ENDOCRINE DISORDERS
| THYROID DYSFUNCTION IN THE ELDERLY —Allan Marks, MD, Associate Professor of Medicine, Section of Endocrinology,
Temple University, School of Medicine, Philadelphia
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| Changes in thyroid function with aging: most elderly people retain normal levorotatory thyroxine (T4 ), triiodothyronine
(T3 ), and thyroid-stimulating hormone (TSH) levels; basal metabolic rate (BMR) remains unchanged; thyroid gland tends to
become more nodular; TSH slightly elevated (5-10 µIU/mL) in 15% of people >60 yr of age; ≈50% with elevated TSH have
decreased T4 levels (primary hypothyroidism), and ≈50% with elevated TSH have normal T4 levels (subclinical hypothyroidism)
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| Causes of hypothyroidism in elderly: chronic lymphocytic thyroiditis—Hashimoto’s disease; look for elevations in antiperoxidase
thyroid antibodies or antimicrosomal antibodies; 7% to 25% of elderly have high antibody titers and elevated
TSH; history of Graves’ disease—>50% of patients treated for Graves’ disease who developed hypothyroidism
received radioactive iodine; 25% underwent subtotal thyroidectomy; 6% to 20% received thiourea drugs (eg, methimazole
[Tapazole], propylthiouracil [PTU])
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| Diagnosis: difficult because many manifestations of hypothyroidism can be attributed to aging, and concomitant illnesses
or medications may blunt presentation
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| Overt primary hypothyroidism: TSH elevated, but free T4 and free T4 indices low; levothyroxine (T4; L-thyroxine)—
give 25 to 50 µg daily; use maintenance dose 10% to 20% less than that used in younger patients, because older patients
at greater risk for arrhythmias, angina, and heart failure
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| Subclinical hypothyroidism: TSH elevated, but free T4 or free T4 index normal; most likely disease of thyroid rather than
hypothalamus or pituitary; over time, T4 level drops and TSH begins to rise; as T4 level nears subnormal range, TSH already
elevated; clinical course—subclinical hypothyroidism can persist for long time; TSH can drop to normal; some
patients progress to overt hypothyroidism; 5% per year of antibody-negative patients become overtly hypothyroid; 1 of 5
patients with high (>1:1600) antibody titers become hypothyroid per year; follow patients closely; therapy—thyroid replacement
may relieve symptoms and prevent overt hypothyroidism; may improve abnormal metabolic parameters; may
increase left ventricular function; treat patients with high antibody titer (especially if TSH >10 µIU/mL); treat patients
with symptoms suggestive of hypothyroidism; literature suggests against lowering TSH level in elderly patients to that of
younger patients (eg, TSH in younger patients 1.0-2.5 µIU/mL, but TSH level of 4.0-6.0 µIU/mL in elderly patients acceptable),
because people have less morbidity and mortality with TSH levels in upper range of normal, compared to
lower TSH levels
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| Hyperthyroidism: younger patients—Graves’ disease (often with infiltrative eye changes); palpable nodule with diffuse
enlargement; symptoms include nervousness, sweating, palpitation, tremor; weight loss or weight gain; older patients—
multiple hypersecreting hyperplastic nodules; single hot adenoma in thyroid; nodular disease may not be palpably
present; eye changes uncommon unless patient has Graves’ disease; present with supraventricular tachycardia or atrial fibrillation;
apathetic presentation; patient may fall into thyroid storm that resembles coma; anorexia; treatment—
radioactive iodine targets hot areas; Tapazole or PTU can be given before radioactive iodine to prevent radiation thyroiditis
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| Thyroid cancer: papillary and follicular cancer common in younger and older patients; anaplastic thyroid carcinoma—
occurs in 4% to 6% of patients with thyroid cancer; rapidly growing and invasive mass in neck with poor prognosis; lymphoma
of thyroid—more likely to occur in elderly patients; rapidly growing hard rubbery mass in thyroid
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| Nodules: risk for benign multinodular goiter increases with age; single palpable nodule seen in 1% to 2% of younger patients,
≥5% of elderly; prevalence of cancer in elderly patients with palpable nodules 5% to 10%
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| Ruling out cancer: fine needle aspiration biopsy; benign findings—observe patient and consider thyroid hormone to suppress
goiter size; indeterminate or suspicious findings or follicular neoplasm—perform radionuclide scanning; if nodules
hot, evaluate for hyperthyroidism; surgery indicated if nodule warm or cold; malignant findings—refer to surgeon
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| Screening for thyroid disease: consider checking TSH of all patients >60 yr of age; screen women >50 yr of age, patients
admitted to geriatric facility with multiorgan problems, and patients with risk factors for thyroid disease; risk factors—
positive family history; personal history of thyroid disease; history of radiation treatment to head, neck, or chest; other
autoimmune diseases; advancing age; use of medications with known antithyroid effects (eg, lithium, amiodarone, iodine)
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| Hyperparathyroidism: systemic disorder caused by effect of chronic excess of parathyroid hormone (PTH) on target tissues
