SLEEP AND THYROID ISSUES
Highlights from the Medical University of South Carolina’s 5th Annual Fall Symposium: Issues in Women’s Health
| SLEEP DISORDERS IN WOMEN —Robert Malcolm, MD, Professor of Psychiatry, Medical University of South
Carolina, Charleston
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| General considerations: sleep disorders more complex in women than in men; iron and ferritin metabolism and
transport in women more complex than in men; iron major factor in dopamine receptor sites in basal ganglion (part
of brain that controls involuntary movement); pregnancy and perimenopausal issues have significant impact on
sleep; affective and mood disorders affect sleep (more common in women than men); average human need for
sleep throughout life ≈8 hr/night; young healthy person falls asleep within ≈10 min; ≈50% of sleep occurs in stage
2 (increases with age) and ≈15% to 25% in stage 3 (deep slow wave; decreases with age); napping occurs at beginning
and end of life
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| Sleep disorders during pregnancy: first trimester—up to ≈12% in woman who does not have restless leg syndrome
(RLS); RLS—defined as persistent, compelling need to adjust legs in bed at night; more common in women
than in men; more common in pregnancy, even in women with no history of RLS; primary RLS probably genetic
disorder; increase in excessive daytime sleepiness often attributed to rise in progesterone; sleep duration increases
by 0.5 to 1 hr/night; slow-wave sleep decreases (reason unclear); decreased sleep efficiency (defined as total time
of sleep divided by total time in bed); second trimester—some women continue to have sleep disturbances and
some improve; third trimester—RLS prevalence 25%; increase in multiple awakenings, napping, back, pelvic, leg
pains, and gastroesophageal reflux disease; difficulty falling asleep and maintaining sleep; postdelivery—mean total
sleep time for average woman <6 hr per night; sleepiness awareness diminished after chronic sleep deprivation
over several days; increase in slow-wave sleep (greater for lactating women than nonlactating women); excessive
daytime sleepiness with napping way of compensating for lack of sleep efficiency at night; sleep hygiene
recommendations—go to bed and get up at same time (maintains circadian rhythm); avoid caffeine and alcohol;
sleep in cool environment with low humidity, noise, and light; sleep in lateral position with pillow support; reduce
fluid intake late in day
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| RLS in pregnancy: risk factors—<7 hr of sleep nightly, daytime napping, smoking, alcohol use, and medications (especially
antidepressants); recommendations—behavioral therapies poorly studied; ferritin level one of best biologic
measures that correlates with worsening of RLS; treat if serum ferritin <30 ng/mL; if warranted, prescribe oral
folate and iron (30 to 60 mg); aerobic exercise (promotes delta sleep, should not be done close to bedtime); stretching
and massaging before bedtime
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| Perimenopausal sleep difficulties: sleep-onset and sleep-maintenance insomnia; hormone replacement therapy (HRT)
improves hot flushes, but not always insomnia; mood difficulties, ie, dysphoria to major depressive disorder more
common; sleep behavioral habit; sleep disrupted by biologic factors; conditioned psychologic stimuli occur, causing
conditioned insomnia which becomes chronic and fixed over time; upper airway resistance—increases postmenopausally;
considered precursor to sleep apnea; look for sleep apnea in perimenopausal woman with metabolic syndrome
(waist diameter >35 in); consider sleep apnea even in slender postmenopausal woman who does not snore
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| Restless leg syndrome: unpleasant limb sensations with desire to move limbs; symptoms worse in evening or night;
symptoms can occur during day (severe form) as well as night; periodic limb movement disorder (PLMD)—
more common than RLS; most patients with PLMD have RLS, but not all patients with RLS have PLMD;
treatment—RLS and PLMD treated similarly; avoid medications that aggravate condition; avoid opiates; exercise
and stretching important interventions for RLS (less evidence that it improves PLMD)
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 | Medications: ropinirole (Requip) approved; levodopa decarboxylase inhibitors (levodopa/carbidopa [Sinemet]),
pergolide, pramipexole, and ropinirole recommended by American Academy of Sleep Medicine; 2003 warning
about association between pergolide and valvular heart disease (speaker does not recommend); speaker recommends
starting with 2.5-mg dose of ropinirole daily, slowly titrating to 3 mg daily; dopamine agonists associated
with nausea, vomiting, nasal stuffiness, sleepiness, and lethargy, even in low doses; if used, start low and go
slow; dosing can be at night only, bid, or tid; gabapentin, carbamazepine, and benzodiazepines effective in small
number of controlled trials; associated with drug interaction and tolerance; opiates associated with tolerance, dependence,
and addiction; speaker does not recommend
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| Newer hypnotics for insomnia: nonbenzodiazapines—act differently at γ-aminobutyric acid (GABA)-A receptor;
tend not to alter ratio of rapid eye movement (REM) to stage 1 to 4 sleep; lower abuse potential; fewer rebound effects
when discontinued; similar in cost to benzodiazepines; ramelteon (Rozerem)—melatonin-receptor agonist; effective
