Sterling Pc

Subclinical Hyperthyroidism

Cheryl P. Sterling, MD, MPH

VCU/MCV Hospitals

February 20, 2003

Case Presentation

48 yo Black female with well controlled HTN, h/o borderline hyperthyroidism

• No specific complaints or concerns

• Meds:– HCTZ for BP control

• FHx remarkable for HTN, DM, no other endocrine D/O’s, no known AIDz

• SHx unremarkable

Case Presentation

48 yo Black female with well-controlled HTN, h/o borderline hyperthyroidism

• ROS positive for low but normal appetite, no wgt loss, no signif fatigue

• Pap UTD • No prior BMD study

– Physical exam = nonobese female; no obvious features c/w hyperthyroid state

Case Presentation

LABS– WBC 6.0, Hgb 12.4,

Platelets 378

– BMP unremarkable except for Ca 8.9

– LFT’s wnl

– Fasting Lipid Profile• Chol 173, HDL 45

• TG 120, LDL 97

Serial thyroid testing– 11/00 TSH – 0.15– 3/01 TSH – 0.35– 7/01 TSH – 0.22– 9/02 TSH – 0.16– 2/03 TFT’s

• TSH - 0.21• Total T4 - 8.4• T3RU – 37.2%• FTI - 10

Clinical Question

Premenopausal female patient with hx of “borderline” hyperthyroidism, no obvious clinical signs nor subjective symptoms of thyroid hormone excess

What are the management options for this patient in your practice?

The Thyroid


- Characterized by the presence of low or undetectable plasma TSH concentration and normal circulating free thyroid hormones.

- Also referred to as mild hyperthyroidism- Exogenous vs. endogenous

Common Signs/Symptoms

FatigueWeight lossHeat intoleranceHyperhidrosisNervousness InsomniaMuscle weaknessHyperdefecation

TremorDyspneaPalpitationsMenstrual irregularityAnxiety IrritabilityExophthalmosLid lag or stare


GoiterExophthalmos

Etiology

Presage to overt hyperthyroidism– Early Graves’ disease– Multinodular goiter– Hashimoto’s

Thyroiditis – Subacute– Silent– Postpartum

Thyroid carcinoma

Iodine-associated hyperthyroidism – e.g. amiodarone

Solitary autonomous adenoma

Nonthyroidal illness Steroid or dopamine

administration Health food supplement

Shrier, D.K., Burman, K.D. American Family Physician, 2002; 65(3).

Biondi, B., et al. Journal of Clinical Endocrinology and Metabolism, 2000; 85(12):4701-4705.

Biochemical Assessment

Thyroid stimulating hormone (TSH):• Is the single most reliable test to diagnose thyroid

disease.• The assay is accurate, widely available, safe, and a

relatively inexpensive diagnostic test.

Also serum free and total T4, free and total T3.

• Free thyroxine index = indirect measure of free T4

• T3 resin uptake = indirect estimate of unsaturated binding sites on thyroxine binding globulin

Ladneson, et al. Arch Intern Med, 2000; 160: 1573-1575.

Supit, et al. South Med J, 2002; 95(5):481-485.

Diagnostic Assessment

Thyroid scan or radioactive iodine (123I) uptake

• “Hot” versus “Cold” nodule

Thyroid ultrasound• Anatomic abnormalities

– Does not reveal information regarding thyroid function

• Serial examination

Diagram of thyroid testing

www.medscape.com/viewarticle/433852

Evidence-based Research?

Detection and management of subclinical thyroid disorders– Small prospective, nonrandomized studies– Cross-sectional studies– Case reports– Meta-analyses– Subgroup analysis in Framingham study

Toft, A.D. New England Journal of Medicine, 2001; 345(7):512–516.


Short/Long-term Effects

Alteration in cardiac morphology and function– Cross-sectional studies demonstrating:

– Increased heart rate

– Increased LV mass

– Enhanced LV function

– Impaired diastolic filling

– Increased risk of atrial fibrillation and stroke in older patients



Adverse Effects

Alteration in bone metabolism– Postmenopausal women with subclinical

hyperthyroidism have increased bone loss

Neuropsychological effects– Reduced quality of life– Anxiety, depression– Increased risk of dementia, Alzheimer’s

diseaseBiondi, B., et al. Journal of Clinical Endocrinology and Metabolism, 2000; 85(12):4701-4705.

Kalmijn, S., Mehta, K.M., et al. Clinical Endocrinology (Oxf), 2000; 53: 733-737.