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| Parathyroid hormone: bone—affects osteoclasts and osteocytes; increases breakdown of bone matrix and releases hydroxyapatite
crystals, resulting in increased serum calcium; kidney—increases ability of distal tubule to reabsorb calcium;
causes loss of phosphorus into urine; gut—causes formation of transport protein for calcium that increases
transport of calcium from lumen of intestine through enterocyte and into bloodstream; role of PTH—if serum calcium
level drops, PTH cells respond by increasing skeletal, gut, and renal handling of calcium to raise serum calcium; 1,25-dihydroxyvitamin
D causes retention of phosphorus by kidney, but PTH causes loss of phosphorus; receptor on chief cells
of parathyroid gland and on distal tubules of kidney can sense small changes in free calcium levels and causes increase in
PTH secretion when free calcium drops
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| Classification of hyperparathyroidism: primary—autonomous hypersecretion of hormone; 75% to 80% of patients
have benign adenoma of ≥1 parathyroid gland, 18% to 20% have 4-gland hyperplasia, and ≈1% have adenocarcinoma of
chief cells of parathyroid gland; secondary—retained phosphates in patients with chronic renal failure results in reciprocal
drop in serum calcium; parathyroid gland responds by increasing PTH secretion; tertiary—prolonged secondary hyperparathyroidism;
parathyroid mass enlarges and serum calcium rises above normal; ectopic—high PTH and high
calcium levels rarely due to ectopic production in nonparathyroid malignancy; PTH-like peptide may be produced (differentiate
by checking for elevated PTH)
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| Causes of adenoma: genetic mutations (eg, monoclonal aberration); rearrangements of PTH gene; overexpression of parathyroid
adenoma 1 gene, resulting in conversion to oncogene; lack of ≥1 tumor suppressor genes
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| Clinical presentations: most patients asymptomatic and have calcium level in upper normal range (may rise 1 mg/dL
above upper normal level of calcium); lysis of bone with osteopenia, osteoporosis, and cystic changes that cause formation
of “chocolate” cysts; neuromuscular manifestations include diffuse weakness and easy fatigability; articular or periarticular
pain; normocytic normochromic anemia; depression; slowed cognitive function; high serum glucose that returns
to normal with treatment; acute hyperparathyroidism life threatening and responds to appropriate therapy; refer for surgery;
gastrointestinal (GI)—more related to hypercalcemia than high PTH level; constipation common; bloating; abdominal
pain; nausea; GI complaints more likely with acute disease; renal—renal stones occur in 15% to 20%; calcium
oxalate stones most common; nephrocalcinosis uncommon; patients may complain of polyuria; hypercalcemia causes dilute
urine and mild dehydration; renal colic; chronic renal failure; skeletal—osteitis fibrosa cystica; fractures; osteoporosis
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| Physical findings: may see band keratopathy (grayish ring around limbus of eye); dry and sparse hair and skin; palpable
parathyroid tumor rare; cataracts
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| Laboratory studies: correct calcium for albumin levels (eg, patients with hypoalbuminemia have proportional reduction
in total calcium; correct by adding 1.0 mg/dL to total calcium for every 0.8 mg/dL drop in serum albumin); intact serum
PTH; serum phosphorus
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| Medical management: adequate hydration; 800 mg of supplemental calcium daily; increase sodium intake; increase calcium
excretion with loop diuretics rather than thiazide diuretics (if 24-hr urinary calcium excretion rate >400 mg/day, patient
should not receive loop diuretic, and calcium supplementation should be reduced to 200-400 mg daily); in
postmenopausal women, estrogen replacement therapy helpful; oral bisphosphonates (eg, alendronate [Fosamax], risedronate
[Actonel]) lower fracture rate and cause mild reduction in serum calcium; for patients with severe hypercalcemia, intravenous
(IV) pamidronate lowers serum calcium abruptly; monobasic sodium and dibasic sodium (Fleet Phospho-soda)
rarely used; active form of vitamin D shown to reduce transcription of PTH formation in chief cells of parathyroid gland,
but not used because actions parallel those of PTH; analog of active form of vitamin D with suppressive effect only on
chief cells and no effect on kidney or bone under development; cinacalcet approved by Food and Drug Administration
(FDA) for chronic renal failure with secondary hyperparathyroidism or parathyroid carcinoma that causes severe osteolysis;
shown to shrink PTH-secreting adenoma and reduce its ability to make hormone
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| World Health Organization (WHO) criteria for surgical referral: age <55 yr; urinary calcium excretion rate >400
mg/day; conglomeration of signs and symptoms resulting in unhappiness and desire for surgery; history of severe hypercalcemia;
serum calcium persistently >12 mg/dL; significant symptoms of hypercalcemia despite medical treatment; significant
end organ damage
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| Surgical approaches: 1) 5- to 6-in collar incision around thyroid cartilage; adenoma or lesions causing hyperplasia removed;
