio.

No diagnosis made.

During the night, the patient became delirious, and the intern ordered lorazepam 1 mg po. The next morning she could not be awakened.

A suspicion of hypothyroidism/myxedema coma arose.

 What signs and symptoms are consistent with hypothyroidism?

 What laboratory tests should be ordered to evaluate this hypothesis?

 What is your interpretation of these?

 What therapeutic options exist for managing this acute problem?  Design an acute and long-term plan for this patient.

Case 2

ID/CC: 74 y/o F presents to hospital with 24h history of severe abdominal pain, inability to sleep x 1 week, husband reports her “acting crazy”.

HPI: as above, except weight loss of 7kg over past 2 months.

PMH: Graves’ disease x 3 years. Rheumatoid arthritis. Cholecystectomy 5y ago.

MEDS: Naproxen 250 po bid, Pantoprazole 40mg PO qd. PharmaNet profile shows Propylthiouracil 100mg bid last filled 9 mos ago.

O/E: Appears agitated, obvious tremor, using accessory muscles. BP 170/95. HR 122. Temp 37.4. RR 30. Marked goitre. Marginal proptosis. Bowel sounds not audible. Chest auscultation: bibasilar crackles.

LABS/DIAGNOSTICS: HgB 98. SCr 145 mcmol/L. ECG: no p-waves, R-R instability. LFTs, BG, WBCs, normal. CXR not done.

The diagnostic suspicion is of thyrotoxicosis.

 What signs and symptoms are consistent with hyperthyroidism/thyrotoxicosis/”thyroid storm”?
 
 What laboratory tests should be ordered to evaluate this hypothesis?

 What is your interpretation of these?

 What therapeutic options exist for managing this acute problem?  Design an acute and long-term plan for this patient.

Case 3

In your primary care clinic today, your 71 y/o F patient whom you're evaluating for possible first-line therapy for her newly-diagnosed HTN shows you her myEhealthBC printout with a TSH of 7.0 and asks you what that means. How do you approach this?

Case 4

In your primary care clinic today, your 63 y/o M patient for whom you've just prescribed bisoprolol and rivaorxaban for CHADS2=3 AF, shows you his myEhealthBC printout with a TSH of 0.1 and asks you what that means. How do you approach this?