Journal Article

Subgroup analysis from Framingham Study– Prospective study w/10 yr follow-up

– Purpose – Is low serum thyrotropin in clinically euthyroid older persons a risk factor for subsequent atrial fibrillation?

– 2007 persons, age > 60 years

– 4 groups: • low, slightly low, normal, high thyrotropin levels

Sawin, C.T., Geller, A., et al. New England Journal of Medicine, 1994; 331(19): 1249-1252.

Results

Sawin, C.T., Geller, A., et al. New England Journal of Medicine, 1994; 331(19): 1249-1252.

Journal Article

Cross-sectional, case-control study in Italy– Purpose – Effects of endogenous subclinical

hyperthyroidism in the young and middle-aged

– 23 patients, 23 controls from areas of mild-moderate iodine deficiency

– Assessment of • Thyroid status

• S/sx of thyroid hormone excess and quality of life

• Cardiac morphology and function


Results


1. Multinodular goiter, solitary autonomous nodule; no antithyroid Ab’s; significant difference in free T3 and free T4 between groups

2. Higher mean SRS score in patients as well as lower SF-36 scores (r = -0.84, p = 0.008)

3. No ECG abnormality; Holter showed higher average HR (p < 0.001) and higher prevalence of APC’s in patients (p = ns)

4. Doppler echo showed increased PWT and IVST in patients as well as higher indices of LV systolic function

Conclusions

• Patients were affected by endogenous subclinical hyperthyroidism as evidenced by increased symptoms and impaired quality of life.

• Cardiac morphology and function affected by increased heart rate, LV mass, enhanced LV function and impaired diastolic filling

• Untreated endogenous subclinical hyperthyroidism may have untoward effects in young and middle-aged so consider early treatment.



Prevention of atrial fibrillation and osteoporosis are the main potential benefits

of treating subclinical hyperthyroidism.

Treatment options include:

- Beta-blockers

- Antithyroid medications

- Radioactive iodine (131I)

- Surgery

- Close clinical follow-up


Screening? Guidelines?

1. ATA (2000) recommends initial screen at age 35 with repeat testing every 5 years

2. RCP of London, ACP (1996, 1998) – no proven excess morbidity; women > 50 years

3. AACE – all women > age 35 and men over age 60

Toft, A.D. New England Journal of Medicine, 2001; 345(7):512–516.

Ladneson, et al. Arch Intern Med, 2000; 160: 1573-1575.

Helfand, M., Redfern, C.C. Annals of Internal Medicine, 15 July 1998. 129:141-143, 144-158.


- Individualize management

- Discuss benefits vs. risks

- Of each treatment option, e.g. periodic monitoring of CBC, LFT’s, TFT’s

- Financial considerations

- Drug interactions, potential toxicities

- Also consider potential issues of nonadherence


The Answer(To My Clinical Question)

Continue close observation with serial TFT’s, including total and free T3

Discuss with patient possible treatment options – Thyroid scan with RAIU

– Antithyroid medications, if necessary

Refer to endocrinology for management

References

Biondi, B., Palmieri, E.A., Fazio, S., et al. Endogenous Subclinical Hyperthyroidism Affects Quality of Life and Cardiac Morphology and Function in Young and Middle-Aged Patients. Journal of Clinical Endocrinology and Metabolism, 2000; 85(12):4701-4705.

Helfand, M., Redfern, C.C. Screening for Thyroid Disease: An Update (Parts 1 & 2). Annals of Internal Medicine, 15 July 1998. 129:141-143, 144-158.

Kalmijn, S., Mehta, K.M., Pols, H.A.P., Hofman, A., et al. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam Study. Clinical Endocrinology (Oxf), 2000; 53: 733-737.

Ladneson, et al. ATA guidelines for Detection of Thyroid Dysfunction. Archives of Internal Medicine, 2000; 160: 1573-1575.

Sawin, C.T., Geller, A., Wolf, P.A., Belanger, A.J., et al. Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons. New England Journal of Medicine, 1994; 331(19): 1249-1252.

References

Shrier, D.K., Burman, K.D. Subclinical Hyperthyroidism: Controversies in Management. American Family Physician, 2002; 65(3).

Supit, et al. Interpretation of Laboratory Thyroid Function Tests for the Primary Care Physician. Southern Medical Journal, 2002; 95(5):481-485.

Toft, A.D. Subclinical hyperthyroidism. New England Journal of Medicine, 2001; 345(7):512–516.

Utiger, R.D. Subclinical Hyperthyroidism – Just a Low Serum Thyrotropin Concentration, or Something More? New England Journal of Medicine, 1994; 331(19): 1302-1303.

Sterling Pc

Health & Medicine

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