2) minimally invasive surgery; 2-cm incision above localized lesion; not used in 4-gland hyperplasia; used only for single
adenoma; technetium sestamibi scanning and ultrasonography target adenoma; intraoperative measurement of PTH necessary
(expensive); postoperative hypocalcemia—temporary drop in calcium normal; permanent hypocalcemia results from
damage of all 4 glands; recurrent laryngeal nerve damage rare
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| Questions and answers: irritable bowel syndrome—symptoms similar to hyperparathyroidism, but no known association;
normal TSH levels—normal TSH range 0.3 to 5.2 µIU/mL; some people with level >3.0 µIU/mL have symptoms of hypothyroidism
that improve when TSH reduced to <3.0 µIU/mL; elderly patients may do well if TSH 4.0 to 6.0 µIU/mL; 1.0 to
2.0 µIU/mL reasonable for younger patients with no risk for cardiac disease; calcium levels and thyroidectomy—follow
calcium levels after thyroidectomy because patients may suffer damage to parathyroid glands (particularly in patients with
near-total thyroidectomy for thyroid cancer); order serum calcium 6 hr, 12 hr, and 24 hr after surgery; look for hypocalcemia;
screening elderly patients—measure TSH; if abnormal, check circulating serum T4 levels; thyroid nodules—present in
4% to 5% of Americans; work up if history suggests risk for cancer, if nodule grows, or if patient young; refer for fine needle
aspiration biopsy; liothyronine (T3; Cytomel) for patients who do not respond to T4—consider that high doses of some
agents (eg, propranolol) reduce conversion of inactive T4 to active T3 ; choose another drug; Cytomel may be useful (follow
free T4 and free T3 ); checking antimicrosomal and antiperoxidase antibody levels in all patients with subclinical
hypothyroidism—not necessary; look for overt hypothyroidism with high TSH and low T4 ; multiple nodules—can harbor
malignancy among benign nodules; perform biopsy
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| GENETIC DISORDERS WITH ENDOCRINE ABNORMALITIES —William Bryant, MD, Chief of Section, Pediatric Endocrinology,
Department of Pediatrics, Scott & White Memorial Hospital and Clinic, Temple, Texas
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| Turner’s syndrome (gonadal dysgenesis): caused by abnormality (eg, loss or absence) of second X chromosome or
structural abnormality of chromosome (resulting in unavailability of genes on short arm of chromosome); karyotypes—
45,X classic; 15% represent mosaic patterns of 45,X/46,XX or 45,X/46,XY; loss of Y chromosome also leads to Turner’s
syndrome; 10% represent structural abnormalities (eg, broken, ring, or malformed chromosome); 10% represent mosaic
patterns with structurally abnormal chromosomes; lymphedema—prominent feature of Turner’s syndrome; accounts for
several dysmorphic features; most consistent finding in newborns with Turner’s syndrome; newborn girls with puffy
hands and feet should be karyotyped; severe scarring around neck (cystic hydroma stretches skin and leads to webbing);
tissue pushes ears back and down, causing low-set posteriorly rotated ears; edema across chest pushes nipples outward;
edema at elbows changes carrying angle; edema in hands and feet changes shape and structure of nails
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| Other findings of Turner’s syndrome: narrow high-arched palate—higher likelihood for dental crowding; girls may
require palate expanders and orthodontic procedures; cubitus valgus—increased carrying angle; girls cannot fully extend
elbow; short metacarpals and metatarsals—may be more clear in feet than in hands; look for short fourth and fifth
toes
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| Concerns of patient with Turner’s syndrome: short stature—average stature of women with untreated Turner’s syndrome
4 ft 8 in; worsens over time; gonadal dysgenesis (pubertal delays); autoimmune disease—chronic lymphocytic
thyroiditis; ≤30% of patients with Turner syndrome have problems with autoimmune thyroiditis; heart disease; left-sided
heart lesions; renal anomalies (duplication of collecting system not uncommon; perform renal ultrasonography at diagnosis);
changes to aortic root can occur over time (echocardiography required every 5 yr)
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| Klinefelter’s syndrome: difficult to diagnose prepubertally; characteristics—patients often have long legs, tall stature,
and gynecomastia; smaller than average testicular size during puberty; decrease in verbal intelligence quotient (IQ); behavioral
changes (eg, easy frustration); as boys become pubertal, testicles begin to scar and become hard and firm; puberty
incomplete; risk for lymphocytic thyroiditis
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| Endocrine problems with Down’s syndrome: thyroid dysfunction; TSH often minimally elevated (6-7 µIU/mL); treatment
required and improves cognitive development; patients at increased risk for autoimmune hypothyroidism and type 1
diabetes; patients tend to be short and heavy, resulting in higher incidence of insulin resistance
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Educational Objectives
| The goal of this program is to educate the listener about thyroid problems in elderly patients and endocrine abnormalities
caused by genetic disorders. After hearing and assimilating this program, the participant will be better able to:
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 | 1. Distinguish normal changes in thyroid function from thyroid problems in elderly patients.