for sleep-onset insomnia; noncontrolled substance; approved for long-term use; not approved for sleep
maintenance; available in 8-mg dose; eszopiclone—approved for long-term use; approved for sleep onset and
sleep maintenance; available in 3 dosages
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| Other agents: temazepam (Restoril)—benzodiazepine hypnotic; trazodone—atypical antidepressant; not approved
for long-term use, sleep onset, or sleep maintenance; induces slow-wave sleep; long half-life can cause sleepiness
next day; zaleplon—approved for sleep onset only; nonbenzodiazepine; zolpidem CR—approved for long-term
use; approved for sleep onset; nonbenzodiazepine; not approved for sleep maintenance
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| THYROID FUNCTION TESTING AND REPLACEMENT THERAPY —William J. Hueston, MD, Chairman and
Professor of Family Medicine, Medical University of South Carolina, Charleston
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| Epidemiology: thyroid disorders affect 0.5% (1/200) adults; prevalence increases with age; 5% of patients in nursing
homes have thyroid disease; 10 times more common in women than in men; prevalence doubles every decade after
65 yr of age
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| Screening recommendations: American Thyroid Association—screen adults >35 yr of age every 5 yr; American
College of Physicians—screen women >50 yr of age; American Academy of Family Physicians—do not do routine
screening in patients <60 yr of age; United States Preventive Services Task Force—insufficient evidence to recommend
routine screening of otherwise healthy, asymptomatic adults; full recommendation at http://www.ahrq.gov/
clinic/3rduspstf/thyroid/thyrrs.htm
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| Elevated thyroxine (T4 ): most T4 protein-bound; T4 increases with higher serum protein levels, eg, pregnancy, adolescence,
estrogen use, birth control pills; triodothyronine (T3 ; more active of 2 thyroid hormones) 99.4% bound to
protein; check thyroid-stimulating hormone (TSH)—indicates whether T4 adequate; hypothyroidism—diagnosed
if T4 low and patient has functional pituitary; thyroid insensitivity—TSH and T4 high; rare; familial condition;
thyroid receptors inadequate; possible causes of hyperthyroidism—Graves’ disease (autoantibodies stimulating
thyroid to make more thyroid hormone), thyroiditis (inflammation of thyroid), or autonomous nodule producing T4
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| Thyroid imaging studies: indications—hyperthyroidism, nodular thyroid disease, or neck mass of unclear source;
radiolabeled thyroid scans—radioactive iodine decays quickly; 99 TcM preferred over 123 I thyroid scan; 99 TcM
can be used in patients on thyroid-suppressing drugs; look for diffuse increase or decrease in uptake or nodules;
nodules must be >1 cm in diameter to show up; Graves’ disease—diffuse increased uptake (entire gland more active);
thyroiditis—patchy decreased uptake (patient looks hyperthyroid, but gland not making much); nodular
disease—focal area of increased uptake with reduced uptake in remainder of gland
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| Thyroid antibodies: TSH receptors—can be helpful; usually seen in patients with Graves’ disease; thyroglobulin—
seen in autoimmune thyroid diseases; not very helpful; thyroid peroxidase—involved in Hashimoto’s thyroiditis;
rarely clinically useful; not helpful in indicating cause of hypothyroidism
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| Findings: hypothyroidism—do not perform work-up (does not matter what caused condition); just treat; nodules—
if thyroid function normal, start with fine-needle aspiration biopsy (FNAB); if thyroid function elevated, patient
may have hyperactive nodule; scan may help differentiate between adenoma (hot nodule) and nonactive mass (cold
nodule); hot nodules—hyperactive nodules; usually represent hypertrophic active thyroid, not cancer; treat by suppressing
with exogenous thyroid hormone; cold nodule—does not take up tracer; suspect malignancy; most cysts
or burned-out adenomas; follow-up ultrasonography useful in distinguishing colloidal cyst from solid and potentially
malignant cold nodule
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| Imaging tests: ultrasonography—useful for follow-up of cold nodules; distinguishes cystic from solid; uniform
solid masses usually burned out nodules; hypoechoic mass more likely carcinoma; computed tomography (CT)—
not good test for neck or thyroid gland; magnetic resonance imaging (MRI)—good resolution between thyroid,
lymph tissue, and muscle; excellent for evaluation of tumor spread or poorly defined neck mass
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| More on findings: hyperthyroidism—obtain work-up; hypothyroidism—Hashimoto’s thyroiditis most common
cause; increasing prevalence in United States; associated with lymphomas; suspect in patient presenting with hypothyroidism
for extended time and beginning to show “knots”; other causes include postirradiation hypothyroidism
(after Graves’ disease), postsurgical hypothyroidism, iodine insufficiency, and idiopathic hypothyroidism
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| Subclinical hypothyroidism (SCH): high TSH with normal T4 ; more common in white women; rare in women of
color and in men; increases with age; ≈50% of all patients have antithyroid antibodies; unclear whether variant of