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| 2. Describe thyroid changes that occur with subclinical hypothyroidism.
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| 3. Explain causes of hyperparathyroidism.
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| 4. Identify features of Turner’s syndrome and Klinefelter’s syndrome.
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| 5. Discuss thyroid problems found in patients with Down’s syndrome.
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Discussed on This Program
Alendronate sodium [Fosamax]
Amiodarone HCl [Cordarone, Pacerone]
Calcium carbonate and elemental calcium (several trade names)
Cinacalcet HCl [Sensipar]
Esterified estrogens and methyltestosterone [Estratest, Estratest H.S.]
Iodine [Iodopen]
Iodine-131-metaiodobenzylguanidine (131 I-MIBG)
Levothyroxine sodium (T4 ; L -thyroxine) [Levothroid, Levoxyl, Synthroid, Unithroid]
Liothyronine sodium (T3 ) [Cytomel, Triostat]
Lithium [Eskalith, Eskalith CR, Lithobid, Lithonate, Lithotabs]
Methimazole [Tapazole]
Monobasic sodium phosphate and dibasic sodium phosphate [Fleet Phospho-soda]
Pamidronate disodium [Aredia]
Propranolol HCl [Inderal, Inderal LA]
Propylthiouracil (PTU)
Risedronate sodium [Actonel]
Suggested Reading
Biondi B et al: Subclinical hyperthyroidism: clinical features and treatment options. Eur J Endocrinol 152:1, 2005; Carel
JC: Growth hormone in Turner syndrome: twenty years after, what can we tell our patients? J Clin Endocrinol Metab
90:3793, 2005; Clarke N et al: Optimizing treatment of hypothyroidism. Treat Endocrinol 3:217, 2004; Cunningham J et
al: Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary
hyperparathyroidism. Kidney Int 68:1793, 2005; Franklyn JA et al: Thyroid function and mortality in patients treated
for hyperthyroidism. JAMA 294:71, 2005; Fraser SA et al: Low yield of thyroid-stimulating hormone testing in elderly patients
with depression. Gen Hosp Psychiatry 26:302, 2004; Heymann R et al: Rapid progression from subclinical to symptomatic
overt hypothyroidism. Endocr Pract 11:115, 2005; Lichiardopol C et al: Metabolic changes in Klinefelter
syndrome. Rom J Intern Med 42:415, 2004; McDanal CE Jr et al: Psychiatric disturbances in a 6-year-old boy with
Klinefelter's syndrome. South Med J 76:1068, 1983; Meneilly GS: Should subclinical hypothyroidism in elderly patients be
treated? CMAJ 172:633, 2005; Pasquino AM et al: Adult height in sixty girls with Turner syndrome treated with growth
hormone matched with an untreated group. J Endocrinol Invest 28:350, 2005; Roos A et al: The starting dose of levothyroxine
in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med 165:1714, 2005;
Ross IL et al: Amiodarone-induced thyroid dysfunction. S Afr Med J 95:180, 2005; van Trotsenburg AS et al: The effect
of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children a
randomized clinical trial. J Clin Endocrinol Metab 90:3304, 2005; Varadkar S et al: Thyroid screening in Down's syndrome
current patterns in the UK. Arch Dis Child 88:647, 2003.
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.
Dr. Marks spoke in Lancaster, Pennsylvania, at the 29th Annual Spring Family Practice Review, presented March 14-
18, 2005, by Temple University School of Medicine and Lancaster General Hospital. Dr. Bryant was recorded on
September 11, 2004, in Round Rock, Texas, at the 6th Annual Pediatric Subspecialty for the Primary Care Provider
course presented by Scott & White General Hospital and Texas A&M University System Health Science Center, College
of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production
of this program.
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