normal, predisease state or actual disease; research flawed (most done on patients who have no thyroid, irradiated
thyroid, or have had previously treated hyperthyroidism); concern that patients may have elevated lipids and cardiovascular
disease; some patients appear to benefit from thyroid hormone replacement; is SCH predisease?—
≈10% of patients with SCH develop overt hypothyroidism within 3 yr; patients with positive thyroid antibodies
likely to become symptomatic; conservative management involves thyroid screening yearly for few years and testing
for thyroid antibodies; aggressive management indicated; is SCH normal variant?—data show no difference
between patients with SCH and euthyroid controls for lipids and inflammatory markers for cardiovascular disease;
Leyden 85-plus trial data showed 9% of patients had SCH; no baseline difference in performance, cognition, or depression
in patients with elevated TSH, compared to those with normal TSH, and no association with decline in
performance, cognition, or increased depression over 5 yr if initial TSH high; patients with SCH had less decline in
dependency on activities of daily living over time, compared to patients with normal TSH; people with SCH had
greater survival over 5-yr period than people with normal TSH; speaker less aggressive in managing patients with
SCH; treatment of SCH controversial; treat cautiously if patient symptomatic (overreplacement can provoke atrial
fibrillation and osteoporosis); diagnosis likely incorrect if symptoms do not improve
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| Thyroid hormone replacement: start low, go slow; 0.025 mg daily recommended for elderly patients and those with
possible cardiac disease; monitor TSH every 6 to 8 wk; increase dosage by 0.025 mg until patient euthyroid; average
person with nonfunctioning thyroid needs about 125 µg of thyroid hormone; small study showed equally good
results with bolus dosing once weekly with 7 times usual dose; T3 (Cytomel)—active form of thyroid hormone; observational
study of small group of elderly patients showed partial substitution of T4 with T3 may improve mood
and neuropsychologic functioning; 2 subsequent studies showed no benefit of adding T3 to T4 therapy; speaker
opines probably worth trying only in patients ≥70 yr of age); use slow-acting T3 agent; drug interaction—
increased thyroid hormone doses increase effects of warfarin (Coumadin) and vice versa; measure patient’s international
normalized ratio (INR) when changing thyroid dose or check TSH if putting patient on warfarin (Coumadin);
increased thyroid hormone increases need for glycemic agents; estrogens and hormone replacement therapy
(HRT) increase thyroid-hormone binding and need higher dose for thyroid replacement; clofibrate may decrease
hormone absorption
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Educational Objectives
| The goal of this program is to educate the listener about the management of sleep disorders in women and evaluation
and treatment of thyroid disease. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Discuss how sleep patterns change during pregnancy and counsel patients on sleep hygiene.
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| 2. Evaluate the patient with involuntary limb movements at night and prescribe appropriate medication.
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| 3. Decide if a patient should undergo thyroid screening.
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| 4. Diagnose and treat thyroid abnormalities.
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| 5. Identify patients with subclinical hypothyroidism and determine if treatment is appropriate.
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Discussed on This Program
Clofibrate [Atromid-S] (discontinued)
Eszopiclone [Lunesta]
Levothyroxine sodium (T4 ; L-thyroxine) [Levothroid, Levoxyl, Synthroid, Thyro-Tabs, Unithroid]
Liothyronine sodium (T3 ) [Cytomel, Triostat]
Pergolide mesylate [Permax]
Pramipexole [Mirapex]
Ramelteon [Rozerem]
Ropinirole HCl [Requip]
Levodopa and carbidopa [Duodopa, Sinemet-10/100, Sinemet-25/100, Sinemet-25/250, Sinemet CR]
Temazepam [Restoril]
Trazodone HCl [Desyrel, Desyrel Dividose]
Warfarin sodium [Coumadin]
Zaleplon [Sonata]
Zolpidem tartrate [Ambien]
Suggested Reading
Dzaja A et al: Women’s sleep in health and disease. J Psychiatry Rest 39(1):55, 2005; Helfand M et al: Clinical
guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med
129(2):144, 1998; Littner MR et al: Practice parameters for the dopaminergic treatment of restless legs syndrome
and periodic limb movement disorder. Sleep 27(3):557, 2004; Moline ML et al: Sleep in women across the life cycle
from adulthood through menopause. Sleep Med Rev 7(2):155, 2003; Pien GW et al: Sleep disorders during pregnancy.
27(7):1405, 2004; Shrier DK et al: Subclinical hyperthyroidism: controversies in management. Am Fam Physician
65(3):431, 2002; Trenkwalder C et al: The restless legs syndrome. Lancet Neurol 4(8):465, 2005; Wilson
GR et al: Subclinical thyroid disease. Am Fam Physician 72(8):1517, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the faculty reported nothing to disclose.
Drs. Malcolm and Hueston spoke at the 5th Annual Symposium: Issues in Women’s Health, on October 28-30, 2005,
in Charleston, South Carolina, and sponsored by the Medical University of South Carolina. The Audio-Digest Foundation
thanks the speakers and the sponsor for their cooperation in the production of this program.
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